Dept of Surgery

DEPT OF SURGERY

Researcher : Au DKK

Project Title:	Electrical tinnitus suppression in hearing-impaired patients
Investigator(s):	Au DKK, Ho WK
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To evaluate the effectiveness of electrical tinnitus suppression in patients with sensorineural hearing loss; to compare the effectiveness of high versus low electrical stimulation rate in tinnitus suppression.

List of Research Outputs

Au D.K.K. , Advance assessment in Vertigo and Dizziness, TVB Jade Night News . 2009.

Au D.K.K. , Audiology and cochlear, Cochlear Implant Course 2010, Celebrating 20 years of Cochlear Implant in Hong Kong, Hong Kong Adventist Hospital, Hong Kong, 24-25 June 2010 . 2010.

Au D.K.K. , Bone Anchored Hearing Aid, Oriental Daily News . 2010.

Au D.K.K. , Co-supervisor of 2 Master of Science students from the Department of Rehabilitative Sciences (2009-2010), Hong Kong Polytechnic University . 2009.

Au D.K.K. , Cochlear Implant Course 2010, Celebrating 20 years of Cochlear Implant in Hong Kong, Hong Kong Adventist Hospital, Hong Kong, 2010.

Au D.K.K. , Fellow (2010), American Academy of Audiology . 2010.

Au D.K.K. , Honorary Audiologist (2010), Queen Mary Hospital . 2010.

Au D.K.K. , Member of the Medical Committee (2009-2010), The Occupational Deafness Compensation Board . 2010.

Au D.K.K. , Occupational deafness, Postgraduate Diploma in Occupational Medicine, Depa rtment of Community and Family Medicine, The Chinese University of Hong Kong, Hong Kong . 2010.

Au D.K.K. , Occupational deafness, Postgraduate Diploma in Occupational Medicine, School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong . 2010.

Au D.K.K. , Pediatric Audiology, Master in Clinical Audiology, Department of Otorhi nolaryngology, Faculty of Medicine and Surgery, The University of Santo Tomas University, the Philippines, 16-20 November 2009 . 2009.

Au D.K.K. , Positional Vertigo, Oriental Daily News . 2010.

Au D.K.K. , Referee Panel of the Food and Health Bureau (2009-2010), HKSAR Government Secretariat . 2009.

Au D.K.K. , Vice-chairman (2010), Hong Kong Society for the Deaf . 2010.

Au D.K.K. , Who are the candidates for Baha?, Cochlear Baha Symposium, Cochlear Pty. Ltd., Sheraton Hotel Hong Kong . 2010.

Schatzer R., Krenmayr A., Au D.K.K. , Kals M. and Zierhofer C., Temporal fine structure in cochlear implants: preliminary speech perception results in Cantonese-speaking implant users, Acta Oto-Laryngologica . 2010, 9: 1-9.

Researcher : Au WH

List of Research Outputs

Au W.H. , Chu S.S.M. , Chu S.S.M. and Tam P.C. , Primary and secondary retrograde intra-renal surgery (RIRS) for renal stones in patients with large stone burden, The 27th World Congress of Endourology and Shock Wave Lithotripsy, Munich, Germany, 6 - 10 October 2009 .

Ho K.L. , Wong C.W.S. , Au W.H. , Chu S.S.M. and Tam P.C. , Early continence outcomes after robotic radical prostatectomy - impact of vesicourethral reconstruction (Poster Present ation), The American Urological Association Annual Meeting, San Francisco, USA, 29 May - 3 June 2010 .

Ho K.L. , Tsui H.L., Au W.H. , Chu S.S.M. and Tam P.C. , Early continence outcomes after robotic radical prostatectomy: impact of vesicourethral reconstruction, Surgical Practice . 2009, 13(Suppl. 2): B7.

Ho K.L. , Tam P.C. , Chu S.S.M. , Au W.H. and Tsu H.L., Robotic-assisted laparoscopic partial nephrectomy - evolution of techniques and peri-operative outcomes, The 1st Hong Kong Congress of Endourology, Hong Kong, 28-29 August 2009 .

Tsu H.L., Ho K.L. , Au W.H. , Chu S.S.M. and Tam P.C. , Robotic-assisted laparoscopic radical cystectomy and construction of neobladder urethral anastomosis for urothelial carcinoma of bladder, The 1st Hong Kong Congress of Endourology, Hong Kong, 28-29 August 2009 .

Researcher : Chan ACY

List of Research Outputs

Chan A.C.Y. , Fan S.T. , Lo C.M. and Poon R.T.P. , Impact of antiviral therapy on the survival outcome of patients after major hepatectomy for hepatitis B-related hepatocellular carcinoma (Oral Presentation), The 9th World Congress of the International Hepato-Pancreato-Bilia ry Association, Buenos Aires, Argentina, 18 - 22 April 2010 .

Chan A.C.Y. , Fan S.T. , Lo C.M. , Liu C.L. , Chan S.C. , Ng K.K.C. , Yong B.H. , Chiu A. and Lam B.K.Y. , Liver transplantation for acute-on-chronic liver failure , Hepatology International . 2009, 3(4): 571-581.

Chan A.C.Y. , Fan S.T. and Lo C.M. , Prediction of hospital mortality after liver transplant ation for acute liver failure, The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 .

Chan A.C.Y. , Lo C.M. and Fan S.T. , Small-for-size syndrome in a small child, The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Chan A.C.Y. , Surgical management of HCC, The 11th Joint Annual Scientific Meeting of Hong Kong Society of Gastrotenterology, September 2009 . 2009.

Chan A.C.Y. , Tutor for Basic Surgical Skills Course, The College of Surgeons of Hong Kong . 2009.

Lau P.P., Chan A.C.Y. and Tsui M.H., Diagnostic cytological features of polyacrylamide gel injection augmentation mammoplasty, Pathology . 2009, 41(5): 443-447.

Ng K.K.C. , Chan S.C. , Chok K.S.H. , Cheung T.T. , Chan A.C.Y. , Lo C.M. and Fan S.T. , Primary versus salvage liver transplantation for hepatocel lular carcinoma within Milan criteria - a single center experience (Abstract and Poster Presentation), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S254.

Researcher : Chan HM

List of Research Outputs

Chen L. , Chan H.M. , Man K. and Guan X.Y. , Identification of the proteins Lsm2 and Apolipoprotein A-1 associated with liver regeneration by proteomic screeing (Abstract), The 16th International Liver Transplantation Society Congress, 16-19 June 2010, Hong Kong. Liver Transplantation . 2010, 16(6): s221.

Researcher : Chan JPH

List of Research Outputs

Wong B.Y.H. , Ng W.M. , Yuen P.W. , Chan J.P.H. , Ho W.K. and Wei W.I. , Early resection and reconstruction of head and neck masses in infants with upper airway obstruction, International Journal of Pediatric Otorhinolaryngo logy . 2010, 74: 287-291.

Researcher : Chan KK

List of Research Outputs

Wang X. , Ongkekp W.M., Chen L. , Yang Z. , Lu P. , Chan K.K. , Lopez J.P., Poon R.T.P. and Fan S.T. , Oct4 mediates chemotherapeutic drug resistance in live r cancer cells through potential Oct4-AKT-ABCG2 pathway, Hepatology . 2010, 52: 528-539.

Researcher : Chan KL

List of Research Outputs

Chan K.L. , Fan S.T. , Lo C.M. , Wei W.I. , Ng W.M. , Chung H.Y., Ng K.K.C. , Chan S.C. , Chan K.W. , Tso W.K. , Tsoi N.S. and Tam P.K.H. , Pediatric liver transplantation in Hong Kong - a domain with scarce deceased donors, Journal of Pediatric Surgery . 2009, 44(12): 2316-2321.

Chan K.L. , Wong K.F. and Luk J.M.C. , Role of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis: pathogenesis and therapeutic implicati ons, World Journal of Gastroenterology . 2009, 15(38): 4745-4752.

Chung P.H.Y., Wong K.K.Y. , Wong R.M.S. , Tsoi N.S. , Chan K.L. and Tam P.K.H. , Clinical experience in managing pediatric patients with ultra-short bowel syndrome using Omega-3 fatty acid, European Journal of Pediatric Surgery . 2010, 20(2): 139-142.

Chung P.H.Y., Chan K.L. and Tam P.K.H. , Risk factors for morbidities in laparoscopic appendectomy for acute appendicitis of paediatric patients, Surgical Practice . 2009, 13(3): 69-72.

Chung P.H.Y., Wong K.K.Y. , Tam P.K.H. , Chan K.L. , Ng K.K.C. , Chan S.C. , Hui T.W.C. , Yong B.H. , Fan S.T. and Lo C.M. , Split graft liver transplant for paediatric patients in Hong Kong, Hong Kong Journal of Paediatrics (New Series) . 2009, 14: 181-185.

Ehsan M.T., Ng A.T.L., Chung P.H.Y., Chan K.L. , Wong K.K.Y. and Tam P.K.H. , Laparoscopic hernioplasties in children: the implication on contralateral groin exploration for unilateral inguinal hernias, Pediatric Surgery International . 2009, 25(9): 759-762.

Hao W. , Liu X. , Chan I.H.Y., Chan K.L. , Tam P.K.H. and Wong K.K.Y. , Comparison study of post-operative stress response between single-port and three-port laparoscopic varicocelectomy in children, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Sun S. , Poon R.T.P. , Lee N.P.Y. , Yeung C. , Chan K.L. , Ng I.O.L. , Day P.J.R. and Luk J.M.C. , Proteomics of hepatocellular carcinoma: serum vimentin as a surrogate marker for small tumors ( £ 2 cm), Journal of Proteome Research . 2010, 9(4): 1923-1930.

Researcher : Chan MS

List of Research Outputs

Ho J.W.C. , Ho M.Y. , Chu A.T.W. and Chan M.S. , Hopefulness predicts residence after hereditary colorectal cancer genetic testing in Hong Kong Chinese: results of a longitudinal study (Abstract and proceeding), National Cancer Research Institute Cancer Conference, Birmingham, U.K., 4-7 October 2009 .

Ho M.Y. , Ho J.W.C. , Bonanno G.A., Chu A.T.W. and Chan M.S. , Hopefulness predicts resilience after hereditary colorecta l cancer genetic testing: a prospective outcome trajectories study, BMC Cancer . 2010, 10: 279.

Researcher : Chan SC

List of Research Outputs

Chan A.C.Y. , Fan S.T. , Lo C.M. , Liu C.L. , Chan S.C. , Ng K.K.C. , Yong B.H. , Chiu A. and Lam B.K.Y. , Liver transplantation for acute-on-chronic liver failure, Hepatology International . 2009, 3(4): 571-581.

Chan K.L. , Fan S.T. , Lo C.M. , Wei W.I. , Ng W.M. , Chung H.Y., Ng K.K.C. , Chan S.C. , Chan K.W. , Tso W.K. , Tsoi N.S. and Tam P.K.H. , Pediatric liver transplantation in Hong Kong - a domain with scarce deceased donors, Journal of Pediatric Surgery . 2009, 44(12): 2316-2321.

Chan S.C. , Advisor (2004 - present), The Hong Kong Liver Transplant Patients' Association . 2010.

Chan S.C. , Lo C.M. , Ng K.K.C. and Fan S.T. , Alleviating the burden of small-for-size graft in right liver living donor liver transplantation through accumulat ion of experience, American Journal of Transplantation . 2010, 10(4): 859-867.

Chan S.C. , Cost and benefit of liver transplantation for hepatocel lular carcinoma, Lunch Symposium, Hong Kong College of Surgeons, St. Teresa’s Hospital, Hong Kong, 7 December 2009 . 2009.

Chan S.C. , Deputy director (1 April 2010 - present), Hong Kong Liver Transplantation Center . 2010.

Chan S.C. , Donor quality of life, The 16th Annual International Congress of the Internatio nal Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Chan S.C. , Editor of the 7th Issue (December 2009), Newsletter of the Hong Kong Society of Transplantation . 2009.

Chan S.C. , Editor of the 8th Issue (April 2010), Newsletter of the Hong Kong Society of Transplantation . 2010.

Chan S.C. , Editorial Board, Hepatobiliary & Pancreatic Diseases International . 2010.

Chan S.C. , Lo C.M. , Chik B.H.Y., Chow L.C. and Fan S.T. , Flowmetry-based portal inflow manipulation for a small-for- size liver graft in a recipient with spontaneous splenorenal shunt, Clinical Transplantation . 2010, 24(3): 410-414.

Chan S.C. , General principles of organ transplantation, Orientation Course, the College of Surgeons of Hong Kong, Hong Kong, 7 August 2009 . 2009.

Chan S.C. , Honorary Secretary (2009 - present), Hong Kong Society of Transplantation . 2010.

Chan S.C. , Liver transplantation course - The Hong Kong experience and challenges, The 20th Conference of the Asian Pacific Association of Study of the Liver, Beijing, China, 25 March 2010 . 2010.

Chan S.C. , Living donor liver transplantation at University of Hong Kong, Miami Transplant Institute, Miami, Florida, U.S.A., 17 November 2009 . 2009.

Chan S.C. , Living donor liver transplantation for hepatocellular carcinoma (Invited Lecture), Lahey Clinic, Burlington, Massachusetts, U.S.A., 30 July 2009 . 2009.

Chan S.C. , Member (Hepatobiliary Pancreatic Surgery) of Task Force of Training in Sub-specialty in General Surgery (May 2010 - present), Hong Kong College of Surgeons . 2010.

Chan S.C. , Member of Central Committee for Liver Diseases (May 2010 - present), Hong Kong Hospital Authority . 2010.

Chan S.C. , Member of Liver Donation Committee (2007 - present), Liver Foundation . 2010.

Chan S.C. , Paired donor exchange programs in transplantation, Annual Scientific Meeting of the Hong Kong Society of Transplantation, Hong Kong, 25 April 2010 . 2010.

Chan S.C. , Lo C.M. , Yong B.H. , Tsui W.J.C., Ng K.K.C. and Fan S.T. , Paired donor interchange to avoid ABO-incompatible living donor liver transplantation, Liver Transplantation . 2010, 16(4): 478-481.

Chan S.C. , Lo C.M. , Ng K.K.C. , Chok K.S.H. , Yong B.H. and Fan S.T. , Portal inflow and pressure changes in right liver living donor liver transplantation including middle hepatic vein (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S92.

Chan S.C. , Portal inflow and pressure changes of right liver living donor liver transplantation (Invited Lecture), Lahey Clinic, Burlington, Massachusetts, U.S.A., 30 July 2009 . 2009.

Chan S.C. , Reviewer, American Journal of Gastroenterology . 2010.

Chan S.C. , Reviewer, American Journal of Transplantation . 2010.

Chan S.C. , Reviewer, Annals of Surgery . 2010.

Chan S.C. , Reviewer, Asian Journal of Surgery . 2010.

Chan S.C. , Reviewer, Clinical Transplantation . 2010.

Chan S.C. , Reviewer, Hepatobiliary Pancreatic Disease International . 2010.

Chan S.C. , Reviewer, Hong Kong Medical Journal . 2010.

Chan S.C. , Reviewer, Journal of Gastroenterology and Hepatology . 2010.

Chan S.C. , Reviewer, Journal of Gastrointestinal Surgery . 2010.

Chan S.C. , Reviewer, Liver International . 2010.

Chan S.C. , Reviewer, Liver Transplantation . 2010.

Chan S.C. , Reviewer, Singapore Medical Journal . 2010.

Chan S.C. , Reviewer, Transplantation . 2010.

Chan S.C. , Reviewer, World Journal of Surgery . 2010.

Chan S.C. , Lo C.M. , Ng K.K.C. , Chok K.S.H. and Fan S.T. , Simplifying hepatic venous outflow reconstruction in sequential living donor liver transplantation, Liver Transplantation . 2009, 15(11): 1514-1518.

Chan S.C. , Lo C.M. and Fan S.T. , Simplifying living donor liver transplantation, Hepatobiliary and Pancreatic Diseases International . 2010, 9(1): 9-14.

Chan S.C. , Small-for-size syndrome, The 7th Meeting of 5 Asian LDLT Centers, Hong Kong, 15 June 2010 . 2010.

Chan S.C. , Lo C.M. and Fan S.T. , Splanchnic hemodynamics in liver regeneration after right liver living donor liver transplantation (Letter to the Editor), Liver Transplantation . 2010, 16(3): 412.

Chan S.C. , Lo C.M. , Wong Y. , Ng K.K.C. , Chok K.S.H. and Fan S.T. , Validating graft and standard liver size predictions in right liver living donor liver transplantation (Abstra ct), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S247.

Chan S.C. , Validating graft and standard liver size predictions in right liver living donor liver transplantation (Oral Presentation), The 20th Conference of the Asian Pacific Association for the Study of the Liver, Beijing, China, 26 March 2010 .

Cheung C.K.Y. , Lo C.M. , Chan S.C. and Fan S.T. , Long-term follow up of hepatitis B virus-specific immune response in liver transplant patient receiving third -generation hepatitis B vaccine (Abstract), The 16th Annual International Congress of the Internatio nal Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 16(Suppl 1): S242.

Cheung T.T. , Ng K.K.C. , Poon R.T.P. , Chan S.C. , Lo C.M. and Fan S.T. , A case of laparoscopic hepatectomy for recurrent hepatocellular carcinoma, World Journal of Gastroenterology . 2010, 16(4): 526-530.

Cheung T.T. , Ng K.K.C. , Chok K.S.H. , Chan S.C. , Poon R.T.P. , Lo C.M. and Fan S.T. , Combined resection and radiofrequency ablation for multifocal hepatocellular carcinoma: prognosis and outcomes, World Journal of Gastroenterology . 2010, 16(24): 3056-3062.

Chok K.S.H. , Lo C.M. , Ng K.K.C. and Chan S.C. , Patients with preoperative hepatorenal syndrome (HRS) have comparable long-term outcomes after live-donor liver transplantation (LDLT) (Abstract), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): S207.

Chok K.S.H. , Chu F.S.K. , Cheung T.T. , Lam V.W.T. , Yuen W.K. , Ng K.K.C. , Chan S.C. , Poon R.T.P. , Yeung C. , Lo C.M. and Fan S.T. , Results of percutaneous transhepatic cholecystostomy for high surgical risk patients with acute cholecystitis, ANZ Journal of Surgery . 2010, 80(4): 280-283.

Chung P.H.Y., Wong K.K.Y. , Tam P.K.H. , Chan K.L. , Ng K.K.C. , Chan S.C. , Hui T.W.C. , Yong B.H. , Fan S.T. and Lo C.M. , Split graft liver transplant for paediatric patients in Hong Kong, Hong Kong Journal of Paediatrics (New Series) . 2009, 14: 181-185.

Fung J.Y.Y. , Lai C.L. , Chan S.C. , But D., Seto W.K., Cheng C.T.K. , Wong D.K.H. , Lo C.M. , Fan S.T. and Yuen R.M.F. , Correlation of liver stiffness and histological features in healthy persons and in patients with occult hepatitis B, chronic active hepatitis B, or hepatitis B cirrhosis., Am J Gastroenterol . 2009, 105(5): 1116-22.

Fung J.Y.Y. , Lai C.L. , Chan S.C. , But D., Seto W.K., Cheng C.T.K. , Wong D.K.H. , Lo C.M. , Fan S.T. and Yuen R.M.F. , Liver stiffness and histological features in healthy persons, and patients with occult hepatitis B, chronic active hepatitis B, and hepatitis B-related cirrhosi s., Hepatology . 2009, 50(4) Suppl: 978A.

Hwang Y.Y., Wong K.Y. , Leung R.Y.Y. , Wong S.H.M., Chan S.C. , Srivastava G. and Au W.Y. , Post-rituximab Burkitt transformation of PTLD: loss of CD20 expression accompanied by a switch in light-chain expression, Annals of Hematology . 2010, 89(1): 97-99.

Ng K.K.C. , Lo C.M. , Chan S.C. and Fan S.T. , Living donor liver transplantation for hepatocellular carcinoma across Milan criteria (Oral Presentation), International Surgical Week 2009, Adelaide, Australia, 6 - 10 September 2009 .

Ng K.K.C. , Chan S.C. , Chok K.S.H. , Cheung T.T. , Chan A.C.Y. , Lo C.M. and Fan S.T. , Primary versus salvage liver transplantation for hepatocellular carcinoma within Milan criteria - a single center experience (Abstract and Poster Presentation), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S254.

Sharr W.W. , Chok K.S.H. , Ng K.K.C. , Chan S.C. , Lo C.M. and Fan S.T. , Impact of donor age on right lobe living donor liver transplantation in a single centre (Abstract), The 15th Annual International Congress of the Internatio nal Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S92.

Researcher : Chan SWW

List of Research Outputs

Chan S.W.W. , Cheung P.S.Y. , Lee J.F.Y., Fung J.T.K., Patil N.G. and Kwok S.P.Y. , Women surgeons in Hong Kong, Surgical Practice . Hong Kong, College of Surgeons of Hong Kong, 2010, 14 (1): 2-7.

Researcher : Chan SY

List of Research Outputs

Chan S.Y. , Endoscopic submucosal dissection (ESD) for a pyloric lesion (Video presentation), Hong Kong Surgical Forum, Department of Surgery, The University of Hong Kong, Queen Mary Hospital and Hong Kong Chapter, American College of Surgeons, 9 January 2010 . 2010.

Chan S.Y. , Surgical management of unresectable or metastatic GIST in the era of imatinib, Hong Kong Surgical Forum, Department of Surgery, The University of Hong Kong, Queen Mary Hospital and Hong Kong Chapter, American College of Surgeons, 9 January 2010 . 2010.

Fan J.K.M. , Chan S.Y. and Chu K.M. , Surgical smoke, Asian Journal of Surgery . 2009, 32: 253-257.

Hung I.F.N. , Chan P., Leung S., Chan S.Y. , Hsu A., But D., Seto W.K., Wong S.Y. , Chan C.K. , Gu Q. , Tong T.S.M., Cheung T.K. , Chu K.M. and Wong B.C.Y. , Clarithromycin-amoxycillin-containing triple therapy: A valid empirical first-line treatment for Helicobacter pylori eradication in Hong Kong?, Helicobacter . 2009, 14: 505-511.

Researcher : Chan VSF

List of Research Outputs

Khoo U.S. , Chan Y.K. , Ching C.Y.J. , Chan V.S.F. , Ip Y.C. , Yam L., Chu C.M., Lai S.T., So K.M., Wong T.Y., Chung P.H., Yip S.P., Sham P.C. , Leung G.M. , Lin C.L. and Peiris J.S.M. , Functional role of ICAM-3 polymorphism in genetic susceptibility to SARS infection, Hong Kong Med Journal . 2009, 26-9.

Researcher : Chan VWM

List of Research Outputs

Liu L. , Lee P.Y. , Chan V.W.M. , Xue W., Zender L., Zhang C., Mao M., Dai H., Wang X.L., Xu Z. , Lee K.W. , Ng I.O.L. , Chen Y., Kung H.F., Lowe S.W., Poon R.T.P. , Wang J.H. and Luk J.M.C. , Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma, Hepatology (Erratum in: Hepatology 2010;51(1):358) . 2009, 50(5): 1453-1463.

Researcher : Chan WS

List of Research Outputs

Wong S.T.S. , Chan W.S. , Li C.H., Liu W.M. , Tang W.W., Tsao G.S.W. , Tsang R.K.Y. , Ho W.K. , Wei W.I. and Chan Y.W. , Curcumin alters the migratory phenotype of nasopharynge al carcinoma cells through up-regulation of E-cadherin , Anticancer Research . 2010, 30: 2851-6.

Researcher : Chan YC

Project Title:	SERUM MATRIX METALLOPROTEINASES (MMPS) AS PROGNOSITIC INDICATOR FOR THORACIC AORTIC DISEASE
Investigator(s):	Chan YC, Cheuk LY
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2009

Abstract:

The pathophysiology of non-traumatic aortic dissection is complex. Whilst it may represent a continual spectrum of acute aortic diseases ranging from intramural hematoma to penetrating atherosclerotic ulcer, the precise patho physiological mechanisms leading to aortic dissection is undefined. Mechanisms that lead to weakening of the aortic media may lead to higher wall stress, which in turn induces dilatation and aneurysm formation, resulting in intram ural haemorrhage, dissection, or rupture (1). Aortic dissection is much more common in patients with inherited connective tissue disorders such as Marfan syndrome (2) or Ehlers–Da nlos syndrome (3), but sporadic cases are also frequent and probably underdetected. For patients without connective tissue diseases, hypertension remains the most important risk factor leading to intimal disruption and aortic dissection (4,5,6). There are different hypotheses regarding the aetiology of intimal disruption. Firstly, intimal disruption may arise from vasa vasorum hemorrhage within the aortic media or rupture of an atherosclerotic plaque, permitting aortic blood flow to create a cleavage plane within the media of the aortic wall (7). This bleeding into the media creates a mass, which results in localised areas of increased stress in the intima during diastole, thus permiting intimal disruption. There are isolated reports in the literature to suggest that coagulopathy or thrombocytopenia leading to spontaneous hemorrhage within the vasa vas orum of the aorta may render the patients more prone to development of aortic dissection (8). Alternatively, the vasodilator capacity of and the flow through vasa vasorum is limited in chronic hypertension, with resultant medial ischaemia, necrosis, and thus contribute to the pathogenesis of weakness and aortic dissection in hypertensive patients (9). Finally, vascular smooth muscle cell apoptosis may play a role, as evident from aortic dissection associated with patients who abuse cocaine (10). From a molecular biology point of view, there are recent interests in matrix metalloproteinases (MMPs) in the pathogenesis of various types of arterial pathology. MMPs belong to a group of extracellular matrix–modifying enzymes. They are responsible for degradation of multiple extracellular matrix components, including fibronectin, collagen, elastin and proteogl ycans, and are important in many physiologic and pathologic vascular processes. They have long been implicated in the pathogenesis of arterial disease and in particular aortic dissection with subsequent aneurysmal formation (11). Koullias et al. recently demonstrated an increase in tissue expression of both MMP-1 and MMP-9 by micr oarray immunostaining in patients affected by aortic dissection compared to control specimens (12). In addition, these investigators found that a relative index of proteolytic state such as tissue inhibitors of metalloproteinases: metalloproteinases ratio was increased in both aortic aneurysm and dissection groups compared to control patients, suggesting that there might be a pathophysiological role. The pathophysiological significance of MMPs in aortic dissection remains poorly understood. Akiyama et al. showed that MMPs could be involved not only in the degradation of aortic tissue but also in tissue remodeling, which may be associated with the healing process (13). There are no studies to date monitoring the levels of serum MMPs in patient who has had successful treatment (either conservative, endovascular or open surgery) of symptomatic thoracic aortic dissection. There is no standardized protocol in the follow up of patients with Type B aortic dissection, although there are many published guidelines (14). Such a follow- up programme may prove difficult, as it is dependent on technologically advanced and expensive imaging modalities such as helical computed tomography angiography, magnetic resonance imaging (MRI), or transoesophageal echocardiogra phy. It is increasingly difficult to obtain aortic tissues in patients with Type B dissection, as most patients are either managed conservatively with anti-hypertensives or with endovascular stent-grafts. Open surgery is rarely performed, unless there are complications arising from the dissection. To date, there are as yet no seru m biological markers with adequate sensitivity or specificity for patients who may have developed complications from the aortic dissection. The use of serum levels of MMPs in follow-up of patients with aortic dissection is a novel and attractive concept because it is rapid, non-invasive, easy to perform, and conceivably less costly than expensive imaging studies. Specfic objective (1) To assess the serum levels of a series of MMPs (MMP-2, MMP-3, and MMP-9) and its inhbitor TIMP-1 in patients who present with symptomatic acute thoracic aortic dissection, and follow up at different time interval, to determine whether these proteolytic enzymes can act as prognostic indicator in follow up. References 1. Santini F, Luciani GB, Montalbano G, Messina A, Faggian G, Mazzucco A.Acute type A aortic dissection: an update on a still challenging disease. J Cardiovasc Med (Hagerstown). 2007; 8: 102-107. 2. Nienaber CA, Eagle KA. Aortic dissection: new frontiers in diagnosis and managemen t: Part I: from etiology to diagnostic strategies. Circulation. 2003; 108: 628-635. 3. Roseborough GS, Williams GM. Marfan and other connective tissue disorders: conservative and surgical considerations. Semin Vasc Surg. 2000; 13: 272-282. 4. Robbins RC, McManus RP, Mitchell RS, Latter DR, Moon MR, Olinger GN, Miller DC. Management of patients with intramural hematoma of the thoracic aorta. Circulation. 1993; 88(5 Pt 2): II1-10. 5. Pretre R, Von Segesser LK. Aortic dissection. Lancet 1997; 349 : 461–1463. 6. Flachskampf FA, Daniel WG. Aortic dissection, Cardiol Clin 2000; 18: 807–817 7. Blanchard DG, Sawhney NS. Aortic Intramural Hematoma: Current Diagnostic and Therapeutic Recommendations. Curr Treat Options Cardiovasc Med. 2004; 6: 99-104. 8. Tsai J, Sherman SC. Aortic dissection in a young man with immune thrombocytopenic purpura. J Emerg Med. 2005; 28(3): 285-288. 9. Marcus ML, Heistad DD, Armstrong ML, Abboud FM. Effects of chronic hypertension on vasa vasorum in the thoracic aorta. Cardiovasc Res. 1985; 19: 777-781. Sangiorgi G, Trimarchi S, Mauriello A, Righini P, Bossone E, Suzuki T, Rampoldi V, Eagle KA. Plasma levels of metalloproteinases- 9 and -2 in the acute and subacute phases of type A and type B aortic dissection. J Cardiovasc Med (Hagerstown). 2006; 7: 307-315. 10. Su J, Li J, Li W, Altura B, Altura B. Cocaine induces apoptosis in primary cultured rat aortic vascular smooth muscle cells: possible relationshi p to aortic dissection, atherosclerosis, and hypertension. Int J Toxicol. 2004; 23: 233-237. 11. Hobeika MJ, Thompson RW, Muhs BE, Brooks PC, Gagne PJ. Matrix metalloproteinases in peripheral vascular disease. J Vasc Surg. 2007; 45: 849-857. 12. Koullias GJ, Ravichandran P, Korkolis DP, Rimm DL, Elefteriades JA. Increased tissue micoarray matrix metalloproteinase expression favors proteolysis in thoracic aortic aneurysms and dissections. Ann Thorac Surg 2004; 78: 2106-2110. 13. Akiyama M, Ohtani H, Sato E, Nagura H, Tabayashi K. Up-regulation of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase were coupled with that of type I procollagen in granulation tissue response after the onset of aortic dissection. Virchows Arch. 2006; 448: 811-821. 14. Trimarchi S, Nienaber CA, Rampoldi V, Myrmel T, Suzuki T, Bossone E, Tolva V, Deeb MG, Upchurch GR Jr, Cooper JV, Fang J, Isselbacher EM, Sundt TM 3rd, Eagle KA; IRAD Investigators.Role and results of surgery in acute type B aortic dissectio n: insights from the International Registry of Acute Aortic Dissection (IRAD). Circulation. 2006; 114(1 Suppl): I357-364.

List of Research Outputs

Chan R.C.L., Chan Y.C. , Ting A.C.W. and Cheng S.W.K. , Superior vena cava obstruction: our experience, current status and future perspective, CSHK/MSA Annual Scientific Meeting 2009, Hong Kong, 6 September 2009 .

Chan Y.C. , Current management of lower limb ischaemia, Orthopaedics Saturday Inter-hospital Meeting, Princ ess Margaret Hospital, Kowloon, Hong Kong, 5 September 2009 . 2009.

Chan Y.C. , Ting A.C.W. , Qing K. and Cheng S.W.K. , Delayed presentation of popliteal pseudo-aneurysm following soccer football injury, Annals of Vascular Surgery . 2010, 24(4): 553.13-16.

Chan Y.C. , Ting A.C.W. , Qing K. and Cheng S.W.K. , Endovascular aneurysm repair in patients with horseshoe kidney: is it safe?, Asian Chapter Meeting of the International Union of Angiology, Tokyo, Japan, 29-30 October 2009 .

Chan Y.C. and Cheng S.W.K. , Endovascular management of Stanford Type A (ascending) aortic dissection, Asian Cardiovascular & Thoracic Annals . 2009, 17(6): 566-567.

Chan Y.C. , Interventional solutions for aortic aneurysms (Invited Moderator), LINC Asia-Pacific Hong Kong 2010, Hong Kong, 25-27 January 2010 . 2010.

Chan Y.C. , Cheung G.C.Y., Ting A.C.W. , Wong A.C.C. , Yiu W.K. and Cheng S.W.K. , The influence of diabetes mellitus on lower limb revascularisatio n, The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 .

Pang Y.C., Chan Y.C. , Ting A.C.W. and Cheng S.W.K. , Embolectomy in patients with acute limb ischemia: a retrospective evaluation of 128 cases over 10 years, The 10th Annual Congress of Asian Society for Vascular Surgery, Busan, Korea, 15-17 October 2009 .

Pang Y.C., Chan Y.C. , Ting A.C.W. and Cheng S.W.K. , Tender inflammatory infrarenal aortic aneurysm simulating acute rupture, Asian Cardiovascular & Thoracic Annals . 2010, 18(2): 180-182.

She W.H., Chan Y.C. , Ting A.C.W. and Cheng S.W.K. , Conservative management of delayed retrograde type A aortic dissection after successful hybrid endovascular repair of distal arch aneurysm, Acta Chirurgica Belgica . 2010, 110: 240-242.

Ting A.C.W. , Chan Y.C. , Wong A.C.C. , Yiu W.K. , Cheung G.C.Y. and Cheng S.W.K. , Clinical and morphological outcomes after endovascular repair for chronic type B thoracic aortic dissection - early and mid-term results, The 10th Annual Congress of Asian Society for Vascular Surgery, Busan, Korea, 14-17 October 2009. Annals of Vascular Diseases . 2009, 2: S100.

Researcher : Chan YW

Project Title:	Curcumin suppresses nasopharyngeal carcinoma cell migration through activation of E-cadherin
Investigator(s):	Chan YW, Wong STS
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2010

Abstract:

Nasopharyngeal carcinoma (NPC) is a common head and neck cancer arises from the epithelial lining covering the nasopharynx. In our locality, undifferentiated NPC is the major histological type (1). Tobacco and alcohol consumption are major risk factors of NPC. In addition, the pathogenesis of NPC is closely associated with Epstein-Barr virus (EBV) infection (2). The viral protein plays a key role in the development of NPC (3). Curcumin (diferuloylmethane) is a polyphenol isolated from the rhizome of Curcuma longa, a common dietary spice (4). Purified curcumin appears as yellowish powder and is widely used as herbal medicine in China and India. Emerging evidence suggests that curcumin is a potent therapeutic agent for cancer. Curcumin has been shown to have anti-inflammatory, anti-metastatic, anti-oxidative, and anti-proliferative effects on cancer cells (5). The diverse function of curcumin is a consequence of its potent effects in inactivating nuclear-factor kappaB (NF- B). NF- B could promote tumorigenesis and is activated by carcinogens (6). In NPC, overexpression of NF- B is frequently observed (7). Upregulation of NF- B is associated with angiogenesis and regional metastasis of NPC (8). E-cadherin, or type 1 cadherin, is a calcium dependent cell-cell adhesion glycoprotein. E-cadherin is a major player in cell-cell adhesion of epithelial cells and acts as a metastatic suppressor in epithelial cancers (9). Loss of E-cadherin is common in NPC and is significantly associated with advanced diseases (10). Recently, several studies revealed that reduction of E-cadherin in epithelial cancers is associated with NF- B upregulation. (11). It is accomplished by the induction of several transcription al suppressors of E-cadherin by NF- B (12). Here, we hypothesized that E-cadherin expression could be re-activated in cancer cells if NF- B is suppressed. In view of the fact that curcumin is a potent suppressor of NF- B, we here examined the use of curcumin as NF- B suppressor and evaluated its potential use to reactivate E-cadherin in NPC cells.

List of Research Outputs

Chan R.C.L. and Chan Y.W. , Mucosal melanoma of the head and neck, 4th World Congress of International Federation of Head and Neck Oncologic Societies (IFHNOS) - Shifting Paradigms in Head and Neck Oncology 2010 - Seoul, Korea . 2010.

Chan Y.W. , Anatomical study and clinical applications of free posterior tibial flap, 4th World Congress of International Federation of Head and Neck Oncologic Societies (IFHNOS) - Shifting Paradigms in Head and Neck Oncology 2010 - Seoul, Ko rea . 2010.

Chan Y.W. , Anatomical study and clinical experience with free posterior tibial flap, XIX ENT World Congress- IFOS 2009 Brazil . 2010.

Chan Y.W. , Editor, Asian Journal of Surgery . 2010.

Chan Y.W. , Editor, Journal of Plastic, Reconstructive and Aesthetic Surgery . 2010.

Chan Y.W. , Ng R.W.M. and Yuen A.P.W., Lateral thoracic flap for donor site repair of pectoralis major myocutaneous flap, Journal of Plastic, Reconstructive and Aesthetic Surgery . 2009, 8: 1004 - 1007.

Chan Y.W. , Management of the neck in head and neck cancer, National Symposium on Head and Neck Tumours and Reconstruction – Basic to Advance 2009 – Genting Highla nds, Malaysia . 2009.

Chan Y.W. , Myocutaneous flaps, International Comprehensive Head & Neck Conference – Xian, China . 2009.

Chan Y.W. , Neck dissection: current concepts, International Comprehensive Head & Neck Conference – Xian, China . 2009.

Chan Y.W. , Other pedicled flaps, International Comprehensive Head & Neck Conference – Xian, China . 2009.

Chan Y.W. , Ho A.C.W. and Wei W.I. , Prediction of surgical outcome using plasma Epstein-Barr virus DNA and 18F-FDG PET scan in recurrent nasopharynge al carcinoma, 4th World Congress of International Federation of Head and Neck Oncologic Societies (IFHNOS) - Shifting Paradigms in Head and Neck Oncology 2010 - Seoul, Korea . 2010.

Chan Y.W. , Reconstruction for recurrent breast cancer, Multi-disciplinary Approach for Breast Cancer Patients Symposium 2010 . 2010.

Chan Y.W. , Reconstruction in palliative surgery, Head and Neck Course . 2010.

Chan Y.W. , Reconstruction of hypopharynx , National Symposium on Head and Neck Tumours and Reconstruction – Basic to Advance 2009 – Genting Highlands, Malaysia . 2009.

Chan Y.W. , Reconstruction of oral cavity after resection, National Symposium on Head and Neck Tumours and Reconstruction – Basic to Advance 2009 – Genting Highlands, Malaysia . 2009.

Chan Y.W. and Wei W.I. , Recurrent head and neck cancer - role of reconstructive surgery, The 3rd International Conference of Facial Plastic Surgery, Nanning, Guangxi, China . 2009.

Chan Y.W. , Results of free flaps and management of complications, International Comprehensive Head & Neck Conference – Xian, China . 2009.

Chan Y.W. , The use of microvascular free flap after Maxillary Swing nasopharyngectomy, 4th World Congress of International Federation of Head and Neck Oncologic Societies (IFHNOS) - Shifting Paradigms in Head and Neck Oncology 2010 - Seoul, Korea . 2010.

Chow V.L.Y., Chan Y.W. , Chung J.H.P. and Wei W.I. , Basal cell carcinoma of the head and neck region (HNBCC) - A 10 year experience , 4th World Congress of International Federation of Head and Neck Oncologic Societies (IFHNOS) - Shifting Paradigms in Head and Neck Oncology 2010 - Seoul, Kor ea . 2010.

Chung J.C.K., Ho A.C.W. , Chan Y.W. and Wei W.I. , Outcomes of head and neck cancers in haemic malignancy patients, 4th World Congress of International Federation of Head and Neck Oncologic Societies (IFHNOS) - Shifting Paradigms in Head and Neck Oncology 2010 - Seoul, Korea . 2010.

Lau G.S.K. and Chan Y.W. , Radiation induced sarcomas of the head and neck. A ten-year experience, 4th World Congress of International Federation of Head and Neck Oncologic Societies (IFHNOS) - Shifting Paradigms in Head and Neck Oncology 2010 - Seoul, Korea . 2010.

Wei W.I. and Chan Y.W. , Neck dissection - practice in Hong Kong, Clinical Management of cervical lymph node metastasis . 2010, Chapter 28: 419 - 430.

Wei W.I. and Chan Y.W. , Pectoralis major flap, Flaps and Reconstructive Surgery . Elsevier Inc., 2009, 175-192.

Wong S.T.S. , Chan W.S. , Li C.H., Liu W.M. , Tang W.W., Tsao G.S.W. , Tsang R.K.Y. , Ho W.K. , Wei W.I. and Chan Y.W. , Curcumin alters the migratory phenotype of nasopharyngeal carcinoma cells through up-regulation of E-cadherin , Anticancer Research . 2010, 30: 2851-6.

Wong S.T.S. , Ho W.K. , Chan Y.W. , Ng W.M. and Wei W.I. , Mature miR-184 and squamous cell carcinoma of tongue, Head and Neck . 2009, 9: 130-132.

Wong S.T.S. , Man O.Y. , Tsang C.M. , Tsao G.S.W. , Tsang R.K.Y. , Chan Y.W. , Ho W.K. , Wei W.I. and To V.S.H. , Microrna Let-7 Suppresses Nasopharyngeal Carcinoma Cells Proliferation Through Downregulating C-myc Expression, Journal of Cancer Research and Clinical Oncology . Berlin, Springer Berlin / Heidelberg, 2010.

Researcher : Chen L

List of Research Outputs

Chen L. , Chan H.M. , Man K. and Guan X.Y. , Identification of the proteins Lsm2 and Apolipoprotein A-1 associated with liver regeneration by proteomic screeing (Abstract), The 16th International Liver Transplantation Society Congress, 16-19 June 2010, Hong Kong. Liver Transpla ntation . 2010, 16(6): s221.

Chen L. , Fatima S. , Peng J. and Leng X., SELDI protein chip technology for the detection of serum biomarkers for liver disease, Protein and Peptide Letters . 2009, 16(5): 467-472.

Wang X. , Ongkekp W.M., Chen L. , Yang Z. , Lu P. , Chan K.K. , Lopez J.P., Poon R.T.P. and Fan S.T. , Oct4 mediates chemotherapeutic drug resistance in liv er cancer cells through potential Oct4-AKT-ABCG2 pathway, Hepatology . 2010, 52: 528-539.

Researcher : Chen L

List of Research Outputs

Chen L. , Fatima S. , Peng J. and Leng X., SELDI protein chip technology for the detection of serum biomarkers for liver disease, Protein and Peptide Letters . 2009, 16(5): 467-472.

Wang X. , Ongkekp W.M., Chen L. , Yang Z. , Lu P. , Chan K.K. , Lopez J.P., Poon R.T.P. and Fan S.T. , Oct4 mediates chemotherapeutic drug resistance in liver cancer cells through potential Oct4-AKT-ABCG2 pathway, Hepatology . 2010, 52: 528-539.

Researcher : Chen Y

Project Title:	The Role of Adiponectin in Preventi on of Grafts Rejection in Mouse Model of Cardiac Transplantation
Investigator(s):	Chen Y, Xu A, Tam PKH
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2008
Completion Date:	03/2010

Abstract:

The organ transplantation is life saving strategy in last stage of organ failure. Despite the advance in immunosuppressive reagents, acute and chronic reje ction still remain a major obstacle in graft survival (1). Both immunological and non-immunological factors contribute to the processes of rejection. In acute rejection immunologi cal factors, namely the activation of CD4+ and CD8+ T cells, infiltration of macrophages and their interaction with graft endothelial cells, all contribute to tissue destruction. In chronic rejection, in addition to immunological factors such as CD4+ T cells activation and IFN-gamma production non-immunological factors which include ischemia reperfusion, hypertension, hyperlipidemia and infection are also involved. Therefore, in order to achieve long-term graft survival it is necessary to control both acute rejection by conventional immunosuppressive agents and to prevent the development of chronic rejec tion. A characteristic of chronic rejection in cardiac transplantation is graft vasculopathy formation which is a key event in parenchymal fibrosis (2). Graft vasculopathy and traditional atherosclerosis have many similarities, such as endothelial cell injury, smooth muscle cell proliferation, collagen deposition, increased adhesion molecule expression, and inflammatory cells infiltration as well as their relationship to the risk factors namely hypertension, obesity and hyperlipidemia (3). These shared features have prompted the development of generic treatments that can be applied to both diseases. Previously we and others (4, 5) have demonstrated that PPAR-gamma agonists prolong graft survival in rodent models of cardiac transplantation, which was accompanied by a marked reduction in vasculopathy an d fibrosis. In our study we used rosiglitazone, a synthetic ligand for peroxisome proliferator activated receptor (PPAR)-gamma, the treatment alone failed to prevent AR but when combined with the pulsed delivery of Cyclosporine A (CsA) long term graft survival was observed. Furth ermore, rosiglitazone abrogated CR induced by high doses of CsA and without continuous delivery of the PPAR-gamma ligand CR developed. In some individuals long term administration of PPAR-gamma agonists may have adverse side effects (6) however since PPAR-gamma signaling regulates many down-stream genes (7) identifying these targets may offer alternatives. Adiponectin is expressed almost exclusively in adipose tissue and is involved in glucose and lipid metabolism (8, 9). It is present abundantly in serum and hypoadiponectinemia is directly associated with obesity-linked complications including type 2 diabetes (10), coronary heart disease including atherosclerosis and hypertension (11). In vitro studie s suggest adiponectin negatively regulates the activation of endothelial cells and macrophages during inflammation, reduces the expression of adhesion molecules and inhibits NF-kB (12). The anti-inflammation and anti-atherosclerot ic functions of adiponectin and PPAR-gamma share many common features. However, there are differences in their effects on the cardiovascular system. For example, PPAR-gamma is associated with the risk of myocardial infarction (6) and has no effects in animal models of ischemia reperfusion (13), whereas adiponectin protects against myocardial ischemia-reperfusion injury through the regulation of AMP-activated protein kinase and cyclooxygenase-2 (14). Exposure to adiponectin reduced TNF-alpha production in myocardial cells in response to LPS stimulation. In addition PPAR-gamma agonists inhibit angiogenesis, whereas it is promoted by adiponectin which induces eNOS production in the endothelial cells of the new vessels (15). These findings raise the possibilit y that adiponectin may have a protective role in cardiac transplantation. Recent studies by Wu et al. have demonstrated that T cells and macrophages accumulate in adipose tissue in obesity when adiponectin expression is low (16). Furthermore, there is one report which demonstrates that adiponectin can suppress T cell proliferation in MLRs (17). However, our knowledge on the effects of adiponectin on innate and adaptive immunity, especially, in transplantation setting is absent. We hypothesize that APN has beneficial effect on grafts rejection in cardiac transplantation. For further enhance our hypothesize, we have performed several preliminary studies, the results has shown (a) long-term cardiac allograft survival in rats treated with CsA and rosiglitaz one serum levels of adiponectin are increased more than 50% (n = 4~6 in each group) (Appendix I, Fig 1) (b) Rapamycin (Rapa) treatment prolongs mean survival time (MST) of mouse cardiac grafts from 7 to 23 days, however, in adiponectin knock out (APN-KO) mice the MST was reduced to 17 days (n=3) (Appendix I, Fig 2) (c) The addition of adiponectin suppresses T cell activation in mixed lymphocyte reactions (MLR) (Appendix I, Fig 3) (d) In bone marrow derived DC culture, the cells expressed the adiponectin receptor 1 and 2 (APNR1 and APNR2) (Appendix I, Fig 4) (Appendix I is attached as attachement I) The objectives of the study are (a) to analyze the kinetics of cardiac allograft survival in mice depleted of or over-expressing adiponectin (b) to examine the effect in combine with immunosuppressive drugs (Rapamycin and Cyclosporine A) References 1. Taylor DO, et al. J Heart Lung Transplant 2005; 24 (8): 945. 2. Libby P, Pober JS. Immunity 2001; 14 (4): 387. 3. Rahmani M, et al. Circ Res 2006; 99 (8): 801. 4. Chen Y, et al. Transplantation 2007; 83 (12): 1602. 5. Kosuge H, et al. Circulation 2006; 113 (22): 2613. 6. Nissen SE, Wolski K. N Engl J Med 2007; 356 (24): 2457. 7. Yu S, et al. J Biol Chem 2003; 278 (1): 498. 8. Maeda K, et al. Biochem Biophys Res Commun 1996; 221 (2): 286. 9. Scherer PE, et al. J Biol Chem 1995; 270 (45): 26746. 10. Berg AH, et al. Nat Med 2001; 7 (8): 947. 11. Pischon T, et al. Jama 2004; 291 (14): 1730. 12. Ouchi N, Walsh K. Clin Chim Acta 2007; 380 (1-2): 24. 13. Xu Y, et al. Am J Physiol Heart Circ Physiol 2005; 288 (3): H1314. 14. Shibata R, et al. Nat Med 2005; 11 (10): 1096. 15. Cheng KK, et al. Diabetes 2007; 56 (5): 1387. 16. Wu H, et al. Circulation, vol 115, 2007: 1029. 17. Nakano T, et al. Transpl Immunol 2007; 17 (2): 130. 18. Liu Y, et al. Transplantation 2007; (in press). 19. Liu Y, et al. Transplant International 2007; (Revised version submitted with minor changes) .

Project Title:	The role of adiponectin in cardiac allograft survival and immune regulation
Investigator(s):	Chen Y, Tam PKH, Xu A
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2008

Abstract:

(1) 1A. To analyze the kinetics of cardiac allograft survival in mice depleted of or over-expressing adiponectin 1B. To examine the effect in combine with immunosuppressive drugs (Rapamycin and Cyclosporine A); (2) To determine if the ability of PPAR-gamma agonists with or without Rapa and CsA to reduce chronic rejection in a mouse model of cardiac transplantation is mediated through modulating adiponectin expression; (3) 3A. To apply in vitro and in vivo approaches in order to dissect the ability of adiponectin to regulate innate and adaptive immunity 3B. To investigate intracellular signaling of Adiponectin in regulation of innate and adaptive immunity.

Project Title:	Analysis the modulation of M2 macrophages activation in response to TGF-β blockade
Investigator(s):	Chen Y, Tam PKH
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2009

Abstract:

Macrophages are an important component in innate immune system. Recently, there has been considerable interest in defining the microenvironments which determine the functional phenotype of different macrophage population s. Broadly, two types of macrophages can be distinguished, M1 macrophages which are classically activated macrophages and M2 macrophages which are alternatively activated macrophages. The classical response of M1 macrophages to stimulation by the bacterial membrane component lipopolysaccharide (LPS) results in the production of pro-inflammatory cytokines such as TNF-α, IL-6, IL-12 etc which belong to TH1 cytokines and thus, has potent microbiocidal function. In contrast, activati on of M2 macrophages by LPS generates only low levels of TH1 cytokines, but the production of anti-inflammatory cytokines (or TH2 cytokines) e.g. IL-10, IL-4, IL-13 etc. is greatly increased. Over the past several decades, the function of M1 macrophages in inflammatory response induced by bacterial infection are well understood but the induction, regulation and effector function of M2 macrophages in a variety of pathological proce sses still remain to be defined. M2 macrophages are heterogeneous and their function and phenotype is determined by the environment. They can be further divided into M2a cells, which correlate to IL-4 and IL-13 elicited macrophages, M2b cells which are induced by cross-linking of Fc-gamma receptors in the presence of a Toll-like receptor (TLR) ligation and M2c cells which are polarized by TGF-β, IL-10 or glucocorticoids. In addition macrophages present in some other non-pathogen related diseases, such as atherosclerosis and tissue injury, express a M2 phenotype (1). Likewise macrophages residing in tumors, namely tumor associated macrophage (TAM), belong to the M2 subset, and targeting TAMs has been suggested as one of the therapeutic strategy in cancer treatment (2). TGF-β plays an important role in macrophage activation. Our previous studies have demonstrated that blockade of TGF-β signaling reduces the expression of the pro- inflammatory cytokine TNF-α both in human and mouse macrophages in vitro. TGF-β blockade in vivo also reduces mortality in a mouse model of LPS induced septic shock. These results indicate the important function of TGF-β in M1 macrophage activation. As regards M2 cells all subtype s (M2a, M2b and M2c) can produce TGF-β1 but its role in M2 macrophage biology has not been studied in detail. Our preliminary data using the mouse macrophage cell line RAW264.7 primed with IL-4/IL-13 and in which TGF-β signaling is blocked either using siRNA for SMAD2 (a TGF-β intracellular pathway molecule) or SB431542 (see below) revealed greatly increased expression of both mRNA and protein for the M2 effector molecule iNOS (inducible nitric oxide synthesis). These results were confirmed for human and mouse primary macrophages using the TGF-β receptor 1 inhibitor SB431542. The treatment greatly reduced the anti-inflammatory activity of the M2 macrophages by reducing TGF-β and increasing iNOS expression. The level of up-regulation was similar to that in IFN-γ primed M1 macrophages. Our hypothesis is that (1) TGF-β is the key molecule in maintaining the phenotype and function of M2 macrophages, (2) The blockade of this signaling pathway will allow M2 macrophages to adopt the phenotype of M1 cells. Objectives 1. To investigate if TGF-β blockade using siRNA for SMAD2 and TGF-β receptor 1 inhibitors alters the phenotype of M2 macrophages to that of M1 cells by inducing phenot ypic changes in the expression of membrane receptors, cytokines / chemokines and their receptors as well as the effector molecules iNOS and Arginase 1 (Arg 1) 2. To analyze the functional effects of TGF-β 1 blockade in M2 macrop hages on phagocytosis and antigen presenting activity 3. To explore the possible mechanism of TGF-β blockade on intracellular signaling pathways by studying the expression of Stat1, Stat3 and Stat6 and NF kB pathway. Try to find out the target gene(s) of TGF-β which can direct affect the change the status of macrophages activation, from M1 to M2 or vice versa Reference: 1. Martinez, F. O., Sica, A., Mantovani, A., and Locati, M. (2008) Macrophage activation and polarization. Front Biosci 13, 453-461 2. Sica, A., Schioppa, T., Mantovani, A., and Allavena, P. (2006) Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer 42, 717-727 3. Chen, Y., Kam, C. S., Liu, F. Q., Liu, Y., Lui, V. C., Lamb, J. R., and Tam, P. K. (2008) LPS-induced up-regulation of TGF-beta receptor 1 is associated with TNF-alpha expression in human monocyte-derived macrophages. J Leukoc Biol 83, 1165-1173 4. Steinkamp, J. A., Wilson, J. S., Saunders, G. C., and Stewart, C. C. (1982) Phagocytosis: flow cytometric quantitation with fluorescent microspheres. Science 215, 64-66 5. Edwards, J. P., Zhang, X., Frauwirth, K. A., and Mosser, D. M. (2006) Biochemical and functional characterization of three activated macrophage populations. J Leukoc Biol 80, 1298-1307 6. Giavazzi, R., Alessandri, G., Spreafico, F., Garattini, S., and Mantovani, A. (1980) Metastasizing capacity of tumour cells from spontaneous metastases of transplanted murine tumours. Br J Cancer 42, 462-472

Project Title:	Keystone Symposia on Molecular and Cellular Biology - Molecular and Cellular Biology of Immune Escape in Cancer Tumor Associated Macrophage Reprogramming – the role of TGF-β and TLR mediated signalling
Investigator(s):	Chen Y
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	02/2010
Completion Date:	02/2010

Abstract:

N/A

List of Research Outputs

Garcia-Barcelo M.M. , Yeung M.Y. , Miao X.P., Tang S.M. , Chen G., So M.T. , Ngan E.S.W. , Lui V.C.H. , Chen Y. , Liu X. , Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y. , Chan D. , Cheung K.M.C. , Chung P.H.Y., Wong K.K.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2, Human Molecular Genetics . 2010, 19 (14): 2917-2925.

Hao W. , Liu X. , Lee P.Y. , Chen Y. and Wong K.K.Y. , A study into the effects of omega-3 fatty acids on macrophages and hepatocytes, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Liu X. , Lee P.Y. , Ho C.M. , Lui V.C.H. , Chen Y. , Che C.M. , Tam P.K.H. and Wong K.K.Y. , Silver nanoparticles mediate differential responses in keratinocytes and fibroblasts during skin wound healing, ChemMedChem . 2010, 5(3): 468-475.

Miao X. , Garcia-Barcelo M.M. , So M.T. , Tang W.K. , Xiao D. , Wang B. , Mao J.X., Ngan E.S.W. , Chen Y. , Lui V.C.H. , Wong K.K.Y. , Liu L. and Tam P.K.H. , Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population, Journal of Pediatric Surgery . 2010, 45: 709-713.

Miao X. , Leon Y.Y. , Ngan E.S.W. , So M.T. , Yuan Z.W., Lui V.C.H. , Chen Y. , Wong K.K.Y. , Tam P.K.H. and Garcia-Barcelo M.M. , Reduced RET expression in gut tissue on individuals carrying risk alleles of Hirschsprung's disease, Human Molecular Genetics . 2010, 19(8): 1461-1467.

Qi H. , Siu S.O. , Chen Y. , Han Y.F., Chu I.K. , Tong Y. , Lau A.S.Y. and Rong J. , Senkyunolide isomers H and I from Rhizoma Chuanxiong attenuate hydrogen peroxide-induced oxidative stress in human liver HepG2 cells via induction of heme oxygenase-1, 8th Meeting of Consortium for Globalization of Chinese Medicine (CGCM) . Nottingham, UK, 2009.

Qi H. , Siu S.O. , Chen Y. , Han Y.F., Chu I.K. , Tong Y. , Lau A.S.Y. and Rong J. , Senkyunolides reduce hydrogen peroxide-induced oxidative damage in human liver HepG2 cells via induction of heme oxygenase-1, Chemico-Biological Interactions . 2010, 183(3): 380-389.

Yang D. , Sun Z. , Peng T. , Wang L.H., Shen J. , Chen Y. and Tam P.K.H. , Synthetic fluorescent probes for imaging of peroxynitrite and hypochlorous acid in living cells, Methods Mol Biol. . 2010, 591: 93-103.

Yang D. , Sun Z. , Peng T. , Wang H.L., Shen J.G., Chen Y. and Tam P.K.H. , Synthetic fluorescent probes for imaging of peroxyni trite and hypochlorous acid in living cells, Methods in Molecular Biology . 2010, 591: 93-103.

Researcher : Cheng CKC

List of Research Outputs

Lam C.Y. , Poon T.C.W., Cheng C.K.C. and Cheung S.T. , Interacting protein of granulin-epithelin precursor in liver cancer, The 101st Annual Meeting of the American Association for Cancer Research, Washington, DC, U.S.A., 17-21 April 2010. Proceedings of the AACR . 2010, 51: 3130.

Researcher : Cheng LC

List of Research Outputs

Lam C.L.D. , Girard L., Sihoe A.D.L. , Cheng L.C. , Lui M.A.C.Y., Wong M.P. , Chung L.P. , Ip M.S.M. , Lam W.K. and Minna J.D., Gene expression signatures associated with combination of female non-smokers in lung adenocarcinomas bearing activating epidermal growth factor receptor (EGFR) gene mutations in Chinese, The American Thoracic Society Annual Meeting 2010 .

Li X. , Cheng L.C. , Cheung Y.F. , Lun K.S., Chau A.K.T. and Chiu S.W., Management of symptomatic congenital tracheal stenosis in neonates and infants by slide tracheoplasty: a 7-year single institution experience, European Journal of Cardio-thoracic Surgery . 2010, Epub ahead of print.

Li X. , Cheng L.C. , Cheung Y.F. , Lun K.S. , Chau A.K.T. and Chiu S.W. , Management of symptomatic congenital tracheal stenosis in neonates and infants by slide tracheoplasty: a 7-year single institution experience, European Journal of Cardio-thoracic Surgery . 2010, 38: 609-614.

Tam I.Y., Leung L.H. , Tin P.C. , Chua D.T.T. , Sihoe A.D.L. , Cheng L.C. , Chung L.P. and Wong M.P. , Double EGFR mutants containing rare EGFR mutant types show reduced in vitro response to gefitinib compared to common activating missense mutations, Molecular Cancer Therapeutics . 2009, 8(8): 2142-51.

Tsang F.H.F., Li X. , Cheung Y.F. , Chau A.K.T. and Cheng L.C. , Pulmonary valve replacement after surgical repair of Tetralogy of Fallot, Hong Kong Medical Journal . 2010, 16: 26-30.

Researcher : Cheng Q

List of Research Outputs

Cheng Q. , Ng T.P. , Fan S.T. , Lim Z.X.H. , Guo D. , Liu X. , Liu Y. , Poon R.T.P. , Lo C.M. and Man K. , Distinct mechanism of small-for-size fatty liver graft injury--Wnt4 signaling activates hepatic stellate cells, American Journal of Transplantation . 2010, 10(5): 1178-1188.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Abstract), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s72.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Rising Star Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft - the significance of aldose reductase signaling on oval cell activation (Travel Award), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009 . 2009.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft – the significance of aldose reducatase signaling on oval cell activation (Abstract), The 15th Annual International Congress of the Internatio nal Liver Transplantation Society, New York, U.S.A., 8-11 July 2009. Liver Transplantation . 2009, 15:S72: #O6.

Man K. , Cheng Q. , Liu Y. , Lam T.T. , Ng T.P. and Lo C.M. , Inflammatory microenvironment accelerates liver tumor growth and metastasis by mobilizing circulating endothelial progenitor cells and increasing cancer stem like cell populations (Abstract), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): S97.

Man K. , Shih K.C. , Ng T.P. , Xiao J. , Guo D. , Sun K.W. , Lim Z.X.H. , Cheng Q. , Liu Y. , Fan S.T. and Lo C.M. , Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts, Annals of Surgery . 2010, 251(6): 1154-1161.

Man K. , Ng T.P. , Xu A. , Cheng Q. , Lo C.M. , Xiao J. , Sun B. , Lim Z.X.H. , Cheung J.S., Wu E.X. , Sun K.W. , Poon R.T.P. and Fan S.T. , Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-inducibl e protein 10/matrix metalloproteinase 9 signaling, Clinical Cancer Research . 2010, 16(3): 967-977.

Researcher : Cheng Q

List of Research Outputs

Cheng Q. , Ng T.P. , Fan S.T. , Lim Z.X.H. , Guo D. , Liu X. , Liu Y. , Poon R.T.P. , Lo C.M. and Man K. , Distinct mechanism of small-for-size fatty liver gra ft injury--Wnt4 signaling activates hepatic stellate cells, American Journal of Transplantation . 2010, 10(5): 1178-1188.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft - the significance of aldose reductase signaling on oval cell activation (Travel Award), The 15th Annual International Congress of the Inte rnational Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009 . 2009.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft – the significance of aldose reducatase signaling on oval cell activation (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York, U.S.A., 8-11 July 2009. Liver Transplantation . 2009, 15:S72: #O6.

Man K. , Cheng Q. , Liu Y. , Lam T.T. , Ng T.P. and Lo C.M. , Inflammatory microenvironment accelerates liver tumor growth and metastasis by mobilizing circulating endo thelial progenitor cells and increasing cancer stem like cell populations (Abstract), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): S97.

Man K. , Ng T.P. , Xu A. , Cheng Q. , Lo C.M. , Xiao J. , Sun B. , Lim Z.X.H. , Cheung J.S., Wu E.X. , Sun K.W. , Poon R.T.P. and Fan S.T. , Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling, Clinical Cancer Research . 2010, 16(3): 967-977.

Researcher : Cheng SWK

Project Title:	Endovascular program for treating thoracic aortic dissections
Investigator(s):	Cheng SWK, Ting ACW
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	04/2004

Abstract:

To initiate medical services for the poor and sic k in the field of endovascular treatment of aortic dissections and provide equipment for such services.

Project Title:	Endovascular aortic stent graft program for treating acute aortic dissections
Investigator(s):	Cheng SWK, Ting ACW
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	01/2007

Abstract:

To initiate medical services for the poor and the sick in the field of endovascular treatment of aortic dissections and provide equipment for such services. The grant allows poor patients to directly benefit from an expensive procedure which is neither supported by the Hospital Authority nor the Samaritan Fund. It also enable patients who are sick and unfit for open thoracic surgery to have minimally invasive alter native treatment in acute aortic dissections, many of which are emergency life-saving procedures. Currently the endovascular stent graft program for aortic dissection is underway and needs recurrent support to continue to benefit patients with this disease.

Project Title:	A prospective randomized trial of endovascular stent graft repair versus best medical treatment for patients with acute Type B aortic dissection
Investigator(s):	Cheng SWK, Tse HF, Ting ACW, Cheng LC
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2007
Completion Date:	12/2009

Abstract:

To evaluate the short term efficacy of endovascular stent grafting for acute type B aortic dissections compared to medical treatment in terms of 30-day mortality; to determine if endovascular stent graft for acute type B aortic dissection will have fewer complications compared to medical treatment; to test whether stent grafting for type B dissections will lead to early false lumen thrombosis and less aneurysm formation compared with medical treatment on the long term; to compare the effects on long term mortality between stent grafting and medical treatment for type B disse ctions.

Project Title:	Percutaneous plaque excision for lower limb salvage in peripheral arterial occlusive disease
Investigator(s):	Cheng SWK, Ting ACW, Chan YC
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	12/2007

Abstract:

To povide medical services for the sick and the poor in the field peripheral arterial disease (PAD) and to provide equipment for such services. The support from the foundation allows patients to benefit from a new medical device which has significant advantages over conventional treatment. The new atherectomy device is currently not supported by the Hospital Authority or the Samaritan Fund. It also allows treatment for patients who are unfit for open bypass surgery and prevent them from deteriorating into limb loss.

List of Research Outputs

Basco M.T.G., Yiu W.K. , Cheng S.W.K. and Sumpio B.E., The effects of freezing versus supercooling on vascular cells: Implications for balloon cryoplasty, Journal of Vascular and Interventional Radiology . 2010, 21(6): 910-915.

Chan R.C.L., Chan Y.C. , Ting A.C.W. and Cheng S.W.K. , Superior vena cava obstruction: our experience, current status and future perspective, CSHK/MSA Annual Scientific Meeting 2009, Hong Kong , 6 September 2009 .

Chan Y.C. , Ting A.C.W. , Qing K. and Cheng S.W.K. , Delayed presentation of popliteal pseudo-aneurysm follo wing soccer football injury, Annals of Vascular Surgery . 2010, 24(4): 553.13-16.

Chan Y.C. , Ting A.C.W. , Qing K. and Cheng S.W.K. , Endovascular aneurysm repair in patients with horseshoe kidney: is it safe?, Asian Chapter Meeting of the International Union of Angiology, Tokyo, Japan, 29-30 October 2009 .

Chan Y.C. and Cheng S.W.K. , Endovascular management of Stanford Type A (ascending) aortic dissection, Asian Cardiovascular & Thoracic Annals . 2009, 17(6): 566-567.

Chan Y.C. , Cheung G.C.Y., Ting A.C.W. , Wong A.C.C. , Yiu W.K. and Cheng S.W.K. , The influence of diabetes mellitus on lower limb revascularisation, The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 .

Cheng S.W.K. , A computational investigation of the hemodynamic factors in thoracic aortic endovascular repair, Medtronic's Asia-Pacific Endovascular Technology Exchange, Auckland, New Zealand, 4-5 December 2009 . 2009.

Cheng S.W.K. , A novel bifurcated endograft for treating aneurysms with short common iliac arteries, Leipzig Interventional Course 2010, Leipzig, Germany, 27-29 January 2010 . 2010.

Cheng S.W.K. , ASVS-ISVS Joint Meeting - Session 1: Arterial (Invited Co-Moderator), The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 . 2010.

Cheng S.W.K. , ASVS-ISVS Joint Symposium on Fenestrated and Branch Stent Grafts (Invited Chairman), The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 . 2010.

Cheng S.W.K. , Asian Venous Forum Free Paper 2: Sclerotherapy (Invi ted Co-Chairman), The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 . 2010.

Cheng S.W.K. , Associated Editor of International Editorial Board (2008 - present), Annals of Vascular Diseases . 2010.

Cheng S.W.K. , Council Member (2004 - present), The College of Surgeons of Hong Kong . 2010.

Cheng S.W.K. , Current management of PAD in Hong Kong: a surgeon's perspective, The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 . 2010.

Cheng S.W.K. , Current mangement of PAD in Hong Kong: a surgeon's perspective (Invited Symposium), Asian Chapter Meetig of the International Union of Angiolgoy, Tokyo, Japan, 29-30 October 2009 . 2009.

Cheng S.W.K. , Current status of endovascular surgery in Hong Kong and China, The 38th Annual Symposium of Society for Clinical Vascular Surgery, Scottsdale, Arizona, U.S.A., 6-10 April 2010 . 2010.

Cheng S.W.K. , Development of endovascular surgery in Hong Kong and China, Annual Scientific Meeting of the Vascular Society, Liverpool, United Kingdom, 18-20 November 2009 . 2009.

Cheng S.W.K. , EVAR: My experiences of a well-done job and a nightmare, Annals of Vascular Diseases . 2009, 2: S27.

Cheng S.W.K. , EVAR: My experiences of a well-done job and a nightmar e, The 10th Annual Congress of Asian Society for Vascular Surgery, Busan, Korea, 14-17 October 2009 . 2009.

Cheng S.W.K. , Editor-in-Chief (2002 - 2010), Asian Journal of Surgery . 2010.

Cheng S.W.K. , Endovascular interventions for peripheral arterial disease: a surgeon's perspective (Invited Lecture), Symposium on "Recent Advances in Cardiovascular Surgery", Taipei, Taiwan, 14 March 2010 . 2010.

Cheng S.W.K. , Endovascular repair of aortic aneurysm (Invited Lecture), Symposium on "Recent Advances in Cardiovascular Surgery", Taipei, Taiwan, 14 March 2010 . 2010.

Cheng S.W.K. , Endovascular thoracic aortic stent graft: Applications (Invited Lecture), TX2 Workshop, Visit the Osaka University, Osaka, Japan, 6-7 January 2010 . 2010.

Cheng S.W.K. , Experience and outcome in Asia, ASVS-ISVS Joint Symposium on Fenestrated and Branch Stent Grafts: The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 . 2010.

Cheng S.W.K. , Experience and outcomes of fenestrated and branched grafts for Asian patients, Pre-congress Workshop sponsored by Cook Medical (Fenestrated and Branch Technology): The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 . 2010.

Cheng S.W.K. , General principles of dealing with dissection using TEVAR, Complex TEVAR Forum: China Endovascular Course 2009, Shanghai, China, 6-8 November 2009 . 2009.

Cheng S.W.K. , Honorary Consultant in Vascular Sugery (June 2008 - June 2010), St. Paul's Hospital . 2010.

Cheng S.W.K. , Honorary Consultant in Vascular Surgery (January 2004 - present), Hong Kong Sanatorium & Hospital . 2010.

Cheng S.W.K. , Honorary Member (2008 - present), Australasian and New Zealand Society for Vascular Surgery . 2010.

Cheng S.W.K. , Honorary Member (2010 - present), Society for Clinical Vascular Surgery . 2010.

Cheng S.W.K. , Improved device design for Asian patients, Session on Assessing and Planning for Iliac Branched Grafts for Iliac Artery Preservation: The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 . 2010.

Cheng S.W.K. , Live demonstrations & recording case demonstration "Proform for EVAR" (Invited Demonstration), China Endovascular Course 2009, Shanghai, China, 6-8 November 2009 . 2009.

Cheng S.W.K. , Member of Editorial Board (1996 - present), Chinese Journal of Vascular Surgery . 2010.

Cheng S.W.K. , Member of Editorial Board (2002 - present), Cutting Edge, College of Surgeons of Hong Kong Newsletter . 2010.

Cheng S.W.K. , Opening session: Hot Topics 2010 (Invited Co-Chairman), LINC Asia-Pacific Hong Kong 2010, Hong Kong 25-27 January 2010 . 2010.

Cheng S.W.K. , Planning for EVAR: critical aspect, Visit the Hospital Kuala Lumpur, Kuala Lumpur, Malaysia , 4 August 2009 . 2009.

Cheng S.W.K. , Pre-congress Workshop sponsored by Cook Medical: Experienc e in using advanced AAA device (Invited Workshop), China Endovascular Course 2009, Shanghai, China, 6-8 November 2009 . 2009.

Cheng S.W.K. , Pre-congress Workshop sponsored by Cook Medical: Techniq ues for EVAR with challenging iliac anatomy (Invited Workshop), The 10th Annual Congress of Asian Society for Vascular Surgery, Busan, Korea, 14-17 October 2009 . 2009.

Cheng S.W.K. , Queen Mary Hospital experience of fenstrated and branched grafts, AAA Basic Endovascular Technique Forum: China Endovascular Course 2009, Shanghai, China, 6-8 November 2009 . 2009.

Cheng S.W.K. , Scientific Session 5: Endovascular treatment (Invited Co-Chairman), Asian Chapter Meeting of the International Union of Angiology, Tokyo, Japan, 29-30 Octber 2009 . 2009.

Cheng S.W.K. , Secretary General (2009 - present), Asian Society for Vascular Surgery . 2010.

Cheng S.W.K. , Serena H.C. Yang Professor in Vascular Surgery (Apri l 2005 - present), Endowed Professorship, The University of Hong Kong . 2010.

Cheng S.W.K. , Short and wide common iliac arteries (Clinical Corner ), The Landing Zone (http://landingzone.cookmedical.com) . 2009, July 2009.

Cheng S.W.K. , Special Lecture 3: Advanced endovascular techniques; fenestrated and branched endografts (Invited Chairman) , The 10th Annual Congress of Asian Society for Vascular Surgery, Busan, Korea, 14-17 October 2009 . 2009.

Cheng S.W.K. , Sponsored Symposium: Asian PAD as Atherothrombosis (Invited Co-Chairman), Asian Chapter Meeting of the International Union of Angiology, Tokyo, Japan, 29-30 October 2009 . 2009.

Cheng S.W.K. , Symposium 2: Current Management of PAD in Asia - New Frontiers (Invited Co-Chairman), The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 . 2010.

Cheng S.W.K. , Transcending traditional standards of aortic repair: device-specific designs for Asian patients, The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 . 2010.

Cheng S.W.K. , Vascular Section Editor (2006 - present), Asian Cardiovascular and Thoracic Annals . 2010.

Cheuk L.Y. and Cheng S.W.K. , Annexin A1 expression in atherosclerotic carotid plaque s and its relationship with plaque characteristics, European Vascular Biology Conference, Marseille, France, 14-17 September 2009 .

Fan Y. , Qing K. , Cheng S.W.K. and Chow K.W. , Computational studies of thoracic aortic dissection, The 8th Asian Computational Fluid Dynamics Conference, Hong Kong . 2010.

Fan Y. , Qing K. , Cheng S.W.K. and Chow K.W. , Studies of thoracic aortic dissection by computational fluid dynamics, The Fifth European Conference on Computational Fluid Dynamics, Lisbon, Portugal, 2010 .

Pang Y.C., Chan Y.C. , Ting A.C.W. and Cheng S.W.K. , Embolectomy in patients with acute limb ischemia: a retrospective evaluation of 128 cases over 10 years, The 10th Annual Congress of Asian Society for Vascular Surgery, Busan, Korea, 15-17 October 2009 .

Pang Y.C., Chan Y.C. , Ting A.C.W. and Cheng S.W.K. , Tender inflammatory infrarenal aortic aneurysm simulating acute rupture, Asian Cardiovascular & Thoracic Annals . 2010, 18(2): 180-182.

She W.H., Chan Y.C. , Ting A.C.W. and Cheng S.W.K. , Conservative management of delayed retrograde type A aortic dissection after successful hybrid endovascular repair of distal arch aneurysm, Acta Chirurgica Belgica . 2010, 110: 240-242.

Ting A.C.W. , Chan Y.C. , Wong A.C.C. , Yiu W.K. , Cheung G.C.Y. and Cheng S.W.K. , Clinical and morphological outcomes after endovascular repair for chronic type B thoracic aortic dissection - early and mid-term results, The 10th Annual Congress of Asian Society for Vascular Surgery, Busan, Korea, 14-17 October 2009. Annals of Vascular Diseases . 2009, 2: S100.

Researcher : Cheuk LY

Project Title:	Expression of anti-inflammatory Annexin-1 protein in atherosclerotic plaques in carotid stenosis patients: Implication of plaque pathology.
Investigator(s):	Cheuk LY, Cheng SWK
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	01/2008
Completion Date:	12/2009

Abstract:

Stroke is a major cause of disability and mortality. Almost one-third of patients admitted with ischemic stroke have significant atherosclerotic narrowing of the ipisilateral internal carotid artery (1). Duplex scanning is used to access carotid artery stenosis with atherosclerotic plaque, both haemodynamically and morphologically. Specifically, unfavorable plaque features most likely associated with lipid-rich, rupture-pron e plaques and contribute to the symptomatic events independently of the degree of stenosis in the vulnerable patients (2). Carotid endarterctomy remains the most common procedure to prevent stroke in carotid stenosis patients (3). The biological examination of carotid endarterecto my specimens definitely provides invaluable snapshot into the cellular and molecular events leading the plaque rupture. Chronic inflammation and apoptosis are important pathogenic features in atherosclerotic disease (4). Recently, a numbers of inflammatory and apoptotic protein families have been demonstrated in carotid plaques from symptomatic patients than from the asymptomat ic patients (5), implicating that those cellular and molecular processes probably converting a stable into an unstable plaque and eventually rupture. Indeed, pro-inflammatory cytokines (such as IL-1, TNF-α, and MCP-1) produced by macrophages and activated vascular smooth muscle cells (VSMCs) are involved in sustaining inflammation and the formation of atherosclerotic plaques in the arterial wall. The infiltration of inflammatory cells is also related to destabilization of the atherosclerotic lesion through the release of proteases (6). In addition, failed or delayed clearance of apoptotic cells can also result in chronic inflammation that characterising carotid stenosis (7). Nevertheless, the in vivo clea rance of apoptotic cells can lead to the release of anti-inflammatory cytokines. Thus, phagocytosis of apoptotic cells probably plays a pivotal role in the resolution of inflammation that may stabilize the atherosclerotic plaque (8). Interestingly, Annexin-1 is found to be a powerful phagocytotic protein and offering an anti-inflammatory signaling that dampening inflammatory responses and allowing safe post-apoptotic clearance of dead cells (9). But, its regulatory role in human atherosclerosis, particularly in carotid stenosis remains unknown. Indeed, Annexin-1 is structurally related, calcium-dependent, phospholipid-binding proteins that have been implicated in diverse cellular roles, including control of inflammatory responses, membrane fusion, cell differentiation and proliferation, phagocytosis, and interaction with cy toskeletal proteins (10). This protein is defined structurally by a conserved core domain containing four to eight repeats and by variable N-terminal regions. The conserved repeats account for the shared abilities of annexin to bind phospholipids in a calcium-dependent manner, whereas the specific N-terminal regions are probably responsible for different effects (11). Annexin-1 ha s been originally identified in leukocytes as a glucocorticoid-inducible protein that inhibits phospholipase A2, thus preventing the formation of pro-inflammatory eicosanoids. Human Annexin-1 and its N-terminal peptides (amino acids 1–188 and 2–26) mimic anti-inflammatory actions of glucocorticoids in many experimental models (12), and anti-annexin antibodies reverse glucocorticoid effects both in vitro and in vivo (13). Annexin-1 may also inhibit leukocyte migration by impairing neutrophil and monocyte adhesion to vascular endothelium and induce apoptosis of inflammatory cells. All these effects contribute to the potent anti-inflammatory action exerted by both Annexin-1 and its induced proteins (14). Given the potential anti-inflammatory effect of Annexin-1 that could stabilize the carotid plaque, we hypothesized that Annexin-1 would be present in a significantly larger amount in the atherosclerotic carotid plaques from asymptomatic patients than from symptomatic patients. Thus, its enhanced expression may be beneficial as endogenous defence property to the inflammatory stimul i that are released in the plaque. To test this hypothesis, carotid plaque specimens from both asymptomatic and symptomatic patients will be examined using molecular biological approaches. We expect this study can provide more biochemical information of the carotid plaques. Understanding the role and mechanism of the powerful anti-inflammatory actions of endogenous Annexin-1 compo unds can be a useful tool in the development of potential therapeutics in resolving atherosclerotic carotid stenosis diseases. Specific objectives (1) Determining the Annexin-1 mRNA and protein content in atherosclerotic plaques obtained from both asymptomatic and symptomatic patients with carotid stenosis. (2) Localizing the Annexin-1 immunohistochemically and (3) Investigating the relationship of expression of Annexin-1 and the vulnerability of patients with carotid stenosis, this may elucidate the role of Annexin-1 in carotid atherosclerosis relative to symptom status. References: 1. Gronholdt ML, Nordestgaard BG, Schroeder TV, Vorstrup S, Sillesen H. Ultrasoni echolucent carotid plaques predict future strokes. Circulation 2001, 104: 68-73. 2. Yadav JS, Wholey MH, Kuntz RE, Fayad P, Katzen BT, Mishkel GJ, Bajwa TK, Whitlow P, Strickman, NE, Jaff MR, Popma JJ, Snead DB,Cutlip DE, Firth BG, Ouriel K. Stenting and angioplasty with protection in patients at high risk for endarterectomy investigators. Protected carotid -artery stenting versus endarterectomy in high-risk patients. N Engl J Med 2004: 351: 1493-1501. 3. Rubio F,Martinez-Yelamos S, Cadona P, Krupinski J. Carotid endarterectomy: is it still the gold standard? Cerebrovasc Dis 2005; 20: 119-122. 4. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med 1999; 340:115-126. 5. Artese L, Ucchino S, Piattelli A, Piccirilli M, Perrotti V, Mezzetti A, Cipollone F. Factors associated with apoptosis in symptomatic and asymptomatic carotid atherosclerotic plaques. Int J Immunopathol Pharmacol 2005, 4: 645-653. 6. Loftus IM, Naylor AR, Goodall S, Crowther M, Tones L, Bell PR, Thompson MM. Increased matrix metalloproteinase-9 activity in unstable carotid plaques. A potential role in acute plaque disruption. Stroke 2000; 31: 40-47. 7. Mitra AK, Dhume AS, Agrawal DK, 2004. Vulnerable plaq ues: ticking of the time bomb. Can J Physiol Pharmacol 2004; 82: 860-871. 8. Mofidi R, Crotty TB, McCarthy P, Sheehan SJ, Mehigan D, Keaveny TV. Association between plaque instability, angiogenesis and symptomatic carotid occlusi ve disease. Br J Surg 2001; 88: 945-950. 9. Arur S, Uche UE, Rezaul K, Fong M, Scranton V, Cowan AE, Mohler W, Han DK. Annexin I is an endogenous ligand that mediates apoptotic cell engulfment. Dev Cel.l 2003; 4: 587-598. 10. Raynal P, Pollard HB. Annexins: the problem of asses sing the biological role for a gene family of multifunctional calcium- and phospholipid-binding proteins. Biochim. Biophys. Acta 1994; 1197: 63–93. 11. Rosengarth A, Gerke V, Luecke H. X-ray structure of full-length annexin 1 and implications for membrane aggregation. J Mol Biol 2001; 306: 489–498. 12. Yang Y, Leech M, Hutchinson P, Holdsworth SR, Morand EF. Antiinflammatory effect of lipocortin 1 in experimental arthritis. Inflammation 1997; 21; 13. Perretti M, Ahluwalia A, Harris JG, Harris HJ, Wheller SK, Flower RJ. Acute inflammatory response in the mouse: exacerbation by immunoneutralization of lipocortin 1. Br J Pharmacol 1996; 117: 1145–1154 . 14. Solito E, de Coupade C, Canaider S, Goulding NJ, Perretti M. Transfection of annexin 1 in monocytic cells produces a high degree of spontaneous and stimulated apoptosis associated with caspase-3 activation. Br J Pharmacol 2001; 133: 217–228.

Project Title:	5th European Meeting on Vascular Biology and Medicine Carotid Plaque Annexin-1 expression in human carotid artery stenosis and its relationship with Plaque Characteristics
Investigator(s):	Cheuk LY
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	09/2009

Abstract:

N/A

List of Research Outputs

Cheuk L.Y. and Cheng S.W.K. , Annexin A1 expression in atherosclerotic carotid plaq ues and its relationship with plaque characteristics, European Vascular Biology Conference, Marseille, France, 14-17 September 2009 .

Researcher : Cheung CKY

List of Research Outputs

Cheung C.K.Y. , Lo C.M. , Chan S.C. and Fan S.T. , Long-term follow up of hepatitis B virus-specific immune response in liver transplant patient receiving third-ge neration hepatitis B vaccine (Abstract), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 16(Suppl 1): S242.

Wang X. , Cheung C.K.Y. , Ng M.W. and Lo C.M. , Hematopoietic chimerism and potential hematopoietic stem cells in liver transplantation (Abstract), The 8th International Society for Stem Cell Resear ch Annual Meeting, San Francisco, U.S.A., June 2010 .

Researcher : Cheung MT

List of Research Outputs

Kwong A. , Ng E.K.O. , Law F.B.F. , Wong L.P., To M.Y., Cheung M.T. , Wong H.N. , Chan V.W., Kurian A., West D.W. , Ford J.M. and Ma E.S., High-resolution melting analysis for rapid screening of BRCA2 founder mutations in Southern Chinese breast cancer patients, Breast Cancer Research and Treatment . 2010, 122(2): 605-607.

Researcher : Cheung PFY

Project Title:	Characterize the functional role of granulin-epithelin precursor in fetal liver
Investigator(s):	Cheung PFY, Cheung ST
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	09/2008
Completion Date:	02/2010

Abstract:

Abstract: Liver performs diverse vital biological functions and its diseases are frequently associated with significant mortality and morbidity. A better understanding of the molecular basis of liver development is essential for the prevention and management of liver diseases. Granulin-epithelin precursor (GEP, also named progranulin, acrogranin, or PC-derived growth factor) is a novel pluripotent growth factor regulat ing development and tissue repair. It also contributes to carcinogenesis in various cancers including breast, ovarian and liver cancers. Our group previously showed that GEP was over-expressed in more than 70% of hepatocellular carcinoma (HCC). Besides, functional studies demonstr ated that GEP was crucial for HCC proliferation, invasion and tumorigenicity. Our pilot study demonstrated that GEP was abundantly expressed in normal fetal and neonatal liver, inactive in normal adult livers, and became reactivated in regenerating and cancerous livers. The current data therefore highly suggest that GEP is an oncofetal protein. In this study, we aim to inves tigate two main aspects: 1) To characterize the GEP-expressing cells and the regulatory mechanism for GEP expression in fetal livers. 2) To investigate the biological roles of GEP in fetal livers. This study will advance our knowledge on fetal liver development, thereby faci litating future applications of hepatocyte transplantation in the treatment of liver diseases, and providing valuable insights into the use of GEP as a therapeutic target in the treatment of liver cancer. Background and objectives: Liver is the largest internal organ in human body and it exhibits diverse biological functi ons including digestion, metabolism, production of various plasma proteins, glycogen storage, detoxification, and hematopoiesis during embryonic development. Liver diseases such as hepatitis, cirrhosis and liver cancer are devastating and frequently associated with significant morbidity and mortality. A better understanding of the molecular basis of embryonic liver development and the key regulatory protein(s) involved is importan t for the prevention and management of liver diseases. Granulin-epithelin precursor (GEP, also named progranulin, acrogranin, or PC-derived growth factor) is a novel pluripotent growth factor that plays crucial role in development and tissue repair (1, 2). It was found to regulate developmental events including cavitation, trophectodermal proliferation and male-specific neonatal hypothalamic differentiation (3-6). Besides, GEP was shown to promote tumor progression in various human cancers including breast, ovarian and liver cancers (7-9). Our group previously demonstrated that over 70% of human HCC revealed over-expression of GEP (9, 10). Besides, serum GEP levels were found to be higher in HCC patients than in normal subjects. Functional studies showed that GEP controlled cell proliferation, tumor invasion and tumorigenicity of HCC (9, 10). These biological roles corresponded to the clinical findings that GEP expression was associated with aggressive cancer features (9). Moreover, our group developed an anti-GEP monoclonal antibody that significantly inhibited the growth of established HCC (11), thereby proving that GEP was a key growth factor controlling the proliferation of liver cancer cells. Despite considerable interest in GEP over-expression in HCC, information for the exact time-frame of GEP expression and the underlying regulatory mechanism is still sca nt. It was reported that mouse fetal livers expressed mRNA of GEP, while adult livers in mouse were devoid of cells expressing GEP (5,6). In our pilot study, we showed that GEP protein was detected in mouse fetal liver at embryonic day 17.5 and neonatal liver at postnatal 2 weeks old (Fig. 1A); while GEP protein was undetectable in the liver of adult mouse at 16 weeks old. In huma n, we found that normal human fetal liver at 10 weeks old expressed GEP protein (Fig. 1B). Besides, we examined maternal serum collected from 30 normal pregnant women at different trimesters. The GEP level in the maternal serum was measured and compared with the level of alpha-fet oprotein (AFP), an oncofetal protein extensively used as serological marker for diagnosis of liver cancer. Results showed that serum GEP was detectable in every serum sample collected at all gestation periods and the serum GEP levels were significantly higher than healthy individu als (Fig. 2). In addition, both maternal serum AFP and GEP revealed gradually increasing levels during normal pregnancy (Fig. 2), indicating the importance of these two proteins in normal fetal development. In addition to fetal liver, liver regeneration is another non-malignant situation where the cells proliferate rapidly in response to a loss of liver mass or massive injury. Our preliminary data showed that GEP was express ed in the rapidly proliferating liver cells during liver regeneration, but it was undetectable after the rapid regenerative phase. In summary, the current data indicate for the first time that GEP is a human oncofetal protein that is expressed in normal fetal livers, normall y silent in adult livers, and reactivated in regenerative and cancerous livers. However, the exact regulatory mechanism(s) for GEP expression and its biological functions in liver development is still unknown. Therefore, we propose further comprehensive studies to delineate the mechanism(s) of GEP activity in controlling fetal liver development. There are two main objectives in the proposed study: 1) To characterize the GEP-expressing cells and the regulatory mechanism(s) for GEP expression in fetal livers. The properties of GEP-expressing cells will be characterized and the signaling mechanism(s) responsible for regulating GEP expression will be studied in fetal liver cells. 2) To investigate the biological roles of GEP in fetal livers. The effects of GEP stimulation and depletion on fetal liver cells will be studied and the underlying signaling pathway(s) involved will be characterized. Reference: 1. He Z et al. (2003) Nature Medicine 9(2):225-229. 2. He Z et al. (2003) Journal of Molecular Medicine 81(10):600-612. 3. Díaz-Cueto L et al. (2000) Developmental Biology 217(2):406-418. 4. Xu K et al. (2007) Journal of Biology Chemistry 282(15) :11347-11355. 5. Daniel R et al. (2000) Journal of Histochemistry and Cytochemistry 48(7):999-1009. 6. Daniel R et al. (2003) Developmental Dynanmics 227(4):593-599. 7. Jones MB et al. (2003) Clinical Cancer Research 9(1):44 -51. 8. Serrero G et al. (2003) Human Pathology 34(11):1148-1154. 9. Cheung ST et al. (2004) Clinical Cancer Research 10(22) :7629-7636. 10. Cheung ST et al. (2006) Oncology Reports 15(6):1507-1511. 11. Ho JC et al. (2008) Hepatology 47(5):1524-1532.

Project Title:	101st Annual Meeting of the American Association for Cancer Research Granulin-epithelin precursor (GEP) is an oncofetal protein involved in fetal liver development and liver cancer
Investigator(s):	Cheung PFY
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	04/2010
Completion Date:	04/2010

Abstract:

N/A

List of Research Outputs

Cheung P.F.Y. and Cheung S.T. , Characterize the role of granulin-epithelin precursor in fetal liver development and hepatocellular carcinoma (Oral and Poster Presentation), The 16th Hong Kong International Cancer Congress and The 6th Annual Meeting Centre for Cancer Research, Hong Kong, 4-6 November 2009 .

Cheung P.F.Y. and Cheung S.T. , Granulin-epithelin precursor (GEP) is an oncofetal protein involved in fetal liver development and liver cancer, The 101st Annual Meeting of the American Association for Cancer Research, Washington, DC, U.S.A., 17-21 April 2010. Proceedings of the AACR . 2010, 51: 4246.

Wong C.L. , Cheung P.F.Y. and Cheung S.T. , Granulin-epithelin precursor modulates chemo-resistance in liver cancer, The 101st Annual Meeting of the American Association for Cancer Research, Washington, DC, U.S.A., 17-21 April 2010. Proceedings of the AACR . 2010, 51: 2556.

Researcher : Cheung PSY

List of Research Outputs

Chan S.W.W. , Cheung P.S.Y. , Lee J.F.Y., Fung J.T.K., Patil N.G. and Kwok S.P.Y. , Women surgeons in Hong Kong, Surgical Practice . Hong Kong, College of Surgeons of Hong Kong, 2010, 14 (1): 2-7.

Researcher : Cheung SOF

List of Research Outputs

Wong K.K.Y. , Cheung S.O.F. , Huang L. , Niu J. , Tao C. , Ho C.M. , Che C.M. and Tam P.K.H. , Further evidence of the anti-inflammatory effects of silver nanoparticles, ChemMedChem . 2009, 4(7): 1129-1135.

Researcher : Cheung ST

Project Title:	Combine targeted therapy with chemotherapy for liver cancer treatment
Investigator(s):	Cheung ST, Ho JCY, Fan ST
Department:	Surgery
Source(s) of Funding:	The Hong Kong Anti-Cancer Society (HKACS) - General Award
Start Date:	10/2007

Abstract:

To examine the functional effect of anti-GEP mAb in combination with chemotoxic agent; to evaluate the treatment efficacy of anti-GEP mAb treatment in combin ation with chemotoxic agent in mouse model.

Project Title:	Sensitize cancer cells to chemothe rapy
Investigator(s):	Cheung ST
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2008
Completion Date:	01/2010

Abstract:

Abstract Hepatocellular carcinoma (HCC) is the fifth common cancer and the third cancer killer in the world, with about half a million individuals died from HCC annually. The disease is frequently diagnosed at an advanced stage and thus precludes curative surgical treatment. The majority of HCC patients have advanced cirrhosis which limited the treatment option, and chemothera py has shown marginal efficacy and is accompanied with severe side-effects [1,2]. A new therapeutic strategy is essential to sensitize cancer cells to chemotoxic agents. We hypothesize that targeted therapy will enhance the sensitivity of HCC cells to chemotoxic agent. In a pilot study, we demonstrated that GEP targeted therapy can sensitize cancer cells with enhanced treatment response to chemodrug cisplatin. We thus propose furt her studies to delineate their actions. Aim 1: To evaluate the response of GEP targeted therapy in chemo-sensitive and chemo-resistant HCC cells. Aim 2: To evaluate the mechanism involved in chemoresponse enhancement through targeting GEP. Background Granulin-epithelin precursor (GEP) is shown to be a potential therapeutic target for HCC treatment in our earlier studies [3-6]. We firstly identified GEP overexpression through the genomic expression profiling studies using the microarray approach [3-4]. The GEP expression on mRNA level [3-4] was subseque ntly validated on protein level in more than 200 HCCs and liver tissue adjacent to tumor samples, and confirmed that more than 70% of HCC tissues revealed GEP overexpression [5-6]. We showed that GEP controls HCC cells proliferati on, invasion and tumorigenicity [5]. These biological roles correspond to the clinical findings that expression of GEP is associated with aggressive cancer features including large tumors, venous infiltration (micrometastasis) and early recurrence after curative surgery [5]. To examine the therapeutic potential of GEP targeted therapy, the anti-GEP monoclonal antibody would be needed. There is no commercial source of such, and we then developed the anti-GEP monoclonal antibody (mAb) A23. We demonstrate d that A23 inhibited the growth of hepatoma cells Hep3B and HepG2, but revealed no significant effect on normal liver cells MIHA. In the nude mice model transplanted with human HCC cells Hep3B, anti-GEP mAb decreased the serum GEP level and inhibited the growth of established tumors in a dose-dependent manner (Figure 1). Increasing evidence has revealed the role of GEP in chemo-resistance [7-9]. We therefore hypothesize that GEP targeted therapy will enhance the sensitivity of HCC cells to chemotoxic agents. We showed that GEP targeted therapy can enhan ce the apoptotic effect induced by cisplatin treatment, while anti-GEP monoclonal antibody A23 alone did not induce cell apoptosis in human HCC cells Hep3B (Figure 2). Nonetheless, the mechanism by which GEP targeted therapy in sensitizing HCC cells to chemo-drugs is unknown. We then examined whether combination therapy is effective in in vivo system with the nude mouse model. In a pilot study on human HCC cells Hep3B in mouse model, we demonstrated GEP targeted therapy in combination with chemotoxic agent can further enhance the treatment efficacy (Figure 3). We propose further comprehensive studies to delineate the role of anti-GEP therapy in sensitizing HCC cells to chemotoxic agents. Objectives 1. To evaluate the response of GEP targeted therapy in chemo-sensitive and chemo-resistant cancer cells. 2. To understand the mechanism involved in sensitizing cancer cells to chemo-toxic agents through targeting GEP.

Project Title:	Circulating cancer biomarkers in liver cancer patients undergoing liver transplantation
Investigator(s):	Cheung ST, Zheng SS, Fan ST
Department:	Surgery
Source(s) of Funding:	NSFC/RGC Joint Research Scheme
Start Date:	03/2008

Abstract:

To carry out in vitro and in vivo experiments to examine the association of cancer loading in relation to the quantitative biomarker data obtained in the circulation; to perform quantitative measurement of the circulating cancerous biomarkers in liver cancer patients who have undergone liver transplan tation.

Project Title:	Liver cancer stem cell and chemo-resistance
Investigator(s):	Cheung ST
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2009

Abstract:

Abstract Primary liver cancer, hepatocellular carcinoma (HCC), is the second cancer killer in China. Surgical resection is the mainstay for curative trea tment. However, the disease is frequently diagnosed at an advanced stage and thus precludes curative surgical treatment. Chemotherapy has been widely used to treat unresectable HCC but with marginal efficacy. There are increasing links between chemo-resistance and cancer stem cells. Cancer stem cells are capable of self-renewal and differentiation, and serial propagation of their original tumor phenotype in animal models. We hypothesize that specific targeting of the cancer stem cells could be a strategy to enhance the treatment response of chemotherapy. Liver cancer stem cells have been reported with CD133 and other markers to be the prominent surface markers. In a pilot study, we demonstrated that there are CD133(+)GEP(+) HCC cells by dual-color flow cytometry analysis. Furthermore, GEP over-expressi on conferred chemo-resistance. We therefore propose further studies to delineate the role of GEP in liver cancer stem cell and in chemo-resistance. Aim 1: To evaluate the treatment response of CD133(+)GEP(+) population on chemo-therapeutic agent, and in combination with GEP targeted therapy. Aim 2: To define the cancer stem cell population by characterizing the CD133(+)GEP(+) population with additional markers. Background Hepatocellular carcinoma (HCC), the commonest form of primary liver cancer, is the third leading cancer killer with more than half a million individuals died globally each year [1]. In China, liver cancer is the second major cause of cancer death [2]. Given its prevalence, there is an urgent need for alternative therapeutic approach es in addition to conventional clinical management to improve patient survival. Surgical resection, in the form of partial hepatectomy or liver transplantation, is the mainstay for curative treatment for liver cancer patients [3]. However, the disease is frequently diagnosed at an advanced stage and so precludes curative surgical treatment. A number of reasons including large tumor burden, co-existing liver disease, or extrahepatic metastasis can result in unresectability. Treatment options for unresectable liver cancer include systemic and loco-regional therapy, but loco-regional therapy is applicable to only a few highly selected patients. Thus, for the majority of patients with unresectable liver cancer, systemic chemotherapy remains the main treatment option. However, low response rate (less then 20%) have been reported for single agent or combination chemotherapy [4-5]. A new therapeutic strategy is essential to sensitize cancer cells to chemo-therapeutic agents. Cancer stem cells are capable of self-renewal and differentiation, and serial propagation of their original tumor phenotype in animal models [6]. Specific targeti ng of cancer stem cells could be a strategy to eradicate cancers that are resistant to chemo-therapeutic agents. CD133 has been reported to be a prominent marker for liver cancer stem cells [7-8]. The CD133(+) tumor cell population has been reported to associate with chemo-resista nce in melanoma and HCC [6,8]. Notably, conventional cancer stem cell theory has suggested that cancer stem cell should constitute a minority population in the tumor bulk. However, expression of CD133 was detected at levels as high as 65% of the population [9]. Therefore, further characterization of the CD133 population will be necessary to better define and enrich the cancer stem cell population. GEP controls proliferation and invasion, and as molecular target for therapeutic development Granulin-epithelin precursor (GEP) is a novel growth factor. We firstly identified GEP overexpression through the genomic expression profiling studies using the microarray approach [10-11]. Over 70% of the HCC tissues revealed GEP overexpression [12-13], and GEP controlled HCC cells proliferation, invasion and tumorig enicity [12]. To examine the therapeutic potential of GEP targeted therapy, the anti-GEP monoclonal antibody (mAb) was developed. We demonstrated that the anti-GEP mAb inhibited the growth of hepatoma cells Hep3B and HepG2, but re vealed no significant effect on normal liver cells MIHA. In the nude mice model transplanted with human HCC cells Hep3B, anti-GEP mAb decreased the serum GEP level and inhibited the growth of established tumors in a dose-dependent manner [14]. We showed that GEP is a therapeutic target for HCC treatment. GEP conferred chemo-resistance Increasing evidence has revealed the role of GEP in drug-resistance in a number of cancer types [15-17]. However, the role of GEP in HCC chemo-resistance has not been examined. We then investigated if modulate GEP level will affect chemo-resistance. Hepatoma cells Hep3B were transfected with the full-length GEP cDNA subcloned into the expression vector. The Hep3B GEP transfectants demonstrated one-fold of GEP overexpression compared to the Hep3B parental cells. The Hep3B GEP transfectants demonstrated an increment in the resistance to doxorubicin by more than two-fold compared with its parental cells as determined using the MTT assay. The IC50 values determined on the Hep3B GEP transfectants and its parental cells was 0.33 ug/ml and 0.11 ug/ml, respectively, at day 4. We showed that over-expression of GEP conferred chemo-resistance. GEP targeted therapy further enhanced the apoptotic effect induced by chemo-therapeuti c agent Anti-GEP mAb treatment alone (100 ug/ml) for 24 hour demonstrated no effect on cell apoptosis compared to the control treatment (saline control or non-specific mouse IgG control) as examined by Flow Cytometry. The in vitro observation was consistent with our earlier in vivo study that anti-GEP mAb treatment on Hep3B xenograft in mouse model only revealed decreased prolif eration but no notable change on apoptosis as determined using TUNEL staining [14]. Nonetheless, combination of anti-GEP mAb (100 ug/ml) with cisplatin (4 ug/ml) demonstrated a synergistic effect on induction of apoptosis (21.8%) compared to single agent treatment with anti-GEP mAb or cisplatin (0.1% and 9.2%, respectively). We demonstrated that anti-GEP mAb enhanced the apoptotic effect induced by chemo-therapeutic agent. GEP and CD133 co-expression Expression of GEP or CD133, or co-expression of GEP with CD133 was performed by single- or dual-color flow cytometry. In a pilot co-expression analysis, the majority of GEP(+) cells were CD133(+), while not all CD133(+) cells were GEP(+). As GEP also controls growth and chemo-resistance, we thus hypothesize that GEP plays an important role in liver cancer stem cell. We therefore propose further studies to delineate the role of GEP in liver cancer stem cell and in chemo-resistance. Objectives 1. To evaluate the treatment response of CD133(+)GEP(+) population on chemo-therapeutic agent, and in combination with GEP targeted therapy. 2. To define the cancer stem cell population by characterizing the CD133(+)GEP(+) population with additional markers.

Project Title:	To further characterize GEP as a potential antibody target for HCC
Investigator(s):	Cheung ST
Department:	Surgery
Source(s) of Funding:	Pfizer - General Award
Start Date:	10/2009
Completion Date:	09/2011

Abstract:

To further characterize GEP as a potential antibody target for HCC

Project Title:	To test putative target of HCC recurrence using locked nucleic acids (LNA) as a tool - GEP
Investigator(s):	Cheung ST
Department:	Surgery
Source(s) of Funding:	Pfizer - General Award
Start Date:	01/2010

Abstract:

To test putative target of HCC recurrence using locked nucleic acids (LNA) as a tool - GEP

Project Title:	Characterize the chemo-resistance cells for stem cell properties in liver cancer
Investigator(s):	Cheung ST
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2010

Abstract:

Abstract Primary liver cancer is the third leading cancer killer in the world. The disease is frequently diagnosed in advanced stage and thus precludes curative surgical treatment. Chemotherapy remains the principle alternative for treating unresectable liver cancer. However, single agent or combination chemotherapy has shown marginal efficacy. The multi-drug resistance (MDR) phenotype renders the cancer cells insensitive to chemo-therapeutic agents. The MDR phenotype is commonly mediated through over-expression of adenosine triphosp hate (ATP)-binding cassette (ABC) drug transporters. Notably, the key genes that regulate chemo-resistance in clinical situation have yet to be identified for liver cancer. A new treatment strategy is essential to render the cancer cells sensitive to chemo-therapeutic agents. Our lab is the first group to demonstrate the therapeutic approach of GEP targeted therapy in human cancer using the home-made GEP monoclonal antibody on animal model. Nonetheless, targeted therapy alone in clinical settings, in general, is not sufficient to cure solid tumors. Recently, we showed that over-expression of GEP would confer chemo-resistance in liver cancer cells. Furth ermore, GEP targeted therapy enhanced the apoptotic effect of chemo-therapeutic agents in the parental cells and the chemo-resistant populations. Thus, combination of GEP targeted therapy with chemo-therapy could be a rational approach to enhance treatment response, which would also be applicable for the difficult-to-treat chemo-resistant cancer cells. The mechanism of chemo-resistance will need to be elucidated to better understand the signaling in chemo-response. We observed that GEP modulated the expression of ABCB5, but not ABCB1, ABCC1 or ABCC2, in liver cancer cells. Furthermore, in chemo-resistance liver cancer cells, ABCB5 expression levels were significantly higher. Notably, in melanoma, ABCB5 populations have shown to be tumor-initiating cells and related to chemo-resistance. We therefore propose further studies to examine the relationship of chemo-resistance and cancer stem-cell. Background The contribution of tumorigenic stem cells to haematopoietic cancers has been established for some time, and cells possessing stem-cell properties have been described in several solid tumors [1]. Although chemotherapeutic agents would kill most of the tumor cells, it is belie ved to leave a small population of tumor stem cell behind, which might be an important mechanism of drug resistance. For example, the ABC transporters have been shown to protect cancer stem cells from chemotherapy, e.g. ABCB1 in glioblastoma [2], and ABCB5 in melanoma [3-4]. Objectives The present study has two specific objectives. 1: To characterize the chemo-resistant liver cancer cells. Genomic and proteomic approach will be used to examine the differential difference on mRNA and protein expression of chemo-resistant liver cancer cells. 2: To examine the expression and function of the genes related to chemo-resistance. The genes identified in Part 1 will be further examined by independent research platform for expression and protein localization, co-expression with stem cell markers, and functional studies to delineate the role in chemo-resistance. The study will help to understand chemo-resistance, and provide the foundation for rational drug design for combination treatment.

Project Title:	AACR 101st Annual Meeting 2010 Interacting protein of granulin-epithelin precursor in liver cancer
Investigator(s):	Cheung ST
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	04/2010
Completion Date:	04/2010

Abstract:

N/A

List of Research Outputs

Chen X., Jorgenson E. and Cheung S.T. , New tools for functional genomic analysis (Invited Review), Drug Discovery Today . 2009, 14(15-16): 754-760.

Cheung P.F.Y. and Cheung S.T. , Characterize the role of granulin-epithelin precursor in fetal liver development and hepatocellular carcinoma (Oral and Poster Presentation), The 16th Hong Kong International Cancer Congress and The 6th Annual Meeting Centre for Cancer Research, Hong Kong, 4-6 November 2009 .

Cheung P.F.Y. and Cheung S.T. , Granulin-epithelin precursor (GEP) is an oncofetal protein involved in fetal liver development and liver cancer, The 101st Annual Meeting of the American Association for Cancer Research, Washington, DC, U.S.A., 17-21 April 2010. Proceedings of the AACR . 2010, 51: 4246.

Cheung S.T. , Invited Reviewer, Research Grants Council, Hong Kong . 2010.

Cheung S.T. , Member of Editorial Board (2009 - present), Liver Cancer Review Letters . 2010.

Cheung S.T. , Member of Editorial Board (Janurary 2006 - present), Chinese Journal of Medicine . 2010.

Cheung S.T. , Project to further characterize GEP as a potential antibody target for HCC (January 2010 - January 2012) (Amount funded: 3,450,920, Project code: 21005954), Pfizer Collaborative Research Grant . 2010.

Cheung S.T. , Project to test putative target of HCC recurrence using locked nucleic acids (LNA) as a tool - GEP (October 2009 - September 2011) (Amount funded: 3,450,920, Project code: 21005955), Pfizer Collaborative Research Grant . 2009.

Cheung S.T. , Reviewer, Applied Genomics and Proteomics . 2010.

Cheung S.T. , Reviewer, Archives of Biochemistry and Biophysics . 2010.

Cheung S.T. , Reviewer, Asian Journal of Surgery . 2010.

Cheung S.T. , Reviewer, BMC Cancer . 2010.

Cheung S.T. , Reviewer, British Journal of Cancer . 2010.

Cheung S.T. , Reviewer, Cancer Epidemiology, Biomarkers and Prevention . 2010.

Cheung S.T. , Reviewer, Carcinogenesis . 2010.

Cheung S.T. , Reviewer, Cell Proliferation . 2010.

Cheung S.T. , Reviewer, Digestive Surgery . 2010.

Cheung S.T. , Reviewer, International Journal of Cancer . 2010.

Cheung S.T. , Reviewer, Journal of Gastroenterology and Hepatology . 2010.

Cheung S.T. , Reviewer, Journal of Hepato-Biliary-Pancreatic Surgery . 2010.

Cheung S.T. , Reviewer, Journal of Pathology . 2010.

Cheung S.T. , Reviewer, Liver International . 2010.

Cheung S.T. , Reviewer, PLoS ONE . 2010.

Cheung S.T. , Reviewer, Singapore Medical Journal . 2010.

Lam C.Y. , Poon T.C.W. and Cheung S.T. , Identification of novel interacting partner of granulin-epithelin precursor in hepatocellular carcinoma (Poster Presentation), The 16th Hong Kong International Cancer Congress and The 6th Annual Meeting Centre for Cancer Research, Hong Kong, 4-6 November 2009 .

Lam C.Y. , Poon T.C.W., Cheng C.K.C. and Cheung S.T. , Interacting protein of granulin-epithelin precursor in liver cancer, The 101st Annual Meeting of the American Associat ion for Cancer Research, Washington, DC, U.S.A., 17-21 April 2010. Proceedings of the AACR . 2010, 51: 3130.

Wong C.L. , Cheung P.F.Y. and Cheung S.T. , Granulin-epithelin precursor modulates chemo-resistance in liver cancer, The 101st Annual Meeting of the American Association for Cancer Research, Washington, DC, U.S.A., 17-21 April 2010. Proceedings of the AACR . 2010, 51: 2556.

Wong C.L. and Cheung S.T. , The role of granulin-epithelin precursor in liver cancer chemo-resistance (Poster Presentation), The 16th Hong Kong International Cancer Congress and The 6th Annual Meeting Centre for Cancer Research, Hong Kong, 4-6 November 2009 .

Xu C.R., Lee S., Ho C., Bommi P., Huang S.A., Cheung S.T. , Dimri G.P. and Chen X., Bmi1 functions as an oncogene independent of Ink4A/Arf repression in hepatic carcinogenesis, Molecular Cancer Research . 2009, 7(12): 1937-1945.

Researcher : Cheung TT

List of Research Outputs

Cheung T.T. , Ng K.K.C. , Poon R.T.P. , Chan S.C. , Lo C.M. and Fan S.T. , A case of laparoscopic hepatectomy for recurrent hepatocellular carcinoma, World Journal of Gastroenterology . 2010, 16(4): 526-530.

Cheung T.T. , Ng K.K.C. , Chok K.S.H. , Chan S.C. , Poon R.T.P. , Lo C.M. and Fan S.T. , Combined resection and radiofrequency ablation for multifocal hepatocellular carcinoma: prognosis and outcomes, World Journal of Gastroenterology . 2010, 16(24): 3056-3062.

Cheung T.T. , Suen D.T.K. and Kwong A. , Is sentinel lymph node biopsy after neoadjuvant chemotherapy feasible in Chinese patients with invasive breast cancers ?, ANZ Journal of Surgery . 2009, 79(10): 719-723.

Cheung T.T. , Peer Reviewer, Surgical Practice . 2010.

Cheung T.T. , Ng K.K.C. , Poon R.T.P. and Fan S.T. , Tolerance of radiofrequency ablation by patients of hepatocellular carcinoma, Journal of Hepato-biliary-pancreatic Surgery . 2009, 16(5): 655-660.

Chok K.S.H. , Ng K.K.C. , Cheung T.T. , Yuen W.K. , Poon R.T.P. , Lo C.M. and Fan S.T. , An update on long-term outcome of curative hepatic resection for hepatocholangiocarcinoma, World Journal of Surgery . 2009, 33(9): 1916-1921.

Chok K.S.H. , Chu F.S.K. , Cheung T.T. , Lam V.W.T. , Yuen W.K. , Ng K.K.C. , Chan S.C. , Poon R.T.P. , Yeung C. , Lo C.M. and Fan S.T. , Results of percutaneous transhepatic cholecystostomy for high surgical risk patients with acute cholecystitis, ANZ Journal of Surgery . 2010, 80(4): 280-283.

Dai W.C., Ng K.K.C. , Chok K.S.H. , Cheung T.T. , Poon R.T.P. and Fan S.T. , Radiofrequency ablation for controlling iatrogenic splenic injury (Letter to the Editor), International Journal of Colorectal Diseases . 2010, 25(5): 667-668.

Ng K.K.C. , Poon R.T.P. , Cheung T.T. , Chu F.S.K. , Tso W.K. and Fan S.T. , High efficacy of high intensity focused ultrasound without transarterial embolization for hepatocellular carcinoma (Poster Presentation), International Liver Cancer Association 3rd Annual Conference, Milan, Italy, 4 - 6 September 2009 .

Ng K.K.C. , Poon R.T.P. , Chok K.S.H. , Cheung T.T. , Tung H., Chu F.S.K. , Tso W.K. , Yu W.C. and Fan S.T. , High efficacy of high-intensity focused ultrasound without transarterial embolization for hepatocellular carcinoma - Hong Kong experience (Abstract), The 1st International Summit of Noninvasive Ultrasound Treatment, Chongqing, China, 22-23 October 2009 .

Ng K.K.C. , Chan S.C. , Chok K.S.H. , Cheung T.T. , Chan A.C.Y. , Lo C.M. and Fan S.T. , Primary versus salvage liver transplantation for hepatocel lular carcinoma within Milan criteria - a single center experience (Abstract and Poster Presentation), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S254.

Yau T.C.C. , Yao T.J. , Chan P., Epstein R. , Ng K.K.C. , Chok K.S.H. , Cheung T.T. , Fan S.T. and Poon R.T.P. , The outcomes of elderly patients with hepatocellular carcinoma treated with transarterial chemoembolization, Cancer . 2009, 115(23): 5507-5515.

Researcher : Chiu SW

List of Research Outputs

Li X. , Cheng L.C. , Cheung Y.F. , Lun K.S. , Chau A.K.T. and Chiu S.W. , Management of symptomatic congenital tracheal stenosis in neonates and infants by slide tracheoplasty: a 7-year single institution experience, European Journal of Cardio-thoracic Surgery . 2010, 38: 609-614.

Researcher : Choi HK

List of Research Outputs

Choi H.K. , Law W.L. and Poon J.T.C. , The optimal number of lymph nodes examined in stage II colorectal cancer and its impact of on outcomes, BMC Cancer . 2010, 10: 267.

Law W.L. , Poon J.T.C. , Fan J.K.M. , Lo O.S.H., Wei R. and Choi H.K. , Comparison of outcomes following resection of right-sided and left-sided colon cancer, International Surgical Week 2009, Adelaide, Australia , 6-10 September 2009 .

Researcher : Chok KSH

List of Research Outputs

Chan S.C. , Lo C.M. , Ng K.K.C. , Chok K.S.H. , Yong B.H. and Fan S.T. , Portal inflow and pressure changes in right liver living donor liver transplantation including middle hepatic vein (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S92.

Chan S.C. , Lo C.M. , Ng K.K.C. , Chok K.S.H. and Fan S.T. , Simplifying hepatic venous outflow reconstruction in sequential living donor liver transplantation, Liver Transplantation . 2009, 15(11): 1514-1518.

Chan S.C. , Lo C.M. , Wong Y. , Ng K.K.C. , Chok K.S.H. and Fan S.T. , Validating graft and standard liver size predictions in right liver living donor liver transplantation (Abstract), The 15th Annual International Congress of the Internat ional Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S247.

Cheung T.T. , Ng K.K.C. , Chok K.S.H. , Chan S.C. , Poon R.T.P. , Lo C.M. and Fan S.T. , Combined resection and radiofrequency ablation for multifocal hepatocellular carcinoma: prognosis and outcomes, World Journal of Gastroenterology . 2010, 16(24): 3056-3062.

Chok K.S.H. , Ng K.K.C. , Cheung T.T. , Yuen W.K. , Poon R.T.P. , Lo C.M. and Fan S.T. , An update on long-term outcome of curative hepatic resection for hepatocholangiocarcinoma, World Journal of Surgery . 2009, 33(9): 1916-1921.

Chok K.S.H. , Bile duct anastomotic stricture in adult-to-adult right lobe living donor liver transplantation (Oral Presentation), The 16th Annual International Congress of International Liver Transplantation Society, Hong Kong, China, 16-19 June 2010 .

Chok K.S.H. , Lo C.M. , Ng K.K.C. and Chan S.C. , Patients with preoperative hepatorenal syndrome (HRS) have comparable long-term outcomes after live-donor liver transplantation (LDLT) (Abstract), The 15th Annual International Congress of the Int ernational Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): S207.

Chok K.S.H. , Chu F.S.K. , Cheung T.T. , Lam V.W.T. , Yuen W.K. , Ng K.K.C. , Chan S.C. , Poon R.T.P. , Yeung C. , Lo C.M. and Fan S.T. , Results of percutaneous transhepatic cholecystostomy for high surgical risk patients with acute cholecystitis , ANZ Journal of Surgery . 2010, 80(4): 280-283.

Chok K.S.H. , Reviewer, British Journal of Surgery . 2010.

Chok K.S.H. , Reviewer, World Journal of Surgical Oncology . 2010.

Dai W.C., Ng K.K.C. , Chok K.S.H. , Cheung T.T. , Poon R.T.P. and Fan S.T. , Radiofrequency ablation for controlling iatrogenic splenic injury (Letter to the Editor), International Journal of Colorectal Diseases . 2010, 25(5): 667-668.

Ng K.K.C. , Poon R.T.P. , Chok K.S.H. , Cheung T.T. , Tung H., Chu F.S.K. , Tso W.K. , Yu W.C. and Fan S.T. , High efficacy of high-intensity focused ultrasound without transarterial embolization for hepatocellular carcinoma - Hong Kong experience (Abstract), The 1st International Summit of Noninvasive Ultrasound Treatment, Chongqing, China, 22-23 October 2009 .

Ng K.K.C. , Chan S.C. , Chok K.S.H. , Cheung T.T. , Chan A.C.Y. , Lo C.M. and Fan S.T. , Primary versus salvage liver transplantation for hepatocellular carcinoma within Milan criteria - a single center experience (Abstract and Poster Presentation), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S254.

Sharr W.W. , Chok K.S.H. , Ng K.K.C. , Chan S.C. , Lo C.M. and Fan S.T. , Impact of donor age on right lobe living donor liver transplantation in a single centre (Abstract), The 15th Annual International Congress of the Internat ional Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S92.

Yau T.C.C. , Yao T.J. , Chan P., Epstein R. , Ng K.K.C. , Chok K.S.H. , Cheung T.T. , Fan S.T. and Poon R.T.P. , The outcomes of elderly patients with hepatocellular carcinoma treated with transarterial chemoembolization, Cancer . 2009, 115(23): 5507-5515.

Researcher : Chow LWC

Project Title:	Chemosensitivity study using a breast cancer cell line
Investigator(s):	Chow LWC
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	05/1996

Abstract:

To test the effect of combination chemotherapy on cell growth in a breast cancer cell line.

Researcher : Chu ATW

List of Research Outputs

Ho J.W.C. , Ho M.Y. , Chu A.T.W. and Chan M.S. , Hopefulness predicts residence after hereditary colorectal cancer genetic testing in Hong Kong Chinese: results of a longitudinal study (Abstract and proceeding), National Cancer Research Institute Cancer Conference, Birmingham, U.K., 4-7 October 2009 .

Ho M.Y. , Ho J.W.C. , Bonanno G.A., Chu A.T.W. and Chan M.S. , Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study, BMC Cancer . 2010, 10: 279.

Researcher : Chu KM

List of Research Outputs

Chen W.Y.W. , Hu X. , Liang C.T., Wong M.L.Y. , Au W.Y. , Wong K.Y. , Choi W.L. , Wan T.S.K. , Chu K.M. , Chim J.C.S. , Chan L.C. , Kwong Y.L. , Liang R.H.S. and Srivastava G. , Molecular features and functional consequence of CD44 activation by a novel recurrent IGH translocation t(11;14) (p13;q32) in mature B-cell lymphoid neoplasm., 101st Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2010. . 2010.

Chu K.M. , Associate Member, Hereditary Gastrointestinal Cancer Registry . 2010.

Chu K.M. , Chairman for the Session "Optimizing GIST therapy", The Novartis Oncology AP Summit 2010, Hong Kong, 10-11 July 2010 . 2010.

Chu K.M. , Chairman for the Session on "Saturday afternoon at the movies", The Hong Kong Surgical Forum, Hong Kong, 9 January 2010 . 2010.

Chu K.M. , Chief External Examiner in Surgery, Final Year Examination (Professional III Examination ), University Putra Malaysia, Malaysia, 25-29 May 2009 . 2009.

Chu K.M. , Clinical management of GIST in Hong Kong, The Novartis Oncology AP Summit 2010, Hong Kong, 10-11 July 2010 . 2010.

Chu K.M. , Council Member, Gerson Lehrman Group's Council of Healthcare Advis ors, Gerson Lehrman Group, New York, U.S.A . 2010.

Chu K.M. , Council Member, Hong Kong Society of Upper Gastrointestinal Surgeons, Hong Kong . 2010.

Chu K.M. , Council Member, The Federation of Medical Societies of Hong Kong, Hong Kong . 2010.

Chu K.M. , Current management of gastric stromal tumour, International College of Surgeons 2009 Beijing Conference, Beijing, China, 13-16 November 2009 . 2009.

Chu K.M. , Current status of laparoscopic gastrectomy for cancer, International College of Surgeons 2009 Beijing Conference, Beijing, China, 13-16 November 2009 . 2009.

Chu K.M. , Current surgical treatment for gastric cancer, The Gastric Cancer Symposium, Hong Kong, 26 June 2010 . 2010.

Chu K.M. , Deputy Chairman, Institutional Review Board of The University of Hong Kong / Hospital Authority Hong Kong West Cluster , Hong Kong . 2010.

Chu K.M. , Director, Integrated Endoscopy Centre, Hospital Authority Hong Kong West Cluster, Queen Mary Hospital, Hong Kong . 2010.

Chu K.M. , Director, Master Workshop on Gastric Surgery, The University of Hong Kong, Hong Kong, 5-6 December 2009 . 2009.

Chu K.M. , Examiner, MHKICBSC Part 3 Examination, Hong Kong Intercollegiate Board of Surgical Colleges, Hong Kong, 16 March 2010 . 2010.

Chu K.M. , Examiner, MHKICBSC Part 3 Examination, Hong Kong Intercollegiate Board of Surgical Colleges, Hong Kong, 17 September 2009 . 2009.

Chu K.M. , Expert Panel in Surgery for HA's Complaint & Potential Medicolegal Cases, Hospital Authority, Hong Kong . 2010.

Chu K.M. , Expert Reviewer, UICC Fellowships Programme, International Union Against Cancer (UICC), Geneva, Switzerland . 2010.

Chu K.M. , External Advisor / Reviewer, Quality Education Fund Projects, Quality Education Fund (QEF), Hong Kong . 2010.

Chu K.M. , Gastric cancer, Integrated Professional Oncology, Palliative & Elderly Care Training Course for Nurses, The Hong Kong Anti-canc er Society, Hong Kong, 8 October 2009 . 2009.

Chu K.M. , Gastric cancer, Integrated professional Oncology, Palliative & Elderly care Training Course for Nurses, The Hong Kong Anti-cancer Society, Hong Kong, 2 April 2009 . 2009.

Chu K.M. , Gastric surgery, Summer Broadening Programme, Faculty of Medicine, The University of Hong Kong, Hong Kong, 23 July 2010 . 2010.

Chu K.M. , Honorary Consultant (Gastrointestinal Surgery), Tung Wah Hospital, Hong Kong . 2010.

Chu K.M. , Honorary Consultant in Surgery, Hong Kong Sanatorium & Hospital, Hong Kong . 2010.

Chu K.M. , Honorary Consultant, Department of Surgery, Queen Mary Hospital, Hong Kong . 2010.

Chu K.M. , Internal Examiner for PhD candidate in Medicine, (Miss Camy Fung-Yu Huang) (Pathogenetic aspects of Helicobacter pylori infection in gastric cancer: a study into the role of inflammatory cytokines and gene methylation), Faculty of Medicine, The University of Hong Kong . 2009.

Chu K.M. , Internal Examiner for PhD candidate in Surgery, (Mr Laurence Rui Zhu) (Liver-Intestine Cadherin CDH17 in Hepatocellular Carcinoma: Molecular analysis and clinical implications), Faculty of Medicine, The University of Hong Kong . 2009.

Chu K.M. , International Advisory Board, Malaysian Journal of Medicine and Health Sciences (from January) . 2010.

Chu K.M. , Invited referee (reviewer) for abstracts, UICC World Cancer Congress, Shenzhen, China . 2010.

Chu K.M. , Invited referee (reviewer), Case Reports in Medicine, February . 2010.

Chu K.M. , Invited referee (reviewer), Hong Kong Medical Journal . 2010.

Chu K.M. , Invited referee (reviewer), McMaster Online Rating of Evidence (MORE) April . 2010.

Chu K.M. , Invited referee (reviewer), McMaster Online Rating of Evidence (MORE) March . 2010.

Chu K.M. , Invited referee (reviewer), McMaster Online Rating of Evidence (MORE), August 2009 . 2009.

Chu K.M. , Invited referee (reviewer), McMaster Online Rating of Evidence (MORE), October . 2009.

Chu K.M. , Invited referee (reviewer), McMaster Online Rating of Evidence (MORE), September . 2009.

Chu K.M. , Invited referee (reviewer), Surgical Practice . 2009.

Chu K.M. , Invited referee (reviewer), Surgical Practice, February . 2010.

Chu K.M. , Invited referee (reviewer), World Journal of Surgery, August 2009 . 2009.

Chu K.M. , Invited referee (reviewer), World Journal of Surgery, March . 2010.

Chu K.M. , Invited referee (reviewer), World Journal of Surgery, October . 2009.

Chu K.M. , Member of Editorial Board (2008 - present), Case Reports in Medicine (www.hindawi.com/journals/crm) . 2010.

Chu K.M. , Member of Editorial Board (2008 - present), International Advisory Board for Schwartz's Principles of Surgery 9th Edition . 2010.

Chu K.M. , Member of Editorial Board, Annals of Cancer Research and Therapy . 2010.

Chu K.M. , Member of Editorial Board, Asian Journal of Surgery (Associate Editor) . 2010.

Chu K.M. , Member of Editorial Board, Cancer Therapy . 2010.

Chu K.M. , Member of Editorial Board, Journal of Chinese Clinical Medicine (www.cjmed.net )(formerly Chinese Journal of Medicine) . 2010.

Chu K.M. , Member of Editorial Board, World Journal of Surgery . 2010.

Chu K.M. , Member of the International Scientific Committee, The 9th International Gastric Cancer Congress, Seoul, Korea, 20-23 April 2010 . 2010.

Chu K.M. , Member, Board of Advisors, Health Action Magazine, Hong Kong . 2010.

Chu K.M. , Member, Board of Examiners, Membership Examination, The College of Surgeons of Hong Kong, Hong Kong . 2010.

Chu K.M. , Member, Cluster Combined Endoscopy Service Task Group, Hong Kong West Cluster, Hospital Authority . 2010.

Chu K.M. , Member, Examination Committee, The College of Surgeons of Hong Kong, Hong Kong . 2010.

Chu K.M. , Member, Examination Sub-Committee, Licentiate Committee, The Medical Council of Hong Kong, Hong Kong . 2010.

Chu K.M. , Member, Hong Kong West Cluster Credentialing Committee, Queen Mary Hospital, Hong Kong . 2010.

Chu K.M. , Member, Institutional Review Board of The University of Hong Kong / Hospital Authority Hong Kong West Cluster, Hong Kong . 2010.

Chu K.M. , Member, Research Committee, The College of Surgeons of Hong Kong, Hong Kong . 2010.

Chu K.M. , Member, Task Force for Subspecialization in General Surgery, The College of Surgeons of Hong Kong, Hong Kong . 2010.

Chu K.M. , Member, Task Force on Procedural Sedation, Queen Mary Hospital, Hong Kong . 2010.

Chu K.M. , Outstanding Team Award - Integrated Endoscopy Centre, Queen Mary Hospital, Hong Kong West Cluster, Hospital Authority, Hong Kong . 2010.

Chu K.M. , Secretary General, Asian Surgical Association . 2010.

Chu K.M. , Sentinel Reader, McMaster Online Rating of Evidence (MORE), McMaster University, Hamilton, Ontario, Canada . 2010.

Chu K.M. , Surgical management of gastric stromal tumour, The 2009 Asian Pacific Digestive Week, Taipei, Taiwan, 27-30 September 2009 . 2009.

Chu K.M. , Surgical management of gastric stromal tumour, Tomorrow's Oncology Today: Innovating Progress, Touching Lives (AP Summit), Taipei, Taiwan, 11-12 July 2009 . 2009.

Fan J.K.M. , Chan S.Y. and Chu K.M. , Surgical smoke, Asian Journal of Surgery . 2009, 32: 253-257.

Hu X. , Chen W.Y.W. , Liang A.C.T., Au W.Y. , Wong K.Y. , Wan T.S.K. , Wong M.L.Y. , Shen L. , Chan K.K. , Guo T. , Chu K.M. , Tao Q. , Chim J.C.S. , Loong F. , Choi W.L. , Lu L. , So J.C.C. , Chan L.C. , Kwong Y.L. , Liang R.H.S. and Srivastava G. , CD44 activation in mature B-cell malignancies by a novel recurrent IGH translocation, Blood . 2010, 115: 2458-2461.

Hung I.F.N. , Chan P., Leung S., Chan S.Y. , Hsu A., But D., Seto W.K., Wong S.Y. , Chan C.K. , Gu Q. , Tong T.S.M., Cheung T.K. , Chu K.M. and Wong B.C.Y. , Clarithromycin-amoxycillin-containing triple therapy: A valid empirical first-line treatment for Helicobacter pylori eradication in Hong Kong?, Helicobacter . 2009, 14: 505-511.

Ng E.K.O. , Leung C.P.H. , Au S., Chan A., Wong L.P. , Ma E.S.K. , Pang R.W.C. , Chua D.T.T. , Chu K.M. , Law W.L. , Poon R.T.P. and Kwong A. , Plasma microRNA as a potential marker for breast cancer detection, The 101st Annual Meeting of the American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Shin V.Y. , Jin H.C., Ng E.K.O. , Sung J.J., Chu K.M. and Cho C.H., Activation of 5-lipoxygenase is required for nicotine mediated epithelial-mesenchymal transition and tumor cell growth, Cancer Lett . 2010, 292(2): 237-245.

Wu W.K.K., Sung J.J., To K.F., Yu L., Li H.T., Li Z.J., Chu K.M. , Yu J. and Cho C.H. , The host defense peptide LL-37 activates the tumor-suppressing bone morphogenetic protein signaling via inhibition of proteasome in gastric cancer cells, Journal of Cell Physiology . 2010, 223: 178-186.

Xia H.H.X. , Yang Y. , Chu K.M. , Gu Q. , Zhang Y.Y., He H. , Wong W.M. , Leung S.Y. , Yuen S.T. , Yuen R.M.F. , Chan A.O.O. and Wong B.C.Y. , Serum macrophage migration-inhibitory factor as a diagnostic and prognostic biomarker for gastric cancer, Cancer . 2009, 115: 5441-5449.

Researcher : Chu SSM

List of Research Outputs

Au W.H. , Chu S.S.M. , Chu S.S.M. and Tam P.C. , Primary and secondary retrograde intra-renal surgery (RIRS) for renal stones in patients with large stone burden, The 27th World Congress of Endourology and Shock Wave Lithotripsy, Munich, Germany, 6 - 10 October 200 9 .

Chan T.Y., Ho K.L. , Chu S.S.M. and Tam P.C. , Robotic-assisted laparoscopic ureteral reimplantation for distal ureteric stricture (Motion Picture), Surgical Practice . 2009, 13(Suppl. 2): B5.

Ho K.L. , Wong C.W.S. , Au W.H. , Chu S.S.M. and Tam P.C. , Early continence outcomes after robotic radical prostatectomy - impact of vesicourethral reconstruction (Poster Presentation), The American Urological Association Annual Meetin g, San Francisco, USA, 29 May - 3 June 2010 .

Ho K.L. , Tsui H.L., Au W.H. , Chu S.S.M. and Tam P.C. , Early continence outcomes after robotic radical pros tatectomy: impact of vesicourethral reconstruction, Surgical Practice . 2009, 13(Suppl. 2): B7.

Ho K.L. , Tam P.C. , Chu S.S.M. , Au W.H. and Tsu H.L., Robotic-assisted laparoscopic partial nephrectomy - evolution of techniques and peri-operative outcomes, The 1st Hong Kong Congress of Endourology, Hong Kong, 28-29 August 2009 .

Ma W.K., Chu S.S.M. and Tam P.C. , Concomitant pyelithotomy during robotic assisted laparoscopic pyeloplasty, The 1st Hong Kong Congress of Endourology, Hong Kong, 28 - 29 August 2009 .

Tsu H.L., Ho K.L. , Au W.H. , Chu S.S.M. and Tam P.C. , Robotic-assisted laparoscopic radical cystectomy and construction of neobladder urethral anastomosis for urothelial carcinoma of bladder, The 1st Hong Kong Congress of Endourology, Hong Kong, 28-29 August 2009 .

Yap D.Y., Chu F.S., Chu S.S.M. , Tam P.C. , Chan D.T.M. , Lai K.N. and Tang S.C.W. , CT angiography versus conventional digital angiography in pre-operative assessment for Chinese living kidney donors [Epub ahead of print 15 June 2010], Journal of Nephrology . 2010.

Yap D.Y., Chu F.S., Chu S.S.M. , Tam P.C. , Tam S., Lai K.N. , Chan D.T.M. and Tang S.C.W. , CT angiography versus conventional digital angiography in pre-operative assessment for Chinese living kidney donors, Nephrology . 2010, 15 (S3): 54.

Researcher : Chui WH

List of Research Outputs

Chan M.C.W. , Chan W.Y. , Yu C.L. , Ho C.C. , Chui W.H. , Lo C.K., Yuen K.M. , Guan Y. , Nicholls J.M. and Peiris J.S.M. , Influenza H5N1 virus infection of polarized human alveol ar epithelial cells and lung microvascular endothelial cells, Respiratory Research . 2009, 10: 102.

Chan M.C.W. , Chan W.Y. , Yu C.L. , Ho C.C. , Yuen K.M. , Fong J.H.M. , Tang L.L.S. , Lai W.W.K. , Lo A.C.Y. , Chui W.H. , Sihoe A.D.L. , Kwong D.L.W. , Tsao G.S.W. , Poon L.L.M. , Guan Y. , Nicholls J.M. and Peiris J.S.M. , Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract, American Journal of Pathology . 2010, 176(4): 1828-40.

Chan W.Y. , Chan M.C.W. , Wong C.N. , Karamanska R., Dell A., Haslam S.M., Sihoe A.D., Chui W.H. , Triana-Baltzer G., Li Q., Peiris J.S.M. , Fang F. and Nicholls J.M. , DAS181 Inhibits H5N1 Influenza virus Infection of Human Lung Tissues., Antimicrobial Agents and Chemotherapy . 2009, 53(9): 3935-3941.

Researcher : Cornes BK

List of Research Outputs

Cornes B.K. , Tang S.M. , Leon Y.Y. , Hui K.J.W.S., So M.T. , Miao X. , Cherny S.S. , Sham P.C. , Tam P.K.H. and Garcia-Barcelo M.M. , Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population, PLoS One . 2010, 5 (6): e10918.

Researcher : Fan JKM

List of Research Outputs

Fan J.K.M. , Lo O.S.H. and Law W.L. , A rare complication of laparoscopic low anterior resecti on (Abstract), Surgical Laparoscopy, Endoscopy & Percutaneous Techniques . 2009, 19(5): e210.

Fan J.K.M. , Tong D.K.H. , Poon J.T.C. , Lo O.S.H., Beh S.L. , Patil N.G. and Law W.L. , Multimodality minimally invasive autopsy -- a feasible and accurate approach to post-mortem examination, Forensic Science International . 2010, 195(1-3): 93-98.

Fan J.K.M. , Natural orifice translumenal endoscopic surgery, Dissertation, Master of Surgery, The University of Hong Kong . 2010.

Fan J.K.M. , Lo C.S.Y. and Law W.L. , Surgeons' attitudes towards natural orifice translumenal endoscopic surgery, The Society of American Gastrointestinal and Endoscopic Surgeons 2010 Annual Meeting and 12th World Congress of Endoscopic Surgery, National Harbor, Maryland, U.S.A., 14-17 April 2010 .

Fan J.K.M. , Lo C.S.Y. and Law W.L. , Surgeons' attitudes towards natural orifice transluminal endoscopic surgery, ANZ Journal of Surgery . 2010, 80(6): 387-389.

Fan J.K.M. , Chan S.Y. and Chu K.M. , Surgical smoke, Asian Journal of Surgery . 2009, 32: 253-257.

Fan J.K.M. , Tam P.C. and Law W.L. , Synchronous trans-abdominal pre-peritoneal (TAPP) hernioplasty in a patient with robotic-assisted prostatectomy for carcinoma of prostate (Multi-Media Article), Surgical Practice . 2010, 14(1): 32.

Fan J.K.M. and Law W.L. , The impact of verbal guidance on laparoscopic skills training and multi-tasking performance, The Society of American Gastrointestinal and Endoscopic Surgeons 2010 Annual Meeting and 12th World Congress of Endoscopic Surgery, National Harbor, Maryland, U.S.A. , 14-17 April 2010 .

Law W.L. , Poon J.T.C. , Fan J.K.M. , Lo O.S.H., Wei R. and Choi H.K. , Comparison of outcomes following resection of right-sided and left-sided colon cancer, International Surgical Week 2009, Adelaide, Austra lia, 6-10 September 2009 .

Law W.L. , Poon J.T.C. , Fan J.K.M. and Lo O.S.H., Laparoscopic colorectal resection for octogenarians is a safe and optimal approach, Annual Meeting of the American Society of Colon and Rectal Surgeons, Minneapolis, Minnesota, U.S.A., 15-19 May 2010 .

Law W.L. , Poon J.T.C. , Fan J.K.M. and Lo O.S.H., Laparoscopic resection following stent insertion for obstructing colorectal cancer, The Society of American Gastrointestinal and Endoscopic Surgeons 2010 Annual Meeting and 12th World Congress of Endoscopic Surgery, National Harbor, Maryland, U.S.A., 14-17 April 2010 .

Law W.L. , Fan J.K.M. and Poon J.T.C. , Single incision laparoscopic left colectomy for carcinoma of distal transverse colon, Colorectal Disease . 2009, 12(7): 698-701.

Law W.L. , Poon J.T.C. and Fan J.K.M. , Single incision laparoscopic right colectomy (Video Presentation), The Society of American Gastrointestinal and Endoscopic Surgeons 2010 Annual Meeting and 12th World Congress of Endoscopic Surgery, National Harbor, Maryland, U.S.A., 14-17 April 2010 .

Law W.L. , Fan J.K.M. and Poon J.T.C. , Single-incision laparoscopic colectomy: early experience, Diseases of the Colon and Rectum . 2010, 53(3): 284-288.

Lim Y.K. , Law W.L. , Poon J.T.C. and Fan J.K.M. , Impact of multimodality treatment on total mesorecta l excision (TME) surgery for very low rectal cancers, International Surgical Week 2009, Adelaide, Australia, 6-10 September 2009 .

Lim Y.K. , Law W.L. , Liu R., Poon J.T.C. , Fan J.K.M. and Lo O.S.H., Impact of neoadjuvant treatment on total mesorectal excision for ultra-low rectal cancers, World Journal of Surgical Oncology . 2010, 8: 23.

Poolton J.M. , Fan J.K.M. , Masters R.S.W. , Patil N.G. and Law W.L. , The impact of verbal guidance on laparoscopic skills training and multi-tasking performance, 12th World Congress of Endoscopic Surgery, Washington DC . 2010.

Poon J.T.C. , Fan J.K.M. and Law W.L. , Early experience in laparo-endoscopic single site colectomy, The 9th Asia Pacific Congress of Endoscopic Surgery and 9th Meeting of Endoscopic and Laparoscopic Surgeons of Asia, Xiamen, China, 4-6 November 2009 .

Poon J.T.C. , Law W.L. , Fan J.K.M. and Lo O.S.H., Impact of the standardized medial-to-lateral approach on outcome of laparoscopic colorectal resection (Reply to Letter), World Journal of Surgery . 2009, 33(10): 2177-2182.

Wong K.P., Poon J.T.C. , Fan J.K.M. , Lo S.H. and Law W.L. , Prognostic value of lymph node ratio in stage III colorectal cancer, Annual Meeting of the American Society of Colon and Rectal Surgeons, Minneapolis, Minnesota, U.S.A., 15-19 May 2010 .

Researcher : Fan ST

Project Title:	S.K. Yee Medical Foundation Fellowship in hepatobiliary surgery
Investigator(s):	Fan ST
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	11/2000

Abstract:

To train surgeons from less developed cities in China to acquire the technique and knowledge in dealing with complex hepatobiliary problems so as to benefit patients who cannot afford the cost of receiving treatmen t in cities like Beijing, Shanghai and Guangzhou.

Project Title:	The significance of focal adhesion kinase and cell adhesion kinas &beta and their C-terminal non-kinases in liver cancer invsasion and migration
Investigator(s):	Fan ST
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2005

Abstract:

The main objective of this project is to study the significance of focal adhesion kinase(FAK) and cell adhesion kinase &beta (CAK&beta) in liver cancer progression and metastasis.

Project Title:	Focal adhesion kinase and cell adhesion kinase β as the potential therapeutic targets of tumor recurrence and metastasis in hepatocellu lar carcinoma
Investigator(s):	Fan ST, Man K, Liu CL
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	07/2006
Completion Date:	12/2009

Abstract:

To investigate the therapeutic strategies for HCC recurrence and metastasis by targeting at FAK/CAKβ in orthotopic liver cancer nude mice models with different local and distant metastatic potentials by various treatment modalities; to explore the underlying precis e molecular mechanisms related to the cell signaling pathways of migration, invasion and angiogenesis.

List of Research Outputs

Chan A.C.Y. , Fan S.T. , Lo C.M. and Poon R.T.P. , Impact of antiviral therapy on the survival outcome of patients after major hepatectomy for hepatitis B-rel ated hepatocellular carcinoma (Oral Presentation), The 9th World Congress of the International Hepat o-Pancreato-Biliary Association, Buenos Aires, Argentina, 18 - 22 April 2010 .

Chan A.C.Y. , Fan S.T. , Lo C.M. , Liu C.L. , Chan S.C. , Ng K.K.C. , Yong B.H. , Chiu A. and Lam B.K.Y. , Liver transplantation for acute-on-chronic liver failure, Hepatology International . 2009, 3(4): 571-581.

Chan A.C.Y. , Fan S.T. and Lo C.M. , Prediction of hospital mortality after liver transplantation for acute liver failure, The 16th Annual International Congress of the Intern ational Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 .

Chan A.C.Y. , Lo C.M. and Fan S.T. , Small-for-size syndrome in a small child, The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Chan K.L. , Fan S.T. , Lo C.M. , Wei W.I. , Ng W.M. , Chung H.Y., Ng K.K.C. , Chan S.C. , Chan K.W. , Tso W.K. , Tsoi N.S. and Tam P.K.H. , Pediatric liver transplantation in Hong Kong - a domain with scarce deceased donors, Journal of Pediatric Surgery . 2009, 44(12): 2316-2321.

Chan S.C. , Lo C.M. , Ng K.K.C. and Fan S.T. , Alleviating the burden of small-for-size graft in right liver living donor liver transplantation through accumulation of experience, American Journal of Transplantation . 2010, 10(4): 859-867.

Chan S.C. , Lo C.M. , Chik B.H.Y., Chow L.C. and Fan S.T. , Flowmetry-based portal inflow manipulation for a small-for-size liver graft in a recipient with spontaneous splenorenal shunt, Clinical Transplantation . 2010, 24(3): 410-414.

Chan S.C. , Lo C.M. , Yong B.H. , Tsui W.J.C., Ng K.K.C. and Fan S.T. , Paired donor interchange to avoid ABO-incompatible living donor liver transplantation, Liver Transplantation . 2010, 16(4): 478-481.

Chan S.C. , Lo C.M. , Ng K.K.C. , Chok K.S.H. , Yong B.H. and Fan S.T. , Portal inflow and pressure changes in right liver livi ng donor liver transplantation including middle hepatic vein (Abstract), The 15th Annual International Congress of the Intern ational Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S92.

Chan S.C. , Lo C.M. , Ng K.K.C. , Chok K.S.H. and Fan S.T. , Simplifying hepatic venous outflow reconstruction in sequential living donor liver transplantation, Liver Transplantation . 2009, 15(11): 1514-1518.

Chan S.C. , Lo C.M. and Fan S.T. , Simplifying living donor liver transplantation, Hepatobiliary and Pancreatic Diseases International . 2010, 9(1): 9-14.

Chan S.C. , Lo C.M. and Fan S.T. , Splanchnic hemodynamics in liver regeneration after right liver living donor liver transplantation (Letter to the Editor), Liver Transplantation . 2010, 16(3): 412.

Chan S.C. , Lo C.M. , Wong Y. , Ng K.K.C. , Chok K.S.H. and Fan S.T. , Validating graft and standard liver size predictions in right liver living donor liver transplantation (Ab stract), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S247.

Cheng Q. , Ng T.P. , Fan S.T. , Lim Z.X.H. , Guo D. , Liu X. , Liu Y. , Poon R.T.P. , Lo C.M. and Man K. , Distinct mechanism of small-for-size fatty liver graft injury--Wnt4 signaling activates hepatic stellate cells, American Journal of Transplantation . 2010, 10(5): 1178-1188.

Cheung C.K.Y. , Lo C.M. , Chan S.C. and Fan S.T. , Long-term follow up of hepatitis B virus-specific immune response in liver transplant patient receiving third-generation hepatitis B vaccine (Abstract), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 16(Suppl 1): S242.

Cheung T.T. , Ng K.K.C. , Poon R.T.P. , Chan S.C. , Lo C.M. and Fan S.T. , A case of laparoscopic hepatectomy for recurrent hepato cellular carcinoma, World Journal of Gastroenterology . 2010, 16(4): 526-530.

Cheung T.T. , Ng K.K.C. , Chok K.S.H. , Chan S.C. , Poon R.T.P. , Lo C.M. and Fan S.T. , Combined resection and radiofrequency ablation for multifocal hepatocellular carcinoma: prognosis and outcomes, World Journal of Gastroenterology . 2010, 16(24): 3056-3062.

Cheung T.T. , Ng K.K.C. , Poon R.T.P. and Fan S.T. , Tolerance of radiofrequency ablation by patients of hepatocellular carcinoma, Journal of Hepato-biliary-pancreatic Surgery . 2009, 16(5): 655-660.

Chiu A. and Fan S.T. , Molecular Adsorbents Recirculating System (MARS): evidence and management pitfalls, Hong Kong Medical Diary . 2009, 14(9): 19-21.

Chok K.S.H. , Ng K.K.C. , Cheung T.T. , Yuen W.K. , Poon R.T.P. , Lo C.M. and Fan S.T. , An update on long-term outcome of curative hepatic resection for hepatocholangiocarcinoma, World Journal of Surgery . 2009, 33(9): 1916-1921.

Chok K.S.H. , Chu F.S.K. , Cheung T.T. , Lam V.W.T. , Yuen W.K. , Ng K.K.C. , Chan S.C. , Poon R.T.P. , Yeung C. , Lo C.M. and Fan S.T. , Results of percutaneous transhepatic cholecystostomy for high surgical risk patients with acute cholecystitis, ANZ Journal of Surgery . 2010, 80(4): 280-283.

Chung P.H.Y., Wong K.K.Y. , Tam P.K.H. , Chan K.L. , Ng K.K.C. , Chan S.C. , Hui T.W.C. , Yong B.H. , Fan S.T. and Lo C.M. , Split graft liver transplant for paediatric patients in Hong Kong, Hong Kong Journal of Paediatrics (New Series) . 2009, 14: 181-185.

Dai W.C., Ng K.K.C. , Chok K.S.H. , Cheung T.T. , Poon R.T.P. and Fan S.T. , Radiofrequency ablation for controlling iatrogenic splenic injury (Letter to the Editor), International Journal of Colorectal Diseases . 2010, 25(5): 667-668.

Fan S.T. , Abstract Chair (Living Donor), The 15th Annual International Congress, the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009 . 2009.

Fan S.T. , Abstract Chair (Surgical Techniques/Complications), The 16th Annual International Congress, the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Fan S.T. , Advisor (2006 - present), Liver Donation Committee, The Hong Kong Liver Foundati on . 2009.

Fan S.T. , Advisor (June 2008 - present), The Hong Kong Transplant Sports Association . 2010.

Fan S.T. , Appointed Director, The Hong Kong Liver Transplant Patients’ Association . 2010.

Fan S.T. , Associate Editor (October 2008 - present), 中華移植雜誌 (電子版), 2009.

Fan S.T. , Chief Panelist (Medicine), Young Women Researcher Award 2009, Third World Organization for Women in Science, Kuala Lumpur, Malaysia, 9 November 2009 . 2009.

Fan S.T. and Wang H. , China Liver Transplant Registry (Oral Presentation), The 15th Annual International Congress, the Inter national Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7): S100.

Fan S.T. , Wang H. , Jiang W.S., Li W., Zhou Z.Y. and Huang Y.Z., China Organ Allocation and Sharing Policy, Ministry of Health, P.R.China . 2010.

Fan S.T. , Comparing results in pediatric patients with < 10kg in LDLT. Monosegments versus full left later segments (Discussant), The 9th World Congress of the International Hepato-Pancreato-Biliary Association, Buenos Aires, Argentina, 18-22 April 20 10 . 2010.

Fan S.T. , Consultant (July 2006 - June 2010), Central South China Academic Association of General Surgery (中南地區普外科學術委員會) . 2010.

Fan S.T. , Consultant (November 2007 - present), Chinese Medical Doctor Association . 2009.

Fan S.T. , Consultant of Editorial Board (April 2007 - present), 中華消化外科雜誌, 2010.

Fan S.T. , Council Member (January 1998 - present), Hong Kong Chapter, American College of Surgeons . 2010.

Fan S.T. , Course Director - Postgraduate Course Session, Transplantation Course: The Art of Liver Transplantation, The 20th Conference of the Asian Pacific Association for the Study of the Liver, Beijing, China, 25 - 28 March 2010 . 2010.

Fan S.T. , Director (January 2009 - present), The Hong Kong Tuberculosis, Chest and Heart Diseases Association . 2010.

Fan S.T. , Expert Clinician, Phoenix Alliance, U.S.A. . 2010.

Fan S.T. , Focused ultrasound ablation of liver cancer in Hong Kong (Invited Lecture), The 1st International Summit of Noninvasive Ultrasound Treatment, Chongqing, China, 22-23 October 2009 . 2009.

Fan S.T. , Genomics and application of molecular/genetics in decision making on HCC (Chairman), The 9th World Congress of the International Hepato-Pa ncreato-Biliary Association, Buenos Aires, Argentina, 18-22 April 2010 . 2010.

Fan S.T. , Going to the right lobe for the adult patient: a necessary step? (Invited Lecture), Celebration of the 20th Anniversary of the First Pediatric Living Donor Liver Transplantation in the United States, University of Chicago Medical Center, Chicago, Illinois, U.S.A., 16 October 2009 . 2009.

Fan S.T. , Hepatoma (I) Mechanisms of HCC Metastasis and Potential Targeted Therapy (Chairman), The Asian Pacific Digestive Week 2009, Taipei, Taiwan, 27-30 September 2009 . 2009.

Fan S.T. , Honorary Consultant (1993 - present), Queen Mary Hospital, Hong Kong West Cluster, Hospital Authority . 2010.

Fan S.T. , Honorary Consultant (1994 - present), Tung Wah Hospital, Hong Kong West Cluster, Hospital Authority . 2010.

Fan S.T. , Honorary Fellowship, The College of Surgeons of Hong Kong . 2010.

Fan S.T. , Informing candidates of donor risks - living donation (Invited Lecture), The 15th Annual International Congress, the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009 . 2009.

Fan S.T. and Liu C.L. , Live-donor liver transplantation in adults, In: Hakim N., Canelo R. and Papalois V. (eds.), Living Related Transplantation . London, Imperial College Press, 2010, 65-93.

Fan S.T. , Liver cancer, transplantation and cancer stem cell (Invited Lecture), Young Women Researcher Award Symposium, Kuala Lump ur, Malaysia, 9-10 November 2009 . 2009.

Fan S.T. , Liver transplantation - Who live? Who die? (Special Article), Hong Kong Practitioner . 2009, 31(3): 133-134.

Fan S.T. , Living donor liver transplantation (Breakfast with the Professor), The 9th World Congress of the International Hepato-P ancreato-Biliary Association, Buenos Aires, Argentina, 18-22 April 2010 . 2010.

Fan S.T. , Living donor liver transplantation (Invited Lecture), The 19th World Congress of the International Associat ion of Surgeons, Gastroenterologists, and Oncologists, Beijing, China, 23-26 September 2009 . 2009.

Fan S.T. , Living donor liver transplantation for HCC (Invited Lecture), The 9th World Congress of the International Hepat o-Pancreato-Biliary Association, Buenos Aires, Argentina, 18-22 April 2010 . 2010.

Fan S.T. , Management of HCC patients on waiting list (Invited Lecture), The 7th Meeting of 5 Asian LDLT Centers, Department of Surgery, The University of Hong Kong, Hong Kong, 15 June 2010 . 2010.

Fan S.T. , Member at Large, Executive Committee, International Gastro-Surgical Club . 2010.

Fan S.T. , Member of Editorial Board (1991 - present), Journal of Gastroenterology and Hepatology . 2010.

Fan S.T. , Member of Editorial Board (1995 - present), Hepato-Gastroenterology . 2010.

Fan S.T. , Member of Editorial Board (1998 - present), Archives of Surgery . 2010.

Fan S.T. , Member of Editorial Board (2001 - present), 中國肝癌雜誌, 2010.

Fan S.T. , Member of Editorial Board (December 2002 - present), 中國普外基礎與臨床雜誌, 2010.

Fan S.T. , Member of Editorial Board (December 2003 - present), 中華外科治療學雜誌, 2010.

Fan S.T. , Member of Editorial Board (December 2003 - present), 移植雜誌, 2010.

Fan S.T. , Member of Editorial Board (January 1993 - present), Hong Kong Practitioner . 2010.

Fan S.T. , Member of Editorial Board (January 1999 - present), 中華普通外科雜誌, 2010.

Fan S.T. , Member of Editorial Board (January 2000 - present), 中華醫學雜誌, 2010.

Fan S.T. , Member of Editorial Board (January 2008 - present), Chinese Journal of Clinical Infectious Diseases . 2010.

Fan S.T. , Member of Editorial Board (July 1999 - present), HPB . 2010.

Fan S.T. , Member of Editorial Board (July 2001 - present), 中國實用外科雜誌, 2010.

Fan S.T. , Member of Editorial Board (March 2008 - present), Hepatology International . 2010.

Fan S.T. , Member of Editorial Board (May 1998 - present), 中華肝膽外科雜誌, 2010.

Fan S.T. , Member of Editorial Board (October 1999 - present), Digestive Surgery . 2010.

Fan S.T. , New Frontiers in Liver Transplantation: Part III (Co-Chairman), The 19th World Congress of the International Association of Surgeons, Gastroenterologists, and Oncologists, Beijing, China, 23-26 September 2009 . 2009.

Fan S.T. and Wang H. , New Key Opinion Leader nKOL of the Transplantation Society, The Transplantation Society New Key Opinion Leader Meeting, Gothenburg, Sweden, August 20-23, 2009. . 2009.

Fan S.T. , Optimizing venous outflow in living donor liver transplantation (Invited Lecture), The Art of Surgery and Medicine in Liver Transplantation: Today and Tomorrow, Satellite Symposium to the Internation al Liver Transplantation Society 16th Annual International Congress, Hong Kong, 16 June 2010 . 2010.

Fan S.T. , Oral abstract session: living donor (Moderator), The 15th Annual International Congress, the International Liver Transplantation Society, New York City, New York, U.S.A., 8-11 July 2009 . 2009.

Fan S.T. , Plenary session II (Moderator), The International Liver Transplantation Society 16th Annual International Congress, Hong Kong, 16-19 June 2010 . 2010.

Fan S.T. , Post-resectional liver failure (Invited Lecture), The 9th World Congress of the International Hepato-Pancreato-B iliary Association, Buenos Aires, Argentina, 18-22 April 2010 . 2010.

Fan S.T. , Present and future of living donor liver transplantation - perspective from Hong Kong (Invited Lecture), The 20th Anniversary of Living Liver Transplantation at Shinshu University, Matsumoto, Nagano, Japan, 26 June 2010 . 2010.

Fan S.T. , Project 1: Identification of source of tumor recurrence after liver transplantation for hepatocellular carcinoma. Project 2: Gene expression profiling of colorectal cancer liver metastasis. Project 3: Toxicity study of AZD1152 in Buffalo rats, AstraZeneca Investment (China) Co., Ltd. . 2009.

Fan S.T. , Recent advances in treatment of HCC - contribution from Hong Kong (Invited Lecture), The 40th Anniversary of Liver Cancer Institute, Fudan University, Shanghai, China, 26 December 2009 . 2009.

Fan S.T. , Reviewer, American Journal of Gastroenterology . 2010.

Fan S.T. , Reviewer, American Journal of Surgery . 2010.

Fan S.T. , Reviewer, American Journal of Transplantation . 2010.

Fan S.T. , Reviewer, Annals of Surgery . 2010.

Fan S.T. , Reviewer, Archives of Surgery . 2010.

Fan S.T. , Reviewer, Asian Journal of Surgery . 2010.

Fan S.T. , Reviewer, British Journal of Surgery . 2010.

Fan S.T. , Reviewer, Digestive Diseases and Sciences . 2010.

Fan S.T. , Reviewer, Digestive Surgery . 2010.

Fan S.T. , Reviewer, Gut . 2010.

Fan S.T. , Reviewer, HBP Surgery . 2010.

Fan S.T. , Reviewer, Hepatobiliary and Pancreatic Diseases International . 2010.

Fan S.T. , Reviewer, Hepatology . 2010.

Fan S.T. , Reviewer, Hepatology International . 2010.

Fan S.T. , Reviewer, Intensive Care Medicine . 2010.

Fan S.T. , Reviewer, International Journal of Surgery . 2010.

Fan S.T. , Reviewer, Journal of Cancer Research and Clinical Oncology . 2010.

Fan S.T. , Reviewer, Journal of Gastroenterology and Hepatology . 2010.

Fan S.T. , Reviewer, Journal of Hepato-Biliary-Pancreatic Sciences . 2010.

Fan S.T. , Reviewer, Journal of Hepato-Biliary-Pancreatic Surgery . 2010.

Fan S.T. , Reviewer, Journal of Surgical Research . 2010.

Fan S.T. , Reviewer, Journal of Transplantation . 2010.

Fan S.T. , Reviewer, Journal of the Pancreas . 2010.

Fan S.T. , Reviewer, Liver Transplantation . 2010.

Fan S.T. , Reviewer, Nutrition . 2010.

Fan S.T. , Reviewer, Surgery . 2010.

Fan S.T. , Reviewer, Transplantation . 2010.

Fan S.T. , Reviewer, Transplantation International . 2010.

Fan S.T. , Reviewer, World Journal of Gastroenterology . 2010.

Fan S.T. , Reviewer, World Journal of Surgery . 2010.

Fan S.T. , Session I: Noninvasive focused ultrasound and minimally-invasiv e thermal ablation (Chairman), The 1st International Summit of Noninvasive Ultrasound Treatment, Chongqing, China, 22-23 October 2009 . 2009.

Fan S.T. , Surgical advances in the treatment of hepatoma (Invited Lecture), Update on Hepatoma, Chennai, India, 29 August 2009 . 2009.

Fan S.T. , The development of liver registry in P.R. China (Invit ed Lecture), The 20th Conference of the Asian Pacific Association for the Study of the Liver, Beijing, China, 25-28 March 2010 . 2010.

Fan S.T. , The development of the liver registry in the PRC (Invited Lecture), The New Key Opinion Leader Meeting, The Transplantation Society, Gothenburg, Sweden, 20 - 23 August 2009 . 2009.

Fan S.T. and Wang H. , The role of China Liver Transplant Registry (Oral Pre sentation), The 20th Conference of Asia Pacific Association of The Study of Liver Disease, Beijing, China, 25 - 28 March 2010 .

Fan S.T. , Video Festival Liver: Surgical Procedures Part IV (Chairma n), The 19th World Congress of the International Association of Surgeons, Gastroenterologists, and Oncologists, Beijing, China, 23-26 September 2009 . 2009.

Fan S.T. , Visiting Professor, Health Manpower Development Plan – FY 2009 Visiting Expert in General Surgery, Ministry of Health, Singapore, 5 - 10 October 2009 . 2009.

Fan S.T. , 腦死亡供體的選擇和管理 (Invited Lecture), 2010新年器官移植與免疫治療高峰論壇, 中國廣州, 2010年1月13日, 2010.

Fan S.T. , 右肝活體肝移植, 育醫造才：探索醫學世界, 香港, 香港大學李嘉誠醫學院, 2010, 24-27.

Fan S.T. , 顧問 (November 2006 - present), 中華人民共和國衛生部人體器官移植技術臨床應用委員審定專家工作組, 2009.

Fan S.T. , 客席教授, 無錫巿第三人民醫院，中國無錫，2010年4月17日, 2010.

Fan S.T. , 客席教授, 中國西安巿第四軍醫大學，中國西安，2009年9月, 2009.

Fan S.T. , 活體肝移植的盛與衰 - 香港視角 (Invited Lecture), 國際肝膽胰協會中國分會第四屆學術研討會, 中國武漢, 2010年5月7-8 日, 2010.

Fan S.T. , 肝癌肝切除術的長期存活 (Invited Lecture), 第六屆中國腫瘤學術大會暨第九屆海峽兩岸腫瘤學術會議, 中國上海, 2010年52 2010.

Fan S.T. , 治療肝細胞肝癌的肝移植 (Invited Lecture), 第十二屆全國肝癌學術會議, 中國沈陽, 2009年9月16-19日, 2009.

Fan S.T. , 治療肝細胞肝癌的肝移植 (Invited Lecture), 2009普通外科高峰論壇, 中國西安, 2009年9月18-20日, 2009.

Fan S.T. , 肝臟移植的血管重建 (Invited Lecture), 中華醫學會第十六屆全國外科學學術會議, 中國北京, 2009年9月25日, 2009.

Fan S.T. , 肝癌肝移植 (Invited Lecture), 2009上海肝病肝移植論壇, 中國上海, 2009年10月24日, 2009.

Fan S.T. , 肝切除手術極限的擴展 (Invited Lecture), 第二屆江蘇省肝膽外科學術會議, 中國蘇州, 2009年10月23-24日, 2009.

Fan S.T. , 原發性肝癌的外科治療－局部切除還是解剖性切除 (Invited Lecture) , 第十四屆全國普通外科學術會議, 中國青島, 2010年6月4-7日, 2010.

Fan S.T. , 肝細胞癌外科的進展 (Invited Lecture), 第十二屆中華肝膽胰脾外科專業學術論壇, 中國無錫, 2010年4月16 -19日, 2010.

Fung J.Y.Y. , Lai C.L. , Chan S.C. , But D., Seto W.K., Cheng C.T.K. , Wong D.K.H. , Lo C.M. , Fan S.T. and Yuen R.M.F. , Correlation of liver stiffness and histological features in healthy persons and in patients with occult hepati tis B, chronic active hepatitis B, or hepatitis B cirrhosis., Am J Gastroenterol . 2009, 105(5): 1116-22.

Fung J.Y.Y. , Lai C.L. , Chan S.C. , But D., Seto W.K., Cheng C.T.K. , Wong D.K.H. , Lo C.M. , Fan S.T. and Yuen R.M.F. , Liver stiffness and histological features in healthy persons, and patients with occult hepatitis B, chronic active hepatitis B, and hepatitis B-related cirrhosis., Hepatology . 2009, 50(4) Suppl: 978A.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Abstract), The 16th Annual International Congress of the Internation al Liver Transplantation Society, Hong Kong, 16 - 19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Young Investigator Award), The 16th Annual International Congress of the Internationa l Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Lam C.T. , Yang Z. , Fan S.T. and Poon R.T.P. , The proangiogenic role of brain-derived neurotrophic factor in tumor development , The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 Apri l 2010 .

Lau C.K. , Yang Z. , Ho D.W.Y. , Ng N.P. , Poon R.T.P. and Fan S.T. , Discruption of Akt/hif1 signaling can enhance the therapeutic efficacy of ischemic hypoxia and chemotherapy, The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Lee Y.K. , Sit W.H. , Fan S.T. , Man K. , Jor W.Y. , Wong L.Y. , Wan L.Y. , Tan-Un K.C. and Wan J.M.F. , The cell cycle effects of docosahexaenoic acid on human metastatic hepatocellular carcinoma proliferation, International Journal of Oncology . 2010, 36(4): 991-998.

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Li X.C., Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplanta tion . 2010, 16(6): s96.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the Internation al Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s72.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Rising Star Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Liu Y., Wen X.M., Lui E.L.H. , Friedman S.L., Cui W., Ho N.P., Li L. , Ye T., Fan S.T. and Zhang H., Therapeutic targeting of the PDGF and TGF-beta-signaling pathways in hepatic stellate cells by PTK787/ZK22258, Laboratory Investigation . 2009, 89(10): 1152-1160.

Man K. , Ng T.P. , Liu X. , Yeung W.H. , Lo C.M. and Fan S.T. , Inflammatory microenvironment accelerates liver tumor growth and metastasis by mobilizing circulating endothelial progenitor cells and increasing cancer stem like cell populations (Abstract), The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Man K. , Shih K.C. , Ng T.P. , Xiao J. , Guo D. , Sun K.W. , Lim Z.X.H. , Cheng Q. , Liu Y. , Fan S.T. and Lo C.M. , Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts, Annals of Surgery . 2010, 251(6): 1154-1161.

Man K. , Ng T.P. , Xu A. , Cheng Q. , Lo C.M. , Xiao J. , Sun B. , Lim Z.X.H. , Cheung J.S., Wu E.X. , Sun K.W. , Poon R.T.P. and Fan S.T. , Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling, Clinical Cancer Research . 2010, 16(3): 967-977.

Man K. , Shao Y. , Ng T.P. , Li C. , Fan S.T. and Lo C.M. , The significance of acute-phase small-for-size liver graft injury in mobilization of circulating EPCS/MDSCS/T REGS after LDLT for HCC patients (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16 - 19 June 2010. Liver Transpl antation . 2010, 16(6): s191.

Ng K.K.C. , Poon R.T.P. , Cheung T.T. , Chu F.S.K. , Tso W.K. and Fan S.T. , High efficacy of high intensity focused ultrasound without transarterial embolization for hepatocellular carcinoma (Poster Presentation), International Liver Cancer Association 3rd Annual Conference, Milan, Italy, 4 - 6 September 2009 .

Ng K.K.C. , Poon R.T.P. , Chok K.S.H. , Cheung T.T. , Tung H., Chu F.S.K. , Tso W.K. , Yu W.C. and Fan S.T. , High efficacy of high-intensity focused ultrasound without transarterial embolization for hepatocellular carcinoma - Hong Kong experience (Abstract), The 1st International Summit of Noninvasive Ultra sound Treatment, Chongqing, China, 22-23 October 2009 .

Ng K.K.C. , Lo C.M. , Chan S.C. and Fan S.T. , Living donor liver transplantation for hepatocellula r carcinoma across Milan criteria (Oral Presentation), International Surgical Week 2009, Adelaide, Australia, 6 - 10 September 2009 .

Ng K.K.C. , Lo C.M. and Fan S.T. , Long-term survival analysis of living donor liver transplantation for hepatocellular carcinoma across Milan criteria (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S143.

Ng K.K.C. , Chan S.C. , Chok K.S.H. , Cheung T.T. , Chan A.C.Y. , Lo C.M. and Fan S.T. , Primary versus salvage liver transplantation for hepatoc ellular carcinoma within Milan criteria - a single center experience (Abstract and Poster Presentation), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S254.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , Identification of circulating protein markers relate d to tumor recurrence after liver transplantation (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s207.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantati on . 2010, 16(6): s77.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Young Investigator Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Sharr W.W. , Chok K.S.H. , Ng K.K.C. , Chan S.C. , Lo C.M. and Fan S.T. , Impact of donor age on right lobe living donor liver transplantation in a single centre (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S92.

Sharr W.W. , Lo C.M. and Fan S.T. , Recurrent hepatitis B infection after liver transplantation for hepatitis B related diseases: long term results of a single centre in Asia (Poster Presentation), The 16th Annual International Congress of the Interna tional Liver Transplantation Society, Hong Kong, June 2010 .

Wang H. and Fan S.T. , China Organ Allocation Policy, China First Procument Transplant Coordinator Training Conference, Shenzhen, China, June 27-28th, 2010 . 2010.

Wang H. , Huang Y.Z., Li W., Jiang W.S. and Fan S.T. , Liver Transplantation for Hepatocellular Carcinoma in China (Poster), The 15th Annual International Congress, the International Liver Transplantation Society, Hong Kong, China, 16 - 19 June 2010 .

Wang H. and Fan S.T. , The development of Liver Registry in China (Oral Presentation), The Transplantation Society New Key Opinion Leader Meeting, Gothenburg, Sweden, August 20-23, 2009. . 2009.

Wang X. , Ongkekp W.M., Chen L. , Yang Z. , Lu P. , Chan K.K. , Lopez J.P., Poon R.T.P. and Fan S.T. , Oct4 mediates chemotherapeutic drug resistance in liver cancer cells through potential Oct4-AKT-ABCG2 pathway, Hepatology . 2010, 52: 528-539.

Yang Z. , Fan S.T. , Ho D.W.Y. , Yu W.C. , Lau C.K. , Ng N.P. and Lam C.Y. , Liver cancer stem cells and HCC recurrence (Oral Prese ntation), The International Liver Cancer Association Third Annual Congress, Milan, Italy, 4 - 6 September 2009 .

Yau T.C.C. , Yao T.J. , Chan P., Epstein R. , Ng K.K.C. , Chok K.S.H. , Cheung T.T. , Fan S.T. and Poon R.T.P. , The outcomes of elderly patients with hepatocellular carcinoma treated with transarterial chemoembolization, Cancer . 2009, 115(23): 5507-5515.

de Villa M.V.H., Concejero A., Gregorio G., Ong J., Labio E., Santos-Ocampo R., Chen C.C., Lo C.M. and Fan S.T. , Regional collaboration in liver transplantation for Filipinos (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S249.

Researcher : Fan YW

List of Research Outputs

Leung G.K.K. , Hung K.N. , Lui W.M. and Fan Y.W. , Combined transcranial and transsphenoidal resection of huge pituitary adenoma, The 7th Meeting of the Asian Society for Neuro-oncolog y, Seoul, Korea, 10 - 12 June 2010 .

Yung A.W.Y. , Wong V.C.N. , Khong P.L. , Mak H.K.F. , Hung K.N. , Chan P.H., Ho W.Y. and Fan Y.W. , Paediatric Epilepsy Surgery Program in Hong Kong - a single centre experience, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009 .

Researcher : Fatima S

List of Research Outputs

Chen L. , Fatima S. , Peng J. and Leng X., SELDI protein chip technology for the detection of serum biomarkers for liver disease, Protein and Peptide Letters . 2009, 16(5): 467-472.

Fatima S. , Lee N.P.Y. , Ng I.O.L. and Luk J.M.C. , The role of Dickkopf 4 (DKK4) on Wnt signaling in hepatocel lular carcinoma (Poster Presentation), The 20th Annual Conference of the Asian Pacific Association for the Study of the Liver (APASL), Beijing, China, 25-28 March 2010 .

Researcher : Ford JM

List of Research Outputs

Kwong A. , Ng E.K.O. , Law F.B.F. , Wong L.P., To M.Y., Cheung M.T. , Wong H.N. , Chan V.W., Kurian A., West D.W. , Ford J.M. and Ma E.S., High-resolution melting analysis for rapid screening of BRCA2 founder mutations in Southern Chinese breast cancer patients, Breast Cancer Research and Treatment . 2010, 122(2): 605-607.

Researcher : Garcia-Barcelo MM

Project Title:	Functional evaluation of RET coding and non-coding sequence mutations in Hirschsprung's disease
Investigator(s):	Garcia-Barcelo MM, Miao X, Ngan ESW, Tam PKH
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2008

Abstract:

Analyse the functional significance of 28 CDS RET variations/mutations found in Chinese HSCR patients. We are particularly interested in R114H since it is found in 10% of the Chinese patients and never been found in the general population, neither Caucasians nor Chinese. R114H is inherited from unaffected parent s and its high frequency in our population suggests a founder effect. RET-CDS mutations that appear de novo in sporadic cases are of particular relevance since its pathogenicity may be determining its penetrance and therefore, their segregation in future generations. Investigating the mechanisms of pathogenicity of those HSCR RET mutations located in “cancer” specific domains of the RET protein are crucial.

Project Title:	Fine mapping of a Hirschsprung’s disease locus on the 3p21candidate region
Investigator(s):	Garcia-Barcelo MM, Cherny SS, Tam PKH
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2008
Completion Date:	06/2010

Abstract:

Hirschsprung’s disease (HSCR) is a congenital disor der characterized by the absence of enteric ganglia in variable portions of the lower digestive tract. Its incidence varies among populations, being more frequent in Asians. HSCR patients are classified according to the severity of the phenotype into short-segment (S-HSCR), long-segment (L-SHCR), or total colonic (TCA) aganglionosis. HSCR presents mostly sporadically although it can be familial with a complex pattern of inherit ance including low, sex-dependent penetrance and phenotypic variability. The male:female ratio (M:F) is ≈4:1 among S-HSCR patients and ≈1:1 among L-HSCR patients(1). The RET gene, encoding a tyrosine-kinase receptor is the major HSCR gene and its expression is crucial for the development of the enteric ganglia from the neural crest cells precursors (NCCs). Reduced penetrance of RET mutations and variable expression of HSCR phen otype suggest that more than one gene is required for the development of the phenotype. Current data indicates that HSCR manifestation always requires RET (major gene) and other interacting susceptibility alleles(2). Thus far, a few loci have been identified: (i) the 9q31 locus, which segregated in families harbouring no or hypomorphic RET mutations, yet the families showed linkage to 10q12 (RET locus)(3); (ii) the 3p21 and 19q12(2) loci, whose joint segregation with RET seemed necessary and sufficient for the manifestation of S-HSCR. Since HSCR does not segregate in the absence of RET, the 3q21, 19q12 and 9q31 loci are thought to be RET-dependent modifiers. Despite these important findings, the genes in these loci are yet to be identified. HSCR is as an oligogenic entity currently being genetically dissected and used as a paradigm for the study of polygenic/complex diseases(2;4). Yet, further insight into the genes governing HSCR is to be gained in order to explain the transmission of HSCR, and other particulars such as gender bias. The basic premise is that common genetic variants (Single Nucleotide Polymorphisms; SNPs) are involved in the manifestation of the HSCR phenotype which in turn may also depend on the type of RET mutation of the patient. Finding additional HSCR loci requires a large-scale SNP analyses on a collection of patients with well-defined phenotypes/RET genotypes. To address these issues, an international HSCR consortium (of which the PI and Co-Is are active participants and the sole source of samples from patients of Chinese origin) was created in 2004. During the latest meeti ng (hosted by Dr. Ceccherini in Genoa, Italy, in March 2007), we accorded to deepen our research on the chromosomal regions in which putative RET-modifiers are located (as described above), in addition to searching for new HSCR loci using high-throughput strategies. In Hong Kong, we have conducted a pilot study on Chinese patients to investigate the 3p21 region. We have identifi ed a HSCR-associated 5-marker haplotype spanning 118Kb and encompassing several genes relevant for neurological phenotypes (p <0.01). We believe that a conclusive replication of the findings is to be achieved before embarking on the labour-intensive/costly investigation require d to (a) sequence these candidate intervals in order to identify common/uncommon causative variants and (b) understand their functional consequences. Also, because our initial studies might have identified markers that are not in strong LD with the causal variants, which could lead to a false refutation in a different population, we will test additional SNPs in this region, which will also provide us with a much more robust set of data to build on. Our objective is therefore to identify the HSCR locus known to exist in the 3p2 1 region by fine-mapping using high-density genotype data. In particular, we propose to: (i) identify the HSCR locus comprised in the 3p21HSCR-associated region (48372050-48490083) by dense genotyping 71 SNPs selected SNPs on 360 Chinse HSCR patients and 360 controls. (ii) proceed with functional analysis of the genes identified. REFERENCES: 1. Amiel J, Lyonnet S 2001 Hirschsprung disease, associated syndromes, and genetics: a review. J Med Genet 38:729-739 2. Gabriel SB, et al. 2002 Segregation at three loci explains familial and population risk in Hirschsprung disease. Nat Genet 31:89-93 3. Bolk S, et al. 2000 A human model for multigenic inheritance: phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus. Proc Natl Acad Sci U S A 97:268-273 4. Passarge E 2002 Dissecting Hirschsprung disease. Nat Genet 31:11-12 5. Chanock SJ, et al. 2007 Replicating genotype-phenotype associations. Nature 447:655-660

Project Title:	Fine mapping of Hirschsprungs disease loci on the 3p21 and 9q31 candidate regions
Investigator(s):	Garcia-Barcelo MM, Cherny SS, Ngan ESW, Tam PKH
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2009

Abstract:

(1) Identify the HSCR locus comprised in the two 9q31 HSCR-associated regions (110714700-111123500 and 112126800-112474100) by dense genotyping selected SNPs in 360 Chinese patients and 360 controls and 120 Dutch trios.

Project Title:	Sequencing of the neuregulin-1 (NRG1) gene in Hisrchprung's disease patients
Investigator(s):	Garcia-Barcelo MM, Tam PKH
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2009

Abstract:

The primary pathology of HSCR is the absence of enteric ganglion cells in variable lengths of the hindgut resulting in functional obstruction. HSCR is attributed to a failure of migration of neural crest cells (enteric ganglion precursors) along the developing gut. RET is a key regulator of the development of the enteric nervous system (ENS) and the major HSCR-causing gene. Deleterious DNA alterations (“mutations”) in RET coding sequence (CDS) account for ≈50% of the familial and 15%-20% of the sporadic cases. Other HSCR genes identified encode protein members of interrelated signalling path ways involved in the ENS development: RET, EDNRB and SOX10[1-4]. Mutations in genes other than RET explain ≈7% of the cases. In addition to RET mutations, RET single nucleotide polymorphisms (SNPs; “common variants”; in >1% of the population) and haplotypes are strongly associated with HSCR, with the largest contribution to risk made by an intron 1 functional SNP (rs2435357)[5] which has low penetrance, a sex-dependent effect and explains only a small fraction of the HSCR cases. It is thought that SNPs could act as modifiers of the mutations in the major HSCR genes and/or act themselves as low susceptib ility loci. KEY ISSUES: (i) DNA alterations in RET (either rare or common) or other HSCR genes cannot account for the totality of the HSCR patients; and (ii) mutations in HSCR genes have reduced penetrance and phenotypic variability (i.e., length of the aganglionosis). This implies that (i) other genes are to be found; (ii) the effect of a mutation is modulated by other loci (modifiers) and (iii) that more than one gene is required for the disease manifestation. HSCR has become a model for the study of other complex disorders. The genetic complexity of HSCR can be understood in light of the molecular events that take place during the ENS developmen t. The success of the colonization of the gut by the enteric ganglion precursors[6] depends on the synchronization and balance of the signalling networks implicated. DNA alterations in the genes encoding the implicated molecules may interfere with the colonization process, and consequently represent a primary etiology for HSCR. HSCR may therefore result from mutations in a major gene encoding a crucial molecule (whose penetrance may be modulated by other alleles) and/or from accumulation of less severe mutations in several genes. The HSCR phenotype may be a consequence of the interplay and/or accumulation of both common and rare functional and deleterious DNA variants in genes involved in ENS development, and despite the importance of RET, additiona l HSCR susceptibility genes exist. NEUREGULIN-1 (NRG1): NRG1 plays an important role in ENS development and maintenance [7-13] and we found it to be an additional major HSCR susceptibility gene through our genome-wide association (GWA) study on Chinese individuals[14]. We showed that aside from the RET SNPs, the strongest associations were found for two SNPs located in intron 1 of NRG1 on 8p12, with rs16879552 and rs7835688 yielding odds ratios of 1.68 [CI95%:(1.40,2.00), p=1.80x10-8] and 1.98 [CI95%:(1.59,2.47), p=1.12x10-9], respectively, for the heterozygous risk genotypes under an additive model. There was also a significant interaction between RET and NRG1 (p=0.0095), increasing the odds ratio 2.3-fold to 19.53 for the RET rs2435357 risk genotyp e (TT) in the presence of the NRG1 rs7835688 heterozygote. Several lines of evidence indicate that in addition to common variants/SNPs, rare variants may contribute substantially to the multifactorial inheritance of complex diseases. Moreover, the genes in which disease-asso ciated common variants are found are to be considered as candidates for the search of deleterious rare variants in the coding regions[15]. Therefore, rare NRG1 variants contributing to HSCR may exist. 1.: Identify CDS NRG1 rare variants by re-sequencing the 16 NRG1 exons, including their conserved intronic flanking regions, in 380 HSCR patients. REFERENCES 1 Puffenberger EG, et al. Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. Hum Mol Genet 1994;3:1217-25. 2 Angrist M, et al.Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient. Nat Genet 1996;14:341-4. 3 Hofstra RM, et al. A loss-of-function mutation in the endothelin-converting enzyme 1 (ECE-1) associated with Hirschsprung disease, cardiac defects, and autonomic dysfunction. Am J Hum Genet 1999;64:304-8. 4 Pingault V, et al. SOX10 mutations in patients with Waardenburg-Hirschsprung disease. Nat Genet 1998;18:171-3. 5 Amiel J, et al. Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet 2008;45:1-14. 6 Gariepy CE. Intestinal motility disorders and development of the enteric nervous system. Pediatr Res 2001;49:605-13. 7 Paratore C, et al. Sox10 haploinsufficiency affects maintenance of progenitor cells in a mouse model of Hirschsprung disease. Hum Mol Genet 2002;11:3075-85. 8 Britsch S. The neuregulin-I/ErbB signaling system in development and disease. Adv Anat Embryol Cell Biol 2007;190:1-65. 9 Britsch S, et al. The transcription factor Sox10 is a key regulator of peripheral glial development. Genes Dev 2001;15:66-78. 10 Press MF, et al. Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene 1990;5:953-62. 11 Prigent SA, et al. Expression of the c-erbB-3 protein in nor mal human adult and fetal tissues. Oncogene 1992;7:1273-8. 12 Meyer D, Birchmeier C. Distinct isoforms of neuregulin are expressed in mesenchymal and neuronal cells during mouse development. Proc Natl Acad Sci U S A 1994;91:1064- 8. 13 Crone SA, et al. Colonic epithelial expression of ErbB2 is required for postnatal maintenance of the enteric nervous system. Neuron 2003;37:29-40. 14 Garcia-Barcelo MM, et al. Genome-wide association study identifies NRG1 as a susceptibility locus for Hirschsprung's diseas e. PNAS 2008;in press. 15 Bodmer W, Bonilla C. Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet 2008;40:695-701.

Project Title:	Identification of functional variants in Neuregulin-1 (NRG1), a newly discovered Hirschsprungs disease gene
Investigator(s):	Garcia-Barcelo MM, Cherny SS, Sham PC, Tam PKH
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2009

Abstract:

1) Identification of functional or causative com mon DNA variants within the NRG1 HSCR-associated region (350 Kb) by genotyping 325 SNPs in 180 HSCR patients and 180 controls and test for association and functional evidence; 2) Identify CDS NRG1 rare variants by re-sequencing the 16 NRG1 exons in 180 HSCR patients.

Project Title:	59th Annual Meeting of the American Society of Human Genetics (ASHG) Identification of rare variants in the NRG1 gene of Hirschsprung’s patients
Investigator(s):	Garcia-Barcelo MM
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2009
Completion Date:	10/2009

Abstract:

N/A

Project Title:	Functional characterization of the V226L, H347Y, and P356L NRG1 mutations identified in Hirschsprung's disease patients
Investigator(s):	Garcia-Barcelo MM, Ngan ESW
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2010

Abstract:

The genetic architecture of complex diseases encompasses both common alleles that alone confer small risk, and rare alleles that are more likely to be functional and confer larger risks in a few people or families. Common variants are also thought to act as modifiers of the effects of rare variants. Several lines of evidence indicate that the genes in which common disea se-associated variants are found are likely to bear rare variants with functional effect. This is best exemplified by the well known contribution of both common and rare variants of the RET gene to the pathology of Hirschsprung’s disease [HSCR; congenital megacolon attributed to a failure of migration of the enteric ganglion precursors (=neural crest cells (NCCs)]. Indeed, HSCR is a complex genetic disorder that has become a paradigm for the study of complex diseases. Genes (known to date) involved in its pathogenesis encode proteins members of the inter-related signalling pathways (RET, EDRB) that govern the development of the enteric nervous system (ENS). The success of the colonization of the gut by NCCs depends on the synchronization and balance of the signalling networks implicated, thus, DNA alterations in those genes encoding the implicated molecules may interfere with the colonization process, and consequently, represent a primary aetiology for HSCR. HSCR may theref ore result from relatively penetrant functional rare variants in a major gene encoding a crucial molecule (whose penetrance may be modulated by other alleles) and/or from accumulation of less severe mutations in several genes, or the combination of both. Through a genome-wide association study (GWAS) conducted on Chinese HSCR patients, we identified a new HSCR contributing locus , the neuregulin 1 gene (NRG1; 8p12). Importantly, NRG1 contributes to the ENS development, providing a strong biological plausibility to our finding as per above. As several lines of evidence indicate that the genes in which common disease-associated variants are found, could be considered candidates for the search for functional rare variants/mutations, we sequenced the coding sequence (CDS) and intron/exon boundaries of the NRG1 gene in 368 sporadic patients and 360 contr ols (the sample size is being enlarged). We identified 4 rare variants among the patients (V266L, H347Y, P356L, E239fsX10) predicted to be deleterious. These were not found in any of the controls. The percentage of individuals with NRG1 mutations equals those reported for other HSCR genes. Of note are the studies conducted by Kryukov and others, which show that the majority of human rare nonsynonymous variants are deleterious, thus of significance to function and phenotype. OBJECTIVES: 1:Functional characterization of the NRG1 rare variants V266L, H347Y, P356L, E239fsX10.

List of Research Outputs

Cherny S.S. , Tang S.M. , Sribudiani Y., Miao X. , So M.T. , Sham P.C. , Tam P.K.H. , Garcia-Barcelo M.M. and Hofstra R.M., Fine mapping of Hirschsprung's disease loci in 9q31 (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Cornes B.K. , Tang S.M. , Leon Y.Y. , Hui K.J.W.S., So M.T. , Miao X. , Cherny S.S. , Sham P.C. , Tam P.K.H. and Garcia-Barcelo M.M. , Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population, PLoS One . 2010, 5 (6): e10918.

Garcia-Barcelo M.M. , Editorial Board Member, Journal of Biochemistry - Molecular Biology at the Post-genomic Era . 2009.

Garcia-Barcelo M.M. , Genetic basis of Hirschsprung's disease (Invited Lecture ), Visit Chanchung Children's Hospital, Changchun, China, 14 November 2009 . 2009.

Garcia-Barcelo M.M. , Genetic studies of Hirschsprung's disease (Invited Lecture), 2010第三屇全國胎兒疾病的診治及產時外科手術新進展培訓班暨全國小兒實 6-9 May 2010 . 2010.

Garcia-Barcelo M.M. , Yeung M.Y. , Miao X.P., Tang S.M. , Chen G., So M.T. , Ngan E.S.W. , Lui V.C.H. , Chen Y. , Liu X. , Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y. , Chan D. , Cheung K.M.C. , Chung P.H.Y., Wong K.K.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2, Human Molecular Genetics . 2010, 19 (14): 2917-2925.

Garcia-Barcelo M.M. , Tang W.Y. , Miao X. , Tang S.M. , So M.T. , Leon Y.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Identification of rare variants in the NRG1 gene of Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Garcia-Barcelo M.M. , Lui V.C.H. , So M.T. , Miao X. , Leon Y.Y. , Yuan Z.W., Ngan E.S.W. , Ehsan T., Chung P.H.Y., Khong P.L. , Wong K.K.Y. and Tam P.K.H. , MNX1 (HLXB9) mutations in Currarino patients, Journal of Pediatric Surgery . 2009, 44(10): 1892-1898.

Garcia-Barcelo M.M. , NRG1: common and rare variants in HSCR patients (Invited Lecture), International Human Stem Cell Research Consortium Meeting, Groningen, The Netherlands, 4-5 June 2010 . 2010.

Garcia-Barcelo M.M. , Review for Research Grant, National Medical Research Council Singapore . 2009.

Garcia-Barcelo M.M. , Reviewer for Research Grant, Associazione Italiana per la Ricerca sul Cancro . 2009.

Garcia-Barcelo M.M. , Reviewer for Research Grant, South African Medical Research Council . 2009.

Garcia-Barcelo M.M. , Reviewer, Annals of Human Genetics . 2009.

Garcia-Barcelo M.M. , Reviewer, BMC Genetics . 2009.

Garcia-Barcelo M.M. , Reviewer, Clinical Chemistry . 2009.

Garcia-Barcelo M.M. , Reviewer, Gastroenterology . 2009.

Garcia-Barcelo M.M. , Reviewer, Genome . 2009.

Garcia-Barcelo M.M. , Reviewer, Genomics . 2009.

Garcia-Barcelo M.M. , Reviewer, Gut . 2009.

Garcia-Barcelo M.M. , Reviewer, Human Molecular Genetics . 2009.

Garcia-Barcelo M.M. , Reviewer, Journal of Medical Genetics . 2009.

Garcia-Barcelo M.M. , Reviewer, Journal of Pediatric Surgery . 2009.

Garcia-Barcelo M.M. , Reviewer, PLoS One . 2009.

Garcia-Barcelo M.M. , Reviewer, Seminars in Pediatric Surgery . 2009.

Garcia-Barcelo M.M. , Reviewer, The New England Journal of Medicine . 2009.

Kenny S.E., Tam P.K.H. and Garcia-Barcelo M.M. , Hirschsprung’s disease, Seminars in Pediatric Surgery . 2010, 19: 194-200.

Lau G.S.K., Lang B.H.H. , Lo C.Y. , Tso A., Garcia-Barcelo M.M. , Tam P.K.H. and Lam K.S.L. , Prohylactic thyroidectomy in ethnic Chinese patients with multiple endocrine neoplasia type 2A syndrome after the introduction of genetic testing, Hong Kong Medical Journal . 2009, 15(5): 326-331.

Leon Y.Y. , Ngan E.S.W. , Poon H.C. , So M.T. , Lui V.C.H. , Tam P.K.H. and Garcia-Barcelo M.M. , Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3, Journal of Pediatric Surgery . 2009, 44(10): 1904-1912.

Miao X. , Garcia-Barcelo M.M. , So M.T. , Tang W.K. , Xiao D. , Wang B. , Mao J.X., Ngan E.S.W. , Chen Y. , Lui V.C.H. , Wong K.K.Y. , Liu L. and Tam P.K.H. , Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population, Journal of Pediatric Surgery . 2010, 45: 709-713.

Miao X. , Leon Y.Y. , Ngan E.S.W. , So M.T. , Yuan Z.W., Lui V.C.H. , Chen Y. , Wong K.K.Y. , Tam P.K.H. and Garcia-Barcelo M.M. , Reduced RET expression in gut tissue on individuals carrying risk alleles of Hirschsprung's disease, Human Molecular Genetics . 2010, 19(8): 1461-1467.

Ngan E.S.W. , Garcia-Barcelo M.M. , Yip B.H.K. , Sham P.C. , Lui V.C.H. and Tam P.K.H. , Hedgehog-notch induced premature gliogenesis of neural crest: a cause of Hirschsprung disease, International Society for Stem Cell Research, the 8th Annual Meeting, Moscone West, San Francisco, U.S. A. 16-19 June 2010 .

Sham P.C. , Cornes B.K., Tang S.M. , Leon Y.Y. , So M.T. , Tam P.K.H. and Garcia-Barcelo M.M. , A RET founder mutation in Chinese Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Tam P.K.H. and Garcia-Barcelo M.M. , Genetic basis of Hrischsprung's disease, Pediatric Surgery International . 2009, 25(7): 543-558.

Tang S.M. , Sribudiani Y., Miao X. , de Vries A.R., Burzynski G., So M.T. , Leon Y.Y. , Yip B.H.K. , Osinga J., Hui K.J.W.S., Verheij J.B.G.M., Cherny S.S. , Tam P.K.H. , Sham P.C. , Hofstra R.M.W. and Garcia-Barcelo M.M. , Fine mapping of the 9q31 Hirschsprung's disease locus, Human Genetics . 2010, 127(6): 675-683.

Tang S.M. , Garcia-Barcelo M.M. , Cherny S.S. , Sham P.C. and Tam P.K.H. , Genome-wide profile of copy number variants for Hirschspr ung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Yip B.H.K. , Ngan E.S.W. , Garcia-Barcelo M.M. , Cherny S.S. , Tang S.M. , Sham P.C. and Tam P.K.H. , Quantifying epistasis between two sets of signaling pathway genes by canonical correlation analysis: with application on Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Researcher : Geng W

List of Research Outputs

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Abstract), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , Identification of circulating protein markers related to tumor recurrence after liver transplantation (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s207.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantat ion . 2010, 16(6): s77.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Young Investigator Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Researcher : Geng W

List of Research Outputs

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Abstract), The 16th Annual International Congress of the Int ernational Liver Transplantation Society, Hong Kong, 16 - 19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Young Investigator Award), The 16th Annual International Congress of the Inte rnational Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Young Investigator Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Researcher : Guo D

List of Research Outputs

Cheng Q. , Ng T.P. , Fan S.T. , Lim Z.X.H. , Guo D. , Liu X. , Liu Y. , Poon R.T.P. , Lo C.M. and Man K. , Distinct mechanism of small-for-size fatty liver graft injury--Wnt4 signaling activates hepatic stellate cells, American Journal of Transplantation . 2010, 10(5): 1178-1188.

Man K. , Shih K.C. , Ng T.P. , Xiao J. , Guo D. , Sun K.W. , Lim Z.X.H. , Cheng Q. , Liu Y. , Fan S.T. and Lo C.M. , Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts, Annals of Surgery . 2010, 251(6): 1154-1161.

Researcher : Hao W

List of Research Outputs

Hao W. , Liu X. , Lee P.Y. , Chen Y. and Wong K.K.Y. , A study into the effects of omega-3 fatty acids on macrophages and hepatocytes, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Hao W. , Liu X. , Chan I.H.Y., Chan K.L. , Tam P.K.H. and Wong K.K.Y. , Comparison study of post-operative stress response between single-port and three-port laparoscopic varicocelectomy in children, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Lee P.Y. , Zhu Y. , Sun R.W.Y. , Hao W. , Liu X. , Che C.M. and Wong K.K.Y. , A safe and efficient lipidic nanoparticle carrier of gold porphryin for the treatment of neuroblastoma, The 3rd European Conference for Clinical Nanomedi cine, Basel, Switzerland, 10-12 May 2010 .

Lee P.Y. , Zhu Y. , Yan J., Sun R.W.Y. , Hao W. , Liu X.L., Che C.M. and Wong K.K.Y. , The cytotoxic effects of lipidic formulated gold-porphyrin nanoparticles for the treatment of neuroblastoma, Nanotechnology, Science and Applications . 2010, 3: 23-28.

Researcher : He GW

Project Title:	1999 American Physiological Society Conference: Biology of Potassium Channels (From Molecules to Disease) Role of K+ Channels in Endothelum-derived Hyperpolarizing Factor (EDHF)-mediated Function in Coronary Microartery 2) Reduced Conductance of Kca and K ATP Channels by University of Wisconsin Soluti on (UWS) in Coronary Microartery
Investigator(s):	He GW
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	09/1999

Abstract:

N/A

Researcher : Ho ACW

List of Research Outputs

Chan Y.W. , Ho A.C.W. and Wei W.I. , Prediction of surgical outcome using plasma Epstein-Barr virus DNA and 18F-FDG PET scan in recurrent nasopharyngeal carcinoma, 4th World Congress of International Federation of Head and Neck Oncologic Societies (IFHNOS) - Shifting Paradigms in Head and Neck Oncology 2010 - Seoul, Kor ea . 2010.

Chung J.C.K., Ho A.C.W. , Chan Y.W. and Wei W.I. , Outcomes of head and neck cancers in haemic malignancy patients, 4th World Congress of International Federation of Head and Neck Oncologic Societies (IFHNOS) - Shifting Paradigms in Head and Neck Oncology 2010 - Seoul, Korea . 2010.

Researcher : Ho DWY

List of Research Outputs

Lau C.K. , Yang Z. , Ho D.W.Y. , Ng N.P. , Poon R.T.P. and Fan S.T. , Discruption of Akt/hif1 signaling can enhance the the rapeutic efficacy of ischemic hypoxia and chemotherapy, The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Yang Z. , Fan S.T. , Ho D.W.Y. , Yu W.C. , Lau C.K. , Ng N.P. and Lam C.Y. , Liver cancer stem cells and HCC recurrence (Oral Presentation), The International Liver Cancer Association Third Annual Congress, Milan, Italy, 4 - 6 September 2009 .

Researcher : Ho JWC

Project Title:	The Hereditary Gastrointestinal Cancer Registry - a programme for the people of Hong Kong
Investigator(s):	Ho JWC, Yuen ST, Chung LP, Kwan KYM
Department:	Surgery
Source(s) of Funding:	Terry Fox Fellowship
Start Date:	06/2000

Abstract:

To achieve colorectal cancer prevention in high risk families through early detection and timely treat ment; to raise awareness of hereditary colorectal cancer through education of the public and the health care profession so as to ensure proper referral of these families to our Registry for the delivery of proper preventive service; to establish support services to improve psychosocial well beings of affected individuals and their at-risk family members; to improve the understandi ng of hereditary colorectal cancer and its management.

Project Title:	A Genome-Wide Association Study on the Predisposition to Colorectal Cancer in the Han Chinese Population in Hong Kong
Investigator(s):	Ho JWC, Sham PC
Department:	Surgery
Source(s) of Funding:	Michael and Betty Kadoorie Cancer Genetics Research Programme (MBKCGRP) II
Start Date:	01/2008

Abstract:

To search for and study colorectal cancer susceptibility alleles in Han Chinese population.

List of Research Outputs

Ho J.W.C. , Ho M.Y. , Chu A.T.W. and Chan M.S. , Hopefulness predicts residence after hereditary colorectal cancer genetic testing in Hong Kong Chinese: results of a longitudinal study (Abstract and proceeding), National Cancer Research Institute Cancer Conferen ce, Birmingham, U.K., 4-7 October 2009 .

Ho J.W.C. , Risk factors, primary and secondary prevention of hereditary and sporadic colorectal cancers, Colorectal Symposium 2010 - Multi-disciplinary Man agement for Colorectal Cancer organized by Queen Mary Hospital, Tung Wah Hospital and The University of Hong Kong, Hong Kong, 19 June 2010 . 2010.

Ho M.Y. , Ho J.W.C. , Bonanno G.A., Chu A.T.W. and Chan M.S. , Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study, BMC Cancer . 2010, 10: 279.

Lee V.H.F. , Ng C.Y. , Liu K.Y. , Law W.L. , Ho J.W.C. , Chua D.T.T. , Kwong D.L.W. , Choy T.S. , Leung T.W. and Au G.K.H. , Dosimetric Analysis of Pre-operative and Post-operative Concurrent Chemotherapy with Conformal Radiotherapy Delivered by 5 or 6 Beams for Rectal Cancer. , Hong Kong College of Radiologists . Hong Kong, Hong Kong College of Radiologists, 2009.

Lee Y.F., Choi A.S.C., Hui T.C.K., Tomlinson I., Houlston R., Cheng K.K., Sham P.C. and Ho J.W.C. , rs10795668 located at 10p14 is associated with colorectal cancer risk in Han Chinese (Abstract and proceeding), National Cancer Research Institute Cancer Conference, Birmingham, U.K., 4-7 October 2009 .

Tomlinson I.P., Dunlop M., Campbell H., Zanke B., Gallinger S., Hudson T., Koessler T., Pharoah P.D., Niittymakix I., Tuupanenx S., Aaltonen L.A., Hemminki K., Lindblom A., Forsti A., Sieber O., Lipton L., van Wezel T., Morreau H., Wijnen J.T., Devilee P., Matsuda K., Nakamura Y., Castellvi-Bel S., Ruiz-Ponte C., Castells A., Carracedo A., Ho J.W.C. , Sham P., Hofstra R.M., Vodicka P., Brenner H., Hampe J., Schafmayer C., Tepel J., Schreiber S., Volzke H., Lerch M.M., Schmidt C.A., Buch S., Moreno V., Villanueva C.M., Peterlongo P., Radice P., Echeverry M.M., Velez A., Carvajal-Carmona L., Scott R., Penegar S., Broderic k P., Tenesa A. and Houlston R.S., COGENT (COlorectal cancer GENeTics): an international consortium to study the role of polymorphic variation on the risk of colorectal cancer, British Journal of Cancer . 2010, 102(2): 447-454.

Researcher : Ho KL

List of Research Outputs

Chan T.Y., Ho K.L. , Chu S.S.M. and Tam P.C. , Robotic-assisted laparoscopic ureteral reimplantation for distal ureteric stricture (Motion Picture), Surgical Practice . 2009, 13(Suppl. 2): B5.

Ho K.L. , Wong C.W.S. , Au W.H. , Chu S.S.M. and Tam P.C. , Early continence outcomes after robotic radical prostatectomy - impact of vesicourethral reconstruction (Poster Presentation), The American Urological Association Annual Meeting, San Francisco, USA, 29 May - 3 June 2010 .

Ho K.L. , Tsui H.L., Au W.H. , Chu S.S.M. and Tam P.C. , Early continence outcomes after robotic radical prostatectomy: impact of vesicourethral reconstruction, Surgical Practice . 2009, 13(Suppl. 2): B7.

Ho K.L. , Tsu J.H.L. , Ng W.M. , Law W.L. , Tam P.C. and Lo B.S.H. , Rectourethral fistula after radical prostatecomy: transperin eal repair in jack-knife position, Surgical Practice . Hong Kong, College of Surgeons of Hong Kong, 2010, 14: 102-104.

Ho K.L. , Tam P.C. , Chu S.S.M. , Au W.H. and Tsu H.L., Robotic-assisted laparoscopic partial nephrectomy - evolution of techniques and peri-operative outcomes, The 1st Hong Kong Congress of Endourology, Hong Kong, 28-29 August 2009 .

Tsu H.L., Ho K.L. , Au W.H. , Chu S.S.M. and Tam P.C. , Robotic-assisted laparoscopic radical cystectomy and construction of neobladder urethral anastomosis for urothelial carcinoma of bladder, The 1st Hong Kong Congress of Endourology, Hong Kong, 28-29 August 2009 .

Researcher : Ho WK

Project Title:	Effect of chemotherapy on cochlear function
Investigator(s):	Ho WK
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	06/1996

Abstract:

To assess the severity of cochlear damage in patient receiving chemotherapy for cancer.

Project Title:	Evaluation of a novel electronic device in screening for obstructive sleep syndrome in snore
Investigator(s):	Ho WK, Chung KF
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	03/2002

Abstract:

To evaluate the accuracy of the SleepStrip as a tool for obstructive sleep apnea screening insnorers .

Project Title:	Study of changes in upper airway pressure in patients before and after upper airway surgery for sleep-related breathing disorders: identification of levels of collapse and prediction of surgical response
Investigator(s):	Ho WK, Wei WI
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To evaluate the using of multi-level pressure measurements to correlate with the result of surgical treatment.

List of Research Outputs

Wong B.Y.H. , Ng W.M. , Yuen P.W. , Chan J.P.H. , Ho W.K. and Wei W.I. , Early resection and reconstruction of head and neck masses in infants with upper airway obstruction, International Journal of Pediatric Otorhinolaryngology . 2010, 74: 287-291.

Wong S.T.S. , Chan W.S. , Li C.H., Liu W.M. , Tang W.W., Tsao G.S.W. , Tsang R.K.Y. , Ho W.K. , Wei W.I. and Chan Y.W. , Curcumin alters the migratory phenotype of nasopharyngeal carcinoma cells through up-regulation of E-cadherin , Anticancer Research . 2010, 30: 2851-6.

Wong S.T.S. , Ho W.K. , Chan Y.W. , Ng W.M. and Wei W.I. , Mature miR-184 and squamous cell carcinoma of tongue, Head and Neck . 2009, 9: 130-132.

Wong S.T.S. , Man O.Y. , Tsang C.M. , Tsao G.S.W. , Tsang R.K.Y. , Chan Y.W. , Ho W.K. , Wei W.I. and To V.S.H. , Microrna Let-7 Suppresses Nasopharyngeal Carcinoma Cells Proliferation Through Downregulating C-myc Expression, Journal of Cancer Research and Clinical Oncology . Berlin, Springer Berlin / Heidelberg, 2010.

Researcher : Huang L

List of Research Outputs

Wong K.K.Y. , Cheung S.O.F. , Huang L. , Niu J. , Tao C. , Ho C.M. , Che C.M. and Tam P.K.H. , Further evidence of the anti-inflammatory effects of silver nanoparticles, ChemMedChem . 2009, 4(7): 1129-1135.

Researcher : Hung KN

List of Research Outputs

Lee V.H.F. , Hung K.N. , Chua D.T.T. , Kwong D.L.W. , Leung T.W. and Au G.K.H. , Evaluation of Three Stratification Systems Predicting Recurrence and Prognosis in Patients with Brain Metastas es after Tumour Removal and Whole-brain Irradiation. , American Society of Clinical Oncology . USA, ASCO, American Society of Clinical Oncology (ASC O), 2010.

Leung G.K.K. , Hung K.N. , Lui W.M. and Fan Y.W. , Combined transcranial and transsphenoidal resection of huge pituitary adenoma, The 7th Meeting of the Asian Society for Neuro-oncology, Seoul, Korea, 10 - 12 June 2010 .

Yung A.W.Y. , Wong V.C.N. , Khong P.L. , Mak H.K.F. , Hung K.N. , Chan P.H., Ho W.Y. and Fan Y.W. , Paediatric Epilepsy Surgery Program in Hong Kong - a single centre experience, Annual Scientific Meeting 2009, The Hong Kong Neurological Society, Hong Kong, 7 November 2009 .

Researcher : Kam KM

List of Research Outputs

Kam K.M. , Lui V.C.H. , Cheung M.C.H. and Tam P.K.H. , Expression of engrailed-Hoxb5 transcriptional repressor by Wnt1-Cre produces neurocristopathies of pigmentatio n and enteric nervous system defects in mice., 43rd Annual Meeting for the Japanese Society of Developmental Biologists Kyoto, Japan, 20 June 2010 . 2010.

Kam K.M. , Lui V.C.H. , Cheung M.C.H. and Tam P.K.H. , Expression of engrailed-Hoxb5 transcriptional repressor by Wnt1-Cre produces neurocristopathies of pigmentation and enteric nervous system defects in mice, 43rd Annual Meeting for the Japanese Society of Developmental Biologists, Jointly Sponsored by the Asia-Pacific Developmental Biology Network, Kyoto, Japan, 20-23 June . 2010.

Researcher : Kong PC

List of Research Outputs

Kong P.C. , Nucleocytoplasmic shuttling of Smad7 that plays paradoxic al roles in hepatocellular carcinoma, Dissertation, Master of Philosophy, Li Ka Shing Faculty of Medicine, The University of Hong Kong . 2010.

Researcher : Kwok SPY

List of Research Outputs

Chan S.W.W. , Cheung P.S.Y. , Lee J.F.Y., Fung J.T.K., Patil N.G. and Kwok S.P.Y. , Women surgeons in Hong Kong, Surgical Practice . Hong Kong, College of Surgeons of Hong Kong, 2010, 14 (1): 2-7.

Researcher : Kwong A

List of Research Outputs

Au A.H.Y. , Lam W.W.T. , Chan M., Or A., Kwong A. , Suen D.T.K. , Wong A.L., Butow P.N. and Fielding R. , Development and evaluation of a decision aid booklet for Chinese women facing a choice of breast cancer surgery (abstract and poster presentation), 16th Hong Kong International Cancer Congress, 4-6 November 2009, Hong Kong . Hong Kong, LKS Faculty of Medicine, HKU, 2009, A60.

Cheung T.T. , Suen D.T.K. and Kwong A. , Is sentinel lymph node biopsy after neoadjuvant chemotherapy feasible in Chinese patients with invasive breast cancers?, ANZ Journal of Surgery . 2009, 79(10): 719-723.

Kwong A. , Choice of management of Chinese women who carry the BRCA mutation (Abstract) (Oral), International Surgical Week, Adelaide, Australia, 6 - 10 September 2009 .

Kwong A. , Wong C.H., Shea C., Suen D.T.K. and Choi C.L., Choice of management of Southern Chinese BRCA mutation carriers, World Journal of Surgery . 2010, 34(7): 1416-1426.

Kwong A. , Wong L.P., Wong H.N. , Law F.B.F. , Ng E.K.O. , Tang Y.H., Chan W.K., Suen D.T.K. , Choi C., Ho L.S., Kwan K.H., Poon M., Wong T.T., Chan K., Chan S.W., Ying M.W., Chan W.C., Ma E.S., Ford J.M. and West D.W., Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer, Hugo Journal . 2010, 3(1-4): 63-76.

Kwong A. , Ng E.K.O. , Law F.B.F. , Wong L.P., To M.Y., Cheung M.T. , Wong H.N. , Chan V.W., Kurian A., West D.W. , Ford J.M. and Ma E.S., High-resolution melting analysis for rapid screening of BRCA2 founder mutations in Southern Chinese breast cancer patients, Breast Cancer Research and Treatment . 2010, 122(2): 605-607.

Kwong A. , Male breast cancer in Chinese population (Abstract) (Poster), International Surgical Week, Adelaide, Australia, 6-10 September 2009 .

Kwong A. , Ng E.K.O. , Leung C.P.H. , Tsang W.P., Wong L.P. , Kwok T.T. and Ma E.S.K. , Role of miR-143 regulating DNA methyltransferases 3A in breast cancer, Ejc Supplements . 2010, 8(3): 172-173.

Kwong A. , To achieve resonance from a single voice, International Surgical Week, Adelaide, Australia, 6 - 10 September 2009 .

Kwong A. and So K.W. , 乳癌治療新知及紓緩護理, 育醫造才：探索醫學世界, 香港, 香港大學李嘉誠醫學院, 2010, 66-68.

Lam W.W.T. , Chan M., Or A., Kwong A. , Suen D.T.K. , Butow P.N. and Fielding R. , Evaluation of a decision aid for Chinese women considering breast cancer surgery for localized breast cancer: A pilot study (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong . Hong Kong, School of Public Health/HKU, 2009, 120.

Law T.T. and Kwong A. , Surgical margins in breast conservation therapy: how much should we excise?, South Medical Journal . 2009, 102(2): 1234-1237.

Ng E.K.O. , Leung C.P.H. , Au S., Chan A., Wong L.P. , Ma E.S.K. , Pang R.W.C. , Chua D.T.T. , Chu K.M. , Law W.L. , Poon R.T.P. and Kwong A. , Plasma microRNA as a potential marker for breast cancer detection, The 101st Annual Meeting of the American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Ng E.K.O. , Kwong A. , Tsang W.P., Leung C.P.H. , Wong L.P. , Kwok T.T. and Ma E.S.K. , Role of miR-143 regulating DNA methyltransferases 3A in breast cancer, Cancer Research . 2009, 69(24): 695S-695S.

Ng K.O. , Wong C.L.P., Ma E.S.K. and Kwong A. , Micro RNAS as new players for diagnosis, prognosis, and therapeutic targets in breast cancer, Journal of Oncology . 2009, 2009: 305420.

Shek H.P. , Luk J.M.C. , Kwong A. and Lee N.P.Y. , The role of serine peptidase inhibitor, Kazal type I (SPINK1) in hepatocellular carcinoma (Poster Presentation), Cancer Omics, Erice, Italy, 3-8 May 2010 .

Suen D.T.K. and Kwong A. , Breast-conserving surgery in Asian women: benefits and potential harm (reply to letter), World Journal of Surgery . 2009, 33(7): 1550-1551.

Suen D.T.K. and Kwong A. , Young Chinese patients with breast cancer have a similar survival to their older counterparts (Abstract) (Poster), International Surgical Week, Adelaide, Australia, 6 - 10 September 2009 .

Researcher : Lam BKY

List of Research Outputs

Chan A.C.Y. , Fan S.T. , Lo C.M. , Liu C.L. , Chan S.C. , Ng K.K.C. , Yong B.H. , Chiu A. and Lam B.K.Y. , Liver transplantation for acute-on-chronic liver failure, Hepatology International . 2009, 3(4): 571-581.

Researcher : Lam CT

Project Title:	The potential role of CD44 in liver regeneration
Investigator(s):	Lam CT
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	01/2010

Abstract:

Introduction and aims of study Liver is an intriguing organ with an almost unlimited capacity to regenerate (1). Liver regeneration is a protective response of liver to injury (1) caused by hepatectomy, virus infection, inflammation or intoxication. Three potential sources of cells are proposed to contribute to the restorati on of liver mass: hepatocytes, oval cells (in rodents; hepatic progenitor cells in human) and bone marrow-derived stem cells (2, 3). Different cell lineages may participate in the process depending on the nature and extent of hepatic injury. In response to routine and moderate cell losses, replication of existing hepatocytes is generally thought to be a major way to restore liver mass (2, 3). Oval cells, locating within the liver lobules, take part in the process and differentiate into hepatocytes when the replication of mature hepatocytes is inhibited (2, 3), for example, during massive liver damage. The involvement of bone marrow cells (BMCs) in liver regeneration, however, remained controversial. Generation of hepatocytes from BMCs were reported in both animal models and clinical studies in which livers from patients who received sex-mismatched liver or bone marrow transplants were examined (4, 5). However, no consistent results could be obtained by different investigators (4, 6), suggesting that hepatocyte replacement by BMCs is inefficient and rare. It was suggested that cell fusion between host hepatocytes and donor BMCs may occur after bone marrow transplantation (7). On the other hand, BMCs have been shown to participate in liver regeneration process by differentiating into sinusoidal endothelial and Kupffer cells after partial hepatectomy (8). CD44 is a multifunctional cell surface glycoprotein (9) and is expressed in many cell types. The major ligand for CD44 is hyaluronic acid, an extracellular matrix (ECM) component (9). Other ECM components including collagen, fibronectin, laminin, and chondroitin sulfate can also serve as ligands for CD44. This receptor has been shown to play roles in various biological processes. It is involved in cell adhesion, migration, cell-cell and cell-matrix intera ctions, lymphocyte homing and activation, inflammation, tumor growth and metastasis (9-12). CD44 exists as multiple variants resulting from alternative splicing (9, 13). Among around 20 different isoforms, CD44s (standard) is the most abundant form (10). Variant forms of CD44 including CD44v6 are involved in tumor development and the metastatic potential of various cancers, such as colorectal, breast, melanoma and hepatocellular carcinoma (HCC) (11, 12, 14-17). Intriguingly, CD44 has been proposed to play a role in liver regeneration by demonstrating the induction of CD44v6 expression after partial hepatectomy (11). In addition, expression of CD44 has been shown in small hepatocytes, a subpopulation of hepatocytes which are regarded as ‘committed progenito r cells’ and have the ability to differentiate into mature hepatocytes (18). The findings suggested that CD44 may play a role in promoting the maturation process of small hepatocytes. Furthermore, CD44 expression in endothelial cells has been demonstrated to be crucial for the development of tubular networks during in vivo angiogenesis (19). Although there is cumulative evidence suggesting the potential linkage between CD44 and liver regeneration, the detailed role of this receptor in the process remained incompletely defined. Provided that CD44 plays a role in modulating cell migration and is involved in angiogenesis (19), it will be interesting to determine if CD44 regulates mobilization of bone marrow-derived endothelial progenitor cells during regeneration-associated hepatic angiogenesis. My prel iminary data showed that over 99% of BMCs express CD44, suggesting the importance of this receptor for BMCs. Taking together, it is tempting to propose that CD44 may be responsibl e for formation of new blood vessels in regenerating liver by recruiting bone marrow-derived progenitor cells. The present study aims at studying the mechanisms of action of CD44 on regulating liver regeneration and elucidating the potential role of CD44 in mobilization of endothelial progenitor cells from bone marrow. References 1. Michalopoulos GK, DeFrances MC. Liver regeneration. Science 1997;27 6:60-6. 2. Fausto N. Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells. Hepatology 2004;39:1477-87. 3. Pai M, Habib NA. Stem Cell Therapy in Liver Disease In: Karaliotas CC, Broelsch CE, Habib NA, editors. Liver and Biliary Tract Surgery Embryological Anatomy to 3D-Imaging and Transplant Innovations New York: SpringerWienNewY ork; 2006. p. 433-9. 4. Theise ND, Badve S, Saxena R, et al. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology 2000;31:235-40. 5. Theise ND, Nimmakayalu M, Gardner R, et al. Liver from bone marrow in humans. Hepatology 2000;32:11-6. 6. Wang X, Montini E, Al-Dhalimy M, Lagasse E, Finegold M, Grompe M. Kinetics of liver repopulation after bone marrow transplantation. Am J Pathol 2002;161:565-74. 7. Wang X, Willenbring H, Akkari Y, et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 2003;422:897-901. 8. Fujii H, Hirose T, Oe S, et al. Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice. J Hepatol 2002;36:653-9. 9. Naor D, Sionov RV, Ish-Shalom D. CD44: structure, function, and association with the malignant process. Adv Cancer Res 1997;71:241-319. 10. Bonder CS, Clark SR, Norman MU, Johnson P, Kubes P. Use of CD44 by CD4+ Th1 and Th2 lymphocytes to roll and adhere. Blood 2006;107:4798-806. 11. Della Fazia MA, Pettirossi V, Ayroldi E, Riccardi C, Magni MV, Servillo G. Differen tial expression of CD44 isoforms during liver regeneration in rats. J Hepatol 2001;34:555-61. 12. Guo Y, Ma J, Wang J, et al. Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody. Cancer Res 1994;54:1561-5. 13. Kikuchi S, Griffin CT, Wang SS, Bissell DM. Role of CD44 in epithelial wound repair: migration of rat hepatic stellate cells utilizes hyaluronic acid and CD44v6. J Biol Chem 2005;280 :15398-404. 14. Gotte M, Yip GW. Heparanase, hyaluronan, and CD44 in cancers : a breast carcinoma perspective. Cancer Res 2006;66:10233-7. 15. Slomiany MG, Grass GD, Robertson AD, et al. Hyaluronan, CD44, and emmprin regulate lactate efflux and membrane localization of monocarboxylate transporters in human breast carcinoma cells. Cancer Res 2009;69:1293-301. 16. Endo K, Terada T. Protein expression of CD44 (standard and variant isoforms) in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, p53 expression, and patient survival. J Hepatol 2000;32:78-84. 17. Yang ZF, Ngai P, Ho DW, et al. Identification of local and circulating cancer stem cells in human liver cancer. Hepatology 2008;47:919-28. 18. Kon J, Ooe H, Oshima H, Kikkawa Y, Mitaka T. Expression of CD44 in rat hepatic progenitor cells. J Hepatol 2006;45:90-8. 19. Cao G, Savani RC, Fehrenbach M, et al. Involvement of endothelial CD44 during in vivo angiogenesis. Am J Pathol 2006;169:325 -36.

Project Title:	AACR 101st Annual Meeting 2010 The proangiogenic role of brain-derived neurotrophic factor in tumor development
Investigator(s):	Lam CT
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	04/2010
Completion Date:	04/2010

Abstract:

N/A

List of Research Outputs

Lam C.T. , Yang Z. , Fan S.T. and Poon R.T.P. , The proangiogenic role of brain-derived neurotrophic factor in tumor development , The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Researcher : Lam CY

List of Research Outputs

Lam C.Y. , Poon T.C.W. and Cheung S.T. , Identification of novel interacting partner of granuli n-epithelin precursor in hepatocellular carcinoma (Poster Presentation), The 16th Hong Kong International Cancer Congress and The 6th Annual Meeting Centre for Cancer Research, Hong Kong, 4-6 November 2009 .

Lam C.Y. , Poon T.C.W., Cheng C.K.C. and Cheung S.T. , Interacting protein of granulin-epithelin precursor in liver cancer, The 101st Annual Meeting of the American Association for Cancer Research, Washington, DC, U.S.A., 17-21 April 2010. Proceedings of the AACR . 2010, 51: 3130.

Yang Z. , Fan S.T. , Ho D.W.Y. , Yu W.C. , Lau C.K. , Ng N.P. and Lam C.Y. , Liver cancer stem cells and HCC recurrence (Oral Presentation), The International Liver Cancer Association Third Annual Congress, Milan, Italy, 4 - 6 September 2009 .

Researcher : Lam TT

List of Research Outputs

Man K. , Cheng Q. , Liu Y. , Lam T.T. , Ng T.P. and Lo C.M. , Inflammatory microenvironment accelerates liver tumor growth and metastasis by mobilizing circulating endo thelial progenitor cells and increasing cancer stem like cell populations (Abstract), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): S97.

Researcher : Lam VWT

List of Research Outputs

Chok K.S.H. , Chu F.S.K. , Cheung T.T. , Lam V.W.T. , Yuen W.K. , Ng K.K.C. , Chan S.C. , Poon R.T.P. , Yeung C. , Lo C.M. and Fan S.T. , Results of percutaneous transhepatic cholecystostomy for high surgical risk patients with acute cholecystitis, ANZ Journal of Surgery . 2010, 80(4): 280-283.

Researcher : Lan LCL

List of Research Outputs

Chan I.H.Y., Wong K.K.Y. , Lan L.C.L. and Tam P.K.H. , Early experience of single port laparoscopic surgery in a tertiary referral centre in Hong Kong, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Chung P.H.Y., Lan L.C.L. , Wong K.K.Y. and Tam P.K.H. , Deflux injection for the treatment of vesicoureteric reflux in children—a single centre's experience, Asian Journal of Surgery . 2009, 32(3): 163-166.

Chung P.H.Y., Wong K.K.Y. , Lan L.C.L. and Tam P.K.H. , Thoracoscopic bullectomy for primary spontaneous pneumothorax in pediatric patients, Pediatric Surgery International . 2009, 25(9): 763-766.

She W.H., Chung H.Y., Lan L.C.L. , Wong K.K.Y. , Saing H. and Tam P.K.H. , Management of choledochal cyst: 30 years of experience and results in a single center, Journal of Pediatric Surgery . 2009, 44(12): 2307-2311.

Wong K.K.Y. , Chung P.H.Y., Lan L.C.L. , Chan I.H.Y. and Tam P.K.H. , The first report of a single-port laparoscopic nephrectomy in a child, Hong Kong Medical Journal . 2010, 16(2): 153-154.

Researcher : Lang BHH

List of Research Outputs

Lang B.H.H. and Lo C.Y. , Cancer: QTNM: a simplified TNM or just another staging system?, Nature Reviews. Endocrinology . 2009, 5(10): 531-532.

Lang B.H.H. and Lo C.Y. , Cushing's disease and syndrome, In: Hubbard J.G.H., Inabnet W. B. and Lo C.Y. (eds), Endocrine Surgery. Principles and Practice . London, Springer-Verlag, 2009, 379-390.

Lang B.H.H. , Minimally invasive thyroid and parathyroid surgery, Hong Kong Medical Diary . 2009, 14(7): 9-11.

Lang B.H.H. and Lo C.Y. , Technological Innovations in Surgical Approach for Thyroid Cancer, Journal of Oncology . 2010, 2010: 6.

Lang B.H.H. and Lo C.Y. , Vitamin D(3) deficiency is associated with late-onset hypocalcemia after minimally invasive parathyroidectomy in a vitamin D borderline area, World Journal of Surgery . 2010, Epub ahead of print.

Lau G.S.K., Lang B.H.H. , Lo C.Y. , Tso A., Garcia-Barcelo M.M. , Tam P.K.H. and Lam K.S.L. , Prohylactic thyroidectomy in ethnic Chinese patients with multiple endocrine neoplasia type 2A syndrome after the introduction of genetic testing, Hong Kong Medical Journal . 2009, 15(5): 326-331.

Romano M.E., Wahlander S.B., Lang B.H.H. , Li G.K.H. and Prager K.M., Mandatory Ethics Consultation Policy, Mayo Clin Proc . 2009, 2009: 5.

Researcher : Lau CK

Project Title:	Combined sorafenib with chemotherapy for HCC treatment
Investigator(s):	Lau CK, Yang Z
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	11/2008
Completion Date:	04/2010

Abstract:

HCC is the fifth most common solid tumor in the world (fifth among men and eighth among women), with its incidence ranging from <10 cases per 100,000 persons in North America and Western Europe to 50-150 cases per 100,000 persons in parts of Africa and Asia. Therefore, HCC is the third most common cause of cancer-related mortality which accounts for about 500,000 deaths each year (1-3). The highest incidence of HCC is seen in China (~100 per 100,000 population). In Hong Kong, the incidence of HCC is 36 per 100,000 population, and it is the second leading cause of cancer deaths (4). Treatment of HCC is classified into three categories: i) systemic treatments including chemotherapy; ii) surgical treat ments including hepatic resection and liver transplantation; and iii) non-surgical treatments including radiofrequency ablation. A variety of systemic chemotherapeutic agents have been tested in HCC, such as 5-fluorouracil, doxoru bicin and cisplatin. However, most research shows that response rates of HCC to chemotherapy are <20%, which is considered to be a low level of treatment effectiveness for most cancers, and very few claims to be able to prolong patient survival (5, 6). The possible reason of poor response is due to chemoresistance developed in tumor cells. Because of lacking effective systemic therapy for HCC, molecular targeting therapy is of particular significance. Initial favorable results of tyrosine kinase inhibitors were reported at the 2005 American Society of Clinical Oncology (ASCO) meeting. A small molecule tyrosine kinase inhibitor named sorafenib, which targets Raf kinase, VEGF, PDGFR-, c-KIT and Flt3 has been used in phase III clinical trial in advanced renal cell carcinoma. The results of this inhibitor led to the approval of the US FDA, and a large international multicenter phase III trial is now underway in patients with advanced HCC based on the promising results in early clinical studies. Several important intracellular signaling pathways such as the Ras/Raf/Mek/Erk pathway and PI3k/Akt/mTOR pathway have been found to relate to chemoresistance (7). It is of interest to investigate the combined effect of molecular targeting therapy with chemothera py. The purpose of this proposed project is to compare the therapeutic efficacy of combined sorafenib and cisplatin treatment with sorafenib or cisplatin alone on HCC. References 1. Bosch FX, Ribes J, Cleries R, Diaz M. Epidemiology of hepatocellular carcinoma. Clin Liver Dis 2005;9:191-211, v. 2. El-Serag HB, Davila JA, Petersen NJ, McGlynn KA. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 2003;139:817- 23. 3. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108. 4. Cancer incidence in five continents. Volume VIII. IARC Sci Publ 2002:1-781. 5. Llovet JM, Beaugrand M. Hepatocellular carcinoma: present status and future prospects. J Hepatol 2003;38 Suppl 1:S136-49. 6. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003;37:429-42. 7. Thompson JE, Thompson CB. Putting the rap on Akt. J Clin Oncol 2004;22:4217-26.

Project Title:	AACR 101st Annual Meeting 2010 Discruption of akt/hif1 signaling can enhance the therapeutic efficacy of ischemic hypoxia and chemotherapy
Investigator(s):	Lau CK
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	04/2010
Completion Date:	04/2010

Abstract:

N/A

List of Research Outputs

Lau C.K. , Yang Z. , Ho D.W.Y. , Ng N.P. , Poon R.T.P. and Fan S.T. , Discruption of Akt/hif1 signaling can enhance the therape utic efficacy of ischemic hypoxia and chemotherapy, The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Lau C.K. , Outstanding Research Postgraduate, Department of Surgery, The University of Hong Kong . 2009.

Yang Z. , Fan S.T. , Ho D.W.Y. , Yu W.C. , Lau C.K. , Ng N.P. and Lam C.Y. , Liver cancer stem cells and HCC recurrence (Oral Presentation) , The International Liver Cancer Association Third Annual Congress, Milan, Italy, 4 - 6 September 2009 .

Researcher : Lau CST

List of Research Outputs

Ngan E.S.W. , Lau C.S.T. , Wo Y.H. , Chan W.K. , Chan G.C.F. , Wang Y. , Kaplan D. and Tam P.K.H. , Endocrine-gland vascular endothelial growth factor (EG-VEGF) in neuroblastoma tumor initiating cells, Advances in Neuroblastoma Research 2010, Stockham, Sweden, 21-24 June 2010 .

Researcher : Law FBF

List of Research Outputs

Kwong A. , Wong L.P., Wong H.N. , Law F.B.F. , Ng E.K.O. , Tang Y.H., Chan W.K., Suen D.T.K. , Choi C., Ho L.S., Kwan K.H., Poon M., Wong T.T., Chan K., Chan S.W., Ying M.W., Chan W.C., Ma E.S., Ford J.M. and West D.W., Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer, Hugo Journal . 2010, 3(1-4): 63-76.

Kwong A. , Ng E.K.O. , Law F.B.F. , Wong L.P., To M.Y., Cheung M.T. , Wong H.N. , Chan V.W., Kurian A., West D.W. , Ford J.M. and Ma E.S., High-resolution melting analysis for rapid screening of BRCA2 founder mutations in Southern Chinese breast cancer patients, Breast Cancer Research and Treatment . 2010, 122(2): 605-607.

Researcher : Law SYK

Project Title:	Potential Roles of RON and Its Ligand Macrophage Stimulating Protein (MSP) as Prognostic Markers in Esophageal Squamous Cell Carcinoma (ESCC)
Investigator(s):	Law SYK, Luk JMC
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2006

Abstract:

Esophageal cancer is the sixth most frequent cause of cancer death in the world. Esophageal squamous cell carcinoma (ESCC) is the commonest histological cell type in Asia and in Hong Kong. Advances in operative techniques and peri-operative care have made esophagectomy a safe procedure in specialized centers. In spite of this and recent advances in multimodality treatments including chemotherapy and radiotherapy, the prognos is of patients with esophageal cancer remains poor because of late diagnosis, the propensity of early spread of disease, and its occurrence in a group of elderly patients with co-morbid illnesses. The identification of a sensitive and specific disease marker is important for prognostication and to guide appropriate treatment. RON (Récepteur d’Origine Nantais) is a 185kDa tyrosine kinase receptor in the MET family. It is a transmembrane protein consists of a 150kDa β-subunit and a 40kDa α-subunit which are disulfide-linked. The receptor is normally expressed on epithelial cells, macrophages, bone marrow stem cells, and osteoclasts. It mediates a broad range of biological activities including cell proliferation, cellular adhesion, invasion, motility, metastasis, epithelial to mesenchymal transition, and inhibitions of apoptosis as well as anoikis. Many of these processes are involved in carcinogenesis. Binding of RON to its ligand macrophage stimulating protein (MSP) leads to tyrosine phosphorylation of the receptor and subsequent signal transduction, such as the focal adhesion kinase (FAK) and PI3-K/Akt or Ras signaling pathways (1). MSP belongs to the plasminogen-related kringle protein family. Inactive 78kDa single-chain pro-MSP is synthesized in hepatocytes and secreted into the circulating blood. Cleavage and activation of pro-MSP in the extravascular compartments result in the formation of disulfide-linked 53kDa α chain and 25kDa β chain, which contains the kringle domains and serine protease domain respectively. MSP was recently named hepatocyte growth factor (HGF)-like protein becaus e of its up to 45% homology to HGF (2). We have shown that serum level of HGF correlates with tumor stage and metastasis in ESCC. It may participate in tumor angiogenesis via autocrine or paracrine mechanisms. Upon binding to c-Met, HGF might play a role in promoting ESCC cell invasion, migration and tumour metastasis. Normal epithelial cells are not affected (3). We hypothesize that MSP could be detected in serum and it may have a prognostic value in ESCC. Currently, commercially available MSP antibody is not well establi shed for the specific detection of the MSP antigen. None has been shown to be efficient and reliable. The first objective of the present proposal is to establish specific monoclonal antibodies against MSP for developing immunoass ay(s) for measurement of MSP serum levels in normal subjects and ESCC patients in order to evaluate the potential usefulness of MSP as a prognostic marker. RON, together with c-Met, which is a proto-oncogene, are the only MET family members that exist in humans (4). c-Met is a receptor for hepatocyte growth factor (HGF), and is found in high levels in esophageal tumour cells (3). Co-expression of RON and c-Met has been observe d in node-negative breast cancers and ovarian cancers (5,6). Over-expression of RON alone was also found to associate with tumor development and metastasis. RON over-expression and constitutive activation were observed in breast cancer, lung cancer, ovarian carcinomas, colorectal adenocarcinomas, and hepatocellular carcinomas (6-11). The increased expression of RON on cell surfac e favors homodimerization and receptor activation which is sufficient to induce subsequent signal transductions. Persistent RON expression and activation leading to the loss of epithelial phenotypes also correlates with cancer cells’ abilities to invade and migrate (12). In addition to the wild-type RON, splicing variants (RONΔ165, RONΔ160, RONΔ155) were detected in various malignancies including colon and gastric cancers. All the variants have the ability to induce cell scatter in a ligand-independent way (9). We hypothesize that dysregulated RON or its splicing variants’ expressions might be involved in tumorigenesis and metastasis in ESCC in a similar manner to that of c-Met, and has a potential role as a disease and prognostic marker in ESCC. Thus, the second objective of the present study is to assess the expression of RON and its variants in patients with ESCC and to correlate their levels with clinicopathological data. References: 1. Leonard EJ, Danilkovitch A. Macrophage stimulating protein. Ad Cancer Res 2000; 77: 139-67. 2. Danilkovitch-Miagkova A, Leonard EJ. Anti-apoptotic action of macrophage stimulating protein (MSP). Apoptosis 2001; 6(3): 183-90. 3. Ren Y, Cao B, Law S, et al. Hepatocyte growth factor promotes cancer cell migration and angiogen ic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res 2005; 11(17): 6190-7. 4. Wang MH, Wang D, Chen YQ. Oncogenic and invasive potentials of human macrophage-stimulating protein receptor, the RON receptor tyrosine kinase. Carcinogenesis 2003; 23(8): 1291-300. 5. Lee WY, Chen HHW, Chow NH, et al. Prognostic significance of co-expression of RON and MET receptors in node-negative breast cancer patients. Clin Cancer Res 2005; 11: 2222-8. 6. Maggiora P, Lorenzato A, Fracchioli S, et al. The RON and MET oncogenes are co-expressed in human ovarian carcinomas and cooperate in activating invasiveness. Exp Cell Res 2003; 288: 382-9. 7. Maggiora P, Marchio S, Stella MC, et al. Overexpression of the RON gene in human breast carcinoma. Oncogene 1998; 16: 2927-33. 8. Willett CG, Wang MH, Emanuel RL, et al. Macrophage-stimulating protein and its receptor in non-small-cell lung tumors: Induction of receptor tyrosine phosphorylation and cell migration. Am J Respir Cell Mol Biol 1998; 18: 489-96. 9. Zhou YQ, He C, Chen YQ, et al. Altered expression of the RON receptor tyrosine kinase in primary human colorectal adenocarcinomas: generation of different splicing RON variants and their oncogenic potential. Oncogene 2003; 22: 186-97. 10. Chen YQ, Zhou YQ, Fisher JH, et al. Targeted expression of the receptor tyrosine kinase RON in distal lung epithelial cells results in multiple tumor formation: Oncogenic potential of RON in vivo. Oncogene 2002; 21: 6382-6. 11. Persons DA, Paulson RF, Loyd MR, et al. Fv2 encodes a truncated form of the Stk receptor tyrosine kinase. Nat Genet 1999; 23: 159-65. 12. Wang D, Shen Q, Chen YQ, et al. Collaborative activities of macrophage-stimulating protein and transforming growth factor-β1 in induction of epithelial to mesenchymal transition: roles of the RON receptor tyrosine kinase. Oncogene 2004; 23: 1668-80.

Project Title:	Identification and characterization of the roles of cancer stem cells (CSCs) in esophageal squamous cell carcinoma (ESCC) and its implications in therapeutic development
Investigator(s):	Law SYK, Lee NPY, Luk JMC
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	12/2007

Abstract:

Cancer stem cells (CSCs) constitute a minority of cell population in a melanoma. In concordant with the behavior of typical stem cells, CSCs possess the self-renewal property and are capable of undergoing proliferations and differentiations (Soltysova et al., 2005; Tang et al., 2007; Tysnes and Bjerkvig, 2007). Apart from that, CSCs, termed alternatively as tumor-initiating cells, are also evidenced to be the prime progenitors, accounting for the espial of malignant tumor mass and the presentation of the cancerous phenotypes. A number of cancer cases, including those in brain (Fomchenko and Holland, 2005), liver (Ma et al., 2007), and breast (Zucchi et al., 2007), as proven in these years, have been studied with regard to their proposed origination from these rare cell types; however, knowledge on the exact mechanism on how tumors derived from CSCs and the roles of CSCs in triggering and sustaining tumor growth are largely not known. It is believed that CSCs alone can be capable of generating the whole neoplasm through rapid and unlimited cell division and clonal expansion, such that the resulting carcinoma comprises mainly two sub-populations of cells: the cancer initiating CSCs (minor population) and the bulk tumor cells (major population), together contributing to the heterogeneity of the tumorous nature (Soltysova et al., 2005). Indeed, the recognition of CSCs makes feasible with the identification of CSC-specific anti gen, the CD133, a CSC marker (Neuzil et al., 2007), such that the accurate detection of CSCs can be performed using a specific antibody targeting against the epitope of CD133. Importantly, the lethality of cancers is partially attributed to the resistance of CSCs against the current available therapies; this observation is frequently found in a number of cancer types, rendering the tumor incurable and insensitive for a specific treatment regime (Soltysova et al., 2005; Neuzil et al., 2007). Amongst those, resistance to concurrent chemoradiotherapy is commonly noticed in patients with esophageal squamous cell carcinoma (ESCC). Esophageal cancer ranks eighth as the most prevalent cancers worldwide and is the sixth most common cause of cancer-related death; and ESCC is the predominant type of esophageal cancer (Parkin et al., 2005). No absolute and defini te treatment is offered for the ESCC patient cohort. Surgical resection is one of the standard treatment methods, however, the post-operative 5-year survival rate remains at ~20% in most cases, associated with severe morbidity and mortality (Hulscher et al., 2001; Law and Wong, 2001; Law and Wong, 2002). Other non-surgical means include chemoradiation, which is proven to be more promising and leads to better prognosis (Law et al., 2003); nevertheless, those subjected to this tre atment sometimes develop resistance over time. Regarding this, it is still not uncovered the underlying mechanism leading to the development of therapy resistance and it is hypothesized for the roles of CSCs in this phenomenon. So, the aim of this proposal is to examine the fund amental roles of CSCs in the advent and progression of ESCC and their contribution to therapy resistance developed in ESCC patients. Specific objectives: 1. Delineation of the relative distribution and abundance of CSCs (CD133+ cells) in clinical tissues from both good respon der (0% viable cells after radio-chemotherapy) and poor responder (> 50% viable cells after radio-chemotherapy), with an aim to assess the roles of CD133+ CSCs in the development of therapy resistance. 2. Investigating whether CD133+ CSCs are the principal cells leading to ESCC formation by assessing the ability of CD133+ CSCs to form tumor in vivo. 3. Comparison of the gene expression profiles of CD133+ CSCs and CD133- tumor cells in clinical samples in order to identify a handful of genes with functional roles in causing therapy resistance in patients. These are also the putative targets for future establishment of persona lized therapeutics. References: (1) Fomchenko E. I. and Holland E. C. (2005). "Stem cells and brain cancer." Exp Cell Res 306(2): 323-9. (2) Hulscher J. B., Tijssen J. G., Obertop H. and van Lanschot J. J. (2001). "Transtho racic versus transhiatal resection for carcinoma of the esophagus: a meta-analysis." Ann Thorac Surg 72(1): 306-13. (3) Law S., Kwong D. L., Kwok K. F., Wong K. H., Chu K. M., Sham J. S. and Wong J. (2003). "Improvement in treatment results and long-term survival of patients with esophageal cancer: impact of chemoradiation and change in treatment strategy." Ann Surg 238(3): 339-4 7; discussion 347-8. (4) Law S. and Wong J. (2001). "Esophageal cancer." Curr Opin Gastroenterol 17(4): 393-9. (5) Law S. and Wong J. (2002). "Changing disease burden and management issues for esophageal cancer in the Asia-Pacific region." J Gastroenterol Hepatol 17(4): 374-81. (6) Ma S., Chan K. W., Hu L., Lee T. K., Wo J. Y., Ng I. O., Zheng B. J. and Guan X. Y. (2007). "Identification and characterization of tumorigenic liver cancer stem/progenitor cells." Gastroenterology 132(7): 2542-56. (7) Neuzil J., Stantic M., Zobalova R., Chladova J., Wang X., Prochazka L., Dong L., Andera L. and Ralph S. J. (2007). "Tumour-initiating cells vs. cancer 'stem' cells and CD133: what's in the name?" Biochem Biophys Res Commun 355(4): 855-9. (8) Parkin D. M., Bray F., Ferlay J. and Pisani P. (2005). "Global cancer statistics, 2002." CA Cancer J Clin 55(2): 74-108 . (9) Soltysova A., Altanerova V. and Altaner C. (2005). "Cancer stem cells." Neoplasma 52(6): 435-40. (10) Tang C., Ang B. T. and Pervaiz S. (2007). "Cancer stem cell: target for anti-cancer therapy." Faseb J. (11) Tysnes B. B. and Bjerkvig R. (2007). "Cancer initiation and progression: Involvement of stem cells and the microenvironment." Biochim Biophys Acta 1775(2): 283-97. (12) Zucchi I., Sanzone S., Astigiano S., Pelucchi P., Scotti M., Valsecchi V., Barbieri O., Bertoli G., Albertini A., Reinbold R. A. and Dulbecco R. (2007). "The properties of a mammary gland cancer stem cell." Proc Natl Acad Sci U S A 104(25): 10476-81.

List of Research Outputs

Cheung P.P.Y. , Deng W. , Man C.W.Y. , Tse W.W. , Srivastava G. , Law S.Y.K. , Tsao G.S.W. and Cheung A. , Genetic alterations in a telomerase-immortalized human esophageal epithelial cell line: Implications for carcinogenesis, Cancer Letters . 2010, 293: 41-51.

Law S.Y.K. , Avoiding and managing complications, Esophagectomy Techniques, Annual Scientific Congress, The Royal Australasian College of Surgeons, Perth, Australia, 4-7 May 2010 . 2010.

Law S.Y.K. , Ca. oesophagus, Post-registration Certificate Course in Intensive Care Nursing, The Institute of Advanced Nursing Studies, Queen Mary Hospital, Hong Kong West Cluster, Hospital Authority, 21 April 2010 . 2010.

Law S.Y.K. , Chairman, Breast Cancer Biology and its Application, Session on " The Lastest Developments and Results", Block I Program of the Joint Surgical Symposium, 2-Year Interactive Program, The University of Hong Kong AND Hong Kong Sanatroium & Hospital, 3 July 2009 . 2009.

Law S.Y.K. , Chairman, Session on "Gastrointestinal Surgery", Hong Kong Surgical Forum, Department of Surgery, The University of Hong Kong, Queen Mary Hospital AND Hong Kong Chapter, American College of Surgeons, 9 January 2010 . 2010.

Law S.Y.K. , Chairman, Lunch Symposium, The College of Surgeons of Hong Kong, St. Teresa's Hospital, Hong Kong, 12 April 2010 . 2010.

Law S.Y.K. , Chairman, Session on "Diagnosis and management of post-operative complications", Block II program of the Joint Surgical Symposium, 2-Year Interactive Program, The University of Hong Kong AND Hong Kong Sanatorium & Hospital, 5 February 2010 . 2010.

Law S.Y.K. , Chapter 64: Surgery techniques: Anastomotic technique and selection of location, In: Jobe B.A., Thomas C.R., Hunter J.G. (eds), Esophageal Cancer: Principles and Practice . demosMEDICAL, 2009, 525-534.

Law S.Y.K. , Esophageal Cancer, Series on "10 Common Cancers in Hong Kong", Health TV Programme named {至fit男女}, Cable TV . 2010.

Law S.Y.K. , Esophageal catastrophe: leaks and perforation, Block II Program of the Joint Surgical Symposium, 2-Year Interactive Program, The University of Hong AND Hong Kong Sanatroium & Hospital, 2 October 2009 . 2009.

Law S.Y.K. , Esophagectomy without mortality: What can surgeons do?, Journal of Gastrointestinal Surgery . 2010, Supplement 1: S101-S107.

Law S.Y.K. , Evolution in the management of esophageal cancer, Abu Rauff Grand Ward Round, Department of Surgery, National University of Singapore, Singapore, 22 July 2009 . 2009.

Law S.Y.K. , Evolution in the management of oesophageal cancer (Abstract) , 16th Hong Kong International Cancer Congress and 6th Annual Meeting of the Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 4-6 November 2009 . 2009.

Law S.Y.K. , Evolving strategies in esophageal perforations and anastomotic leaks - surgery, drains, endoscopy or what else?, VII International Meeting on Esophageal and Gastric Surgery, Porto, Portugal, 10-11 May 2010 . 2010.

Law S.Y.K. , How I do it: Minimally invasive esophagectomy, Esophagectomy Techniques, Annual Scientific Congress, The Royal Australasian College of Surgeons, Perth, Australia, 4-7 May 2010 . 2010.

Law S.Y.K. , Individualized therapeutic strategies for esophageal cancer, VII International Meeting on Esophageal and Gastric Surgery, Porto, Portugal, 10-11 May 2010 . 2010.

Law S.Y.K. , Journal Editor, World Journal of Gastrointestinal Endoscopy . 2010.

Law S.Y.K. , Laparoscopic inversion esophagectomy, Symposium: Barrett's oesophagus and early cancer, Annual Scientific Congress, The Royal Australasian College of Surgeons, Perth, Australia, 4-7 May 2010 . 2010.

Law S.Y.K. , Laparoscopic stripping of the esophagus (video presentation), International College of Surgeons 2009 Beijing Conference on Minimally Invasive Surgery: State of the Art, Beij ing, China, 13-16 November 2009 .

Law S.Y.K. , Management of esophageal cancer - Hong Kong perspectives, Keynote Lecture, Annual Scientific Congress, The Royal Australasian College of Surgeons, Perth, Australia, 4-7 May 2010 . 2010.

Law S.Y.K. , Management of esophageal leaks, International Surgical Week ISW 2009, Adelaide South Australia, 6-10 September 2009 .

Law S.Y.K. , Methods of anastomosis after esophageal resection, International Surgical Week ISW 2009, Adelaide South Australia, 6-10 September 2009 .

Law S.Y.K. , Minimal invasive treatment for esophageal carcinoma, 2009 World Conference of Endoscopy Physicians (19th General Assembly Session of Chinese Endoscopy Physicia ns) and World Endoscopy Technology, Hong Kong, China, 18-20 December 2009 .

Law S.Y.K. , Minimally invasive esophagectomy and interventional endoscopy, Keynote Lecture, Annual Scientific Congress, The Royal Australasian College of Surgeons, Perth, Australia, 4-7 May 2010 . 2010.

Law S.Y.K. , Minimally invasive esophagectomy for cancer, International College of Surgeons 2009 Beijing Conferen ce on Minimally Invasive Surgery: State of the Art, Beijing, China, 13-16 November 2009 .

Law S.Y.K. , Minimally invasive esophagectomy, 17th International Postgraduate Course: New Frontiers in the Management of Abdominal Diseases, The Internationa l Association of Surgeons, Gastroenterologists and Oncologists & The International School of Surgical Oncology, Athens, Greece, 4-5 December 2009 . 2009.

Law S.Y.K. , Minimally invasive esophagectomy, XVII National Meeting of Surgery of the Association of Spanish Surgeons, Canary Islands, Spain, 21-24 October 2009 . 2009.

Law S.Y.K. , Moderator, ISDS ISS/SIC Symposium, Gastroesophageal neoplasia: from Barrett's to esophageal cancer, International Surgical Week ISW 2009, Adelaide South Australia, 6-10 September 2009 . 2009.

Law S.Y.K. , Optimal surgical approach for esophagectomy: The debate still goes on? (Editorial), Annals of Thoracic and Cardiovascular Surgery . 2009, 15(5): 277-279.

Law S.Y.K. , Palliation for dysphagia (Abstract), Head & Neck Course: Palliative Therapy for Head and Neck Cancer, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 3-4 June 2010 . 2010.

Law S.Y.K. , Polish Journal of Surgery . 2010.

Law S.Y.K. , Prognostication following esophagectomy, Symposium: Current issues in esophageal cancer, Annual Scientific Congress, The Royal Australasian College of Surgeons, Perth, Australia, 4-7 May 2010 . 2010.

Law S.Y.K. , Prognostication for patients with esophageal cancer, Esophagus . 2009, 6(4): 215-219.

Law S.Y.K. , Surgical treatment of esophageal cancer (Abstract), The Second International Conference of Sudanese Society of Gastroenterology, Khartoum, Sudan, 22-28 February 2010 .

Law S.Y.K. , The value of lymphadenectomy in esophageal cancer, XVII National Meeting of Surgery of the Association of Spanish Surgeons, Canary Islands, Spain, 21-24 October 2009 . 2009.

Law S.Y.K. , Thoracoscopic and laparoscopic esophagectomy, Lunch Symposium, The College of Surgeons of Hong Kong, St. Teresa's Hospital, Hong Kong, 12 April 2010 . 2010.

Law S.Y.K. , Upper Gastrointestinal Surgery, RTHK Chinese radio programme [Ad Wise] [精靈一點] on Radio 1 at RTHK, The College of Surgeons of Hong Kong Series, 18 January 2010 . 2010.

Law S.Y.K. , What cannot be found in the books: complications during minimally invasive esophagogastrectomy - getting out of trouble in the operating room, VII International Meeting on Esophageal and Gastric Surgery, Porto, Portugal, 10-11 May 2010 . 2010.

Law S.Y.K. , World Journal of Gastroenterology . 2010.

Lo P.H.Y. , Lung H.L. , Cheung A.K.L. , Apte S.S., Chan K.W. , Kwong F.M. , Ko J.M.Y. , Cheng Y. , Law S.Y.K. , Srivastava G. , Zabarovsky E.R., Tsao G.S.W. , Tang J.C.O., Stanbridge E.J. and Lung M.L. , Extracellular Protease ADAMTS9 Suppresses Esophageal and Nasopharyngeal Carcinoma Tumor Formation by Inhibiting Angiogenesis, Cancer Research . 2010, 70(13): 5567-76.

Omloo J.M.T., Law S.Y.K. , Launois B., Le Prise E., Wong J. , van Berge Henegouwen M.I. and van Lanschot J.J.B., Short and long-term advantages of transhiatal and transtho racic oesophageal cancer resection (Review Article), European Journal of Surgical Oncology. 2009 . 2009, 35(8): 793-797.

Rizk N.P., Ishwaran H., Rice T.W., Chen L.Q., Schipper P.H., Kesler K.A., Law S.Y.K. , Lerut T.E.M.R., Reed C.E., Salo J.A., Scott W.J., Hofstetter W.L., Watson T.J., Allen M.S., Rusch V.W. and Blackstone E.H., Optimum lymphadenectomy for esophageal cancer, Annals of Surgery . 2010, 251(1): 46-50.

So H.K., Sung R., Lau E., Lam P., Law S.Y.K. and Tseng R., Growth in Rural Shanxi Primary School for Low Income Families, 8th Guangdong-Hong Kong & 2nd Hong Kong-Guangdong-Sha nghai-Chongqing Paediatric Exchange Meeting, The Chinese University of Hong Kong and Private Practice and The University of Hong Kong, Shanxi, China, 2-6 April 2010 . 2010.

Tong D.K.H. , Law S.Y.K. , Kwong D.L.W. , Chan K.W. , Lam A.K.Y. and Wong K.H. , Histopathological regression of the primary tumor in dicated by percentage of residual viable cells is an important prognostic factor after neoadjuvant chemoradiation therapy for esophageal cancer (Abstract), GASTRO 2009 UEGW/WCOG, London, United Kingdom, 21-25 November 2009 .

Tong D.K.H. , Law S.Y.K. , Kwong D.L.W. , Chan K.W. , Lam A.K.Y. and Wong K.H. , Histopathological regression of the primary tumor indicated by percentage of residual viable cells is an important prognostic factor after neoadjuvant chemoradiation therapy for esophageal cancer, Gut . 2009, Supplement No II Vol 58 - Endoscopy Supplement No I Vol 41: A74.

Tong D.K.H. and Law S.Y.K. , Management of oesophageal cancer (Review Article), Indian Journal of Surgery . 2009, 71: 317-325.

Tong D.K.H. and Law S.Y.K. , Management strategies for advanced stage esophageal cancer, Thesis, Master of Surgery, The University of Hong Kong. 2009 . 2009.

Tong D.K.H. and Law S.Y.K. , Minimally invasive oesophageal stripping, Hong Kong Surgical Forum, Department of Surgery, The University of Hong Kong AND Hong Kong Chapter, American College of Surgeons, 18 July 2009 . 2009.

Tong D.K.H. , Wong K.H. and Law S.Y.K. , Myotomy for achalasia, Hong Kong Surgical Forum, Department of Surgery, The University of Hong Kong, Queen Mary Hospital AND Hong Kong Chapter, American College of Surgeons, 9 January 2010 . 2010.

Tong D.K.H. and Law S.Y.K. , Robotic myotomy for achalasia (Video presentation), Hong Kong Surgical Forum, Department of Surgery, The University of Hong Kong, Queen Mary Hospital AND Hong Kong Chapter, American College of Surgeons, 9 January 2010 . 2010.

Tseng R., So H.K., Sung R., Lau E., Lam P. and Law S.Y.K. , "M.E.R.I.T" Survey in Rural Shanxi Boai Primary School, 8th Guangdong-Hong Kong & 2nd Hong Kong-Guangdong-Shanghai-Chongqi ng Paediatric Exchange Meeting, The Chinese University of Hong Kong and Private Practice and The University of Hong Kong, Shanxi, China, 2-6 April 2010 . 2010.

Researcher : Law WL

Project Title:	Self-expanding metallic stents for the poor patients with malignant colorectal obstructi on
Investigator(s):	Law WL, Chu KW
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	04/2004

Abstract:

To provide the insertion of self-expanding metallic stents to the poor patients who cannot afford the devices.

Project Title:	To evaluate the accuracy of 3 T MRI and early PET CT scan to assess the response to neoadjuvant chemoradiation in patients with advanced rectal cancer
Investigator(s):	Law WL, Khong PL, Zhang J, Leung SY
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	12/2008

Abstract:

The objectives of the research proposal are 1. to evaluate the accuracy of 3 Tesla (3T) MRI in the assessment of response to neoadjuvant therapy; and 2. to evaluate the assessment of metabolic response by early PET scan (2 weeks after chemoradiation) in predicting the response to neoadjuvant chemoradiation in patients with advanced rectal cancer. Colorectal cancer is the second most common malignancy in Hong Kong and rectal cancer constitutes about one third of cases of colorectal malignancy. Local recurrence remains a significant problem in rectal cancer and the reported rate ranged 3 to 30%. Recently, the important of circumferential margin has been emphasized and surgery aims at sharp mesorectal dissection to reduce local recurrence1. Increasing evidence also suggested that preoperative radiation can help to reduce the rate of local recurrence2 and combined preoperative chemoradiation is the optimal treatment of patients with advanced rectal caner3. Currently, PET CT scan and Magnetic Resonance Imaging (MRI) are recommended as the preoperative staging investigation for patients with rectal cancer and to determine the patients for neoadjuvant therapy in our institution. Accurate preoperative staging is important to tailor the optimal treatment for patients with advanced rectal cancer. Conventional assessments with digital examination and rigid sigmoidoscopy are inaccurate. Transrectal ultrasound examination has been demonstrated to be of over 90% accurate in the assessment of the depth of invasion. However, the accur acy of this examination depends on the experience of the operator and its accuracy after radiation is not as high as in primary cancer. Magnetic resonance imaging (MRI) provides images in multiple planes with high contrast soft tissue resolution without ionizing radiation. The use of phased array coil MRI has eliminated many of the problems of endoluminal MRI and has similar accuracy. Preoperative MRI has been shown to have a high accuracy for rectal cancer staging and a predictio n for a negative circumferential margin and it has become the standard staging for rectal cancer in the United Kingdom4 . However, there are only few data on the use of MRI in the assessment rectal cancer following chemoradiaiton. Moreover, most of the current data come from the 1.5 T MRI scanner. With availability of the 3T scanner in Queen Mary Hospital, The University of Hong Kong, this proposal aims to assess the accuracy of the 3T scanner in the evaluation of staging before and after chemoradiation. Neoadjuvant chemoradiation has the benefit of downstaging the tumor to allow a sphincter saving operation for patients with rectal cancer. However, the response rate is about 30-50%. The responders have been reported to have more favorable outcome in terms of a lower local recurrence and a better survival. However, it is difficult to predict the patients who will respond to neoadjuvant therapy at an early period of thearpy. Previous studies with PET scan immediate before surgery showed that the meta bolic response correlated with the histological response and prognosis of patients5,6. However, a PET scan before surgery would not be helpful to change the treatment strategy. It would be preferred if metabolic response can be detected earlier so that treatment strategy can be changed to the unresponders. From the data from the MUNICON trial in which, the authors used PET scan after 2 weeks of neoadjuvant therapy to predict the responders in patients with esophageal cancer, early metabolic response was associated with a higher chance of histological response7. However, in case of rectal cancer, very few data with the early assessment of metabolic response by PET scan have been published8. The present proposal aims to evaluate the possibility of the use of an early PET scan to assess the response to chemoradiation. This proposal is a pilot study on the use of 3T MRI and early PET scan in the assessment of response to neoadjuvant therapy in patients with advanced rectal cancer. The data from the sequential MRI and PET scan will be compared and all these data will be verified with the final histology. It is anticipated that this will generate data which are significant in rectal cancer staging and assessment after chemoradiation. References 1. Law WL, Chu KW. Anterior resection for rectal cancer with mesorectal excision: a prospective evaluation of 622 patients. Ann Surg 2004; 240:260-268. 2. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001; 345:638-646. 3. Sauer R, Becker H, Hohenberger W, Rodel C, Wittekin d C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351:1731-1740. 4. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ 2006; 333:779. 5. Calvo FA, Domper M, Matute R, Martinez-Lazaro R, Arranz JA, Desco M, Alvarez E, Carreras JL. 18F-FDG positron emission tomography staging and restaging in rectal cancer treated with preoperative chemoradiation. Int J Radiat Oncol Biol Phys 2004; 58:528-535. 6. Guillem JG, Moore HG, Akhurst T, Klimstra DS, Ruo L, Mazumdar M, Minsky BD, Saltz L, Wong WD, Larson S. Sequential preoperative fluorodeoxyglucose-positron emission tomography assessment of response to preoperati ve chemoradiation: a means for determining longterm outcomes of rectal cancer. J Am Coll Surg 2004; 199:1-7. 7. Swisher SG, Erasmus J, Maish M, Correa AM, Macapinlac H, Ajani JA, Cox JD, Komaki RR, Hong D, Lee HK, Putnam JB, Jr., Rice DC, Smythe WR, Thai L, Vaporciyan AA, Walsh GL, Wu TT, Roth JA. 2-Fluoro-2-deoxy-D-glucose positron emission tomography imaging is predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma. Cancer 2004; 101:1776-1785. 8. Cascini GL, Avallone A, Delrio P, Guida C, Tatangelo F, Marone P, Aloj L, De Martinis F, Comella P, Parisi V, Lastoria S. 18F-FDG PET is an early predictor of pathologic tumor response to preoperative radiochemotherapy in locally advanced rectal cancer. J Nucl Med 2006; 47:1241-1248.

List of Research Outputs

Cheung J.P., Tsang H.H., Cheung J.J., Yu H.H., Leung G.K.K. and Law W.L. , Adjuvant therapy for the reduction of postoperative intra-abdominal adhesion formation, Asian Journal of Surgery . 2009, 32(3): 180-186.

Choi H.K. , Law W.L. and Poon J.T.C. , The optimal number of lymph nodes examined in stage II colorectal cancer and its impact of on outcomes, BMC Cancer . 2010, 10: 267.

Dellinger R.P., Tomayko J.F., Angus D.C., Opal S., Cupo M.A., McDermott S., Ducher A., Calandra T., Cohen J. and Law W.L. , Efficacy and safety of a phospholipid emulsion (GR270 773) in Gram-negative severe sepsis: results of a phase II multicenter, randomized, placebo-controlled, dose-finding clinical trial, Critical Care Medicine . 2009, 37(11): 2929-2938.

Fan J.K.M. , Lo O.S.H. and Law W.L. , A rare complication of laparoscopic low anterior resection (Abstract), Surgical Laparoscopy, Endoscopy & Percutaneous Techniques . 2009, 19(5): e210.

Fan J.K.M. , Tong D.K.H. , Poon J.T.C. , Lo O.S.H., Beh S.L. , Patil N.G. and Law W.L. , Multimodality minimally invasive autopsy -- a feasible and accurate approach to post-mortem examination, Forensic Science International . 2010, 195(1-3): 93-98.

Fan J.K.M. , Lo C.S.Y. and Law W.L. , Surgeons' attitudes towards natural orifice translumenal endoscopic surgery, The Society of American Gastrointestinal and Endoscopic Surgeons 2010 Annual Meeting and 12th World Congress of Endoscopic Surgery, National Harbor, Maryland, U.S.A., 14-17 April 2010 .

Fan J.K.M. , Lo C.S.Y. and Law W.L. , Surgeons' attitudes towards natural orifice transluminal endoscopic surgery, ANZ Journal of Surgery . 2010, 80(6): 387-389.

Fan J.K.M. , Tam P.C. and Law W.L. , Synchronous trans-abdominal pre-peritoneal (TAPP) hernioplasty in a patient with robotic-assisted prostatectomy for carcinoma of prostate (Multi-Media Article), Surgical Practice . 2010, 14(1): 32.

Fan J.K.M. and Law W.L. , The impact of verbal guidance on laparoscopic skills training and multi-tasking performance, The Society of American Gastrointestinal and Endoscopic Surgeons 2010 Annual Meeting and 12th World Congress of Endoscopic Surgery, National Harbor, Maryland, U.S.A., 14-17 April 2010 .

Foo C.C., Poon J.T.C. and Law W.L. , Self-expanding metallic stents for acute left-sided large bowel obstruction: a review of 130 patients, Colorectal Disease . 2010, Epub ahead of print.

Gu J. , Khong P.L. , Wang S. , Liu K.Y. , Law W.L. , Chan Q. and Zhang J. , Correlation study of quantitative indexes from DWI and PET-CT in primary rectal cancer, 3rd Joint Scientific Meeting of The RCR & HKCR and 17th ASM of HKCR, 31 October-1 November 2009 .

Gu J. , Khong P.L. , Wang S. , Liu K.Y. , Law W.L. , Chan Q. and Zhang J. , Dynamic contrast-enhanced MRI of primary rectal cancer at 3T: correlation with positron emission tomography, 16th Hong Kong International Cancer Congress and 6th Annual Meeting Centre for Cancer Research ,The University of Hong Kong Li Ka Shing Faculty of Medicine, 4-6 November 2009 .

Ho K.L. , Tsu J.H.L. , Ng W.M. , Law W.L. , Tam P.C. and Lo B.S.H. , Rectourethral fistula after radical prostatecomy: transperineal repair in jack-knife position, Surgical Practice . Hong Kong, College of Surgeons of Hong Kong, 2010, 14: 102-104.

Law W.L. , Anastomotic leakage: the problem and its impact, International College of Surgeons Beijing Conference 2009, Beijing, China, 13-16 November 2009 . 2009.

Law W.L. , Poon J.T.C. , Fan J.K.M. , Lo O.S.H., Wei R. and Choi H.K. , Comparison of outcomes following resection of right-si ded and left-sided colon cancer, International Surgical Week 2009, Adelaide, Australia, 6-10 September 2009 .

Law W.L. , Controversies in ventral hernia repair, Advanced Animal Course in Minimally Invasive & Emergency Hernia Surgery, Hong Kong, 9 January 2010 . 2010.

Law W.L. , Editorial Board Member , International Journal of Surgical Oncology . 2010.

Law W.L. , Editorial Board Member, World Journal of Gastrointestinal Surgery . 2009.

Law W.L. , Emerging techniques and technology in laparoscopic colorectal surgery, Joint HK Sanatorium and HKU Surgical Symposium, Hong Kong, 7 August 2009 . 2009.

Law W.L. , Improving outcomes of laparoscopic colorectal resection: the experience of a tertiary center, International College of Surgeons Beijing Conference 2009, Beijing, China, 13-16 November 2009 . 2009.

Law W.L. , Incisionless surgery: the next paradigm, The 5th International Congress of Laparoscopic Colorectal Surgery, Fort Lauderdale, Florida, U.S.A., 9-10 Februa ry 2010 . 2010.

Law W.L. , Laparoscopic anterior resection, International College of Surgeons Beijing Conference 2009, Beijing, China, 13-16 November 2009 . 2009.

Law W.L. , Laparoscopic approach for obstructing colorectal cancer, 2009 Samsung Medical Center-Kyungpook National University Hospital Joint International Symposium, Daegu, Korea, 3-4 July 2009 . 2009.

Law W.L. , Poon J.T.C. , Fan J.K.M. and Lo O.S.H., Laparoscopic colorectal resection for octogenarians is a safe and optimal approach, Annual Meeting of the American Society of Colon and Rectal Surgeons, Minneapolis, Minnesota, U.S.A., 15-19 May 2010 .

Law W.L. , Poon J.T.C. , Fan J.K.M. and Lo O.S.H., Laparoscopic resection following stent insertion for obstructing colorectal cancer, The Society of American Gastrointestinal and Endosc opic Surgeons 2010 Annual Meeting and 12th World Congress of Endoscopic Surgery, National Harbor, Maryland, U.S.A., 14-17 April 2010 .

Law W.L. , Laparoscopic resection for rectal cancer, The 17th Postgraduate Course of the International Association of Surgeons, Gastroenterologists and Oncologists, Athens, Greece, 4-5 December 2009 . 2009.

Law W.L. , Laparoscopic surgery for rectal cancer: its oncologic safety, 2009 Samsung Medical Center-Kyungpook National Universi ty Hospital Joint International Symposium, Daegu, Korea, 3-4 July 2009 . 2009.

Law W.L. , Laparosocpic colectomy: the standardized technique, The 3rd Advanced Laparoscopic Surgery Course for Higher Surgical Trainee 2009, Hospital Authority, Hong Kong, 25 July 2009 . 2009.

Law W.L. , Management of malignant left colon obstruction, The 24th Biennial Congress of the International Society of University Colon and Rectal Surgeons, Seoul, Korea, 19-23 March 2010 . 2010.

Law W.L. , Minimally invasive palliation for advanced colorectal malignancy, International Surgical Week 2009 and 21st World Congress of Digestive Surgery, Adelaide, Australia, 6-10 September 2009 . 2009.

Law W.L. , NOTES and colorectal surgery, The 20th International Colorectal Scientific Congress 2009, Singapore, 17-20 November 2009 . 2009.

Law W.L. , New development in diagnosis and treatment in colorectal cancer, Colorectal Symposium organized by Hong Kong Anticancer Society and Hong Kong Hospital Authority, Hong Kong, 8 August 2009 . 2009.

Law W.L. , Robotic assisted TME, Advanced Laparoscopic Colorectal Course, Milan, Italy, 23-24 September 2009 . 2009.

Law W.L. , Robotic assisted rectal surgery, The 9th Asia Pacific Congress of Endoscopic Surgery and 9th Meeting of Endoscopic and Laparoscopic Surgeons of Asia, Xiamen, China, 4-6 November 2009 . 2009.

Law W.L. , Single incision laparoscopic colectomy: the initial experience, Hong Kong Surgical Forum, Summer 2009, Hong Kong, 18 July 2009 . 2009.

Law W.L. , Single incision laparoscopic colectomy, Pre-forum Advanced Cadaver Workshop, Hong Kong Surgical Forum, Summer 2009, Hong Kong, 17 July 2009 . 2009.

Law W.L. , Single incision laparoscopic colectomy, The 11th Colorectal Surgery Course, Hong Kong Society of Coloproctology, Hong Kong, 24-25 April 2010 . 2010.

Law W.L. , Single incision laparoscopic inguinal hernia repair, Advanced Animal Course in Minimally Invasive & Emergency Hernia Surgery, Hong Kong, 9 January 2010 . 2010.

Law W.L. , Fan J.K.M. and Poon J.T.C. , Single incision laparoscopic left colectomy for carcinoma of distal transverse colon, Colorectal Disease . 2009, 12(7): 698-701.

Law W.L. , Poon J.T.C. and Fan J.K.M. , Single incision laparoscopic right colectomy (Video Presentation), The Society of American Gastrointestinal and Endoscopic Surgeons 2010 Annual Meeting and 12th World Congress of Endoscopic Surgery, National Harbor, Maryland, U.S.A., 14-17 April 2010 .

Law W.L. , Single incision laparoscopic surgery: the next frontier of minimally invasive surgery (Leading Article), Surgical Practice . 2010, 14(1): 29-31.

Law W.L. , Fan J.K.M. and Poon J.T.C. , Single-incision laparoscopic colectomy: early experien ce, Diseases of the Colon and Rectum . 2010, 53(3): 284-288.

Law W.L. , Training in Asia, The 5th International Congress of Laparoscopic Colorec tal Surgery, Fort Lauderdale, Florida, U.S.A., 9-10 February 2010 . 2010.

Lee V.H.F. , Ng C.Y. , Liu K.Y. , Law W.L. , Ho J.W.C. , Chua D.T.T. , Kwong D.L.W. , Choy T.S. , Leung T.W. and Au G.K.H. , Dosimetric Analysis of Pre-operative and Post-operative Concurrent Chemotherapy with Conformal Radiotherapy Delivered by 5 or 6 Beams for Rectal Cancer. , Hong Kong College of Radiologists . Hong Kong, Hong Kong College of Radiologists, 2009.

Li S.W.V. , Yuen S.T. , Chan T.L. , Yan H.H.N. , Law W.L. , Yeung H.Y. , Chan A.S.Y. , Tsui W.Y. , So S., Chen X. and Leung S.Y. , Frequent inactivation of axon guidance molecule RGMA in human colon cancer through genetic and epigenetic mechanisms, Gastroenterology . 2009, 137(1): 176-87.

Lim Y.K. , Law W.L. , Poon J.T.C. and Fan J.K.M. , Impact of multimodality treatment on total mesorectal excision (TME) surgery for very low rectal cancers, International Surgical Week 2009, Adelaide, Australia, 6-10 September 2009 .

Lim Y.K. , Law W.L. , Liu R., Poon J.T.C. , Fan J.K.M. and Lo O.S.H., Impact of neoadjuvant treatment on total mesorectal excision for ultra-low rectal cancers, World Journal of Surgical Oncology . 2010, 8: 23.

Lo O.S.H. and Law W.L. , Ileocolonic mucormycosis in adult immunocompromised patients: a surgeon's perspective, World Journal of Gastroenterology . 2010, 16(9): 1165-1170.

Ng E.K.O. , Leung C.P.H. , Au S., Chan A., Wong L.P. , Ma E.S.K. , Pang R.W.C. , Chua D.T.T. , Chu K.M. , Law W.L. , Poon R.T.P. and Kwong A. , Plasma microRNA as a potential marker for breast cancer detection, The 101st Annual Meeting of the American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Pang R.W.C. , Law W.L. , Chu A.C.Y. , Poon J.T.C. , Lam S.C. , Chow K.M. , Ng L. , Cheung W.H. , Lan X.R. , Lan H.Y. , Tan V.P.Y. , Yau T.C.C. , Poon R.T.P. and Wong B.C.Y. , A Subpopulation of CD26+ Cancer Stem Cells with Metastatic Capacity in Human Colorectal Cancer, Cell Stem Cell . 2010, 6: 603-615.

Poolton J.M. , Fan J.K.M. , Masters R.S.W. , Patil N.G. and Law W.L. , The impact of verbal guidance on laparoscopic skills training and multi-tasking performance, 12th World Congress of Endoscopic Surgery, Washington DC . 2010.

Poon J.T.C. , Fan J.K.M. and Law W.L. , Early experience in laparo-endoscopic single site colectomy, The 9th Asia Pacific Congress of Endoscopic Surgery and 9th Meeting of Endoscopic and Laparoscopic Surgeons of Asia, Xiamen, China, 4-6 November 2009 .

Poon J.T.C. , Law W.L. , Fan J.K.M. and Lo O.S.H., Impact of the standardized medial-to-lateral approac h on outcome of laparoscopic colorectal resection (Reply to Letter), World Journal of Surgery . 2009, 33(10): 2177-2182.

Poon J.T.C. and Law W.L. , Laparoscopic resection for rectal cancer: a review, Annuals of Surgical Oncology . 2009, 16(11): 3038-3047.

Wong H., Yau T.C.C. , Chan P., Ng I.O.L. , Chan G.S.W. , Hui P., Law W.L. , Lo C.M. , Hedley A.J. and Epstein R. , PPI-delayed diagnosis of gastrinoma: oncologic victim of pharmacologic success, Pathology and Oncology Research . 2010, 16(1): 87-91.

Wong K.P., Poon J.T.C. , Fan J.K.M. , Lo S.H. and Law W.L. , Prognostic value of lymph node ratio in stage III colorectal cancer, Annual Meeting of the American Society of Colon and Rectal Surgeons, Minneapolis, Minnesota, U.S.A., 15-19 May 2010 .

Zhang J., Liu R., Law W.L. and Phong K.L., Correlation of ADC on DWI and SUV max on PET/CT in primary rectal cancer - a preliminary experience, Radiological Society of North America 2009, The 95th Scientific Assembly and Annual Meeting, Chicago, Illinois, U.S.A., 29 November - 4 December 2009 .

Researcher : Lee KW

Project Title:	The novel role of a splice variant of carboxypeptidase E (CPE-deltaN) in HCC metastasis
Investigator(s):	Lee KW, Ng IOL
Department:	Pathology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	09/2008
Completion Date:	03/2010

Abstract:

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and is the second leading cause of cancer death in Hong Kong (1,2) When presented at the early stage, HCC can be treated with surgical resection or liver transplantation. Unfortunately, more than 80% of HCC patients are presented at their late stage and thus the above treatment cannot provid e a cure. The high recurrence rate is commonly associated with a propensity of HCC for intrahepatic and extrahepatic metastases even after surgical resection, leading to poor prognosis (3). Therefore, identification of molecular mechanism of HCC metastasis might lead us to biomark ers to predict the metastatic potential of primary tumors is essential for improving prognosis, treatment strategies, and providing targets for cancer therapy. Acquisition of genetic changes is believed to be critically involve d in progression of primary to metastatic tumors. Despite the advances in molecular technologies including comparative genomic hybridisation (CGH), fluorescence in situ hybridizat ion analysis (FISH) and cDNA microarray, which allow the identification of novel targets involved in HCC metastasis, the precise mechanisms involved remain elusive. Recently, establishment of two metastatic HCC cell lines named MHCC-97L and MHCC-97H by Li et al (4), originated fro m the same parental cell line, MHCC-97 but different in metastatic potential provides a useful tool for studying the molecular mechanism of HCC metastasis. By comparing the gene expression profiles between these two cell lines by cDNA microarray approach, we found 15 fold higher expression of carboxypeptidase E (CPE) with an accession number of NM_001873 in the highly metastatic (MHCC97H) versus low metastatic (MHCC97L) cells. CPE, also known as carboxypeptidase H (CPH) , a ~55kD protein, first identified as a processing enzyme for prohormones (5) which is found primarily in endocrine tissues and peptidergic neurons. However, CPE has recently been reported to be expressed in neuroendocrine tumors in lung (6) and therefore has been proposed to be a useful marker for identifying such tumor, although its role in cancer progression was unknown. Since CPE was first identified in the neuronal system, Dr. Y.P. Loh (Section on Cellular Neurobiology, NICHD, NIH) stably transfected wild-type CPE cDNA into a clone of Neuro2A (WT) cells (a mouse neuroblastoma-glioma cell line) that does not express CPE, they surprisingly found that Neuro2A clones expressing CPE proliferated faster than WT cells (premininary data). This result prompted an exhaustive non-redundant nucleotide sequence database search which uncovered a novel splice variant isoform of CPE (CPE-deltaN) that lacks the N-terminus (preliminary data). By RT-PCR using primer specific for CPE-deltaN mRNA, there showed 10 fold higher expression in MHCC-97H cells when compared with MHCC97L, which is consistent to the result of cDNA microarray. Moreover, WT CPE mRNA were not expressed in these epithelial-derived MHCC97H cells. Taken together, we hypothesize that CPE-deltaN may play a role in cell proliferation during development and controls growth and metastasis of tumor cells, consistent with the notion that cancer represents development gone awry. CPE-deltaN might be a reliable biomarkers that can predict the metastatic potential of HCC tumors, as well as provide targets for therapy. There are 4 main objectives to this study: 1.To examine CPE-deltaN expression HCC clinical samples. 2.To understand the regulatory mechanism of CPE-deltaN in HCC cells. 3.To examine whether CPE-deltaN over-expression or down-regulation would affect HCC cell growth and invasion. 4.To examine the therapeutic role of CPE-deltaN suppression in HCC tumor growth and metastasis in nude mice animal model .

Project Title:	The significance of nucleophosmin phosphorylation (Threonine 234) in HCC metastasis
Investigator(s):	Lee KW, Ng IOL
Department:	Pathology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2010

Abstract:

HCC is the fifth most common malignancy worldwide and is the second most fatal cancer in Southeast Asia and Hong Kong (1,2). When presented at the early stage, HCC can be treated with surgical resection or liver transplantation. However, HCC is frequently complicat ed by occurrence of intrahepatic and extrahepatic metastases even after surgical resection, thereby leading to poor prognosis (3). To improve the prognosis of HCC patients, there is an urgent need to understand the molecular mechanism of metastasis in HCC. Metastasis is a complica ted process attributed to the accumulation of genetic alternations. Despite the recent advances in biomedical technologies, the molecular mechanism underlying cancer metastasis is unclear. As a continuous pursuit in the molecular mechanism of HCC metastasis, we have recently established a pair of primary and its corresponding metastatic lung counterparts (PLC-PT and PLC-LM) by orthotopic injection of parental PLC cell line into the liver of the SCID mice. These two matched HCC cell lines share the same genetic background but differ in invasive ability which was evidenced by wound healing and cell invasion assays. These two cell lines provide an indispe nsable tools to study HCC metastasis. Since protein kinases and their phosphorylated substrates play key role in signaling process leading to metastasis, we aim to identify a phosphorylated substrate and its pathway which is critical in HCC metastasis. Using CelluSpot™ Serine/Threonine kinase peptide array analysis, we compare the phosphorylation profiling of these two matched HCC cell lines and found phosphorylated level of nucleophosmin (NPM) at Threonine 234 had remarkably high level in metastatic HCC cells (PLC-LM) than the corresponding primary HCC cell line (PLC-PT). Specifi c phosphorylation of NPM on Threonine 234 was mediated by Cyclin-dependent kinase 1 (CDK1). Western blot analysis confirmed elevated phosphorylated level of NPM at Threonine 234 (Thr234) in PLC-LM cells using phospho-NPM (T234) antibody. The role of NPM (Thr234) in HCC metastasis was further verified in two metastatic HCC cell lines named MHCC-97L and MHCC-97-H by Li et al (4). Consistently, elevated phosphorylated level of NPM (Thr234) was also found in higher metastatic HCC cell line, MHCC97-H when compared with lower metastatic one, MHCC97-L, further suggesting the role of NPM (Thr234) in HCC metastasis. NPM, also known as B23, and located on chromosome 5q35, is a protein of 35 to 40 KD was originally identified as a non-ribosomal necleolar phosphoprotein found at high levels in the granular regions of the nucleolus (5). NPM was implicated in multiple cellular functions including ribosomal protein assembly and transport (5), centrosome duplication (6), and cell cycle progression (7) by direct or ind irect mechanism. Although NPM was found to be over-expressed in certain types of carcinomas including colon, bladder and prostate, its role in cancer is far from fully understood. NPM exists in cells as a phosphoprotein and contains multiple phosphorylation sites . Therefore, phosphorylation of NPM can play major role in the funct ional regulation of NPM. Phosphorylation of NPM at several sites has been previously reported by several different kinases including casein kinase II (CKII), nuclear kinase II, polo-like kinase (Plk) and cdc type kinase during centrosome duplication (8). However, there are no reports showing phosphorylation events on NPM in pathogenesis of cancer. Our pilot study has shown that phosphorylated level of NPM at Threonine 234 was elev ated by CDK1 in HCC metastatic cells, suggesting that it may potentially promote HCC progression and metastasis. Further characterization of phosphorylation of NPM in HCC growth and metastasis is warranted. There are three main objectives to this study: 1. To examine NPM (Thr234) expression in HCC clinical samples. 2. To evaluate the biological characteristics, and invasive ability of NPM (Thr234) in HCC both in vitro and in vivo. 3. To delineate the molecular mechanism of NPM (Thr234) in HCC growth and metastasis.

Project Title:	AACR 101st Annual Meeting 2010 Nucleophosmin (Theronine 234) is a novel mediator of tumor metastasis
Investigator(s):	Lee KW
Department:	Pathology
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	04/2010
Completion Date:	04/2010

Abstract:

N/A

List of Research Outputs

Liu L. , Lee P.Y. , Chan V.W.M. , Xue W., Zender L., Zhang C., Mao M., Dai H., Wang X.L., Xu Z. , Lee K.W. , Ng I.O.L. , Chen Y., Kung H.F., Lowe S.W., Poon R.T.P. , Wang J.H. and Luk J.M.C. , Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma, Hepatology (Erratum in: Hepatology 2010;51(1):358) . 2009, 50(5): 1453-1463.

Researcher : Lee NPY

Project Title:	Tight-junction claudin-19 in kidney development and renal disease
Investigator(s):	Lee NPY, Luk JMC, Tam PC
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To isolate, identify and characterize a novel tight -junction molecule, claudin 19, which was initially found highly expressed in kidney.

Project Title:	Autoantibodies in early and late stages of liver cancer patients: a proteome-wide array analysis
Investigator(s):	Lee NPY, Luk JMC, Sham PC
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	11/2007
Completion Date:	11/2009

Abstract:

Liver cancer is often diagnosed at advanced or late stages with intra-hepatic and distant metastases, when curative treatment options are limited in general. Thus, early detection of the aggressive malignant tumor could allow more available therapeutic approache s and offer patients better chance for long-term survival. Frequent surveillance of at-risk patients (with liver cirrhosis and/or hepatitis carriers) is recommended, but current efficacy of screening regimes, by measuring serum alpha-fetoprotein (AFP) and transabdominal ultrasoun d imaging, however suffers from low diagnostic sensitivity and specificity particularly with high operator-dependent false-negative diagnosis based on imaging. Tumor recurrence is the major cause of cancer death in liver malignan cy. Post-operative prediction of early recurrence (ER) ( < 1 year) of liver cancer patients would allow clinicians to offer necessary cares to cancer patients after surgery prior to disease relapse. While resection is not suitab le in many of the relapse cases, patients are mostly given palliative support cares or systemic chemotherapies. Despite that, HCC is known to be a highly chemo-resistant tumor, and the response rate is less than 5 – 10 %. Patients diagnosed at late stages are dismal, and new therapeutic targets are urgently needed. Specific aims 1. To identify specific auto-antibodies and protein patterns or profiles in HCC patients that can be used as diagnostic and prognostic markers for liver cancer in a proteome-wide array analysis. 2. To characterize and evaluate any protective autoantibodies in HCC serum proteome that may offer better survival rate in the advanced stages of cancer patients.

Project Title:	Ankyrin repeat and SOCS box protein 4 (ASB4) as a candidate for developing targeted therapy of hepatocellular carcinoma
Investigator(s):	Lee NPY, Luk JMC
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2009

Abstract:

Liver cancer, or hepatocellular carcinoma (HCC), is the sixth most common malignancy in the world and it accounts for half a million deaths annually. HCC patients have poor prognosis and the overall 5-year survival rate remains dim, at ~ 5% (Parkin et al. 2005). Even nowadays, there is no absolute treatment for HCC patients for the following reasons. Because of the late presentation of the symptoms, HCC patients are often in the late-stage of this malignancy when first diagnosed. This cohort of patients is usually incurable due to the malignant and invasive nature of this tumor . In addition, liver tumor is highly resistant to most chemotherapy and this limits the treatment options offered for HCC patients. In view of this situation, it is our long-term goal to identify novel therapeutic targets for developing medication for HCC patients. In a previous proteomic study, in which we profiled and analyzed the protein patterns of mouse livers at different stages of liver development and then correlated the results with the progression of HCC, we identified several putative oncofetal molecules in HCC. We showed also that the gene expressions of a panel of fetal proteins in various human liver cancer cell lines and clinical tissues were induced in hepatocarcinogenesis (Lee et al. 2008). The translation of molecular information from mice to humans was largely comparative because of the fetal proteins that are found in mouse livers, such as proliferating cell nuclear antigen, have high expression levels in human liver cancer tissues as well (Lee et al. 2007; Sun et al. 2007; Lee et al. 2008). Among the oncofetal molecules identified in our previous study, ankyrin repeat and SOCS box protein 4 (ASB4) is one of the putative candidates. It is found to have elevated expressions in two highly metastatic human liver cancer cell lines (MHCC97-H and MHCC97-L) among several human liver cancer cell lines (Hep3B, HuH-7, HepG2, and HepAD38) and immortalized normal human hepatocytes (MIHA), implicating its potential roles in liver carcinogenesis (Lee et al. 2008). ASB4 is a family member of ankyrin repeat and SOCS box protein (ASB), which is a subfamily of suppressors of cytokine signaling (SOCS) (Krebs and Hilton 2000). ASB family composes of 18 members and they are found to involve in protein ubiquitination by associating with E3 ubiquitin protein ligase complex (Kohroki et al. 2005). Some of the family members are reported to involve in carcinogenesis. For instance, ASB8 is shown relating to the growth of lung cancer cells (Liu et al. 2003). However, there is no study yet to decipher the roles of ASB4 in cancers. Herein, we undertook a study to examine the roles of ASB4 in liver tumorigenesis using various in vitro assays and in vivo mouse model of liver cancers. Based on this study, new knowledge on the roles of ASB4 in liver cancers can be derived and can form the basis for investigating the use of ASB4 as a target for developing HCC therapy. Specific objectives: 1. Statistical analyses will be performed to correlate the expression of ASB4 with the clinical features of HCC patient cohorts. This will give information on how ASB4 is related to HCC pathogenesis. 2. Tumor phenotypes, such as cell proliferation, cell invasive ability, and apoptosis, will be examined in MHCC97-H cells when the expression of ASB4 in the tumor cells is suppressed using microRNA (miRNA)-based knockdown approach. This will delineat e the involvements of ASB4 in the presentation of tumor phenotypes in vitro. 3. Mouse model of HCC will be developed. MHCC97-H cells with suppressed expression of ASB4 will be inoculated subcutaneously into nude mice and the formation of tumors will be monitored. This will demonstrate the functional roles of ASB4 in liver tumor formation in an in vivo condition. References [1] Kohroki J, Nishiyama T, Nakamura T, Masuho Y (2005). ASB proteins interact with Cullin5 and Rbx2 to form E3 ubiquitin ligase complexes. FEBS Lett 579(30): 6796-802. [2] Krebs DL, Hilton DJ (2000). SOCS: physiological suppressors of cytokine signaling. J Cell Sci 113 ( Pt 16): 2813-9. [3] Lee NP, Cheung ST, Poon RT, Fan ST, Luk JM (2007). Genomic and proteomic biomarkers for diagnosis and prognosis of hepatocellular carcinoma. Biomarkers Med 1: 273-284. [4] Lee NP, Leung KW, Cheung N, Lam BY, Xu MZ, Sham PC, Lau GK, Poon RT, Fan ST, Luk JM (2008). Comparative proteomic analysis of mouse livers from embryo to adult reveals an association with progression of hepatocellular carcinoma. Proteomics 8(10): 2136-2149. [5] Liu Y, Li J, Zhang F, Qin W, Yao G, He X, Xue P, Ge C, Wan D, Gu J (2003). Molecular cloning and characterization of the human ASB-8 gene encoding a novel member of ankyrin repeat and SOCS box containing protein family. Biochem Biophy s Res Commun 300(4): 972-9. [6] Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA Cancer J Clin 55(2): 74-108. [7] Sun S, Lee NP, Poon RT, Fan ST, He QY, Lau GK, Luk JM (2007). Oncoproteomics of hepatocellular carcinoma: from cancer markers' discov ery to functional pathways. Liver Int 27(8): 1021-38.

Project Title:	3rd Annual Meeting of BIT Life Sciences (PepCon-2010) The Role and Regulation of Eukaryotic Translation Initiation Factor 5A2 (eIF5A2) in Liver Cancer and Implications for Treatment
Investigator(s):	Lee NPY
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	03/2010
Completion Date:	03/2010

Abstract:

N/A

List of Research Outputs

Fatima S. , Lee N.P.Y. , Ng I.O.L. and Luk J.M.C. , The role of Dickkopf 4 (DKK4) on Wnt signaling in hepatocellula r carcinoma (Poster Presentation), The 20th Annual Conference of the Asian Pacific Association for the Study of the Liver (APASL), Beijing, China, 25-28 March 2010 .

Lee N.P.Y. , Conference Award, Cancer Omics, Erice, Italy, 3-8 May 2010 . 2010.

Lee N.P.Y. and Luk J.M.C. , Hepatic tight junctions: from viral entry to cancer metastasis, World Journal of Gastroenterology . 2010, 16(3): 289-295.

Lee N.P.Y. , Poon R.T.P. , Shek H.P. , Ng I.O.L. and Luk J.M.C. , Role of cadherin-17 in oncogenesis and potential therapeutic implications in hepatocellular carcinoma, Biochimica et Biophysica Acta . 2010, Epub ahead of print (May): 1-8.

Lee N.P.Y. , The role and regulation of eukaryotic translation initiation factor 5A2 (eIF5A2) in liver cancer and implications for treatment (Invited Presentation), BIT Life Sciences’ 3rd Annual PepCon-2010, Beijing, China, 21-23 March 2010 .

Shek H.P. , Luk J.M.C. , Kwong A. and Lee N.P.Y. , The role of serine peptidase inhibitor, Kazal type I (SPINK1) in hepatocellular carcinoma (Poster Presentation), Cancer Omics, Erice, Italy, 3-8 May 2010 .

Sun S. , Poon R.T.P. , Lee N.P.Y. , Yeung C. , Chan K.L. , Ng I.O.L. , Day P.J.R. and Luk J.M.C. , Proteomics of hepatocellular carcinoma: serum vimentin as a surrogate marker for small tumors ( £ 2 cm), Journal of Proteome Research . 2010, 9(4): 1923-1930.

Tsang F.H. , Luk J.M.C. and Lee N.P.Y. , Clinical implication of ectopic expression of microRNA-125b in liver cancer (Poster Presentation), Cancer Omics, Erice, Italy, 3-8 May 2010 .

Tsang F.H. , Luk J.M.C. and Lee N.P.Y. , MicroRNA-125b as a negative regulator for eukaryotic translation initiation factor 5A2 (eIF5A2) in liver cancer (Poster Presentation), The 16th Hong Kong International Cancer Congress (HKICC) and 6th Annual Meeting of Center for Cancer Research, Hong Kong, 2009 .

Researcher : Lee PY

Project Title:	Tight-junction claudin-19 in kidney development and renal disease
Investigator(s):	Lee NPY, Luk JMC, Tam PC
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	11/2004

Abstract:

To isolate, identify and characterize a novel tight-junction molecule, claudin 19, which was initially found highly expressed in kidney.

Project Title:	Autoantibodies in early and late stages of liver cancer patients: a proteome-wide array analysis
Investigator(s):	Lee NPY, Luk JMC, Sham PC
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	11/2007
Completion Date:	11/2009

Abstract:

Liver cancer is often diagnosed at advanced or late stages with intra-hepatic and distant metastase s, when curative treatment options are limited in general. Thus, early detection of the aggressive malignant tumor could allow more available therapeutic approaches and offer patients better chance for long-term survival. Frequent surveillance of at-risk patients (with liver cirrhosis and/or hepatitis carriers) is recommended, but current efficacy of screening regimes, by measur ing serum alpha-fetoprotein (AFP) and transabdominal ultrasound imaging, however suffers from low diagnostic sensitivity and specificity particularly with high operator-dependent false-negative diagnosis based on imaging. Tumor recurrence is the major cause of cancer death in liver malignancy. Post-operative prediction of early recurrence (ER) ( < 1 year) of liver cancer patients would allow clinicians to offer necessary cares to cancer patients after su rgery prior to disease relapse. While resection is not suitable in many of the relapse cases, patients are mostly given palliative support cares or systemic chemotherapies. Despite that, HCC is known to be a highly chemo-resista nt tumor, and the response rate is less than 5 – 10 %. Patients diagnosed at late stages are dismal, and new therapeutic targets are urgently needed. Specific aims 1. To identify specific auto-antibodies and protein patterns or profiles in HCC patients that can be used as diagnostic and prognostic markers for liver cancer in a proteome-wide array analysis. 2. To characterize and evaluate any protective autoantibodies in HCC se rum proteome that may offer better survival rate in the advanced stages of cancer patients.

Project Title:	Ankyrin repeat and SOCS box protein 4 (ASB4) as a candidate for developing targeted ther apy of hepatocellular carcinoma
Investigator(s):	Lee NPY, Luk JMC
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2009

Abstract:

Liver cancer, or hepatocellular carcinoma (HCC), is the sixth most common malignancy in the world and it accounts for half a million deaths annually. HCC patients have poor prognosis and the overall 5-year survival rate remains dim, at ~ 5% (Parkin et al. 2005). Even nowadays, there is no absolute treatment for HCC patients for the following reasons. Because of the late presentation of the symptoms, HCC patients are often in the late-stage of this malignancy when first diagnosed. This cohort of patients is usually incurable due to the malignant and invasive nature of this tumor. In addition, liver tumor is highly resistant to most chemotherapy and this limits the treatment options offered for HCC patients. In view of this situation, it is our long-term goal to identify novel therapeutic targets for developing medication for HCC patients. In a previous proteomic study, in which we profiled and analyzed the protein patterns of mouse livers at different stages of liver development and then correlated the results with the progression of HCC, we identified several putative oncofetal molecules in HCC. We showed also that the gene expressions of a panel of fetal proteins in various human liver cancer cell lines and clinical tissues were induced in hepatocarcinogenesis (Lee et al. 2008). The translation of molecular info rmation from mice to humans was largely comparative because of the fetal proteins that are found in mouse livers, such as proliferating cell nuclear antigen, have high expression levels in human liver cancer tissues as well (Lee et al. 2007; Sun et al. 2007; Lee et al. 2008). Among the oncofetal molecules identified in our previous study, ankyrin repeat and SOCS box protein 4 (ASB4) is one of the putative candidates. It is found to have elevated expressions in two highly metastatic human liver cancer cell lines (MHCC97-H and MHCC97-L) among several human liver cancer cell lines (Hep3B, HuH-7, HepG2, and HepAD38) and immortaliz ed normal human hepatocytes (MIHA), implicating its potential roles in liver carcinogenesis (Lee et al. 2008). ASB4 is a family member of ankyrin repeat and SOCS box protein (ASB), which is a subfamily of suppressors of cytokine signaling (SOCS) (Krebs and Hilton 2000). ASB family composes of 18 members and they are found to involve in protein ubiquitination by associating with E3 ubiquitin protein ligase complex (Kohroki et al. 2005). Some of the family members are reported to involve in carcinogenesis. For instance, ASB8 is shown relating to the growth of lung cancer cells (Liu et al. 2003). However, the re is no study yet to decipher the roles of ASB4 in cancers. Herein, we undertook a study to examine the roles of ASB4 in liver tumorigenesis using various in vitro assays and in vivo mouse model of liver cancers. Based on this study, new knowledge on the roles of ASB4 in liver cancers can be derived and can form the basis for investigating the use of ASB4 as a target for developi ng HCC therapy. Specific objectives: 1. Statistical analyses will be performed to correlate the expression of ASB4 with the clinical features of HCC patient cohorts. This will give information on how ASB4 is related to HCC pathogenesis. 2. Tumor phenotypes, such as cell proliferation, cell invasive ability, and apoptosis, will be examined in MHCC97-H cells when the expression of ASB4 in the tumor cells is suppressed using microRNA (miRNA)-based knockdown approach. This will delineate the involvements of ASB4 in the presentation of tumor phenotypes in vitro. 3. Mouse model of HCC will be developed. MHCC97-H cells with suppressed expression of ASB4 will be inoculated subcutaneously into nude mice and the formation of tumors will be monitored. This will demonstrate the functional roles of ASB4 in liver tumor formation in an in vivo condition. References [1] Kohroki J, Nishiyama T, Nakamura T, Masuho Y (2005). ASB proteins interact with Cullin5 and Rbx2 to form E3 ubiquitin ligase complexes. FEBS Lett 579(30): 6796-802. [2] Krebs DL, Hilton DJ (2000). SOCS: physiological suppressors of cytokine signaling. J Cell Sci 113 ( Pt 16): 2813-9. [3] Lee NP, Cheung ST, Poon RT, Fan ST, Luk JM (2007). Genomic and proteomic biomarkers for diagnosis and prognosis of hepatocellular carcinoma. Biomarkers Med 1: 273-284. [4] Lee NP, Leung KW, Cheung N, Lam BY, Xu MZ, Sham PC, Lau GK, Poon RT, Fan ST, Luk JM (2008). Comparative proteomic analysis of mouse livers from embryo to adult reveals an association with progression of hepatocellular carcinoma. Proteomics 8(10): 2136-2149. [5] Liu Y, Li J, Zhang F, Qin W, Yao G, He X, Xue P, Ge C, Wan D, Gu J (2003). Molecular cloning and characterization of the human ASB-8 gene encoding a novel member of ankyrin repeat and SOCS box containing protein family. Biochem Biophys Res Commun 300(4): 972-9. [6] Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA Cancer J Clin 55(2): 74-108. [7] Sun S, Lee NP, Poon RT, Fan ST, He QY, Lau GK, Luk JM (2007). Oncoprote omics of hepatocellular carcinoma: from cancer markers' discovery to functional pathways. Liver Int 27(8): 1021-38.

Project Title:	3rd Annual Meeting of BIT Life Sciences (PepCon-2010) The Role and Regulation of Eukaryotic Translation Initiation Factor 5A2 (eIF5A2) in Liver Cancer and Implications for Treatment
Investigator(s):	Lee NPY
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	03/2010
Completion Date:	03/2010

Abstract:

N/A

List of Research Outputs

Hao K., Luk J.M.C. , Lee P.Y. , Mao M., Zhang C., Ferguson M.D., Lamb J., Dai H., Ng I.O.L. , Sham P.C. and Poon R.T.P. , Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters, BMC Cancer . 2009, 9: 389.

Hao W. , Liu X. , Lee P.Y. , Chen Y. and Wong K.K.Y. , A study into the effects of omega-3 fatty acids on macrophages and hepatocytes, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Lee P.Y. , Zhu Y. , Sun R.W.Y. , Hao W. , Liu X. , Che C.M. and Wong K.K.Y. , A safe and efficient lipidic nanoparticle carrier of gold porphryin for the treatment of neuroblastoma, The 3rd European Conference for Clinical Nanomedicine, Basel, Switzerland, 10-12 May 2010 .

Lee P.Y. , Delivery strategy of cancer therapeutics, Surgical Research Workshop 2010, The Univeristy of Hong Kong . 2010.

Lee P.Y. , Zhu Y. , Yan J., Sun R.W.Y. , Hao W. , Liu X.L., Che C.M. and Wong K.K.Y. , The cytotoxic effects of lipidic formulated gold-porph yrin nanoparticles for the treatment of neuroblastoma, Nanotechnology, Science and Applications . 2010, 3: 23-28.

Liu L. , Lee P.Y. , Chan V.W.M. , Xue W., Zender L., Zhang C., Mao M., Dai H., Wang X.L., Xu Z. , Lee K.W. , Ng I.O.L. , Chen Y., Kung H.F., Lowe S.W., Poon R.T.P. , Wang J.H. and Luk J.M.C. , Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma, Hepatology (Erratum in: Hepatology 2010;51(1):358) . 2009, 50(5): 1453-1463.

Liu X. , Lee P.Y. , Ho C.M. , Lui V.C.H. , Chen Y. , Che C.M. , Tam P.K.H. and Wong K.K.Y. , Silver nanoparticles mediate differential responses in keratinocytes and fibroblasts during skin wound healing, ChemMedChem . 2010, 5(3): 468-475.

Researcher : Lee PY

Project Title:	Inkjet printing of tissue-engineered skin construct for vascular regeneration in wound healing
Investigator(s):	Lee PY, Wong KKY, Tam PKH
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	11/2009

Abstract:

Highlight of tissue engineering Cell behavior is directed by spatial and temporal cues from the extracellular matrix in the tissue microenvironment. This inspires a current tissue engineering concept that successful tissue regeneration requires a precise match of the molecular and cellular composition that is responsible for hierarchy architecture and anatomical shapes with the host tissue microenvironment. Current tissue engineering therapy approaches are based on biomimetic extracellular matrices (bECMs) integrated with specific growth factors or seeded with cells to promote and guide tissue regeneration metered by bECM biodegradation. These approaches have been applied to several tissues such as bone, blood vessels, skin and nerve (1-3). This grant application builds on the knowledge that spatial patterning of ECM and hormones, including morphogens and growth factors, directs cell organizational behavior by providing positional information required for post-embryonic tissue repair or regeneration (4). Positional information can occu r via the diffusion of soluble signaling molecules from cells in ECM. Potential therapeutic application of tissue engineering in wound healing Skin graft is a common treatment option for severe injuries or burns, but poor vascularization in recipient sites, in most cases of Diabetic Mellitus, contributes to graft failure. Diabetic patients are known to have poor cellular turnover and excessive fibrosis, resulting in the reduced success rate of skin graft (5). In case of the deeper skin damage in chronic ulcer that requires the full thickness dermal and hypodermal graft, it is more critical to have sufficient blood supply to nourish the thick tissue graft. Recently, several world-renowned tissue engineers have attempted to develop strategies for promoting vascularization to enhance tissue regeneration (6, 7) Careful control of angiogenic signaling factor distribution and concentration is crucial for proper structure and function of the vascularization. It enables vessel development with minimal side effects at distant site including undesirable vasculature growth inside tumors or in sites of diabetic retinopathy. Furthermor e, scar formation i.e. hypertrophic scars and keloids, is closely related to abnormal vascularization pattern characterized with higher amount and more dilated blood vessels (8). Thus effective tissue engineering technique for a spatial control in molecular level or cellular level would be advantageous to improve an optimized vascularization. Despite a well-vascularized environment, skin structural integrity is responsible for cell-cell interaction, cell-matrix interaction that is important for regenerating normal function of skin. Exploration of 3D freeform fabrication provides a possibility for addressing the architectural and structural concerns. Recent exciting report showed that 3D freeform fabri cation by rapid prototyping successfully generates the stratified skin cellular layer (9). For the production of stratified cellular layer structure, lithography, a conventional rapid prototyping method, requires highly sophistica ted co-alignment of individual masks. Compared with the stratified skin layers, incorporation of precisely deposited angiogenic factors within the skin layers becomes more challenging. It requires placement of multiple masks in micron-scale accuracy for each individual layer. A new technique inkjet printing which is direct on demand technique provides an effective tool to produce such a complicated structure. And the design of direct bioink dispenser allows dispensing multiple biological materials simultaneously. This eliminates the tendency to distort the morphology of the tissue construct because subsequent dispensing two drops at the same location will form an undesirably large drop due to surface tension. With the incorporation of the CT scan image, computer-aided design provides the potential to produce the cellular construct that fits on the different wound defect site. In case of the conventional method, 3D organotypic culture construct that match the anatomical site cannot be readily made. Using a sophisticated thermal inkjet printing system incorporated with computer aided design (CAD), I have developed a micron-scale fabrication technique to construct biomatrix scaffold loaded with therapeutic agents including signaling proteins or genes and cells (Lee, PY et al manuscript submitted to Biomaterials). The use of human mesenchymal stem cells will be ideally suited in this project because it will be relatively easy to get harvested and expanded compared with other stem cells. Thus it is feasible to use autologous cell source for development of organotypic structure, reducing the immune rejection. Furthermore, possible replacement for embryonic cells in regenerating skin tissue has been demonstrated with the use of non- epithelial stem cells (10). The multipotency of human mesenchymal stem cells has been reported since they are capable to differentiate into various lineages including endothelial and epithelial lineages (11, 12). Recent evidence has shown the potential of hMSC in promoting vascular repair in response to angiogenic factors (13). Moreover hMSCs produce the VEGF, one of the potent mitogenic factors during endothelial cell proliferation (14). This following research plan is driven by the hypothesis that the spatial control of angiogenic microenvironment can induce the vascular development in stratified skin cellular layers. The ultimate goal is the use of construct to promote woun d repair and reduce graft loss. Three specific aims are listed below 1) To control the spatial distribution of the stem cells derived endothelial cells by inkjet printing. 2) To generate the vasculature-like structures embedded in stratified cellular skin layers 3) To evaluate the in vivo response of the vascularized cellular construct in wound healing (Please find the references in the attachment)

List of Research Outputs

Lee P.Y. , Delivery strategy of cancer therapeutics, Surgical Research Workshop 2010, The Univeristy of Hong Kong . 2010.

Lee P.Y. , Zhu Y. , Yan J., Sun R.W.Y. , Hao W. , Liu X.L., Che C.M. and Wong K.K.Y. , The cytotoxic effects of lipidic formulated gold-porphyrin nanoparticles for the treatment of neuroblastoma, Nanotechnology, Science and Applications . 2010, 3: 23-28.

Researcher : Leon YY

List of Research Outputs

Cornes B.K. , Tang S.M. , Leon Y.Y. , Hui K.J.W.S., So M.T. , Miao X. , Cherny S.S. , Sham P.C. , Tam P.K.H. and Garcia-Barcelo M.M. , Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population, PLoS One . 2010, 5 (6): e10918.

Garcia-Barcelo M.M. , Tang W.Y. , Miao X. , Tang S.M. , So M.T. , Leon Y.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Identification of rare variants in the NRG1 gene of Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Garcia-Barcelo M.M. , Lui V.C.H. , So M.T. , Miao X. , Leon Y.Y. , Yuan Z.W., Ngan E.S.W. , Ehsan T., Chung P.H.Y., Khong P.L. , Wong K.K.Y. and Tam P.K.H. , MNX1 (HLXB9) mutations in Currarino patients, Journal of Pediatric Surgery . 2009, 44(10): 1892-1898.

Leon Y.Y. , Ngan E.S.W. , Poon H.C. , So M.T. , Lui V.C.H. , Tam P.K.H. and Garcia-Barcelo M.M. , Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3, Journal of Pediatric Surgery . 2009, 44(10): 1904-1912.

Miao X. , Leon Y.Y. , Ngan E.S.W. , So M.T. , Yuan Z.W., Lui V.C.H. , Chen Y. , Wong K.K.Y. , Tam P.K.H. and Garcia-Barcelo M.M. , Reduced RET expression in gut tissue on individuals carrying risk alleles of Hirschsprung's disease, Human Molecular Genetics . 2010, 19(8): 1461-1467.

Sham P.C. , Cornes B.K., Tang S.M. , Leon Y.Y. , So M.T. , Tam P.K.H. and Garcia-Barcelo M.M. , A RET founder mutation in Chinese Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Tang S.M. , Sribudiani Y., Miao X. , de Vries A.R., Burzynski G., So M.T. , Leon Y.Y. , Yip B.H.K. , Osinga J., Hui K.J.W.S., Verheij J.B.G.M., Cherny S.S. , Tam P.K.H. , Sham P.C. , Hofstra R.M.W. and Garcia-Barcelo M.M. , Fine mapping of the 9q31 Hirschsprung's disease locus, Human Genetics . 2010, 127(6): 675-683.

Researcher : Leung ACF

List of Research Outputs

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s96.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Researcher : Leung CPH

List of Research Outputs

Kwong A. , Ng E.K.O. , Leung C.P.H. , Tsang W.P., Wong L.P. , Kwok T.T. and Ma E.S.K. , Role of miR-143 regulating DNA methyltransferases 3A in breast cancer, Ejc Supplements . 2010, 8(3): 172-173.

Ng E.K.O. , Leung C.P.H. , Au S., Chan A., Wong L.P. , Ma E.S.K. , Pang R.W.C. , Chua D.T.T. , Chu K.M. , Law W.L. , Poon R.T.P. and Kwong A. , Plasma microRNA as a potential marker for breast cancer detection, The 101st Annual Meeting of the American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Ng E.K.O. , Kwong A. , Tsang W.P., Leung C.P.H. , Wong L.P. , Kwok T.T. and Ma E.S.K. , Role of miR-143 regulating DNA methyltransferases 3A in breast cancer, Cancer Research . 2009, 69(24): 695S-695S.

Researcher : Leung GKK

Project Title:	A prospective study on platelet functions in neurosurgical patients receiving acetylsalicylic acid (aspirin).
Investigator(s):	Leung GKK, Ng JKF, Fan YW
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	12/2005

Abstract:

OBJECTIVE To assess platelet functions in hospitalized neurosurgical patients who receive aspirin immediately prior to admission. BACKGROUND Acetylsalicylic acid, or aspirin, is commonly used for the treatment of thrombotic vascular diseases such as coronary artery disease or cerebrovascular diseases. Aspirin-users may sometimes present with concurrent neurosurgical conditions, such as brain tumours and intracranial haemorrhages. Aspirin, by impairing platelet functions, may cause clinical deterioration or severe intra-opera tive haemorrhages in these patients. [1-2] In stable patients, it is current neurosurgical practice to withhold aspirin and to post-pone surgery until platelet functions normalize . In unstable patients, it may be necessary to proceed with immediate surgery despite impaired platelet functions. Attempts would be made in the latter situation to improve haemostasis by means of platelet transfusion. [3] Patients on aspirin, however, represent a heterogeneous population. Although the pharmacokinetics and pharmacodynamics of aspirin have been well studied, the actual clinical effect within and between individuals may vary widely due to differences in dosage, individual response, treatment duration and compliance. For an individual taking aspirin who presents with a neurosurgical condit ion, there is no reliable clinical method to assess platelet functions, or to ascertain if it is safe to proceed with immediate surgery, or for how long surgery should be withheld. The clinical effects of empirical corrective measures such as platelet transfusion are also unknown. Platelet functions can be assessed quantitatively using PFA-100® analyzer, which is a newly developed and validated method for the monitoring of various platelet dysfunctions. It requires venous whole blood samples only, and unlike the template bleeding-time method, PFA-100® analysis is more accurate and reproducible, and do not leave any extra scars. Actual aspirin consumpt ion in patients who give a drug history of aspirin usage can be verified using serum thromboxaneB2 level analysis. [4-6] We therefore design this study to address the following questions, using PFA-100® and thromboxaneB2 level analysis as quantitative assessment of platelet functions and consumption: QUESTIONS TO BE ANSWERED • To what extent do PFA-100® results vary amongst patients who give history of aspirin consumption immediately prior to hospital admission? • How do PFA-100® results change after cessation of aspirin consumption? And can the changes be formulated using clinically applicable parameters such as body size, age and aspirin dosage ? • To what extent does platelet transfusion alter PFA-100® results in aspirin- users. REFERENCES 1. Palmer JD, Sparrow OC, Iannotti F. Postoperative Hematoma: A 5-Year Survey and Identification of Avoidable Risk Factors. Neurosurgery 1994;36:1061-1065. 2. Stroobandt G, Fransen P, Thauvoy C, Menato hospital enetic factor s in chronic subdural haematoma and causes of recurrence after drainage. Acta Neurochir (Wien) 1995;137:6-14. 3. Harder S, Klinkhardt U, Alvarez JM. Avoidance of bleeding during surgery in patients receiving anticoagulant and/or antiplatelet therapy: pharmacokinetic and pharmacod ynamic considerations. Clin Pharmacokinet 2004; 43:963-981.- 4. Goh KY, Tsoi WC, Feng CS, Wickham N, Poon WS. Haemostatic changes during surgery for primary brain tumours. J Neurol Neurosurg Psychiatry 1997; 63: 334-338. 5. Favaloro EJ. Clinical application of the PFA-100. Curr Opin Hematol 2002; 9:407-415. 6. Jacoby RC, Owings JT, Holmes J, Battistella FD, Gosselin RC, Paglieroni TG. Platelet activation and function after trauma. J Trauma 2001; 51:639-647.

List of Research Outputs

Cheung J.P., Tsang H.H., Cheung J.J., Yu H.H., Leung G.K.K. and Law W.L. , Adjuvant therapy for the reduction of postoperative intra-abdominal adhesion formation, Asian Journal of Surgery . 2009, 32(3): 180-186.

Lam C.L.K. , Chan G.C.F. , Lam T.H. , Lee P.P.W. , Leung A.Y.M. , Leung G.K.K. and Tsao G.S.W. , 育醫造才: 探索醫學世界, 2010.

Leung G.K.K. , Clinical undergraduate examination - voluntary patients' perspective, Medical Teacher . 2010, Jan;32(1): e1-4.

Leung G.K.K. , Hung K.N. , Lui W.M. and Fan Y.W. , Combined transcranial and transsphenoidal resection of huge pituitary adenoma, The 7th Meeting of the Asian Society for Neuro-oncology, Seoul, Korea, 10 - 12 June 2010 .

Leung G.K.K. , Faculty Teaching Medal 2009, Li Ka Shing Faculty of Medicine, The University of Hong Kong . 2009.

Leung G.K.K. , Functional survival after acute hospital admission for severe head injury at a trauma centre in Hong Kong, The 7th Academy for Multidisciplinary Neurotraumat ology Congress and 16th Annual Scientific Meeting of Hong Kong Neurosurgical Society, Neurotraumatology: Head Injury and Spinal Cord Injury, Hong Kong, 12 - 14 November 2009 .

Leung G.K.K. , Glial reaction of the brain after bipolar coagulation: a pilot study, The 7th Academy for Multidisciplinary Neurotraumatology Congress and 16th Annual Scientific Meeting of Hong Kong Neurosurgical Society, Neurotraumatology: Head Injury and Spinal Cord Injury, Hong Kong, 12 - 14 Novemb er 2009 .

Leung G.K.K. , Hong Kong brain tumour epidemiology, The 16th Hong Kong International Cancer Congress, 6th Annual Meeting for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 4 - 6 November 2009 .

Leung G.K.K. , Hong Kong intracranial and central nervous system tumor registry, The 7th Academy for Multidisciplinary Neurotraumatology Congress and 16th Annual Scientific Meeting of Hong Kong Neurosurgical Society, Neurotraumatology: Head Injury and Spinal Cord Injury, Hong Kong, 12 - 14 November 2009 .

Leung G.K.K. , Medicine as our liberal arts, In: The Federation of Medical Societies of Hong Kong, Medical Diary . 2009.

Leung G.K.K. , Outcome of severely injured trauma patients at a designated trauma centre in the Hong Kong Special Administrative Region, Chinese Medical Journal . 2010, 123(10): 1251-1254.

Leung G.K.K. and Patil N.G. , Patient safety in the undergraduate curriculum: medical students' perception, Hong Kong Medical Journal . 2010, 16(2): 101-105.

Leung G.K.K. , Self-assembling peptide nanofiber scaffold (SAPNS) as a potiental neuro-regenerative biomaterial in surg ically induced brain injury, The 7th Academy for Multidisciplinary Neurotraumatology Congress and 16th Annual Scientific Meeting of Hong Kong Neurosurgical Society, Neurotraumatology: Head Injury and Spinal Cord Injury, Hong Kong, 12 - 14 November 2009 .

Leung G.K.K. , Technical competency in neurosurgery - trainees versus specialists in expectations and perceptions, The 7th Academy for Multidisciplinary Neurotraumatolog y Congress and 16th Annual Scientific Meeting of Hong Kong Neurosurgical Society, Neurotraumatology: Head Injury and Spinal Cord Injury, Hong Kong, 12 - 14 November 2009 .

Leung G.K.K. , Thalamo-perforating artery aneurysm in Moyamoya disease - case report, British Journal of Neurosurgery . 2010, Early Online: 1-3.

Leung G.K.K. , Wong S.T.S. and Zhang X. , The potential use of microRNA-21 inhibitors to overcome temozolomide resistance in glioblastoma multiforme, The 7th Meeting of the Asian Society for Neuro-onc ology, Seoul, Korea, 10 - 12 June 2010 .

Leung G.K.K. , Thrombolysis of extensive cerebral sinus thrombosis by local infusion of urokinase via microcatheter inserted transcranially, The 7th Academy for Multidisciplinary Neurotraumatology Congress and 16th Annual Scientific Meeting of Hong Kong Neurosurgical Society, Neurotraumatology: Head Injury and Spinal Cord Injury, Hong Kong, 12 - 14 November 2009 .

Leung G.K.K. , Trauma system in Hong Kong, Surgical Practice . 2010, 14: 38-43.

Leung G.K.K. , Traumatic brain injury in a developing trauma system in Hong Kong, The 7th Academy for Multidisciplinary Neurotraumatology Congress and 16th Annual Scientific Meeting of Hong Kong Neurosurgical Society, Neurotraumatology: Head Injury and Spinal Cord Injury, Hong Kong, 12 - 14 November 2009 .

Leung G.K.K. , Validation and application of two Quality of Life (QQL ) Instruments specific for local Chinese patients with malignant brain tumour, The 16th Hong Kong International Cancer Congress, 6th Annual Meeting Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 4 - 6 November 2009 .

Researcher : Leung MC

List of Research Outputs

Tang S.M. , Tang W.K. , So M.T. , Miao X.P. and Leung M.C. , Fine mapping of the NRG1 Hirschsprung’s disease locus, Human Molecular Genetics . 2010, Submitted.

Researcher : Li C

List of Research Outputs

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the Internat ional Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Li X.C., Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplanta tion . 2010, 16(6): s141.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s96.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobiliz ed circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Man K. , Shao Y. , Ng T.P. , Li C. , Fan S.T. and Lo C.M. , The significance of acute-phase small-for-size liver graft injury in mobilization of circulating EPCS/MDSCS/TREG S after LDLT for HCC patients (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16 - 19 June 2010. Liver Transplant ation . 2010, 16(6): s191.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , Identification of circulating protein markers related to tumor recurrence after liver transplantation (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transpla ntation . 2010, 16(6): s207.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Abstract), The 16th International Liver Transplantation Soci ety Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s77.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Young Investigator Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Researcher : Li GKH

List of Research Outputs

Romano M.E., Wahlander S.B., Lang B.H.H. , Li G.K.H. and Prager K.M., Mandatory Ethics Consultation Policy, Mayo Clin Proc . 2009, 2009: 5.

Researcher : Li L

List of Research Outputs

Liu Y., Wen X.M., Lui E.L.H. , Friedman S.L., Cui W., Ho N.P., Li L. , Ye T., Fan S.T. and Zhang H., Therapeutic targeting of the PDGF and TGF-beta-signaling pathways in hepatic stellate cells by PTK787/ZK22258 , Laboratory Investigation . 2009, 89(10): 1152-1160.

Researcher : Li X

Project Title:	The impact of pressure overload on apoptosis in cardiomyocytes
Investigator(s):	Li X, Cheung YF
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2010

Abstract:

Congenital heart diseases associated with right ventricular (RV) pathologies are common. Advances in paediatric cardiology, peri-operative care, and paediatric cardiac surgical techniques have significantly reduced the surgical mortality and therefore survival of congenital heart patients to adulthood is currently the rule rath er than exception. Nonetheless, despite the so-called “corrective” surgery, progressive RV dysfunction remains a concern in patients with chronic pressure loading of the right ventricle. Progressive dysfunction of the systemic right ventricle is well documented in patients with chronic pressure overload of the systemic RV after atrial switch operation for complete transposition of the great arteries and in those with congenitally corrected transposition. Notwithstanding the well documented clinical progression of RV dysfunction in the aforementioned conditions, the cause of RV dysfunction remains poorly understood. Apoptosis, or programmed cell death, of cardiomyocytes has attracted increasing interests given the accumulating strong scientific evidence of a pivotal role of apoptotic cell death in the development of heart failure and potential for apoptosis-based therapeutic approaches. The possible role of cardiomyocyte apoptosis in progressive RV dysfunction in the setting of chronic RV pressure overload has nonetheless not been explored. The proposed study is to test the hypothesis, that abnormal loading, in terms of pressure loading of the right ventricle is associated with apoptosis of RV cardiomyocytes. Issues to be addressed in this study will include i) the impact of RV pressure overloading on RV cardiomyocyte apoptosis in children and adolescents with significant pulmonary stenosis, ii) the role of microRNAs in cardiomyocyte apoptosis in chronic RV pressure overload. The proposed study would shed light on the possible role of cardiomyocyte apoptosis in the development of RV failure in pressure overloaded conditions, which has important therapeutic implications in terms of developing anti-apoptotic strategies. The possible role of microRNAs in the myocardial remodeling process by regulation of cardiomyocyte apoptosis, changes in the extracellular matrix and neurohormonal activation may also contribute to the future development of therapeutic strategies for right ventricular failure whereby cert ain microRNAs may potentially become therapeutic targets in such conditions.

List of Research Outputs

Li X. , Heart Surgery for Congenital Heat Disease, Special Nursing Diploma Course in Cardiac Care for Nurses From Guangdong Province . Hospital Authority, 2010.

Li X. , Cheng L.C. , Cheung Y.F. , Lun K.S., Chau A.K.T. and Chiu S.W., Management of symptomatic congenital tracheal stenosis in neonates and infants by slide tracheoplasty: a 7-year single institution experience, European Journal of Cardio-thoracic Surgery . 2010, Epub ahead of print.

Li X. , Cheng L.C. , Cheung Y.F. , Lun K.S. , Chau A.K.T. and Chiu S.W. , Management of symptomatic congenital tracheal stenosis in neonates and infants by slide tracheoplasty: a 7-ye ar single institution experience, European Journal of Cardio-thoracic Surgery . 2010, 38: 609-614.

Tsang F.H.F., Li X. , Cheung Y.F. , Chau A.K.T. and Cheng L.C. , Pulmonary valve replacement after surgical repair of Tetralogy of Fallot, Hong Kong Medical Journal . 2010, 16: 26-30.

Researcher : Lim YK

List of Research Outputs

Lim Y.K. , Law W.L. , Poon J.T.C. and Fan J.K.M. , Impact of multimodality treatment on total mesorectal excision (TME) surgery for very low rectal cancers, International Surgical Week 2009, Adelaide, Australia, 6-10 September 2009 .

Lim Y.K. , Law W.L. , Liu R., Poon J.T.C. , Fan J.K.M. and Lo O.S.H., Impact of neoadjuvant treatment on total mesorectal excision for ultra-low rectal cancers, World Journal of Surgical Oncology . 2010, 8: 23.

Researcher : Lim ZXH

List of Research Outputs

Cheng Q. , Ng T.P. , Fan S.T. , Lim Z.X.H. , Guo D. , Liu X. , Liu Y. , Poon R.T.P. , Lo C.M. and Man K. , Distinct mechanism of small-for-size fatty liver graft injury--Wnt4 signaling activates hepatic stellate cells , American Journal of Transplantation . 2010, 10(5): 1178-1188.

Man K. , Shih K.C. , Ng T.P. , Xiao J. , Guo D. , Sun K.W. , Lim Z.X.H. , Cheng Q. , Liu Y. , Fan S.T. and Lo C.M. , Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts, Annals of Surgery . 2010, 251(6): 1154-1161.

Man K. , Ng T.P. , Xu A. , Cheng Q. , Lo C.M. , Xiao J. , Sun B. , Lim Z.X.H. , Cheung J.S., Wu E.X. , Sun K.W. , Poon R.T.P. and Fan S.T. , Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling, Clinical Cancer Research . 2010, 16(3): 967-977.

Researcher : Lin C

Project Title:	The effect of SARS-associated coronavirus Spike protein on immune regulation of SARS
Investigator(s):	Lin CL, Chan VSF
Department:	Surgery
Source(s) of Funding:	VCO SARS Research Fund
Start Date:	07/2003

Abstract:

To delineate the immune regulatory mechanisms in the afferent and efferent phases of immune responses against SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus) infection.

Project Title:	Development of DNA and viral vector vaccines against Epstein-Barr virus-positive nasopharyngeal carcinoma
Investigator(s):	Lin CL
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	09/2003

Abstract:

To design and parpare DNA vaccine encoding EBNA1 and LMP2, and the MVA vaccine encoding the cytokine GM-CSF, the chemokine RANTES, the EBV- specific lytic antigen EBNA-1, and EBV-specific latent antigen LMP2; to identify the efficacy of these vaccines in vitro on their capacity in attracting dendritic cells and also in the induction of EBNA-1 specific CD4+T cell response and LMP2-specific CTL immunity; to verify the efficacy of these vaccines in a mouse NPC and a B cell lymphoma model, including the potency of CD4+ and CTL immunity, and also to test the effect of the dosage, route, and the effect of combinational use of both the DNA and MVA vaccines.

Project Title:	Development and clinical evaluation of peptide vaccines for immunotherapy of Epstein-Barr virus-positive nasopharyngeal carcinoma
Investigator(s):	Lin CL, Tam PKH, Che CM
Department:	Surgery
Source(s) of Funding:	NSFC/RGC Joint Research Scheme
Start Date:	12/2004

Abstract:

To design and prepare peptide vaccines composed of novel peptide analogues of the Epstein-Barr virus (EBV)-specific antigen latent membrane protein 2 (LMP2), EBV-specific nuclear antigen type 1 (EBNA1), the DC-specific monocyte-derived chemokine (MDC), and the dendritic cell (DC) activator CD40 ligand; to assess the efficacy of this peptide vaccine in vitro and in vivo in a NO D/SCID mouse model in terms of the capacity in attracting DCs and inducing LMP2- and EBNA1-specific T cell immunity; to conduct a phase I clinical trial to verify in vivo the efficacy of peptide vaccine in human subjects, including the safety and toxicity, the EBV-specific CD4 and CD8 T cell responsiveness, and the effect of the dosage and regimen in boosting and maintaining the longevity of effective T cell immunity.

List of Research Outputs

Researcher : Lin CL

Project Title:	The effect of SARS-associated coro navirus Spike protein on immune regulation of SARS
Investigator(s):	Lin CL, Chan VSF
Department:	Surgery
Source(s) of Funding:	VCO SARS Research Fund
Start Date:	07/2003

Abstract:

To delineate the immune regulatory mechanisms in the afferent and efferent phases of immune responses against SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus) infection.

Project Title:	Development of DNA and viral vector vaccines against Epstein-Barr virus-positive nasophary ngeal carcinoma
Investigator(s):	Lin CL
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	09/2003

Abstract:

To design and parpare DNA vaccine encoding EBNA1 and LMP2, and the MVA vaccine encoding the cytokine GM-CSF, the chemokine RANTES, the EBV- specific lyti c antigen EBNA-1, and EBV-specific latent antigen LMP2; to identify the efficacy of these vaccines in vitro on their capacity in attracting dendritic cells and also in the induction of EBNA-1 specific CD4+T cell response and LMP2-specific CTL immunity; to verify the efficacy of these vaccines in a mouse NPC and a B cell lymphoma model, including the potency of CD4+ and CTL immunity, and also to test the effect of the dosage, route, and the effect of combinational use of both the DNA and MVA vaccines.

Project Title:	Development and clinical evaluation of peptide vaccines for immunotherapy of Epstein-Barr virus-positive nasopharyngeal carcinoma
Investigator(s):	Lin CL, Tam PKH, Che CM
Department:	Surgery
Source(s) of Funding:	NSFC/RGC Joint Research Scheme
Start Date:	12/2004

Abstract:

To design and prepare peptide vaccines composed of novel peptide analogues of the Epstein-Barr virus (EBV)-specific antigen latent membrane protein 2 (LM P2), EBV-specific nuclear antigen type 1 (EBNA1), the DC-specific monocyte-derived chemokine (MDC), and the dendritic cell (DC) activator CD40 ligand; to assess the efficacy of this peptide vaccine in vitro and in vivo in a NOD/SC ID mouse model in terms of the capacity in attracting DCs and inducing LMP2- and EBNA1-specific T cell immunity; to conduct a phase I clinical trial to verify in vivo the efficacy of peptide vaccine in human subjects, including the safety and toxicity, the EBV-specific CD4 and CD8 T cell responsiveness, and the effect of the dosage and regimen in boosting and maintaining the longevity of effective T cell immunity.

List of Research Outputs

Khoo U.S. , Chan Y.K. , Ching C.Y.J. , Chan V.S.F. , Ip Y.C. , Yam L., Chu C.M., Lai S.T., So K.M., Wong T.Y., Chung P.H., Yip S.P., Sham P.C. , Leung G.M. , Lin C.L. and Peiris J.S.M. , Functional role of ICAM-3 polymorphism in genetic susceptibility to SARS infection, Hong Kong Med Journal . 2009, 26-9.

Researcher : Ling C

List of Research Outputs

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulato ry T cells (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Li X.C., Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s96.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-deri ved suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the Interna tional Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , Identification of circulating protein markers related to tumor recurrence after liver transplantation (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplant ation . 2010, 16(6): s207.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Abstract), The 16th International Liver Transplantation Societ y Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s77.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Young Investigator Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Researcher : Liu AML

List of Research Outputs

Liu A.M.L. , Poon R.T.P. and Luk J.M.C. , MicroRNA-375 targets Hippo-signaling effector YAP in liver cancer and inhibits tumor properties, Biochemical and Biophysical Research Communications . 2010, 394(3): 623-627.

Researcher : Liu CL

Project Title:	The significance of intra-graft expression profile and ultrastructural features at early phase after liver transplantation-a prospective study of liver transplantation using cadaver and live donors
Investigator(s):	Liu CL, Man K
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To investigate the gene expression profiles of the donor and graft at the early phase after liver transplantation associated with hepatic ultrastructural features in liver transplantation using cadaver and live donors; to study the correlation of graft status, gene expression patterns with early and late clinical outcome functionally and morphologically.

Project Title:	Portal vein embolization before major right hepatic resection for hepatocellular carcinoma: a prospective randomized study
Investigator(s):	Liu CL, Fan ST, Tso WK
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2006

Abstract:

To evaluate the role of preoperative PVE in patients undergoing major right hepatic resection for HCC, and to determine whether the treatment can result in reduction of postoperative morbidities of these patients by a prospective randomized trial.

List of Research Outputs

Chan A.C.Y. , Fan S.T. , Lo C.M. , Liu C.L. , Chan S.C. , Ng K.K.C. , Yong B.H. , Chiu A. and Lam B.K.Y. , Liver transplantation for acute-on-chronic liver failu re, Hepatology International . 2009, 3(4): 571-581.

Fan S.T. and Liu C.L. , Live-donor liver transplantation in adults, In: Hakim N., Canelo R. and Papalois V. (eds.), Living Related Transplantation . London, Imperial College Press, 2010, 65-93.

Researcher : Liu L

List of Research Outputs

Liu L. , Lee P.Y. , Chan V.W.M. , Xue W., Zender L., Zhang C., Mao M., Dai H., Wang X.L., Xu Z. , Lee K.W. , Ng I.O.L. , Chen Y., Kung H.F., Lowe S.W., Poon R.T.P. , Wang J.H. and Luk J.M.C. , Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma, Hepatology (Erratum in: Hepatology 2010;51(1):358) . 2009, 50(5): 1453-1463.

Researcher : Liu WM

List of Research Outputs

Wong S.T.S. , Chan W.S. , Li C.H., Liu W.M. , Tang W.W., Tsao G.S.W. , Tsang R.K.Y. , Ho W.K. , Wei W.I. and Chan Y.W. , Curcumin alters the migratory phenotype of nasopharyngeal carcinoma cells through up-regulation of E-cadherin , Anticancer Research . 2010, 30: 2851-6.

Researcher : Liu X

Project Title:	Unfolded protein response (UPR)-regul ated adaptation to hypoxia in hepatocellular carcinoma (HCC)
Investigator(s):	Liu X, Man K
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	01/2010

Abstract:

Purpose We aim to investigate the molecular mechanisms of unfolded protein response (UPR) pathways regulatin g the cellular adaptation to hypoxia in hepatocellular carcinoma (HCC). Key issues and problems Hypoxia (oxygen deficiency) occurs in the majority of solid tumors including HCC. Increasing evidence has demonstrated that hypoxia alters tumor pathophysiology towards a more aggressive phenotype, which is strongly associated with tumor growth, metastasis and poor response to therapies. However, how the tumor cells adapt to hypoxia and further survive in the hypoxic environment, especially in HCC, remains poorly elucidated. The endoplasmic reticulum (ER) is a major organelle for the regulation of cellular homeostasis. Recently, it has been shown that ER-mediated adaptive responses, particularly the unfolded protein response (UPR) pathways are activated by hostile challenges such as hypoxia in tumor micro environments. This indicates that activation of UPR may condition the intrinsic capacity of tumor cells to allow for adaptation to stressful stimulus. Also, UPR pathways have been observed to provide unique and specific roles in diverse developmental and metabolic processes in professional secretory cells such as hepatocytes, whic h harbor an extensive and highly evolved ER structure. Based on these findings, we propose that UPR pathways may play essential roles in developing adaptation to hypoxia in HCC. On the other hand, it has been demonstrated that activation of UPR also set in motion apoptotic signaling cascades in cells under hypoxic stress. The adaptation and survival of tumor cells thus requires that adaptive responses be perpetuated, whereas those lead to apoptosis are suppressed. We therefore hypothesize that inhibition of UPR downstream signaling, which triggers apoptosis, may be one of the mechanisms to facilitate tumor cell survival under hypoxia rather than to induce cell death. Furthermore, since UPR has been reported to be a strong activator of other anti-apoptotic cellular cascades such as PI3K/Akt pathway and MEK/ERK pathway, we assume that the interplay between UPR and these pathways may be additional adaptive mechanism involved in response to hypoxic stress in HCC.

List of Research Outputs

Cheng Q. , Ng T.P. , Fan S.T. , Lim Z.X.H. , Guo D. , Liu X. , Liu Y. , Poon R.T.P. , Lo C.M. and Man K. , Distinct mechanism of small-for-size fatty liver graft injury--Wnt4 signaling activates hepatic stellate cells, American Journal of Transplantation . 2010, 10(5): 1178-1188.

Garcia-Barcelo M.M. , Yeung M.Y. , Miao X.P., Tang S.M. , Chen G., So M.T. , Ngan E.S.W. , Lui V.C.H. , Chen Y. , Liu X. , Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y. , Chan D. , Cheung K.M.C. , Chung P.H.Y., Wong K.K.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2, Human Molecular Genetics . 2010, 19 (14): 2917-2925.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Abstract), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Hao W. , Liu X. , Lee P.Y. , Chen Y. and Wong K.K.Y. , A study into the effects of omega-3 fatty acids on macrophages and hepatocytes, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Hao W. , Liu X. , Chan I.H.Y., Chan K.L. , Tam P.K.H. and Wong K.K.Y. , Comparison study of post-operative stress response between single-port and three-port laparoscopic varicocelect omy in children, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Lee P.Y. , Zhu Y. , Sun R.W.Y. , Hao W. , Liu X. , Che C.M. and Wong K.K.Y. , A safe and efficient lipidic nanoparticle carrier of gold porphryin for the treatment of neuroblastoma, The 3rd European Conference for Clinical Nanomedicine, Basel, Switzerland, 10-12 May 2010 .

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Li X.C., Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s96.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigat or Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantat ion . 2010, 16(6): s72.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Rising Star Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Liu X. , Lam G., Wong K.K.Y. and Tam P.K.H. , Perioperative and late outcomes of laparoscopic fundoplicatio n for neurologically impaired children, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Liu X. , Lee P.Y. , Ho C.M. , Lui V.C.H. , Chen Y. , Che C.M. , Tam P.K.H. and Wong K.K.Y. , Silver nanoparticles mediate differential responses in keratinocytes and fibroblasts during skin wound healing, ChemMedChem . 2010, 5(3): 468-475.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft - the significance of aldose reductase signaling on oval cell activation (Travel Award), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009 . 2009.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft – the significance of aldose reducatase signaling on oval cell activation (Abstract), The 15th Annual International Congress of the Internatio nal Liver Transplantation Society, New York, U.S.A., 8-11 July 2009. Liver Transplantation . 2009, 15:S72: #O6.

Man K. , Ng T.P. , Liu X. , Yeung W.H. , Lo C.M. and Fan S.T. , Inflammatory microenvironment accelerates liver tumor growth and metastasis by mobilizing circulating endothelial progenitor cells and increasing cancer stem like cell populations (Abstract), The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , Identification of circulating protein markers related to tumor recurrence after liver transplantation (Abstract), The 16th International Liver Transplantation Soci ety Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s207.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Abstra ct), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s77.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Young Investigator Award), The 16th International Liver Transplantation Soci ety Congress, Hong Kong, 16-19 June 2010 . 2010.

Researcher : Liu X

List of Research Outputs

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Abstract), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 Ju ne 2010. Liver Transplantation . 2010, 16(6): s141.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 Jun e 2010 . 2010.

Hao W. , Liu X. , Chan I.H.Y., Chan K.L. , Tam P.K.H. and Wong K.K.Y. , Comparison study of post-operative stress response between single-port and three-port laparoscopic varicocele ctomy in children, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investig ator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 Ju ne 2010 . 2010.

Liu X. , Lam G., Wong K.K.Y. and Tam P.K.H. , Perioperative and late outcomes of laparoscopic fundoplicat ion for neurologically impaired children, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft – the significance of aldose reducatase signaling on oval cell activation (Abstract), The 15th Annual International Congress of the Internat ional Liver Transplantation Society, New York, U.S.A., 8-11 July 2009. Liver Transplantation . 2009, 15:S72: #O6.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , Identification of circulating protein markers related to tumor recurrence after liver transplantation (Abstract) , The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s207.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Abst ract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s77.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-f or size liver graft injury and tumor invasiveness (Young Investigator Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Researcher : Liu Y

Project Title:	The effects of FTY720 on suppression of circulating myeloid-derived suppressor cells/endothelial progenitor cells mobilization during tumor recurrence in a rat liver cancer model
Investigator(s):	Liu Y, Man K, Lo CM
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	01/2009

Abstract:

Purpose We aim to investigate the effects of FTY720 on suppression of circulating MDSC and EPC mobilizat ion during tumor recurrence after hepatectomy underwent hepatic ischemia/reperfusion injury. Key issues and problems Recurrence is the most frequent cause if treatment failure after curative resection of hepatocellular carcinoma (HCC). From our previous animal studies and clinical experiences, acute phase liver graft injury may important roles in late phase tumor recurrence/me tastasis in liver transplantation. Ischemia and reperfusion (I/R) injury develops when blood flow is interrupted for a long period of time and then restarted. The pathogenesis of IRI represents a complex interplay between biochemi cal, cellular, vascular endothelial and tissue specific factors, with inflammation being a common feature. Chronic inflammation promotes tumor progression was proposed for a long time. Inflammation promotes malignancy via proinflammatory cytokines, such as IL-1, which enhance immune suppression through the induction of myeloid-derived suppressor cells (MDSCs), thereby counteracti ng immune surveillance and allowing the outgrowth and proliferation of malignant cells. MDSC also contributes to tumor escape, immune tolerance, and suppression, respond to a variety of pro-inflammatory and anti-inflammatory stimuli, which driving their recruitment and activation. Understanding the underlying mechanism of the inflammatory milieu favours tumor escape through the accumulation of MDSCs could be very useful to improve the efficacy of cancer immunotherapy. Importantly, these cells have been shown to be able to promote angiogenesis by releasing soluble factor, such as vascular endothelial growth factor (VEGF). VEGF is a potent angiogenic factor that plays a critical role in mediating angiogenesis in HCC. The VEGF can function on various types of cells, such as endothelial cells, hepatic stellate cells, endothelial progenitor cells (EPC) to induce vascular changes in HCC. In response to cytokine, these cells released from damaged vessel wall and adhered platelets, circulating progenitor cells home in on the damaged areas. It was also reported that the adhered progenitor cells can engraft into endothelium and may different iate into mature endothelial cells. Mobilized EPCs participate in tumor vasculogenesis of HCC. Vasculogenesis and angiogenesis may constitute complementary mechanisms for tumor recurrence/metastasis. Taken together, the evidence presented here leads us to suppose that most immune cells in acute inflammation phase or microvasculatu re changes induce angiogenesis. Therefore, immunity should be a pharmaceutical target for overcome late phase tumor recurrence/metastasis Possible solution to the problems Our previous animal studies have demonstrated that ischemia-reperfusion of small liver remnant promot es liver tumor growth and metastases--activation of cell invasion and migration pathways. FTY720 can attenuate ischemia-reperfusion injury in both normal and cirrhotic livers and FTY720 is an effective anticancer agent for liver tumor in a rat model. FTY720 treatment pre and/or post hepatic ischemia/reperfusion injury and major hepatectomy might potentially attenuate small liver remnant injury and subsequently suppress tumor recurrence/metastasis. Possible outcome of the research project Hepatic ischemia/reperfusion injury during liver surgery may increase the possibility of intrahepatic recurrence after liver resection. Mobilized EPCs participate in tumor vasculogenesis of HCC. MDSC contributes to tumor escape, immune tolerance, and suppression, respond to a variety of inflammatory stimuli, which drive their recruitment and activation. MDSC and EPC play important roles in tumor recurrence/metastasis, especially after ischemia/reperfusion injury. FTY720 treatment may decrease the incidence of tumor recurrence and metastasis by (1) attenuating liver IRI and subsequently suppression of inflammation cytokines or chemokines, which was related to MDSC and EPC mobilization, and (2) directly suppression of circulating MDSCs and EPCs.

Project Title:	15th Annual International Congress of International Liver Transplantation Society THE DISTINCT REGENERATION PATTERN OF SMALL-FOR-SIZE FATTY LIVER GRAFT-THE SIGNIFICANCE OF ALDOSE REDUCTASE SIGNALING ON OVAL CELL ACTIVATION A NOVEL APPROACH TO PROTECT LIVER GRAFT AGAINST ISCHEMIA/REPERFUSION INJURY VIA A CELL PENETRATING HEME OXYGENASE PROTEIN
Investigator(s):	Liu Y
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	07/2009
Completion Date:	07/2009

Abstract:

N/A

List of Research Outputs

Cheng Q. , Ng T.P. , Fan S.T. , Lim Z.X.H. , Guo D. , Liu X. , Liu Y. , Poon R.T.P. , Lo C.M. and Man K. , Distinct mechanism of small-for-size fatty liver graft injury--Wnt4 signaling activates hepatic stellate cells, American Journal of Transplantation . 2010, 10(5): 1178-1188.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Abstract), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s72.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Rising Star Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Liu Y. , Man K. , Nashan B., Schlitt H.J. and Tsui T.Y., A novel approach to protect liver graft against ischemia/reperfusion injury via a cell penetrating heme oxygenase protein (Abstract), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): s117.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft - the significance of aldose reductase signaling on oval cell activation (Travel Award), The 15th Annual International Congress of the Inter national Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009 . 2009.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft – the significance of aldose reducatase signaling on oval cell activation (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York, U.S.A., 8-11 July 2009. Liver Transplantation . 2009, 15:S72: #O6.

Man K. , Cheng Q. , Liu Y. , Lam T.T. , Ng T.P. and Lo C.M. , Inflammatory microenvironment accelerates liver tumor growth and metastasis by mobilizing circulating endot helial progenitor cells and increasing cancer stem like cell populations (Abstract), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): S97.

Man K. , Shih K.C. , Ng T.P. , Xiao J. , Guo D. , Sun K.W. , Lim Z.X.H. , Cheng Q. , Liu Y. , Fan S.T. and Lo C.M. , Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts, Annals of Surgery . 2010, 251(6): 1154-1161.

Researcher : Lo BSH

List of Research Outputs

Ho K.L. , Tsu J.H.L. , Ng W.M. , Law W.L. , Tam P.C. and Lo B.S.H. , Rectourethral fistula after radical prostatecomy: transperineal repair in jack-knife position, Surgical Practice . Hong Kong, College of Surgeons of Hong Kong, 2010, 14: 102-104.

Researcher : Lo CM

Project Title:	Post-operative adjuvant therapy with recombinant interferon-[alpha] following curative resection of hepatocellular carcinoma: a randomised dose-response controlled trial
Investigator(s):	Lo CM, Fan ST
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	02/1999

Abstract:

To assess the efficacy and safety of interferon [alpha]-2b in reducing the incidence of recurrence after resection of hepatocellular carcinoma.

Project Title:	Development of anti-HBsAb in patients with chronic hepatitis B after liver transplantation using lamivudine prophylaxis: the possible role of adoptive immunity
Investigator(s):	Lo CM
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	01/2000

Abstract:

To investigate effects of donor immune status on the development of anti-HBsAb in patients with chronic hepatitis B after liver transplantation.

Project Title:	The impact of acute phase liver graft injury on tumor recurrence after liver transplantation in patients with hepatocellular carcinoma
Investigator(s):	Lo CM, Man K, Fan ST
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2007

Abstract:

To study the significance of early phase liver graft injury related to graft size on late phase tumor recurrence and metastasis after liver transplantation for hepatocellular carcinoma; to investigate the underlying molecular mechanisms.

Project Title:	Local and systemic liver cancer cell migration patterns during recurrence after liver resection
Investigator(s):	Lo CM, Man K
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	01/2008
Completion Date:	12/2009

Abstract:

We aim to investigate the local and systemic liver cancer cell migration patterns during recurrence after liver resection with or without hepatic ischemia/reper fusion injury. Key issues and problems Recurrence is the most frequent cause of treatment failure after curative resection of hepatocellular carcinoma (HCC). Liver transplantation is a salvage treatment to cure recurrent HCC and the underlying liver diseases. However, the high tumor recurrence rate after salvage transplantatio n remains the major concern. It has been reported that a proportion of the intrahepatic metastases may be resulted from systemic tumor cell dissemination after operation. From our previous animal studies and clinical experiences, acute phase liver graft injury may play important roles in late phase tumor recurrence/metastasis in liver transplantation. If the liver tumor recurrence is from systemic circulating cancer cells in the HCC patients after curative surgery, the patients may have a higher chance to develop recurrence after salvage transplantation because of the homing of the circulating tumor cells to the liver graft. On the other hand, if the tumor recurrence after surgical resection is from the intrahepatic migrating cancer cell through microcirculation within the liver, the salvage transplantatio n, especially living donor liver transplantation (LDLT), may allow an early operation to eradicate the source of tumor recurrence with good prognosis. Therefore, understanding the local and systemic liver tumor cell migration patterns during recurrence after curative liver surgery is pivotal to predict tumor recurrence after salvage transplantation. hepatic ischemia/reperfusion injury. Possible solution to the problems The investigation of sequential migration route and patterns of liver cancer cells locally and systemically during recurrence after curative surgery with or without hepatic ischemia/re perfusion injury using a novel real-time in vivo imaging system will provide direct evidence of the tumor cell migration patterns. It will be further confirmed by two orthotopic liver transplantation models: (1) to detect the tumo r recurrence after liver transplantation using the liver remnant after resection of the tumor-bearing lobe as the graft; and (2) to detect the tumor recurrence in the graft or distant metastasis using the rat-bearing liver tumor as the receipt. The liver tumor cell line will be stably labeled by luciferase gene. Any tiny early tumor recurrence/metastasis will be detected by its luciferase light signal under the Xenogen in vivo imaging system (IVIS 100). Possible outcome of the research project Hepatic ischemia/reperfusion injury during liver surgery may increase the possibili ty of intrahepatic recurrence after liver resection. The recurrent tumor in the rats that underwent ischemia/reperfusion injury may present more aggressive features linking to invasiveness. A proportion of the tumor recurrence might be from intrahepatic migration of the tumor cell rather than systemic migration. In the liver transplantation models, if we find any tumor recurrence in the liver graft from the liver remnant after resection of tumor-bearing lobe (model 1), it will be confirmed that the recurre nce is mainly from the intrahepatic migrating cancer cell through microcirculation. On the other hand, if we find any tumor developed in the lung or graft implanted in the recipient with liver tumor (model 2), the tumor recurrence will be confirmed to be from systemic circulating cancer cells.

Project Title:	Tumor recurrence after living donor liver transplantation – the significance of small-for -size graft injury on mobilization of circulating cancer stem like cells/endothelial progenitor cells
Investigator(s):	Lo CM, Man K, Liu Y
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	01/2009

Abstract:

Purpose To study the significance of acute phase small-for-size liver graft injury on mobilization of circulating cancer stem like/endothelial progenitor cells and subsequently promoting tumor recurrence and metastasis after living donor liver transplantation (LDLT) for the patients with hepatocellular carcinoma. Key issues and problems Liver transplantation is considered the ultimate curative treatment for HCC because it not only cures the liver tumor but also the underlying chronic liver disease. Although adult-to-adult LDLT has significantly relieved the crisis of donor organ shortage, and allowed early transplantation for HCC patients, a liver graft from a living donor is frequentl y small-for-size for the adult recipient. The acute phase shear stress in small-for-size liver grafts will not only trigger a series of inflammatory cascades, which subsequently activate cell signaling pathways leading to cell adhesion, migration and invasion, but it will also be the major cause of microvascular barrier dysfunctio n. Together with a higher potential ability of liver angiogenesis because of liver regeneration, the small liver graft may provide a favorable environment for liver tumor growth and metastasis. Our animal experiments demonstrated that hepatic ischemia/reperfusion injury of a small liver remnant after major hepatectomy promoted liver tumor growth and metastasis. Furthermore, our preliminary clinical data also suggested that HCC pa tients who received a graft  60% of the standard liver weight had a higher incidence of tumor recurrence and metastasis. Therefore, it will be worthwhile to investigate the mechanism of tumor recurrence and metastasis after LDLT.

Project Title:	Liver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury
Investigator(s):	Lo CM, Man K, Guan XY, Xu A
Department:	Surgery
Source(s) of Funding:	Collaborative Research Fund (CRF) - Group Research Project
Start Date:	06/2009

Abstract:

To elucidate the molecular changes induced by acute phase injury after transplantation using small-for-si ze liver graft in a series of animal experiments and to validate the mechanism in clinical studies; to characterize the cellular signaling pathways involved in fatty liver graft injury with liver regeneration impairment and late phase liver fibrosis in various animal models and clinical series; to investigate the impact of acute phase liver graft injury on late phase tumor recurre nce and metastasis in in vivo functional studies and to further validate it in prospective clinical study; to explore the biological implications of acute phase inflammatory response on the liver microenvironment and tumor behavior by investigating the mobilized endothelial progenitor cells/myeloid-derived suppressor cells/regulat ory T cells/cancer initiate cells in a series of in vivo and in vitro functional studies together with prospective clinical investigations; to define circulating markers associated with acute phase inflammatory injury and prediction of tumor recurrence and metastasis after liver transplantation; to explore potential therapeutic targets and develop novel strategies for the attenuat ion of acute phase small-for-size liver graft/fatty liver injury and prevention of late phase tumor recurrence

Project Title:	Angiopoietin-like protein 4 (ANGPLT4) as a novel therapy for liver cancer growth, metastasis and recurrence
Investigator(s):	Lo CM, Man K
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	01/2010

Abstract:

Objectives of the research proposal: Liver cancer is a common lethal malignancy. It is the fifth cancer killer worldwide and the second major cause of cancer death in Hong Kong. Although surgical resection is the first front treatment, tumor recurrence or metastasis remains the major problem, significantly affecting long-term disease-free survival. Recurrence and metastasis after curative liver surgery in HCC are common and associated with poor prognosis. The possible molecular mechanism of HCC recurrence/metastasis may be attribut ed to the activation of cell signaling related to invasion, migration and angiogenesis. The liver inflammatory injury under surgical stress such as ischemia/reperfusion or major hepatectomy may potentially provide a favorable microenvironment for tumor recurrence. Therefore, the development of novel adjuvant therapies targeting liver cancer growth and recurrence/metastasis together with underlying liver disease including inflammatory injury will be essential. Angiopoietin-like protein 4 (ANGPLT4), a secreted glycoprotein of the angiopoietin-like family, has been recently demonstrated to be able to inhibit tumor invasiveness by modification of cytoskel eton organization in addition to its role in regulating lipid metabolism and insulin sensitivity. More recently studies demonstrated that ANGPLT4 inhibited angiogenesis together with down-regulation of Raf/MEK/ERK signaling cascade, suggesting its potential as a novel therapy for liver tumor growth and recurrence/metastasis and underlying liver inflammatory injury. In the proposed project, we intend to investigate the correlation of tumor recurrence/metastasis with circulating ANGPLT4 levels and tumor tissue ANGPLT4 expression in patients with hepatocellular carcinoma. We will also explore the potential anti-cancer effect of ANGPLT4 in hepatocellular carcinoma through in vitro functional studies and novel orthotopic liver tumor animal models with different local and distant metastatic potentials. With the application of a novel in vivo animal imaging system, the tumor growth and metastasis will be accurately monitored /compared longitudinally in live animals with or without ANGPLT4 treatment. The underlying molecular mechanism s of ANGPLT4 for the suppression of liver cancer cell proliferation, invasion, migration and angiogenesis will also be investigated. The role of ANGPLT4 in suppression of liver cancer recurrence will be further investigated in a liver tumor mouse model with inflammatory injury. The significance of the outcomes of the proposed stud y will be in opening a new window to the development of a novel therapy targeting liver cancer growth and metastasis together with the underlying inflammatory stress. Aims of the proposed research work: To study the correlation between circulating ANGPLT4 level/tumor ANGPLT4 expression with tumor progression in patients with hepatocellular carcinoma. To investigate the potential anti-cancer effect of ANGPLT4 on human liver cancer cell lines with different metastatic potentials and endothelial cell lines by in vitro functional studies in relation with cell proliferation, invasion and migration, and angiogenesis signaling pathways. To explore the therapeutic potential of ANGPLT4 on tumor growth and metastasis in an orthotopic nude mice liver tumor model with different metastatic potentials by the comparison of orthotopic liver tumor growth, local and distant metastasis together with the fraction of circulating and tumor tissue cancer stem like cells/progenitor cells and cell signaling linking to tumor invasion and proliferation. To further confirm the role of ANGPLT4 in liver cancer recurrence/metastasis in a mouse liver tumor model with inflammatory stress and its inhibitory function for the mobilization of bone marrow endothelial progenitor cells/bone marrow derived suppressor cells. Key issues and problems Liver cancer is a common lethal malignancy. It is the fifth cancer killer worldwide and the second major cause of cancer death in Hong Kong. Although surgical resection is the first front treatment, tumor recurrence or metastasis remains the major problem, significantly affecting long-term disease-free survival. Therefore, development of novel adjuvant therapies targeting liver cancer growth and recurrence/metastasis without obvious toxicity to the liver itself will be essential.

List of Research Outputs

Chan A.C.Y. , Fan S.T. , Lo C.M. and Poon R.T.P. , Impact of antiviral therapy on the survival outcome of patients after major hepatectomy for hepatitis B-related hepatocellular carcinoma (Oral Presentation), The 9th World Congress of the International Hepato-Pan creato-Biliary Association, Buenos Aires, Argentina, 18 - 22 April 2010 .

Chan A.C.Y. , Fan S.T. , Lo C.M. , Liu C.L. , Chan S.C. , Ng K.K.C. , Yong B.H. , Chiu A. and Lam B.K.Y. , Liver transplantation for acute-on-chronic liver failure, Hepatology International . 2009, 3(4): 571-581.

Chan A.C.Y. , Fan S.T. and Lo C.M. , Prediction of hospital mortality after liver transplantation for acute liver failure, The 16th Annual International Congress of the Internation al Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 .

Chan A.C.Y. , Lo C.M. and Fan S.T. , Small-for-size syndrome in a small child, The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Chan K.L. , Fan S.T. , Lo C.M. , Wei W.I. , Ng W.M. , Chung H.Y., Ng K.K.C. , Chan S.C. , Chan K.W. , Tso W.K. , Tsoi N.S. and Tam P.K.H. , Pediatric liver transplantation in Hong Kong - a domain with scarce deceased donors, Journal of Pediatric Surgery . 2009, 44(12): 2316-2321.

Chan S.C. , Lo C.M. , Ng K.K.C. and Fan S.T. , Alleviating the burden of small-for-size graft in right liver living donor liver transplantation through accumulation of experience, American Journal of Transplantation . 2010, 10(4): 859-867.

Chan S.C. , Lo C.M. , Chik B.H.Y., Chow L.C. and Fan S.T. , Flowmetry-based portal inflow manipulation for a small-for-size liver graft in a recipient with spontaneous splenorenal shunt, Clinical Transplantation . 2010, 24(3): 410-414.

Chan S.C. , Lo C.M. , Yong B.H. , Tsui W.J.C., Ng K.K.C. and Fan S.T. , Paired donor interchange to avoid ABO-incompatible living donor liver transplantation, Liver Transplantation . 2010, 16(4): 478-481.

Chan S.C. , Lo C.M. , Ng K.K.C. , Chok K.S.H. , Yong B.H. and Fan S.T. , Portal inflow and pressure changes in right liver living donor liver transplantation including middle hepatic vein (Abstract), The 15th Annual International Congress of the Internation al Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S92.

Chan S.C. , Lo C.M. , Ng K.K.C. , Chok K.S.H. and Fan S.T. , Simplifying hepatic venous outflow reconstruction in sequential living donor liver transplantation, Liver Transplantation . 2009, 15(11): 1514-1518.

Chan S.C. , Lo C.M. and Fan S.T. , Simplifying living donor liver transplantation, Hepatobiliary and Pancreatic Diseases International . 2010, 9(1): 9-14.

Chan S.C. , Lo C.M. and Fan S.T. , Splanchnic hemodynamics in liver regeneration after right liver living donor liver transplantation (Letter to the Editor), Liver Transplantation . 2010, 16(3): 412.

Chan S.C. , Lo C.M. , Wong Y. , Ng K.K.C. , Chok K.S.H. and Fan S.T. , Validating graft and standard liver size predictions in right liver living donor liver transplantation (Abstrac t), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S247.

Cheng Q. , Ng T.P. , Fan S.T. , Lim Z.X.H. , Guo D. , Liu X. , Liu Y. , Poon R.T.P. , Lo C.M. and Man K. , Distinct mechanism of small-for-size fatty liver graft injury--Wnt4 signaling activates hepatic stellate cells, American Journal of Transplantation . 2010, 10(5): 1178-1188.

Cheung C.K.Y. , Lo C.M. , Chan S.C. and Fan S.T. , Long-term follow up of hepatitis B virus-specific immune response in liver transplant patient receiving third-generation hepatitis B vaccine (Abstract), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 16(Suppl 1): S242.

Cheung T.T. , Ng K.K.C. , Poon R.T.P. , Chan S.C. , Lo C.M. and Fan S.T. , A case of laparoscopic hepatectomy for recurrent hepatocellu lar carcinoma, World Journal of Gastroenterology . 2010, 16(4): 526-530.

Cheung T.T. , Ng K.K.C. , Chok K.S.H. , Chan S.C. , Poon R.T.P. , Lo C.M. and Fan S.T. , Combined resection and radiofrequency ablation for multifocal hepatocellular carcinoma: prognosis and outcomes, World Journal of Gastroenterology . 2010, 16(24): 3056-3062.

Chok K.S.H. , Ng K.K.C. , Cheung T.T. , Yuen W.K. , Poon R.T.P. , Lo C.M. and Fan S.T. , An update on long-term outcome of curative hepatic resection for hepatocholangiocarcinoma, World Journal of Surgery . 2009, 33(9): 1916-1921.

Chok K.S.H. , Lo C.M. , Ng K.K.C. and Chan S.C. , Patients with preoperative hepatorenal syndrome (HRS) have comparable long-term outcomes after live-donor liver transplantation (LDLT) (Abstract), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): S207.

Chok K.S.H. , Chu F.S.K. , Cheung T.T. , Lam V.W.T. , Yuen W.K. , Ng K.K.C. , Chan S.C. , Poon R.T.P. , Yeung C. , Lo C.M. and Fan S.T. , Results of percutaneous transhepatic cholecystostomy for high surgical risk patients with acute cholecystitis, ANZ Journal of Surgery . 2010, 80(4): 280-283.

Chung P.H.Y., Wong K.K.Y. , Tam P.K.H. , Chan K.L. , Ng K.K.C. , Chan S.C. , Hui T.W.C. , Yong B.H. , Fan S.T. and Lo C.M. , Split graft liver transplant for paediatric patients in Hong Kong, Hong Kong Journal of Paediatrics (New Series) . 2009, 14: 181-185.

Fung J.Y.Y. , Lai C.L. , Chan S.C. , But D., Seto W.K., Cheng C.T.K. , Wong D.K.H. , Lo C.M. , Fan S.T. and Yuen R.M.F. , Correlation of liver stiffness and histological features in healthy persons and in patients with occult hepatitis B, chronic active hepatitis B, or hepatitis B cirrhosis. , Am J Gastroenterol . 2009, 105(5): 1116-22.

Fung J.Y.Y. , Lai C.L. , Chan S.C. , But D., Seto W.K., Cheng C.T.K. , Wong D.K.H. , Lo C.M. , Fan S.T. and Yuen R.M.F. , Liver stiffness and histological features in healthy persons, and patients with occult hepatitis B, chronic active hepatitis B, and hepatitis B-related cirrhosis., Hepatology . 2009, 50(4) Suppl: 978A.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Abstract), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Hepp J. and Lo C.M. , Gallbladder Cancer, In: PA Clavien, S Breitenstein, J Belghiti, RS Chari, JM Llovet, CM Lo, MA Morse, T Takayama, JN Vauthey (eds), Malignant liver tumors: Current & Emerging Therapies (3rd Edition) . Switzerland, A Jihn Wiley & Sons, Lyd, Publication, 2009, 333-341.

Ji J., Shi J., Budhu A., Yu Z., Forgues M., Roessler S., Ambs S., Chen Y., Meltzer P.S., Croce C.M., Qin L.X., Man K. , Lo C.M. , Lee J., Ng I.O.L. , Fan J., Tang Z.Y., Sun H.C. and Wang X.W., MicroRNA expression, survival, and response to inter feron in liver cancer, New England Journal of Medicine . 2009, 361(15): 1437-1447.

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Li X.C., Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplanta tion . 2010, 16(6): s96.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the Internation al Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s72.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Rising Star Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft - the significance of aldose reductase signaling on oval cell activation (Travel Award), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009 . 2009.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft – the significance of aldose reducatase signaling on oval cell activation (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York, U.S.A., 8-11 July 2009. Liver Transplantation . 2009, 15:S72: #O6.

Lo C.M. , Addressing cultural barriers to transplantation, International Surgical Week 2009, Adelaide, Australia, 6-10 September 2009 . 2009.

Lo C.M. , Are we ready for minimally invasive living donor hepatectomy? No., The Art of Surgery & Medicine inLiver Transplantatio n: Today & Tomorrow. Satellite Symposium to the ILTS 16th Annual International Congress, Hong Kong, China, 16 June 2010 . 2010.

Lo C.M. , Associate Editor (2001 - present), Digestive Surgery . 2010.

Lo C.M. , Associate Editor (2006 - present), American Journal of Transplantation . 2010.

Lo C.M. , Associate Editor (2007 - present), Chinese Journal of Digestive Surgery . 中華消化外科雜誌, 2010.

Lo C.M. , Associate Editor (2007 - present), Liver Transplantation . 2010.

Lo C.M. , Chairman of Research Committee, The College of Surgeons of Hong Kong . 2010.

Lo C.M. , Chairman, Liver Donation Committee, The Hong Kong Liver Fou ndation . 2010.

Lo C.M. , Council Member (2005 - present), The College of Surgeons of Hong Kong . 2010.

Lo C.M. , Council Member (July 2005 - present), International Liver Transplantation Society . 2010.

Lo C.M. , Council Member, The Hong Kong Liver Foundation . 2010.

Lo C.M. , Deputy Editor (2008 - present), Liver Transplantation . 2010.

Lo C.M. , Examiner in Licentiate Examination, the Licentiate Committee (1995 - present), Medical Council of Hong Kong . 2010.

Lo C.M. , Examiner, MRCS Examination, The College of Surgeons of Hong Kong . 2010.

Lo C.M. , Executive Committee Member (1998 - present), International Society for Digestive Surgery . 2010.

Lo C.M. , Governor - Hong Kong Chapter (2009 - present), American College of Surgeons . 2009.

Lo C.M. , Guest Professor (2002 - present), The Peking University Health Science Centre, Peking University First Hospital, China . 2010.

Lo C.M. , Guest Professor (2004 - present), Army Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, China . 2010.

Lo C.M. , Honorary Consultant (2002 - present), King Faisal Hospital & Research Centre, Kingdom of Saudi Arabia . 2010.

Lo C.M. , Honorary Consultant (2005 - present), Hong Kong Sanatorium & Hospital . 2010.

Lo C.M. , Honorary Senior Consultant (2002 - present), Department of Surgery, Tung Wah Hospital, Hong Kong . 2010.

Lo C.M. , International Basic Science Mentor Travel Award (2010 ), XXIII International Congress of The Transplantation Society . 2010.

Lo C.M. , Introduction, In: PA Clavien, S Breitenstein, J Belghiti, RS Chari, JM Llovet, CM Lo, MA Morse, T Takayama, JN Vauthey (eds), Malignant liver tumors: Current & Emerging Therapies (3rd Edition) . Switzerland, A Jihn Wiley & Sons, Lyd, Publication, 2009, 29.

Lo C.M. , LT technical considerations and techniques (Invited Lecture), The 15th Annual International Congress of the Internati onal Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009 . 2009.

Lo C.M. , Liver transplantation - indications and treatment success (Invited Lecture), The Annual Scientific Meeting of the Malaysian Society of Gastroenterology and Hepatology, Langkawi, Malaysia, 14 - 16 August 2009 . 2009.

Lo C.M. , Living donor liver transplantation - Asian experience (Invited Lecture), The 6th Shanghai International Conference of Gastroenterology, Shanghai, China, 1 - 4 July 2009 . 2009.

Lo C.M. , Living liver donor with a vascular complication, American Transplant Congress 2010, San Diego, USA, 1-5 May 2010 . 2010.

Lo C.M. , Member of Editorial Board (2002 - present), Hepatobiliary & Pancreatic Diseases International . 2010.

Lo C.M. , Member of Editorial Board (2002 - present), Surgery . 2010.

Lo C.M. , Member of Editorial Board (2006 - present), Annals of Surgery . 2010.

Lo C.M. , Member of Editorial Board (2007 - present), Chinese Journal of Digestive Surgery . 中華普通外科雜誌, 2010.

Lo C.M. , Member of Editorial Board (2009 - present), World Journal of Surgery . 2010.

Lo C.M. , Member of Education Committee, International Liver Transplantation Society . 2010.

Lo C.M. , Member of Institutional Review Board (2003 - present), Hong Kong West Cluster, Hospital Authority . 2010.

Lo C.M. , Member of Scientific Committee (1998 - present), Cheng Si Yuan China-International Hepatitis Research Foundation . 2010.

Lo C.M. , Member of Steering Committee (2002 - present), Asian Pacific Digestive Week . 2010.

Lo C.M. , Member, Board of Examiners (2002 - present), The College of Surgeons of Hong Kong . 2010.

Lo C.M. , Member, Exemptions Sub-Committee, the Licentiate Com mittee (2003 - present), Medical Council of Hong Kong . 2010.

Lo C.M. , Member, Panel of Assessors (2004 - present), Medical Council of Hong Kong . 2010.

Lo C.M. , National Delegate (1998 - present), International Society for Digestive Surgery . 2010.

Lo C.M. , National Editor (2005 - present), Hepato-Gastroenterology . 2010.

Lo C.M. , Overview of MELD/PELD, The 20th Conference of the Asian Pacific Association for the Study of the Liver, Beijing, China, 25-28 March 2010 . 2010.

Lo C.M. , President (June 2010 - May 2011), International Liver Transplantation Society . 2010.

Lo C.M. , Program Chair, The 16th Annual Meeting of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Lo C.M. , Program Committee Member (1997 - present), International Society for Digestive Surgery . 2010.

Lo C.M. , Program Committee Member (2006 - present), International Liver Transplantation Society . 2009.

Lo C.M. , Pylorus-preserving pancreaticoduodenectomy (Video Presentation), International Surgical Week 2009, Adelaide, Australia, 6-10 September 2009 . 2009.

Lo C.M. , Reviewer, UICC Fellowship Selection Committee (1997 - present), Internaional Union Against Cancer . 2010.

Lo C.M. , Reviewer, American Journal of Transplantation . 2010.

Lo C.M. , Reviewer, Annals of Surgery . 2010.

Lo C.M. , Reviewer, Annals of the College of Surgeons of Hong Kong . 2010.

Lo C.M. , Reviewer, Asian Journal of Surgery . 2010.

Lo C.M. , Reviewer, British Journal of Surgery . 2010.

Lo C.M. , Reviewer, Endoscopy . 2010.

Lo C.M. , Reviewer, Hepatology . 2010.

Lo C.M. , Reviewer, Hong Kong Medical Journal . 2010.

Lo C.M. , Reviewer, Liver Transplantation . 2010.

Lo C.M. , Reviewer, Surgery . 2010.

Lo C.M. , Small for size LDLT, Innovations in Liver Transplantation 2009: An International Effort, Beijing, China, 12-13 September 2009 . 2009.

Lo C.M. , Small-for-size syndrome: diagnosis and management (Invited Lecture), Satellite Symposium to the 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 July 2009 . 2009.

Lo C.M. , Strategy to minimize biliary duct complication, The 5th International Conference: Living Donor Abdominal Organ Transplantation: State of the Art, Florence, Italy, 25-26 June 2010 . 2010.

Lo C.M. , Transplant or liver resection (Invited Lecture), The Annual Scientific Meeting of the Malaysian Society of Gastroenterology and Hepatology, Langkawi, Malaysia, 14 - 16 August 2009 . 2009.

Lo C.M. , Treasurer of Steering Committee (2008 - present), Asian Pacific Digestive Week . 2009.

Lo C.M. , Visiting Professor (March 2010 - February 2012), The First Affiliated Hospital, Sun Yat-sen University, China . 2010.

Lo C.M. , Why living donor liver transplantation works in Asia and not in the Western World? Is it only a matter of cultural differences?, The 5th International Conference: Living Donor Abdomin al Organ Transplantation: State of the Ar., Florence, Italy, 25-26 June 2010 . 2010.

Lo C.M. , 癌症是否不治之症？, 育醫造才：探索醫學世界, 香港, 香港大學李嘉誠醫學院, 2010, 54-56.

Man K. , Ng T.P. , Liu X. , Yeung W.H. , Lo C.M. and Fan S.T. , Inflammatory microenvironment accelerates liver tumor growth and metastasis by mobilizing circulating endothelia l progenitor cells and increasing cancer stem like cell populations (Abstract), The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Man K. , Cheng Q. , Liu Y. , Lam T.T. , Ng T.P. and Lo C.M. , Inflammatory microenvironment accelerates liver tumor growth and metastasis by mobilizing circulating endothelial progenitor cells and increasing cancer stem like cell populations (Abstract), The 15th Annual International Congress of the Inter national Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): S97.

Man K. , Shih K.C. , Ng T.P. , Xiao J. , Guo D. , Sun K.W. , Lim Z.X.H. , Cheng Q. , Liu Y. , Fan S.T. and Lo C.M. , Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts, Annals of Surgery . 2010, 251(6): 1154-1161.

Man K. , Ng T.P. , Xu A. , Cheng Q. , Lo C.M. , Xiao J. , Sun B. , Lim Z.X.H. , Cheung J.S., Wu E.X. , Sun K.W. , Poon R.T.P. and Fan S.T. , Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling, Clinical Cancer Research . 2010, 16(3): 967-977.

Man K. , Shao Y. , Ng T.P. , Li C. , Fan S.T. and Lo C.M. , The significance of acute-phase small-for-size liver graft injury in mobilization of circulating EPCS/MDSCS/T REGS after LDLT for HCC patients (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16 - 19 June 2010. Liver Transpl antation . 2010, 16(6): s191.

Ng K.K.C. , Lo C.M. , Chan S.C. and Fan S.T. , Living donor liver transplantation for hepatocellular carcinoma across Milan criteria (Oral Presentation), International Surgical Week 2009, Adelaide, Australia, 6 - 10 September 2009 .

Ng K.K.C. , Lo C.M. and Fan S.T. , Long-term survival analysis of living donor liver transplantation for hepatocellular carcinoma across Milan criteria (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S143.

Ng K.K.C. , Chan S.C. , Chok K.S.H. , Cheung T.T. , Chan A.C.Y. , Lo C.M. and Fan S.T. , Primary versus salvage liver transplantation for hepatoce llular carcinoma within Milan criteria - a single center experience (Abstract and Poster Presentation), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S254.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , Identification of circulating protein markers related to tumor recurrence after liver transplantation (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s207.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantatio n . 2010, 16(6): s77.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Young Investigator Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Sharr W.W. , Chok K.S.H. , Ng K.K.C. , Chan S.C. , Lo C.M. and Fan S.T. , Impact of donor age on right lobe living donor liver transplantation in a single centre (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S92.

Sharr W.W. , Lo C.M. and Fan S.T. , Recurrent hepatitis B infection after liver transplantation for hepatitis B related diseases: long term results of a single centre in Asia (Poster Presentation), The 16th Annual International Congress of the Internat ional Liver Transplantation Society, Hong Kong, June 2010 .

Wang X. , Cheung C.K.Y. , Ng M.W. and Lo C.M. , Hematopoietic chimerism and potential hematopoietic stem cells in liver transplantation (Abstract), The 8th International Society for Stem Cell Research Annual Meeting, San Francisco, U.S.A., June 2010 .

Wong H., Yau T.C.C. , Chan P., Ng I.O.L. , Chan G.S.W. , Hui P., Law W.L. , Lo C.M. , Hedley A.J. and Epstein R. , PPI-delayed diagnosis of gastrinoma: oncologic victim of pharmacologic success, Pathology and Oncology Research . 2010, 16(1): 87-91.

de Villa M.V.H., Concejero A., Gregorio G., Ong J., Labio E., Santos-Ocampo R., Chen C.C., Lo C.M. and Fan S.T. , Regional collaboration in liver transplantation for Filipinos (Abstract), The 15th Annual International Congress of the Intern ational Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S249.

Researcher : Lo CY

Project Title:	Establishment of a comprehensive service and registry for hereditary familial endocri nopathy syndromes in Hong Kong
Investigator(s):	Lo CY, Lam KSL
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	01/2005

Abstract:

To provide a comprehensive clinical, genetic and counseling services for the diagnosis, management, screening and education of familial endocrinopathy syndromes; to establish a registry on all index patients as well as their family members with familial endocrinopathy syndromes in Hong Kong with respect to detailed information including the type of endocrinopathy sydromes, familial pedigrees, patients' demographics, presentation, surgical treatment, pathology of tumours, genetic changes, outco me and follow-up; to improve the standard of care for patients with familial endocrinopathy syndromes through this program; to educate the public and the medical professions advance and the role of genetics in management of these hereditary conditions; to conduct on-going research on familial endocrine diseases by establishing a tissue and serum bank from patients and relatives with familial endocrinopathy sydromes.

List of Research Outputs

Hubbard J.G.H., Inabnet W.B. and Lo C.Y. , Endocrine Surgery. Principles and Practice . London, Springer-Verlag, 2009.

Lang B.H.H. and Lo C.Y. , Cancer: QTNM: a simplified TNM or just another staging system?, Nature Reviews. Endocrinology . 2009, 5(10): 531-532.

Lang B.H.H. and Lo C.Y. , Cushing's disease and syndrome, In: Hubbard J.G.H., Inabnet W. B. and Lo C.Y. (eds), Endocrine Surgery. Principles and Practice . London, Springer-Verlag, 2009, 379-390.

Lang B.H.H. and Lo C.Y. , Technological Innovations in Surgical Approach for Thyroid Cancer, Journal of Oncology . 2010, 2010: 6.

Lang B.H.H. and Lo C.Y. , Vitamin D(3) deficiency is associated with late-onset hypocalcemia after minimally invasive parathyroidectomy in a vitamin D borderline area, World Journal of Surgery . 2010, Epub ahead of print.

Lau G.S.K., Lang B.H.H. , Lo C.Y. , Tso A., Garcia-Barcelo M.M. , Tam P.K.H. and Lam K.S.L. , Prohylactic thyroidectomy in ethnic Chinese patients with multiple endocrine neoplasia type 2A syndrome after the introduction of genetic testing, Hong Kong Medical Journal . 2009, 15(5): 326-331.

Researcher : Lu P

List of Research Outputs

Wang X. , Ongkekp W.M., Chen L. , Yang Z. , Lu P. , Chan K.K. , Lopez J.P., Poon R.T.P. and Fan S.T. , Oct4 mediates chemotherapeutic drug resistance in liver cancer cells through potential Oct4-AKT-ABCG2 pathway , Hepatology . 2010, 52: 528-539.

Researcher : Lui ELH

List of Research Outputs

Liu Y., Wen X.M., Lui E.L.H. , Friedman S.L., Cui W., Ho N.P., Li L. , Ye T., Fan S.T. and Zhang H., Therapeutic targeting of the PDGF and TGF-beta-signa ling pathways in hepatic stellate cells by PTK787/ZK22258, Laboratory Investigation . 2009, 89(10): 1152-1160.

Researcher : Lui VCH

Project Title:	15th International Society of De velopment Biologists Congress (ISDB 2005) Perturbation of Hoxb5 Signalling in Vagal Neural Crest Cells Causes Defective Development of the Enteric Nervous System
Investigator(s):	Lui VCH
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	09/2005

Abstract:

N/A

Project Title:	Investigation of cell autonomous function of Hedgehog signaling on vagal neural crest cells by conditional knockout of Smoothened in mice
Investigator(s):	Lui VCH, Ngan ESW, Tam PKH, Sham MH
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2007
Completion Date:	12/2009

Abstract:

(1) Cross floxed Smo mice with a vagal NCC specific cre mouse strain (b3-IIIa-cre); (2) analyze the abnormal phenotypes in the developing ENs of the transgenic mutant mice; (3) analyze the effects of mesenchyme-deriv ed factors on NCCs of the transgenic mutant mice.

Project Title:	Evaluation of HOXB5 as a Hirschsprung’s disease locus
Investigator(s):	Lui VCH, Garcia-Barcelo MM, Tam PKH
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2008
Completion Date:	08/2009

Abstract:

Purposes: (1) To elucidate the mechanisms by which HOXB5 gene transcription is regulated (2) To evaluate HOXB5 as a novel Hirschsprung’s disease locus Key Issues: The enteric nervous system (ENS) comprises a network of neuronal ganglia and glia within the gut wall, which controls intestinal peristalsis. In mammals, vagal neural crest cells (NCC) migrate from the neural tube, enter the foregut and colonize the intestine, where they differentiate into neurons and glia (1). Defective ENS development results in fewer ganglia (hypoganglionosis), and/or absence of ganglia (agangli onosis) at the caudal-most gut in newborns with Hirschsprung’s disease (HSCR). Affected neonates develop a life-threatening condition of intestinal obstruction due to defective peristalsis and require surgery. HSCR causes consider able mortality and morbidity. There is a significant variation in the disease incidence among races with the highest incidence in Asians (2.8 per 10,000 life births). HSCR has a complex pattern of inheritance and manifests with incomplete penetrance and variable length of the aganglionic segment (2), indicating that HSCR results from the interaction of several genes. ENS development is regulated by molecular signals from within the NCC and the intestinal environment. The receptor tyrosine kinase gene RET encodes a receptor for glial cell-line derived neurotrophic factor (GDNF) on NCC and is crucial for ENS development (3-6). Loss-of-function mutations in RET account for up to 50% of familial cases and between 7-35% of sporadic cases of HSCR indicating that RET is the major HSCR gene (7-9). Other genes implicated in this disease that account for 7% of HSCR cases encode proteins involved in signaling pathways such as the endothelin 3/endothelin receptor B, and transcription factors SOX10, PHOX2B, TITF-1 which govern ENS development (1,10,11). SOX10 and TITF-1 bind to the RET promoters and induce the transcription from the RET promoter (10,12). Among the molecular regulators of gut development are the homeobox (HOX) genes, whi ch consist of four gene clusters (A, B, C, D) encoding a family of transcription factors (13). In mammals, a total of 39 Hox genes located in 4 chromosomal clusters are organized in 13 paralogous groups. Some of the Hox genes of paralogous groups 4 and 5 are expressed in embryonic gut suggesting that these genes might form the Hox code for enteric development (14,15). In particular, Hoxb5 displays a distinct pattern of expression in mouse and human embryonic gut, suggesting a unique role of Hoxb5 in ENS and gut musculature develop ment (14-17). Homozygous Hoxb5 knockout mice showed homeotic transformation of the skeleton but no abnormality of the ENS was reported (18). The lack of an ENS defect could be due to functional redundancy among Hox proteins. To investigate Hoxb5 function in ENS development and to circumvent the problem of functional redundancy, we generated transgenic mice that can be induced to express a chimaeric protein (enb5) in the NCC in mice by Cre/loxP. In this, the C-terminal DNA-binding homeodomain of Hoxb5 is linked to the N-terminal repressor domain of the Drosophila engrailed protein which has been shown to confer repressor activity when linked with heterologous DNA-binding domains. This chimeric enb5 repressor competes with wild-type Hoxb5 for binding to target genes and inhibits transcription, thereby blocking the developmental pathways that normally requ ire Hoxb5. Our findings showed that NCC expressing enb5 failed to migrate to the distal intestine. We observed hypoganglionosis and slow peristalsis, and occasionally aganglionosis and intestinal obstruction in enb5-expressing mice (enb5/Cre). Ret expression was markedly reduced or absent in NCC and ganglia. More importantly, we demonstrated Hoxb5 trans-activated RET expression, which was abolished by enb5 (19) (Figures of the ENS phenotypes of enb5-expressing mice (enb5/Cre) and Hoxb5 transactivation of Ret are shown as Fig. 1 & 2 as attachment 1). Our data indicate Ret is a downstream target of Hoxb5 whose perturbation causes Ret haploinsufficiency, impairs NCC migration and leads to ENS phenotypes. The ENS defects in enb5-expressing mice resemble those in HSCR, suggesting the human HOXB5 gene may be mutated in this disease and/or defects in the acti vation of RET by HOXB5 could lead to RET haploinsufficiency and HSCR. We screened HOXB5 exons and those conserved non-coding sequences (CNS) flanking HOXB5 with significant homology between human and mouse for mutations or variati ons. In total, 188 HSCR patients and 189 healthy individuals of Chinese origin were screened, and three SNPs in the 3’ untranslated (UTR) region of the HOXB5 gene were found to be differentially represented (19). It is not know if these SNPs are functional or are markers in linkage disequilibrium with SNPs at the regulatory region implicated in HOXB5 expression. Regulatory element s for Hoxb5 expression in developing mouse have been identified at the 3’ end of HOXB5 (20). From the enb5 mouse data, it is tempting to speculate that a reduced amount of HOXB5 due to DNA variations in control regions could modulate RET expression and consequently the HSCR phenotype. By applying the HapMap data on Chinese Han from Beijing (CHB) and Sequenom technology for tag-SNPs distributed along the HOX clusters, genetic interactions were found among HOXA and HOXB loci and the RET loci tested, suggesting the interacting HOX loci may affect the penetrance of the RET-risk allele (21,22). Taken together all the data from us and others suggest that genes implicated in the signaling pathways governing ENS development may ultimately alter RET expression leading to HSCR. The penetrance of HSCR could be affected by combinations of mutations and/or DNA alterations (SNPs) in RET and in other HSCR genes (23,24) or other yet unidentified modifier loci (25,26). HSCR-associated SNPs in RET regulatory regions have been shown to decrease RET expression (10,21,27,28). Therefore, cis- and/or trans-regulatory defects in the activation of RET gene by transcription factors could lead to RET haploinsufficiency and HSCR disease. Our findings in mouse indicated that HOXB5 may represent a novel HSCR gene. Problems being addressed: (1) What are the roles of SNPs in the control regions implicated in the expression of HOXB5 gene (2) What are the roles of SNPs in the control regions of HOXB5 gene in the etiology of HSCR?

Project Title:	HOXB5 and RET promoter: regulation of RET transcription in Hirschsprungs disease
Investigator(s):	Lui VCH, Garcia-Barcelo MM, Tam PKH
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2008

Abstract:

(1) To elucidate the mechanisms by which HOXB5 trans-activate RET; (2) To evaluate HOXB5 as a novel Hirschsprung’s disease locus.

Project Title:	Investigation of role of Hoxb5 in neural crest cell induction and maintenance in mous e embryos
Investigator(s):	Lui VCH, Cheung MCH
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	04/2009

Abstract:

Key Issues Neural crest cells (NCCs) are multipotent stem cells generated in the dorsal neural tube along the entire anterior posterior (A-P) axis of the neural tube. NCC progenitors initiate a distinct program of gene expression, undergo an epithelium to mesenchyme transition that will confer them ability to migrate. NCCs migrate throughout the body, where they differentiate into many different cell types including neurons and glia, cartilage, and melanoblasts (pigment cells). The generation of NCC progenitors and their lineage determinations are complex multistep process involving many genes. Abnormal NCC development give rises to a number of malformations collectively known as neur ocristopathies, that affects many tissues including the nervous systems, skin pigmentation, skeletal structures, heart, dentures , and endocrine organs. Homeobox (Hox) genes, a group of highly conserved developmental control genes, are crucial in embryo patterning. In mammals, a total of 39 Hox genes located in 4 chromosomal clusters (Hoxa, Hoxb, Hoxc and Hoxd) are organized in 13 paralogous groups based on the structural and sequence homology. The dynamic expression patterns of Hox genes along the A-P axis of the neural tube are crucial in patterning the body axis and neuronal differentiation in the hindbrain. Hox genes also display dynamic patterns of expression along the dorsal-ventral (D-V) axis of the neural tube that correlate with the formation of different types of neurons. Abnormal D-V patterning of the neural tube may not only affect the formation of neurons, but could also influence the formation of NCC at the dorsal neural tube. Very little is known about the functions of Hox genes in the D-V patterning of the neural tube. Hoxb5 is expressed at low level at E8.5 in the presumptive hindbrain. At E12.5, Hoxb5 expression extends from the hindbrain throughout the entire neural tube with dorsally-restricted expression (1-3). The vagal NCCs that emigrate from the neural tube at the level of somite 1-7 also express Hoxb5 migrate to the developing gut and form the enteric nervous system (ENS). To investigate Hoxb5 function in vagal NCCs and to circumvent the problem of functional redundancy, we generated transgenic mice that can be induced by Cre recombinase to express a dominant negative chimaeric protein (enb5) containing the mouse Hoxb5 homeodomain fused to the transcription repressor of Drosophila engrailed repressor. Enb5 is expected to function as a dominant transcriptional repressor to compete with the endogenous Hoxb5 for binding to the regulatory elements of its downstream target genes and repress their transcription thereby inactivating Hoxb5 functions. By crossing with transgenic mice that express Cre recombinase specifically in vagal NCCs, we previously showed that perturbation of Hoxb5 function caused defective vagal NCC migration in the developing intestine (4). To investigate the functions of Hoxb5 in ner vous system development, we crossed our enb5 transgenic mice to Wnt1Cre mice. Wnt1 regulatory elements direct the expression of Cre to the dorsal neural tube, NCC progenitors, the midbrain and the cerebellum in Wnt1Cre mice (5,6). Wnt1Cre/enb5 double transgenic mice display hydrocephalus, enlarged and domed craniae, abnormal skin pigmentation, and ENS defects. In this proposal, we shall investigate the molecular mechanisms by whic h skin pigmentation is disrupted in Wnt1Cre/enb5 mice. Melanoblasts differentiate from the NCC and migrate along the dorsolateral pathway between the dermatome and the epidermis giving rises to all the pigment cells of the skin. The skin pigmentation defects were first noticeable in Wnt1Cre/enb5 mice at postnatal day 3 (Fig.1A), and white hair was clearly seen at the time of weaning at the trunk (Fig. 1B). To monitor the localization of Wnt1Cre expressing cells, Wnt1Cre mice were crossed with Cre reporter mouse strain Rosa26-Cre reporter mouse (R26R) (7) to generate Wnt1Cre/R26R mice, which were then crossed with enb5 mice to obtain Wnt1Cre/enb5/R26R mutant and Wnt1Cre/R26R control mice. X-gal staining and sectioning of adult skin revealed no melanocytes at the unpigmented skin of Wnt1Cre/enb5/R 26R mouse (Fig. 1C). Melanoblasts were found residing in the dermis and also penetrating into the epidermis of Wnt1Cre/R26R E12.5 embryos. In contrast, melanoblasts were undetectable in Wnt1Cre/enb5/R26R embryos (Fig. 2). The number of NCC progenitors was drastically reduced at the dorsal neural tube of Wnt1Cre/enb5/R26R embryos as compared to that of Wnt1Cre/R26R mice. Our data suggested that early induction and/or maintenance of NCC progenitors may be impaired leading to a reduction of melanoblasts, and hypopigmentation in Wnt1Cre/enb5 mice. Problems being addressed We shall determine the molecular mechanisms by which (i) perturbation of Hoxb5 functions in the neural tube causes the reduction of NCC in Wnt1Cre/enb5 embryos, and (ii) Hoxb5 induces and/or maintains the NCC progenitors pool in early embryos. References :(PI is highlighted with *): 1. Holland, P. W., and Hogan, B. L. (1988) Spatially restricted patterns of expression of the homeobox-containing gene Hox 2.1. during mouse embryogenesis. Development 102, 159-174 2. Krumlauf, R., Holland, P. W., McVey, J. H., and Hogan, B. L. (1987) Developmental and spatial patterns of expression of the mouse homeobox gene, Hox 2.1. Development 99, 603-617 3. Kuratani, S. C., and Wall, N. A. (1992) Expression of Hox 2.1 protein in restricted populations of neural crest cells and pharyngeal ectoderm. Dev Dyn 195, 15-28 4. Lui, V. C*., Cheng, W. W., Leon, T. Y., Lau, D. K., Garcia-Barcelo, M. M., Miao, X. P., Kam, M. K., So, M. T., Chen, Y., Wall, N. A., Sham, M. H., and Tam, P. K. (2008) Perturbation of hoxb5 signaling in vagal neural crests down-regulates ret leading to intestinal hypoganglionosis in mice. Gastroenterology 134, 1104-1115 5. Chai, Y., Jiang, X., Ito, Y., Bringas, P., Jr., Han, J., Rowitch, D. H., Soriano, P., McMahon, A. P., and Sucov, H. M. (2000) Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127, 1671-167 9 6. Danielian, P. S., Muccino, D., Rowitch, D. H., Michael, S. K., and McMahon, A. P. (1998) Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase. Curr Biol 8, 1323-1326 7. Soriano, P. (1999) Generalized lacZ expression with the ROSA26 Cre reporter strain. Nature genetics 21, 70-71

Project Title:	Wif-1 regulates cloaca septation via Wnt signaling in urorectal development
Investigator(s):	Lui VCH
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2010

Abstract:

Objectives of the research proposal Key Issues Urorectal development includes 3 distinct processes: outgrowth of the genital tubercle (GT), cloaca septation and urethra tubularization (sex differentiation). Cloaca is the primitive outlet of the urinary and intestinal stream, locating at the caudal extreme end of the embryo. It is an endoderm-lined hollow region covered by a two to three-cell-thick membrane, known as cloaca me mbrane. A sheet of mesenchyme called urorectal septum (urs) originated from the cranial cloaca grows and descends to separate the hindgut (intestinal stream) from the urethra (urinary stream), and eventually reaches the cloaca membrane. This process is termed as cloaca septation. Cloaca septation is a complex multistep process requiring lateral-to-medial and cranial-to-caudal growth of endodermally lined mesenchyme that involves many genes (Dravis, Yokoyama et al. 2004). Failure of cloaca septation leads to anorectal malformations (ARMs) or hypospadias. The urs descent and cloaca septation initiate and complete between E12.5 and E13.5 in mice, and between E14.5 and E15.5 in rats. Wnt signaling pathway controls diverse developmental processes including palate, limbs, kidneys and CNS. There are 19 Wnt ligands and several signaling pathway inhibitors such as Dickkop f, Wnt inhibitory factor-1 (Wif-1), sFRP and cerberus. Wnt signaling polymerase chain reaction array analysis and immunohistochemistry indicate that Wnt ligands and Wif-1 are expressed in the developing mouse and rat urorectal region (Fig. 1, 2 and data not shown. See Attachment). Wnt5a is expressed at the developing GT mesenchyme, and it modulates the outgrowth of GT. The interaction between Wnt and Sonic Hedgehog (Shh) signaling is indispensable in the development of many tissues including papilla, neural tube, and midbrain floor plate. Wnt and Shh have also been implicated in urorectal development at the initial GT outgrowth and the late androgen-dependent tubularization. Sonic Hedgehog (Shh), Wnt5a and Tcf1/Tcf4 (target gene of Wnt canonical signaling) homozygous knockout embryos displayed complete agenesis of the GT (Yamaguchi, Bradley et al. 1999; Haraguchi, Mo et al. 2001). Knocking out Hoxa13, a downstream target of Shh, reduced androgen signal and disturbed the closure of urethral groove in the ventral proximal GT leading to hypospadias (Morga n, Nguyen et al. 2003). Gli2 and Gli3 are the downstream mediators of Sonic Hedgehog (Shh) signaling. Gli2 and Gli3 mutant mice demonstrated different forms of ARMs (Kimmel, Mo et al. 2000; Mo, Kim et al. 2001). However, there is lack of knowledge about genetic programs governing cloaca septation, the descent of urs separating urogenital sinus and rectum. To investigate the molecular changes associated with cloaca septation and the possibilities of the associations between the urs descent and hypospadias as well as ARMs, Affymetrix GeneChip analysis was perfo rmed to identify differentially expressed genes between ETU-treated and normal rat embryos at E14.5. ETU is a well-established drug to induce ARMs in rat fetuses by intragastric administration to pregnant rats. Array analysis and subsequent confirmation by real-time RT-PCR in biological replicates revealed up-regulation of Wnt inhibitory factor-1 (Wif-1) in ETU-treated embryos (Fig. 2 and data not shown. See Attachment). ETU-tre ated embryos displayed urorectal developmental defects typified in human hypospadisis and ARMs including delayed genital development, untubularized penile urethra, and the presence of internal fistula of vagina to rectum and urethra. Immuno-histochemical analysis on E14.5 to E16.5 rat embryos revealed that Wif-1 was highly expres sed at the ventral cloaca canal, ventral urethral endoderm and anal opening. The spatiotemporal distribution of Wif-1 protein at the cloaca epithelium was disrupted in ETU-treated rats (Fig.2). Taken together all these data suggest that Wif1 is spatiotemporally expressed around the cloaca epithelium revealing a presumable involvement in the descent of urs. We hypothesize that disturbance of Wif1 expression in the urorectal septum could result in defective urorectal development. In this proposal, we aim to investigate the functional roles of Wif-1, Wnt and Shh signaling pathways in cloaca septation, in particular, the descent of urs separating urogenital sinus and hindgut using in vitro organotypic culture and mutant mice. Problems being addressed We shall investigate the molecular mechanisms of urorectal development in which (i) Dorsal-ventral differential expression of Wif-1 governs the process of cloaca septation, (ii) Wnt and Shh signaling pathways coordinately regulate urorectal development. References: Dravis, C., N. Yokoyama, et al. (2004). "Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development." Dev Biol 271(2): 272-90. Haraguchi, R., R. Mo, et al. (2001). "Unique functions of Sonic hedgehog signaling during external genitalia development." Development 128(21): 4241-50. Kimmel, S. G., R. Mo, et al. (2000). "New mouse models of congenital anorectal malformations." J Pediatr Surg 35(2): 227-30; discussion 230-1. Mo, R., J. H. Kim, et al. (2001). "Anorectal malformations caused by defects in sonic hedgehog signaling." Am J Pathol 159(2): 765-74. Morgan, E. A., S. B. Nguyen, et al. (2003). "Loss of Bmp7 and Fgf8 signaling in Hoxa13-mutant mice causes hypospadia." Development 130(14): 3095-109. Yamaguchi, T. P., A. Bradley, et al. (1999). "A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo." Development 126(6): 1211-23.

List of Research Outputs

Garcia-Barcelo M.M. , Yeung M.Y. , Miao X.P., Tang S.M. , Chen G., So M.T. , Ngan E.S.W. , Lui V.C.H. , Chen Y. , Liu X. , Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y. , Chan D. , Cheung K.M.C. , Chung P.H.Y., Wong K.K.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Genome-wide association study identifies a susceptibilit y locus for biliary atresia on 10q24.2, Human Molecular Genetics . 2010, 19 (14): 2917-2925.

Garcia-Barcelo M.M. , Lui V.C.H. , So M.T. , Miao X. , Leon Y.Y. , Yuan Z.W., Ngan E.S.W. , Ehsan T., Chung P.H.Y., Khong P.L. , Wong K.K.Y. and Tam P.K.H. , MNX1 (HLXB9) mutations in Currarino patients, Journal of Pediatric Surgery . 2009, 44(10): 1892-1898.

Kam K.M. , Lui V.C.H. , Cheung M.C.H. and Tam P.K.H. , Expression of engrailed-Hoxb5 transcriptional repressor by Wnt1-Cre produces neurocristopathies of pigmentation and enteric nervous system defects in mice., 43rd Annual Meeting for the Japanese Society of Developmental Biologists Kyoto, Japan, 20 June 2010 . 2010.

Kam K.M. , Lui V.C.H. , Cheung M.C.H. and Tam P.K.H. , Expression of engrailed-Hoxb5 transcriptional repressor by Wnt1-Cre produces neurocristopathies of pigmentation and enteric nervous system defects in mice, 43rd Annual Meeting for the Japanese Society of Developmental Biologists, Jointly Sponsored by the Asia-Pacific Developmental Biology Network, Kyoto, Japan, 20-23 June . 2010.

Leon Y.Y. , Ngan E.S.W. , Poon H.C. , So M.T. , Lui V.C.H. , Tam P.K.H. and Garcia-Barcelo M.M. , Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3, Journal of Pediatric Surgery . 2009, 44(10): 1904-1912.

Liu X. , Lee P.Y. , Ho C.M. , Lui V.C.H. , Chen Y. , Che C.M. , Tam P.K.H. and Wong K.K.Y. , Silver nanoparticles mediate differential responses in keratinocytes and fibroblasts during skin wound healing, ChemMedChem . 2010, 5(3): 468-475.

Lui V.C.H. , HOXB5 and Hirschsprung’s Disease, Symposium of Pediatric Experimental Surgery and Perinatology in Sheng Jing Hospital of China Medical University, Shenyang. 6-9 May 2010 . 2010.

Lui V.C.H. , Reviewer, Development . 2009.

Lui V.C.H. , Reviewer, Developmental Dynamics . 2009.

Lui V.C.H. , Reviewer, Genesis . 2009.

Lui V.C.H. , Reviewer, Journal of Pediatric Surgery . 2009.

Lui V.C.H. , Reviewer, Mechanisms of Development . 2009.

Lui V.C.H. , Reviewer, PLoS One . 2009.

Miao X. , Garcia-Barcelo M.M. , So M.T. , Tang W.K. , Xiao D. , Wang B. , Mao J.X., Ngan E.S.W. , Chen Y. , Lui V.C.H. , Wong K.K.Y. , Liu L. and Tam P.K.H. , Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population, Journal of Pediatric Surgery . 2010, 45: 709-713.

Miao X. , Leon Y.Y. , Ngan E.S.W. , So M.T. , Yuan Z.W., Lui V.C.H. , Chen Y. , Wong K.K.Y. , Tam P.K.H. and Garcia-Barcelo M.M. , Reduced RET expression in gut tissue on individuals carrying risk alleles of Hirschsprung's disease, Human Molecular Genetics . 2010, 19(8): 1461-1467.

Ngan E.S.W. , Garcia-Barcelo M.M. , Yip B.H.K. , Sham P.C. , Lui V.C.H. and Tam P.K.H. , Hedgehog-notch induced premature gliogenesis of neural crest: a cause of Hirschsprung disease, International Society for Stem Cell Research, the 8th Annual Meeting, Moscone West, San Francisco, U.S.A. 16-19 June 2010 .

Zhang M. , Leung C. , Lui V.C.H. , Tam P.K.H. and Sham M.H. , Sox10 affects enteric neural crest cells migration in a Sox10NGFP/+ mutant , 2010 Hong Kong Inter-University Biochemistry Postgrad uate Symposium, CUHK, Hong Kong, 15 May, . 2010.

Zhang M. , Leung C. , Lui V.C.H. , Tam P.K.H. and Sham M.H. , Sox10 is required for proliferation and migration of enteric neural crest stem cells, International Society for Stem Cell Research, 8th Annual Meeting, Moscone West, San Francisco, CA, USA, June 16-19, 2010 .

Zhang M. , Leung C. , Lui V.C.H. , Tam P.K.H. and Sham M.H. , Sox10 mediates proliferation and migration behavior of enteric neural crest cells, 43rd Annual Meeting for the Japanese Society of Developmental Biologists, Jointly Sponsored by the Asia-Pacific Developmental Biology Network, Kyoto, Japan, 20-23 June . 2010.

Researcher : Lui WM

List of Research Outputs

Leung G.K.K. , Hung K.N. , Lui W.M. and Fan Y.W. , Combined transcranial and transsphenoidal resection of huge pituitary adenoma, The 7th Meeting of the Asian Society for Neuro-onc ology, Seoul, Korea, 10 - 12 June 2010 .

Researcher : Luk JMC

Project Title:	Investigating Liver Intestine-Cadherin Function In Hepatocellular Carcinoma
Investigator(s):	Luk JMC, Lee NPY, Ng IOL, Fan ST
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	12/2005

Abstract:

Purpose: - The purpose of this study is to investigate the functions and pathogenic roles of a novel cadher in, CDH17, recently identified in HCC, which is found to be a potential disease marker and correlated with poor prognosis. Key issues: - Cadherins are a superfamily of Ca2+-dependent cell adhesion molecules, which are important in mediating adherent junction formation and maintaining tissue integrity. LI-cadherin (CDH17) is involved in the embryonic development of liver and gastrointestinal tract, and functions as an intestinal peptide transporter. However, CDH17 is not detectable in normal adult liver. Our earlier observations, however, have shown that over-expression of LI-cadherin is found in over 80% of HCC, but not in non-cancerous tissues or normal liver tissues from these patients. Moreover, our group has identified an alternative splicing form with exon 7 skipped in the LI-cadherin gene among 50 % of the HCC tumors. Expression of the LI-cadherin splice variant in HCC is significantly associated with venous infiltration and early intra-hepatic recurrence of tumor as well as shorter overall survival of HCC patients. Because of its high prevalence and association with poor clinical outcomes, LI-cadherin is suggested to be a potential disease marker for HCC. More interestingl y, we did not observe the splice variant in over 100 gastric adenocarcinoma specimens that were tested, indicating that the splice variant is HCC specific. Problems to be addressed: - The functions of the LI-cadherin wild-type form or exon 7-skipped splice variant in HCC remain unknown. Will over-expression of LI-cadherin affect classical E-cadherin expression and function? Does the splice variant have a dominant-negative functio n to cause cell-cell disintegration, thereby promoting tumorigenesis and cancer metastasis? Our future goal is to establish a mouse model to determine what will happen if CDH17 is forcibly expressed in postnatal and adult liver, when transcription of the gene is normally repressed or silenced in these stages? To address these issues, there is a need to obtain specific antibodies that could differentiate the wild type and splicing forms of LI-cadherin, since the current commercial antibodies failed to detect the exon 7-spliced variant in HCC. The proposed study will also investigate the expression pattern and biological functions of LI-cadherin molecule in HCC using both in vitro culture and xenograft mouse models, to confirm our hypothesis of its pathogeni c roles in mediating tumor invasiveness and enhancing the metastatic potentials. Specific Aims: 1. To generate and characterize monoclonal antibodies that could differentiate wild-type and exon 7-spliced form of LI-cadherin mole cules; 2. To study and correlate the expression patterns of LI-cadherin and E-cadherin/catenin complexes in HCC specimens of different clinical stages and features; 3. To establish stable transfectants expressing wild-type and splice variants of LI-cadherin, and examine the tumorigenic properties in experimental invasion and intra-hepatic metastasis animal models; 4. To design and characterize anti-sense oligonucleotides to block LI-cadherin function in high metastatic HCC cell lines.

Project Title:	The therapeutic effects of GC7, a specific inhibitor of deoxyhypusine synthase, and its molecular mechanisms in reversing the development of hepatocellular carcinoma
Investigator(s):	Luk JMC, Lee NPY, Poon RTP
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	09/2007
Completion Date:	08/2009

Abstract:

Hepatocellular carcinoma (HCC) ranks sixth as the most prevalent global malignancy, accounting for ~598 000 deaths annually. The prognosis of HCC is poor, with an overall 5-year survival rate of ~ 5% (Parkin et al., 2005). The high mortality rate is mainly attrib uted to the late presentation of the symptoms, when patients were first diagnosed at advanced tumor stages. Available options for treatments are limited and ineffective, and very often, patients suffer from early tumor recurrence and shorter overall survival. As such, early detection of HCC in the high-risk populations (hepatitis carriers and cirrhosis) is a prime goal for the clinical management of patients (Gish, 2006). To tackle such dismal situation, it is our continuous endeavor to identify diagnostic marker(s) and therapeutic target(s) for this aggressive neoplasm. Previous findings from our laboratory and other contemporary studies have proven the usefulness of heat shock proteins in differentiating tumor from non-tumor liver tissues (Chuma et al., 2003; Luk et al., 2006). In addition, LI-cadherin, belonging to 7D-cadherin superfamily, demonstrates clinical relevance in hepatic oncogenesis due to its elevated expression in cancerous liver specimens (Wong et al., 2003). However, the research on innovating therapeutic targets in curing HCC is rather rare and leaps behind. Recently, we employed comparative proteomic approach and successfully segregated onco-proteins from the pool of "healthy " liver proteins (Lee et al., 2007). This approach allows us to identify candidate oncofetal proteins in a high throughput manner. Amongst the proteins, eukaryotic translation initiation factor 5A (eIF5A) gains particular attention due to its induced expression in a panel of HCC cell lines, as compared to the non-tumorigenic liver cell lines, implicating its potential roles in carcinogenesis (Lee et al., 2007). eIF5A, highly co nserved among eukaryotes, is a small protein of ~18 kDa. It is the sole protein carrying a unique polyamine-derived amino acid, hypusine, which is formed in mature eIF5A after post-translational modification of its precursor; and these steps involve two enzymes, namely deoxyhypus ine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) (Park, 2006; Wolff et al., 2007). Hypusine is shown to be related to cell proliferation (Park et al., 1997); recently, a study also illuminated a preferential expression of eIF5A isoforms (eIF5A-1 and eIF5A-2) in a wide vari ety of human cancer cell lines (Clement et al., 2006), further strengthening the supportive roles of eIF5A in tumorigenesis. However, understanding of this molecule in HCC pathogenesis is very limited and no detailed analysis has yet to be performed with regard to the function(s) of eIF5A in HCC. Herein, we will address this notion with the application of GC7 (N1-guanyl-1,7-diam inoheptane), a specific DHS inhibitor, in HCC cell line, aiming to reveal the potential therapeutic effects of this inhibitor on malignant growth via blocking the physiological effects of eIF5A. In addition, the molecular mechani sm underlying this inhibition will also be examined. Specific objectives: 1. The cancerous phenotypes, such as cell growth, proliferation, and apoptosis, will be examined in HCC cell lines, Hep3B, after treatment with GC7, with an aim to delineate the effects of GC7 on tumor progression. 2. Cell junction proteins and its associated signaling pathway are usually altered during tumor formation; so, the expression of cell junction proteins and their associated signaling proteins, such as E-cadherin, occludin, connexin-34, and p38 mitogen-activated protei n kinase (MAPK) will be studied in order to see whether they are the prime targets of GC7 in suppressing carcinogenesis. 3. Two-dimensional gel electrophoresis will be performed to profile the protein patterns in Hep3B cells with or without GC7 treatment, this will identify proteins associated with tumor inhibiting effects of GC7 in a high throughput approach. References (1) Chuma M., Sakamoto M., Yamazaki K., Ohta T., Ohki M., Asaka M. and Hirohashi S. (2003). "Expression profiling in multistage hepatocarcinogenesis: identification of HSP70 as a molecular marker of early hepatocellular carcinoma." Hepatology 37(1): 198-207. (2) Clement P. M., Johansson H. E., Wolff E. C. and Park M. H. (2006). "Differential expression of eIF5A-1 and eIF5A-2 in human cancer cells." FEBS J 273(6): 1102-14. (3) Gish R. G. (2006). "Hepatocellular carcinoma: overco ming challenges in disease management." Clin Gastroenterol Hepatol 4(3): 252-61. (4) Lee N. P., Leung K. W., Cheung N., Lam B. Y., Lau G. K., Sham P., Fan S. T. and Luk J. M. (2007). "Comparative proteomic analysis of mouse livers from embryo to adult reveals association with hepatocellular carcinoma progression." submitted. (5) Luk J. M., Lam C. T., Siu A. F., Lam B. Y., Ng I. O., Hu M. Y., Che C. M. and Fan S. T. (2006). "Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values." Proteomics 6(3): 1049-57. (6) Park M. H. (2006). "The post-translational synthesis of a polyamine-derived amino acid, hypusine, in the eukaryotic translation initiation factor 5A (eIF5A)." J Biochem (Tokyo) 139(2): 161-9. (7) Park M. H., Lee Y. B. and Joe Y. A. (1997). "Hypusine is essential for eukaryotic cell proliferation." Biol Signals 6(3): 115-23. (8) Parkin D. M., Bray F., Ferlay J. and Pisani P. (2005). "Global cancer statistics, 2002." CA Cancer J Clin 55(2): 74-108. (9) Wolff E. C., Kang K. R., Kim Y. S. and Park M. H. (2007). "Posttranslational synthesis of hypusine: evolutionary progression and specificity of the hypusine modification." Amino Acids: in press. (10) Wong B. W., Luk J. M., Ng I. O., Hu M. Y., Liu K. D. and Fan S. T. (2003). "Identificati on of liver-intestine cadherin in hepatocellular carcinoma--a potential disease marker." Biochem Biophys Res Commun 311(3): 618-24.

Project Title:	Cadherin-17 Signaling in tumorigenesis and metastasis
Investigator(s):	Luk JMC, Lui VCH
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	09/2007
Completion Date:	08/2009

Abstract:

To elucidate CDH17-mediated intracellular signaling pathways in cancer; to determine the CDH17 tumorigen ic and invasive potentials; to evaluate/validate the oncogenic functions of CDH17 in mouse model.

Project Title:	Liver cancer biomarker test: diagnostic use of CDH17 monoclonal antibodies
Investigator(s):	Luk JMC
Department:	Surgery
Source(s) of Funding:	Innovation and Technology Fund Internship Programme
Start Date:	10/2007

Abstract:

To develop novel immunodiagnostic assay for detect ion of cadherin-17 as bona fide timor biomarker in liver cancer patients

Project Title:	Molecular Analysis of miR-122a in Liver Metabolic Functions
Investigator(s):	Luk JMC, Lee NPY, Liu AML
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	10/2008
Completion Date:	03/2010

Abstract:

Hepatocellular carcinoma (HCC) is the most prevalent primary malignant cancer of the liver. It is a major health problem worldwide, and its incidence is increasing. A recent report indicates that HCC has risen to become the fifth commonest malignancy and the third leading cause of cancer-related death worldwide. The estimated incidence of new cases is about 500,000 – 1,000,000 per year, causing 600, 000 deaths globally per year (Gomaa et al. 2008). Currently, there is no effective drug for the treatment of HCC, and surgical intervention remains the only potentially curative treatment. Unfortunately, not all HCC patients are eligible for the surgical intervention, especially for those patients diagnosed in the late stage of HCC. Because of the inability to diagnose HCC patients in early stage and the lack of effective therapies for advanced patients, the ove rall 5-year survival rate is less than 5% (Parkin et al. 2005). As such, there is an urgent need to improve prognosis and treatment of HCC. Information regarding the molecular pathogenesis associated with the development of the disease needs to be determined. The recently discovered small RNA molecules known as microRNAs (miRN As) offer a new tool to study the molecular alterations involved in HCC pathogenesis. miRNAs are non-coding single-stranded RNA molecules of 18-25 nucleotides long. Studies on these small molecules reveal that they play important roles in proliferation, development, oncogenesis, and cell fate determination (Boyd 2008). MiR-122a is a well-known dominant miRNA in liver, accounting for about 70% of the total liver miRNA population (Jopling et al. 2005). Recent studies have uncovered its profound roles in diverse aspects of hepatic function and dysfunction, including viral infection, oncogenesis, and metabolism (Girard et al. 2008). In HCC, miR-122a expression level is significantly reduced (Kutay et al. 2006). The importance of miR-122a in the regulation of metabolism can be shown in a study, which used a chemically engineered oligonucleotide to silence miR-122a in mice. The decrea sed miR-122a levels resulted in reduction of plasma cholesterol and lipid levels (Krützfeldt et al. 2005). Our data on gene expression profiling of primary hepatocytes treated with anti-miR-122a reveal that many of the miR-122a correlated transcripts are associated with metabolic process, including carbohydrate, amino acid, and lipid metabolism. These results imply the important role of miR-122 in maintaining normal liver metaboli sm. Altered cell-intrinsic metabolism is an essential hallmark of HCC. Studying the association between miR-122a and its regulation on genes related to metabolism can shed light on the pathogenesis of the development of the disease. Specific Objectives: (1) A list of miR-122a correlated transcripts was established from our pervious study. From the list, genes that are asso ciated with metabolic function will be selected for validation using real-time quantitative polymerase chain reaction (Q-PCR). (2) The change in protein expression level of the target genes in response to anti-miR-122a treatment will be examined using Western blot analysis. (3) The functional interactions between miR-122a and 3’UTR sites of the target genes confirmed in Part (1) and (2) will be evaluated using luciferase reporter assay. The influence of 3’UTR on expression of the target gene will be analyzed. References: Boyd SD. Everything you wanted to know about small RNA but were afraid to ask. In: Lab Invest. Vol. 88, Series Everything you wanted to know about small RNA but were afraid to ask. 2008; p. 569-78. Girard M, Jacquemin E, Munnich A et al. miR-122, a paradigm for the role of microRNA s in the liver. In: J Hepatol. Vol. 48, Series miR-122, a paradigm for the role of microRNAs in the liver. 2008; p. 648-56. Gomaa AI, Khan SA, Toledano MB et al. Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis. In: World J Gastroenterol. Vol. 14, Series Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis. 2008; p. 4300-8. Jopling CL, Yi M, Lancaster AM et al. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. In: Science. Vol. 309, Series Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. 2005; p. 1577-81. Krützfeldt J, Rajewsky N, Braich R et al. Silencing of microRNAs in vivo with 'antagomirs'. In: Nature. Vol. 438, Series Silencing of microRNAs in vivo with 'antagomirs'. 2005; p. 685-9. Kutay H, Bai S, Datta J et al. Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. In: J Cell Biochem. Vol. 99, Series Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. 2006; p. 671-8. Parkin DM, Bray F, Ferlay J et al. Global cancer statistics, 2002. In: CA: a cancer journal for clinicians. Vol. 55, Series Global cancer statistics, 2002. 2005; p. 74-108.

List of Research Outputs

Chan K.L. , Wong K.F. and Luk J.M.C. , Role of LPS/CD14/TLR4-mediated inflammation in necrot izing enterocolitis: pathogenesis and therapeutic implications, World Journal of Gastroenterology . 2009, 15(38): 4745-4752.

Fatima S. , Lee N.P.Y. , Ng I.O.L. and Luk J.M.C. , The role of Dickkopf 4 (DKK4) on Wnt signaling in hepatocellular carcinoma (Poster Presentation), The 20th Annual Conference of the Asian Pacific Association for the Study of the Liver (APASL), Beijin g, China, 25-28 March 2010 .

Hao K., Luk J.M.C. , Lee P.Y. , Mao M., Zhang C., Ferguson M.D., Lamb J., Dai H., Ng I.O.L. , Sham P.C. and Poon R.T.P. , Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters, BMC Cancer . 2009, 9: 389.

Lee N.P.Y. and Luk J.M.C. , Hepatic tight junctions: from viral entry to cancer metastasis, World Journal of Gastroenterology . 2010, 16(3): 289-295.

Lee N.P.Y. , Poon R.T.P. , Shek H.P. , Ng I.O.L. and Luk J.M.C. , Role of cadherin-17 in oncogenesis and potential therapeutic implications in hepatocellular carcinoma, Biochimica et Biophysica Acta . 2010, Epub ahead of print (May): 1-8.

Liu A.M.L. , Poon R.T.P. and Luk J.M.C. , MicroRNA-375 targets Hippo-signaling effector YAP in liver cancer and inhibits tumor properties, Biochemical and Biophysical Research Communications . 2010, 394(3): 623-627.

Liu L. , Lee P.Y. , Chan V.W.M. , Xue W., Zender L., Zhang C., Mao M., Dai H., Wang X.L., Xu Z. , Lee K.W. , Ng I.O.L. , Chen Y., Kung H.F., Lowe S.W., Poon R.T.P. , Wang J.H. and Luk J.M.C. , Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma, Hepatology (Erratum in: Hepatology 2010;51(1):358) . 2009, 50(5): 1453-1463.

Luk J.M.C. , Academic Editor 2010, PLoS ONE . 2010.

Luk J.M.C. , Associate Editor - Asia, 2010, Journal of Integrated Omics . 2010.

Luk J.M.C. , Associate Editor-in-Chief (2009 - present), Journal of Molecular Diagnostics and Therapy . 2010.

Luk J.M.C. , Associate Editor-in-Chief (2010), World Journal of Gastroenterology . 2010.

Luk J.M.C. , Cancer biomarkers and molecular targets of hepatocellular carcinoma (Keynote paper), International conference of cancer diagnosis and therapy - cancer resistance and personalized therapies. Nanjing Medical University, Nanjing, China. 11-13 June 2010 .

Luk J.M.C. , Cancer biomarkers and molecular targets of hepatocellular carcinoma, International conference of cancer diagnosis and therapy: cancer resistance and personalized therapies. Nanjing Medical University, Nanjing, China, 11-13 June 2010 . 2010.

Luk J.M.C. , Cancer genomes; Cancer biomarkers and RNAi medicines , Food and Nutritional Toxicology Lecture Series 6: Diet, nutrition, genes and the life-course approach to cancer and disease prevention. School of Public Health and Clinical Nutrition, University of Kuopio, Finland, 5-8 August 2009 . 2009.

Luk J.M.C. , Circulating vimentin as a novel serological marker for detection of small ( < 2cm) hepatocellular carcinoma (Invited paper), The 8th HUPO Annual World Congress, The Westin Harbour Castle, Toronto, Canada, 26-30 September 2009 .

Luk J.M.C. , Circulating vimentin as a novel serological marker for detection of small (≒ 2cm) hepatocellular carcino ma, The 8th HUPO Annual World Congress, Toronto, Ontario, Canada, 26-30 September 2009 . 2009.

Luk J.M.C. , Editorial Board Member (2009 - present), Journal of Chinese Clinical Medicine . 2010.

Luk J.M.C. , Editorial Board Member (2009 - present), World Journal of Gastrointestinal Surgery . 2010.

Luk J.M.C. , Editorial Board Member (2009 - present), World Journal of Hepatology . 2010.

Luk J.M.C. , Editorial Board Member 2009, Liver Cancer Review Letters . 2009.

Luk J.M.C. , Editorial Board Member 2010, American Journal of Analytical Chemistry . 2010.

Luk J.M.C. , Editorial Board Member 2010, World Journal of Clinical Oncology . 2010.

Luk J.M.C. , Editorial board member, Journal of Clinical Bioinformatic Science . 2009.

Luk J.M.C. , Enhanced detection of early HCC using SELDI signature combined with serum AFP, College of biotechnology and health science, Jinan University, Guangzhou, China, 27 October 2009 . 2009.

Luk J.M.C. , External examiner, Effects of HBx and hypoxia on Bid in HCC (M.Phil. candidate Mr. Davor Chau), Supervisor: Prof. George G. Chen, Department of Surgery, The Chinese University of Hong Kong . 2009.

Luk J.M.C. , Gene expression in human hepatocellular carcinoma and prognostic signatures in tumor-and-nontumor tissues predicting survivals of patients with liver cancer (Invited paper), James Watson Symposium on Cancer. Cold Spring Harbour Asia Conference Center, Suzhou, China. 6-11 April 2010 .

Luk J.M.C. , Gene expression in human hepatocellular carcinoma and prognostic signatures in tumor-and-nontumor tissues predicting survivals of patients with liver cancer, The 1st James Watson Cancer Symposium, Cold Sprin g Harbor Asia Conferences, Suzhou, China, 6-11 April 2010 . 2010.

Luk J.M.C. , Genomics and proteomics of hepatitis B-associated hepatocellular carcinoma, Annual scientific meeting of Egyptian Microbiology Society, Cairo, Egypt, 25 April 2010 . 2010.

Luk J.M.C. , Genomics of hepatocellular carcinoma (Invited paper), The 20th APASL annual meeting. China National Conv ention Center, Beijing, China. 25-28 March 2010 .

Luk J.M.C. , Genomics of hepatocellular carcinoma, The 20th APASL annual meeting, Beijing, China, 25-28 March 2010 . 2010.

Luk J.M.C. , HnRNPK is a novel binding protein of YAP in hepatocellula r carcinoma, The 6th annual conference of China Human Proteome Organization (CNHUPO), Taizhou, Jiangsu, China, 28-30 July 2009 . 2009.

Luk J.M.C. , Honorary Professor (2005 - present), Jiangsu University, Jiangsu, China . 2010.

Luk J.M.C. , Honorary Professor (2006 - present), Southern Medical University, Guangzhou, China . 2010.

Luk J.M.C. , Honorary Professor (2006 - present), Zhongshan Hospital, Fudan University, Shanghai, China . 2010.

Luk J.M.C. , Honorary Professor (2010), First affiliated hospital, Nanjing Medical University, China . 2010.

Luk J.M.C. , Integrative oncogenomics profiling identifies novel molecular targets against liver carcinoma, Merck research laboratories, Merck & Co., Boston, MA, USA, 6 November 2009 . 2009.

Luk J.M.C. , Liver cancer biomarkers (Plenary paper), Hepatitis and Liver Cancer Meeting and Clinical Workshop. National Blood Transfusion Center, Cairo, Egypt. 26-28 April 2010 .

Luk J.M.C. , Liver cancer biomarkers and molecular targets, Center for clinical oncology, Nanjing Medical University, Nanjing, China, 28 July 2009 . 2009.

Luk J.M.C. , Liver cancer biomarkers and targets, Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical Universi ty, Shanghai, China, 13-14 June 2010 . 2010.

Luk J.M.C. , Liver cancer biomarkers, Hepatitis and Liver Cancer Meeting and Clinical Workshop, National Blood Transfusion Center, Cairo, Egypt, 26-28 April 2010 . 2010.

Luk J.M.C. , Peer Reviewer (2004 - present), Analytical Biochemistry . 2010.

Luk J.M.C. , Peer Reviewer, Amino Acids . 2010.

Luk J.M.C. , Peer Reviewer, Developmental Biology . 2010.

Luk J.M.C. , Peer Reviewer, Hepatology . 2010.

Luk J.M.C. , Peer Reviewer, Human Pathology . 2010.

Luk J.M.C. , Peer Reviewer, International Journal of Cancer Research . 2010.

Luk J.M.C. , Peer Reviewer, International Journal of Pharmaceutics . 2010.

Luk J.M.C. , Peer Reviewer, Journal of National Cancer Institute . 2010.

Luk J.M.C. , Peer Reviewer, Journal of Proteome Research . 2010.

Luk J.M.C. , Peer Reviewer, Journal of Surgical Oncology . 2010.

Luk J.M.C. , Peer Reviewer, PLoS One . 2009.

Luk J.M.C. , Peer Reviewer, Stem Cell & Development . 2010.

Luk J.M.C. , Peer Reviewer, World Journal of Gastroenterology . 2009.

Luk J.M.C. , Peer Reviewer, World Journal of Surgery . 2010.

Luk J.M.C. , Proteomics of hepatocellular carcinoma (Plenary paper), The 10th Advanced Meeting on Cancer Omics. Ettore Majorana Foundation and Centre for Scientific Culture, Erice, Sicily, Italy. 3-8 May 2010 .

Luk J.M.C. , Proteomics of hepatocellular carcinoma: discovery of cancer biomarkers and molecular targets, Department of Gastroenterology, Hannover Medical School, Germany, 10 May 2010 . 2010.

Luk J.M.C. , Proteomics of hepatocellular carcinoma, The 10th Advanced Meeting on Cancer Omics - Ettore Majorana Foundation and Centre for Scientific Culture. Eric, Sicily, Italy, 3-8 May 2010 . 2010.

Luk J.M.C. , Reviewer (2004 - present), Journal of Hepatology . 2009.

Luk J.M.C. , Reviewer (2007 - 2008), Journal of Cell Science . 2009.

Luk J.M.C. , Reviewer, British Journal of Cancer . 2009.

Luk J.M.C. , Reviewer, Cancer . 2009.

Luk J.M.C. , Reviewer, Clinical Sciences . 2009.

Luk J.M.C. , Reviewer, European Journal of Cancer . 2009.

Luk J.M.C. , Reviewer, Proteomics . 2009.

Luk J.M.C. , Reviewer, Transplantation . 2009.

Luk J.M.C. , The "3Ps" world--from disease markers to biological therapeutics, Protein and Peptide Letters . 2009, 16(5): 457-459.

Luk J.M.C. , siRNA as a tool for biomarker development and target validation (Plenary paper), Drug discovery technology world. Raffles City Convention Center, Singapore. 17-18 March 2010 .

Luk J.M.C. , siRNA as a tool for biomarker development and target validation, Drug discovery technology world. Raffles City Convention Center, Singapore, 17-18 March 2010 . 2010.

Shek H.P. , Luk J.M.C. , Kwong A. and Lee N.P.Y. , The role of serine peptidase inhibitor, Kazal type I (SPINK1) in hepatocellular carcinoma (Poster Presentation), Cancer Omics, Erice, Italy, 3-8 May 2010 .

Sun S. , Yi X. , Poon R.T.P. , Yeung C. , Day P.J. and Luk J.M.C. , A protein-based set of reference markers for liver tissues and hepatocellular carcinoma, BMC Cancer . 2009, 9: 309.

Sun S. , Xu Z. , Poon R.T.P. , Day P.J. and Luk J.M.C. , Circulating Lamin B1 (LMNB1) biomarker detects early stages of liver cancer in patients, Journal of Proteome Research . 2010, 9(1): 70-78.

Sun S. , Poon R.T.P. , Lee N.P.Y. , Yeung C. , Chan K.L. , Ng I.O.L. , Day P.J.R. and Luk J.M.C. , Proteomics of hepatocellular carcinoma: serum vimentin as a surrogate marker for small tumors ( £ 2 cm), Journal of Proteome Research . 2010, 9(4): 1923-1930.

Tsang F.H. , Luk J.M.C. and Lee N.P.Y. , Clinical implication of ectopic expression of microRNA-125b in liver cancer (Poster Presentation), Cancer Omics, Erice, Italy, 3-8 May 2010 .

Tsang F.H. , Luk J.M.C. and Lee N.P.Y. , MicroRNA-125b as a negative regulator for eukaryotic translation initiation factor 5A2 (eIF5A2) in liver cancer (Poster Presentation), The 16th Hong Kong International Cancer Congress (HKICC) and 6th Annual Meeting of Center for Cancer Research, Hong Kong, 2009 .

Tung K.K. , Mak K.M. , Lee M.F. , Li J.J., Poon R.T.P. , Lai C.L. , Luk J.M.C. and Ng I.O.L. , Serum level of DKK1 as a marker for predicting tumor recurrence of hepatocellular carcinoma , American Association for Cancer Research 101st Annual Meeting 2010 .

Wong K.F. and Luk J.M.C. , Endotoxin-neutralizing peptides as gram-negative seps is therapeutics, Protein and Peptide Letters . 2009, 16(5): 539-542.

Wong K.F., Wo J., Ho D., Poon R.T.P. , Casasnovas J.M. and Luk J.M.C. , Prophylactic uses of integrin CD18-betaA peptide in a murine polymicrobial peritonitis model, World Journal of Gastroenterology . 2010, 16(21): 2648-2656.

Researcher : Man K

Project Title:	The significance of lipocalin2 in liver cancer growth and metastasis
Investigator(s):	Man K, Xu A, Lo CM
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2008
Completion Date:	06/2010

Abstract:

Summary Liver cancer is a common lethal malignancy. It is the fifth cancer killer worldwide and the second major cause of cancer death in Hong Kong. Although surgical resection is the first front treatment, tumor recurrence or metastasis remains to be the major problem, which significantly affects the long-term disease-free survival. To identify novel therapeutic target will be important to develop new treatments for liver cancer growth and metastasis. Lipocalin-2 (also known as neutrophil gelatinase-associated lipocalin), an inflammatory marker closely associated with obesity, insulin resistance and hyperglycemia in humans, has been recently demonstrated to be not only a predicto r of poor prognosis in breast cancer, but also to sever as a early screening biomarker for ovarian cancer. Lipocalin-2 is also involved in differentiation pathway and invasive progression in gastric cancer. Recently, Lipocalin-2 was suggested to be a desirable molecular marker for further study in liver carcinogenesis and progression. In addition, our animal study for liver transplantation showed that lipocalin-2 was over-express ed in small-for-size fatty liver graft and correlated to acute phase graft injury. Therefore, it is worthwhile to investigate the role of lipocalin-2 in liver tumor growth and metastasis and its potential molecular mechanism. Aim of the study We intend to investigate the role of lipocalin-2 in liver cancer growth and metastasis and to explore the potential molecular mechanism by series of in vivo animal models and in vitro functional studies.

Project Title:	The significance of hepatic ischemia /reperfusion injury on tumor recurrence after major hepatectomy in a rat orthotopic liver tumor model – the impact of surgical stress mobilizing of circulating cancer stem like cells/endothelial progenitor cells
Investigator(s):	Man K, Liu Y, Lo CM
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2009

Abstract:

Objectives of the research proposal: Purpose We aim to investigate the precise mechanism of surgical stress mobilizing circulating cancer stem like cells/end othelial progenitor cells during tumor recurrence after hepatectomy underwent hepatic ischemia/reperfusion injury. Key issues and problems Tumor recurrence and metastasis remains the major concern of LDLT for liver cancer patients. The inferior oncologic outcome of LDLT has frequently been found in clinical studies despite the theoretical intention-to-treat survival advantage. The graft from a living donor is usually small-for-size for the adult recipient. Small-for-size liver graft injury is frequently observed. The impact of acute phase liver injury on later phase tumor invasiveness has been investigated. The significant association between graft size and tumor invasiveness/metastasis has also been elucidated. The acute phase small-for-size graft injury plays important roles in late phase tumor recurrence after liver transplantation. The inflammator y response in small-for-size liver graft not only affected the liver microenvironment to favor the tumor cell invasion, but also subsequently activated numbers of chemokines and cytokines to directly regulate the invasive-associat ed properties of tumor cells. To improve the inferior oncologic outcome of LDLT, investigation of the underlying mechanism of tumor recurrence and metastasis after LDLT will be essential for the development of potential therapeutic strategies to reduce post-LDLT tumor recurrence. Therefore, it is necessary to investigate the impact of surgical stress on tissue microenvironment, which play important role in mobilizing circulating cancer stem like cells/endothelial progenitor cells/T regulatory cells and subsequently promote tumor recurrence and metastasis. Possible solution to the problems A well designed animal study (hepatic ischemia reperfusion injury and major hepatectomy) will be important for the investigating the mechanism of acute phase liver injury under surgical stress mobilizing circulating cancer stem like cells/endothelial progenitor cells/ T regulatory cells. The potential underlying precise mechanism will be further explored by a series of in vitro functional studies for the development of therapeutic strategies in the future. Possible outcome of the research project Hepatic ischemia/reperfusion injury during liver surgery may increase the possibility of intrahepatic recurrence after liver resection. The acute phase liver injury significantly mobilized EPCs to participate in tumor angiogenesis during recurrenc e and metastasis. Furthermore, the surgical stress also enriched the population of regulatory T cells, which also contribute to tumor escape and immune tolerance. Key inflammatory regulators including chemokines/cytokines activated during acute phase liver injury will be further defined for the future treatment targets.

Project Title:	15th International Liver Transplantat ion Society Congress 2009 INFLAMMATORY MICROENVIRONMENT ACCELERATES LIVER TUMOR GROWTH AND METASTASIS BY MOBILIZING CIRCULATING ENDOTHELIAL PROGENITOR CELLS AND INCREASING CANCER STEM LIKE CELL POPULATIONS
Investigator(s):	Man K
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	07/2009
Completion Date:	07/2009

Abstract:

N/A

List of Research Outputs

Chen L. , Chan H.M. , Man K. and Guan X.Y. , Identification of the proteins Lsm2 and Apolipoprotei n A-1 associated with liver regeneration by proteomic screeing (Abstract), The 16th International Liver Transplantation Socie ty Congress, 16-19 June 2010, Hong Kong. Liver Transplantation . 2010, 16(6): s221.

Cheng I.K., Ching A.K., Chan T.C., Chan A.W., Wong C.K., Choy K.W., Man K. , Lai P.B. and Wong N., Reduced CRYL1 expression in hepatocellular carcinoma confers cell growth advantages and correlates with adverse patient prognosis, The Journal of Pathology . 2010, 220(3): 348-360.

Cheng Q. , Ng T.P. , Fan S.T. , Lim Z.X.H. , Guo D. , Liu X. , Liu Y. , Poon R.T.P. , Lo C.M. and Man K. , Distinct mechanism of small-for-size fatty liver graft injury--Wnt4 signaling activates hepatic stellate cells, American Journal of Transplantation . 2010, 10(5): 1178-1188.

Chua C.W. , Chiu Y.T. , Yuen H.F. , Chan K.W. , Man K. , Wang X. , Ling M.T. and Wong Y.C. , Suppression of androgen-independent prostate cancer cell aggressiveness by FTY720: validating Runx2 as a potential antimetastatic drug screening platform, Clinical Cancer Research . 2009, 15(13): 4322-4335.

Fan S. , Chow A.M.K. , Zhang J. , Man K. and Wu E.X. , Diffusion tensor imaging of renal ischemia reperfusion injury in an experimental model, NMR in Biomedicine . 2010, 23(5): 496-502.

Fu L. , Dong S. , Xie Y.W., Tai L.S. , Chen L. , Kwong D.L.W. , Man K. , Xie D., Li Y., Cheng Y., Tao Q. and Guan X.Y. , Down-regulation of tyrosine aminotransferase at a frequently deleted region 16q22 contributes to the pathogenesis of hepatocellular carcinoma, Hepatology . 2010, 51: 1624-34.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Abstract), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 Jun e 2010. Liver Transplantation . 2010, 16(6): s141.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Ji J., Shi J., Budhu A., Yu Z., Forgues M., Roessler S., Ambs S., Chen Y., Meltzer P.S., Croce C.M., Qin L.X., Man K. , Lo C.M. , Lee J., Ng I.O.L. , Fan J., Tang Z.Y., Sun H.C. and Wang X.W., MicroRNA expression, survival, and response to interferon in liver cancer, New England Journal of Medicine . 2009, 361(15): 1437-1447.

Lee Y.K. , Sit W.H. , Fan S.T. , Man K. , Jor W.Y. , Wong L.Y. , Wan L.Y. , Tan-Un K.C. and Wan J.M.F. , The cell cycle effects of docosahexaenoic acid on human metastatic hepatocellular carcinoma proliferation, International Journal of Oncology . 2010, 36(4): 991-998.

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Li X.C., Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s96.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investig ator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 Ju ne 2010 . 2010.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplant ation . 2010, 16(6): s72.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Rising Star Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Liu Y. , Man K. , Nashan B., Schlitt H.J. and Tsui T.Y., A novel approach to protect liver graft against ischemia/reperfu sion injury via a cell penetrating heme oxygenase protein (Abstract), The 15th Annual International Congress of the Internati onal Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): s117.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft - the significance of aldose reduct ase signaling on oval cell activation (Travel Award), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009 . 2009.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft – the significance of aldose reducatase signaling on oval cell activation (Abstract), The 15th Annual International Congress of the Internationa l Liver Transplantation Society, New York, U.S.A., 8-11 July 2009. Liver Transplantation . 2009, 15:S72: #O6.

Ma S.K.Y. , Tang K.H. , Chan Y.P. , Lee K.W. , Castilho A.G. , Ng I.O.L. , Man K. , To K.F., Zheng B. , Chan K.W. and Guan X.Y. , miR-130b is preferentially upregulated in CD133+ liver cancer stem cells and regulates tumor growth and self-renewal via tumor protein 53-induced nuclear protein 1, Gordon Research Conference - Stem Cells and Cancer . 2009.

Man K. , Abstract Chair, Basic Science of the 16th International Liver Transplantation Society Congress, Dallas, U.S.A., 4 February 2010 . 2010.

Man K. , Application of optical imaging in liver cancer research, 2010 Small Animal Molecular Imaging Symposium, Shanghai, China, 20 May 2010 . 2010.

Man K. , Basic Science Committee Member (2009 - 2010), International Liver Transplantation Society Annual Meeting . 2009.

Man K. , Chairperson, 2010 Small Animal Imaging Symposium, Shanghai, China, 20 May 2010 . 2010.

Man K. , Chairperson, Basic Science Session of the 16th International Liver Transplantation Society Congress, Hong Kong, 18 June 2010 . 2010.

Man K. , Co-chairperson, The 16th Hong Kong International Cancer Congress, Hong Kong, 4-6 November 2009 . 2009.

Man K. , Committee Member, Basic Science of Liver Transplantation, the Inter national Liver Transplantation Society . 2010.

Man K. , HCC recurrence – the impact of acute phase graft injury on tumor behaviors, Basic Science Symposium, International Liver Transplantation Society Congress, Hong Kong, 19 June 2010 . 2010.

Man K. , Ng T.P. , Liu X. , Yeung W.H. , Lo C.M. and Fan S.T. , Inflammatory microenvironment accelerates liver tumor growth and metastasis by mobilizing circulating endothelial progenitor cells and increasing cancer stem like cell populations (Abstract), The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Man K. , Cheng Q. , Liu Y. , Lam T.T. , Ng T.P. and Lo C.M. , Inflammatory microenvironment accelerates liver tumor growth and metastasis by mobilizing circulating endothelial progenitor cells and increasing cancer stem like cell populations (Abstract), The 15th Annual International Congress of the Intern ational Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): S97.

Man K. , Liver transplantation research centre – a multidisciplin ary study for liver graft injury, School of Chinese Medicine, Hong Kong Baptist University . 香港浸會大學中醫藥學院, 2010.

Man K. , Member of Editorial Board (2007 - present), Liver Transplantation . 2010.

Man K. , Member of Scholarship Review Committee, The International Liver Transplantation Society . 2010.

Man K. , Shih K.C. , Ng T.P. , Xiao J. , Guo D. , Sun K.W. , Lim Z.X.H. , Cheng Q. , Liu Y. , Fan S.T. and Lo C.M. , Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts, Annals of Surgery . 2010, 251(6): 1154-1161.

Man K. , New Key Opinion Leader, The Transplantation Society . 2010.

Man K. , Reviewer (2008 - present), Annals of Surgery . 2010.

Man K. , Reviewer, Acta Pharmacologica Sincia . 2010.

Man K. , Reviewer, American Journal of Transplantation . 2010.

Man K. , Reviewer, Annual Meetings of International Liver Transplantat ion Society . 2010.

Man K. , Reviewer, British Journal of Cancer . 2010.

Man K. , Reviewer, British Journal of Surgery . 2010.

Man K. , Reviewer, European Journal of Cancer . 2010.

Man K. , Reviewer, Gut . 2010.

Man K. , Reviewer, Hepatology . 2010.

Man K. , Reviewer, Journal of Gastroenterology and Hepatology . 2010.

Man K. , Reviewer, Liver . 2010.

Man K. , Reviewer, Liver International . 2010.

Man K. , Reviewer, Liver Transplantation . 2010.

Man K. , Reviewer, Surgery . 2010.

Man K. , Reviewer, Transplant Immunology . 2010.

Man K. , Reviewer, Transplantation . 2010.

Man K. , Reviewer, World Journal of Surgery . 2010.

Man K. , Ng T.P. , Xu A. , Cheng Q. , Lo C.M. , Xiao J. , Sun B. , Lim Z.X.H. , Cheung J.S., Wu E.X. , Sun K.W. , Poon R.T.P. and Fan S.T. , Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-induci ble protein 10/matrix metalloproteinase 9 signaling, Clinical Cancer Research . 2010, 16(3): 967-977.

Man K. , Targeting invasiveness of HCC – the story of Pyk2 and beyond, Run Run Shaw Hospital, Zhejiang University . 浙江大學邵逸夫醫院, 2010.

Man K. , Shao Y. , Ng T.P. , Li C. , Fan S.T. and Lo C.M. , The significance of acute-phase small-for-size liver graft injury in mobilization of circulating EPCS/MDSCS/TREGS after LDLT for HCC patients (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16 - 19 June 2010. Liver Transplantation . 2010, 16(6): s191.

Ng T.P. and Man K. , Hepatocellular carcinoma: overexpression of hemeoprotein six1 as a marker for predicting survival, In: Hayat, M.A. (ed), Methods of Cancer Diagnosis, Therapy and Prognosis (Volume 5: Liver Cancer) . Netherlands, Springer, 2010, 5: 313-324.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , Identification of circulating protein markers related to tumor recurrence after liver transplantation (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s207.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase smal l-for size liver graft injury and tumor invasiveness (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s77.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Young Investigator Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Shih K.C. and Man K. , Reviewer (for the article "Small-for-size liver graft injury – impact on tumor behavior"), Transplantation Reviews . 2009, 24(1): 1-10.

Shih K.C. and Man K. , Small-for-size liver graft injury – impact on tumor behavior (Invited review), Transplantation Reviews . 2010, 24(1): 1-10.

Shih K.C. and Man K. , Small-for-size liver graft injury--impact on tumor behavior, Transplantation Reviews (Orlando) . 2010, 24(1): 1-10.

Wong L.Y. , Jor W.Y. , Lee Y.K. , Jiang P. , Sit W.H. , Man K. and Wan J.M.F. , A Proteomic Analysis of Carbon Tetrachloride-Induced Hepatotoxicity In Rat Livers, 41st Annual Symposium, Society of Toxicology of Canada . 2009, No.48.

Yao H. , Ng S.M. , Tucker W.O. , Tsang Y.K.T. , Man K. , Wang X.M., Chow B.K.C. , Kung H.F., Tang G. and Lin M.C. , The gene transfection efficiency of a folate-PEI600-cyclodextrin nanopolymer, Biomaterials . 2009, 30(29): 5793-5803.

Researcher : Man OY

List of Research Outputs

Wong S.T.S. , Man O.Y. , Tsang C.M. , Tsao G.S.W. , Tsang R.K.Y. , Chan Y.W. , Ho W.K. , Wei W.I. and To V.S.H. , Microrna Let-7 Suppresses Nasopharyngeal Carcinoma Cells Proliferation Through Downregulating C-myc Expre ssion, Journal of Cancer Research and Clinical Oncology . Berlin, Springer Berlin / Heidelberg, 2010.

Researcher : Miao X

List of Research Outputs

Cherny S.S. , Tang S.M. , Sribudiani Y., Miao X. , So M.T. , Sham P.C. , Tam P.K.H. , Garcia-Barcelo M.M. and Hofstra R.M., Fine mapping of Hirschsprung's disease loci in 9q31 (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Cornes B.K. , Tang S.M. , Leon Y.Y. , Hui K.J.W.S., So M.T. , Miao X. , Cherny S.S. , Sham P.C. , Tam P.K.H. and Garcia-Barcelo M.M. , Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population, PLoS One . 2010, 5 (6): e10918.

Garcia-Barcelo M.M. , Tang W.Y. , Miao X. , Tang S.M. , So M.T. , Leon Y.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Identification of rare variants in the NRG1 gene of Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Garcia-Barcelo M.M. , Lui V.C.H. , So M.T. , Miao X. , Leon Y.Y. , Yuan Z.W., Ngan E.S.W. , Ehsan T., Chung P.H.Y., Khong P.L. , Wong K.K.Y. and Tam P.K.H. , MNX1 (HLXB9) mutations in Currarino patients, Journal of Pediatric Surgery . 2009, 44(10): 1892-1898.

Miao X. , Garcia-Barcelo M.M. , So M.T. , Tang W.K. , Xiao D. , Wang B. , Mao J.X., Ngan E.S.W. , Chen Y. , Lui V.C.H. , Wong K.K.Y. , Liu L. and Tam P.K.H. , Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population, Journal of Pediatric Surgery . 2010, 45: 709-713.

Miao X. , Leon Y.Y. , Ngan E.S.W. , So M.T. , Yuan Z.W., Lui V.C.H. , Chen Y. , Wong K.K.Y. , Tam P.K.H. and Garcia-Barcelo M.M. , Reduced RET expression in gut tissue on individuals carrying risk alleles of Hirschsprung's disease, Human Molecular Genetics . 2010, 19(8): 1461-1467.

Tang S.M. , Sribudiani Y., Miao X. , de Vries A.R., Burzynski G., So M.T. , Leon Y.Y. , Yip B.H.K. , Osinga J., Hui K.J.W.S., Verheij J.B.G.M., Cherny S.S. , Tam P.K.H. , Sham P.C. , Hofstra R.M.W. and Garcia-Barcelo M.M. , Fine mapping of the 9q31 Hirschsprung's disease locus, Human Genetics . 2010, 127(6): 675-683.

Researcher : Ng EKO

Project Title:	Systemic identification of circulating tumor-derived microRNAs: Potential noninvasive diagno stic or prognostic biomarkers for breast cancer
Investigator(s):	Ng EKO, Kwong A
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	11/2008
Completion Date:	10/2009

Abstract:

Purpose of the proposed project To develop a panel of tumor-assoicated microRNA markers in plasma that can be used as a noninvasive diagnostic or prognostic biomarker for breast cancer.. Key issues and problems being addressed Breast cancer is one of the three most commonly diagnosed cancers among women, accounting for about 30% of patients [1]. Screening for breast cancer allowing early stage diagnosis of the malignancy and hence potential to reduce mortality. In the past decades, despite the dedication of research and resour ces to the development of biomarkers for diagnosis and prognosis, unpredictable response and development of resistance to adjuvant therapy remain major challenges in breast cancer management. Breast cancer patients have diverse pathologic and clinical features. Based on the previous molecular profiling, breast cancer could be divided into those with high expression of the estrogen receptor (ER) gene (luminal A and luminal B subtypes), and those that do not express ER. Recently, the emergence of microRNAs (miRNAs) as regulators of gene expression identifies as novel candidate diagnostic and prognostic indicators and therapeutic targets. MicroRNAs are 19-25-nucleotides regulatory non-protein-coding RNA molecules, playing important role in oncogenesis has open new opportunities of noninvasive test for early cancer diagnosis. Studies have shown that profiles of miRNA expression differ between normal tissue and tumor and vary among tumor types. Evidence suggests that miRNA expression profiles can cluster similar tumor types together more accurately than the expression profiles of protein-coding mRNA genes [2]. Importantly, expression of some miRNAs correlated with the molecular subtypes and with two major features of breast cancer (grade and ER status) [3]. More recently, several report s suggest that cell-free circulating miRNAs existed in serum and plasma [4-6]. Accordingly, it raises the possibility of using miRNAs as novel noninvasive molecular markers for cancer detection and prognosis. In the present study, we plan to evaluate the feasibility of using plasma miRNAs as a noninvasive diagnostic or prognostic biomarker for breast cancer. Work done by us Previous studies by the PI and other collaborators overcame technical difficulties and developed a robust protocol for RNA extraction and quantification from plasma [7, 8]. With the help of ultracentrifugation or filtration, we have also developed a unique and novel nucleic acids fractionation procedure for disease evaluation [7]. Recently, based on our previously developed protocol, we have developed another robust protocol for miRNA extraction and quantification from plasma of colorectal cancer (CRC) patients [9]. In that study, we used real-time qPCR-based array to profile miRNAs from plasma, corresponding colorectal tumor and adja cent normal tissues. We did demonstrate that miRNAs can be profiled and quantified in plasma. By comparing the miRNA profiles from different sample types, we have identified 5 miRNAs were up-regulated both in plasma and tissue samples. The plasma levels of these markers were significantly reduced after surgery. Further validation with 180 plasma samples including 90 CRC, 50 healthy controls, 20 gastric cancer and 20 inflammatory bowel disease patients indicated that one of the 5 miRNAs alone provided the best markers for cancer di agnosis. That marker yielded a receiver operating characteristic curve area of 88.5%. At a cutoff of 240, the sensitivity was 89% and the specificity was 70% in discriminating colorectal cancer from control subjects. Encouraged by the promising results from that study, we believe that if plasma miRNAs are implicated in cancer then they may be useful as biomarkers or cancer indicators. Furthermore, miRNA markers have several advantages: (i) unlike screening for large number of mRNA expression that can add up to complexity on a systems biology scale, a modest number of miRNAs might be sufficient to differentiate cancers from normal. In our previous study, profiling of 95 miRNAs is possible to identify at least two miRNA markers for discriminating CRC; and (ii) unlike plasma mRNAs, miRNAs in plasma remain largely intact because of their size and so are more stable for detection. Accordingly, we believe using miRNAs as diagnostic markers could offer an effective and highly significant solution.

Project Title:	Differential expression of tumor-derived exosomal microRNAs from the plasma of breast cancer patients: A potential biomarker for breast cancer screening
Investigator(s):	Ng EKO, Kwong A, Suen DTK
Department:	Surgery
Source(s) of Funding:	The Hong Kong Anti-Cancer Society (HKACS) - General Award
Start Date:	10/2009

Abstract:

Breast cancer is one of the three most commonly diagnosed cancers among women, accounting for about 30% of patients. Screening for breast cancer allowing early stage diagnosis of the malignancy and hence potential to reduce mortality. In the past decades, despite the dedication of research and resources to the development of biomarkers for diagnosis and prognosis, unpredictable response and development of resistance to adjuvant therapy remain major challenges in breast cancer management. Breast cancer patients have diverse pathologic and clinical features. The role of serum tumor markers is also less well established. The most widely used serum markers in breast cancer are CA 15-3 and carcinoembryonic antigen. Less widely used markers include CA 27.29, tissue polypeptide antigen and the shed form of HER-2. Those serum markers have been used to monitor treatment response in patients with metastatic breast cancer. Despite the frequent use of such markers, they lack high sensitivity and specificity for breast cancer progression. The prognostic significance of these ma rkers remains indeterminate because of the conflicting outcome of many clinical trials. Therefore, none of the available markers is of value for the detection of early breast cancer. Based on the previous molecular profiling, breast cancer could be divided into those with high expression of the estrogen receptor (ER) gene (lumina l A and luminal B subtypes), and those that do not express ER. Recently, the emergence of small non-protein-coding RNAs, so-called microRNAs (miRNAs), playing important roles in oncogenesis has opened new opportunities for early cancer diagnosis. MiRNAs are 19-25-ucleotides regulatory non-coding RNA molecules that regulate the expressions of a wide variety of genes by sequence-spe cific base pairing on the 3’ untranslated regions of the target mRNA resulting in mRNA degradation or inhibition of translation. Evidence suggests that miRNA expression profiles can cluster similar tumor types together more accurately than the expression profiles of protein-coding mRNA genes. Furthermore, miRNA expression signatures have been used to predict prognosis. Importantly, expression of some miRNAs correlated with the molecular subtypes and with two major features of breast cancer (grade and ER status). Recently, several reports suggest that circulating miRNAs are stable and detectable in serum/pl asma and the levels of some miRNAs specifically elevated in the patients with lung cancer, prostate cancer, ovarian cancer, and colorectal cancer. These findings suggest that blood-based miRNAs could emerge as revolutionary sources of biomarker for breast cancer diagnosis. On the other hand, exosomes are small (50–90 nm) membrane vesicles of endocytic origin that are released into the extracellular environment such as blood circulation. Many cells have the capacity to release exosomes, including dendritic cells, B cells, T cells, mast cells, epithelial cells and tumor cells. Recent study demonstrated that released exosomes contain a subset of both cellular mRNA and microRNA, which could be a useful source of biomarkers for cancer detection. More Recently, study showed that circulating exosomal miRNAs signatures could be useful for diagnosis of ovarian cancer. While the primary source of circulating exosomes in cancer patients is the tumor, other normal cells within the peripheral circulation can contribute to the level exosome population. To isolate circulating exosomes of tumor origin, adherence to specific magnetic beads is utilized. A limited number of markers are used for the isolation (ie, cell surface antigens) of circulati ng exosomes. These markers include epithelial cell surface markers, such as the epithelial cell adhesion molecule (EpCAM), cytokeratins 7, 8, 18, 19, and 20 for breast carcinoma. In this proposed study, we have developed a protocol for isolation of tumor-derived exosomes from plasma samples by bounding to anti-EpCAM antibodies coupled to microscopic iron beads. With the help of the circulating tumor-derived exosome isolated, we will perform miRNA profiling on 10 breast cancer pati ents and 10 normal subjects. Differential expression signatures will be identified. Then putative miRNA biomarkers identified will be verified on plasma samples from the breast cancer patients before and after 14 days after surgery. If the putative biomarkers are really derived from tumors, we would expect that those plasma miRNA levels are completely or significantly reduced in the post-operative samples as compared to pre-operat ive samples. Finally, we will validate those markers on an independent set of plasma samples. Multivariate logistic regression analysis will be used to determine the best combination of the putative biomarkers to obtain the best prediction of breast cancer. Sensitivity, specificity and predictive cutoff value of our developed diagnostic test will be calculated based on this large- scale validation study. Encouraged by the promising results from our previous study, we believe that if circulating exosomal miRNAs are implicated in cancer then they may be useful as biomarkers or cancer indicators. Furthermore, miRNA markers have several advantages: (i) unlike screening for large number of mRNA expression that can add up to complexity on a systems biology scale, a modest number of miRNAs might be sufficient to differentiate cancers from normal. In our previous study, profiling of 95 miRNAs is possible to identify at least two miRNA markers for discriminating CRC; and (ii) unlike plasma mRNAs, miRNAs in plasma remain largely intact because of their size and so are more stable for detection. Accordingly, we believe using miRNAs as diagnostic markers could offer an effective and highly significant solution. The long-term goal of this study is to develop rapid, accurate and reliable assays for early breast cancer diagnosis and prognosis by simply analyzing the blood from patients. Our main aims are: (i) To identify aberrant miRNA expression patterns in the plasma of patients with breast cancers. (ii) To develop a blood-based quantitative assay with a panel of miRNAs which are obtained from aim (i). (iii) To evaluate those miRNA biomarkers on large number of patient samples so as to determine the potential usefulness in early breast cancer diagnosis and the monitoring of disease progress.

Project Title:	Third International Symposium on Hereditary Breast and Ovarian Cancer Clinical, pathological and genetics characteristics of Chinese patients with BRCA related breast cancer
Investigator(s):	Ng EKO
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2009
Completion Date:	10/2009

Abstract:

N/A

Project Title:	Novel and systemic identification of aberrant methylated DNA in plasma for breast cancer detection
Investigator(s):	Ng EKO, Kwong A
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2010

Abstract:

Purpose of the proposed project: To develop a panel of circulating tumor-derived methylated DNA markers in plasma for breast cancer detection. Key issues and problems being addressed: Breast cancer (BC) is one of the three most commonly diagnosed cancers among women, accounting for about 30% of patients [1]. Screenin g for breast cancer allowing early stage diagnosis of the malignancy and hence potential to reduce mortality. In the past decades, despite the dedication of research and resources to the development of biomarkers for diagnosis and prognosis, unpredictable response and development of resistance to adjuvant therapy remain major challenges in breast cancer management. Although mammography diagnosis for BC is the currently used non-invasive screening tool, the cost incurred and expertise required for mammogram has hampered wide application of this procedure. In addition, it has limited sensitivity in its use in young women and women with dense breasts. On the other hand, sensitivity of ultrasound screening is very operator dependent. Thus, there is still a pressing need to develop a cost-effective and accurate screening method for this cancer. Epigenetic changes, such as DNA methylation, are one of the most common molecular alterations in human cancer [2], in cluding breast cancer [3]. DNA methylation is the enzymatic addition of a methyl group to cytosines in CG dinucleotide DNA sequences (often at CpG-islands, CGI’s) without changing primary DNA sequences. Emerging studies have been shown that tumor-specific epigenetic alterations can be detected DNA from plasma or serum of patients with various malignancies [4-6]. It has been reported that breast cancer patients contained approximately 4 times more cell-free DNA in serum compared with that of healthy individuals [7]. Recent study has also shown that hypermethylation of RASSF1A and APC genes identified in serum DNA from breast cancer patients is associated with a worse outcome [8] and methylated RASSF1A DNA in serum potential biomarkers for monitoring the eff icacy of adjuvant therapy in breast cancer patients [6]. While these studies have shown promise, they all were performed by testing a single methylated DNA marker. The diagnostic sensitivity and specificity were thus limited. Recently, we developed a novel methodology to profile and quantify DNA methylation in plasma. In this project, we will embark on examining and analyzing methylated DNA profiling in plasma from breast cancer patients compared to normal control. Aberrant hyperm ethylated DNA identified will be validated in independent group of patients’ plasma. The DNA methylation profiling in plasma is expected to help identify more informative biomarkers for breast cancer detection. Work done by us: Previous studies by the PI and other collaborators overcame technical difficulties and developed a robust protocol for DNA and RNA extraction and quantification from plasma [9-13]. Recently, we have developed another protocol for miRNA extraction and quantification from plasma of colorectal cancer (CRC) patients [14]. In that study, we are the first to profile miRNAs from plasma. We also identified useful biomarkers in discrimin ating colorectal cancer from control subjects. Regarding DNA methylation study in cancer, PI and collaborators recently published a paper on this so that we did have experience in this field [15]. Co-investigator has been in breast surgical oncology field since 2000 and has been working on breast cancer genetics since 2005. She is the founder and director of Hong Kong Hereditary and High Risk Breast Cancer Programme and Hong Kong Hereditary Breast Cancer Family Registry since 2007. She has been principle investigator in over 20 clinical trials. Encouraged by the promising results from that study, we believe using methylated DNA as diagnostic markers could offer an effective and highly significant solution. References: 1. Parkin DM, Bray F, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108. 2. Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004 May 27;429(6990):457-63. 3. Widschwendter M, Jones PA. DNA methylation and breast carcinogenesis. Oncogene. 2002 Aug 12;21(35):5462-82. 4. Widschwendter A, Muller HM, Fiegl H, et al. DNA methylation in serum and tumors of cervical cancer patients. Clin Cancer Res. 2004 Jan 15;10(2):565-71. 5. Widschwendter M, Menon U. Circulating methylated DNA: a new generation of tumor markers. Clin Cancer Res. 2006 Dec 15;12(24):7205-8. 6. Fiegl H, Millinger S, Mueller-Holzner E, et al. Circul ating tumor-specific DNA: a marker for monitoring efficacy of adjuvant therapy in cancer patients. Cancer Res. 2005 Feb 15;65(4):1141-5. 7. Gal S, Fidler C, Lo YM, et al. Quantitation of circulating DNA in the serum of breast cancer patients by real-time PCR. Br J Cancer. 2004 Mar 22;90(6):1211-5. 8. Muller HM, Widschwendter A, Fiegl H, et al. DNA methylation in serum of breas t cancer patients: an independent prognostic marker. Cancer Res. 2003 Nov 15;63(22):7641-5. 9. Lo YM, Chan WY, Ng EK, et al. Circulating Epstein-Barr virus DNA in the serum of patients with gastric carcinoma. Clin Cancer Res. 2001 Jul;7(7):1856-9. 10. Ng EK, Tsui NB, Lam NY, et al. Presence of filterable and nonfilterable mRNA in the plasma of cancer patients and healthy individuals. Clin Chem. 2002 Aug;48(8):1212-7. 11. Ng EK, Tsui NB, Lau TK, et al. mRNA of placental origi n is readily detectable in maternal plasma. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4748-53. 12. Chiu RW, Chan LY, Lam NY, Tsui NB, Ng EK, et al. Quantitative analysis of circulating mitochondrial DNA in plasma. Clin Chem. 2003 May;49(5):719-26. 13. Chiu RW, Lui WB, El-Sheikhah A, et al. Comparison of protocols for extracting circulating DNA and RNA from maternal plasma. Clin Chem. 2005 Nov;51(11):2209-10. 14. Ng EK, Chong WW, Jin H, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut. 2009 Oct;58(10):1 375-81.

List of Research Outputs

Kwong A. , Wong L.P., Wong H.N. , Law F.B.F. , Ng E.K.O. , Tang Y.H., Chan W.K., Suen D.T.K. , Choi C., Ho L.S., Kwan K.H., Poon M., Wong T.T., Chan K., Chan S.W., Ying M.W., Chan W.C., Ma E.S., Ford J.M. and West D.W., Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer, Hugo Journal . 2010, 3(1-4): 63-76.

Kwong A. , Ng E.K.O. , Law F.B.F. , Wong L.P., To M.Y., Cheung M.T. , Wong H.N. , Chan V.W., Kurian A., West D.W. , Ford J.M. and Ma E.S., High-resolution melting analysis for rapid screening of BRCA2 founder mutations in Southern Chinese breast cancer patients, Breast Cancer Research and Treatment . 2010, 122(2): 605-607.

Kwong A. , Ng E.K.O. , Leung C.P.H. , Tsang W.P., Wong L.P. , Kwok T.T. and Ma E.S.K. , Role of miR-143 regulating DNA methyltransferases 3A in breast cancer, Ejc Supplements . 2010, 8(3): 172-173.

Ng E.K.O. , MicroRNAs in breast cancer: From scientist’s bench to patient’s bedside , The Chinese University of Hong Kong, Department of Chemical Pathology . 2010.

Ng E.K.O. , Leung C.P.H. , Au S., Chan A., Wong L.P. , Ma E.S.K. , Pang R.W.C. , Chua D.T.T. , Chu K.M. , Law W.L. , Poon R.T.P. and Kwong A. , Plasma microRNA as a potential marker for breast can cer detection, The 101st Annual Meeting of the American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Ng E.K.O. , Kwong A. , Tsang W.P., Leung C.P.H. , Wong L.P. , Kwok T.T. and Ma E.S.K. , Role of miR-143 regulating DNA methyltransferases 3A in breast cancer, Cancer Research . 2009, 69(24): 695S-695S.

Shin V.Y. , Jin H.C., Ng E.K.O. , Sung J.J., Chu K.M. and Cho C.H., Activation of 5-lipoxygenase is required for nicotine mediated epithelial-mesenchymal transition and tumor cell growth, Cancer Lett . 2010, 292(2): 237-245.

Tsang W.P., Ng E.K.O. , Ng S.S., Jin H., Yu J., Sung J.J. and Kwok T.T., Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer, Carcinogenesis . 2010, 31(3): 350-358.

Researcher : Ng KKC

List of Research Outputs

Chan A.C.Y. , Fan S.T. , Lo C.M. , Liu C.L. , Chan S.C. , Ng K.K.C. , Yong B.H. , Chiu A. and Lam B.K.Y. , Liver transplantation for acute-on-chronic liver failure, Hepatology International . 2009, 3(4): 571-581.

Chan K.L. , Fan S.T. , Lo C.M. , Wei W.I. , Ng W.M. , Chung H.Y., Ng K.K.C. , Chan S.C. , Chan K.W. , Tso W.K. , Tsoi N.S. and Tam P.K.H. , Pediatric liver transplantation in Hong Kong - a dom ain with scarce deceased donors, Journal of Pediatric Surgery . 2009, 44(12): 2316-2321.

Chan S.C. , Lo C.M. , Ng K.K.C. and Fan S.T. , Alleviating the burden of small-for-size graft in right liver living donor liver transplantation through accumulation of experience, American Journal of Transplantation . 2010, 10(4): 859-867.

Chan S.C. , Lo C.M. , Yong B.H. , Tsui W.J.C., Ng K.K.C. and Fan S.T. , Paired donor interchange to avoid ABO-incompatible living donor liver transplantation, Liver Transplantation . 2010, 16(4): 478-481.

Chan S.C. , Lo C.M. , Ng K.K.C. , Chok K.S.H. , Yong B.H. and Fan S.T. , Portal inflow and pressure changes in right liver living donor liver transplantation including middle hepatic vein (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New Yo rk, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S92.

Chan S.C. , Lo C.M. , Ng K.K.C. , Chok K.S.H. and Fan S.T. , Simplifying hepatic venous outflow reconstruction in sequential living donor liver transplantation, Liver Transplantation . 2009, 15(11): 1514-1518.

Chan S.C. , Lo C.M. , Wong Y. , Ng K.K.C. , Chok K.S.H. and Fan S.T. , Validating graft and standard liver size predictions in right liver living donor liver transplantation (Abstra ct), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S247.

Cheung T.T. , Ng K.K.C. , Poon R.T.P. , Chan S.C. , Lo C.M. and Fan S.T. , A case of laparoscopic hepatectomy for recurrent hepatocel lular carcinoma, World Journal of Gastroenterology . 2010, 16(4): 526-530.

Cheung T.T. , Ng K.K.C. , Chok K.S.H. , Chan S.C. , Poon R.T.P. , Lo C.M. and Fan S.T. , Combined resection and radiofrequency ablation for multifocal hepatocellular carcinoma: prognosis and outcomes, World Journal of Gastroenterology . 2010, 16(24): 3056-3062.

Cheung T.T. , Ng K.K.C. , Poon R.T.P. and Fan S.T. , Tolerance of radiofrequency ablation by patients of hepatocellular carcinoma, Journal of Hepato-biliary-pancreatic Surgery . 2009, 16(5): 655-660.

Chok K.S.H. , Ng K.K.C. , Cheung T.T. , Yuen W.K. , Poon R.T.P. , Lo C.M. and Fan S.T. , An update on long-term outcome of curative hepatic resection for hepatocholangiocarcinoma, World Journal of Surgery . 2009, 33(9): 1916-1921.

Chok K.S.H. , Lo C.M. , Ng K.K.C. and Chan S.C. , Patients with preoperative hepatorenal syndrome (HRS) have comparable long-term outcomes after live-donor liver transplantation (LDLT) (Abstract), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): S207.

Chok K.S.H. , Chu F.S.K. , Cheung T.T. , Lam V.W.T. , Yuen W.K. , Ng K.K.C. , Chan S.C. , Poon R.T.P. , Yeung C. , Lo C.M. and Fan S.T. , Results of percutaneous transhepatic cholecystostomy for high surgical risk patients with acute cholecystitis, ANZ Journal of Surgery . 2010, 80(4): 280-283.

Chung P.H.Y., Wong K.K.Y. , Tam P.K.H. , Chan K.L. , Ng K.K.C. , Chan S.C. , Hui T.W.C. , Yong B.H. , Fan S.T. and Lo C.M. , Split graft liver transplant for paediatric patients in Hong Kong, Hong Kong Journal of Paediatrics (New Series) . 2009, 14: 181-185.

Dai W.C., Ng K.K.C. , Chok K.S.H. , Cheung T.T. , Poon R.T.P. and Fan S.T. , Radiofrequency ablation for controlling iatrogenic splenic injury (Letter to the Editor), International Journal of Colorectal Diseases . 2010, 25(5): 667-668.

Ng K.K.C. , An update on the surgical management of hepatocellular carcinoma, The 16th Hong Kong International Cancer Congress 2009, Hong Kong, China . 2009.

Ng K.K.C. , Poon R.T.P. , Cheung T.T. , Chu F.S.K. , Tso W.K. and Fan S.T. , High efficacy of high intensity focused ultrasound without transarterial embolization for hepatocellular carcinoma (Poster Presentation), International Liver Cancer Association 3rd Annual Conference, Milan, Italy, 4 - 6 September 2009 .

Ng K.K.C. , Poon R.T.P. , Chok K.S.H. , Cheung T.T. , Tung H., Chu F.S.K. , Tso W.K. , Yu W.C. and Fan S.T. , High efficacy of high-intensity focused ultrasound without transarterial embolization for hepatocellular carcinoma - Hong Kong experience (Abstract), The 1st International Summit of Noninvasive Ultrasound Treatment, Chongqing, China, 22-23 October 2009 .

Ng K.K.C. , Laparoscopy-assisted gastrectomy for early gastric cancer is safe and effective in elderly patients (Commentary), Journal of Surgical Research . 2010, 158(1): 30-32.

Ng K.K.C. , Lo C.M. , Chan S.C. and Fan S.T. , Living donor liver transplantation for hepatocellular carcinoma across Milan criteria (Oral Presentation), International Surgical Week 2009, Adelaide, Austral ia, 6 - 10 September 2009 .

Ng K.K.C. , Living donor liver transplantation for hepatocellular carcinoma, Asia Transplantation & Immunology Forum 2009, Beijing, China . 2009.

Ng K.K.C. , Lo C.M. and Fan S.T. , Long-term survival analysis of living donor liver tran splantation for hepatocellular carcinoma across Milan criteria (Abstract), The 15th Annual International Congress of the Inte rnational Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S143.

Ng K.K.C. , Chan S.C. , Chok K.S.H. , Cheung T.T. , Chan A.C.Y. , Lo C.M. and Fan S.T. , Primary versus salvage liver transplantation for hepatocellul ar carcinoma within Milan criteria - a single center experience (Abstract and Poster Presentation), The 15th Annual International Congress of the Inter national Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S254.

Ng K.K.C. , Reviewer, Acta Haematologica . 2010.

Ng K.K.C. , Reviewer, American Journal of Transplantation . 2010.

Ng K.K.C. , Reviewer, Annals of Surgery . 2010.

Ng K.K.C. , Reviewer, Annals of Surgical Oncology . 2010.

Ng K.K.C. , Reviewer, Asian Journal of Surgery . 2010.

Ng K.K.C. , Reviewer, British Journal of Radiology . 2010.

Ng K.K.C. , Reviewer, British Journal of Surgery . 2010.

Ng K.K.C. , Reviewer, Cancer . 2010.

Ng K.K.C. , Reviewer, Cytokine . 2010.

Ng K.K.C. , Reviewer, Digestive Diseases and Sciences . 2010.

Ng K.K.C. , Reviewer, Digestive Surgery . 2010.

Ng K.K.C. , Reviewer, European Journal of Surgical Oncology . 2010.

Ng K.K.C. , Reviewer, European Surgical Research . 2010.

Ng K.K.C. , Reviewer, Hepatobiliary and Pancreatic Diseases International . 2010.

Ng K.K.C. , Reviewer, Hong Kong Medical Journal . 2010.

Ng K.K.C. , Reviewer, Journal of Gastroenterology . 2010.

Ng K.K.C. , Reviewer, Journal of Gastroenterology and Hepatology . 2010.

Ng K.K.C. , Reviewer, Journal of Surgical Research . 2010.

Ng K.K.C. , Reviewer, Lancet Oncology . 2010.

Ng K.K.C. , Reviewer, Liver Cancer Review Letters . 2010.

Ng K.K.C. , Reviewer, Liver International . 2009.

Ng K.K.C. , Reviewer, Liver Transplantation . 2009.

Ng K.K.C. , Reviewer, Surgical Laparoscopy, Endoscopy & Percutaneous Technique s . 2009.

Ng K.K.C. , Reviewer, Surgical Oncology . 2009.

Ng K.K.C. , Reviewer, Surgical Practice of The College of Surgeons of Hong Kong . 2009.

Ng K.K.C. , Reviewer, Urology . 2009.

Ng K.K.C. , Reviewer, World Journal of Surgery . 2009.

Sharr W.W. , Chok K.S.H. , Ng K.K.C. , Chan S.C. , Lo C.M. and Fan S.T. , Impact of donor age on right lobe living donor liver transplantation in a single centre (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New Yor k, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S92.

Yau T.C.C. , Yao T.J. , Chan P., Epstein R. , Ng K.K.C. , Chok K.S.H. , Cheung T.T. , Fan S.T. and Poon R.T.P. , The outcomes of elderly patients with hepatocellular carcinoma treated with transarterial chemoembolization, Cancer . 2009, 115(23): 5507-5515.

Researcher : Ng KO

Project Title:	Systemic identification of circulati ng tumor-derived microRNAs: Potential noninvasive diagnostic or prognostic biomarkers for breast cancer
Investigator(s):	Ng EKO, Kwong A
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	11/2008
Completion Date:	10/2009

Abstract:

Purpose of the proposed project To develop a panel of tumor-assoicated microRNA markers in plasma that can be used as a noninvasive diagnostic or prognostic biomarker for breast cancer.. Key issues and problems being addressed Breast cancer is one of the three most commonly diagnosed cancers among women, accounting for about 30% of patients [1]. Screening for breast cancer allowing early stage diagnosis of the malignancy and hence potential to reduce mortality. In the past decades, despite the dedication of research and resources to the development of biomarkers for diagnosis and prognosis, unpredictable response and development of resistance to adjuvant therapy remain major challenges in breast cancer management. Breast cancer patients have diverse pathologic and clinical features. Based on the previous molecular profiling, breast cancer could be divided into those with high expression of the estrogen receptor (ER) gene (luminal A and luminal B subtypes), and those that do not express ER. Recentl y, the emergence of microRNAs (miRNAs) as regulators of gene expression identifies as novel candidate diagnostic and prognostic indicators and therapeutic targets. MicroRNAs are 19-25-nucleotides regulatory non-protein-coding RNA molecules, playing important role in oncogenesis has open new opportunities of noninvasive test for early cancer diagnosis. Studies have shown that profi les of miRNA expression differ between normal tissue and tumor and vary among tumor types. Evidence suggests that miRNA expression profiles can cluster similar tumor types together more accurately than the expression profiles of protein-coding mRNA genes [2]. Importantly, expression of some miRNAs correlated with the molecular subtypes and with two major features of breast cancer (grade and ER status) [3]. More recently, several reports suggest that cell-free circulating miRNAs existed in serum and plasma [4-6]. Accordingly, it raises the possibility of using miRNAs as novel noninvasive molecular markers for cancer detection and prognosis. In the present study, we plan to evaluate the feasibility of using plasma miRNAs as a noninvasive diagnostic or prognostic biomarker for breast cancer. Work done by us Previous studies by the PI and other collaborators overcame technical difficulties and developed a robust protocol for RNA extraction and quantification from plasma [7, 8]. With the help of ultracentrifugation or filtration, we have also developed a unique and novel nucleic acids fractionation procedure for disease evaluation [7]. Recently, based on our previously developed protocol, we have developed another robust protocol for miRNA extraction and quantification from plasma of colorectal cancer (CRC) patients [9]. In that study , we used real-time qPCR-based array to profile miRNAs from plasma, corresponding colorectal tumor and adjacent normal tissues. We did demonstrate that miRNAs can be profiled and quantified in plasma. By comparing the miRNA profiles from different sample types, we have identified 5 miRNAs were up-regulated both in plasma and tissue samples. The plasma levels of these markers were significantly reduced after surgery. Further validation with 180 plasma samples including 90 CRC, 50 healthy controls, 20 gastric cancer and 20 inflammat ory bowel disease patients indicated that one of the 5 miRNAs alone provided the best markers for cancer diagnosis. That marker yielded a receiver operating characteristic curve area of 88.5%. At a cutoff of 240, the sensitivity was 89% and the specificity was 70% in discriminatin g colorectal cancer from control subjects. Encouraged by the promising results from that study, we believe that if plasma miRNAs are implicated in cancer then they may be useful as biomarkers or cancer indicators. Furthermore, miRNA markers have several advantages: (i) unlike screening for large number of mRNA expression that can add up to complexity on a systems biology scale, a modest number of miRNAs might be sufficient to differentiate cancers from normal. In our previous study, profiling of 95 miRNAs is possible to identify at least two miRNA markers for discriminating CRC; and (ii) unlike plasma mRNAs, miRNAs in plasma remain largely intact because of their size and so are more stable for detection. Accordingly, we believe using miRNAs as diagnostic markers could offer an effective and highly significant solution.

Project Title:	Differential expression of tumor-der ived exosomal microRNAs from the plasma of breast cancer patients: A potential biomarker for breast cancer screening
Investigator(s):	Ng EKO, Kwong A, Suen DTK
Department:	Surgery
Source(s) of Funding:	The Hong Kong Anti-Cancer Society (HKACS) - General Award
Start Date:	10/2009

Abstract:

Breast cancer is one of the three most commonly diagnosed cancers among women, accounting for about 30% of patients. Screening for breast cancer allowing early stage diagnosis of the malignancy and hence pote ntial to reduce mortality. In the past decades, despite the dedication of research and resources to the development of biomarkers for diagnosis and prognosis, unpredictable response and development of resistance to adjuvant therapy remain major challenges in breast cancer manageme nt. Breast cancer patients have diverse pathologic and clinical features. The role of serum tumor markers is also less well established. The most widely used serum markers in breast cancer are CA 15-3 and carcinoembryonic antigen. Less widely used markers include CA 27.29, tissue polypeptide antigen and the shed form of HER-2. Those serum markers have been used to monitor treatmen t response in patients with metastatic breast cancer. Despite the frequent use of such markers, they lack high sensitivity and specificity for breast cancer progression. The prognostic significance of these markers remains indeterminate because of the conflicting outcome of many clinical trials. Therefore, none of the available markers is of value for the detection of early breast cancer. Based on the previous molecular profiling, breast cancer could be divided into those with high expression of the estrogen receptor (ER) gene (luminal A and luminal B subtypes), and those that do not express ER. Recently, the emergence of small non-protein-coding RNAs, so-called microRNAs (miRNAs), playing important roles in oncogenesis has opened new opportunities for early cancer diagnosis. MiRNAs are 19-25-ucleotides regulatory non-coding RNA molecules that regulate th e expressions of a wide variety of genes by sequence-specific base pairing on the 3’ untranslated regions of the target mRNA resulting in mRNA degradation or inhibition of translation. Evidence suggests that miRNA expression profiles can cluster similar tumor types together more accurately than the expression profiles of protein-c oding mRNA genes. Furthermore, miRNA expression signatures have been used to predict prognosis. Importantly, expression of some miRNAs correlated with the molecular subtypes and with two major features of breast cancer (grade and ER status). Recently, several reports suggest that circulating miRNAs are stable and detectable in serum/plasma and the levels of some miRNAs specifically elevated in the patients with lung cancer, prostate cancer, ovarian cancer, and colorectal cancer. These findings suggest that blood-based miRNAs could emerge as revolutionary sources of biomarker for breast cancer diagnosis. On the other hand, exosomes are small (50–90 nm) membrane vesicles of endocytic origin that are released into the extracellular environment such as blood circulation. Many cells have the capacity to release exosomes, including dendritic cells, B cells, T cells, mast cells, epitheli al cells and tumor cells. Recent study demonstrated that released exosomes contain a subset of both cellular mRNA and microRNA, which could be a useful source of biomarkers for cancer detection. More Recently, study showed that circulating exosomal miRNAs signatures could be useful for diagnosis of ovarian cancer. While the primary source of circulating exosomes in cancer patients is the tumor, other normal cells within the peripheral circulation can contribute to the level exosome population. To isolate circulating exosomes of tumor origin, adherence to specific magnetic beads is utilized. A limited number of markers are used fo r the isolation (ie, cell surface antigens) of circulating exosomes. These markers include epithelial cell surface markers, such as the epithelial cell adhesion molecule (EpCAM), cytokeratins 7, 8, 18, 19, and 20 for breast carcinoma. In this proposed study, we have developed a protocol for isolation of tumor-derived exosomes from plasma samples by bounding to anti-EpCAM antibodie s coupled to microscopic iron beads. With the help of the circulating tumor-derived exosome isolated, we will perform miRNA profiling on 10 breast cancer patients and 10 normal subjects. Differential expression signatures will be identified. Then putative miRNA biomarkers identified will be verified on plasma samples from the breast cancer patients before and after 14 days after surgery. If the putative biomarkers are really derived from tumors, we would expect that those plasma miRNA levels are completely or significantly reduced in the post-operative samples as compared to pre-operative samples. Finally, we will validate those markers on an independent set of plasma samples. Multivariate logistic regression analysis will be used to determine the best combination of the putative biomarkers to obtain the best prediction of breast cancer. Sensitivity, specificity and predictive cutoff value of our developed diagnostic test will be calculated based on this large-scale validation study. Encouraged by the promising results from our previous study, we believe that if circulating exosomal miRNAs are implicated in cancer then they may be useful as biomarkers or cancer indicators. Further more, miRNA markers have several advantages: (i) unlike screening for large number of mRNA expression that can add up to complexity on a systems biology scale, a modest number of miRNAs might be sufficient to differentiate cancers from normal. In our previous study, profiling of 95 miRNAs is possible to identify at least two miRNA markers for discriminating CRC; and (ii) unlike plasma mRNAs, miRNAs in plasma remain largely intact because of their size and so are more stable for detection. Accordingly, we believe using miRNAs as diagnostic markers could offer an effective and highly significant solution. The long-term goal of this study is to develop rapid, accurate and reliable assays for early breast cancer diagnosis and prognosis by simply analyzing the blood from patients. Our main aims are: (i) To identify aberrant miRNA expression patterns in the plasma of patients with breast cancers. (ii) To develop a blood-based quantitative assay with a panel of miRNAs which are obtained from aim (i). (iii) To evaluate those miRNA biomarkers on large number of patient samples so as to determine the potential usefulness in early breast cancer diagnosis and the monitoring of disease progress.

Project Title:	Third International Symposium on Hereditary Breast and Ovarian Cancer Clinical, pathological and genetics characteristics of Chinese patients with BRCA related breast cancer
Investigator(s):	Ng EKO
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2009
Completion Date:	10/2009

Abstract:

N/A

Project Title:	Novel and systemic identification of aberrant methylated DNA in plasma for breast cancer detection
Investigator(s):	Ng EKO, Kwong A
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2010

Abstract:

Purpose of the proposed project: To develop a panel of circulating tumor-derived methylated DNA markers in plasma for breast cancer detection. Key issues and problems being addressed: Breast cancer (BC) is one of the three most commonly diagnosed cancers among women, accounting for about 30% of patients [1]. Scr eening for breast cancer allowing early stage diagnosis of the malignancy and hence potential to reduce mortality. In the past decades, despite the dedication of research and resources to the development of biomarkers for diagnosis and prognosis, unpredictable response and development of resistance to adjuvant therapy remain major challenges in breast cancer management. Although mammography diagnosis for BC is the currently used non-invasive screening tool, the cost incurred and expertise required for mammogram has hampered wide application of this procedure. In addition, it has limited sensitivity in its use in young women and wo men with dense breasts. On the other hand, sensitivity of ultrasound screening is very operator dependent. Thus, there is still a pressing need to develop a cost-effective and accurate screening method for this cancer. Epigenetic changes, such as DNA methylation, are one of the most common molecular alterations in human cancer [2], including breast cancer [3]. DNA methylation is the enzymatic addition of a methyl group to cytosines in CG dinucleotide DNA sequences (often at CpG-islands, CGI’s) without changing primary DNA sequences. Emerging studies have been shown that tumor-specific epigenetic alterations can be detected DNA from plasma or serum of patients with various malignancies [4-6]. It has been reported that breast cancer patients contained approximately 4 times more cell-free DNA in serum compared with that of healthy individuals [7]. Recent study has also shown that hypermethylation of RASSF1A and APC genes identified in serum DNA from breast cancer patients is associat ed with a worse outcome [8] and methylated RASSF1A DNA in serum potential biomarkers for monitoring the efficacy of adjuvant therapy in breast cancer patients [6]. While these studies have shown promise, they all were performed by testing a single methylated DNA marker. The diagnostic sensitivity and specificity were thus limited. Recently, we developed a novel methodology to profile and quantify DNA methylation in plasma. In this project, we will embark on examining and analyzing methylated DNA profiling in plasma from breast cancer patients compared to normal control. Aberrant hypermethylated DNA identified will be validated in independent group of patients’ plasma. The DNA methylation profiling in plasma is expected to help identify more informative biomarkers for breast cancer detection. Work done by us: Previous studies by the PI and other collaborators overcame technical difficulties and developed a robust protocol for DNA and RNA extraction and quantification from plasma [9-13]. Recently, we have developed another protocol for miRNA extraction and quantification from plasma of colorectal cancer (CRC) patients [14]. In that study, we are the first to profile miRNAs from plasma. We also identified useful biomarkers in disc riminating colorectal cancer from control subjects. Regarding DNA methylation study in cancer, PI and collaborators recently published a paper on this so that we did have experience in this field [15]. Co-investigator has been in breast surgical oncology field since 2000 and has been working on breast cancer genetics since 2005. She is the founder and director of Hong Kong Heredit ary and High Risk Breast Cancer Programme and Hong Kong Hereditary Breast Cancer Family Registry since 2007. She has been principle investigator in over 20 clinical trials. Encouraged by the promising results from that study, we believe using methylated DNA as diagnostic markers could offer an effective and highly significant solution. References: 1. Parkin DM, Bray F, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108. 2. Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004 May 27;429(6990):457-63. 3. Widschwendter M, Jones PA. DNA methylation and breast carcinogenesis. Oncogene. 2002 Aug 12;21(35):5462-82. 4. Widschwendter A, Muller HM, Fiegl H, et al. DNA methylation in serum and tumors of cervical cancer patients. Clin Cancer Res. 2004 Jan 15;10(2):565-71. 5. Widschwendter M, Menon U. Circulating methylated DNA: a new generation of tumor markers. Clin Cancer Res. 2006 Dec 15;12(24):7205-8. 6. Fiegl H, Millinger S, Mueller-Holzner E, et al. Circulating tumor-specific DNA: a marker for monitoring efficacy of adjuvant therapy in cancer patients. Cancer Res. 2005 Feb 15;65(4):1141-5. 7. Gal S, Fidler C, Lo YM, et al. Quantitation of circulating DNA in the serum of breast cancer patients by real-time PCR. Br J Cancer. 2004 Mar 22;90(6):1211-5. 8. Muller HM, Widschwendter A, Fiegl H, et al. DNA methylation in serum of breast cancer patients: an independent prognostic marker. Cancer Res. 2003 Nov 15;63(22):7641-5. 9. Lo YM, Chan WY, Ng EK, et al. Circulating Epstein-Barr virus DNA in the serum of patients with gastric carcinoma. Clin Cancer Res. 2001 Jul;7(7):1856-9. 10. Ng EK, Tsui NB, Lam NY, et al. Presence of filterable and nonfilterable mRNA in the plasma of cancer patients and healthy individuals. Clin Chem. 2002 Aug;48(8):1212-7. 11. Ng EK, Tsui NB, Lau TK, et al. mRNA of placental origin is readily detectable in maternal plasma. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4748-53. 12. Chiu RW, Chan LY, Lam NY, Tsui NB, Ng EK, et al. Quantitative analysis of circulating mitochondrial DNA in plasma. Clin Chem. 2003 May;49(5):719-26. 13. Chiu RW, Lui WB, El-Sheikhah A, et al. Comparison of protocols for extracting circulating DNA and RNA from maternal pla sma. Clin Chem. 2005 Nov;51(11):2209-10. 14. Ng EK, Chong WW, Jin H, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut. 2009 Oct;58( 10):1375-81.

List of Research Outputs

Li J., Ng K.O. , Ng Y.P., Wong C.Y., Yu J., Jin H., Cheng V.Y., Go M.Y., Cheung P.K., Ebert M.P., Tong J., To K.F., Chan F.K., Sung J.J., Ip N.Y. and Leung W.K., Identification of retinoic acid-regulated nuclear matr ix-associated protein as a novel regulator of gastric cancer, Br J Cancer . 2009, 101(4): 691-8.

Liu X., Lam E.K., Wang X., Zhang J., Cheng Y.Y. , Lam Y.W., Ng K.O. , Yu J., Chan F.K., Jin H. and Sung J.J., Promoter Hypermethylation Mediates Downregulation of Thiamine Receptor SLC19A3 in Gastric Cancer, Tumour Biol . 2009, 30(5): 242-248.

Lung R.W., Tong J.H., Sung Y.M., Leung P.S., Ng D.C., Chau S.L., Chan A.W., Ng K.O. , Lo K.W. and To K.F., Modulation of LMP2A expression by a newly identified Epstein-Barr virus-encoded microRNA miR-BART22, Neoplasia . 2009, 11(11): 1174-84.

Ng K.O. , Wong C.L.P., Ma E.S.K. and Kwong A. , Micro RNAS as new players for diagnosis, prognosis, and therapeutic targets in breast cancer, Journal of Oncology . 2009, 2009: 305420.

Ng K.O. , Tsang W.P., Ng S.S., Jin H.C., Yu J., Li J.J., Rocken C., Ebert M.P., Kwok T.T. and Sung J.J., MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer, Br J Cancer . 2009, 101(4): 699-706.

Researcher : Ng MW

List of Research Outputs

Wang X. , Cheung C.K.Y. , Ng M.W. and Lo C.M. , Hematopoietic chimerism and potential hematopoietic stem cells in liver transplantation (Abstract), The 8th International Society for Stem Cell Research Annual Meeting, San Francisco, U.S.A., June 2010 .

Researcher : Ng NP

List of Research Outputs

Lau C.K. , Yang Z. , Ho D.W.Y. , Ng N.P. , Poon R.T.P. and Fan S.T. , Discruption of Akt/hif1 signaling can enhance the thera peutic efficacy of ischemic hypoxia and chemotherapy, The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Yang Z. , Fan S.T. , Ho D.W.Y. , Yu W.C. , Lau C.K. , Ng N.P. and Lam C.Y. , Liver cancer stem cells and HCC recurrence (Oral Presentation), The International Liver Cancer Association Third Annual Congress, Milan, Italy, 4 - 6 September 2009 .

Researcher : Ng TP

Project Title:	Functional and mechanistic characterizations of homeoprotein Six1 in hepatocellular carcinoma
Investigator(s):	Ng TP, Man K
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	01/2010

Abstract:

Purpose of the project We aim to investigate the role of homeoprotein Six1 in carcinogenesis and metastasis in hepatocellular carcinoma and explore the regulation mechanism of Six1 in hepatocellular carcinoma. Key issues and problems Hepatocellular carcinoma (HCC) is one of the most malignant tumors in the world, causin g more than 600 000 deaths per year. Increasing prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and underlying liver cirrhosis lead to increasing propensity of hepatocarcinogenesis. The heterogenic nature, drug resistant genius and continuous mutations of HCC hinder the possibility of elimination of HCC. In fact, most of HCC patients diagnosed with advanced stage. Surgical treatments in terms of hepatic resection and orthotopic liver transplantation are frontline treatments for HCC, but the long-term disease-free survival remains unsatisfactory. Tumor recurrence and metastases are the major causes of death in HCC patients after surgical treatments, indicating the necessity of developing new therapeutic strategies targeting at tumor recurrenc e and metastases in HCC. Up to now, the molecular mechanisms of HCC metastasis remain unclear; hence continuous identification and characterization of novel metastasis-associated genes are indispensable for development of effective treatment of HCC patients.

List of Research Outputs

Cheng Q. , Ng T.P. , Fan S.T. , Lim Z.X.H. , Guo D. , Liu X. , Liu Y. , Poon R.T.P. , Lo C.M. and Man K. , Distinct mechanism of small-for-size fatty liver graft injury--Wnt4 signaling activates hepatic stellate cells, American Journal of Transplantation . 2010, 10(5): 1178-1188.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Abstract), The 16th Annual International Congress of the Internationa l Liver Transplantation Society, Hong Kong, 16 - 19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the Internat ional Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Li X.C., Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplanta tion . 2010, 16(6): s141.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s96.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobiliz ed circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s72.

Liu X. , Lo C.M. , Cheng Q. , Liu Y. , Ng T.P. , Fan S.T. and Man K. , Epithelial to mesenchymal transition in development of liver fibrosis in small-for-size fatty liver graft (Rising Star Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft - the significance of aldose reductase signaling on oval cell activation (Travel Award), The 15th Annual International Congress of the Int ernational Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009 . 2009.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft – the significance of aldose reducatase signaling on oval cell activation (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York, U.S.A., 8-1 1 July 2009. Liver Transplantation . 2009, 15:S72: #O6.

Man K. , Ng T.P. , Liu X. , Yeung W.H. , Lo C.M. and Fan S.T. , Inflammatory microenvironment accelerates liver tumo r growth and metastasis by mobilizing circulating endothelial progenitor cells and increasing cancer stem like cell populations (Abstract), The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Man K. , Cheng Q. , Liu Y. , Lam T.T. , Ng T.P. and Lo C.M. , Inflammatory microenvironment accelerates liver tumor growth and metastasis by mobilizing circulating endothe lial progenitor cells and increasing cancer stem like cell populations (Abstract), The 15th Annual International Congress of the International Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7 Suppl 1): S97.

Man K. , Shih K.C. , Ng T.P. , Xiao J. , Guo D. , Sun K.W. , Lim Z.X.H. , Cheng Q. , Liu Y. , Fan S.T. and Lo C.M. , Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts, Annals of Surgery . 2010, 251(6): 1154-1161.

Man K. , Ng T.P. , Xu A. , Cheng Q. , Lo C.M. , Xiao J. , Sun B. , Lim Z.X.H. , Cheung J.S., Wu E.X. , Sun K.W. , Poon R.T.P. and Fan S.T. , Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling, Clinical Cancer Research . 2010, 16(3): 967-977.

Man K. , Shao Y. , Ng T.P. , Li C. , Fan S.T. and Lo C.M. , The significance of acute-phase small-for-size liver graft injury in mobilization of circulating EPCS/MDSCS/TREGS after LDLT for HCC patients (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16 - 19 June 2010. Liver Transplantation . 2010, 16(6): s191.

Ng T.P. and Man K. , Hepatocellular carcinoma: overexpression of hemeoprotein six1 as a marker for predicting survival, In: Hayat, M.A. (ed), Methods of Cancer Diagnosis, Therapy and Prognosis (Volume 5: Liver Cancer) . Netherlands, Springer, 2010, 5: 313-324.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , Identification of circulating protein markers related to tumor recurrence after liver transplantation (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s207.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantatio n . 2010, 16(6): s77.

Ng T.P. , Lo C.M. , Liu X. , Geng W. , Ling C. , Li C. , Fan S.T. and Man K. , MicroRNA signatures associated with acute phase small-for size liver graft injury and tumor invasiveness (Young Investigator Award), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010 . 2010.

Researcher : Ng WM

List of Research Outputs

Chan K.L. , Fan S.T. , Lo C.M. , Wei W.I. , Ng W.M. , Chung H.Y., Ng K.K.C. , Chan S.C. , Chan K.W. , Tso W.K. , Tsoi N.S. and Tam P.K.H. , Pediatric liver transplantation in Hong Kong - a domain with scarce deceased donors, Journal of Pediatric Surgery . 2009, 44(12): 2316-2321.

Ho K.L. , Tsu J.H.L. , Ng W.M. , Law W.L. , Tam P.C. and Lo B.S.H. , Rectourethral fistula after radical prostatecomy: transperineal repair in jack-knife position, Surgical Practice . Hong Kong, College of Surgeons of Hong Kong, 2010, 14: 102-104.

Wong B.Y.H. , Ng W.M. , Yuen P.W. , Chan J.P.H. , Ho W.K. and Wei W.I. , Early resection and reconstruction of head and neck masses in infants with upper airway obstruction, International Journal of Pediatric Otorhinolaryngology . 2010, 74: 287-291.

Wong S.T.S. , Ho W.K. , Chan Y.W. , Ng W.M. and Wei W.I. , Mature miR-184 and squamous cell carcinoma of tongue, Head and Neck . 2009, 9: 130-132.

Researcher : Ngan ESW

Project Title:	Thyroid transcription factor-1 (TTF-1), a potential susceptibility gene for familial papillary thyroid carcinoma
Investigator(s):	Ngan ESW, Garcia-Barcelo MM, Khoo US, Lang BHH, Tam PKH
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2009

Abstract:

(1) To assess the implication of TTF-1 mutations in the familial PTC by a) identifying the prevalence of TTF-1 germ-line mutations in familial PTC patients and their kindreds; b) obtaining a complete profile on the somatic genetic alterations in patients bearing TTF-1 mutations; (2) To investigate the biological consequences of the mutations to disease predisposition by a) characterizing the impacts of the mutations on transactivation activity of TTF-1; b) delineating the biological implications of TTF-1 mutants in tumorigenesis.

Project Title:	Prokineticin signaling in Neuroblastoma stem cell
Investigator(s):	Ngan ESW
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2009

Abstract:

Purpose of the proposed investigation The purpose of this study is to elucidate how Prokineticin signaling modulates the behavior of the neuroblastoma (NB) cancer stem cell (CSC)/tumor initiating cell (TIC) population, and influences progression and drug resistance of these tumors. Our previous study showed that aberrant Prokineticin signaling is implicated in NB progression. Here, we hypothesize that Prokineticin(s) expands the malignant NB CSC/TIC population, and promotes tumor progression and development of resistance to chemotherapeutic agents. Objectives 1) To investigate whether Prokineticin signaling promotes tumor progression by increasing the size of the CSC/TIC subpopulation(s) 2) To elucidate the molecular basis of Prokineticin mediated tumor progression Key issues and problems being addressed Neuroblastoma (NB) is the most common pediatric solid tumor and accounts for 7 percent of all childhood but 15 percent of childhood cancer deaths. A peculiar feature of this tumor is that tumors found in infants very frequently regress spontaneously while those in children over one year of age are very aggressive and relentless. Emerging evidence suggests that NB comprises heterogeneous populations of improperly differentiated neural crest cells and a small subset of NB cells behaves as stem cells. These NB stem cells may represent the cancer stem cells (CSCs)/tumor initiating cells (TICs) of the tumor and contribute to the enigmatic and paradoxical clinical outcomes of the tumors. Commitment of CSCs/TICs to the fibromuscular lineage may give a favorable outcome, while to the neuronal lineage results in a malignant tumor progression. Therefore, identification of the molecular determinants of CSC/TIC may suggest new targets for development of more effective and specific therapeutic agents. Nevertheless, the molecular mechanisms under lying the maintenance of CSCs/TICs and their progression to the malignant neurogenic lineage in NB are still poorly understood. We have previously reported a novel role for Prokineticin signaling in the growth and differentiation of NCCs. Later, our data also indicated that overexpression of Prokineticin receptors is associated with the malignancy of NB. Furthermore, we showed that Prokineticins promote NB progression by stimulating the proliferation and migration of NB cells. However, how aberrant Prokineticin signaling favors NB development remains unknown. Intriguingly, while these data indicate that Prokineticin promotes NCC and NB cell proliferation, we have also shown that Prokineticin is a modifier for RET/Glial cell line-derived neurotrophic factor (GDNF) signaling during neuronal differentiation of NCCs. Together, these observations raise the interesting possibility that Prokineticin signaling might play a dual role in NB progression, i.e. stimulating the growth of drug-resistant CSCs/TICs as well as promoting the differentiation of highly malignant neuroblast. Given the clinical relevance of cancer stem cells in tumor progression and the deve lopment of drug-resistance, much effort has been focused on the identification of the growth factors for CSCs/TICs. Thus, precise examination of functional implications of Prokineticin signaling in NB stem cells is warranted.

Project Title:	Small molecule inhibitors for use in the treatments for thyroid diseases
Investigator(s):	Ngan ESW, Chiu P, Garcia-Barcelo MM, Lang BHH, Wong KKY, Tam PKH, Vanhoutte PMGR
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Applied Research
Start Date:	06/2009
Completion Date:	06/2010

Abstract:

Background: Thyroid nodules and cancer About 200 million people in the world have some form of thyroid disease. In fact, thyroid nodule, a thyroid lump or an enlargement of the thyroid known as goiter, is the most common endocrine problem. It is estimated that 4-8% of adult women and 1-2% of adult men have thyroid nodules that can be felt on physical examination, bu t closer to 30% of women have nodules detectable by ultrasound. Although the majority of thyroid nodules are benign (not cancerous), about 10% of nodules do contain cancer. Goiter can develop into thyroid cancer More importantly, it is know that about 11-14% of goiter patients eventually develop thyroid cancer. It suggests a possible progression from benign thyroid lesions (non-cancerous mass) to malignant disease (cancer) [1-6]. Thyroid cancer cases on the rise in Hong Kong Thyroid cancer is the seventh most common cancer for female in Hong Kong, and there are about 500 new cases each year. Approximately 80% of all primary thyroid cancers consist of papillary thyroid carcinoma (PTC) [7]. Females are more likely to have thyroid cancer than male at a ratio of three to one [8]. In fact, there is a three to four fold increase in new thyroid cancer cases over the past 20 years, with the figure increased from 167 in 1983 to 539 in 2006 (www3.ha.org.hk/cancereg/e_stat.asp). PTC can occur in any age group, although it is most common after the age of 30 and its aggressiveness increases significantly in older patients. DNA testing assesses the risk for hereditary goiter and thyroid cancer In addition, about 6% to 10% of PTC are inherited, these patients have one or more first-degree relatives wit h PTC and/or goiter, and the inherited PTC is usually more aggressive [9-11]. Recently, we have identified a germline mutation of a gene called “thyroid transcription factor-1” (TTF-1) which predisposes goiter patients to development thyroid cancer. This mutation is one base pair DNA alternation which causes one amino acid change and alters the function of the protein it produc es[12]. This mutation was found in 20% (4/20) of thyroid cancer patients with history of goiter (PTC/MNG). The patients with this mutation developed substantially more advanced tumors than MNG/PTC or PTC patients without the mutat ion. Notably, this germline mutation was dominantly inherited in two families, and all members who bear this mutation were affected with MNG, associated with either PTC or colon cancer. In addition, the mutation was not found among the 349 healthy control subjects nor among the 284 PTC patients who had no history of MNG [12]. These findings suggest that it is possible to assess the risk for hereditary goiter/thyroid cancer by DNA testing, in particular, using our newly identified mutation as the molecular marker. STAT3 and Akt are the therapeutic targets for the goiter/PTC Activations of STAT3 and Akt have been shown to promote cell proliferation in many cancer cells [13] and implicated in the devel opment of several different subtypes of thyroid cancers including PTC [14-17]. More importantly, we also demonstrated that both STAT3 and Akt signaling are the key pathways for the uncontrolled cell proliferation of thyroid cells [12], suggesting that activations of these cell proliferation and survival pathways may contribute to the development of goiter and/or their progression to thyroid tumors. Therefore, STAT3 and Akt signals are the potential therapeutic targets for the treatment for goiter and/or PTC, and for the development of the preventive medicine for the high-risk goiter patients to prevent the progression from goiter to thyroid cancer. Key issues and problems being addressed Thyroid diseases for the most part are treatable; however, it is difficult to diagnose in the sometimes slowly developing initial phases, in particular, determining the malignant potential of goiter. Until recently, our group has identified the first germline DNA mutation which could be used as a prognostic marker for the development of goiter and the progression from goiter to thyroid cancer. This finding makes the early or even preventive treatment become feasible. In addition, we have also identified the key signaling pathways implicated in the disease development and it paved a way for the development of a new drug with maximal efficacy and minimal side effects. Currently, the radioactiv e iodine is the most commonly used medication for the thyroid cancer treatment, but it possesses the major drawback of its non-specificity and it kills all the cells picking up iodine. Thus, it is not suitable for being used as a preventive treatment. Taking the advantage of a unique characteristic of thyroid of a strong potency to pickup iodine and the fact that STAT3 and Akt are implicated in goiter and thyroid cancer development, we propose to generate a new small molecule inhibitor of STAT3/Akt tagged with iodine. With this modification, the small molecule will be largely picked up by the thyroid and specifically targeting the “bad” signaling of the thyroid cells to minimize the side effect. Given that the data from this study will allow us to assess the use of iodine for the development of the drug delivery system for thyroid diseases, precise evaluation of the use of this thyroid specific small molecular is warranted. Purpose of the proposed investigation The purpose of this study is to develop a new small molecule inhibitor of STAT3 which will be specifically picked-up by the thyroid for use in the treatments for goiter and/or thyroid cancer. Here, we propose to make use of iodine for the thyroid delivery. A small molecule inhibitor of STAT3 will be modified by adding an iodine-tag, the efficiency of being taken up by the thyroid cells and its inhibitory effect to STAT3 will be assessed in this study. Establishment of this delivery method would be useful for the development of drugs not only for thyroid cancer, but also for the preventive treatments for other thyroid diseases. Objectives 1. To generate the small molecule inhibitors of STAT3 tagged with iodine. 2. To evaluate the efficiency of drug uptake by thyroid and other non-thyroid cells. 3. To validate effectiveness of the compound on STAT3 inhibition and establish the ED50 and LD50 of the compound.

Project Title:	7th Annual Meeting of the Intern ational Society for Stem Cell Research Prokineticin signaling in the c-kit expressing neuroblastoma cells
Investigator(s):	Ngan ESW
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	07/2009
Completion Date:	07/2009

Abstract:

N/A

Project Title:	Prokineticin signaling in neuroblastom a
Investigator(s):	Ngan ESW, Chan GCF, Tam PKH
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2010

Abstract:

1) To investigate whether Prokineticin signaling promotes tumor progression by increasing the size of the CSC/TIC subpopulation(s); 2) To elucidate the molecular basis of Prokineticin mediated tumor progression.

Project Title:	Implication of Hedgehog signaling in premature gliogenesis of neural crest cells
Investigator(s):	Ngan ESW
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2010

Abstract:

During enteric nervous system (ENS) development, sequential waves of neurogenesis and gliogenesis require an appropriate balance between the proliferation and differentiation of enteric neural crest cells (NCCs) and their progenies. Imbalance of these processes may result in an absence of enteric ganglia, as seen in HSCR in humans. However, it is unclear how the pool sizes of these neuronal and glial precursor cells are regulated. Furthermore, whether a premature switch from neurogenesis to gliogenesis will lead to HSCR and whether genetic pathways controlling proliferation and differentiation of NCCs may contribute to HSCR susceptibility are not known. We have previously reported Shh maintains the enteric progenitor pool by promoting proliferation and inhibiting neuronal differentiation of enteric NCCs. More recently, our genome-wide association study on HSCR demonstrated that the neuregulin-1 gene (NRG1), which modulates gliogenesis, is a susceptibility gene for HSCR disease. Thus, it is conceivable that improper glial cell differ entiation during ENS development may lead to HSCR disease. Intriguingly, epistasis analysis of the SNPs in the SHH and NOTCH signaling pathway genes showed a prominent genetic interaction between these two pathways. Our data ind icate that specific allelic distribution of SNPs in these genes in HSCR patients may contribute to disease development. Importantly, our functional studies also showed that a constitutive activation of hedgehog by conditional knockout of Ptch in enteric NCCs results in intestinal hypoganglionosis in the mutant mice. In vitro study further illustrated that Shh induces an irreversible gliogenesis of enteric NCCs by activating the Notch pathway. Together, these observations raise the interesting possibility that Shh, through activation of the Notch pathway, is playing a central role in ENS development by balancing the proliferation of enteric NCCs, and their neuronal and glial differentiation. Therefore, aberrant Shh signal may cause incomplete neurogenesis , leading to the reduction of ganglion cells in mature bowel as seen in HSCR disease. Nevertheless, the coordination mechanism between the Shh and Notch pathways in ENS development has not yet been fully elucidated. Given that a significant progress has been made recently in the isolation of enteric precursor cells, understanding their fate determining factors would facilitate the establishment of an effective strategy for autologous transplantation in the treatment of HSCR. Thus, precise examination of functional implications of Shh-Notch signaling in NCC proliferation and differentiation is warranted. The purposes of this study are to elucidate (i) how Sonic hedgehog (Shh) signaling modulates the behavior of the neural crest cells (NCCs) and their progenies; (ii) its implication in Hirschsprung (HSCR ) disease development; as well as (iii) to establish an effective cell-based therapy for HSCR. Our previous study showed that Shh is an essential trophic factor mediating the proliferation and neuronal differentiation of NCCs to maintain the enteric progenitor pool. Preliminary data from a genome-wide association study on HSCR dem onstrated a genetic association exists between SHH and NOTCH, implicating functional interaction of these two pathways in disease development. Importantly, we also found that Shh activates the Notch pathway and induces premature glial differentiation of NCCs. Thus, we hypothesize that (i) aberrant Shh-Notch signaling may contribute to HSCR disease by causing pre-mature or improper gliogenesis; (ii) Shh-Notch could be used for improving glial differentiatio n of transplanted progenitors in the diseased bowel. Objectives 1. To decipher how aberrant Shh-Notch pathway causes pre-mat ure glial differentiation of enteric NCCs 2. To determine the capacity of Shh-Notch to induce glial differentiation in the diseased environment for assessing their therapeutic potential as an effective transplant strategy for HS CR

List of Research Outputs

Garcia-Barcelo M.M. , Yeung M.Y. , Miao X.P., Tang S.M. , Chen G., So M.T. , Ngan E.S.W. , Lui V.C.H. , Chen Y. , Liu X. , Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y. , Chan D. , Cheung K.M.C. , Chung P.H.Y., Wong K.K.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Genome-wide association study identifies a susceptibili ty locus for biliary atresia on 10q24.2, Human Molecular Genetics . 2010, 19 (14): 2917-2925.

Garcia-Barcelo M.M. , Lui V.C.H. , So M.T. , Miao X. , Leon Y.Y. , Yuan Z.W., Ngan E.S.W. , Ehsan T., Chung P.H.Y., Khong P.L. , Wong K.K.Y. and Tam P.K.H. , MNX1 (HLXB9) mutations in Currarino patients, Journal of Pediatric Surgery . 2009, 44(10): 1892-1898.

Leon Y.Y. , Ngan E.S.W. , Poon H.C. , So M.T. , Lui V.C.H. , Tam P.K.H. and Garcia-Barcelo M.M. , Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3, Journal of Pediatric Surgery . 2009, 44(10): 1904-1912.

Miao X. , Garcia-Barcelo M.M. , So M.T. , Tang W.K. , Xiao D. , Wang B. , Mao J.X., Ngan E.S.W. , Chen Y. , Lui V.C.H. , Wong K.K.Y. , Liu L. and Tam P.K.H. , Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population, Journal of Pediatric Surgery . 2010, 45: 709-713.

Miao X. , Leon Y.Y. , Ngan E.S.W. , So M.T. , Yuan Z.W., Lui V.C.H. , Chen Y. , Wong K.K.Y. , Tam P.K.H. and Garcia-Barcelo M.M. , Reduced RET expression in gut tissue on individuals carrying risk alleles of Hirschsprung's disease, Human Molecular Genetics . 2010, 19(8): 1461-1467.

Ngan E.S.W. , Lau C.S.T. , Wo Y.H. , Chan W.K. , Chan G.C.F. , Wang Y. , Kaplan D. and Tam P.K.H. , Endocrine-gland vascular endothelial growth factor (EG-VEGF) in neuroblastoma tumor initiating cells, Advances in Neuroblastoma Research 2010, Stockham, Sweden, 21-24 June 2010 .

Ngan E.S.W. , Garcia-Barcelo M.M. , Yip B.H.K. , Sham P.C. , Lui V.C.H. and Tam P.K.H. , Hedgehog-notch induced premature gliogenesis of neur al crest: a cause of Hirschsprung disease, International Society for Stem Cell Research, the 8th Annual Meeting, Moscone West, San Francisco, U.S.A. 16-19 June 2010 .

Ngan E.S.W. and Tam P.K.H. , Prokineticin signaling in the c-kit expressing neuroblastoma cells, In: ISSCR, The 7th Annual Meeting for the International Society for Stem Cell Research, Barcelona, Spain, 8-11 July 2009 .

Ngan E.S.W. , Reviewer Board Member, The Journal of Pediatric Biochemistry . 2009.

Ngan E.S.W. , Reviewer for Research Grant, Grant Agency of the Academy of Sciences of the Czech Republic . 2009.

Ngan E.S.W. , Reviewer, Current Pharmacogenomics and Personalized Medicine . 2009.

Ngan E.S.W. , Reviewer, Endocrine-related Cancer . 2009.

Ngan E.S.W. , Reviewer, Endocrinology . 2009.

Ngan E.S.W. , Reviewer, Expert Opinion On Therapeutic Targets . 2009.

Ngan E.S.W. , Reviewer, Genetics and Molecular Biology . 2009.

Ngan E.S.W. , Reviewer, Journal of Biological Chemistry . 2009.

Ngan E.S.W. , Reviewer, Journal of Pediatric Surgery . 2009.

Ngan E.S.W. , Reviewer, Molecular Biology Reports . 2009.

Ngan E.S.W. , Reviewer, Neurogastroenterology & Motility . 2009.

Ngan E.S.W. , Reviewer, PLoS One . 2009.

Ngan E.S.W. , Reviewer, Pediatric Surgery International . 2009.

Yip B.H.K. , Ngan E.S.W. , Garcia-Barcelo M.M. , Cherny S.S. , Tang S.M. , Sham P.C. and Tam P.K.H. , Quantifying epistasis between two sets of signaling pathway genes by canonical correlation analysis: with application on Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Researcher : Niu J

List of Research Outputs

Wong K.K.Y. , Cheung S.O.F. , Huang L. , Niu J. , Tao C. , Ho C.M. , Che C.M. and Tam P.K.H. , Further evidence of the anti-inflammatory effects of silver nanoparticles, ChemMedChem . 2009, 4(7): 1129-1135.

Researcher : Patil NG

Project Title:	Audit of deaths and complications in surgical patients admitted to university surgical unit
Investigator(s):	Patil NG
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	01/1992

Abstract:

To assess: (1) quality and standard of care; (2) educational value; (3) reporting of complications; (4) incidence and prevalence of life threatening surgical conditions; (5) improvements in surgical techniques, investigation procedures, clinical practice and infrastructure.

Project Title:	Risk factors for inguinal hernia in adults: a case-control study
Investigator(s):	Patil NG, Lau H
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	11/2002

Abstract:

To evaluate and identify the risk factors for the development of inguinal hernia in adults.

Project Title:	Risk factors for hernia development in patients receiving continuous ambulatory peritoneal dialysis (CAPD)
Investigator(s):	Patil NG, Lau H
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To evaluate the incidence of and identify the risk factors for the development of hernia in patients who are undergoing CAPD.

List of Research Outputs

Chan L.K. , Patil N.G. and Ip M.S.M. , Enhancement of student learning in PBL by video triggers, 7th Asian Pacific Medical Education Conference (APMEC), Singapore, 6-7 February 2010, Medical Education . 2010, 44 (Suppl 1): 1.

Chan L.K. and Patil N.G. , Graphical representation of assessments in a medical curriculum, South East Asian Journal of Medical Education . 2009, 3(1): 57-59.

Chan S.W.W. , Cheung P.S.Y. , Lee J.F.Y., Fung J.T.K., Patil N.G. and Kwok S.P.Y. , Women surgeons in Hong Kong, Surgical Practice . Hong Kong, College of Surgeons of Hong Kong, 2010, 14 (1): 2-7.

Fan J.K.M. , Tong D.K.H. , Poon J.T.C. , Lo O.S.H., Beh S.L. , Patil N.G. and Law W.L. , Multimodality minimally invasive autopsy -- a feasible and accurate approach to post-mortem examination, Forensic Science International . 2010, 195(1-3): 93-98.

Leung G.K.K. and Patil N.G. , Patient safety in the undergraduate curriculum: medic al students' perception, Hong Kong Medical Journal . 2010, 16(2): 101-105.

Patil N.G. , Adjunct Professor , Maharashtra University of Health Sciences in India . 2010.

Patil N.G. and Chan L.K. , Assessment in Medical and Health Sciences Education . Hong Kong, Institute of Medical and Health Sciences Education, HKU, 2009.

Patil N.G. , Delegate on behalf of the College of Surgeons of Hong Kong, Observation of the Objective and Structural Clinic al Examination of the Royal College of Surgeons of Edinburgh, Edinburgh, United Kingdom, 3-7 October 2009 . 2009.

Patil N.G. and Wall D., Early years of postgraduate training, In: Dent J.A. and Harden R.M. (eds), A Practical Guide for Medical Teachers . Edinburgh, Churchill Livingstone, 2009.

Patil N.G. , Expert Faculty, National Conference on Health Professionals' Education (NCHPE) 2009, Pune, India, 10-13 December 2009 . 2009.

Patil N.G. , Member of External Review Visiting Committee, Faculty of Medicine, the University of Pelita Harapan in Lippo Karawaci, Tangerang, Indonesia, 10-12 December 2009 . 2009.

Patil N.G. , PBL - What works and what doesn't, National Conference on Health Professionals' Education 2009, Pune, India, 10-13 December 2009 .

Poolton J.M. , Fan J.K.M. , Masters R.S.W. , Patil N.G. and Law W.L. , The impact of verbal guidance on laparoscopic skills training and multi-tasking performance, 12th World Congress of Endoscopic Surgery, Washington DC . 2010.

Researcher : Poon HC

List of Research Outputs

Leon Y.Y. , Ngan E.S.W. , Poon H.C. , So M.T. , Lui V.C.H. , Tam P.K.H. and Garcia-Barcelo M.M. , Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3, Journal of Pediatric Surgery . 2009, 44(10): 1904-1912.

Researcher : Poon JTC

List of Research Outputs

Choi H.K. , Law W.L. and Poon J.T.C. , The optimal number of lymph nodes examined in stage II colorectal cancer and its impact of on outcomes, BMC Cancer . 2010, 10: 267.

Fan J.K.M. , Tong D.K.H. , Poon J.T.C. , Lo O.S.H., Beh S.L. , Patil N.G. and Law W.L. , Multimodality minimally invasive autopsy -- a feasible and accurate approach to post-mortem examination, Forensic Science International . 2010, 195(1-3): 93-98.

Foo C.C., Poon J.T.C. and Law W.L. , Self-expanding metallic stents for acute left-sided large bowel obstruction: a review of 130 patients, Colorectal Disease . 2010, Epub ahead of print.

Law W.L. , Poon J.T.C. , Fan J.K.M. , Lo O.S.H., Wei R. and Choi H.K. , Comparison of outcomes following resection of right-sided and left-sided colon cancer, International Surgical Week 2009, Adelaide, Austra lia, 6-10 September 2009 .

Law W.L. , Poon J.T.C. , Fan J.K.M. and Lo O.S.H., Laparoscopic colorectal resection for octogenarians is a safe and optimal approach, Annual Meeting of the American Society of Colon and Rectal Surgeons, Minneapolis, Minnesota, U.S.A., 15-19 May 2010 .

Law W.L. , Poon J.T.C. , Fan J.K.M. and Lo O.S.H., Laparoscopic resection following stent insertion for obstructing colorectal cancer, The Society of American Gastrointestinal and Endoscopic Surgeons 2010 Annual Meeting and 12th World Congress of Endoscopic Surgery, National Harbor, Maryland, U.S.A., 14-17 April 2010 .

Law W.L. , Fan J.K.M. and Poon J.T.C. , Single incision laparoscopic left colectomy for carcinoma of distal transverse colon, Colorectal Disease . 2009, 12(7): 698-701.

Law W.L. , Poon J.T.C. and Fan J.K.M. , Single incision laparoscopic right colectomy (Video Presentation), The Society of American Gastrointestinal and Endoscopic Surgeons 2010 Annual Meeting and 12th World Congress of Endoscopic Surgery, National Harbor, Maryland, U.S.A., 14-17 April 2010 .

Law W.L. , Fan J.K.M. and Poon J.T.C. , Single-incision laparoscopic colectomy: early experience, Diseases of the Colon and Rectum . 2010, 53(3): 284-288.

Lim Y.K. , Law W.L. , Poon J.T.C. and Fan J.K.M. , Impact of multimodality treatment on total mesorecta l excision (TME) surgery for very low rectal cancers, International Surgical Week 2009, Adelaide, Australia, 6-10 September 2009 .

Lim Y.K. , Law W.L. , Liu R., Poon J.T.C. , Fan J.K.M. and Lo O.S.H., Impact of neoadjuvant treatment on total mesorectal excision for ultra-low rectal cancers, World Journal of Surgical Oncology . 2010, 8: 23.

Pang R.W.C. , Law W.L. , Chu A.C.Y. , Poon J.T.C. , Lam S.C. , Chow K.M. , Ng L. , Cheung W.H. , Lan X.R. , Lan H.Y. , Tan V.P.Y. , Yau T.C.C. , Poon R.T.P. and Wong B.C.Y. , A Subpopulation of CD26+ Cancer Stem Cells with Metastatic Capacity in Human Colorectal Cancer, Cell Stem Cell . 2010, 6: 603-615.

Poon J.T.C. , Fan J.K.M. and Law W.L. , Early experience in laparo-endoscopic single site colectomy, The 9th Asia Pacific Congress of Endoscopic Surgery and 9th Meeting of Endoscopic and Laparoscopic Surgeons of Asia, Xiamen, China, 4-6 November 2009 .

Poon J.T.C. , Law W.L. , Fan J.K.M. and Lo O.S.H., Impact of the standardized medial-to-lateral approach on outcome of laparoscopic colorectal resection (Reply to Letter), World Journal of Surgery . 2009, 33(10): 2177-2182.

Poon J.T.C. and Law W.L. , Laparoscopic resection for rectal cancer: a review, Annuals of Surgical Oncology . 2009, 16(11): 3038-3047.

Poon J.T.C. , Laparosopic colorectal resection: the impact on clinical outcomes and strategies to further optimize its results, Dissertation, Master of Surgery, The University of Hong Kong . 2010.

Wong K.P., Poon J.T.C. , Fan J.K.M. , Lo S.H. and Law W.L. , Prognostic value of lymph node ratio in stage III colorectal cancer, Annual Meeting of the American Society of Colon and Rectal Surgeons, Minneapolis, Minnesota, U.S.A., 15-19 May 2010 .

Researcher : Poon RTP

Project Title:	American Association for Cancer Research 96th Annual Meeting Blockade of Vascular Endothelial Growth Factor (VEGF) Receptor Enhances the Therapeutic Efficacy of Hypoxia and Chemotherapy in Hepatocellular Carcinoma
Investigator(s):	Poon RTP
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	04/2005

Abstract:

N/A

Project Title:	Training courses on radiofrequenc y ablation for liver cancers
Investigator(s):	Poon RTP, Fan ST, Lam CM, Tso WK
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	01/2006

Abstract:

To provide comprehensive training courses for do ctors from Hong Kong, Macau and China on treatment of liver cancers using radiofrequency ablation (RFA) before they embark on this treatment in their respective hospitals.

Project Title:	Prospective randomized trial of radiofrequency ablation combined with transarterial chemoembolization versus radiofrequency ablation alo ne for unresectable hepatocellular carcinoma
Investigator(s):	Poon RTP
Department:	Surgery
Source(s) of Funding:	Hospital Authority - General Award
Start Date:	01/2007

Abstract:

A randomized clinical trila to evaluate the efficacy of combining transarterial chemoembolization to radiofrequency ablation for treatment of liver cancer.

Project Title:	A study of the effect of vascular endothelial growth factor (VEGF) on chemoresistance of hepatocellular carcinoma (HCC) and blockade of VEGF to enhance chemosensitivity of HCC
Investigator(s):	Poon RTP, Yang Z
Department:	Surgery
Source(s) of Funding:	NSFC/RGC Joint Research Scheme
Start Date:	01/2007

Abstract:

To study the effect of VEGF on chemoresistance of HCC; to investigate the possible mechanism of VEGF-induced chemoresistance in HCC; to study whether inhibition of VEGF could increase chemosensitivity of HCC.

Project Title:	Outstanding Researcher Award 2006-2007
Investigator(s):	Poon RTP
Department:	Surgery
Source(s) of Funding:	Outstanding Researcher Award
Start Date:	11/2007

Abstract:

Nil

Project Title:	Enhancement of therapeutic efficacy of hypoxia and chemotherapy in hepatocellular carcino ma by blockade of Chemokine (C-X-C motif) receptor 4 (CXCR4)
Investigator(s):	Poon RTP, Yang Z
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	01/2008

Abstract:

Objective Hepatocellular carcinoma (HCC) is the second most common cause of cancer death in Hong Kong. Induction of tumor hypoxia combined with chemotherapy, by means of transcatheter arterial chemoembolization (TACE), has been widely used in treating unresectabl e hepatocellular carcinoma (HCC) (1-3). Oxygen depletion arrests tumor cell proliferation and leads to apoptosis and necrosis (4-6), and chemo-cytotoxicity of drugs, such as cisplatin and doxorubincin, can directly “kill” tumor cells (7,8). However, tumor response rate is unsatisfactory, and only a small population of patients benefit from this treatment protocol (1,9). Our previo us study reported that hepatic artery blockade induced an increased production of vascular endothelial growth factor (VEGF) by the residual tumor cells, leading to hypoxia-mediated tumor angiogenesis. To explore the cellular mechanisms underlying hypoxia-induced tumor angiogenesis, we design the present study to investigate the potential role of acute recruitment of bone marrow derived hemangiocytes (a cell lineage which concomitantly expresses Chemokine [C-X-C motif] receptor 4 [CXCR4] and VEGF receptor 1 [Flt-1]) in hypoxia-induced angiogenesis, and to evaluate the effect of inhibition of hemangiocyte mobilization as a novel strategy to enhance the therapeutic efficacy of TACE. CXCR4 is a chemokine receptor that is expressed by a variety of cell types, including lymphocytes, tumor cells and bone marrow derived hematopoietic stem cells. In addition to its role in mediating tumor cell metastasis, recent work demonstrated that bone marrow derived hemangiocytes could accelerate revascularization through interaction with the ligand of CXCR4, stromal-deriv ed factor 1 (SDF-1) (10). Based on the above findings, we hypothesized that HCC tumor cells might release SDF-1 and VEGF under the stress of hepatic artery blockade, leading to the mobilization of hemangiocytes to the tumor tissues to form neovasculature that helped the survival of tumor cells. Therefore, in the proposed study, we will first determine the alterations of hemangioc ytes in the bone marrow, circulation and tumor tissues after hepatic artery blockade, and then inhibit the mobilization of hemangiocytes to assess the therapeutic efficacy.

Project Title:	Study of hypoxia-induced recruitm ent of bone marrow-derived endothelial progenitor cells (EPCs) in tumor angiogenesis of hepatocellular carcinoma (HCC)
Investigator(s):	Poon RTP, Yang Z
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	12/2008

Abstract:

(1) To investigate the potential role of hypoxia-induced EPC recruitment in tumor angiogenesis; (2) To explore the effects of blockade of mTOR, VEGFR or HIF-1alpha on inhibition of EPC mobilization.

List of Research Outputs

Buell J.F., Cherqui D., Geller D.A., O'Rourke N., Iannitti D., Dagher I., Koffron A.J., Thomas M., Gayet B., Han H.S., Wakabayashi G., Belli G., Kaneko H., Ker C.G., Scatton O., Laurent A., Abdalla E.K., Chaudhury P., Dutson E., Gamblin C., D'Angelica M., Nagorney D., Testa G., Labow D., Manas D., Poon R.T.P. , Nelson H., Martin R., Clary B., Pinson W.C., Martinie J., Vauthey J.N., Goldstein R., Roayaie S., Barlet D., Espat J., Abecassis M., Rees M., Fong Y., McMasters K.M., Broelsch C., Busuttil R., Belghiti J., Strasberg S. and Chari R.S., The international position on laparoscopic liver surgery: The Louisville Statement, 2008, Annals of Surgery / The 2008 International Laparoscopic Liver Resection Consensus Conference . 2009, 250(5): 825-830.

Chan A.C.Y. , Fan S.T. , Lo C.M. and Poon R.T.P. , Impact of antiviral therapy on the survival outcome of patients after major hepatectomy for hepatitis B-r elated hepatocellular carcinoma (Oral Presentation), The 9th World Congress of the International Hepato-Pancreato-Biliary Association, Buenos Aires, Argentina, 18 - 22 April 2010 .

Cheng Q. , Ng T.P. , Fan S.T. , Lim Z.X.H. , Guo D. , Liu X. , Liu Y. , Poon R.T.P. , Lo C.M. and Man K. , Distinct mechanism of small-for-size fatty liver graft injury--Wnt4 signaling activates hepatic stellate cell s, American Journal of Transplantation . 2010, 10(5): 1178-1188.

Cheung K.F. , Ye D. , Yang Z. , Lu L. , Liu C.H., Wang X.L., Poon R.T.P. , Tong Y. , Liu P., Chen Y. and Lau G. , Therapeutic efficacy of Traditional Chinese Medicine 319 recipe on hepatic fibrosis induced by carbon tetrachloride in rats, Journal of Ethnopharmacology . 2009, 124(1): 142-150.

Cheung T.T. , Ng K.K.C. , Poon R.T.P. , Chan S.C. , Lo C.M. and Fan S.T. , A case of laparoscopic hepatectomy for recurrent hepatocellular carcinoma, World Journal of Gastroenterology . 2010, 16(4): 526-530.

Cheung T.T. , Ng K.K.C. , Chok K.S.H. , Chan S.C. , Poon R.T.P. , Lo C.M. and Fan S.T. , Combined resection and radiofrequency ablation for multifocal hepatocellular carcinoma: prognosis and outcomes, World Journal of Gastroenterology . 2010, 16(24): 3056-3062.

Cheung T.T. , Ng K.K.C. , Poon R.T.P. and Fan S.T. , Tolerance of radiofrequency ablation by patients of hepatocellular carcinoma, Journal of Hepato-biliary-pancreatic Surgery . 2009, 16(5): 655-660.

Chok K.S.H. , Ng K.K.C. , Cheung T.T. , Yuen W.K. , Poon R.T.P. , Lo C.M. and Fan S.T. , An update on long-term outcome of curative hepatic resection for hepatocholangiocarcinoma, World Journal of Surgery . 2009, 33(9): 1916-1921.

Chok K.S.H. , Chu F.S.K. , Cheung T.T. , Lam V.W.T. , Yuen W.K. , Ng K.K.C. , Chan S.C. , Poon R.T.P. , Yeung C. , Lo C.M. and Fan S.T. , Results of percutaneous transhepatic cholecystostomy for high surgical risk patients with acute cholecystitis, ANZ Journal of Surgery . 2010, 80(4): 280-283.

Chow K.M. , Chu A.C.Y. , Poon R.T.P. and Pang R.W.C. , Blockade of Raf/MEK/ERK Pathway by Raf265 Inhibits Tumor Growth in Colorectal Cancer, 101st Annual Meeting 2010 of American Association for Cancer Research . Washington DC, 2010.

Chow K.M. , Chu A.C.Y. , Poon R.T.P. and Pang R.W.C. , Inhibition of Tumour Growth by Raf265 Via Blockade of Raf/MEK/ERK Pathway in Colorectal Cancer, 15th Medical Research Conference . Hong Kong, 2010.

Dai W.C., Ng K.K.C. , Chok K.S.H. , Cheung T.T. , Poon R.T.P. and Fan S.T. , Radiofrequency ablation for controlling iatrogenic splenic injury (Letter to the Editor), International Journal of Colorectal Diseases . 2010, 25(5): 667-668.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Abstract), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Geng W. , Man K. , Cheng Q. , Liu Y. , Ng T.P. , Liu X. , Poon R.T.P. , Fan S.T. and Lo C.M. , The potential role of early-phase liver graft injury in induction of late-phase chemoresistance after liver transplantation (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Hao K., Luk J.M.C. , Lee P.Y. , Mao M., Zhang C., Ferguson M.D., Lamb J., Dai H., Ng I.O.L. , Sham P.C. and Poon R.T.P. , Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters, BMC Cancer . 2009, 9: 389.

Ko F.C.F. , Yeung Y.S. , Wong C.M. , Chan L.K. , Poon R.T.P. , Ng I.O.L. and Yam J.W.P. , Deleted in liver cancer 1 isoforms are distinctly expressed in human tissues, functionally different and under differential transcriptional regulation in hepatocellular carcinoma, Liver International . 2010, 30: 139-148.

Lam C.T. , Yang Z. , Fan S.T. and Poon R.T.P. , The proangiogenic role of brain-derived neurotrophic factor in tumor development , The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Lau C.K. , Yang Z. , Ho D.W.Y. , Ng N.P. , Poon R.T.P. and Fan S.T. , Discruption of Akt/hif1 signaling can enhance the therapeutic efficacy of ischemic hypoxia and chemotherapy, The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Lee N.P.Y. , Poon R.T.P. , Shek H.P. , Ng I.O.L. and Luk J.M.C. , Role of cadherin-17 in oncogenesis and potential therapeutic implications in hepatocellular carcinoma, Biochimica et Biophysica Acta . 2010, Epub ahead of print (May): 1-8.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s96.

Ling C. , Lo C.M. , Liu X. , Ng T.P. , Li C. , Leung A.C.F. , Fan S.T. , Poon R.T.P. and Man K. , Acute phase liver graft injury significantly mobilized circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Liu A.M.L. , Poon R.T.P. and Luk J.M.C. , MicroRNA-375 targets Hippo-signaling effector YAP in liver cancer and inhibits tumor properties, Biochemical and Biophysical Research Communications . 2010, 394(3): 623-627.

Liu L. , Lee P.Y. , Chan V.W.M. , Xue W., Zender L., Zhang C., Mao M., Dai H., Wang X.L., Xu Z. , Lee K.W. , Ng I.O.L. , Chen Y., Kung H.F., Lowe S.W., Poon R.T.P. , Wang J.H. and Luk J.M.C. , Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma, Hepatology (Erratum in: Hepatology 2010;51(1):358) . 2009, 50(5): 1453-1463.

Man K. , Ng T.P. , Xu A. , Cheng Q. , Lo C.M. , Xiao J. , Sun B. , Lim Z.X.H. , Cheung J.S., Wu E.X. , Sun K.W. , Poon R.T.P. and Fan S.T. , Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-indu cible protein 10/matrix metalloproteinase 9 signaling, Clinical Cancer Research . 2010, 16(3): 967-977.

Ng E.K.O. , Leung C.P.H. , Au S., Chan A., Wong L.P. , Ma E.S.K. , Pang R.W.C. , Chua D.T.T. , Chu K.M. , Law W.L. , Poon R.T.P. and Kwong A. , Plasma microRNA as a potential marker for breast cancer detection, The 101st Annual Meeting of the American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Ng K.K.C. , Poon R.T.P. , Cheung T.T. , Chu F.S.K. , Tso W.K. and Fan S.T. , High efficacy of high intensity focused ultrasound without transarterial embolization for hepatocellular carcinoma (Poster Presentation), International Liver Cancer Association 3rd Annual Conference, Milan, Italy, 4 - 6 September 2009 .

Ng K.K.C. , Poon R.T.P. , Chok K.S.H. , Cheung T.T. , Tung H., Chu F.S.K. , Tso W.K. , Yu W.C. and Fan S.T. , High efficacy of high-intensity focused ultrasound without transarterial embolization for hepatocellular carcinoma - Hong Kong experience (Abstract), The 1st International Summit of Noninvasive Ultra sound Treatment, Chongqing, China, 22-23 October 2009 .

Ng L. , Poon R.T.P. , Wong B.C.Y. and Pang R.W.C. , A novel regulator of cell migration and invasion in human hepatocellular carcinoma, 16th Hong Kong INternational Cancer Congress . 2009.

Ng L. , Poon R.T.P. , Wong B.C.Y. and Pang R.W.C. , Actopaxin: A Novel Regulator Of Cell Migration And Invasion In Human Hepatocellular Carcinoma , 15th Medical Research Conference, Hong Kong . 2010.

Omata M., Lesmana L.A., Tateishi R., Chen P.J., Lin S.M., Yoshida H., Kudo M., Lee J.M., Choi B.I., Poon R.T.P. , Shiina S., Cheng A.L., Jia J.D., Obi S., Han K.H., Jafri W., Chow P., Lim S.G., Chawla Y.K., Budihusodo U., Gani R.A., Lesmana C.R., Putranto T.A., Liaw Y.F. and Sarin S.K., Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma, Hepatology International . 2010, 4(2): 439-474.

Pang R.W.C. , Law W.L. , Chu A.C.Y. , Poon J.T.C. , Lam S.C. , Chow K.M. , Ng L. , Cheung W.H. , Lan X.R. , Lan H.Y. , Tan V.P.Y. , Yau T.C.C. , Poon R.T.P. and Wong B.C.Y. , A Subpopulation of CD26+ Cancer Stem Cells with Metastatic Capacity in Human Colorectal Cancer, Cell Stem Cell . 2010, 6: 603-615.

Poon R.T.P. , Advances in the treatment of hepatocellular carcinoma, Greater China BESTT Meeting, Ching Mai, Thailand, 6 March 2010 . 2010.

Poon R.T.P. , Advances in treatment of liver cancer (AUGIS Invited Lecture), Annual Scientific Meeting of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, Nottingham, U.K., 3 September 2009 . 2009.

Poon R.T.P. , Advisory Board Member, Advisory Committee of Cancer Research Institute, Seoul National University, Korea . 2010.

Poon R.T.P. , Advisory Board Member, Asia Pacific Brivanib Advisory Board Meeting, Seoul, Korea . 2010.

Poon R.T.P. , Advisory Board Member, Asia Pacific Cancer Conference, Working Group – Hepatocellular Carcinoma . 2010.

Poon R.T.P. , Advisory Board Member, Astra Zeneca Clinical Trial Workshop, Shanghai . 2010.

Poon R.T.P. , Advisory Board Member, GSK Global HCC Advisory Board Meeting, Shanghai . 2010.

Poon R.T.P. , Advisory Board Member, HCC Advisory Board for the Clinical Development of Mage-A3, Shanghai . 2010.

Poon R.T.P. , Advisory Board Member, Liver Cancer Therapy, MSD . 2010.

Poon R.T.P. , Advisory Board Member, Pfizer GI Advisory Board Meeting, Barcelona, Spain . 2010.

Poon R.T.P. , Advisory Board Member, Sanofi-Aventis Asian Hepatocellular Carcinoma Advisory Board, Chiang Mai . 2010.

Poon R.T.P. , Advisory Board Member, Sanofi-Aventis Asian Hepatocellular Carcinoma Advisory Board, Shanghai . 2010.

Poon R.T.P. , Advisory Board Member, Scientific Advisory Board for APASL Meeting, Bangkok . 2010.

Poon R.T.P. , Associate Director (2005 - present), Continuous Medical Education Office, the Hong Kong Academy of Medicine . 2010.

Poon R.T.P. , Associate Editor (2006 - present), HBP Surgery . 2010.

Poon R.T.P. , Associate Editor (2008 - present), World Journal of Surgery . 2009.

Poon R.T.P. , Associate Editor (July 2003 - present), Cancer Reviews: Asia-Pacific . 2010.

Poon R.T.P. , Breakthroughs in management of HCC (Postgraduate Course Lecture), Diploma Course on Medical Oncology, the University of Hong Kong, Hong Kong, 4 July 2009 . 2009.

Poon R.T.P. , Cancer stem cells in hepatocellular carcinoma, Cancer Stem Cell Symposium, Cancer Research Institute of Seoul National University, Seoul, Korea, 10 November 2009 . 2009.

Poon R.T.P. , Chairman - Free Paper General Session, Annual Meeting of the International Liver Cancer Association 2009, Milan, Italy, 4 September 2009 . 2009.

Poon R.T.P. , Chairman - Symposium "Improving clinical outcomes: emerging role of mTOR inhibition in HCC", Annual Meeting of the International Liver Cancer Association 2009, Milan, Italy, 4 September 2009 . 2009.

Poon R.T.P. , Chairman of Scientific Committee, International Hepato-Pancreato-Biliary Association . 2010.

Poon R.T.P. , Chairman of the Advisory Board (2009 - present), The Asian Foundation of Cancer Research . 2010.

Poon R.T.P. , Committee Member (2003 - present), Research Support for Higher Surgical Trainees Committee, The College of Surgeons of Hong Kong . 2010.

Poon R.T.P. , Committee Member (2006 - present), Central Committee on Liver Diseases, Hospital Authorit y, Hong Kong . 2009.

Poon R.T.P. , Committee Member (2006 - present), Scientific Committee and Research Committee, the International Hepato-Pancreato-Biliary Association . 2010.

Poon R.T.P. , Committee member (2005 - present), Research Committee, The College of Surgeons of Hong Kong . 2010.

Poon R.T.P. , Current and potential therapies for primary and recurrent HCC (Invited Lecture), Asian Pacific Digestive Week 2009, Taipei, Taiwan, 27-30 September 2009 . 2009.

Poon R.T.P. , Current standard of care and the next generation of targeted agents in hepatobiliary tumours, Asia Pacific Advisory Conference on Solid Tumors Meeting, Taipei, Taiwan, 22-23 May 2010 . 2010.

Poon R.T.P. , Current standard of care in HCC, Asia Pacific Advisory Conference on Solid Tumors, Taipei, Taiwan, 26-27 March 2010 . 2010.

Poon R.T.P. , Current trend and unmet need of treatment of advanced HCC (Invited Lecture), Annual Meeting of the International Liver Cancer Association 2009, Milan, Italy, 5 September 2009 . 2009.

Poon R.T.P. , Deputy Chairman (2003 - present), Institutional Review Board of The University of Hong Kong / Hospital Authority Hong Kong West Cluster, Hong Kong . 2010.

Poon R.T.P. , Early HCC: is transplantation necessary when resection will do?, World Conference on Interventional Oncology, Philadelphia, U.S.A., 9 June 2010 . 2010.

Poon R.T.P. , Editor (August 2005 - present), Cutting Edge (College Newsletter), The College of Surgeons of Hong Kong . 2009.

Poon R.T.P. , Editor (November 2002 - present), Digestive Surgery (China) . 2010.

Poon R.T.P. , Extended lymphadenectomy in assoication with panctreaticoduodenecto my (Invited Lecture), International Surgical Week 2009, Adelaide, Australi a, 6 - 10 September 2009 . 2009.

Poon R.T.P. , Future directions in hepatocellular carcinoma management, Scientific Symposium on HCC, Hong Kong Society of Clinical Oncology, Hong Kong, China, 5 May 2010 . 2010.

Poon R.T.P. , Hepatic resection for colorectal liver metastasis in the era of Bevacizumab , Colorectal Cancer Sympoisum: From Theory to Practice”, Hong Kong, 17 October 2009 . 2009.

Poon R.T.P. , Honorary Advisor for Continuing Medical Education Programm e (December 1999 - present), The Association of Licentiates of Medical Council of Hong Kong . 2010.

Poon R.T.P. , Honorary Fellow (2005 - present), National Chapter of European Hepatobiliary-Pancreatic Association, Republic of Serbia and Montenegro . 2010.

Poon R.T.P. , Improving results of surgical treatment of hepatocellular carcinoma, XXXIII International Congress of Surgery, Madrid, Spain, 24-29 May 2010 . 2010.

Poon R.T.P. , Instructor of Advanced Trauma Life Support Course (199 8 - present), The American College of Surgeons . 2010.

Poon R.T.P. , International Advisory Committee Member, Cancer Research Institute, Seoul National University, Korea . 2010.

Poon R.T.P. , Laparoscopic resection for hepatocellular carcinoma, Seminar on Minimal Access Therapy for Hepato-Pancreatico-Biliary Diseases, Hong Kong, China, 19-20 November 2009 . 2009.

Poon R.T.P. , Leading investigator, Phase II & Phase III trials of sorafenib combined with Xeloda and Oxaliplatin for advanced hepatocellular carcinoma . 2010.

Poon R.T.P. , Leading investigator, Phase II randomized trial of Everolimus combined with transarterial chemoembolization for hepatocellular carcinoma . 2010.

Poon R.T.P. , Local ablative therapy in HCC, The 9th World Congress of the International Hepato-Pancreato-Biliary Association, Buenos Aires, Argentina, 18-22 April 2010 . 2010.

Poon R.T.P. , Management of HCC in Asia Pacific: clinical experience of treating patients with nexavar (Invited Lecture), Asia-Pacific Bayer Expert Symposium on Targeted Therapies, Tapei, Taiwan, 26 September 2009 . 2009.

Poon R.T.P. , Management of advanced HCC: state of art (Invited Lecture), International Surgical Week 2009, Adelaide, Australia, 6 - 10 September 2009 . 2009.

Poon R.T.P. , Member of Advisory Board on Liver Cancer, Sanofi-Aventis . 2010.

Poon R.T.P. , Member of Editorial Board (2007 - present), Annals of Surgical Oncology . 2010.

Poon R.T.P. , Member of Editorial Board (2007 - present), Journal of Gastrointestinal Surgery . 2010.

Poon R.T.P. , Member of Editorial Board (2008 - present), Journal of Gastroenterology and Hepatology . 2009.

Poon R.T.P. , Member of Editorial Board (2008 - present), World Journal of Gastroenterology . 2010.

Poon R.T.P. , Member of Editorial Board (March 2003 - present), Cancer Therapy . 2010.

Poon R.T.P. , Member of International Advisory Board, First Asia-Pacific Consensus Meeting on Pirmary Liver Cancer, Seoul, Korea, 2010 . 2010.

Poon R.T.P. , Member of Research Commiittee (2006 - present), International Hepato-Pancreato-Biliary Association . 2010.

Poon R.T.P. , Member of Steering Committee, Clinical Trials for Liver Cancer, Bristol-Myer-Squibb, U.S.A. . 2010.

Poon R.T.P. , Member of the Clinical Advisory Board, Celsion Limited, USA . 2010.

Poon R.T.P. , Member of the Clinical Advisory Board, Progens Pharmaceuticals, Australia . 2010.

Poon R.T.P. , Member of the Liver Cancer Advisory Board , Astra-Zeneca Pharmaceuticals, USA . 2010.

Poon R.T.P. , Member of the Liver Cancer Advisory Board, Bayer Pharmaceuticals, USA . 2010.

Poon R.T.P. , Member of the Liver Cancer Advisory Board, Novartis Pharmaceuticals . 2010.

Poon R.T.P. , Member of the Liver Cancer Advisory Panel, Biocompatibles UK Limited . 2010.

Poon R.T.P. , Molecular targeted therapy for advanced HCC, XXXIII International Congress of Surgery, Madrid, Spain, 24-29 May 2010 . 2010.

Poon R.T.P. , Muiltidisciplinary approach to liver cancer: early to advanced liver cancer, The 20th Conference of the APASL, Beijing, China, 25 March 2010 . 2010.

Poon R.T.P. , Overview of surgical management of colorectal liver metastases and experience in Hong Kong, Singapore-Hong Kong Multidisciplinary Expert Meeting, Hong Kong, China, 14 May 2010 . 2010.

Poon R.T.P. , Permanent Committee/Council member (2004 - present), International Hepatocellular Carcinoma Meeting: Eastern and Western Experiences . 2010.

Poon R.T.P. , Phase I trial of Thermodox combined with radiofrequency ablation in liver cancer patients, Research and Development Session of ThermoDox, New York, U.S.A., 24 February 2010 . 2010.

Poon R.T.P. , Radiofrequency ablation (RFA) in HCC, Wuhan HPBA Meeting, Wuhan, China, 8 May 2010 . 2010.

Poon R.T.P. , Radiofrequency ablation (RFA), Current Management of Hepatocellular Carcinoma Sympo sium, Hong Kong, China, 28 November 2009 . 2009.

Poon R.T.P. , Recent advances in ablative therapies of liver tumors, XXXIII International Congress of Surgery, Madrid, Spain, 24-29 May 2010 . 2010.

Poon R.T.P. , Recent advances in management of hepatocellular carcinoma (CME Webinar Lecture), American Liver Foundation, Washington D.C., U.S.A. , 24 August 2009 . 2009.

Poon R.T.P. , Reviewer, American Journal of Gastroenterology . 2010.

Poon R.T.P. , Reviewer, American Journal of Surgery . 2010.

Poon R.T.P. , Reviewer, Annals of Surgery . 2010.

Poon R.T.P. , Reviewer, Asian Journal of Surgery . 2010.

Poon R.T.P. , Reviewer, British Journal of Surgery . 2010.

Poon R.T.P. , Reviewer, Cancer . 2010.

Poon R.T.P. , Reviewer, Cancer Letters . 2010.

Poon R.T.P. , Reviewer, European Journal of Surgery . 2010.

Poon R.T.P. , Reviewer, Gene Therapy . 2010.

Poon R.T.P. , Reviewer, HBP Surgery . 2010.

Poon R.T.P. , Reviewer, Hepatology . 2010.

Poon R.T.P. , Reviewer, International Journal of Cancer . 2010.

Poon R.T.P. , Reviewer, Journal of American College of Surgeons . 2010.

Poon R.T.P. , Reviewer, Journal of Biomedical Science . 2010.

Poon R.T.P. , Reviewer, Journal of Clinical Oncology . 2010.

Poon R.T.P. , Reviewer, Journal of Gastroenterology and Hepatology . 2010.

Poon R.T.P. , Reviewer, Journal of Hepatology . 2010.

Poon R.T.P. , Reviewer, Journal of National Cancer Institute . 2010.

Poon R.T.P. , Reviewer, Lancet . 2010.

Poon R.T.P. , Reviewer, Liver International . 2010.

Poon R.T.P. , Reviewer, Liver Transplantation . 2010.

Poon R.T.P. , Reviewer, Medical Science Monitor . 2010.

Poon R.T.P. , Reviewer, New England Journal of Medicine . 2010.

Poon R.T.P. , Role of Sorafenib in evolving management of hepatocellular carcinoma, Malaysian Oncology Society Annual Meeting, Johor Bahru, Malaysia, 7 November 2009 . 2009.

Poon R.T.P. , Role of TNM staging in HCC stratification, EASL Special Conference, Dubrovnik, Croatia, 25-26 June 2010 . 2010.

Poon R.T.P. , SECOX Study for HCC: results and discussions, Sanofi-aventis 2nd Asian Hepatocellular Carcinoma Advisory Board (AHCCAB), Singapore, January 2010 . 2010.

Poon R.T.P. , Stages of hepatocellular carcinoma in Asian countries, The 20th Asia-Pacific Cancer Conference, Tsukuba, Japan, 13 November 2009 . 2009.

Poon R.T.P. , Synergy between RFA and Thermodox?, World Conference on Interventional Oncology, Philadelphia, U.S.A., 9 June 2010 . 2010.

Poon R.T.P. , Targeted therapy for HCC (State-of-the-Art Lecture), Chinese Conference of Medical Oncology, Beijing, China, 25 July 2009 . 2009.

Poon R.T.P. , The recent progress in liver nutritional management for patients with HCC, The First Liver Nutrition Conference in TOKAI, Japan, 26 February 2010 . 2010.

Poon R.T.P. , Update on biological agents in HCC, Sanofi-aventis 2nd Asian Hepatocellular Carcinoma Advisory Board (AHCCAB), Singapore, January 2010 . 2010.

Poon R.T.P. , Use of lyso-thermosensitive Liposomal Doxorubicin in combination with radiofrequency ablation for liver cancer, Interventional Hepatology Postgraduate Course, Revello, Italy, 27-30 May 2010 . 2010.

Poon R.T.P. , Use of lyso-thermosensitive Liposomal Doxorubicin in treatment of liver cancer, Society of Thermal Medicine Annual Meeting, Miami, U.S.A., 24 April 2010 . 2010.

Sun S. , Yi X. , Poon R.T.P. , Yeung C. , Day P.J. and Luk J.M.C. , A protein-based set of reference markers for liver tissues and hepatocellular carcinoma, BMC Cancer . 2009, 9: 309.

Sun S. , Xu Z. , Poon R.T.P. , Day P.J. and Luk J.M.C. , Circulating Lamin B1 (LMNB1) biomarker detects early stages of liver cancer in patients, Journal of Proteome Research . 2010, 9(1): 70-78.

Sun S. , Poon R.T.P. , Lee N.P.Y. , Yeung C. , Chan K.L. , Ng I.O.L. , Day P.J.R. and Luk J.M.C. , Proteomics of hepatocellular carcinoma: serum vimentin as a surrogate marker for small tumors ( £ 2 cm), Journal of Proteome Research . 2010, 9(4): 1923-1930.

Tung K.K. , Mak K.M. , Lee M.F. , Li J.J., Poon R.T.P. , Lai C.L. , Luk J.M.C. and Ng I.O.L. , Serum level of DKK1 as a marker for predicting tumor recurrence of hepatocellular carcinoma , American Association for Cancer Research 101st Annual Meeting 2010 .

Wang X. , Zhang W. and Poon R.T.P. , Nanog promoter methylation and chromatin modification in different cancer cells, The International Society for Cancer Stem Cell 7th Annual Meeting, Barcelona, Spain, 8 - 11 July 2009 .

Wang X. , Ongkekp W.M., Chen L. , Yang Z. , Lu P. , Chan K.K. , Lopez J.P., Poon R.T.P. and Fan S.T. , Oct4 mediates chemotherapeutic drug resistance in liver cancer cells through potential Oct4-AKT-ABCG2 pathway, Hepatology . 2010, 52: 528-539.

Wong K.F., Wo J., Ho D., Poon R.T.P. , Casasnovas J.M. and Luk J.M.C. , Prophylactic uses of integrin CD18-betaA peptide in a murine polymicrobial peritonitis model, World Journal of Gastroenterology . 2010, 16(21): 2648-2656.

Yau T.C.C. , Yao T.J. , Chan P., Epstein R. , Ng K.K.C. , Chok K.S.H. , Cheung T.T. , Fan S.T. and Poon R.T.P. , The outcomes of elderly patients with hepatocellular carcinoma treated with transarterial chemoembolization, Cancer . 2009, 115(23): 5507-5515.

Yau W.L. , Pang R.W.C. and Poon R.T.P. , Identification Of Mir-106b And Mir-21 Overexpression In Hepactocellular Carcinoma By An Orthotopic Metastasis Mouse Model , Hong Kong International Cancer Congress, November 2009, Hong Kong . 2009.

Researcher : Qing K

List of Research Outputs

Chan Y.C. , Ting A.C.W. , Qing K. and Cheng S.W.K. , Delayed presentation of popliteal pseudo-aneurysm following soccer football injury, Annals of Vascular Surgery . 2010, 24(4): 553.13-16.

Chan Y.C. , Ting A.C.W. , Qing K. and Cheng S.W.K. , Endovascular aneurysm repair in patients with horseshoe kidney: is it safe?, Asian Chapter Meeting of the International Union of Angiology, Tokyo, Japan, 29-30 October 2009 .

Fan Y. , Qing K. , Cheng S.W.K. and Chow K.W. , Computational studies of thoracic aortic dissection, The 8th Asian Computational Fluid Dynamics Conference , Hong Kong . 2010.

Fan Y. , Qing K. , Cheng S.W.K. and Chow K.W. , Studies of thoracic aortic dissection by computational fluid dynamics, The Fifth European Conference on Computational Fluid Dynamics, Lisbon, Portugal, 2010 .

Researcher : Qing K

List of Research Outputs

Chan Y.C. , Ting A.C.W. , Qing K. and Cheng S.W.K. , Delayed presentation of popliteal pseudo-aneurysm following soccer football injury, Annals of Vascular Surgery . 2010, 24(4): 553.13-16.

Fan Y. , Qing K. , Cheng S.W.K. and Chow K.W. , Computational studies of thoracic aortic dissection, The 8th Asian Computational Fluid Dynamics Conference, Hong Kong . 2010.

Researcher : Ren Y

Project Title:	XL VIII Annual International Conference of the British Association of Paediatric Surgeons Macrophage Migration Inhibitory Factor in Necrotizing Enterocolitis
Investigator(s):	Ren Y
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	07/2001

Abstract:

N/A

Project Title:	Proteomics computational analysis of Severe Acute Respiratory Syndrome
Investigator(s):	Ren Y, Tam PKH, Peiris JSM, He Q
Department:	Surgery
Source(s) of Funding:	VCO SARS Research Fund
Start Date:	07/2003

Abstract:

To investigate by using proteomics approach, combining Western blotting and ELISA: (a) identification of specific pattern in serum for the diagnosis and prognosis, (b) detection of immune-relevant proteins in SARS, (c) detection of proteins in different stages of SARS patients, (d) proteome analysis of SCV (proteome maps), (e) detecti on of expression patterns in virus infected cells.

List of Research Outputs

Li W., Xie Y. , Sun R.W.Y. , Liu Q., Young J., Yu W.Y. , Che C.M. , Tam P.K.H. and Ren Y. , Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition, British Journal of Cancer . 2009, 101(2): 342-349.

Researcher : Saing H

List of Research Outputs

She W.H., Chung H.Y., Lan L.C.L. , Wong K.K.Y. , Saing H. and Tam P.K.H. , Management of choledochal cyst: 30 years of experience and results in a single center, Journal of Pediatric Surgery . 2009, 44(12): 2307-2311.

Researcher : Shao Y

List of Research Outputs

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Young Investigator Award), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, 16 - 19 June 2010 . 2010.

Li C. , Shao Y. , Liu X. , Ling C. , Ng T.P. , Li X.C., Fan S.T. , Lo C.M. and Man K. , FTY720 suppresses liver tumor metastasis by reducing the population of circulating endothelial progenitor cells, myeloid-derived suppressor cells and regulatory T cells (Abstract), The 16th International Liver Transplantation Soci ety Congress, Hong Kong, 16-19 June 2010. Liver Transplantation . 2010, 16(6): s141.

Man K. , Shao Y. , Ng T.P. , Li C. , Fan S.T. and Lo C.M. , The significance of acute-phase small-for-size liver graft injury in mobilization of circulating EPCS/MDSCS/T REGS after LDLT for HCC patients (Abstract), The 16th International Liver Transplantation Society Congress, Hong Kong, 16 - 19 June 2010. Liver Transpl antation . 2010, 16(6): s191.

Shao Y. , Kim S.Y., Shin D., Kim M.S., Suh H.W., Piao Z.H., Jeong M., Lee S.H., Yoon S.R., Lim B.H., Kim W.H., Ahn J.K. and Choi I., TXNIP regulates germinal center generation by suppressing BCL-6 expression, Immunol Lett . 2010, 129(2): 78-84.

Researcher : Sharr WW

List of Research Outputs

Sharr W.W. , Chok K.S.H. , Ng K.K.C. , Chan S.C. , Lo C.M. and Fan S.T. , Impact of donor age on right lobe living donor liver transplantation in a single centre (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(Suppl 7): S92.

Sharr W.W. , Liver transplantation for hepatitis B and hepatitis C (Oral Presentation), Annual Scientific Meeting and Annual General Meeting of the Hong Kong Society of Transplantation, Hong Kong, 25 April 2010 .

Sharr W.W. , Lo C.M. and Fan S.T. , Recurrent hepatitis B infection after liver transplantation for hepatitis B related diseases: long term results of a single centre in Asia (Poster Presentation), The 16th Annual International Congress of the International Liver Transplantation Society, Hong Kong, June 2010 .

Researcher : Shek HP

List of Research Outputs

Lee N.P.Y. , Poon R.T.P. , Shek H.P. , Ng I.O.L. and Luk J.M.C. , Role of cadherin-17 in oncogenesis and potential therapeutic implications in hepatocellular carcinoma, Biochimica et Biophysica Acta . 2010, Epub ahead of print (May): 1-8.

Shek H.P. , Luk J.M.C. , Kwong A. and Lee N.P.Y. , The role of serine peptidase inhibitor, Kazal type I (SPINK1) in hepatocellular carcinoma (Poster Presentation), Cancer Omics, Erice, Italy, 3-8 May 2010 .

Researcher : Shek HP

List of Research Outputs

Shek H.P. , Luk J.M.C. , Kwong A. and Lee N.P.Y. , The role of serine peptidase inhibitor, Kazal type I (SPINK1) in hepatocellular carcinoma (Poster Presenta tion), Cancer Omics, Erice, Italy, 3-8 May 2010 .

Researcher : Shih KC

List of Research Outputs

Man K. , Shih K.C. , Ng T.P. , Xiao J. , Guo D. , Sun K.W. , Lim Z.X.H. , Cheng Q. , Liu Y. , Fan S.T. and Lo C.M. , Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts, Annals of Surgery . 2010, 251(6): 1154-1161.

Shih K.C. and Man K. , Small-for-size liver graft injury – impact on tumor behavior (Invited review), Transplantation Reviews . 2010, 24(1): 1-10.

Researcher : Shin VY

Project Title:	Detection of circulating cancer cells after resection of gastric cancer: laparoscopic approach versus conventional open approach
Investigator(s):	Shin VY, Chu KM
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	01/2010

Abstract:

Gastric cancer is the second leading cause of cancer mortality in the world, and it has a particularly high incidence in Asian countries including China. Despite the declining incidence of gastric cancer, there are still more than 1 million cases newly diagnosed and 850,000 deaths globally each year (1). The high mortality rate is mainly due to late presentation, since early stage of gastric cancer is either asymptomatic or presents with non-specific symptoms. The survival rate depends on the stage of gastric cancer at the time of diagnosis (2). Today, surgery remains the mainstay of potentially curative treatment for gastric cancer. Patients who have undergone curative resection may still develop recurrence. In general, the 5-year survival rate for patients who have undergone surgical resection ranges from 47% to 60.4% (3). It has been suspected that surgical resection of gastric cancer may increase the risk of spreading cancer cells into the blood or lymph atic system and these cells then invade or migrate into the extracellular space to form a secondary tumour (4). Circulating cancer cells in the blood were detected in 46% of patients after a gastrectomy. Detection of circulating cancer cells in the pre- or post-operative period is suspected to be related to subsequent recurrence. In recent years, laparoscopic gastrectomy has been introduced for the treatment of gastric cancer. In general, the laparoscopic approach is associated with less surgical blood loss, less wound pain, quicker recovery, improved blood glucose homeostasis, less complications, and shorter hospital stay in comparison to the conventional open approach (5, 6). Moreover, it has been shown in various studies that the short-term recurrence-free survival of patients having the laparoscopi c approach is comparable to that of the open approach (7). Nevertheless, long-term follow-up study of the oncologic outcome after laparoscopic gastrectomy for cancer is still lacking, especially for advanced gastric cancer. Since the laparoscopic approach involves less manipulation of the primary tumour, we hypothesize that the laparoscopic approach is associated with less dissemination of circulating cancer cells in compariso n to the conventional open approach after resection of gastric cancer. To the best of our knowledge, there has been no published report comparing the difference in detection of circulating cancer cells between the laparoscopic and open approaches for gastrectomy in patients with gastric cancer. The aim of the present study is to detect circulating cancer cells expressing carcinoembryonic antigen (CEA) and cytokeratin-19 (CK19) by real-time RT-PCR in the peripheral circulation of patients with gastric cancer during the pre- and post-resection period. The expressions of the two epithelial cell markers in the plasma after the laparoscopic and open approaches will be compared. The correlation of the expression levels of CEA and CK19 with tumour stage will also be examined. 1. Bertuccio P, Chatenoud L, Levi F, Praud D, Ferlay J, Negri E, Malvezzi M, La Vecchia C. Recent patterns in gastric cancer: A global overview. Int J Cancer 2009;125:666-73. 2. Gastric cancer studies focus on prolonging survival and finding molecular markers for targeted therapies. OncoLog 2004. (http://www2.mdanderson.org/depts/oncolog/articles/pf/04/4-apr /4-04-1-pf.html) 3. Chan AO, Chu KM, Lam SK, Cheung KL, Law S, Kwok KF, Wong WM, Yuen MF, Wong BC. Early prediction of tumor recurrence after curative resection of gastric carcin oma by measuring soluble E-cadherin. Cancer 2005;104:740-6. 4. Ikeguchi M, Kaibara N. Detection of circulating cancer cells after a gastrectomy for gastric cancer. Surg Today 2005;35:436-41. 5. Guzman EA, Pigazzi A, Lee B, Soriano PA, Nelson RA, Benjamin Paz I, Trisal V, Kim J, Ellenhorn JD. Totally Laparoscopic Gastric Resectio n with Extended Lymphadenectomy for Gastric Adenocarcinoma. Ann Surg Oncol. 2009 [Epub ahead of print] 6. Kanno H, Kiyama T, Fujita I, Tani A, Kato S, Tajiri T, Barbul A. Laparoscopic Surgery Improves Blood Glucose Homeostasis and Insulin Resistance Following Distal Gastrectomy for Cancer. JPEN J Parenter Enteral Nutr 2009 [Epub ahead of print] 7. Strong VE, Devaud N, Allen PJ, Gonen M, Brennan MF, Coit D. Laparoscopic versus open subtotal gastrectomy for adenocarcinoma: a case-control study. Ann Surg Oncol 2009;16:1507-13.

List of Research Outputs

Shin V.Y. , Jin H.C., Ng E.K.O. , Sung J.J., Chu K.M. and Cho C.H., Activation of 5-lipoxygenase is required for nicotine mediated epithelial-mesenchymal transition and tumor cell growth, Cancer Lett . 2010, 292(2): 237-245.

Researcher : Sihoe ADL

List of Research Outputs

Chan M.C.W. , Chan W.Y. , Yu C.L. , Ho C.C. , Yuen K.M. , Fong J.H.M. , Tang L.L.S. , Lai W.W.K. , Lo A.C.Y. , Chui W.H. , Sihoe A.D.L. , Kwong D.L.W. , Tsao G.S.W. , Poon L.L.M. , Guan Y. , Nicholls J.M. and Peiris J.S.M. , Tropism and innate host responses of the 2009 pandemic H1N1 influenza virus in ex vivo and in vitro cultures of human conjunctiva and respiratory tract, American Journal of Pathology . 2010, 176(4): 1828-40.

Lam C.L.D. , Girard L., Sihoe A.D.L. , Cheng L.C. , Lui M.A.C.Y., Wong M.P. , Chung L.P. , Ip M.S.M. , Lam W.K. and Minna J.D., Gene expression signatures associated with combination of female non-smokers in lung adenocarcinomas bearing activating epidermal growth factor receptor (EGFR) gene mutations in Chinese, The American Thoracic Society Annual Meeting 2010 .

Tam I.Y., Leung L.H. , Tin P.C. , Chua D.T.T. , Sihoe A.D.L. , Cheng L.C. , Chung L.P. and Wong M.P. , Double EGFR mutants containing rare EGFR mutant types show reduced in vitro response to gefitinib compared to common activating missense mutations, Molecular Cancer Therapeutics . 2009, 8(8): 2142-51.

Researcher : So MT

List of Research Outputs

Cherny S.S. , Tang S.M. , Sribudiani Y., Miao X. , So M.T. , Sham P.C. , Tam P.K.H. , Garcia-Barcelo M.M. and Hofstra R.M., Fine mapping of Hirschsprung's disease loci in 9q31 (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Cornes B.K. , Tang S.M. , Leon Y.Y. , Hui K.J.W.S., So M.T. , Miao X. , Cherny S.S. , Sham P.C. , Tam P.K.H. and Garcia-Barcelo M.M. , Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population, PLoS One . 2010, 5 (6): e10918.

Garcia-Barcelo M.M. , Yeung M.Y. , Miao X.P., Tang S.M. , Chen G., So M.T. , Ngan E.S.W. , Lui V.C.H. , Chen Y. , Liu X. , Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y. , Chan D. , Cheung K.M.C. , Chung P.H.Y., Wong K.K.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2, Human Molecular Genetics . 2010, 19 (14): 2917-2925.

Garcia-Barcelo M.M. , Tang W.Y. , Miao X. , Tang S.M. , So M.T. , Leon Y.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Identification of rare variants in the NRG1 gene of Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Garcia-Barcelo M.M. , Lui V.C.H. , So M.T. , Miao X. , Leon Y.Y. , Yuan Z.W., Ngan E.S.W. , Ehsan T., Chung P.H.Y., Khong P.L. , Wong K.K.Y. and Tam P.K.H. , MNX1 (HLXB9) mutations in Currarino patients, Journal of Pediatric Surgery . 2009, 44(10): 1892-1898.

Leon Y.Y. , Ngan E.S.W. , Poon H.C. , So M.T. , Lui V.C.H. , Tam P.K.H. and Garcia-Barcelo M.M. , Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3, Journal of Pediatric Surgery . 2009, 44(10): 1904-1912.

Miao X. , Garcia-Barcelo M.M. , So M.T. , Tang W.K. , Xiao D. , Wang B. , Mao J.X., Ngan E.S.W. , Chen Y. , Lui V.C.H. , Wong K.K.Y. , Liu L. and Tam P.K.H. , Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population, Journal of Pediatric Surgery . 2010, 45: 709-713.

Miao X. , Leon Y.Y. , Ngan E.S.W. , So M.T. , Yuan Z.W., Lui V.C.H. , Chen Y. , Wong K.K.Y. , Tam P.K.H. and Garcia-Barcelo M.M. , Reduced RET expression in gut tissue on individuals carrying risk alleles of Hirschsprung's disease, Human Molecular Genetics . 2010, 19(8): 1461-1467.

Sham P.C. , Cornes B.K., Tang S.M. , Leon Y.Y. , So M.T. , Tam P.K.H. and Garcia-Barcelo M.M. , A RET founder mutation in Chinese Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Tang S.M. , Sribudiani Y., Miao X. , de Vries A.R., Burzynski G., So M.T. , Leon Y.Y. , Yip B.H.K. , Osinga J., Hui K.J.W.S., Verheij J.B.G.M., Cherny S.S. , Tam P.K.H. , Sham P.C. , Hofstra R.M.W. and Garcia-Barcelo M.M. , Fine mapping of the 9q31 Hirschsprung's disease locus, Human Genetics . 2010, 127(6): 675-683.

Tang S.M. , Tang W.K. , So M.T. , Miao X.P. and Leung M.C. , Fine mapping of the NRG1 Hirschsprung’s disease locus, Human Molecular Genetics . 2010, Submitted.

Researcher : Suen DTK

List of Research Outputs

Au A.H.Y. , Lam W.W.T. , Chan M., Or A., Kwong A. , Suen D.T.K. , Wong A.L., Butow P.N. and Fielding R. , Development and evaluation of a decision aid booklet for Chinese women facing a choice of breast cancer surgery (abstract and poster presentation), 16th Hong Kong International Cancer Congress, 4-6 November 2009, Hong Kong . Hong Kong, LKS Faculty of Medicine, HKU, 2009, A60.

Cheung T.T. , Suen D.T.K. and Kwong A. , Is sentinel lymph node biopsy after neoadjuvant chemotherapy feasible in Chinese patients with invasive breast canc ers?, ANZ Journal of Surgery . 2009, 79(10): 719-723.

Kwong A. , Wong C.H., Shea C., Suen D.T.K. and Choi C.L., Choice of management of Southern Chinese BRCA mutation carriers, World Journal of Surgery . 2010, 34(7): 1416-1426.

Kwong A. , Wong L.P., Wong H.N. , Law F.B.F. , Ng E.K.O. , Tang Y.H., Chan W.K., Suen D.T.K. , Choi C., Ho L.S., Kwan K.H., Poon M., Wong T.T., Chan K., Chan S.W., Ying M.W., Chan W.C., Ma E.S., Ford J.M. and West D.W., Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer, Hugo Journal . 2010, 3(1-4): 63-76.

Lam W.W.T. , Chan M., Or A., Kwong A. , Suen D.T.K. , Butow P.N. and Fielding R. , Evaluation of a decision aid for Chinese women considering breast cancer surgery for localized breast cancer: A pilot study (poster presentation), The Hong Kong Public Health Forum 2009, 20 September 2009, Hong Kong . Hong Kong, School of Public Health/HKU, 2009, 120.

Suen D.T.K. and Kwong A. , Breast-conserving surgery in Asian women: benefits and potential harm (reply to letter), World Journal of Surgery . 2009, 33(7): 1550-1551.

Suen D.T.K. and Kwong A. , Young Chinese patients with breast cancer have a similar survival to their older counterparts (Abstract) (Poster) , International Surgical Week, Adelaide, Australia, 6 - 10 September 2009 .

Researcher : Sun B

List of Research Outputs

Man K. , Ng T.P. , Xu A. , Cheng Q. , Lo C.M. , Xiao J. , Sun B. , Lim Z.X.H. , Cheung J.S., Wu E.X. , Sun K.W. , Poon R.T.P. and Fan S.T. , Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling, Clinical Cancer Research . 2010, 16(3): 967-977.

Researcher : Sun KW

List of Research Outputs

Man K. , Shih K.C. , Ng T.P. , Xiao J. , Guo D. , Sun K.W. , Lim Z.X.H. , Cheng Q. , Liu Y. , Fan S.T. and Lo C.M. , Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts, Annals of Surgery . 2010, 251(6): 1154-1161.

Man K. , Ng T.P. , Xu A. , Cheng Q. , Lo C.M. , Xiao J. , Sun B. , Lim Z.X.H. , Cheung J.S., Wu E.X. , Sun K.W. , Poon R.T.P. and Fan S.T. , Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling, Clinical Cancer Research . 2010, 16(3): 967-977.

Researcher : Sun S

List of Research Outputs

Sun S. , Yi X. , Poon R.T.P. , Yeung C. , Day P.J. and Luk J.M.C. , A protein-based set of reference markers for liver tissues and hepatocellular carcinoma, BMC Cancer . 2009, 9: 309.

Sun S. , Xu Z. , Poon R.T.P. , Day P.J. and Luk J.M.C. , Circulating Lamin B1 (LMNB1) biomarker detects early stages of liver cancer in patients, Journal of Proteome Research . 2010, 9(1): 70-78.

Sun S. , Poon R.T.P. , Lee N.P.Y. , Yeung C. , Chan K.L. , Ng I.O.L. , Day P.J.R. and Luk J.M.C. , Proteomics of hepatocellular carcinoma: serum vimentin as a surrogate marker for small tumors ( £ 2 cm), Journal of Proteome Research . 2010, 9(4): 1923-1930.

Researcher : Sun S

List of Research Outputs

Sun S. , Yi X. , Poon R.T.P. , Yeung C. , Day P.J. and Luk J.M.C. , A protein-based set of reference markers for liver tissues and hepatocellular carcinoma, BMC Cancer . 2009, 9: 309.

Researcher : Tam PC

List of Research Outputs

Au W.H. , Chu S.S.M. , Chu S.S.M. and Tam P.C. , Primary and secondary retrograde intra-renal surgery (RIRS) for renal stones in patients with large stone burden, The 27th World Congress of Endourology and Shock Wave Lithotripsy, Munich, Germany, 6 - 10 October 2009 .

Chan T.Y., Ho K.L. , Chu S.S.M. and Tam P.C. , Robotic-assisted laparoscopic ureteral reimplantation for distal ureteric stricture (Motion Picture), Surgical Practice . 2009, 13(Suppl. 2): B5.

Fan J.K.M. , Tam P.C. and Law W.L. , Synchronous trans-abdominal pre-peritoneal (TAPP) hernioplasty in a patient with robotic-assisted prostatectomy for carcinoma of prostate (Multi-Media Article), Surgical Practice . 2010, 14(1): 32.

Ho K.L. , Wong C.W.S. , Au W.H. , Chu S.S.M. and Tam P.C. , Early continence outcomes after robotic radical prostatectomy - impact of vesicourethral reconstruction (Poster Presentation), The American Urological Association Annual Meeting , San Francisco, USA, 29 May - 3 June 2010 .

Ho K.L. , Tsui H.L., Au W.H. , Chu S.S.M. and Tam P.C. , Early continence outcomes after robotic radical prost atectomy: impact of vesicourethral reconstruction, Surgical Practice . 2009, 13(Suppl. 2): B7.

Ho K.L. , Tsu J.H.L. , Ng W.M. , Law W.L. , Tam P.C. and Lo B.S.H. , Rectourethral fistula after radical prostatecomy: transperinea l repair in jack-knife position, Surgical Practice . Hong Kong, College of Surgeons of Hong Kong, 2010, 14: 102-104.

Ho K.L. , Tam P.C. , Chu S.S.M. , Au W.H. and Tsu H.L., Robotic-assisted laparoscopic partial nephrectomy - evolution of techniques and peri-operative outcomes, The 1st Hong Kong Congress of Endourology, Hong Kong, 28-29 August 2009 .

Ma W.K., Chu S.S.M. and Tam P.C. , Concomitant pyelithotomy during robotic assisted laparoscopic pyeloplasty, The 1st Hong Kong Congress of Endourology, Hong Kong, 28 - 29 August 2009 .

Tam P.C. , Chairman, Urology Board, The College of Surgeons of Hong Kong . 2010.

Tam P.C. , Corresponding Member (1996 - present), American Urological Association . 2010.

Tam P.C. , Council Member (2004 - present), Asia Pacific Society of Sexual Medicine . 2010.

Tam P.C. , Deputy Secretary General (1996 - present), Asian Surgical Association . 2010.

Tam P.C. , Management of male subfertility: urologist's perspective, Symposium on Update on Subfertility Care, Departmen t of Obstetrics & Gynaecology, Queen Mary Hospital, Hong Kong, 29 November 2009 . 2009.

Tam P.C. , Member of Editorial Board (2005 - present), Hong Kong Medical Journal . 2010.

Tam P.C. , Premature ejaculation - an overview, the challenges of management and recent evidence-based drug treatment (Expert Panel), Seminar on Premature Ejaculation, The Hong Kong Urological Association, Hong Kong . 2009.

Tam P.C. , Radical prostatectomy in the next decade - from open to robotic-assisted, Urology Symposium - Prostate Cancer Update 2009, Division of Urology, Department of Surgery, Tung Wah Hospital and Queen Mary Hospital, The University of Hong Kong, Hong Kong, 25 September 2009 . 2009.

Tam P.C. , Robotic prostatectomy, Hong Kong Surgical Forum, The University of Hong Kong, Hong Kong, 18 July 2009 .

Tam P.C. , Vice President (2008 - present), The College of Surgeons of Hong Kong . 2010.

Tsu H.L., Ho K.L. , Au W.H. , Chu S.S.M. and Tam P.C. , Robotic-assisted laparoscopic radical cystectomy and construction of neobladder urethral anastomosis for urothelial carcinoma of bladder, The 1st Hong Kong Congress of Endourology, Hong Kong, 28-29 August 2009 .

Yap D.Y., Chu F.S., Chu S.S.M. , Tam P.C. , Chan D.T.M. , Lai K.N. and Tang S.C.W. , CT angiography versus conventional digital angiography in pre-operative assessment for Chinese living kidne y donors [Epub ahead of print 15 June 2010], Journal of Nephrology . 2010.

Yap D.Y., Chu F.S., Chu S.S.M. , Tam P.C. , Tam S., Lai K.N. , Chan D.T.M. and Tang S.C.W. , CT angiography versus conventional digital angiography in pre-operative assessment for Chinese living kidney donors, Nephrology . 2010, 15 (S3): 54.

Yip S.K.H. and Tam P.C. , Live surgery demonstration: robotic prostatectomy (Moderator), The Robotic Surgery Workshop: Meet the Startup Chall enge, The Hong Kong Society of Endourology & Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Hong Kong, 15 August 2009 . 2009.

Yuen J.W.M., Gohel M...D...I..., Poon M.W., Shum D.K.Y. , Tam P.C. and Au D.W.T., The initial and subsequent inflammatory events during calcium oxalate lithiasis, Clinica Chimica Acta . 2010, 411: 1018-1026.

Researcher : Tam PKH

Project Title:	Establishing a "train-the-trainers" programme for paediatric surgery in China
Investigator(s):	Tam PKH, Lin CL
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	10/1998

Abstract:

To improve the standard of surgical care of children in China through the establishment of a scheme of "train-the-train ers"; to improve our understanding of special paediatric surgical issues relevant to the Chinese population (e.g. disease patterns, transferability of western "advances" to China etc.) through systematic exchanges with major centres in China and hence enhance our ability to deliver better surgical care to children in Hong Kong.

Project Title:	Expanding the "Train-the-Trainers" programme for paediatric surgery in China
Investigator(s):	Tam PKH, Lin CL
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	10/2000

Abstract:

To improve the standard of surgical care of children in China through the consolidation and expansion of a scheme of "Train-the-Trainers"; to improve our understanding of special paediatric surgical issues relevant to the Chinese population (e.g. disease patterns, transferab ility of western "advances" to China etc) through systematic exchanges with major centres in China and hence enhance our ability to deliver better surgical care to children in Hong Kong; to promote modern concepts of medical education among leaders of the new generation of doctors through the introduction of structured training, problem-based learning, life-long learning, and the use of evidence-based medicine and information technology.

Project Title:	Improving the survival and quality of life of children with cancers in China
Investigator(s):	Tam PKH, Wong IHN, Chan GCF, Ren Y, Lin CL
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	10/2003

Abstract:

To improve the survival and quality of life of poor and sick children suffering from cancer through the establishment of a Chinese Children Cancer Consortium which will be responsible for the introduction and implementation of modern, comprehensive management protocols, and for training and educating health care workers around the country to adopt the new standard of cares for children with cancer.

Project Title:	The study of co-stimulatory function of sonic hedgehog in CD ⁴⁺ lymphocytes
Investigator(s):	Tam PKH, Chan VSF
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003

Abstract:

To study the distribution of Shh and its receptors on the surface of T cells during T cell activation; to study the effect of Shh on TH1 and TH2 cell differentiation; to identify the downstream targets of Shh signaling pathway in CD ⁴⁺ T lymphocytes.

Project Title:	Further expansion of the "Train-the-T rainers" programme for paediatric surgery in China
Investigator(s):	Tam PKH, Chan KL, Zhan JH, Jin XQ, Wong KKY
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	05/2005

Abstract:

The project aims to improve the standard of surgical care of children in China; to improve understanding of special paediatric surgical issues relevant to the Chinese population; and to promote modern concepts of medical education among leaders of the new generation of doctors in China.

Project Title:	Offering Iaparoscopic surgical workshops in China
Investigator(s):	Tam PKH, Wong KKY, Yip PKF, Li L, Zhan JH, Jin XQ
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	01/2007

Abstract:

To improve the standard of surgical care of children in China through the introduction of new laparoscopic techniques in the treatment of paediatric surgical diseases through a series of Iaparoscopic workshops in participating centres; to improve our understanding of special paediatric surgical issues relevant to the Chinese population (e.g. disease patterns, transferabilit y of western 'advances' to China etc) through systematic exchanges with major centres in China and hence enhance our ability to deliver better surgical care to children in Hong Kong; to promote modern concepts of Iaparoscopic surgery among leaders of the new generation of doctors, so that they in turn can teach others in respective centres (i.e.) Train the Trainer concept.

Project Title:	Genetic dissection of Hirschsprung 's disease
Investigator(s):	Tam PKH, Cherny SS, Garcia-Barcelo MM, Miao X, Sham PC
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	09/2007

Abstract:

To analyze the 72 trios with the complete GeneChip@Mapping 500K set; to conduct a case-control study using the 500K set on 400 S-HSCR cases and 400 controls; to proceed with “in silico” and functional analyses of the candidate regions identified.

Project Title:	Dissecting Hirchsprung's disease: international Hirschsprung's disease consortium
Investigator(s):	Tam PKH, Garcia-Barcelo MM
Department:	Surgery
Source(s) of Funding:	France/Hong Kong Joint Research Scheme - Travel Grants
Start Date:	01/2008
Completion Date:	12/2009

Abstract:

1) Finding new Hirschsprung's disease predisposing loci in both Chinese and Caucasian populations; 2) fine mapping of the candidate chromosomal regions identified in 1; 3) assess risks to Hirschsprung's disease in different populations.

Project Title:	Offering surgical care to poor children with major congenital anomalies in rural China
Investigator(s):	Tam PKH, Wong KKY, Yip PKF
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	04/2008

Abstract:

To provide funding for children with major congeni tal anomalies who come from poor families and cannot afford specialist treatment to receive curative operations at Shenzhen Children Hospital, by visiting paediatric surgical team from Hong Kong.

Project Title:	Sequencing of the HOXD13 gene in patients with anorectal malformations
Investigator(s):	Tam PKH, Garcia-Barcelo MM
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2008
Completion Date:	03/2010

Abstract:

Anorectal malformations (congenital obstruction of the anal opening) are among the most common pediatr ic surgical problems (1 in 4000 live birth) and carry a significant chronic morbidity. The spectrum of ARM ranges from anal stenosis to imperforated anus (IA) with/without fistula (abnormal communication to the exterior: recto-vesical; recto-prostatric; recto-urethral; recto-vaginal) to persistent cloaca, in which the intestinal and genitourinary tracts remain a common channel. ARMs may present isolated, syndromic and as part of the phenotypic spectrum of many chromosomal anomalies such as trisomy 13, 18, 21 or 22 to mention a few [1-3]. In fact, approximately 50% of babies with anorectal malformations have other coexisting abnormalities including duodenal atresia, spinal abnormalities, kidney and urinary tract malformations, congenital heart defects, tracheal and esophageal defects, limb (particularly forearm) defects, Down syndrome and Hirschsprung's disease. The etiology of ARM remains unknown, although several lines of evidence indicate that there is a genetic component. Indeed, even though ARMs appear mostly sporadically, they also segregate within families with patterns of inheritance ranging from autosomal-dominant, to X-linked, to autosomal-recessive [4,5]. Moreover, higher risk of anal atresia/stenosis has been associated with consanguinity [6,7]. In addition, the morphological differences among the various types of ARM may be reflecting different embryonic origins thus, implicating the invo lvement of several genes/pathways acting at different stages [2,3]. This means that DNA alterations in any of the genes governing the development of the anoreactal region may result in the ARM phenotype. As in many other instances, animal models have provided clues to genes and pathways that may be operating in ARMs. Mice mut ants for the Mid1, Zic3, Hox, Shh and Shh downstream genes (Gli2, Gli3, Sall1) display different congenital defects with ARM as a common feature and, in most cases, mutations in the human orthologs give rise to similar or related phenotypes [8-15]. Shh and Gli3 mutant mice present with a series of congenital defects including ARMs that highly resemble the VACTERL association in humans (Vertebral defects, Anal atresia, Cardiac septal defects, Tracheoesophageal fistula, Renal anomalies and Limb anomalies) whose genetic cause is not yet known. Mice with homozygous deletions of any of the Hoxd genes, and in particular Hoxd12 and Hoxd13 mutant mice, present with severe malformations of the most distal hingut structures yet the phenotypes resulting from human HOXD13 mutations do not include ARM [9,16]. Interestingly Hoxd13 is thought to be a target of Shh signaling and it has been suggested that Shh (including Shh downstream genes) and Hoxd genes are part of the signaling cascades that establish the patterning of the gut [17-20]. In fact, defects in the Shh signaling pathway are irre futably the cause of anorectal malformations in mice [19,21,22]. This said, exceptions to the human-mouse phenotype correlation also exist (table 1). For instance, Hlxb9 mutant mice do not present with ARMs while mutations in the human HLXB9 give rise to the Currarino syndrome (CS) which includes ARMs. Surprisingly enough, not many systematic genetic analyses of these genes have been conducted in a large enough number of ARM patients. To our knowledge, only SHH has been screened for mutations in a few patients with ARM as a part of a syndrome or in a group of females with persistent cloaca. Therefor e, the role of these genes in human ARM is inconclusive and these genes still represent excellent candidate genes for human ARMs. KEY POINT: In a preliminary screening of 12 VACTERL patients, we have detected a 21base-pair deletion in the exon 1 triplet repeats of HOXD13, a sonic hedgehog (SHH) downstream target. Noteworthy, the mutation results in a polyalanine contraction. Our data provides the first piece of evidence of the implication of the SHH pathway in VACTERL and may corroborate the role of polyalanine contraction s in disease. OBJECTIVE: In this study, we propose to investigate mutations and polymorphisms of the HOXD13 gene in 200 ARM patients and compare the results to those obtatined for 200 ethnically matched controls. REFERENCES: (1) Cuschieri A. Anorectal anomalies associated with or as part of other anomalies. Am J Med Genet 2002;110(2):122-30. (2) Cuschieri A. Anorectal anomalies associated with or as part of other anomalies. Am J Med Genet 2002;110(2):122-30. (3) Cuschieri A. Descriptive epidemiology of isolated anal anomalies: a survey of 4.6 million births in Europe. Am J Med Genet 2001;103(3):207-15. (4) Landau D, Mordechai J, Karplus M et al. Inheritance of familial congenital isolated anorectal malformations: case report and review. Am J Med Genet 1997;71(3):280-2. (5) Falcone RA, Jr., Levitt MA, Pena A et al. Increased heritability of certain types of anorectal malformations. J Pediatr Surg 2007;42(1):124-7. (6) Stoll C, Alembik Y, Roth MP et al. Risk factors in congenital anal atresias. Ann Genet 1997;40(4):197-204. (7) Asindi AA, Al-Daama SA, Zayed MS et al. Congenital malformation of the gastrointestinal tract in Aseer region, Saudi Arabia. Saudi Med J 2002;23(9):1078-82. (8) De Santa BP, Roberts DJ. Tail gut endoderm and gut/genitourinary/tail development: a new tissue-specific role for Hoxa13. Development 2002;129(3):551-61. (9) Debeer P, Bacchelli C, Scambler PJ et al. Severe digital abnormalities in a patient heterozygous for both a novel missense mutation in HOXD13 and a polyalanine tract expansion in HOXA13. J Med Genet 2002;39(11):852-6. (10) Goodman FR, Bacchelli C, Brady AF et al. Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome. Am J Hum Gene t 2000;67(1):197-202. (11) Nowaczyk MJ, Huggins MJ, Tomkins DJ et al. Holoprosencephaly, sacral anomalies, and situs ambiguus in an infant with partial monosomy 7q/trisomy 2p and SHH and HLXB9 haploinsufficiency. Clin Genet 2000;57(5):388-93. (12) Johnston JJ, Olivos-Glander I, Killoran C et al. Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall sy ndromes: robust phenotype prediction from the type and position of GLI3 mutations. Am J Hum Genet 2005;76(4):609-22. (13) Kohlhase J, Wischermann A, Reichenbach H et al. Mutation s in the SALL1 putative transcription factor gene cause Townes-Brocks syndrome. Nat Genet 1998;18(1):81-3. (14) Trockenbacher A, Suckow V, Foerster J et al. MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation. Nat Genet 2001;29(3):287-94. (15) Gebbia M, Ferrero GB, Pilia G et al. X-linked situs abnormalities result from mutati ons in ZIC3. Nat Genet 1997;17(3):305-8. (16) Kondo T, Dolle P, Zakany J et al. Function of posterior HoxD genes in the morphogenesis of the anal sphincter. Development 1996;122(9):2651-9. (17) Roberts DJ, Johnson RL, Burke AC et al. Sonic hedgehog is an endodermal signal induci ng Bmp-4 and Hox genes during induction and regionalization of the chick hindgut. Development 1995;121(10):3163-74. (18) Harmon EB, Ko AH, Kim SK. Hedgehog signaling in gastroint estinal development and disease. Curr Mol Med 2002;2(1):67-82. (19) Mo R, Kim JH, Zhang J et al. Anorectal malformations caused by defects in sonic hedgehog signaling. Am J Pathol 2001;159(2):765-74. (20) Mandhan P, Quan QB, Beasley S et al. Sonic hedgehog, BMP4, and Hox genes in the development of anorectal malformations in Eth ylenethiourea-exposed fetal rats. J Pediatr Surg 2006;41(12):2041-5. (21) Lees C, Howie S, Sartor RB et al. The hedgehog signal ling pathway in the gastrointestinal tract: implications for development, homeostasis, and disease. Gastroenterology 2005;129(5):1696-710. (22) Kim J, Kim P, Hui CC. The VACTERL association: lessons from the Sonic hedgehog pathway. Clin Genet 2001;59(5):306-15.

Project Title:	Genome-wide association study for the identification of genes underlying anorectal malformations
Investigator(s):	Tam PKH, Cherny SS, Garcia-Barcelo MM, Sham PC
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	09/2008

Abstract:

(1) To identify ARM susceptibility genes by analyzing 1.8 million genetic markers typed on 300 isolated-ARM Chinese patients and 300 ethnically and gender matched controls; (2) Follow up and validation of the top 500 SNPs/CNVs of largest effect on an independent sample of 180 isolated-ARM Chinese patients and 180 ethnically and gender matched controls.

Project Title:	Establishing a quaternary peadiatric gastrointestinal centre for Hong Kong
Investigator(s):	Tam PKH, Wong KKY, Wong RMS
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	12/2008

Abstract:

(1) Obtaining funding for the center; (2) contact and quotation of major equipments needed; (3) conversion of existing space into the center.

Project Title:	Improving the surgical care of sick children in Hong Kong by providing cutting edge minimally invasive and robotic surgery
Investigator(s):	Tam PKH
Department:	V-C's Office
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	03/2009

Abstract:

n/a

Project Title:	NRG1 intron 1 SNPs in Hirschsprung’s disease
Investigator(s):	Tam PKH, Garcia-Barcelo MM
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2010

Abstract:

HSCR is a complex genetic disorder that has become a paradigm for the study of complex diseases. Genes (known to date) involved in its pathogenesis encode proteins members of the inter-related signalling pathways (RET, EDRB) that govern the development of the enteric nervous system (ENS). The success of the colonization of the gut by NCCs depends on the synchronization and balance of the signalling networks implicated, thus, DNA alterations in those genes encoding the implicated molecules may interfere with the colonization process, and consequently, represent a primary aetiology for HSCR. HSCR may therefore result from relatively penetr ant functional rare variants in a major gene encoding a crucial molecule (whose penetrance may be modulated by other alleles) and/or from accumulation of less severe mutations in several genes, or the combination of both. Through a genome-wide association study (GWAS) conducted on Chinese HSCR patients, we identified a new HSCR contributing locus, the neuregulin 1 gene (NRG1; 8p12). Importantly, NRG1 contributes to the ENS development, providing a strong biological plausibilit y to our finding as per above. Subsequent fine-mapping of the 350 Kb HSCR-associated NRG1 region revealed potentially functional single nucleotide polymorphism (SNP) variants with lower association p-values than those initially detected through the GWA. These variants are in conserved regions upstream the transcription start site of all NRG1 isoforms and overlap with several transcription binding sites. Therefore, the objective of this proposal is to test whether the HSCR-associated NRG1 SNPs identified through fine-mapping are involved in the pathogenesis of HSCR by affecting NRG1 gene-regulation by: • Investigating, in cell-based reporter assays, whether the conserved non-coding sequences (CNS) comprising the HSCR-associated SNPs have regulatory potential and whether the latter is altered by the SNPs. • Assessing whether the CNS encompassing the NRG1 SNPs bind to the nuclear proteins and whether the binding is compromised by the HSCR-associated alleles.

Project Title:	43rd Annual Meeting of Pacific Association of Pediatric Surgeons Perioperative and late outcomes of laparoscopic fundoplication for neurologically impaired children
Investigator(s):	Tam PKH
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	05/2010
Completion Date:	05/2010

Abstract:

N/A

List of Research Outputs

Chan I.H.Y., Wong K.K.Y. , Lan L.C.L. and Tam P.K.H. , Early experience of single port laparoscopic surgery in a tertiary referral centre in Hong Kong, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Chan I.H.Y., Lam W.W.M., Wong K.K.Y. and Tam P.K.H. , Renal pelvis haematoma causing pelvirureter obstruction: a first case of Antopol-Goldman lesion in neonate (Letter to the Editor), Journal of Paediatrics and Child Health . 2010, 46(6): 361-362.

Chan I.H.Y., Wong K.K.Y. , Chan G.C.F. and Tam P.K.H. , Surgical outcomes of patients with neuroblastoma in a tertiary centre in Hong Kong: a 12-year experience, Hong Kong Journal of Paediatrics (New Series) . 2009, 14(3): 186-193.

Chan K.L. , Fan S.T. , Lo C.M. , Wei W.I. , Ng W.M. , Chung H.Y., Ng K.K.C. , Chan S.C. , Chan K.W. , Tso W.K. , Tsoi N.S. and Tam P.K.H. , Pediatric liver transplantation in Hong Kong - a domain with scarce deceased donors, Journal of Pediatric Surgery . 2009, 44(12): 2316-2321.

Cherny S.S. , Tang S.M. , Sribudiani Y., Miao X. , So M.T. , Sham P.C. , Tam P.K.H. , Garcia-Barcelo M.M. and Hofstra R.M., Fine mapping of Hirschsprung's disease loci in 9q31 (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Chung P.H.Y., Wong K.K.Y. , Wong R.M.S. , Tsoi N.S. , Chan K.L. and Tam P.K.H. , Clinical experience in managing pediatric patients with ultra-short bowel syndrome using Omega-3 fatty acid, European Journal of Pediatric Surgery . 2010, 20(2): 139-142.

Chung P.H.Y., Lan L.C.L. , Wong K.K.Y. and Tam P.K.H. , Deflux injection for the treatment of vesicoureteric reflux in children—a single centre's experience, Asian Journal of Surgery . 2009, 32(3): 163-166.

Chung P.H.Y., Chan K.L. and Tam P.K.H. , Risk factors for morbidities in laparoscopic appendectomy for acute appendicitis of paediatric patients, Surgical Practice . 2009, 13(3): 69-72.

Chung P.H.Y., Wong K.K.Y. , Tam P.K.H. , Chan K.L. , Ng K.K.C. , Chan S.C. , Hui T.W.C. , Yong B.H. , Fan S.T. and Lo C.M. , Split graft liver transplant for paediatric patients in Hong Kong, Hong Kong Journal of Paediatrics (New Series) . 2009, 14: 181-185.

Chung P.H.Y., Wong K.K.Y. , Lan L.C.L. and Tam P.K.H. , Thoracoscopic bullectomy for primary spontaneous pneumothorax in pediatric patients, Pediatric Surgery International . 2009, 25(9): 763-766.

Cornes B.K. , Tang S.M. , Leon Y.Y. , Hui K.J.W.S., So M.T. , Miao X. , Cherny S.S. , Sham P.C. , Tam P.K.H. and Garcia-Barcelo M.M. , Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population, PLoS One . 2010, 5 (6): e10918.

Ehsan M.T., Ng A.T.L., Chung P.H.Y., Chan K.L. , Wong K.K.Y. and Tam P.K.H. , Laparoscopic hernioplasties in children: the implication on contralateral groin exploration for unilateral ingu inal hernias, Pediatric Surgery International . 2009, 25(9): 759-762.

Garcia-Barcelo M.M. , Yeung M.Y. , Miao X.P., Tang S.M. , Chen G., So M.T. , Ngan E.S.W. , Lui V.C.H. , Chen Y. , Liu X. , Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y. , Chan D. , Cheung K.M.C. , Chung P.H.Y., Wong K.K.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2, Human Molecular Genetics . 2010, 19 (14): 2917-2925.

Garcia-Barcelo M.M. , Tang W.Y. , Miao X. , Tang S.M. , So M.T. , Leon Y.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Identification of rare variants in the NRG1 gene of Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Garcia-Barcelo M.M. , Lui V.C.H. , So M.T. , Miao X. , Leon Y.Y. , Yuan Z.W., Ngan E.S.W. , Ehsan T., Chung P.H.Y., Khong P.L. , Wong K.K.Y. and Tam P.K.H. , MNX1 (HLXB9) mutations in Currarino patients, Journal of Pediatric Surgery . 2009, 44(10): 1892-1898.

Gooi Z., Lee R., Wong K.K.Y. and Tam P.K.H. , The use of splenic artery embolisation as a bridge to safe laparoscopic splenectomy in a patient with resistant immune thrombocytopenic purpura, Journal of Paediatrics and Child Health . 2009, 45(12): 767-769.

Hao W. , Liu X. , Chan I.H.Y., Chan K.L. , Tam P.K.H. and Wong K.K.Y. , Comparison study of post-operative stress response between single-port and three-port laparoscopic varicocelectomy in children, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Kam K.M. , Lui V.C.H. , Cheung M.C.H. and Tam P.K.H. , Expression of engrailed-Hoxb5 transcriptional repressor by Wnt1-Cre produces neurocristopathies of pigmentation and enteric nervous system defects in mice., 43rd Annual Meeting for the Japanese Society of Developmental Biologists Kyoto, Japan, 20 June 2010 . 2010.

Kam K.M. , Lui V.C.H. , Cheung M.C.H. and Tam P.K.H. , Expression of engrailed-Hoxb5 transcriptional repressor by Wnt1-Cre produces neurocristopathies of pigmentation and enteric nervous system defects in mice, 43rd Annual Meeting for the Japanese Society of Developmental Biologists, Jointly Sponsored by the Asia-Pacific Developmental Biology Network, Kyoto, Japan, 20-23 June . 2010.

Kenny S.E., Tam P.K.H. and Garcia-Barcelo M.M. , Hirschsprung’s disease, Seminars in Pediatric Surgery . 2010, 19: 194-200.

Lau G.S.K., Lang B.H.H. , Lo C.Y. , Tso A., Garcia-Barcelo M.M. , Tam P.K.H. and Lam K.S.L. , Prohylactic thyroidectomy in ethnic Chinese patients with multiple endocrine neoplasia type 2A syndrome after the introduction of genetic testing, Hong Kong Medical Journal . 2009, 15(5): 326-331.

Leon Y.Y. , Ngan E.S.W. , Poon H.C. , So M.T. , Lui V.C.H. , Tam P.K.H. and Garcia-Barcelo M.M. , Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3, Journal of Pediatric Surgery . 2009, 44(10): 1904-1912.

Li W., Xie Y. , Sun R.W.Y. , Liu Q., Young J., Yu W.Y. , Che C.M. , Tam P.K.H. and Ren Y. , Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition, British Journal of Cancer . 2009, 101(2): 342-349.

Liu X. , Lam G., Wong K.K.Y. and Tam P.K.H. , Perioperative and late outcomes of laparoscopic fundoplic ation for neurologically impaired children, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Liu X. , Lee P.Y. , Ho C.M. , Lui V.C.H. , Chen Y. , Che C.M. , Tam P.K.H. and Wong K.K.Y. , Silver nanoparticles mediate differential responses in keratinocytes and fibroblasts during skin wound healing, ChemMedChem . 2010, 5(3): 468-475.

Miao X. , Garcia-Barcelo M.M. , So M.T. , Tang W.K. , Xiao D. , Wang B. , Mao J.X., Ngan E.S.W. , Chen Y. , Lui V.C.H. , Wong K.K.Y. , Liu L. and Tam P.K.H. , Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population, Journal of Pediatric Surgery . 2010, 45: 709-713.

Miao X. , Leon Y.Y. , Ngan E.S.W. , So M.T. , Yuan Z.W., Lui V.C.H. , Chen Y. , Wong K.K.Y. , Tam P.K.H. and Garcia-Barcelo M.M. , Reduced RET expression in gut tissue on individuals carrying risk alleles of Hirschsprung's disease, Human Molecular Genetics . 2010, 19(8): 1461-1467.

Ngan E.S.W. , Lau C.S.T. , Wo Y.H. , Chan W.K. , Chan G.C.F. , Wang Y. , Kaplan D. and Tam P.K.H. , Endocrine-gland vascular endothelial growth factor (EG-VEGF) in neuroblastoma tumor initiating cells, Advances in Neuroblastoma Research 2010, Stockham, Sweden, 21-24 June 2010 .

Ngan E.S.W. , Garcia-Barcelo M.M. , Yip B.H.K. , Sham P.C. , Lui V.C.H. and Tam P.K.H. , Hedgehog-notch induced premature gliogenesis of neural crest: a cause of Hirschsprung disease, International Society for Stem Cell Research, the 8th Annual Meeting, Moscone West, San Francisco, U.S.A. 16-19 June 2010 .

Ngan E.S.W. and Tam P.K.H. , Prokineticin signaling in the c-kit expressing neuroblastoma cells, In: ISSCR, The 7th Annual Meeting for the International Society for Stem Cell Research, Barcelona, Spain, 8-11 July 2009 .

Rees C.M., Eaton S., Khoo A.K., Kiely E.M., Members of the NET Trial Group -., Tam P.K.H. and Pierro A., Peritoneal drainage does not stabilize extremely low birth weight infants with perforated bowe: data from the NET trial, Journal of Pediatric Surgery . 2010, 45(2): 324-329.

Sham P.C. , Cornes B.K., Tang S.M. , Leon Y.Y. , So M.T. , Tam P.K.H. and Garcia-Barcelo M.M. , A RET founder mutation in Chinese Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

She W.H., Chung H.Y., Lan L.C.L. , Wong K.K.Y. , Saing H. and Tam P.K.H. , Management of choledochal cyst: 30 years of experience and results in a single center, Journal of Pediatric Surgery . 2009, 44(12): 2307-2311.

Tam P.K.H. , Advisor (2007 - present), Wah Yan One Family Foundation, Hong Kong . 2009.

Tam P.K.H. , Board Member, The 37th Annual Combined Meeting of the Scientific Advisory Council and the Board of the Sophia Children's Hospital Foundation, Rotterdam, Netherlands, 12-13 November 2009 . 2009.

Tam P.K.H. and Wong K.K.Y. , Cures and hopes for birth defects (Invited Lectures), Medical Education: Public Lecture Series 2009 at Hong Kong Central Library, Hong Kong, 20 October 2009 . 2009.

Tam P.K.H. , Editorial Board Member, Annals of College of Surgeons of Hong Kong . 2009.

Tam P.K.H. , Editorial Board Member, Current Pediatric Reviews . 2009.

Tam P.K.H. , Editorial Board Member, Pediatric Surgery International . 2009.

Tam P.K.H. , Editorial Consultant, Journal of Pediatric Surgery . 2009.

Tam P.K.H. , Endos Award in Medical Sciecne & Technology: "China Outstanding Leadership Award in Endoscopy", Evaluation Committee of Endos Award in Medical Science & Technology . 2009.

Tam P.K.H. , Executive Committee Member (2008 - 2011), The World Federation of Assocaition of Pediatric Surgeons . 2010.

Tam P.K.H. and Garcia-Barcelo M.M. , Genetic basis of Hrischsprung's disease, Pediatric Surgery International . 2009, 25(7): 543-558.

Tam P.K.H. , HOXB5 and Hirschsprung's disease (Invited Lecture), 2010第三屇全國胎兒疾病的診治及產時外科手術新進展培訓班暨全國小兒實 6-9 May 2010 . 2010.

Tam P.K.H. , HapMap and genome-wide association studies for newborn diseases (Invited Lecture), The 20th Fukuoka International Symposium on Pediatric/Materna l-Child Health Research, Fukuoka, Japan, 29 August 2009 . 2009.

Tam P.K.H. , Honorary Patron (September 2008 - present), Hong Kong Society of Medical Professionals, Hong Kong . 2009.

Tam P.K.H. , Honorary Professor (July 2009 - June 2012), Shenzhen Children's Hospital, Shenzhen, China . 2009.

Tam P.K.H. , Made in Asia: genes, stem cell and surgery (Invited Lecture), 2010第三屇全國胎兒疾病的診治及產時外科手術新進展培訓班暨全國小兒實 6-9 May 2010 . 2010.

Tam P.K.H. , Management of short bowel syndrome in children (Invited Lecture), Southern China Conference of Pediatric Surgery, Wuhan, China, 25 June 2010 . 2010.

Tam P.K.H. , Member of the Award Panel (2007 - present), China Oxford Scholarship Fund . 2009.

Tam P.K.H. , Minimal access surgery in children: the Hong Kong expe rience [Invited Lecture], Chinese Pediatric Minimally Invasive Surgery Symposium and Workshop at the Children's Hospital of Fudan University, Shanghai, China, 30 June 2010 . 2010.

Tam P.K.H. , Molecular biological research and its relevance to paediatric surgery (Invited Lecture), The 22nd Congress of the Asian Association of Pediatric Surgeons, Kuala Lumpur, Malaysia, 20-24 February 2010 . 2010.

Tam P.K.H. , Paediatric minimal invasive surgery: experience and opportunities (Invited Lecture), World Conference of Endoscopy Physicians, World Endoscopy Technology Expo & 19th General Assembly Session of Chinese Endoscopy Physicians, Hong Kong, 18-20 December 2009 . 2009.

Tam P.K.H. , Pediatric surgical oncology research (Invited Lecture), International Surgical Week 2009, Adelaide, Australia, 6-10 September 2009 . 2009.

Tam P.K.H. , Prokineticin-signaling neural crest and HSCR (Invited Lecture), International Human Stem Cell Research Consortium Meeting, Groningen, The Netherlands, 4-5 June 2010 . 2010.

Tam P.K.H. , Reviewer , Archives of Disease in Childhood . 2009.

Tam P.K.H. , Reviewer , Current Pediatric Review . 2009.

Tam P.K.H. , Reviewer , Journal of Pediatric Surgery . 2009.

Tam P.K.H. , Reviewer , Pediatric Surgery International . 2009.

Tam P.K.H. , Reviewer, Annals of Human Genetics . 2009.

Tam P.K.H. , Reviewer, Annals of Surgery . 2009.

Tam P.K.H. , Reviewer, Cancer Research . 2009.

Tam P.K.H. , Reviewer, Gastroenterology . 2009.

Tam P.K.H. , Reviewer, Genetics in Medicine . 2009.

Tam P.K.H. , Reviewer, Hong Kong Journal of Paediatrics . 2009.

Tam P.K.H. , Reviewer, Hong Kong Medical Journal . 2009.

Tam P.K.H. , Reviewer, Mechanisms of Development . 2009.

Tam P.K.H. , Reviewer, Transplant Immunology . 2009.

Tam P.K.H. , Reviewer, World Journal of Gastroenterology . 2009.

Tam P.K.H. , Suruga Lecture: Made in Asia: genes, stem cell and surgery (Invited Lecture), The 22nd Congress of the Asian Association of Pediatric Surgeons, Kuala Lumpur, Malaysia, 20-24 February 2010 . 2010.

Tam P.K.H. , Visiting Professor at the Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan, 28-30 August 2009 . 2009.

Tang S.M. , Sribudiani Y., Miao X. , de Vries A.R., Burzynski G., So M.T. , Leon Y.Y. , Yip B.H.K. , Osinga J., Hui K.J.W.S., Verheij J.B.G.M., Cherny S.S. , Tam P.K.H. , Sham P.C. , Hofstra R.M.W. and Garcia-Barcelo M.M. , Fine mapping of the 9q31 Hirschsprung's disease locus, Human Genetics . 2010, 127(6): 675-683.

Tang S.M. , Garcia-Barcelo M.M. , Cherny S.S. , Sham P.C. and Tam P.K.H. , Genome-wide profile of copy number variants for Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Wong K.K.Y. , Cheung S.O.F. , Huang L. , Niu J. , Tao C. , Ho C.M. , Che C.M. and Tam P.K.H. , Further evidence of the anti-inflammatory effects of silver nanoparticles, ChemMedChem . 2009, 4(7): 1129-1135.

Wong K.K.Y. , Chung P.H.Y., Lan L.C.L. , Chan I.H.Y. and Tam P.K.H. , The first report of a single-port laparoscopic nephrectomy in a child, Hong Kong Medical Journal . 2010, 16(2): 153-154.

Wong K.K.Y. and Tam P.K.H. , Thoracoscopic repair of esophageal atresia through the right chest in neonates with right-sided aortic arch, Journal of Laparoendoscopic & Advanced Surgical Techniques . 2010, 20(4): 403-404.

Yang D. , Sun Z. , Peng T. , Wang H.L., Shen J.G., Chen Y. and Tam P.K.H. , Synthetic fluorescent probes for imaging of peroxynitr ite and hypochlorous acid in living cells, Methods in Molecular Biology . 2010, 591: 93-103.

Yip B.H.K. , Ngan E.S.W. , Garcia-Barcelo M.M. , Cherny S.S. , Tang S.M. , Sham P.C. and Tam P.K.H. , Quantifying epistasis between two sets of signaling pathway genes by canonical correlation analysis: with application on Hirschsprung's disease (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Zhang M. , Lui V.C.H. , Tam P.K.H. and Sham M.H. , Abnormal Enteric Nervous System Development in a Sox10 ^NGFP Mouse Mutant, 14th Research Postgraduate Symposium, December 2 & 3, 2009, The University of Hong Kong . 2009.

Zhang M. , Leung C. , Lui V.C.H. , Tam P.K.H. and Sham M.H. , Sox10 affects enteric neural crest cells migration in a Sox10NGFP/+ mutant , 2010 Hong Kong Inter-University Biochemistry Postgraduate Symposium, CUHK, Hong Kong, 15 May, . 2010.

Zhang M. , Leung C. , Lui V.C.H. , Tam P.K.H. and Sham M.H. , Sox10 is required for proliferation and migration of enteric neural crest stem cells, International Society for Stem Cell Research, 8th Annual Meeting, Moscone West, San Francisco, CA, USA, June 16-19, 2010 .

Zhang M. , Leung C. , Lui V.C.H. , Tam P.K.H. and Sham M.H. , Sox10 mediates proliferation and migration behavior of enteric neural crest cells, 43rd Annual Meeting for the Japanese Society of Developmental Biologists, Jointly Sponsored by the Asia-Pacific Developmental Biology Network, Kyoto, Japan, 20-23 June . 2010.

Zhou M. , Xu A. , Tam P.K.H. , Lam K.S.L. and Wang Y. , Adiponectin deficiency diminishes the anti-inflammatory activities of rosiglitazone in liver , The American Association for the Study of Liver Diseases . 2009.

Researcher : Tang WK

List of Research Outputs

Miao X. , Garcia-Barcelo M.M. , So M.T. , Tang W.K. , Xiao D. , Wang B. , Mao J.X., Ngan E.S.W. , Chen Y. , Lui V.C.H. , Wong K.K.Y. , Liu L. and Tam P.K.H. , Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population, Journal of Pediatric Surgery . 2010, 45: 709-713.

Tang S.M. , Tang W.K. , So M.T. , Miao X.P. and Leung M.C. , Fine mapping of the NRG1 Hirschsprung’s disease locus, Human Molecular Genetics . 2010, Submitted.

Researcher : Tang WY

List of Research Outputs

Garcia-Barcelo M.M. , Tang W.Y. , Miao X. , Tang S.M. , So M.T. , Leon Y.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Identification of rare variants in the NRG1 gene of Hirschsprung's patients (Poster), The 59th Annual Meeting of the American Society of Human Genetics, Honolulu, U.S.A., 21-26 October 2009 .

Researcher : Tao C

List of Research Outputs

Wong K.K.Y. , Cheung S.O.F. , Huang L. , Niu J. , Tao C. , Ho C.M. , Che C.M. and Tam P.K.H. , Further evidence of the anti-inflammatory effects of silver nanoparticles, ChemMedChem . 2009, 4(7): 1129-1135.

Researcher : Tian L

Project Title:	Basic Sciences Symposium 2003: Transplantation Immunology in the Real World Orthotopic Small Bowel but not Heterotopic Cardiac Allograft Recipients Treated with an Unique FK506 Regimen Contributes to the Induction of Egulatory T Cells
Investigator(s):	Tian L
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	09/2003

Abstract:

N/A

Researcher : Ting ACW

List of Research Outputs

Chan R.C.L., Chan Y.C. , Ting A.C.W. and Cheng S.W.K. , Superior vena cava obstruction: our experience, current status and future perspective, CSHK/MSA Annual Scientific Meeting 2009, Hong Kong, 6 September 2009 .

Chan Y.C. , Ting A.C.W. , Qing K. and Cheng S.W.K. , Delayed presentation of popliteal pseudo-aneurysm following soccer football injury, Annals of Vascular Surgery . 2010, 24(4): 553.13-16.

Chan Y.C. , Ting A.C.W. , Qing K. and Cheng S.W.K. , Endovascular aneurysm repair in patients with horseshoe kidney: is it safe?, Asian Chapter Meeting of the International Union of Angiology, Tokyo, Japan, 29-30 October 2009 .

Chan Y.C. , Cheung G.C.Y., Ting A.C.W. , Wong A.C.C. , Yiu W.K. and Cheng S.W.K. , The influence of diabetes mellitus on lower limb revasc ularisation, The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 .

Pang Y.C., Chan Y.C. , Ting A.C.W. and Cheng S.W.K. , Embolectomy in patients with acute limb ischemia: a retrospective evaluation of 128 cases over 10 years, The 10th Annual Congress of Asian Society for Vascular Surgery, Busan, Korea, 15-17 October 2009 .

Pang Y.C., Chan Y.C. , Ting A.C.W. and Cheng S.W.K. , Tender inflammatory infrarenal aortic aneurysm simulating acute rupture, Asian Cardiovascular & Thoracic Annals . 2010, 18(2): 180-182.

She W.H., Chan Y.C. , Ting A.C.W. and Cheng S.W.K. , Conservative management of delayed retrograde type A aortic dissection after successful hybrid endovascular repair of distal arch aneurysm, Acta Chirurgica Belgica . 2010, 110: 240-242.

Ting A.C.W. , Chan Y.C. , Wong A.C.C. , Yiu W.K. , Cheung G.C.Y. and Cheng S.W.K. , Clinical and morphological outcomes after endovascular repair for chronic type B thoracic aortic dissection - early and mid-term results, The 10th Annual Congress of Asian Society for Vascular Surgery, Busan, Korea, 14-17 October 2009. Annals of Vascular Diseases . 2009, 2: S100.

Researcher : To VSH

Project Title:	The role of microRNA let 7 in control ling proliferation of nasopharyngeal carcinoma cells
Investigator(s):	To VSH, Wong STS
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2010

Abstract:

MicroRNAs (miRNAs) are endogenous non-coding RNA molecules (18 to 25 nucleotides in length), which function as post-transcriptional modulators (1). MiRNAs are expressed as long precursor RNAs. After processing by cellular nuclease such as Drosha, the miRNA are actively transported into cytoplasm through Exportin-5-depende nt mechanism. Cytoplasmic miRNAs become functionally mature after processing by cellular nuclear Dicer. Mature miRNAs are associated with a cellular complex that is similar to the RNA-induced silencing complex that participates in RNA interference. The imperfect complementary binding of miRNA to mRNA could lead to transcription repression by promoting degradation of the mRNA mole cule and/or hindering the translation process. In addition, the partial complementary binding of the miRNA to the mRNA could promote poly (A) tail removal and thus accelerating mRNA degradation (3) Nasopharyngeal carcinoma (NPC) is one of the commonest head and neck cancers with an especially high prevalence in Southern China. In our locality, undifferentiated NPC is the most prevalent histology (4). NPC is a multi-factorial disease. Genetic predisposition (5) and epigenetic alterations (6) play a significant part in the tumorigenic process. In addition , the pathogenesis of NPC is closely linked to Epstein-Barr virus infection. Tobacco consumption may be a risk factor as well (7). Recently, it has been shown that miRNA dysregulation is implicated in carcinogenesis of human cancers. The upregulated/ downregulated miRNAs in cancer cells could function as oncogenic/ tumor suppressing modulators. In NPC, however, the critical miRNA changes involved has yet to be clearly defined (8, 9). Let-7 is a family of tumor suppressing miRNAs and its expression is reduced in the majority of human malignancies. High let-7 expression has an anti-proliferative effect on cancer cells. In head and neck squamous cell carcinoma, it has been report ed that low let-7d expression is a prognostic factor for poor survival. (10). However, in cancers such as breast, lymphoma, and ovarian cancers, several let-7 members are upregulated (11). In view of the conflicting nature of the expression patterns across human cancers, we first tested the expression levels of let-7 in NPC and normal nasopharyngeal cultures. Preliminary results show that all the candidate let-7 family members wer e expressed in the nasopharyngeal cultures and we suggested that let-7 might play a part in the high proliferative rate of NPC cells. In this study, the potential involvement of miRNA let-7 in NPC will be investigated. We will examine the let-7 expression levels in nasopharynge al carcinoma cells (HK1 and HONE1) and will compare it with normal epithelial-derived nasopharyngeal cells (NP69 & NP460). To examine whether the reduced let-7 levels has an implicative role in NPC cells, ectopic expression of let-7 precursor molecules will be performed on the NPC cells and the effects on c-Myc expression will be evaluated. In addition, based on a report that several let-7 family members are located in CpG island s which suggests its potential regulation by epigenetic mechanisms (12), we will also assess whether demethylation treatment could reactivate let-7 expression in nasopharyngeal carcinoma cells.

List of Research Outputs

Wong S.T.S. , Man O.Y. , Tsang C.M. , Tsao G.S.W. , Tsang R.K.Y. , Chan Y.W. , Ho W.K. , Wei W.I. and To V.S.H. , Microrna Let-7 Suppresses Nasopharyngeal Carcinoma Cells Proliferation Through Downregulating C-myc Expression, Journal of Cancer Research and Clinical Oncology . Berlin, Springer Berlin / Heidelberg, 2010.

Researcher : Tong DKH

List of Research Outputs

Fan J.K.M. , Tong D.K.H. , Poon J.T.C. , Lo O.S.H., Beh S.L. , Patil N.G. and Law W.L. , Multimodality minimally invasive autopsy -- a feasible and accurate approach to post-mortem examination, Forensic Science International . 2010, 195(1-3): 93-98.

Tong D.K.H. , Law S.Y.K. , Kwong D.L.W. , Chan K.W. , Lam A.K.Y. and Wong K.H. , Histopathological regression of the primary tumor indicated by percentage of residual viable cells is an important prognostic factor after neoadjuvant chemoradiation therapy for esophageal cancer (Abstract), GASTRO 2009 UEGW/WCOG, London, United Kingdom, 21-25 November 2009 .

Tong D.K.H. , Law S.Y.K. , Kwong D.L.W. , Chan K.W. , Lam A.K.Y. and Wong K.H. , Histopathological regression of the primary tumor indic ated by percentage of residual viable cells is an important prognostic factor after neoadjuvant chemoradiation therapy for esophageal cancer, Gut . 2009, Supplement No II Vol 58 - Endoscopy Supplement No I Vol 41: A74.

Tong D.K.H. and Law S.Y.K. , Management of oesophageal cancer (Review Article), Indian Journal of Surgery . 2009, 71: 317-325.

Tong D.K.H. and Law S.Y.K. , Minimally invasive oesophageal stripping, Hong Kong Surgical Forum, Department of Surgery, The University of Hong Kong AND Hong Kong Chapter, American College of Surgeons, 18 July 2009 . 2009.

Tong D.K.H. , Wong K.H. and Law S.Y.K. , Myotomy for achalasia, Hong Kong Surgical Forum, Department of Surgery, The University of Hong Kong, Queen Mary Hospital AND Hong Kong Chapter, American College of Surgeons, 9 January 2010 . 2010.

Tong D.K.H. and Law S.Y.K. , Robotic myotomy for achalasia (Video presentation), Hong Kong Surgical Forum, Department of Surgery, The University of Hong Kong, Queen Mary Hospital AND Hong Kong Chapter, American College of Surgeons, 9 January 2010 . 2010.

Researcher : Tsang FH

List of Research Outputs

Tsang F.H. , Luk J.M.C. and Lee N.P.Y. , Clinical implication of ectopic expression of microRNA-125b in liver cancer (Poster Presentation), Cancer Omics, Erice, Italy, 3-8 May 2010 .

Tsang F.H. , Luk J.M.C. and Lee N.P.Y. , MicroRNA-125b as a negative regulator for eukaryotic translation initiation factor 5A2 (eIF5A2) in liver cancer (Poster Presentation), The 16th Hong Kong International Cancer Congress (HKICC) and 6th Annual Meeting of Center for Cancer Research, Hong Kong, 2009 .

Researcher : Tsang JYS

Project Title:	T cell receptor gene transfer for adoptive regulatory T cell therapy in transplantation tolerance
Investigator(s):	Tsang JYS, Tam PKH
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	01/2009
Completion Date:	06/2010

Abstract:

Exploitation of the natural immunoregulatory mechanism s that are responsible for peripheral T cell tolerance offers possibilities for controlling allograft rejection with minimal side-effects from immunosuppression. Compelling evidence has been shown that a distinct subset of natural ly occurring regulatory T cells, CD4+CD25+ regulatory T cells (Tregs), plays a key role in peripheral T cell tolerance. In vivo generation and expansion of Tregs has been documented in animals after a variety of tolerance induction protocols [1]. Donor specific transplantation tolerance can be achieved in naïve animals by adoptive transfer of Tregs from tolerant animals [1]. Recently, there is emerging interest in several centres around the world in clinical trials using Treg to promote immune tolerance[2]. In vitro studies have shown that the suppressive functions of Tregs require activation via their T cell receptors (TcRs), suggesting that antigen specificity is critical for in vivo Treg functions [3]. Thus, effective clinical therapy will be benefi t from administration of antigen specific Tregs. In autoimmune diabetic models, several lines of evidence have shown that islet-specific Tregs were more potent suppressor than polyclonal populations in suppressing ongoing autoimmune diabetes [4]. In solid organ transplantation, both direct and indirect allorecognition contribute to allograft rejection [5]. In the direct pathway, intact MHC molecules are presented by donor derived antigen presenting cells (APCs). The direct response may decline with time after transplantation as the donor derived APCs only have a limited lifespan. In contrast, in the indirect pathway, represents the normal antigen presentation pathway, donor antigens are processed and presented by recipient APCs. As long as the graft existed, the indirect alloresponse will persist. It is likely that this process will continue in long term after transplantation and become the dominant pathway with time driving chronic graft rejection [5]. Interestingly, a recent report has shown that Tregs expanded to recognize both direct and indirect pathway prevented both acute and chronic graft rejection. On the contrary, Tregs expanded to recognize direct pathway only were not effective in controlling chronic graft rejection [6]. Hence, Tregs with indirect allospecificity is likely to be a key component for achieving transplantation tolerance. Although several strategies have been developed to expand Tregs in an antigen specific manner, the effectiveness of these protocols is not satisfactory so far [7, 8]. With the advancement in gene therapy, a more efficient way to generate Treg with alloantigen specificity is by TcR gene transfer. The potential of TcR gene transfer for antigen specific immunotherap y has been demonstrated in cancer studies. TcR gene modified T cells have been recently applied in a first clinical trial to treat melanoma patients. [9] We have developed TcR gene transfer as an alternative approach to generate Tregs with alloantigen specificity. Using retroviral transduction, we have successfully generated Treg lines with indirect allospecificity which recognized Kd peptide on H2-Ab from C57BL/6 mice. These lines were functional in vitro and adoptive transfer of the TcR transduced Tregs together with short term CD8 depletion and Rapamyci n treatment can prolong graft survival in fully immunocompetent mice (see attachment Figure 1) [JYS Tsang, PhD thesis 2008, KCL; manuscript submitted to JCI]. Despite the advantages of using TcR gene therapy, it is associated with some specific problems. Since the introduced TcR has to compete for cell surface expression with the endogenous TcR, the introduced TcR chains will be expressed at a reduced level. It will be a concern as it may result in lower avidity of the TcR transduced T cells, thus a reduced the ability to respond to low concentrations of the TcR-recognized antigen and lower functional activity [10]. It has been demonstrated that adoptive transfer of lower avidity T cells has has lower ability to eliminate viral infection than high avidity T cells [11]. It could be an issue also for adoptive Treg therapy. Ex vivo expanded antigen specific Tregs from wild type mice are not as efficient as TcR transgenic Tregs in controlling autoimmunity [8]. It has been suggested that the decrease in efficacy is attributed to the lower ability of the cells to recognise antigen. T cell avidity depends not only on TcR expression, but also on TcR affinity. By transferring high affinity TcRs, it is possible to compensate for the lower TcR expression and sufficient to engineer high avidity T cells. We therefore sought to explore the possibility of improving Treg cell therapy in transplantation by TcR transfer using a well-expressed, high affinity TcRs. TcR genes have been isolated from two T cell clones with high and low peptide affinity and cloned into retroviral vector [12] (see attachment Figure 2). We propose in this project (1)To generate Treg lines with high or low TcR affinity to alloantigen by retroviral transduction of TcR genes. (2)To test the efficacy of Tregs with different TcR affinity in vitro and in vivo in controlling graft rejection. (3)To investigate the in vivo actions of Tregs in controlling alloresponses [Reference list see attachment]

Researcher : Tsang RKY

Project Title:	Evaluation of the anti-migration effects of curcumin in squamous cell carcinoma of tongue
Investigator(s):	Tsang RKY, Wong STS
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2010

Abstract:

In 2009, cancer of oral cavity and pharynx constitu ted 3% of new cases of cancer in United States, among which, tongue cancer represented 10530 new cases of cancers and caused 1910 deaths. Despite the effort put into the improvement of prognosis, treatment and management over the decades, the incidence of oral tongue squamous cell carcinoma (SCCOT) is still increasing, with its 5-year survival rate remaining unsatisfactory (around 50%). Among SCC of other oral cavity, survival rate of SCCOT is comparatively low, probably due to its exceptionally high rate of locoregional recurrence and metastasis. Standard treatment regimen includes resection of the tumor, radiotherapy and chemotherapy. These treatment modalities can result in loss of form and function of the patient, yet local and nodal recurrences are not uncommon after treatment. Presence of metastasis in cervical lymph nodes is widely accepted as the key prognostic indicator of regional and distant treatment failure. However, a high rate of occult nodal metastasis (42%), in which there is no evidence of regional spread, was reported. There has been a search for novel treatment strategies to improve the disease control yet to reduce the morbidities of the treatments. Curcumin, a natural polyphenol derived from the rhizome of the plant, was first isolated in 1815. The use of curcumin as a home remedy for various disease has a long history, particularly in Ayurveda, Nepal, Siddha and Chinese medicine. Curcumin has drawn much attention in modern medical science with over 3000 in the National Institutes of Health PubMed database (www.ncbi.nlm.nih.gov/sites/entrez), mainly due to its wide range of bioactivities and low cytotoxicity. Its anti-inflammatory and anti-oxidant properties, chemopreventive, chemotherapeutic and chemosensit izing activity, and radiosenitization and radioprotection effects were well documented. In lung cancer, breast cancer, prostate cancer, liver cancer and melanoma, anti-metastastic effect of curcumin was observed. Despite the ability to suppress head and neck SCC growth being reported both in vitro and in vivo, its effect on SCCOT metastasis has not yet been investigated. In this proposed study, we will investigated the impact of curcumin on SCCOT and dissected the mechanism of curcumin-mediated anti-metastasic effect on SCCOT cells. We will specificall y evaluate the genes involved in anti-migration effect on tongue cancer cells in vitro.

List of Research Outputs

Wong S.T.S. , Chan W.S. , Li C.H., Liu W.M. , Tang W.W., Tsao G.S.W. , Tsang R.K.Y. , Ho W.K. , Wei W.I. and Chan Y.W. , Curcumin alters the migratory phenotype of nasopharyngeal carcinoma cells through up-regulation of E-cadherin , Anticancer Research . 2010, 30: 2851-6.

Wong S.T.S. , Man O.Y. , Tsang C.M. , Tsao G.S.W. , Tsang R.K.Y. , Chan Y.W. , Ho W.K. , Wei W.I. and To V.S.H. , Microrna Let-7 Suppresses Nasopharyngeal Carcinoma Cells Proliferation Through Downregulating C-myc Expres sion, Journal of Cancer Research and Clinical Oncology . Berlin, Springer Berlin / Heidelberg, 2010.

Researcher : Tsu JHL

List of Research Outputs

Ho K.L. , Tsu J.H.L. , Ng W.M. , Law W.L. , Tam P.C. and Lo B.S.H. , Rectourethral fistula after radical prostatecomy: transperineal repair in jack-knife position, Surgical Practice . Hong Kong, College of Surgeons of Hong Kong, 2010, 14: 102-104.

Researcher : Tsui TY

Project Title:	54th Annual Meeting of the American Association for the Study of Liver Diseases Controlling the Development of Liver Cirrhosis by rAAV Mediated Stable HO-1 Expression
Investigator(s):	Tsui TY
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2003

Abstract:

N/A

Project Title:	Identification possible role of heme oxygenase-1 on the regulation of T cell activation
Investigator(s):	Tsui TY
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2004

Abstract:

To identify the possible role of HO-1 in the process of T cell activation. The findings obtained from thi s study might be essential in the establishment of the link between cellular defense system and the T cell immunity. HO-1 and its products could be used as novel therapeutic agents to control the disorders of T cell immunity in the future.

Researcher : Wang B

List of Research Outputs

Miao X. , Garcia-Barcelo M.M. , So M.T. , Tang W.K. , Xiao D. , Wang B. , Mao J.X., Ngan E.S.W. , Chen Y. , Lui V.C.H. , Wong K.K.Y. , Liu L. and Tam P.K.H. , Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population, Journal of Pediatric Surgery . 2010, 45: 709-713.

Researcher : Wang H

List of Research Outputs

Fan S.T. and Wang H. , China Liver Transplant Registry (Oral Presentation), The 15th Annual International Congress, the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation . 2009, 15(7): S100.

Fan S.T. , Wang H. , Jiang W.S., Li W., Zhou Z.Y. and Huang Y.Z., China Organ Allocation and Sharing Policy, Ministry of Health, P.R.China . 2010.

Fan S.T. and Wang H. , New Key Opinion Leader nKOL of the Transplantation Society, The Transplantation Society New Key Opinion Leader Meeting, Gothenburg, Sweden, August 20-23, 2009. . 2009.

Fan S.T. and Wang H. , The role of China Liver Transplant Registry (Oral Presentation), The 20th Conference of Asia Pacific Association of The Study of Liver Disease, Beijing, China, 25 - 28 March 2010 .

Wang H. , China Liver Transplant Registry progress report (Invited Lecture), 2010新年器官移植與免疫治療高峰論壇, 中國廣州, 2010年1月13日, 2010.

Wang H. and Fan S.T. , China Organ Allocation Policy, China First Procument Transplant Coordinator Training Conference, Shenzhen, China, June 27-28th, 2010 . 2010.

Wang H. , Huang Y.Z., Li W., Jiang W.S. and Fan S.T. , Liver Transplantation for Hepatocellular Carcinoma in China (Poster), The 15th Annual International Congress, the International Liver Transplantation Society, Hong Kong, China, 16 - 19 June 2010 .

Wang H. and Fan S.T. , The development of Liver Registry in China (Oral Pre sentation), The Transplantation Society New Key Opinion Leader Meeting, Gothenburg, Sweden, August 20-23, 2009. . 2009.

Wang H. , Voting Member (March 2009 - present), National Human Organ Transplant Clinical Application Committee, the Ministry of Health, People's Republic of China . 2010.

Researcher : Wang X

Project Title:	Chemo resistant cells contain cancer stem like cells and the potential role of Oct4 in cancer stem cell metastasis and drug resistance
Investigator(s):	Wang X
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2007

Abstract:

(1) To investigate whether chemo-resistant cancer cells contain cancer stem like cells and to determine whether the chemo-selected stem cell phenotype is only associated with cancer cells but not normal cells. Stem cell markers, the ability of self-renewal and migration, tumorigenesis and metastasis in a xenograf t model will be tested on chemo-resistant cancer cells. A normal line and pluripotent embryonic carcinoma cell line will be used as controls. (2) The role of Oct4 in cancer stem cell metastasis and drug resistance. Oct4 is a critical gene in sustaining self-renewal and pluripotency for stem cells but also displays oncogenic properties, although its definitive role and pathways have not been fully elucidated. Our recent study show ed that the chemo-resistant cancer cells displayed increased cell migration and Oct4 expression. We aim to further investigate the particular role of Oct4 in cancer stem cells. The objective has two aspects: a) Over-expressing Oct4 in a human cancer cell line to observe whether these cells gain cancer stem-like cell properties, particularly drug resistance and metastasis. We will investigate the potential molecular pathways (Wnt-β-catenin, putative Oct4 target FGF etc.) that are affected. Alternatively, the siRNA technique will be used to knock down Oct4 in embryonic teratocarcinoma cells to study the role of Oct4 in cancer stem cells. b) Oct4 expression pattern in hepatocellular carcinoma and other gastric cancer patients and its clinical correlation with tumor metastasis and chemo-responses. (3) Potential aberrant regulation of Oct4 at transcriptional level. Aberrant expression of Oct4, functioning as an oncoprotein, might occur at the transcription regulation level because there has been no report of Oct4 mutation. Oct4 is post-transcriptionally modified. We aim to explore Oct4 regulation at a number of levels (ubiquitinylation, sumoylation, and mRNA stability), which might lead to Oct4 accumulation in the cancer stem-like cells. Oct4 sumoylation will be the main focus, as a consensus motif ψKXE of SUMO-1 was found in Oct4 sequence in our preliminary data.

Project Title:	Stem cell gene Oct3/4 and Nanog expression and methylation regulation in hepatocellular carcinoma
Investigator(s):	Wang X
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2008
Completion Date:	07/2009

Abstract:

Background: Transcription factor Oct4 is essential for maintaining an undifferentiated cell fate in embryon ic stem cells. Recently, several studies have displayed oncogenic properties of Oct4: a) Oct4 is able to determine ES cells’ oncogenic potential in a dose-dependent manner; b) ectopic expression of Oct4 drives reversible epithelia l dysplasia in transgenic mice; and c) Oct4 is detected in a few tumors. Therefore, one of the cancer stem cell hypothesis is that Oct3/4 expression is "restored" in tumor cells during transformation process. Yet, it is largely unknow that how restored Oct3/4 expression in cancer is regulated. Hypothesis and rational: 1. Studies have shown that stem cell gene Oct3/4 is heterogeneticly expressed in several cancer cell lines and a few kind of tumors; therefore Oct3/4 expressio n by its "restoration" might also play a role in HCC tumorigenesis. 2. Nanog is also an essential gene to support stem cell potency. But little is known about about Nanog expression in cancers. 3. There is no report of Oct3/4 mutation; if aberrant Oct3/4 expression is contributed to HCC tumorigenesis, epigenetic changes of Oct3/4 might play an important role in accumulation of Oct3/4 in cancers. Objectives: 1. To investigate stem cell genes, Oct3/4 and Nanog expression in hepatocellular carcinoma and its association with HCC clinical parameters, such as TNM staging, tumor venous infiltration, micro satellite, and patients’ overall and disease free survivals. 2. To understanding whether epigenitic modification play a role in the stem cell genes regulation in HCC by determining DNA methylation of the Oct3/4 and Nanog upstream region in HCC non-tumor and tumor tissue. 3. To establish profile of DNA methylation of the Oct3/4 and Nanog upstream region in normal liver tissue and HCC non-tumor and tumor tissue. To analyze the correlation between Oct3/4 promoter region with its particular CpGs methylat ion status. Key issues being addressed: 1.This will be the first study to investigate the stem cell gene Oct3/4 and Nanog expression patterns in HCC; to understand whether Oct3/4 also acts as an oncogene in HCC disease; whether Oct3/4 would be a biomarker for HCC progression . 2. This will be the first study to investigate DNA methylation of the Oct3/4 and Nanog upstream regions in HCC (also the first study of understanding stem cell gene methylation in cancer). The study will demonstrate whether and how epigenetic modification contributes to abnormal expression of Oct3/4 in HCC or other cancers by demethylation of its promoters.

Project Title:	Importance of DNA damage mediated S and G2 checkpoint as a protective mechanism in stem cells
Investigator(s):	Wang X, Lui VCH
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	09/2008

Abstract:

(1) Understanding the role of S and G2 checkpoint as a protective mechanism for stem cells. a) Investigation of the cell cycle kinetics and ionizing radiation (IR) mediated DNA damage check points in parallel in human EC and differentiated EC cells. Using DNA synthesis inhibition and BrdU labeling assay to confirm the S phase arrest. b) Cyclins, Cdc25 family, and Plks expression pattern in response to IR, which might contribute to the regulation of cell cycle kinetics, especially for S phase arrest. c) Comparison of DNA damage response protein levels and DNA repair efficiency between und ifferentiated and differentiated EC cells. d) Biological effects of differential DNA damage cell cycle checkpoint pattern of EC and differentiated EC cells, such as cell survival and apoptosis. e) Abrogation of S phase checkpoint to see its functional effect; (2) To characterize and compare ionizing radiation mediated cell cycle checkpoints pattern in vivo by using wild type and ATM deficient mouse embryo blastocyst as a model. Although many DNA repair genes are found expressing in early and late mammalian (mouse, rhesus, and human) embryos, there are very limited reports on DNA damage mediated cell cycle features in vivo. a) Blastocyst of mouse embryo from wild type and ATM-/- mouse will be used as a in vivo model; ATM is a master regulator in DNA damage response and double strand break (DBS) repair. b) Investigations will cover the aspects of IR mediated S and G2 cell cycle arrests, DNA damage foci, apoptosis, and cell cycle checkpoint related proteins; analyzing which of the survival strategies (cell cycle delay, DNA repair, and cell death) is the main mechanism, or how they are coordinated to protect embryonic stem cells. c) Functional importance of S phase delay in vivo in an ATM deficiency background.

Project Title:	Incidence and significance of hepatopoeitic chimerism in long term survival patients of liver transpla ntation.
Investigator(s):	Wang X
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2009
Completion Date:	07/2010

Abstract:

Background: Liver transplantation has become a cure method for many liver diseases. Chimerisms often develop after liver transplantation with the chimerical cells either circulating in blood or integrated into the parenchyma. Several kinds of reciprocal chimerism after liver transplantation has been reported, including: 1. Recipient-derived cells in the donor organ; 2. Hemato poietic chimerism of donor origin in the recipient blood; and 3. Donor origin cells in the skin and lymph nodes. Clinically, the effect of chimerism in the recipients of solid-organ transplantation is uncertain, but developing hematopoietic chimerism could be a desirable situation after liver transplantation, as the chimerism is often associated with allograft tolerance. Liver transplantation is a cure method for liver tumors, but liver cancer recurrence after transplantation is not uncommon. The recurrent liver cancer could be of either recipient or donor origin. With the understanding of cancer stem cells, it is possible that cancer stem cells in circ ulation, which escape chemotherapy and the diseased liver removal, are the source of the cancer recurrence. Thus, recipient-deri ved tumor recurrence can be explained by the cancer stem cell theory. However, de novo cancer (of donor origin) recurrence, including that located in the liver and other organs after liver transplantation, has gained more and more attention, as it often happens in long-term transplant survivors. The mechanism of de novo cancer recurrence is a mystery but is strongly linked to chim erism formation. Objectives: 1. The incidence of donor origin hematopoietic chimerism in a large cohort of long-term survived liver transplantation patients and its clinical associations. Hypothesis: With liver transplantation, adult stem cells of donor origin in the allograft (most likely hematopoietic stem cells) will self-renew, migrate, and differentiate to generate donor-specific chimerical cells in the recipients. a) To evaluate the incidence of donor origin chimerism in 200 patients with long-term survival after liver transplantation using highly sensitive and quantitative microsatellite alleles analysis. b) Understanding the dynamic change of chimerism formation within 1, 3, and 6 months and 1-2 year after liver transplantation to see correlation between percentage of donor cells and time of liver allografts. c) Chimerism formation and clinical outcomes such as transplant tolerance, HBV re-infection, and liver tumor recurrence. d) Chimerism formation comparisons between aged liver donors versus young liver donors, and cadaveric livers versus live livers to understand whether aged adult stem cells can still be functional for generating chimerical cells. 2. Explore if donor hematopoietic stem cells or other progenitor cells could be target cells during liver tumor development in the chimera bone marrow and induced carcinogenesis mouse model. Hypothesis: adult stem cells (including hematopoietic stem cells) in the donor organ not only contribute to chimerism formation but also could be a target cell during tumor development and recurrence. a) Inducing carcinogenesis in the liver in the BM-reconstituted chimera mouse model to explore whether donor hematopoietic stem cells or other progenitor cells could be the target cells during tumor development. Key issues to be addressed: 1. The incidence of donor origin chimerism in a large cohort of long-term liver transplantatio n survivors, and its clinical associations. 2. The potential link between de novo tumor recurrence and chimerism formation after liver transplantation.

Project Title:	The link between adult stem cells and chimerism of liver transplantation
Investigator(s):	Wang X
Department:	Surgery
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2010

Abstract:

1) The incidence of donor origin chimerism in a large cohort of long-term survived liver transplantation patients and its clinical associations. a) To evalua te the incidence of donor origin chimerism in 200 patients with long-term survival after liver transplantation using highly sensitive and quantitative microsatellite alleles analysis. b) Chimerism formation and clinical outcomes such as transplant tolerance, HBV re-infection, and liver tumor recurrence. c) Chimerism formation comparisons between aged liver donors versus young liver donors, and cadaveric livers versus live livers to understand whether aged adult stem cells can stil l be functional for generating chimerical cells; 2) Purification of hematopoietic stem cells and from adult mouse liver. a) To isolate the CD45mid lin- Rho- side population (known for long-term self-renewal and hematopoietic repopulating activities in vitro and in vivo) from adult mouse liver, to see if liver contains hematopoieti c stem cells and the proportion of these cells. b) Ability of liver-sourced hematopoietic stem cells to reconstitute bone marrow (BM) and form chimerisms in other tissues after injury in vivo in a mouse model. c) Try to isolate Sca1+ lin- CD45-, a non-hematopoietic embryonic stem cell-like population with plasticity, from the adult mouse liver; 3) Explore if donor hematopoietic stem cells or other progenitor cells could be target cells during liver tumor development in the chimera BM and induced carcinogenesis mouse model. a) To determine chimerism in the tumor tissue and blood DNA in patients with the recurrence of liver cancer or cancer at other locations after liver transplantation to distinguish cell origin of donor or recipient. b Inducing carcinogene sis in the liver in the BM-reconstituted chimera mouse model to explore whether donor hematopoietic stem cells or other progenitor cells could be the target cells during tumor development.

Project Title:	Cell cycle regulation and drug resistance in stem and cancer stem cells
Investigator(s):	Wang X
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2010

Abstract:

Background: Since the elucidation of the mechanisms of mammalian cell division in the 1970s and 1980s by the work of Lee Hartwell, Paul Nurse and Tim Hunt1, gene products that regulate the key cell cycle machinery have been investigated as cancer drug targets. Cell cycle is rapidly arrested by activation of the ATM, ATR and their downstream effectors CHK1 and CHK2. This gives the cell time to attempt the repair of the DNA lesion to preserve genome integrity and constitute a protective barrier against cancer. In most human cancers, however, the function of the DNA damage checkp oint in G1 is impaired owing to mutations in p53 or pRB. Treatment of these tumor cells with DNA-damaging agents, such as ionizing radiation and DNA-targeting drugs, results in S or G2 checkpoint-mediated arrest, which protects the cancer cells from radiation or cytotoxic agents. Then, the combination of DNA-damaging drugs or ionizing radiation with inhibitors of the S or G2 checkpoints, or ‘S or G2 checkpoint abrogators’ should force cancer cells carrying DNA lesions into mitosis , a condition which prompts mitotic catastrophe and associated cell death. Abrogation of the DNA damage checkpoint in S or G2 is an attractive strategy for selectively targeting G1 checkpoint-defective cancer cells and is currently being explored in clinical trials. However, compared with somatic cells, ES cells have many unusu al proliferative properties, one of which is a distinct cell cycle distribution with a large proportion of cells in S-phase and small proportion of cells in G1- and G2-phase in mouse, primate, and human ES cells. A short G1-phase and the absence of a DNA damage mediated G1 checkpoint are also an unique cell cycle characteristics of ES cells, although our previous study identified human EC cells displayed a S and G2 checkpoint in response to DNA damage. On the other hands, stem cells have been found to be more resistant with increased activation of anti-apoptotic pathways. Thus, whether and how cell cycle kinases inhibitors can be used for targeting stem cells proliferation or enhancing drug sensitivity is not well studied. Hypothesis and rational: Although increased activation of anti-apoptotic pathways and DNA damage repair system result in stem cell resistance, differential cell cycle distribution and checkpoint in stem cells may also contribute to the drug resistance. A recent study has identified that p21, a cell cycle inhibitor, has been shown to not only limiting DNA damage but also maintaining self-renewal of leukemia stem cells in a mouse model indicating potential a novel anti-leukemia strategies by inhibiting cell cycle checkpoint and DNA repair. Therefore, understanding the mechanisms of stem cells resistance from cell cycle regulation point of view may imply whether cell cycle kinases and DNA repair inhibitors could be a potential therapeutic reagent for targeting cancer stem cells. Objectives: 1. To understand the mechanisms of drug resistance in stem cells from cell cycle regulation point of the view. Stem cells have special cell cycle features, which is dramatically different compared to somatic cells. That how these special cell cycle features contribute to drug resistant in stem cells is not well defined. 2. In a mouse model, p21, a cell cycle inhibitor, has been shown to not only limiting DNA damage but also maintaining self-renewal of leukemia stem cells. Thus we wish to determine that by targeting p21 in human stem cells (human embryonal carcinoma cells), whether it could enhance drug sensitivity through inhibition of cell cycle arrest upon DNA damage (by drug treatment) and inhibition of self- renewal ability. Key issues to be addressed: This would be the first study on drug sensitivity in stem cells from cell cycle reg ulation point of view. Using known knowledge on the role of p21 in regulation of leukemia stem cell cycle and self renew, it would be the first study to investigate the drug sensitivity regulation in stem cells by targeting p21.

List of Research Outputs

Wang X. , Cheung C.K.Y. , Ng M.W. and Lo C.M. , Hematopoietic chimerism and potential hematopoietic stem cells in liver transplantation (Abstract), The 8th International Society for Stem Cell Research Annual Meeting, San Francisco, U.S.A., June 2010 .

Wang X. , Zhang W. and Poon R.T.P. , Nanog promoter methylation and chromatin modification in different cancer cells, The International Society for Cancer Stem Cell 7th Annual Meeting, Barcelona, Spain, 8 - 11 July 2009 .

Wang X. , Ongkekp W.M., Chen L. , Yang Z. , Lu P. , Chan K.K. , Lopez J.P., Poon R.T.P. and Fan S.T. , Oct4 mediates chemotherapeutic drug resistance in liver cancer cells through potential Oct4-AKT-ABCG2 pathway, Hepatology . 2010, 52: 528-539.

Researcher : Wei WI

Project Title:	Intra-arterial chemoradiation for advanced head and neck cancer
Investigator(s):	Wei WI, Sham JST
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	07/2002

Abstract:

To see if chemotherapy and radiotherapy given can help patients with advanced head and neck cancer.

Project Title:	Quantitative analysis of plasma Epstein-Barr-Virus DNA in nasopharyngeal carcinoma after salvage nasopharyngectomy
Investigator(s):	Wei WI
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	09/2002

Abstract:

To study early detection of recurrence after radiothe rapy for nasopharyngeal cancer.

Project Title:	Modifications of techniques of cochlear implantation
Investigator(s):	Wei WI, Au DKK, Ho WK
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	09/2002

Abstract:

To study the technique and mode of insertion of cochlear implant aiming to improve the efficacy of the implant.

Project Title:	Management of snoring and OSA
Investigator(s):	Wei WI, Ho WK
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	09/2002

Abstract:

To find the incidence of snoring and OSA and advance their treatments.

Project Title:	VEGF in nasopharyngeal cancer
Investigator(s):	Wei WI, Kwong DLW, Poon RTP
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	03/2003

Abstract:

To carry out early detection of nasopharyngeal cancer before radiotherapy and after treatment.

Project Title:	Study the spread of aerosol during tracheostomy or intubation
Investigator(s):	Wei WI, Sham JST, Irwin MG
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	04/2003

Abstract:

To investigate the distance and pattern of aerosol spread during surgical procedures in application to SARS.

Project Title:	Head and neck course in China - to teach techniques of contemporary operations and patient care for doctors and nurses working in underdeveloped areas in China. This will benefit those poor patients suffereing from head and neck cancer in China
Investigator(s):	Wei WI, Lam LK, Hui Y, Ng WM
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	10/2003

Abstract:

To teach head and neck surgeons in China the contemporary methods of managing patients suffering from head and neck cancer and also to introduce the concept of optimal nursing care for these patients.

Project Title:	Speech rehabilitation after total laryngectomy - self help and mutual help
Investigator(s):	Wei WI, Ho WK
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	10/2003

Abstract:

To visit the hospitals and centres in China where total laryngectomy is performed for patients suffering from cancer of the larynx.

Project Title:	Cochlear implant for 14 profoundly deaf children in China
Investigator(s):	Wei WI, Au DKK, Hui Y
Department:	Surgery
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	10/2003

Abstract:

To help Chinese children who are profoundly deaf in China to receive the cochlear implant, so that they will be able to hear, speak and to receive education effectively.

Project Title:	Cochlear implant for 14 profoundly deaf Chinese children in China
Investigator(s):	Wei WI, Hui Y, Au DKK
Department:	Surgery - Otorhinolaryngology Un
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	07/2005

Abstract:

To provide profoundly deaf in China a chance to received cochlear implant so that they can learn to hear and speak, and receive normal mainstream educati on.

Project Title:	Speech rehabilitation after total laryngectomy - self help and mutual help
Investigator(s):	Wei WI, Ho LM, Kwok ICL
Department:	Surgery - Otorhinolaryngology Un
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	07/2005

Abstract:

To provide coaching to another laryngectomee who has learned to speak again after surgery to teach patients to speak again.

Project Title:	Head and neck course in China - to teach techniques of contemporary operations and patient care for doctors and nurses working in relatively underdeveloped areas in China
Investigator(s):	Wei WI, Lam LK, Hui Y, Li GKH
Department:	Surgery - Otorhinolaryngology Un
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	07/2005

Abstract:

To teach head and neck surgeons in China the contemp orary methods of managing patients suffering from head and neck cancer and also to introduce the concept of optimal nursing care for these patients.

Project Title:	Bone-anchored hearing aid for the severe deaf patients
Investigator(s):	Wei WI, Ho WK, Au DKK
Department:	Surgery - Otorhinolaryngology Un
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	07/2007

Abstract:

To improve hearing abilities of certain groups of patients who cannot be helped by conventional hearing aids and to provide hearing rehabilitation to children to enhance their speech and language development.

Project Title:	Speech rehabilitation after total laryngectomy - self help and mutual help
Investigator(s):	Wei WI, Kwok ICL
Department:	Surgery - Otorhinolaryngology Un
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	08/2007

Abstract:

To visit the hospitals and centres in China where total laryngectomy are performed for patients suffering from advanced cancer of the larynx. During the visit, the members will introduce to patients the various methods of speech rehabilitation and to show how patients can help each other during the convalescent period.

Project Title:	Head and neck course in China - to introduce techniques of contemporary operations and patient care for doctors and nurses working in relatively underdeveloped areas in China
Investigator(s):	Wei WI, Ng WM, Ho WK
Department:	Surgery - Otorhinolaryngology Un
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	08/2007

Abstract:

Project Title:	American Academy of Otolaryngology - Head and Neck Surgery 2007 Annual Meeting Nasopharyngeal cancer: early diagnosis, treatment and salvage
Investigator(s):	Wei WI
Department:	Surgery - Otorhinolaryngology Un
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	09/2007

Abstract:

N/A

Project Title:	Three-dimensional evaluation of tumor extension patterns of nasopharyngeal carcinoma
Investigator(s):	Wei WI, Wong STS
Department:	Surgery - Otorhinolaryngology Un
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2008

Abstract:

Nasopharyngeal cancer is a common disease in our locality. The primary treatment modality is radiation and concurrent chemotherapy. In a small number of patients the tumour unfortunately recurs after this combined mortality of treatment. The surgical salvage is now possible with the maxillary swing approach nasopharyngect omy. We however, are not sure of the exact infiltrative pattern at the primary site of these recurrent nasopharyngeal cancer. The aim of the project is to study the pattern of tumour extension in the nasopharynx; whether it involves cartilage, the prevertebral muscle, and the skull base. It is known that recurrent tumour after radiation is difficult to diagnose and as it may be well located in submusocal region. We have collected over 50 specimens of nasopharyngectomy performed for recurrent nasopharyngeal cancer after chemoradiation. We plan to perform whole specimen section of these specimens so that, we can have a three-dimensional recognition of the pattern of tumour extension. This could greatly aid the planning of surgical savage. Molecular markers such as hypermethylated CpG rich locus can also be examined on these specimen to define exactly where the margin of resection are and whether further resection is possible to achieve a better surgical clearance. Most nasopharyngeal cancer tissues were obtained through biopsies and we have a unique collection of surgical specimen to allow this type of whole specimen section with histological examination as well as with molecular tests to be carried out. This will determine clearly the pattern of tumour extension of nasophary ngeal cancer after chemoradiation.

Project Title:	Head and neck course in China - to introduce current surgical techniques and patient care for doctors and nurses working in relatively underdevel oped areas in China
Investigator(s):	Wei WI, Ng WM, Ho WK
Department:	Surgery - Otorhinolaryngology Un
Source(s) of Funding:	S.K. Yee Medical Foundation - General Award
Start Date:	09/2008

Abstract:

We will conduct head and neck surgery teaching course in different cities of China for 3 to 4 days annually. Senior surgeons and nurses from other cities and provinces in China would come and get acquainted with the latest developments in surgical technique and treatment plan. The knowledge they gained will help the poor and sick patients suffering from head and neck cancer in China.

List of Research Outputs

Chan K.L. , Fan S.T. , Lo C.M. , Wei W.I. , Ng W.M. , Chung H.Y., Ng K.K.C. , Chan S.C. , Chan K.W. , Tso W.K. , Tsoi N.S. and Tam P.K.H. , Pediatric liver transplantation in Hong Kong - a domain with scarce deceased donors, Journal of Pediatric Surgery . 2009, 44(12): 2316-2321.

Chan Y.W. , Ho A.C.W. and Wei W.I. , Prediction of surgical outcome using plasma Epstein-Barr virus DNA and 18F-FDG PET scan in recurrent nasopharyngeal carcinoma, 4th World Congress of International Federation of Head and Neck Oncologic Societies (IFHNOS) - Shifting Paradigms in Head and Neck Oncology 2010 - Seoul, Korea . 2010.

Chan Y.W. and Wei W.I. , Recurrent head and neck cancer - role of reconstructive surgery, The 3rd International Conference of Facial Plastic Surgery, Nanning, Guangxi, China . 2009.

Chow V.L.Y., Chan Y.W. , Chung J.H.P. and Wei W.I. , Basal cell carcinoma of the head and neck region (HNBCC) - A 10 year experience , 4th World Congress of International Federation of Head and Neck Oncologic Societies (IFHNOS) - Shifting Paradigms in Head and Neck Oncology 2010 - Seoul, Kor ea . 2010.

Chung J.C.K., Ho A.C.W. , Chan Y.W. and Wei W.I. , Outcomes of head and neck cancers in haemic malignancy patients, 4th World Congress of International Federation of Head and Neck Oncologic Societies (IFHNOS) - Shifting Paradigms in Head and Neck Oncology 2010 - Seoul, Korea . 2010.

Wei W.I. , Advisor (2009 – 2010) , Alliance for Patients’ Mutual Help Organizations, Hong Kong . 2010.

Wei W.I. , Advisory Board Member (August 2008 – present) , Head & Neck Oncology . 2010.

Wei W.I. , Advisory Panel (January 2005 - present) , Selection of Heads of Teaching Departments, Faculty of Medicine, The University of Hong Kong . 2010.

Wei W.I. , Advisory Professor (June 2004 – present) , 寧夏醫學院附屬醫院, 2010.

Wei W.I. , Advisory Professor (March 2002 – present), Zhengzhou University, Henan, China . 2010.

Wei W.I. , Alumni Member (1981 - present) , Bernard O'Brien Society, The Microsurgery Research Centre, Australia . 2010.

Wei W.I. , Associate Editor (2007 - 2010) , Head & Neck . 2010.

Wei W.I. , Associate Editor (August 2008 - present) , Japanese Journal of Clinical Oncology . 2010.

Wei W.I. , Audit Committee Member (October 2002 – June 2009) , International Federation of Oto-Rhino-Laryngologi cal Societies . 2010.

Wei W.I. , Cancer of larynx in China (Invited Lecture), Visit to Fudan University Cancer Hopsital, Shanghai, China, 11-13 December 2009 . 2009.

Wei W.I. , Cancer of the larynx in China (Invited Lecture), XIX World Congress of Oto-Rhino-Laryngology, Sao Paulo, Brazil, 1-5 June 2009 . 2010.

Wei W.I. , Chief of Service (November 1994 - June 2010), Department of ENt, Queen Mary Hospital, Hong Kong . 2010.

Wei W.I. , Cluster Chief of Service (Ear, Nose and Throat) (April 2009 – June 2010), Hong Kong West Cluster, Hospital Authority, Hong Kong . 2010.

Wei W.I. , Complications of neck dissection: avoidance and treatment (Invited Lecture), The 15th Combined Congress of Otorhinolaryngology Head and Neck Surgery, Kyungju, Korea, 23 – 24 October 2009 . 2009.

Wei W.I. , Corresponding Fellow (April 1995 - present) , American Laryngological Association . 2010.

Wei W.I. , Corresponding Member (April 1997 – present) , American Academy of Otolaryngology - Head and Neck Surgery . 2010.

Wei W.I. , Corresponding Member (October 1998 – present) , American Head and Neck Society . 2010.

Wei W.I. , Council Member (2003 - present) , Hong Kong College of Otorhinolaryngologists . 2010.

Wei W.I. , Councilor (November 2005 – 2009) , The International Academy of Oral Oncology . 2010.

Wei W.I. , Course Co-director and speaker, Basic techniques of microsurgery, International Comprehensive Head & Neck Course 2008, Qingdao, China (11-12 September 2008) . 2009.

Wei W.I. , Course Co-director and speaker, Myocutaneous free flap, International Comprehensive Head & Neck Course 2008, Qingdao, China (11-12 September 2008) . 2009.

Wei W.I. , Course Co-director and speaker, Results of free flaps and management of complications, International Comprehensive Head & Neck Course 2008, Qingdao, China (11-12 September 2008) . 2009.

Wei W.I. , Course Co-director and speaker, Visceral free flaps (video), International Comprehensive Head & Neck Course 2008, Qingdao, China, 11-12 September 2008 . 2009.

Wei W.I. and Kwong D.L.W. , Current management strategy of nasopharyngeal carcinoma, Clinical and Experimental Otorhinolaryngology . 2010, 3: 1-12.

Wei W.I. , Deputy Chief of Service (2002 - 2010), Department of Surgery, Queen Mary Hospital, Hong Kong . 2010.

Wei W.I. , Director (June 2010 – June 2014) , International Federation of Head and Neck Oncologic Societies . 2010.

Wei W.I. , Editorial Board Honorary Member (1999 - present) , Chinese Journal of Cancer . 2010.

Wei W.I. , Editorial Board Member (1996 – present) , Chinese Journal of Otolaryngology . 2010.

Wei W.I. , Editorial Board Member (2003 - present) , Medical Progress . 2010.

Wei W.I. , Editorial Board Member (2005 – present) , Skull Base . 2010.

Wei W.I. , Editorial Board Member (August 2007 - present) , The Laryngoscope . 2010.

Wei W.I. , Editorial Board Member (January 1997 - present) , Journal of Clinical Otorhinolaryngology (China) . 2010.

Wei W.I. , Editorial Board Member (January 2005 – December 2009) , Auris Nasus Larynx . 2010.

Wei W.I. , Editorial Board Member (January 2008 – December 2011) , The Hong Kong Medical Diary . 2010.

Wei W.I. , Editorial Board Member (July 2007 – June 2010) , European Archives of Oto-Rhino-Laryngology . 2010.

Wei W.I. , Editorial Board Member (May 1997 - present) , The Asean ORL Head and Neck Journal . 2010.

Wei W.I. , Editorial Board Member (November 1994 – present) , The American Journal of Otolaryngology . 2010.

Wei W.I. , Editorial Board Member (November 2006 – present) , Chinese Archives of Otolaryngology & Head and Neck Surgery . 2010.

Wei W.I. , Editorial Board Member (October 1995 - present) , Chinese Journal of Clinical Oncology . 2010.

Wei W.I. , Elected Council Member (December 2009 - present), Hong Kong Academy of Medicine . 2010.

Wei W.I. , Elected Senate Member (November 2006 – November 2009) , The University of Hong Kong . 2010.

Wei W.I. , Examiner (FRCS) - Intercollegiate examination in oto rhinolaryngology (March 2001 - February 2010) , Royal College of Surgeons of Edinburgh . 2010.

Wei W.I. , Executive Committee Member (3 October 2002 – June 2009), International Federation of Oto-Rhino-Laryngological Societies . 2010.

Wei W.I. , Executive Council Member (2009 – present) , SLOBA Medical Link, St. Louis College, Hong Kong . 2010.

Wei W.I. , Executive Member – representing East Asia (October 2002 – June 2009) , International Federation of Oto-Rhino-Laryngological Societies . 2010.

Wei W.I. , Expert Panel – Policies on the Introduction of New Technology, Cyberknife Stereotactic Radiosurgery (March 2007 – present) , The College of Surgeons of Hong Kong . 2010.

Wei W.I. , Flaps and how I do it. Application in ENT – Jejunal freeflap (Invited Lecture), National Symposium Head and Neck Tumours and Reconstruction , Basic to Advance 2009, Awana Genting Highlands, Malaysia, 17-20 August 2009 . 2010.

Wei W.I. , Founding Member (November 2001 - present) , Association of University Surgeons of Asia . 2010.

Wei W.I. , Founding Member and Elected Councillor (May 2005 – July 2009) , The International Academy of Oral Oncology . 2010.

Wei W.I. , Guest Professor (October 2002 – present) , Tongji Medical College, Huazhong University of Science & Technology, China . 2010.

Wei W.I. , History of otology development in China and Hong Kong (Invited Lecture), The 13th British Academic Conference in Otolaryngology, Liverpool, U.K., 8-10 July 2009 . 2010.

Wei W.I. , Hong Kong quality of life of patients with recurrent nasopharyngeal carcinoma (Invited Lecture), XIX World Congress of Oto-Rhino-Laryngology, Sao Paulo, Brazil, 1-5 June 2009 . 2010.

Wei W.I. , Honorary Advisor (1987 - present) , The New Voice Club of Hong Kong . 2010.

Wei W.I. , Honorary Advisor (February 1993 - present) , Alliance for Patients' Mutual Help Organizations, Hong Kong . 2010.

Wei W.I. , Honorary Advisor (February 1995 - present) , Kin Lok Club, Hong Kong (Nasopharyngeal Carcinoma patient support group) . 2010.

Wei W.I. , Honorary Advisor (October 1995 – present) , Driver Rehabilitation Service, ReHabAid Centre, Hong Kong Polytechnic University, Hong Kong . 2010.

Wei W.I. , Honorary Consultant (December 1991 - present) , Department of Surgery, Queen Mary Hospital, Hong Kong . 2010.

Wei W.I. , Honorary Consultant (July 2010 – June 2012) , Department of Surgery, Hong Kong West Cluster Hospital Authority, Hong Kong . 2010.

Wei W.I. , Honorary Consultant in Otorhinolaryngology (January 2009 – December 2011), Hong Kong Sanatorium & Hospital . 2010.

Wei W.I. , Honorary Director (December 1997 – present) , The First Medical School, West China University of Medical Sciences, Chengdu, Sichuan, China . 2010.

Wei W.I. , Honorary Fellow (February 2000 - present) , Philippine Society of Otolaryngology-Head and Neck Surgery, Philippines . 2010.

Wei W.I. , Honorary Fellow (May 2006 - present) , German Society of Otolaryngology and Head & Neck Surgery . 2010.

Wei W.I. , Honorary Medical Advisor (August 1994 - present) , The Cancer Crusade Angels Service Society of Hong Kong . 2010.

Wei W.I. , Honorary Member (September 1997 - present) , Philippine Academy for Head & Neck Surgery, Philippines . 2010.

Wei W.I. , Honorary Professor (August 2007 - present) , Department of Otolaryngology, Xiang Ya Hospital, Central South University, Hunan, China . 2010.

Wei W.I. , Honorary Professor (February 2006 – present) , The First Affiliated Hospital of Chongqing Medical Sciences . 2010.

Wei W.I. , Honorary Research Fellow (September 2008 – August 2011) , Centre on Behavioral Health, The University of Hong Kong . 2010.

Wei W.I. , Honorary Reviewer, Archives of Otolaryngology – Head & Neck Surgery, U.S.A. . 2010.

Wei W.I. , Honorary Reviewer, Asian Journal of Surgery, Hong Kong . 2010.

Wei W.I. , Honorary Reviewer, Bone Marrow Transplantation, U.K. . 2010.

Wei W.I. , Honorary Reviewer, British Journal of Surgery, U.K. . 2010.

Wei W.I. , Honorary Reviewer, Cancer (Interdiscipline International Journal of the American Cancer Society), U.S.A. . 2010.

Wei W.I. , Honorary Reviewer, Clinical Cancer Research, U.S.A. . 2010.

Wei W.I. , Honorary Reviewer, Head & Neck (Journal for the Sciences and Specialtie s of the Head and Neck), U.S.A. . 2010.

Wei W.I. , Honorary Reviewer, International Journal of Cancer (Official Journal of UICC), Germany . 2010.

Wei W.I. , Honorary Reviewer, Oncology (International Journal of Cancer Research and Treatment), Switzerland . 2010.

Wei W.I. , Honorary Reviewer, The American Journal of Rhinology, U.S.A. . 2010.

Wei W.I. , Honorary Reviewer, The American Journal of Surgery, U.S.A. . 2010.

Wei W.I. , Honorary Reviewer, The Hong Kong Practitioner (Journal of Hong Kong College of Family Physicians), Hong Kong . 2010.

Wei W.I. , Honorary Reviewer, The Laryngoscope, U.S.A. . 2010.

Wei W.I. , Honorary Treasurer (1991 - 2009) , Hong Kong Society of Otorhinolaryngology . 2010.

Wei W.I. , How my philosophy has changed over the past two decades (Invited Lecture), The 13th British Academic Conference in Otolaryngology, Liverpool, U.K., 8-10 July 2009 . 2010.

Wei W.I. , 面部修復整形專題 (Invited Lecture), Inaugural Meeting for Pan Pacific Academy of Facial Plastic Reconstructive Surgery, Nanning, China, 11-1 4 September 2009 . 2009.

Wei W.I. , International Advisor Board Member (2001 - present) , Otolaryngology Head and Neck Surgery – American Academy of Otolaryngology, Head & Neck Surgery . 2010.

Wei W.I. , International Editorial Board Member (February 2007 – present) , The Clinical and Experimental Otorhinolaryngology . 2010.

Wei W.I. , International Editorial Board Member (September 2010 - present) , Acta Oto-Laryngolocia . 2010.

Wei W.I. , Larynx & Pharynx (Panelist), The International Federation of Head and Neck Oncologic Societies –Global Continuing Education Program (Worl d Tour), "Current Concepts in Head and Neck Surgery and Oncology", London, United Kingdom,Barcelona, Spain, Rome, Italy, Athens, Greece, Warsaw, Poland, Moscow, Russia, Mumbai, India, Bangkok, Thailand, Beijing, China, Buenos Aires, Argentina, Bogota, Colombia . 2009.

Wei W.I. , Li Shu Pui Professor of Surgery, Chair in Otorhinolaryngology (November 2007 – Present), Department of Surgery, HKU . 2010.

Wei W.I. , Maxillary swing approach for central skull base tumors , The 1st International Advanced Skull Base Surgery Approaches Course and Workshop, Riyadh Military Hospital, Riyadh, The Kingdom of Saudi Arabia, 5-8 April 2009 . 2010.

Wei W.I. , Member (1984 - present), Association of Head & Neck Oncologists of Great Britain . 2010.

Wei W.I. , Member (1984 - present), Hong Kong Society of Otorhinolaryngology . 2010.

Wei W.I. , Member (1985 - present), Otorhinolaryngological Research Society of Great Britain . 2010.

Wei W.I. , Member (1987 - present), Asian Oceanic Clinical Oncology Association . 2010.

Wei W.I. , Member (1992 - present), Collegium Oto-Rhino-Laryngologicum Amicitiae Sacrum . 2010.

Wei W.I. , Member (March 2003 – present) , Hong Kong Adventist Hospital Foundation Children’s Hearing Fund . 2010.

Wei W.I. , Member (November 1992 - present) , Hong Kong Institution of Science . 2010.

Wei W.I. , Member, the Board of Governors (August 2005 – July 2009) , Prince Philip Dental Hospital, Hong Kong . 2010.

Wei W.I. , Nasopharyngeal Cacner: Early Diagnosis and Treatment (Invited Lecture), AAO-HNSF Annual Meeting 2009, San Diego, United States, 4 – 7 October 2009 . 2009.

Wei W.I. , National Delegate, Hong Kong Representative (1987 - present) , Asian Federation of Laryngectomees Association . 2010.

Wei W.I. , Neck Metastases (Panelist), The International Federation of Head and Neck Oncologic Societies –Global Continuing Education Program (Worl d Tour), "Current Concepts in Head and Neck Surgery and Oncology", London, United Kingdom,Barcelona, Spain, Rome, Italy, Athens, Greece, Warsaw, Poland, Moscow, Russia, Mumbai, India, Bangkok, Thailand, Beijing, China, Buenos Aires, Argentina, Bogota, Colombia . 2009.

Wei W.I. and Chan Y.W. , Neck dissection - practice in Hong Kong, Clinical Management of cervical lymph node metasta sis . 2010, Chapter 28: 419 - 430.

Wei W.I. , Neck dissection – problems and solutions (Invited Lec ture), The 65th Annual Clinical Congress of Philippine College of Surgeons, Pasay City, the Philippines, 6 – 9 December 2009 . 2009.

Wei W.I. , Oral Cancer (Panelist) , The International Federation of Head and Neck Onco logic Societies –Global Continuing Education Program (World Tour), "Current Concepts in Head and Neck Surgery and Oncology", London, United Kingdom,Barcelona, Spain, Rome, Italy, Athens, Greece, Warsaw, Poland, Moscow, Russia, Mumbai, India, Bangkok, Thailand, Beijing, China, Buenos Aires, Argentina, Bogota, Colombia . 2009.

Wei W.I. , Parapharyngeal space and soft tissue tumours, The International Federation of Head and Neck Oncologic Societies –Global Continuing Education Program (World Tour), "Current Concepts in Head and Neck Surgery and Oncology", London, United Kingdom,Barcelona, Spain, Rome, Italy, Athens, Greece, Warsaw, Poland, Moscow, Russia, Mumbai, India, Bangkok, Thailand, Beijing, China, Buenos Aires, Argentina, Bogota, Colombia . 2009.

Wei W.I. and Chan Y.W. , Pectoralis major flap, Flaps and Reconstructive Surgery . Elsevier Inc., 2009, 175-192.

Wei W.I. , Pedicle flap and free flap for head and neck reconstruction (Invited Lecture), The 3rd International Conference and Workshop on Reconstruction of Head & Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China, 5-7 September 2009 . 2009.

Wei W.I. , President (April 2008 - present), Hong Kong Voice Foundation . 2010.

Wei W.I. , Professional Advisor (1 February 1996 - present), The Hong Kong Society for Rehabilitation, Hong Kong . 2010.

Wei W.I. , Reconstructive Surgery (Panelist) , The International Federation of Head and Neck Onco logic Societies –Global Continuing Education Program (World Tour), "Current Concepts in Head and Neck Surgery and Oncology", London, United Kingdom,Barcelona, Spain, Rome, Italy, Athens, Greece, Warsaw, Poland, Moscow, Russia, Mumbai, India, Bangkok, Thailand, Beijing, China, Buenos Aires, Argentina, Bogota, Colombia . 2009.

Wei W.I. , Recurrent head and neck cancer – challenges & limitations (Invited Lecture) , Yearsley Lecture speaker, Helmuth Goepfert The Thirteenth British Academic Conference in Otolaryngology, Liverp ool, U.K., 8-10 July 2009 . 2010.

Wei W.I. , Representative of the Hong Kong Society of Otorhinola ryngology, Head and Neck Surgery (March 2005 – present) , International Federation of Oto-rhino-laryngological Societies . 2010.

Wei W.I. , Result of surgical salvage for recurrent nasopharyngeal carcinoma, The 1st International Advanced Skull Base Surgery Approaches Course and Workshop, Riyadh Military Hospital, Riyadh, The Kingdom of Saudi Arabia, 5-8 April 2009 . 2010.

Wei W.I. , Robotic surgery in ENT (Invited Lecture), Otic Hearing Professional Seminar 2010, Hong Kong, China, 29 June 2010 . 2010.

Wei W.I. , Robotic surgery in head and neck cancer (Invited Lecture), The 4th World Congress of IFHNOS, Seoul, Korea, 15-19 June 2010 . 2010.

Wei W.I. , Role of surgery in head & neck palliation (Invited Lecture), The 13th British Academic Conference in Otolaryngology, Liverpool, U.K., 8-10 July 2009 . 2010.

Wei W.I. , Secretary General (June 2006 – June 2010) , International Federation of Head and Neck Oncologic Societies . 2010.

Wei W.I. , Sinuses & Skull Base (Panelist), The International Federation of Head and Neck Oncologic Societies –Global Continuing Education Program (World Tour), "Current Concepts in Head and Neck Surgery and Oncology", London, United Kingdom,Barcelona, Spain, Rome, Italy, Athens, Greece, Warsaw, Poland, Moscow, Russia, Mumbai, India, Bangkok, Thailand, Beijing, China, Buenos Aires, Argentina, Bogota, Colombia . 2009.

Wei W.I. , Soft tissue and parapharyngeal space tumors (Invited Lecture), Advanced Education Course in Plastic Surgery, British Association of Plastic Reconstructive and Aesthetic Surgeons, Manchester, U. K., 2 – 3 October 2009 . 2010.

Wei W.I. , Surgery for nasopharyngeal cancer in Asia – the path we have treaded (Invited Lecture), The 1st Congress of Asian Society of Head and Neck Oncology (ASHNO), Asian Society of Head and Neck Oncolo gy (ASHNO), Taipei, Taiwan, 18-19 September 2009 . 2010.

Wei W.I. , Surgery for recurrent nasopharyngeal carcinoma, Nasopharyngeal Carcinoma: Multidisciplinary Management . Springer Science and Business Media, 2009, 253-265.

Wei W.I. , Surgical management of NPC (Invited Lecture), Post-registration Certificate Course in Advanced Surgical Nursing, Hospital Authority, Hong Kong, 13 January 2010 . 2010.

Wei W.I. , Surgical management of recurrent nasopharyngeal cancer (Invited Lecture), The 17th Annual Current Concepts in Head and Neck Surgery, New York, U.S.A., 14-15 November 2009 . 2009.

Wei W.I. , Thyroid & Parathyroid Glands (Moderator), The International Federation of Head and Neck Oncologic Societies –Global Continuing Education Program (World Tour), "Current Concepts in Head and Neck Surgery and Oncology", London, United Kingdom,Barcelona, Spain, Rome, Italy, Athens, Greece, Warsaw, Poland, Moscow, Russia, Mumbai, India, Bangkok, Thailand, Beijing, China, Buenos Aires, Argentina, Bogota, Colombia . 2009.

Wei W.I. , Transoral robotic resection of recurrent nasopharyngeal carcinoma (Invited Lecture), World Robotic Symposium 2010, Transoral Robotic Surgery, Orlando, U.S.A., 11 April 2010 . 2010.

Wei W.I. , Yearsley Lecture: Recurrent head and neck cancer - challenges and limitations, The 13th British Academic Conference in Otolaryngology and ENT Expo, 8-10 July 2009, Clinical Otolaryngology . 2009, 34: 10.

Wei W.I. and Kwong D.L.W. , 鼻咽癌診斷與治療新趨向, 育醫造才：探索醫學世界, 香港, 香港大學李嘉誠醫學院, 2010, 57-59.

Wong B.Y.H. , Ng W.M. , Yuen P.W. , Chan J.P.H. , Ho W.K. and Wei W.I. , Early resection and reconstruction of head and neck masses in infants with upper airway obstruction, International Journal of Pediatric Otorhinolaryngology . 2010, 74: 287-291.

Wong S.T.S. , Chan W.S. , Li C.H., Liu W.M. , Tang W.W., Tsao G.S.W. , Tsang R.K.Y. , Ho W.K. , Wei W.I. and Chan Y.W. , Curcumin alters the migratory phenotype of nasopharyngeal carcinoma cells through up-regulation of E-cadherin , Anticancer Research . 2010, 30: 2851-6.

Wong S.T.S. , Ho W.K. , Chan Y.W. , Ng W.M. and Wei W.I. , Mature miR-184 and squamous cell carcinoma of tongue, Head and Neck . 2009, 9: 130-132.

Wong S.T.S. , Man O.Y. , Tsang C.M. , Tsao G.S.W. , Tsang R.K.Y. , Chan Y.W. , Ho W.K. , Wei W.I. and To V.S.H. , Microrna Let-7 Suppresses Nasopharyngeal Carcinoma Cells Proliferation Through Downregulating C-myc Expression, Journal of Cancer Research and Clinical Oncology . Berlin, Springer Berlin / Heidelberg, 2010.

Researcher : West DW

List of Research Outputs

Kwong A. , Ng E.K.O. , Law F.B.F. , Wong L.P., To M.Y., Cheung M.T. , Wong H.N. , Chan V.W., Kurian A., West D.W. , Ford J.M. and Ma E.S., High-resolution melting analysis for rapid screening of BRCA2 founder mutations in Southern Chinese breast cancer patients, Breast Cancer Research and Treatment . 2010, 122(2): 605-607.

Researcher : Wo YH

List of Research Outputs

Ngan E.S.W. , Lau C.S.T. , Wo Y.H. , Chan W.K. , Chan G.C.F. , Wang Y. , Kaplan D. and Tam P.K.H. , Endocrine-gland vascular endothelial growth factor (EG-VEGF) in neuroblastoma tumor initiating cells, Advances in Neuroblastoma Research 2010, Stockham, Sweden, 21-24 June 2010 .

Researcher : Wong ACC

List of Research Outputs

Chan Y.C. , Cheung G.C.Y., Ting A.C.W. , Wong A.C.C. , Yiu W.K. and Cheng S.W.K. , The influence of diabetes mellitus on lower limb reva scularisation, The 11th Annual Congress of Asian Society for Vascular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 .

Ting A.C.W. , Chan Y.C. , Wong A.C.C. , Yiu W.K. , Cheung G.C.Y. and Cheng S.W.K. , Clinical and morphological outcomes after endovascular repair for chronic type B thoracic aortic dissection - early and mid-term results, The 10th Annual Congress of Asian Society for Vascular Surgery, Busan, Korea, 14-17 October 2009. Annals of Vascular Diseases . 2009, 2: S100.

Researcher : Wong BYH

List of Research Outputs

Wong B.Y.H. , Ng W.M. , Yuen P.W. , Chan J.P.H. , Ho W.K. and Wei W.I. , Early resection and reconstruction of head and neck masses in infants with upper airway obstruction, International Journal of Pediatric Otorhinolaryngology . 2010, 74: 287-291.

Researcher : Wong CL

List of Research Outputs

Wong C.L. , Cheung P.F.Y. and Cheung S.T. , Granulin-epithelin precursor modulates chemo-resistance in liver cancer, The 101st Annual Meeting of the American Association for Cancer Research, Washington, DC, U.S.A., 17-21 April 2010. Proceedings of the AACR . 2010, 51: 2556.

Wong C.L. and Cheung S.T. , The role of granulin-epithelin precursor in liver cancer chemo-resistance (Poster Presentation), The 16th Hong Kong International Cancer Congress and The 6th Annual Meeting Centre for Cancer Research, Hong Kong, 4-6 November 2009 .

Researcher : Wong CWS

List of Research Outputs

Ho K.L. , Wong C.W.S. , Au W.H. , Chu S.S.M. and Tam P.C. , Early continence outcomes after robotic radical prostate ctomy - impact of vesicourethral reconstruction (Poster Presentation), The American Urological Association Annual Meeting, San Francisco, USA, 29 May - 3 June 2010 .

Researcher : Wong HN

List of Research Outputs

Kwong A. , Wong L.P., Wong H.N. , Law F.B.F. , Ng E.K.O. , Tang Y.H., Chan W.K., Suen D.T.K. , Choi C., Ho L.S., Kwan K.H., Poon M., Wong T.T., Chan K., Chan S.W., Ying M.W., Chan W.C., Ma E.S., Ford J.M. and West D.W., Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer, Hugo Journal . 2010, 3(1-4): 63-76.

Kwong A. , Ng E.K.O. , Law F.B.F. , Wong L.P., To M.Y., Cheung M.T. , Wong H.N. , Chan V.W., Kurian A., West D.W. , Ford J.M. and Ma E.S., High-resolution melting analysis for rapid screening of BRCA2 founder mutations in Southern Chinese breast cancer patients, Breast Cancer Research and Treatment . 2010, 122(2): 605-607.

Researcher : Wong J

Project Title:	Thoracoscopic cardiomyotomy for achalasia
Investigator(s):	Wong J, Law SYK
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	01/1994

Abstract:

To study the efficacy of a new approach of surgical treatment for achalasia, using endoscopic instruments via tiny incisions into the thoracic cavity, thus avoiding the complications and discomforts if long surgical incision from traditional surgical approach.

Project Title:	Randomised prospective trial comparing the use of neck drain after oesophagectomy with cervical anastomosis
Investigator(s):	Wong J, Law SYK
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	01/1994

Abstract:

To evaluate the need of routine cervical drains after oesophagectomy.

Project Title:	Prospective study of the use of chemoradiotherapy in the treatment of advanced carcinoma of the oesophagus not suitable for resection
Investigator(s):	Wong J, Law SYK
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	01/1995

Abstract:

To evaluate the use of chemoradiotherapy in the treatment of advanced carcinoma of the oesophagus no t suitable for resection.

Project Title:	Retrospective and prospective study on the use of chemotherapy and chemoradiotherapy in the treatment of recurrent disease after oesophagectomy for cancer
Investigator(s):	Wong J, Law SYK
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	01/1995

Abstract:

To evaluate the use of chemotherapy and spare chemoradiotherapy in the treatment of recurrent disease.

Project Title:	Randomised prospective trial investigat ing the effect of preoperative chemo-radiation for resectable carcinoma of the oesophagus
Investigator(s):	Wong J, Law SYK
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	01/1995

Abstract:

To evaluate the use of preoperative chemo-radiation for treatment of oesophageal cancer.

Project Title:	Thoracoscopic oesophagectomy for carcinoma of the oesophagus
Investigator(s):	Wong J, Law SYK
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	04/1996

Abstract:

To study the efficacy of an endoscopic approach in the resection of oesophageal carcinoma without the necessity of a conventional open thoracotomy. This would have the benefit of decreasing the incidence of pulmonary complications and deaths related to these complications associated with conventional surgery. Thoracoscopic oesophagectomy will also be compared with the transhiatal approach to see whether there are differences in morbidit, mortality and survival.

Project Title:	The use of endoscopic ultrasound in staging of esophageal cancer
Investigator(s):	Wong J, Chu KM, Law SYK
Department:	Surgery
Source(s) of Funding:	Other Funding Scheme
Start Date:	07/1996

Abstract:

To evaluate the accuracy and use of endoscopic ultrasound in the management of esophageal cancer.

List of Research Outputs

Omloo J.M.T., Law S.Y.K. , Launois B., Le Prise E., Wong J. , van Berge Henegouwen M.I. and van Lanschot J.J.B., Short and long-term advantages of transhiatal and transthora cic oesophageal cancer resection (Review Article), European Journal of Surgical Oncology. 2009 . 2009, 35(8): 793-797.

Researcher : Wong KF

Project Title:	Targeting cadherin-17 for treatment of hepatocellular carcinoma by monoclonal antibody
Investigator(s):	Wong KF, Poon RTP, Luk JMC
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	10/2009

Abstract:

Hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Surgical intervention is the only potentially curative treatment so far, but unfortunately, only few HCC patients are eligible for this intervening approach, and patients are under high risk of post-operative recurrence (El-Serag et al., 2008). Small-molecule kinase inhibitors and monocl onal antibodies (mAbs) against growth receptors have emerged as targeted therapies for HCC. Despite their success in animal models, therapeutic efficacy of these experimental agents remains to be established (Spangenberg et al., 2009). In this context, we analyzed both genome and proteome of clinical HCC cohorts and laboratory animal models, and identified cadherin-17 as a promising therapeutic target for HCC. Cadherin-17 (CDH17), also known as liver-intestine cadherin (LI-cadherin), is a cell-surface adhesion molecule that consists of seven extracellular domains and a very short cytoplasmic tail (Wendeler et al., 2006). CDH17 is not expressed in health adult liver, but we have detected its over-expression in liver malignancy of Chinese HCC cohorts (Wong et al., 2003). In addition, over-expression of an alternatively spliced isoform lacking exon 7 in HCC patients is associated with poor prognosis (Wang et al., 2005). Furthermore, Chinese individuals inherited with this specific CDH17 haplotype are under increased risk of developing HCC (Wang et al., 2006). To validate CDH17 as a therapeutic target of HCC, we knocked down the CDH17 expression in a xenograft mouse model by RNA interference (RNAi). Knocking down CDH17 expression suppressed tumor growth and angiogenesis. It also led to inactivation of the Wnt signaling pathway, a pathway widely known essential to HCC tumorigenesis (Liu et al., 2009). All these data suggested clearly that targeting CDH17 holds promise for HCC treatment. Although abrogating CDH17 expression in liver malignancy by RNAi is a promising strategy to intervene HCC, use of RNAi as therapeutic is gene rally not accepted in most country because of the lentivirus-based delivery method. As such, this work aims to develop a mAb that specifically targets and abrogates CDH17 functions in HCC tumor. Therapeutic mAbs are generally accepted for treatment of diseases, and indeed, the first clinical uses of therapeutic mAbs in can be date d back to 1980s. Because of its high specificity towards antigen, antibody-therapy shows enhanced pharmacokinetics with reduced toxicity and undesirable side effects (Luk et al., 2006). Specific Objectives: 1) A mouse mAb targeting the extracellular domain of CDH17 will be generated using hybridoma fusion technology. To this end, recombinant CDH17 extracellular domain (EC) protein will be produced, purified, and injected to immunize BALB/c mice. 2) The anti-cdh17 mAb generated in Part (1) will be assessed for its ability to inhibit HCC cell proliferation, to reduce cellular invasion, and to induce cancer cell apoptosis using different in vitro assays. 3) The effect of anti-cdh17 mAb on tumor growth, angiogenesis, and metastasis of will be examined in a HCC xenograft mouse model. References: El-Serag HB, Marrero JA, Rudolph L, et al. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology 2008; 134(6): 1752-63. Liu LX, Lee NP, Chan VW, et al. Targeting cadherin-17 inactivates wnt signaling and inhibits tumor growth in liver carcinoma. Hepatology 2009; In press. Luk JM and Wong KF. Monoclonal antibodies as targeting and therapeutic agents: prospects for liver transplantation, hepatitis and hepatocellular carcinoma. Clin Exp Pharmacol Physiol 2006; 33(5-6): 482-8. Spangenberg HC, Thimme R and Blum HE. Targeted therapy for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2009; 6(7): 423-32. Wang XQ, Luk JM, Garcia-Barcelo M, et al. Liver intestine-cadherin (CDH17) haplotype is associated with increased risk of hepatocellular carcinoma. Cli n Cancer Res 2006; 12(17): 5248-52. Wang XQ, Luk JM, Leung PP, et al. Alternative mRNA splicing of liver intestine-cadherin in hepatocellular carcinoma. Clin Cancer Res 2005; 11(2 Pt 1): 483-9. Wendeler MW, Jung R, Himmelbauer H, et al. Unique gene structure and paralogy define the 7D-cadherin family. Cell Mol Life Sci 2006; 63(13): 1564-73. Wong BW, Luk JM, Ng IO, et al. Identification of liver-intestine cadherin in hepatocellular carcinoma--a potential disease marker. Biochem Biophys Res Commun 2003; 311(3): 618-24.

List of Research Outputs

Chan K.L. , Wong K.F. and Luk J.M.C. , Role of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis: pathogenesis and therapeutic implications, World Journal of Gastroenterology . 2009, 15(38): 4745-4752.

Wong K.F. and Luk J.M.C. , Endotoxin-neutralizing peptides as gram-negative sepsis therapeutics, Protein and Peptide Letters . 2009, 16(5): 539-542.

Researcher : Wong KF

List of Research Outputs

Chan K.L. , Wong K.F. and Luk J.M.C. , Role of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis: pathogenesis and therapeutic implicat ions, World Journal of Gastroenterology . 2009, 15(38): 4745-4752.

Wong K.F. and Luk J.M.C. , Endotoxin-neutralizing peptides as gram-negative sepsis therapeutics, Protein and Peptide Letters . 2009, 16(5): 539-542.

Researcher : Wong KH

List of Research Outputs

Tong D.K.H. , Law S.Y.K. , Kwong D.L.W. , Chan K.W. , Lam A.K.Y. and Wong K.H. , Histopathological regression of the primary tumor indicated by percentage of residual viable cells is an important prognostic factor after neoadjuvant chemoradiation therapy for esophageal cancer (Abstract), GASTRO 2009 UEGW/WCOG, London, United Kingdom, 21-25 November 2009 .

Tong D.K.H. , Law S.Y.K. , Kwong D.L.W. , Chan K.W. , Lam A.K.Y. and Wong K.H. , Histopathological regression of the primary tumor indicated by percentage of residual viable cells is an important prognostic factor after neoadjuvant chemoradiation therapy for esophageal cancer, Gut . 2009, Supplement No II Vol 58 - Endoscopy Supplement No I Vol 41: A74.

Tong D.K.H. , Wong K.H. and Law S.Y.K. , Myotomy for achalasia, Hong Kong Surgical Forum, Department of Surgery, The University of Hong Kong, Queen Mary Hospital AND Hong Kong Chapter, American College of Surgeons, 9 January 2010 . 2010.

Researcher : Wong KKY

Project Title:	Gene polymorphism in the Sonic Hedgehog, Notch and Wnt signalling pathways in patients with keloid
Investigator(s):	Wong KKY
Department:	Surgery
Source(s) of Funding:	Queen Mary Hospital Charitable Trust - Training and Research Assistance Scheme
Start Date:	06/2006

Abstract:

The study is expected to: (1) Advance our current knowledge on the aetiology of hypertrophic scar and keloid. (2) Be able to predict the likelihood of keloid after wound healing. (3) Generate publications in peer-reviewed journals.

Project Title:	Investigation into the use of ther mosensitive hydrogel PEG-PLGA-PEG as a nano-metallic drug carrier
Investigator(s):	Wong KKY, Ho CM
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	12/2008
Completion Date:	05/2010

Abstract:

Problems being addressed: In our preliminary experiments, we showed that gold porphyrin was efficient in killing tumor cells in culture. Although the efficacy of gold porphyrin is not in doubt in in-vitro experiments, the side effects due to systemic toxicity in vivo remains a significant problem. Many animals died due to the inherent toxicity of the nano-drug. If this drug is to be used eventually in clinical settings, the proble m of a narrow therapeutic window of gold porphyrin needs to be overcome. The overall aim of the proposed study is to investigate if the systemic toxicity of gold porphyrin can be reduced by its conjugation to a thermal sensitive gel formulation. The objectives of the proposed project are therefore: 1. To produce a new nano-compound by conjugating gold porphyrin and PEG-PLAG-PE G 2. To test the biological properties of the new nano-compound, in terms of anti-tumor efficacy and toxicity in an animal model of neuroblastoma.

Project Title:	The use of encapsulated gold-por phyrin nanoparticles as a novel treatment for neuroblastoma
Investigator(s):	Wong KKY, Lee PY
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	11/2009

Abstract:

The proposed project is to investigate the potential of encapsulated gold-porphyrin nanoparticles as a nov el chemotherapy agent for neuroblastoma. In our previous experiments using naked gold-porphyrin molecules, we showed that this agent had very significant effect in neuroblastoma cell lines in-vitro. However, when translated to in-vivo model, gold-porphyrin proved to have systemic side effects. We propose that this is due to the inherent non-selectivity and high toxicity of the drug. To overcome this, we plan to encapsulate the molecule into a nano-sized particle. This will provide, on one hand, an enhanced uptake into tumour cells. On the other hand, give a controlled release of the drug.

Project Title:	3rd EUROPEAN CONFERENCE FOR CLINICAL NANOMEDICINE A safe and efficient lipidic nanoparticle carrier of gold porphryin for the treatment of neuroblastoma
Investigator(s):	Wong KKY
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	05/2010
Completion Date:	05/2010

Abstract:

N/A

List of Research Outputs

Chan I.H.Y., Wong K.K.Y. , Lan L.C.L. and Tam P.K.H. , Early experience of single port laparoscopic surgery in a tertiary referral centre in Hong Kong, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Chan I.H.Y., Lam W.W.M., Wong K.K.Y. and Tam P.K.H. , Renal pelvis haematoma causing pelvirureter obstruction: a first case of Antopol-Goldman lesion in neonate (Letter to the Editor), Journal of Paediatrics and Child Health . 2010, 46(6): 361-362.

Chan I.H.Y., Wong K.K.Y. , Chan G.C.F. and Tam P.K.H. , Surgical outcomes of patients with neuroblastoma in a tertiary centre in Hong Kong: a 12-year experience, Hong Kong Journal of Paediatrics (New Series) . 2009, 14(3): 186-193.

Chung P.H.Y., Wong K.K.Y. , Wong R.M.S. , Tsoi N.S. , Chan K.L. and Tam P.K.H. , Clinical experience in managing pediatric patients with ultra-short bowel syndrome using Omega-3 fatty acid, European Journal of Pediatric Surgery . 2010, 20(2): 139-142.

Chung P.H.Y., Lan L.C.L. , Wong K.K.Y. and Tam P.K.H. , Deflux injection for the treatment of vesicoureteric reflux in children—a single centre's experience, Asian Journal of Surgery . 2009, 32(3): 163-166.

Chung P.H.Y., Wong K.K.Y. , Tam P.K.H. , Chan K.L. , Ng K.K.C. , Chan S.C. , Hui T.W.C. , Yong B.H. , Fan S.T. and Lo C.M. , Split graft liver transplant for paediatric patients in Hong Kong, Hong Kong Journal of Paediatrics (New Series) . 2009, 14: 181-185.

Chung P.H.Y., Wong K.K.Y. , Lan L.C.L. and Tam P.K.H. , Thoracoscopic bullectomy for primary spontaneous pne umothorax in pediatric patients, Pediatric Surgery International . 2009, 25(9): 763-766.

Ehsan M.T., Ng A.T.L., Chung P.H.Y., Chan K.L. , Wong K.K.Y. and Tam P.K.H. , Laparoscopic hernioplasties in children: the implication on contralateral groin exploration for unilateral inguinal hernias, Pediatric Surgery International . 2009, 25(9): 759-762.

Garcia-Barcelo M.M. , Yeung M.Y. , Miao X.P., Tang S.M. , Chen G., So M.T. , Ngan E.S.W. , Lui V.C.H. , Chen Y. , Liu X. , Hui K.J.W.S., Li L., Guo W.H., Sun X.B., Tou J.F., Chan K.W., Wu X.Z., Song Y. , Chan D. , Cheung K.M.C. , Chung P.H.Y., Wong K.K.Y. , Sham P.C. , Cherny S.S. and Tam P.K.H. , Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2, Human Molecular Genetics . 2010, 19 (14): 2917-2925.

Garcia-Barcelo M.M. , Lui V.C.H. , So M.T. , Miao X. , Leon Y.Y. , Yuan Z.W., Ngan E.S.W. , Ehsan T., Chung P.H.Y., Khong P.L. , Wong K.K.Y. and Tam P.K.H. , MNX1 (HLXB9) mutations in Currarino patients, Journal of Pediatric Surgery . 2009, 44(10): 1892-1898.

Gooi Z., Lee R., Wong K.K.Y. and Tam P.K.H. , The use of splenic artery embolisation as a bridge to safe laparoscopic splenectomy in a patient with resistant immune thrombocytopenic purpura, Journal of Paediatrics and Child Health . 2009, 45(12): 767-769.

Hao W. , Liu X. , Lee P.Y. , Chen Y. and Wong K.K.Y. , A study into the effects of omega-3 fatty acids on macrophages and hepatocytes, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Hao W. , Liu X. , Chan I.H.Y., Chan K.L. , Tam P.K.H. and Wong K.K.Y. , Comparison study of post-operative stress response between single-port and three-port laparoscopic varicocelectomy in children, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Lee P.Y. , Zhu Y. , Sun R.W.Y. , Hao W. , Liu X. , Che C.M. and Wong K.K.Y. , A safe and efficient lipidic nanoparticle carrier of gold porphryin for the treatment of neuroblastoma, The 3rd European Conference for Clinical Nanomedicine , Basel, Switzerland, 10-12 May 2010 .

Lee P.Y. , Zhu Y. , Yan J., Sun R.W.Y. , Hao W. , Liu X.L., Che C.M. and Wong K.K.Y. , The cytotoxic effects of lipidic formulated gold-por phyrin nanoparticles for the treatment of neuroblastoma, Nanotechnology, Science and Applications . 2010, 3: 23-28.

Liu X. , Lam G., Wong K.K.Y. and Tam P.K.H. , Perioperative and late outcomes of laparoscopic fundoplic ation for neurologically impaired children, The 43rd Annual Meeting of Pacific Association of Pediatric Surgeons, Kobe, Japan, 23-27 May 2010 .

Liu X. , Lee P.Y. , Ho C.M. , Lui V.C.H. , Chen Y. , Che C.M. , Tam P.K.H. and Wong K.K.Y. , Silver nanoparticles mediate differential responses in keratinocytes and fibroblasts during skin wound healing, ChemMedChem . 2010, 5(3): 468-475.

Miao X. , Garcia-Barcelo M.M. , So M.T. , Tang W.K. , Xiao D. , Wang B. , Mao J.X., Ngan E.S.W. , Chen Y. , Lui V.C.H. , Wong K.K.Y. , Liu L. and Tam P.K.H. , Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population, Journal of Pediatric Surgery . 2010, 45: 709-713.

Miao X. , Leon Y.Y. , Ngan E.S.W. , So M.T. , Yuan Z.W., Lui V.C.H. , Chen Y. , Wong K.K.Y. , Tam P.K.H. and Garcia-Barcelo M.M. , Reduced RET expression in gut tissue on individuals carrying risk alleles of Hirschsprung's disease, Human Molecular Genetics . 2010, 19(8): 1461-1467.

She W.H., Chung H.Y., Lan L.C.L. , Wong K.K.Y. , Saing H. and Tam P.K.H. , Management of choledochal cyst: 30 years of experience and results in a single center, Journal of Pediatric Surgery . 2009, 44(12): 2307-2311.

Tam P.K.H. and Wong K.K.Y. , Cures and hopes for birth defects (Invited Lectures), Medical Education: Public Lecture Series 2009 at Hong Kong Central Library, Hong Kong, 20 October 2009 . 2009.

Wong K.K.Y. and Lam G., A rare anatomical variation of type B esophageal atresia (Short Communication), Journal of Peditaric Surgery . 2009, 44(12): 2433-2434.

Wong K.K.Y. , Current status of paediatric surgery in Queen Mary Hospital, Hong Kong (Invited Lecture), Visit Changchun Children Hospital, Changchun, Jilin, Chna, 13 November 2009 . 2009.

Wong K.K.Y. , Development of minimally invasive paediatric surgery in Hong Kong (Invited Lecture), Visit Harbin Children Hospital, Harbin, Heilongjiang, China, 30 January 2010 . 2010.

Wong K.K.Y. , Editorial Board Member, Nanomedicine: Nanotechnology, Biology and Medicine . 2009.

Wong K.K.Y. , Editorial Board Member, World Journal of Gastrointestinal Endoscopy . 2009.

Wong K.K.Y. , Cheung S.O.F. , Huang L. , Niu J. , Tao C. , Ho C.M. , Che C.M. and Tam P.K.H. , Further evidence of the anti-inflammatory effects of silver nanoparticles, ChemMedChem . 2009, 4(7): 1129-1135.

Wong K.K.Y. , Minimally invasive surgery in children in Hong Kong (Invited Lecture), Visit Changchun Children Hospital, Changchun, Jilin, China, 13 November 2009 . 2009.

Wong K.K.Y. , New horizons in minimally invasive surgery in children (Invited Lecture), The 2nd Second Hospital of Shandong University, Jinan, Shandong . 2010.

Wong K.K.Y. , Reviewer , Archives of Diseases of Childhood . 2009.

Wong K.K.Y. , Reviewer, American Journal of Physiology . 2009.

Wong K.K.Y. , Reviewer, Current Pediatric Review . 2009.

Wong K.K.Y. , Reviewer, Journal of Investigative Dermatology . 2009.

Wong K.K.Y. , Reviewer, Journal of Magnetic Resonance Imaging . 2009.

Wong K.K.Y. , Reviewer, Journal of Nanobiotechnology . 2009.

Wong K.K.Y. , Reviewer, Journal of Pediatric Gastroenterology and Nutrition . 2009.

Wong K.K.Y. , Reviewer, Journal of Pediatric Surgery . 2009.

Wong K.K.Y. , Reviewer, Journal of Pediatrics and Child Health . 2009.

Wong K.K.Y. , Reviewer, Molecular Genetics and Metabolism . 2009.

Wong K.K.Y. , Reviewer, Pediatric Surgery International . 2009.

Wong K.K.Y. , Reviewer, World Journal of Pediatrics . 2009.

Wong K.K.Y. , Single port laparoscopic nephrectomy in children (Invited Lecture), Hong Kong Surgical Forum, Hong Kong, 17 July 2009 . 2009.

Wong K.K.Y. , Chung P.H.Y., Lan L.C.L. , Chan I.H.Y. and Tam P.K.H. , The first report of a single-port laparoscopic nephrect omy in a child, Hong Kong Medical Journal . 2010, 16(2): 153-154.

Wong K.K.Y. , Thoracoscopic repair of congenital esophageal atresia (Invited Lecture), Children Hospital of Fudan University, Shanghai, China, 30 June 2010 . 2010.

Wong K.K.Y. and Tam P.K.H. , Thoracoscopic repair of esophageal atresia through the right chest in neonates with right-sided aortic arch, Journal of Laparoendoscopic & Advanced Surgical Techniques . 2010, 20(4): 403-404.

Wong K.K.Y. , Visiting Professor (2009-2010), Changchun Children Hospital, Jilin, China . 2009.

Wong K.K.Y. , Visiting Professor (2009-2010), Shenzhen Children Hospital, Shenzhen, China . 2009.

Wong K.K.Y. , Visiting Professor (2010-2011), Harbin Children Hospital, Heilongjiang, China . 2010.

Wong K.K.Y. , Visiting Professor (2010-2011), Jiangxi Children Hospital, Jiangxi, China . 2010.

Wong K.K.Y. , Visiting Professor, Changchun Children Hospital . 2009.

Wong K.K.Y. , Visiting Professor, Shenzhen Children Hospital . 2009.

Researcher : Wong STS

Project Title:	Identifying the differential microRNA signatures in squamous cell carcinoma of oral tongue
Investigator(s):	Wong STS, Wei WI
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2009

Abstract:

Objective 1: to identify the aberrantly expressed microRNA (miRNA) in oral tongue carcinomas MicroRNA is a relatively new discovery. MicroRNAs (miRNAs) are small non-coding RNA with size about 19-24 nucleotide in length. MiRNA involves in the post-transcriptional regulation of gene expression. This small RNA could bind to the 3’UTR of the target mRNA. Binding of the miRNA could hinder translation by promoting degradation or inducing deadenylation. MiRNAs are transcribed by RNA polymerase II and III. The primary miRNAs are long precursor RNA molecules. Before transporting into the cytoplasm, these long precursor molecules are processed by cellular nuclease, such as Drosha, into shorter pre-miRNAs. In the cytoplasm, the pre-miRNAs are proc essed by RNA III (Dicer) into the functionally mature form (single-stranded, ~ 22 nucleotides). Mature miRNAs are usually associated with a cellular complex that is similar to the RNA-induced silencing complex participating in RNA interference. There are already strong evidences showing that miRNAs are aberrantly expressed in cancers including oral tongue carcinomas. In order to understand the pathogenesis of oral tongue cancer, there is a compelling need to examine the miRNA expression patterns. Identifying the differentiated expressed miRNA in oral tongue carcinoma will have significant values in diagn osis and prognosis. In year 2007, we performed a pioneer work on miRNA profiling in oral tongue carcinoma. By that time, only 156 miRNAs was reported in human tissues. In addition, the functional role of these miRNAs was unknown. Up to Mar 2009, the reported miRNA is increased from 156 to more than 1500. There is a need for us to perform an updated miRNA screening in oral tongue carcinoma in order to identify significant miRNAs fo r diagnosis and prognosis of oral tongue carcinomas.

Project Title:	Gordon Research Conferences on Mechanisms Of Cell Signalling Mature miR-184 as Potential Oncogenic microRNA in Tongue Cancer
Investigator(s):	Wong STS
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	08/2009
Completion Date:	08/2009

Abstract:

N/A

List of Research Outputs

Leung G.K.K. , Wong S.T.S. and Zhang X. , The potential use of microRNA-21 inhibitors to overcome temozolomide resistance in glioblastoma multiforme, The 7th Meeting of the Asian Society for Neuro-oncology, Seoul, Korea, 10 - 12 June 2010 .

Wong S.T.S. , Chan W.S. , Li C.H., Liu W.M. , Tang W.W., Tsao G.S.W. , Tsang R.K.Y. , Ho W.K. , Wei W.I. and Chan Y.W. , Curcumin alters the migratory phenotype of nasophary ngeal carcinoma cells through up-regulation of E-cadherin , Anticancer Research . 2010, 30: 2851-6.

Wong S.T.S. , Ho W.K. , Chan Y.W. , Ng W.M. and Wei W.I. , Mature miR-184 and squamous cell carcinoma of tongue, Head and Neck . 2009, 9: 130-132.

Wong S.T.S. , Man O.Y. , Tsang C.M. , Tsao G.S.W. , Tsang R.K.Y. , Chan Y.W. , Ho W.K. , Wei W.I. and To V.S.H. , Microrna Let-7 Suppresses Nasopharyngeal Carcinoma Cells Proliferation Through Downregulating C-myc Expr ession, Journal of Cancer Research and Clinical Oncology . Berlin, Springer Berlin / Heidelberg, 2010.

Researcher : Wong TS

Project Title:	Identifying the differential microRNA signatures in squamous cell carcinoma of oral tongue
Investigator(s):	Wong STS, Wei WI
Department:	Surgery
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	06/2009

Abstract:

Objective 1: to identify the aberrantly expressed microRNA (miRNA) in oral tongue carcinomas MicroRNA is a relatively new discovery. MicroRNAs (miRNAs) are small non-coding RNA with size about 19-24 nucleotide in length. MiRNA involves in the post-transcriptional regulation of gene expression. This small RNA could bind to the 3’UTR of the target mRNA. Binding of the miRNA could hinder translation by promoting degradation or inducing deadenylation. MiRNAs are transcribed by RNA polymerase II and III. The primary miRNAs are long precursor RNA molecules. Before transporting into the cytoplasm, these long precursor molecules are processed by cellular nuclease, such as Drosha, into shorter pre-miRNAs. In the cytoplasm, the pre-miRNAs are processed by RNA III (Dicer) into the functionally mature form (single-stranded, ~ 22 nucleotides). Mature miRNAs are usually associated with a cellular complex that is similar to the RNA-induced silencing complex participating in RNA interference. There are already strong evidences showing that miRNAs are aberrantly expressed in cancers including oral tongue carcinomas. In order to underst and the pathogenesis of oral tongue cancer, there is a compelling need to examine the miRNA expression patterns. Identifying the differentiated expressed miRNA in oral tongue carcinoma will have significant values in diagnosis and prognosis. In year 2007, we performed a pioneer work on miRNA profiling in oral tongue carcinoma. By that time, only 156 miRNAs was reported in human tissues. In addition, the functional role of these miRNAs was unknown. Up to Mar 2009, the reported miRNA is increased from 156 to more than 1500. There is a need for us to perform an updated miRNA screening in oral tongue carcinoma in order to identify significant miRNAs for diagnosis and prognosis of oral tongue carcinomas.

Project Title:	Gordon Research Conferences on Mechanisms Of Cell Signalling Mature miR-184 as Potential Oncogenic microRNA in Tongue Cancer
Investigator(s):	Wong STS
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	08/2009
Completion Date:	08/2009

Abstract:

N/A

List of Research Outputs

Researcher : Xiao D

List of Research Outputs

Miao X. , Garcia-Barcelo M.M. , So M.T. , Tang W.K. , Xiao D. , Wang B. , Mao J.X., Ngan E.S.W. , Chen Y. , Lui V.C.H. , Wong K.K.Y. , Liu L. and Tam P.K.H. , Lack of association between nNOS -84G>A polymorphism and risk of infantile hypertrophic pyloric stenosis in a Chinese population, Journal of Pediatric Surgery . 2010, 45: 709-713.

Researcher : Xiao J

List of Research Outputs

Man K. , Shih K.C. , Ng T.P. , Xiao J. , Guo D. , Sun K.W. , Lim Z.X.H. , Cheng Q. , Liu Y. , Fan S.T. and Lo C.M. , Molecular signature linked to acute phase injury and tumor invasiveness in small-for-size liver grafts, Annals of Surgery . 2010, 251(6): 1154-1161.

Man K. , Ng T.P. , Xu A. , Cheng Q. , Lo C.M. , Xiao J. , Sun B. , Lim Z.X.H. , Cheung J.S., Wu E.X. , Sun K.W. , Poon R.T.P. and Fan S.T. , Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of Rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling, Clinical Cancer Research . 2010, 16(3): 967-977.

Researcher : Xie Y

List of Research Outputs

Li W., Xie Y. , Sun R.W.Y. , Liu Q., Young J., Yu W.Y. , Che C.M. , Tam P.K.H. and Ren Y. , Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition, British Journal of Cancer . 2009, 101(2): 342-349.

Researcher : Xu Z

List of Research Outputs

Liu L. , Lee P.Y. , Chan V.W.M. , Xue W., Zender L., Zhang C., Mao M., Dai H., Wang X.L., Xu Z. , Lee K.W. , Ng I.O.L. , Chen Y., Kung H.F., Lowe S.W., Poon R.T.P. , Wang J.H. and Luk J.M.C. , Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma, Hepatology (Erratum in: Hepatology 2010;51(1):358) . 2009, 50(5): 1453-1463.

Sun S. , Xu Z. , Poon R.T.P. , Day P.J. and Luk J.M.C. , Circulating Lamin B1 (LMNB1) biomarker detects early stages of liver cancer in patients, Journal of Proteome Research . 2010, 9(1): 70-78.

Xu Z. , Yes-associated protein (YAP) in hepatocellular carcinoma: oncogenic functions and molecular targeting, Disseration, Doctor of Philosophy, Li Ka Shing Faculty of Medicine, The University of Hong Kong . 2010.

Researcher : Xu Z

List of Research Outputs

Researcher : Yang Z

List of Research Outputs

Chan B.P. , Wong H.L. , Wong M.Y. , Chan G.C.F. and Yang Z. , Methods to Enhance Mesenchymal Stem Cell Migration, Provisional Patent Application (filed on 15 June 2010) (Application No. 61/354,871) . 2010.

Cheung K.F. , Ye D. , Yang Z. , Lu L. , Liu C.H., Wang X.L., Poon R.T.P. , Tong Y. , Liu P., Chen Y. and Lau G. , Therapeutic efficacy of Traditional Chinese Medicine 319 recipe on hepatic fibrosis induced by carbon tetrachloride in rats, Journal of Ethnopharmacology . 2009, 124(1): 142-150.

Lam C.T. , Yang Z. , Fan S.T. and Poon R.T.P. , The proangiogenic role of brain-derived neurotrophic factor in tumor development , The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Lau C.K. , Yang Z. , Ho D.W.Y. , Ng N.P. , Poon R.T.P. and Fan S.T. , Discruption of Akt/hif1 signaling can enhance the therape utic efficacy of ischemic hypoxia and chemotherapy, The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Wang X. , Ongkekp W.M., Chen L. , Yang Z. , Lu P. , Chan K.K. , Lopez J.P., Poon R.T.P. and Fan S.T. , Oct4 mediates chemotherapeutic drug resistance in liver cancer cells through potential Oct4-AKT-ABCG2 pathway, Hepatology . 2010, 52: 528-539.

Wong H.L. , Wong M.Y. , Chan G.C.F. , Yang Z. and Chan B.P. , Functionally selecting human mesenchymal stem cell subpopulations with better migratory activities using a collagen barrier. , 7th Annual Meeting of International Society for Stem Cell Research, Jul 8-11, 2009. Barcelona, Spain. . 2009, 1265.

Yang Z. , Fan S.T. , Ho D.W.Y. , Yu W.C. , Lau C.K. , Ng N.P. and Lam C.Y. , Liver cancer stem cells and HCC recurrence (Oral Presentation), The International Liver Cancer Association Third Annual Congress, Milan, Italy, 4 - 6 September 2009 .

Yang Z. , Liver cancer stem cells and recurrence of hepatocellular carcinoma (Invited Lecture), The Asian Pacific Digestive Week 2009, Taipei, Taiwan, 27-30 September 2009 . 2009.

Researcher : Yau WL

List of Research Outputs

Yau W.L. , Pang R.W.C. and Poon R.T.P. , Identification Of Mir-106b And Mir-21 Overexpression In Hepactocellular Carcinoma By An Orthotopic Metastasis Mouse Model , Hong Kong International Cancer Congress, November 2009, Hong Kong . 2009.

Researcher : Yeung C

List of Research Outputs

Chok K.S.H. , Chu F.S.K. , Cheung T.T. , Lam V.W.T. , Yuen W.K. , Ng K.K.C. , Chan S.C. , Poon R.T.P. , Yeung C. , Lo C.M. and Fan S.T. , Results of percutaneous transhepatic cholecystostomy for high surgical risk patients with acute cholecystitis, ANZ Journal of Surgery . 2010, 80(4): 280-283.

Sun S. , Yi X. , Poon R.T.P. , Yeung C. , Day P.J. and Luk J.M.C. , A protein-based set of reference markers for liver tissues and hepatocellular carcinoma, BMC Cancer . 2009, 9: 309.

Sun S. , Poon R.T.P. , Lee N.P.Y. , Yeung C. , Chan K.L. , Ng I.O.L. , Day P.J.R. and Luk J.M.C. , Proteomics of hepatocellular carcinoma: serum viment in as a surrogate marker for small tumors ( £ 2 cm), Journal of Proteome Research . 2010, 9(4): 1923-1930.

Researcher : Yeung WH

List of Research Outputs

Man K. , Ng T.P. , Liu X. , Yeung W.H. , Lo C.M. and Fan S.T. , Inflammatory microenvironment accelerates liver tumor growth and metastasis by mobilizing circulating endotheli al progenitor cells and increasing cancer stem like cell populations (Abstract), The 101st American Association for Cancer Research Annual Meeting, Washington D.C., U.S.A., 17 - 21 April 2010 .

Researcher : Yi X

List of Research Outputs

Sun S. , Yi X. , Poon R.T.P. , Yeung C. , Day P.J. and Luk J.M.C. , A protein-based set of reference markers for liver tissues and hepatocellular carcinoma, BMC Cancer . 2009, 9: 309.

Researcher : Yiu WK

List of Research Outputs

Basco M.T.G., Yiu W.K. , Cheng S.W.K. and Sumpio B.E., The effects of freezing versus supercooling on vascular cells: Implications for balloon cryoplasty, Journal of Vascular and Interventional Radiology . 2010, 21(6): 910-915.

Chan Y.C. , Cheung G.C.Y., Ting A.C.W. , Wong A.C.C. , Yiu W.K. and Cheng S.W.K. , The influence of diabetes mellitus on lower limb revascularisation, The 11th Annual Congress of Asian Society for Vas cular Surgery held jointly with the 4th Annual Meeting of World Federation of Vascular Societies and the 5th Asian Venous Forum, Kyoto, Japan, 29 June - 2 July 2010 .

Ting A.C.W. , Chan Y.C. , Wong A.C.C. , Yiu W.K. , Cheung G.C.Y. and Cheng S.W.K. , Clinical and morphological outcomes after endovascular repair for chronic type B thoracic aortic dissection - early and mid-term results, The 10th Annual Congress of Asian Society for Vascular Surgery, Busan, Korea, 14-17 October 2009. Annals of Vascular Diseases . 2009, 2: S100.

Yiu W.K. , Best Research Award with Distinction , The Hong Kong College of Surgeons . 2009.

Yiu W.K. , The effects of supercooling and re-warming on vascula r cells survival and proliferation, Dissertation, Doctor of Philosophy, Li Ka Shing Faculty of Medicine, The University of Hong Kong . 2010.

Researcher : Yu WC

List of Research Outputs

Ng K.K.C. , Poon R.T.P. , Chok K.S.H. , Cheung T.T. , Tung H., Chu F.S.K. , Tso W.K. , Yu W.C. and Fan S.T. , High efficacy of high-intensity focused ultrasound without transarterial embolization for hepatocellular carcinoma - Hong Kong experience (Abstract), The 1st International Summit of Noninvasive Ultrasound Treatment, Chongqing, China, 22-23 October 2009 .

Yang Z. , Fan S.T. , Ho D.W.Y. , Yu W.C. , Lau C.K. , Ng N.P. and Lam C.Y. , Liver cancer stem cells and HCC recurrence (Oral Pre sentation), The International Liver Cancer Association Third Annual Congress, Milan, Italy, 4 - 6 September 2009 .

Researcher : Yuen PW

Project Title:	Crile Centennial Symposium Pathology and Staging: Problems and Future Directions
Investigator(s):	Yuen PW
Department:	Surgery
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2006

Abstract:

N/A

List of Research Outputs

Wong B.Y.H. , Ng W.M. , Yuen P.W. , Chan J.P.H. , Ho W.K. and Wei W.I. , Early resection and reconstruction of head and neck masses in infants with upper airway obstruction, International Journal of Pediatric Otorhinolaryngology . 2010, 74: 287-291.

Researcher : Yuen WK

List of Research Outputs

Chok K.S.H. , Ng K.K.C. , Cheung T.T. , Yuen W.K. , Poon R.T.P. , Lo C.M. and Fan S.T. , An update on long-term outcome of curative hepatic resection for hepatocholangiocarcinoma, World Journal of Surgery . 2009, 33(9): 1916-1921.

Chok K.S.H. , Chu F.S.K. , Cheung T.T. , Lam V.W.T. , Yuen W.K. , Ng K.K.C. , Chan S.C. , Poon R.T.P. , Yeung C. , Lo C.M. and Fan S.T. , Results of percutaneous transhepatic cholecystostomy for high surgical risk patients with acute cholecystitis, ANZ Journal of Surgery . 2010, 80(4): 280-283.

Loong F. , Chan A.C.L., Ho B.C.S., Chau Y.P., Lee H.Y., Cheuk W., Yuen W.K. , Ng W.S., Cheung H.L. and Chan J.K.C., Diffuse large B-cell lymphoma associated with chronic inflammation as an incidental finding and new clinical scenarios, Modern Pathology . 2010, 23(4): 493-501.

Yuen W.K. , Outstanding Staff Award, Hong Kong West Cluster, Hospital Authority, Hong Kong . 2010.

Researcher : Zhang W

List of Research Outputs

Wang X. , Zhang W. and Poon R.T.P. , Nanog promoter methylation and chromatin modification in different cancer cells, The International Society for Cancer Stem Cell 7th Annual Meeting, Barcelona, Spain, 8 - 11 July 2009 .

Researcher : Zhang X

List of Research Outputs

Leung G.K.K. , Wong S.T.S. and Zhang X. , The potential use of microRNA-21 inhibitors to overcome temozolomide resistance in glioblastoma multiforme, The 7th Meeting of the Asian Society for Neuro-oncology, Seoul, Korea, 10 - 12 June 2010 .

Researcher : Zhu R

List of Research Outputs

Zhu R. , Liver-Intestine Cadherin (CDH17) in hepatocellular carcinoma: molecular analysis and clinical implications, Dissertation, Doctor of Philosophy, Li Ka Shing Faculty of Medicine, The University of Hong Kong . 2010.

Researcher : Zhu Y

List of Research Outputs

Lee P.Y. , Zhu Y. , Sun R.W.Y. , Hao W. , Liu X. , Che C.M. and Wong K.K.Y. , A safe and efficient lipidic nanoparticle carrier of gold porphryin for the treatment of neuroblastoma, The 3rd European Conference for Clinical Nanomedicine, Basel, Switzerland, 10-12 May 2010 .

Lee P.Y. , Zhu Y. , Yan J., Sun R.W.Y. , Hao W. , Liu X.L., Che C.M. and Wong K.K.Y. , The cytotoxic effects of lipidic formulated gold-porphyrin nanoparticles for the treatment of neuroblastoma, Nanotechnology, Science and Applications . 2010, 3: 23-28.

Researcher : de Villa MVH

List of Research Outputs

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft - the significance of aldose reductase signaling on oval cell activation (Travel Award), The 15th Annual International Congress of the Internatio nal Liver Transplant Society, New York City, New York, U.S.A., 8 - 11 July 2009 . 2009.

Liu Y. , Man K. , Cheng Q. , Ng T.P. , Liu X. , de Villa M.V.H. and Lo C.M. , The distinct regeneration pattern of small-for-size fatty liver graft – the significance of aldose reducatase signaling on oval cell activation (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York, U.S.A., 8-11 July 2009. Liver Transplantation . 2009, 15:S72: #O6.

-- End of Listing -- Dept of Surgery

DEPT OF SURGERY

Researcher : Au DKK

Project Title:	Electrical tinnitus suppression in hearing-impaired patients
Investigator(s):	Au DKK, Ho WK
Department:	Surgery
Source(s) of Funding:	Small Project Funding
Start Date:	11/2003