DEPT OF CLINICAL ONCOLOGY



Researcher : Au GKH

List of Research Outputs

Lai T.L., Yung S.T., Chua D.T.T., Au G.K.H., Kwong D.L.W. and Tsang J.W.H., Body Mass Index Is Associated With Breast Cancer Of Large Size And Positive Lymph Nodes In Pre-menopausal Women But Not Post-menopausal Women, 2010.
Lai T.L., Yung S.T., Chua D.T.T., Au G.K.H., Kwong D.L.W. and Tsang J.W.H., Body Mass Index Is Associated With Breast Cancer Of Large Size And Positive Lymph Nodes In Pre-menopausal Women But Not Post-menopausal Women, In: John Smyth, Jeap Verweij, Lilian Siu et al., European Journal of Cancer. Oxford, UK, ElsevierO, 2010, Volume 8 (Supplements): 98.
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 Metastases after Tumour Removal and Whole-brain Irradiation. , American Society of Clinical Oncology. USA, ASCO, American Society of Clinical Oncology (ASCO), 2010.
Lee V.H.F., Kwong D.L.W., Khong P.L., Chua D.T.T., Ng C.Y., Wong G.K.W., Chan K.S., Leung T.W. and Au G.K.H., Co-registration and application of positron emission tomography (PET), computed tomography (CT) as compared with magnetic resonance imaging (MRI) in target localization for undifferentiated carcinoma of the nasopharynx (NPC), ASTRO 2009 Annual Meeting, Chicago, USA, 1-5 November 2009.
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 V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Leung T.W. and Au G.K.H., Dosimetric Predictors of Radiation-induced Acute Nausea and Vomiting in Intensity Modulated Radiation Therapy for Undifferentiated Carcinoma of the Nasopharynx, 10th Biennial ESTRO Conference on Physics and Radiation Technology for Clinical Radiotherapy 2009.
Lee V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Ng T.M.C., Leung T.W. and Au G.K.H., Shrinkage of Volumes of Parotid and Submandibular Glands but Elevated Radiation Doses during Intensity Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma., 4th World Congress of International Federation of Head and Neck Oncologic Societies 2010. Seoul, South Korea, International Federation of Head and Neck Oncologic Societie.
Lee V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Khong P.L., Ng T.M.C., Leung T.W. and Au G.K.H., Shrinkage of Volumes of Parotid and Submandibular Glands but Elevated Radiation Doses during Intensity Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma., Hong Kong International Cancer Congress. Hong Kong, 16th Hong Kong International Cancer Congress, 2009.
Lee V.H.F., Kwong D.L.W., Khong P.L., Chua D.T.T., Ng C.Y., Wong G.K.W., Chan K.S., Leung T.W. and Au G.K.H., The optimal window-setting of Positron Emission Tomography when co-registered with Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) in Target Localization For Undifferentiated Carcinoma of the Nasopharynx (NPC). , European Society of Therapeutic Radiology and Oncology. The Netherlands, ESTRO, European Society of Therapeutic Radiology and Oncology, 2010.
Tsang J.W.H., Lau T.T.S., Lee V.K.H., Yung S.T., Li V.W.K., Cheung T.K., Lam W.W.T., Lee V.H.F., Au G.K.H. and Kwong D.L.W., Higher Education And Younger Age Are Associated With Better Understanding Of Clinical Trials Among Hong Kong Cancer Patients, 16th Hong Kong International Cancer Congress & 6th Annual Meeting Centre For Cancer Researach. 2009.
Tsang J.W.H., Li V.W.K., Lai T.L., Au G.K.H., Chua D.T.T. and Kwong D.L.W., Triple Negative Breast Cancer Patients With Brain Metastasis Are Associated With More Concurrent Lung Metastasis., 32 Annual CTRC-AACR San Antonio Breast Cancer Symposium. 2009.
Tsang J.W.H., Lau T.T.S., Lee V.K.H., Yung S.T., Li V.W.K., Cheung T.K., Lam W.W.T., Lee V.H.F., Au G.K.H. and Kwong D.L.W., Young Investigator Award In Psychosocial Oncology : Higher Education And Younger Age Are Associated With Better Understanding Of Clinical Trials Among Hong Kong Cancer Patients, 16th Hong Kong International Cancer Congress & 6th Annual Meeting Centre For Cancer Research. 2009.


Researcher : Bi J

List of Research Outputs

Bi J., Lau B.S.H., Lv Z.L., Xie D., Li W., Lai Y.R., Zhong J.M., Wu H.Q., Su Q., He Y.L., Zhan W.H., Wen J.M. and Guan X.Y., Overexpression of YKL-40 is an independent prognostic marker in gastric cancer., Human Pathology. 2009, 40: 1790-7.


Researcher : Chan HM

List of Research Outputs

Chen L., Chan H.M., Yuan Y.F., Hu L., Huang J., Ma S.K.Y., Wang J., Dong S., Tang K.H., Xie D., Li Y. and Guan X.Y., CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients, Journal of Clinical Investigation. 2010, 120: 1178-1191.


Researcher : Chan KC

List of Research Outputs

Chan K.C., Ko J.M.Y., Lung H.L., Sedlacek R. and Lung M.L., Importance of zinc-binding domain of matrix metalloproteinase 19 (MMP19) in tumor suppression and anti-angiogenesis of nasopharyngeal carcinoma , the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21. 2010.


Researcher : Chen L

List of Research Outputs

Chen L., Chan H.M., Yuan Y.F., Hu L., Huang J., Ma S.K.Y., Wang J., Dong S., Tang K.H., Xie D., Li Y. and Guan X.Y., CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients, Journal of Clinical Investigation. 2010, 120: 1178-1191.
Chen M., Huang J., Hu L., Zheng B., Chen L., Tsang S.L. and Guan X.Y., Transgenic CHD1L expression in mouse induces spontaneous tumors, PLoS One. 2009, 4: e6727.
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.
Tang D., Dong S., Ma N.F., Xie D., Chen L., Fu L., Lau S.H., Li Y., Li Y. and Guan X.Y., Overexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma, Hepatology. 2010, 51: 1255-63.


Researcher : Chen M

List of Research Outputs

Chen M., Huang J., Hu L., Zheng B., Chen L., Tsang S.L. and Guan X.Y., Transgenic CHD1L expression in mouse induces spontaneous tumors, PLoS One. 2009, 4: e6727.


Researcher : Cheng Y

List of Research Outputs

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.


Researcher : Cheung AKL

Project Title:Functional investigation of candidate tumor suppressor gene, Protein tyrosine phosphatase receptor type G functional domains and angiogenesis effect.
Investigator(s):Cheung AKL, Lung ML
Department:Clinical Oncology
Source(s) of Funding:Small Project Funding
Start Date:01/2010
Abstract:
Nasopharyngeal carcinoma (NPC) is a unique cancer, which is prevalent in southeast China including Hong Kong. The reasons contributing to high incidence rate of NPC are still not very clear. Chemotherapy and radiotherapy are the most effective methods for NPC patient treatment. However, a specific target for chemotherapy for NPC treatment is still lacking and increases the difficulty for NPC patient treatment. Allelic loss on chromosome 3 is commonly found in NPC patient tumors (Mutirangura et al., 1997; Lo et al., 2000). In our previous study, a critical region (CR) for tumor suppression was identified on chromosome 3p21.3 region by a microcell-mediated chromosome transfer (MMCT) approach (Cheng et al., 1998); elements associated with this CR can functionally complement the defect in the NPC cell line. Tumor suppressor genes (TSGs) such as BLU and RASSF1A were identified in our previous studies (Yau et al., 2006; Lo et al., 2007). A candidate TSG, Protein tyrosine phosphatase receptor type G (PTPRG), which maps to the chromosome 3p21 region, was identified in the previous chromosome 3 MMCT study. We showed it to be a candidate TSG in NPC (Cheung et al., 2008). This gene was also found to be important in other cancers including gastric (Wu et al., 2006), lung, and ovarian (van Niekerk and Poels, 1999) cancers. Recent studies report variable levels of expression of PTPRG observed by immunohistochemical (IHC) staining of tissue sections in different cancers (Vezzalini et al., 2007). In particular, IHC staining of PTPRG shows loss of expression in lung, breast, and ovarian cancers, while high grade lymphomas and astrocytomas show PTPRG over-expression. These findings highlight variations reported for PTPRG functions during different stages of tumor development. Functional studies of PTPRG were performed in the breast cancer cell line, MCF7. Over-expression of wild-type PTPRG prolonged doubling times of the MCF7 cell line in proliferation assays, when compared to the vector-alone and antisense controls. Thus, PTPRG can inhibit cell proliferation. In the same study, by using the soft agar assay, significant reduction of colony-forming ability of MCF7 was observed. This suggests the PTPRG has the ability to inhibit anchorage-independent growth ability. In our previous NPC TSG study, down-regulation of PTPRG was observed in both RNA and protein levels with 41% and 67.7%, respectively. PTPRG stable expressing clones were established with a tetracycline-regulated inducible system (Protopopov et al., 2002). Over-expression of PTPRG can suppress tumor growth in in vivo nude mouse assays and induce G0/G1 arrest if interacting with the extracellular matrix (ECM). Inhibition ability of PTPRG occurs through down-regulation of cyclin D1 protein in order to inhibit pRB phosphorylation (Cheung et al., 2008). These results clearly show the importance of PTPRG in NPC development. These results now provide the impetus for the following PTPRGstudies. This gene contains different functional domains; the alpha carbonic anhydrase alpha related protein (CARP) receptor like domain, fibronectin type 3 domain (FNIII), and two protein tyrosine phosphatase (PTPase) domains. In a colon cancer mutation study, mutations on the FNIII and the two PTPase domains were found in patient samples (Wang et al., 2004); losses of function of those domains appear to contribute to cancer development. Detailed investigations of PTPRG protein domains will contribute to our understanding of the functional role of PTPRG and may identify useful future targets for NPC therapeutics. Based on the above information, specifically, the objectives of this project are to: 1. Create PTPRG functional domain constructs to investigate its functions and target molecules. 2. Investigate the ability of PTPRG to inhibit angiogenesis. References Cheng Y et al (1998). Functional evidence for a nasopharyngeal carcinoma tumor suppressor gene that maps at chromosome 3p21.3. Proc Natl Acad Sci USA 95: 3042-7. Cheung AK et al (2008). Functional analysis of a cell cycle-associated, tumor-suppressive gene, protein tyrosine phosphatase receptor type G, in nasopharyngeal carcinoma. Cancer Res 68: 8137-45. Lo KW et al (2000). High resolution allelotype of microdissected primary nasopharyngeal carcinoma. Cancer Res 60: 3348-53. Lo PH et al (2007). Reduced expression of RASSF1A in esophageal and nasopharyngeal carcinomas significantly correlates with tumor stage. Cancer Lett 257: 199-205. Mutirangura A et al (1997). Genomic alterations in nasopharyngeal carcinoma: loss of heterozygosity and Epstein-Barr virus infection. Br J Cancer 76: 770-6. Protopopov AI et al (2002). Human cell lines engineered for tetracycline-regulated expression of tumor suppressor candidate genes from a frequently affected chromosomal region, 3p21. J Gene Med 4: 397-406. van Niekerk CC, Poels LG (1999). Reduced expression of protein tyrosine phosphatase gamma in lung and ovarian tumors. Cancer Lett 137: 61-73. Vezzalini M et al (2007). Expression of transmembrane protein tyrosine phosphatase gamma (PTPgamma) in normal and neoplastic human tissues. Histopathology 50: 615-28. Wang Z et al (2004). Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science 304: 1164-6. Wu CW et al (2006). Protein tyrosine-phosphatase expression profiling in gastric cancer tissues. Cancer Lett 242: 95-103. Yau WL et al (2006). Functional studies of the chromosome 3p21.3 candidate tumor suppressor gene BLU/ZMYND10 in nasopharyngeal carcinoma. Int J Cancer 119: 2821-6.


Project Title:AACR 101st Annual Meeting 2010 Functional studies of a cell cycle and angiogenesis-related candidate tumor suppressor gene, Mirror image polydactyly 1, in nasopharyngeal carcinoma
Investigator(s):Cheung AKL
Department:Clinical Oncology
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 A.K.L., Lung H.L., Ko J.M.Y., Cheng Y., Stanbridge E.J., Zabarovsky E.R., Nicholls J.M., Chua D.T.T., Tsao G.S.W., Guan X.Y. and Lung M.L., Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, mirror image polydactyly 1, in nasopharyngeal carcinoma., In: George Klein, Proc Natl Acad Sci. 2009, 106: 14478-14483.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Cheng Y., Stanbridge E.J., Zabarovsky E.R., Nicholls J.M., Chua D.T.T., Tsao G.S.W., Guan X.Y. and Lung M.L., Functional Studies of a Cell Cycle and Angiogenesis-related Candidate Tumor Suppressor Gene, Mirror Image Polydactyly 1 , in Nasopharyngeal Carcinoma, 16th Hong Kong International Cancer Congress. 2009.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Stanbridge E.J., Zabarovsky E.R. and Lung M.L., Functional studies of a cell cycle and angiogenesis-related candidate tumor suppressor gene, Mirror image polydactyly 1, in nasopharyngeal carcinoma , The 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21. 2010.
Ko J.M.Y., Cheung A.K.L. and Lung M.L., Tumor suppressive and angiogenic role of THSD1 in esophageal squamous cell carcinoma and nasopharyngeal carcinoma, In: Josephine Mun Yee Ko, Arthur KL Cheung, Maria Li Lung., AACR 101st Annual Meeting 2010. Washington, DC, U.S.A., 2010 Apr 17-21: 1.
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.
Lung H.L., Lo P.H.Y., Cheung A.K.L., Apte S.S. and Lung M.L., ADAMTS9 inhibits angiogenesis and induces apoptosis in nasopharyngeal carcinoma , The 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21. 2010.
Lung H.L., Cheung A.K.L., Cheng Y., Kwong F.M., Lo P.H.Y., Law W.L., Chua D.T.T., Zabarovsky E.R., Wang N., Tsao G.S.W., Stanbridge E.J. and Lung M.L., Functional characterization of THY1 as a tumor suppressor gene with anti-invasive activity in nasopharyngeal carcinoma, International Journal of Cancer. 2009, 127: 304-312.


Researcher : Choy TS

List of Research Outputs

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.


Researcher : Chua DTT

Project Title:2000 Annual Meeting of the American Society for Therapeutic Radiology and Oncology Patterns of Failure after Induction Chemotherapy and Radiotherapy for Loco-Regionally Advanced Nasopharyngeal Carcinoma: The Queen Mary Hospital Experience
Investigator(s):Chua DTT
Department:Clinical Oncology
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:10/2000
Abstract:
N/A


Project Title:2001 Annual Scientific Meeting of the American Society for Therapeutic Radiology and Oncology Control of Regional Metastasis after Induction Chemotherapy and Radiotherapy for Nasopharyngeal Carcinoma
Investigator(s):Chua DTT
Department:Clinical Oncology
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:11/2001
Abstract:
N/A


Project Title:The Radiological Society of North America 89th Scientific Assembly and Annual Meeting Prognostic Value of Tumor Volume in Early Stage Nasopharyngeal Carcinoma Treated by Radiotherapy
Investigator(s):Chua DTT
Department:Clinical Oncology
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:11/2003
Abstract:
N/A


Project Title:46th Annual Meeting of the American Society for Therapeutic Radiology and Oncology Prognostic Impact of Hemoglobin Level on Treatment Outcome in Patients with Nasopharyngeal Carcinoma Treated with Sequential Chemoradiotherapy or Radiotherapy Alone
Investigator(s):Chua DTT
Department:Clinical Oncology
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:10/2004
Abstract:
N/A


Project Title:Nasopharyngeal Carcinoma (NPC)
Investigator(s):Chua DTT, Nicholls JM
Department:Clinical Oncology
Source(s) of Funding:Croucher Foundation - Research Grants
Start Date:01/2007
Abstract:
To investigate nasopharyngeal carcinoma.


List of Research Outputs

Cheung A.K.L., Lung H.L., Ko J.M.Y., Cheng Y., Stanbridge E.J., Zabarovsky E.R., Nicholls J.M., Chua D.T.T., Tsao G.S.W., Guan X.Y. and Lung M.L., Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, mirror image polydactyly 1, in nasopharyngeal carcinoma., In: George Klein, Proc Natl Acad Sci. 2009, 106: 14478-14483.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Cheng Y., Stanbridge E.J., Zabarovsky E.R., Nicholls J.M., Chua D.T.T., Tsao G.S.W., Guan X.Y. and Lung M.L., Functional Studies of a Cell Cycle and Angiogenesis-related Candidate Tumor Suppressor Gene, Mirror Image Polydactyly 1 , in Nasopharyngeal Carcinoma, 16th Hong Kong International Cancer Congress. 2009.
Lai T.L., Yung S.T., Chua D.T.T., Au G.K.H., Kwong D.L.W. and Tsang J.W.H., Body Mass Index Is Associated With Breast Cancer Of Large Size And Positive Lymph Nodes In Pre-menopausal Women But Not Post-menopausal Women, 2010.
Lai T.L., Yung S.T., Chua D.T.T., Au G.K.H., Kwong D.L.W. and Tsang J.W.H., Body Mass Index Is Associated With Breast Cancer Of Large Size And Positive Lymph Nodes In Pre-menopausal Women But Not Post-menopausal Women, In: John Smyth, Jeap Verweij, Lilian Siu et al., European Journal of Cancer. Oxford, UK, ElsevierO, 2010, Volume 8 (Supplements): 98.
Lee D.C.W., Lin S.S., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., Epstein-Barr virus latent membrane protein-1 induces cytokine expression through protein kinase PKR., Hong Kong Society for Immunology 2010 Annual General Meeting and Scientific Meeting, LKS Faculty of Medicine, The University of Hong Kong, 17 April. 2010.
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 Metastases after Tumour Removal and Whole-brain Irradiation. , American Society of Clinical Oncology. USA, ASCO, American Society of Clinical Oncology (ASCO), 2010.
Lee V.H.F., Kwong D.L.W., Khong P.L., Chua D.T.T., Ng C.Y., Wong G.K.W., Chan K.S., Leung T.W. and Au G.K.H., Co-registration and application of positron emission tomography (PET), computed tomography (CT) as compared with magnetic resonance imaging (MRI) in target localization for undifferentiated carcinoma of the nasopharynx (NPC), ASTRO 2009 Annual Meeting, Chicago, USA, 1-5 November 2009.
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 V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Leung T.W. and Au G.K.H., Dosimetric Predictors of Radiation-induced Acute Nausea and Vomiting in Intensity Modulated Radiation Therapy for Undifferentiated Carcinoma of the Nasopharynx, 10th Biennial ESTRO Conference on Physics and Radiation Technology for Clinical Radiotherapy 2009.
Lee V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Ng T.M.C., Leung T.W. and Au G.K.H., Shrinkage of Volumes of Parotid and Submandibular Glands but Elevated Radiation Doses during Intensity Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma., 4th World Congress of International Federation of Head and Neck Oncologic Societies 2010. Seoul, South Korea, International Federation of Head and Neck Oncologic Societie.
Lee V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Khong P.L., Ng T.M.C., Leung T.W. and Au G.K.H., Shrinkage of Volumes of Parotid and Submandibular Glands but Elevated Radiation Doses during Intensity Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma., Hong Kong International Cancer Congress. Hong Kong, 16th Hong Kong International Cancer Congress, 2009.
Lee V.H.F., Kwong D.L.W., Khong P.L., Chua D.T.T., Ng C.Y., Wong G.K.W., Chan K.S., Leung T.W. and Au G.K.H., The optimal window-setting of Positron Emission Tomography when co-registered with Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) in Target Localization For Undifferentiated Carcinoma of the Nasopharynx (NPC). , European Society of Therapeutic Radiology and Oncology. The Netherlands, ESTRO, European Society of Therapeutic Radiology and Oncology, 2010.
Lin S.S., Lee D.C.W., Law H.Y., Fang J.W., Chua D.T.T. and Lau A.S.Y., A role for protein kinase PKR in the medication of Epstien-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression., Cytokine. 2010, 50(2): 210-9.
Lung H.L., Cheung A.K.L., Cheng Y., Kwong F.M., Lo P.H.Y., Law W.L., Chua D.T.T., Zabarovsky E.R., Wang N., Tsao G.S.W., Stanbridge E.J. and Lung M.L., Functional characterization of THY1 as a tumor suppressor gene with anti-invasive activity in nasopharyngeal carcinoma, International Journal of Cancer. 2009, 127: 304-312.
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.
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 J.W.H., Li V.W.K., Lai T.L., Au G.K.H., Chua D.T.T. and Kwong D.L.W., Triple Negative Breast Cancer Patients With Brain Metastasis Are Associated With More Concurrent Lung Metastasis., 32 Annual CTRC-AACR San Antonio Breast Cancer Symposium. 2009.


Researcher : Dong S

List of Research Outputs

Chen L., Chan H.M., Yuan Y.F., Hu L., Huang J., Ma S.K.Y., Wang J., Dong S., Tang K.H., Xie D., Li Y. and Guan X.Y., CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients, Journal of Clinical Investigation. 2010, 120: 1178-1191.
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.
Tang D., Dong S., Ma N.F., Xie D., Chen L., Fu L., Lau S.H., Li Y., Li Y. and Guan X.Y., Overexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma, Hepatology. 2010, 51: 1255-63.


Researcher : Fu L

Project Title:Functional study of a candidate tumor suppressor gene UPK1A in esophageal sqamous cell carcinoma
Investigator(s):Fu L, Guan XY
Department:Clinical Oncology
Source(s) of Funding:Small Project Funding
Start Date:10/2008
Abstract:
Background: Esophageal squamous cell carcinoma (ESCC), the major histologic subtype of esophageal cancer, is one of the most common malignancies and ranked as the sixth leading cause of cancer death worldwide (1). ESCC is characterized by its remarkable geographic distribution, and >50% of ESCC cases in the world occur in China. Linzhou (formerly Linxian) and the nearby counties in Henan province of Northern China have the highest incidence of ESCC in the world (1, 2). It has been hypothesized that ESCC arises as a consequence of cumulative genetic and epigenetic alterations in multiple cancer-related genes. Therefore, identifying these key genes and determining their functional roles are critical for better understanding of ESCC pathogenesis. Our earlier studies have concentrated on identifying frequently deleted loci and candidate TSGs within these loci on chromosome 3p. We utilized the high-throughput SNP-Mass-Spectrometry-Genotyping (SMSG) technology to analyze 100 primary ESCCs with 350 SNP markers at 3p (3pter-3p14.2) and found several candidate 3p TSGs, including CHL1, PCAF, RBMS3, PLCD1 and CACNA2D3 (3). One candidate TSG, PLCD1, was further characterized and the results demonstrated that PLCD1 expression was frequently down-regulated in ESCC, which was mainly caused by DNA copy loss and hypermethylation of the promoter region (4). To obtain an accurate overview of genetic changes occurring in ESCC patients from the high-risk region in China, our group recently performed the Affematrix cDNA microarray to compare differentially expressed genes between ESCC tumors and their corresponding nontumorous tissues. Using an arbitrary cutoff line at Signal Log Ratio ≥2.0 or ≤-2.0, 185 up-regulated genes and 225 down-regulated genes were detected in ESCC tumors as compared to normal controls (unpublished data). One of the down-regulated genes we identified is the uroplakin 1A (UPK1A), a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. Although several TM4SF molecules have been identified and implicated in the regulation of cell development, differentiation, proliferation, motility and tumor cell invasion (5), the biochemical functions of this class of molecules are still largely undefined. Our preliminary results showed that UPK1A was frequently down-regulated in 88.9% (8/9) of ESCC cell lines and 84% (42/50) of primary ESCCs. In this proposal, we aim to investigate the role of UPK1A in ESCC development with three specific objectives: Objectives: 1) To study the molecular mechanism by which UPK1A expression is inactivated in ESCC. 2) To characterize tumor-suppressive function of UPK1A. 3) To study the clinical significance of UPK1A in ESCC. Key issue: The key issue of this proposal is to investigate the tumor-suppressive function of UPK1A and its role in ESCC pathogenesis. Problems: The major problem is to prove that UPK1A is a tumor suppressor in the development and progression of ESCC. Genetic (gene mutation) and epigenetic (hypermethylation at promoter region) alterations of UPK1A gene will be investigated. UPK1A gene will be cloned into expressing vector and transfected into ESCC cell lines with low or absent expression of UPK1A. Soft agar assay and tumor formation in nude mice will be used to investigate the tumor-suppressive role of UPK1A. Reference: 1. Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer 2001;37:S4–66. 2. Ke L. Mortality and incidence trends from esophagus cancer in selected geographic areas of China circa 1970-90. Int J Cancer 2002;102:271–274. 3. Qin YR*, Fu L*, Sham PC, Kwong DLW, Zhu CL, Chu KKW, Li Y, Guan XY. Single-nucleotide polymorphism-mass array reveals commonly deleted regions at 3p22 and 3p14.2 associate with poor clinical outcome in esophageal squamous cell carcinoma. Int J Cancer 2008;123: 826-830. (*Co-first author) 4. Fu L, Qin YR, Xie D, Hu L, Kwong KL, Srivastava G, Tsao SW, Guan XY. Characterization of a novel tumor-suppressor gene PLCδ1 at 3p22 in esophageal squamous cell carcinoma. Cancer Res 2007;67:10720-10726. 5. Maecker HT, Todd SC and Levy S. The tetraspanin superfamily: molecular facilitators. FASEB J 1997;11:428-442.


Project Title:The role of tumor fibroblasts secreted Wnt2 in esophageal squamous cell carcinoma
Investigator(s):Fu L, Guan XY
Department:Clinical Oncology
Source(s) of Funding:Small Project Funding
Start Date:10/2009
Abstract:
Background Cancer has long been considered a cell-autonomous process in which progressive genetic and epigenetic alterations transform cells independent of the external context. However, a growing body of evidence suggests that the tumor microenvironment, composed of non-cancer cells and their stroma, plays an important role in cancer development and progression (1, 2). Our previous study has described a broad range of deregulated genes between fibroblasts isolated from esophageal squamous cell carcinoma (ESCC) and their corresponding nontumorous tissues. About 43% (126/292) of known deregulated genes in TFs were associated with cell proliferation, extracellular matrix remodeling, and immune response. Notably, several members of Wnt pathway, including WNT2, WNT5A, LEF1, and WISP1, were up-regulated in TFs, suggesting that Wnt signaling might be involved in the tumor-stromal interactions in esophageal cancer (3). The Wnt proteins are secreted ligand proteins (about 40 kDa in size) that act in a paracrine fashion by activating diverse signaling cascades inside their target cells. The Wnt signaling pathway diversifies into 3 main branches (4). The best understood is the so-called canonical pathway, which activates target genes through stabilization of β-catenin in the nucleus. Wnt proteins can also signal by activating calmodulin kinase II and protein kinase C (known as the Wnt/Ca2+ pathway), which involves an increase in intracellular Ca2+, or Jun N-terminal kinase (known as the planar cell polarity pathway), which controls cytoskeletal rearrangements and cell polarity. The canonical Wnt pathway is the most prevalent Wnt signaling pathways in the development of cancer. Secreted Wnt proteins act on target cells by binding to two distinct families of cell surface receptors: the Frizzled receptors and the single-pass transmembrane low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6, Ref. 5). These receptor complexes transduce a signal to β-catenin via disheveled proteins. In benign cells, most of the β-catenin molecules are transcriptionally inactive and localized at the plasma membrane where they link E-cadherin to the actin cytoskeleton via α-catenin. Additionally, β-catenin is inactivated by a multimolecular complex containing the adenomatous polyposis coli protein, axin, and glycogen synthase kinase-3β (GSK-3β). Serine/threonine phosphorylation of β-catenin by GSK-3β results in its ubiquitination and proteolysis. Canonical Wnt signaling inhibits β-catenin degradation by inactivation of GSK-3β. Hypophosphorylated β-catenin then translocates to the nucleus, where it binds to transcription factors of the T cell factor/lymphocyte enhancer factor (TCF/LEF) family and initiates transcription of target genes, such as MYC, CCND1, and MMP7 (6). One of the up-regulated WNT genes in TFs we identified is WNT2 (log ratio 2.4), which is located on human chromosome 7q31. WNT2 mRNA is expressed in human fetal lung and placenta, but almost undetectable in normal gastrointestinal tract. WNT2 mRNA is frequently up-regulated in human gastric cancer, and WNT2 gene is rarely amplified in human gastric cancer (7). Our preliminary results showed WNT2 mRNA was up-regulated in TFs isolated from ESCC tissues; however, no WNT2 expression was detected in ESCC cancer cell lines. In addition, we also found Wnt2-positive cells were co-localized with TFs inside the primary ESCC tissues by using immunofluorescent double-staining. Based on these findings, we hypothesize that up-regulation of TF secreted Wnt2 could promote ESCC cancer cell development via a paracrine Wnt signaling pathway. In this proposal, we aim to investigate the role of TF secreted Wnt2 in ESCC development with three specific objectives: Objectives 1) To determine the influence of Wnt2 secretion on ESCC tumor cells. 2) To elucidate the mechanism responsible for induction of these influences. 3) To check the potential therapeutic role of Wnt2 monoclonal antibody in ESCC. Key issue The key issue of this proposal is to investigate the role of Wnt2 produced by tumor fibroblasts in ESCC pathogenesis. Problems The major problem is to prove the stromal influence on epithelia cells- tumor fibroblasts secreted Wnt2 is critical for ESCC tumor cell initiation and progression. WNT2 gene will be cloned into expressing vector and transfected into CHO cell line with high secretion ability but without endogenous WNT2 expression. Conditional medium (CM) will be collected from WNT2-expressing CHO cells and empty-vector transfected CHO cells. ESCC tumor cells will be incubated with these CM and functional assays including cell proliferation assay, wound healing assay, and invasion assay will be used to investigate the role of Wnt2 secretion in ESCC tumorigenesis. Reference 1. Bissell MJ, Radisky D. Putting tumours in context. Nat Rev Cancer 2001;1:46 54. 2. Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer 2006;6:392 401. 3. Zhang C, Fu L, Fu J, Hu L, Yang H, Rong TH, Li Y, Liu H, Fu SB, Zeng YX, Guan XY. Fibroblast growth factor receptor positive fibroblasts provide a suitable microenvironment for tumor development and progression in esophageal carcinoma. Clin Cancer Res 2009;15:4017-4027. 4. Widelitz R. Wnt signaling through canonical and non-canonical pathways: recent progress. Growth Factors 2005;23:111-116. 5. Tamaik K, Semenov M, Kato Y et al. LDL-receptor-related proteins in Wnt signal transduction. Nature 2000;407:530-535. 6. Nusse R. Wnt signaling in disease and in development. Cell Res 2005;15:28–32. 7. Katoh M. WNT2 and human gastrointestinal cancer (review). Int J Mol Med 2003;12:811-816.


List of Research Outputs

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.
Tang D., Dong S., Ma N.F., Xie D., Chen L., Fu L., Lau S.H., Li Y., Li Y. and Guan X.Y., Overexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma, Hepatology. 2010, 51: 1255-63.


Researcher : Guan XY

Project Title:49th Annual Meeting of the American Society of Human Genetics The Association of Chromosome 8p Deletion and Tumor Metastasis in Human Hepatocellular Carcinoma
Investigator(s):Guan XY
Department:Clinical Oncology
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:10/1999
Abstract:
N/A


Project Title:51st Annual Meeting of the American Society of Human Genetics Loss of Tyrosine Aminotransferase may Contribute to the Development of Hepatocellular Carcinoma
Investigator(s):Guan XY
Department:Clinical Oncology
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:10/2001
Abstract:
N/A


Project Title:Characterization of role and mechanism of eIF-5A2 in tumor metastasis
Investigator(s):Guan XY
Department:Clinical Oncology
Source(s) of Funding:General Research Fund (GRF)
Start Date:10/2007
Abstract:
To investigate the roles eIF-5A2 in tumor invasion and metastasis; to define the role of DHPS in eIF-5A2-associated metastasis; to identify other metastasis related genes in DHPS/eIF-5A2/metastasis pathway.


Project Title:Evaluation of an Oxygen Therapeutic (IKOR-2084) in the Enhancement of Chemotherapy and Radiotherapy in Rodent Cancer Models
Investigator(s):Guan XY, Man K, Kwong DLW
Department:Clinical Oncology
Source(s) of Funding:Matching Grant for Joint Research
Start Date:09/2008
Completion Date:03/2010
Abstract:
(1) To determine the efficacy of IKOR-2084 in the delivery of oxygen to tumor area; (2) To evaluate the efficacy of IKOR-2084 in the sensitization of chemo-therapy with a rat orthotopic liver cancer model; (3) To evaluate the efficacy of IKOR-2084 in the sensitization of radiation therapy with a mouse xenografic head and neck cancer model.


Project Title:Characterization of anti-apoptotic mechanism of ALC1 in the development of hepatocellular carcinoma
Investigator(s):Guan XY
Department:Clinical Oncology
Source(s) of Funding:Small Project Funding
Start Date:10/2008
Abstract:
Research Background: Hepatocellular carcinoma (HCC) is the sixth most common human cancer in the world, and its prognosis is extremely poor [1]. Significant efforts have been directed towards charting the genetic alterations in HCC in order to further understanding the genetic basis of the disease and identify new therapeutic targets. Amplification of 1q21 is one of the most frequent genetic alterations in HCC; it has been detected in over 50% of HCC patients [2, 3], strongly suggesting the existence of an oncogene within this region. Recently, we isolated a candidate oncogene ALC1 within the 1q21 region by hybrid selection using microdissected DNA from this region [4]. In that work, we found that ALC1 has strong oncogenic activities, including promoting cell proliferation, increasing colony formation in soft agar, inducing tumor formation in nude mice, and inhibiting cell apoptosis [4]. These data strongly suggest that ALC1 is the target oncogene responsible for the 1q21 amplification event and that it plays important role in HCC development. To further explore the molecular mechanism of ALC1 in HCC pathogenesis, a yeast two-hybrid assay was used to identify proteins that interact with ALC1. One protein, Nur77, which is a unique transcriptional factor belonging to the orphan nuclear receptor superfamily was isolated. The interaction between ALC1 and Nur77 has been confirmed by co-immunoprecipitation (unpublished data). Similar to the death signaling that occurs when p53 interacts with anti- and pro-apoptotic Bcl-2 family members in mitochondria, Nur77 directly targets mitochondria and initiates cell apoptosis by binding to Bcl-2 [5]. Several studies have demonstrated that Nur77 protein translocates from the nucleus to the mitochondria in response to pro-apoptotic stimuli [6, 7]. In the mitochondria, Nur77 interacts with Bcl-2 and induces the latter to adopt a pro-apoptotic conformation that triggers downstream apoptotic events, including cytochrome c (Cyt c) release, activation of Apaf-1 and Caspase-9 (Casp 9), and cleavage of pro-Caspase-3 [7]. Escaping apoptosis is one of the major mechanisms of cancer progression, because it extends cell survival and allows for the accumulation of genetic instability and mutations. Therefore, these findings prompted us to assume that the anti-apoptotic activity of ALC1 may involve its interaction with Nur77 in HCC cells. Although Nur77-mediated apoptosis continues to attract attention of researchers, how it is regulated in cancer cells remains unknown. In this proposal, I plan to investigate the effect of ALC1 on Nur77-mediated apoptosis, especially the effect on the translocation of Nur77 from nucleus to mitochondrial membrane. The effect of ALC1 on Nur77-mediated apoptosis pathway, including the release of Cyt c and activation of apoptosis-associated proteins (cleaved Casp 9 and Casp 3), will be addressed. Objectives: 1) To study the effect of ALC1 on the nucleus-mitochondria translocation of Nur77. 2) To study the effect of ALC1 on Nur77-mediated apoptosis pathway. Key issue and problem: Amplification of 1q21 is one of the most frequent genetic changes in HCC. Recently, we isolated a candidate oncogene ALC1 within 1q21 region. Although the oncogenic function of ALC1 has been clearly demonstrated by our previous in vitro and in vivo studies, the molecular mechanism of ALC1 in HCC development remains unknown. Our recent work showed that ALC1 interacts with Nur77, suggesting that the oncogenic function of ALC1 may be associated with its anti-apoptotic ability through the inhibiting Nur77-mediated apoptosis pathway. To elucidate the molecular mechanism of ALC1 in HCC development, two key issues will be addressed in this study. The first key issue is whether ALC1 is able to block the nucleus-mitochondria translocation of Nur77 when ALC1 binds to Nur77? The second key issue is whether ALC1/Nur77 interaction will inhibit Nur77-mediated apoptosis pathway? References: 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108. 2. Wong N, Lai P, Lee SW, Fan S, Pang E, Liew CT, Sheng Z, Lau JW, Johnson PJ. Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis: relationship to disease stage, tumor size, and cirrhosis. Am J Pathol 1999;154:37-43. 3. Guan XY, Fang Y, Sham JS, Kwong DL, Zhang Y, Liang Q, Li H, Zhou H, Trent JM. Recurrent chromosome alterations in hepatocellular carcinoma detected by comparative genomic hybridization. Genes Chromosomes Cancer 2000;29:110-6. 4. Ma NF, Hu L, Fung JM, Xie D, Zheng BJ, Chen L, Tang DJ, Fu L, Wu Z, Chen M, Fang Y, Guan XY. (2008). Isolation and characterization of a novel oncogene, amplified in liver cancer 1, within a commonly amplified region at 1q21 in hepatocellular carcinoma. Hepatology 2008;47:503-10. 5. Moll UM, Marchenko N, Zhang XK. p53 and Nur77/TR3 - transcription factors that directly target mitochondria for cell death induction. Oncogene 2006;25:4725-43. 6. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997;91:479-89. 7. Li H, Kolluri SK, Gu J, Dawson MI, Cao X, Hobbs PD, Lin B, Chen G, Lu J, Lin F, et al. Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science 2000;289, 1159-64.


Project Title:Evaluation of an Oxygen Therapeutic (IKOR-2084) in the Enhancement of Chemotherapy and Radiotherapy in Rodent Cancer Models
Investigator(s):Guan XY
Department:Clinical Oncology
Source(s) of Funding:Innovation and Technology Fund Internship Programme
Start Date:03/2009
Abstract:
(1) To determine the efficacy of IKOR-2084 in the delivery of oxygen to tumor area; (2) To evaluate the efficacy of IKOR-2084 in the sensitization of chemo-therapy with a rat orthotopic liver cancer model; (3) To evaluate the efficacy of IKOR-2084 in the sensitization of radiation therapy with a mouse xenografic head and neck cancer model.


Project Title:Evaluation of an Oxygen Therapeutic (IKOR-2084) in the Enhancement of Chemotherapy and Radiotherapy in Rodent Cancer Models
Investigator(s):Guan XY
Department:Clinical Oncology
Source(s) of Funding:Innovation and Technology Fund Internship Programme
Start Date:03/2009
Abstract:
(1) To determine the efficacy of IKOR-2084 in the delivery of oxygen to tumor area; (2) To evaluate the efficacy of IKOR-2084 in the sensitization of chemo-therapy with a rat orthotopic liver cancer model; (3) To evaluate the efficacy of IKOR-2084 in the sensitization of radiation therapy with a mouse xenografic head and neck cancer model.


Project Title:AACR 100th Annual Meeting 2009 FGFR2-positive fibroblasts provide a suitable microenvironment for tumor development and progression in esophageal carcinoma
Investigator(s):Guan XY
Department:Clinical Oncology
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:04/2009
Abstract:
N/A


Project Title:Characterization of metastatic role of CHD1L in hepatocellular carcinoma
Investigator(s):Guan XY
Department:Clinical Oncology
Source(s) of Funding:Small Project Funding
Start Date:10/2009
Abstract:
Research Background: Hepatocellular carcinoma (HCC) is ranked as the fifth most frequent cancer in the world and affects one million people annually [1]. The prognosis of HCC is very poor, and the worldwide 5-year survival rate worldwide is less than 5%, mainly because of a high potential for vascular invasion, metastasis, and recurrence even after surgical resection [2]. Our previous study showed that amplification of 1q was one of the most frequent genetic alterations in primary hepatocellular carcinoma (HCC) [3]. Using a hybrid-selection strategy, we have isolated a candidate oncogene named chromodomain helicase DNA binding protein 1-like gene (CHD1L) from the 1q21 amplicon [4]. Our preliminary studies have indicated that the amplification and overexpression of CHD1L was detected in over 50% of HCC cases. In addition, CHD1L-transfected cells possess a strong oncogenic ability, including an increase in the colony formation capacity in soft agar and an increase in the tumorigenicity in nude mice, which could be effectively suppressed by using siRNA against CHD1L. Recently, we found that one of the oncogenic functions of CHD1L was associated with its apoptosis-inhibiting effect [5]. CHD1L belongs to SNF2-like family, which contains an SNF2_N domain and a helicase superfamily domain, suggesting that CHD1L may be able to stabilize protein-DNA interactions and play important roles in transcriptional regulation. In order to identify CHD1L-regulated genes, chromatin immunoprecipitation combined with subsequent cloning (ChIP-cloning) was applied to isolate DNA loci bound by CHD1L. Eighteen CHD1L-bound DNA sequences (all contain a specific CHD1L binding motif) and candidate CHD1L-regulated genes were isolated. One candidate CHD1L-regulated gene, RhoGEF9, was selected for further study because RhoGEF9 is a recently described regulator of the Rho GTPase-mediated signaling cascade. One of the important molecular mechanisms in cancer metastasis is the activation of the Rho family of small GTPases, which in turn leads to the rearrangement of the actin cytoskeleton and modulates cadherin-dependent cell-cell contacts. Therefore, characterization of the effect of CHD1L on HCC metastasis will greatly facilitate our understanding of the molecular mechanism of tumor metastasis. Objectives: The proposed study aims to elucidate the molecular mechanisms by which CHD1L manipulates the Rho GTPase signaling networks via the up-regulation of RhoGEF9 expression. Follows are two specific objectives: 1) To validate the up-regulatory effect of CHD1L on RhoGEF9 expression 2) To characterize the role of CHD1L/RhoGEF9 signaling in HCC metastasis Key issues and problems: Although the oncogenic function of CHD1L has been clearly demonstrated by our previous in vitro and in vivo studies, the molecular mechanism of CHD1L in HCC metastasis remains unknown. Our recent work has indicated that CHD1L can specifically bind to the SNF2-binding sequence and regulate the expression of the corresponding target gene. In this proposal, I select one target gene, RhoGEF9, for further study since Rho GTPase signaling networks have been associated with the development and progression of cancer by increasing cell proliferation and mobility. I hypothesize that the oncogenic function of CHD1L is associated with its role in manipulating the Rho GTPase signaling pathway via the transcriptional regulation of RhoGEF9 expression. The first key issue that will be addressed in this proposal is whether or not the expression of RhoGEF9 is regulated by CHD1L, and if this regulation is observed, I propose to determine the mechanism of regulation. Our preliminary data has indicated that the ectopic expression of CHD1L in both stable and transient CHD1L-transfectants is capable of up-regulating RhoGEF9 expression. Since the CHD1L-binding sequence is within the promoter region of RhoGEF9, it is likely that CHD1L is able to directly up-regulate RhoGEF9 expression as a transcription factor. In this proposal, the electrophoretic mobility shift assay will be used to confirm that CHD1L can specifically bind to the promoter region of RhoGEF9. The promoter region of RhoGEF9 will be also cloned into a vector containing the luciferase reporter gene, whereby luciferase activity will be evaluated to determine whether or not RhoGEF9 expression is regulated by CHD1L. The second key issue in this proposal is to determine whether or not the oncogenic function of CHD1L is facilitated through the activation of the Rho GTPase signaling pathway, and to determine the molecular mechanism for this process. Although the oncogenic role of CHD1L has been demonstrated in our previous studies, the molecular mechanism remains unclear. Since CHD1L can up-regulate the expression of RhoGEF9, it is reasonable to propose that the oncogenic function of CHD1L is facilitated through the activation of the Rho GTPases signaling pathway. The Rho GTPase signaling pathway has been associated with cell proliferation, cell invasion and migration. In this proposal, functional assays will be used to investigate the effect of CHD1L on cell growth, proliferation, invasion, and migration. In addition, in order to study the molecular mechanism, I will determine which downstream member of the Rho GTPases (Rho, Rac or Cdc42) is involved in the CHD1L-mediated pathway. I also propose to investigate whether or not the epithelial-mesenchymal transition (EMT) is involved in CHD1L-induced cell invasion and migration. References: [1] Thorgeirsson SS and Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 2002;31:339-46. [2] Poon RT, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 2000;232:10-24. [3] Guan XY, Fang Y, Sham JS, Kwong DL, Zhang Y, Liang Q, Li H, Zhou H, Trent JM. Recurrent chromosome alterations in hepatocellular carcinoma detected by comparative genomic hybridization. Genes Chromosomes Cancer 2000;29:110-6. [4] Ma NF, Hu L, Fung JM, Xie D, Zheng BJ, Chen L, Tang DJ, Fu L, Wu Z, Chen M, Fang Y, Guan XY. Isolation and characterization of a novel oncogene, amplified in liver cancer 1, within a commonly amplified region at 1q21 in hepatocellular carcinoma. Hepatology 2008;47:503-10. [5] Chen L, Hu L, Chan TH, Tsao GSW, Xie D, Huo KK, Fu L, Zheng BJ, Guan XY. Chromodomain helicase/adenosine triphosphatase DNA binding protein 1-like (CHD1L) suppresses the nucleus-to-mitochondria translocation of Nur77 to sustain hepatocellular carcinoma cell survival. Hepatology 2009;50:122-9.


List of Research Outputs

Bi J., Lau B.S.H., Lv Z.L., Xie D., Li W., Lai Y.R., Zhong J.M., Wu H.Q., Su Q., He Y.L., Zhan W.H., Wen J.M. and Guan X.Y., Overexpression of YKL-40 is an independent prognostic marker in gastric cancer., Human Pathology. 2009, 40: 1790-7.
Bi J., Guo A., Lai Y.R., Li B., Zhong J.M., Wu H.Q., Xie Z., He Y.L., Lv Z.L., Lau B.S.H., Wang Q., Huang X.H., Zhang L.J., Wen J.M. and Guan X.Y., Overexpression of clusterin correlates with tumor progression, metastasis in gastric cancer: a study on tissue microarrays, Neoplasma. 2010, 57: 191-197.
Cai M.Y., Zhang B., He W.P., Yang G.F., Rao H.L., Rao Z.Y., Wu Q.L., Guan X.Y., Kung H.F., Zeng Y.X. and Xie D., Decreased expression of PinX1 protein is correlated with tumor development and is a new independent poor prognostic factor in ovarian carcinoma., Cancer Science. 2010, 101(6): 1543-1549.
Chen L., Chan H.M., Yuan Y.F., Hu L., Huang J., Ma S.K.Y., Wang J., Dong S., Tang K.H., Xie D., Li Y. and Guan X.Y., CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients, Journal of Clinical Investigation. 2010, 120: 1178-1191.
Chen M., Huang J., Hu L., Zheng B., Chen L., Tsang S.L. and Guan X.Y., Transgenic CHD1L expression in mouse induces spontaneous tumors, PLoS One. 2009, 4: e6727.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Cheng Y., Stanbridge E.J., Zabarovsky E.R., Nicholls J.M., Chua D.T.T., Tsao G.S.W., Guan X.Y. and Lung M.L., Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, mirror image polydactyly 1, in nasopharyngeal carcinoma., In: George Klein, Proc Natl Acad Sci. 2009, 106: 14478-14483.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Cheng Y., Stanbridge E.J., Zabarovsky E.R., Nicholls J.M., Chua D.T.T., Tsao G.S.W., Guan X.Y. and Lung M.L., Functional Studies of a Cell Cycle and Angiogenesis-related Candidate Tumor Suppressor Gene, Mirror Image Polydactyly 1 , in Nasopharyngeal Carcinoma, 16th Hong Kong International Cancer Congress. 2009.
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.
He L.R., Liu M.Z., Li B.K., Rao H.L., Deng H.X., Guan X.Y., Zeng Y.X. and Xie D., Clusterin as a predictor for chemoradiotherapy sensitivity and patient survival in esophageal squamous cell carcinoma., Cancer Science . 2009, 100: 1591-1596.
Lu S., Lu L., Guan X.Y. and Huang J., The Phenotype Study of Pdss2 Conditional Knockout Mouse, 14th Research Postgraduate Symposium, December 2 & 3, 2009, The University of Hong Kong. 2009.
Ma S.K.Y., Chan K.W. and Guan X.Y., Cancer Stem Cells - Concepts, Methodologies and Therapeutic Implications, In: XY Guan, Cancer Stem Cells. Research Signpost, 2009.
Ma S.K.Y., Tang K.H., Chan K.W. and Guan X.Y., Liver Cancer Stem Cells - A Review of Current Literature and Protocols, In: XY Guan, Cancer Stem Cells. Research Signpost, 2009.
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.
Ma S.K.Y., Chan Y.P., Kwan P.S., Tang K.H., Vielkind J.V., Guan X.Y. and Chan K.W., microRNA-616 induces androgen-independent growth of prostate cancer cells through suppression of TFPI-2 expression , American Association for Cancer Research. 2010.
Tang K.H., Ma S.K.Y. and Guan X.Y., Liver Tumor-initiating Cells / Cancer Stem Cells: Past Studies, Current Status And Future Perspectives, In: R Scatena, A Mordente, B Giardina, Advances In Cancer Stem Cell Biology. Springer, 2010.
Wang Z., Guan X.Y. and Chen J., Anti-tumor effects and mechanisms of Spatholobus suberectus water extracts in vitro and in vivo., HK, 2009, 98.
Wang Z., Loo T.Y., Wang D., Cheng Y., Guan X.Y. and Chen J., Spatholobus suberectus, a potential Chinese herb for cancer treatment, In: OOTR the 6th Annual Conference, OOTR the 6th Annual Conference. Kyoto, Japan, 2010.
Wen J., Zheng B., Hu Y., Zhang X., Yang H., Li Y., Zhang C.Y., Luo K.J., Zang X., Li Y.F., Guan X.Y. and Fu J.H., Comparative proteomic analysis of the esophageal squamous carcinoma cell line EC109 and its multi-drug resistant subline EC109/CDDP, International Journal of Oncology. 2010, 36: 265-74.
Yang G.F., He W.P., Cai M.Y., He L.R., Luo J.H., Deng H.X., Guan X.Y., Zeng M.S., Zeng Y.X. and Xie D., Intensive expression of Bmi-1 is a new independent predictor of poor outcome in patients with ovarian carcinoma, BMC Cancer. 2010, 10: 133.
Zhou J., Huang J., Poon K.M., Chen D., Chan C.S., Ng F., Guan X.Y., Watt R.M., Lu L., Yuen K.Y. and Zheng B., Functional dissection of an IFN-alfa/belta receptor 1 promoter variant that confers higher risk to chronic hepatitis B virus infection. , J Hepat.. 2009, 51(2):: 322-332.


Researcher : Hu L

List of Research Outputs

Chen L., Chan H.M., Yuan Y.F., Hu L., Huang J., Ma S.K.Y., Wang J., Dong S., Tang K.H., Xie D., Li Y. and Guan X.Y., CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients, Journal of Clinical Investigation. 2010, 120: 1178-1191.
Chen M., Huang J., Hu L., Zheng B., Chen L., Tsang S.L. and Guan X.Y., Transgenic CHD1L expression in mouse induces spontaneous tumors, PLoS One. 2009, 4: e6727.


Researcher : Ko JMY

Project Title:Mutations in PALB2 in Chinese esophageal cancer families
Investigator(s):Ko JMY, Lung ML
Department:Clinical Oncology
Source(s) of Funding:Small Project Funding
Start Date:12/2009
Abstract:
Background In the year 2003 the age-adjusted incidence and mortality rates of esophageal cancers (EC) were 81.78 and 68.47 per 100,000 in Linzhou city of Henan, respectively (Sun et al., 2007a; Sun et al., 2007b). Henan EC incidence rate is about 8-fold higher than that in Hong Kong. The male to female sex ratio for developing EC is 3.7. The incidence and mortality rates of EC in male ranks eighth and seventh, respectively, in Hong Kong. Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with a high mortality rate in the Chinese population. Within the high-risk area, there is evidence of familial aggregation suggesting that genetic susceptibility may be one of the etiologic factors for ESCC in addition to environmental exposures. PALB2, stands for partner and localizer of BRCA2, is reported as a cancer susceptibility gene for breast (Erkko et al., 2007; Foulkes et al., 2007; Rahman et al., 2007; Simpson, 2007; Tischkowitz et al., 2007) and pancreatic cancers (Jones et al., 2009). Its monoallelic truncating mutations contribute a 2.3-fold higher risk for breast cancer (Rahman et al., 2007), while biallelic truncations cause Fanconi anemia (FA) as well as childhood cancer (Reid et al., 2007). Finnish cancer families carrying the founder mutation of 1592delT at PALB2 were associated with a roughly four-fold increase of relative risk for breast cancer (Erkko et al., 2007). PALB2 1592delT mutation testing was suggested to Finnish women with breast cancer, especially for patients with an early age at onset or a positive breast or other related cancer history (Erkko et al., 2008). Two high penetrance mutations at 229delT and 2521delA at PALB2 were associated with strong family history of breast cancer (Tischkowitz et al., 2007). PALB2-BRCA2 interaction is essential for BRCA2 to function as a DNA repair protein involved in homologous recombination of DNA double-strand break repair (DSBR) (Fig. 1). PALB2 is the molecular adaptor essential for the loading of BRCA2/RAD51 DNA repair complex to DNA (Xia et al., 2006). This functional relationship makes PALB2 of high interest as a candidate susceptibility gene for inherited EC. The FA-BRCA pathway is shown in Fig.1. It is clearly evident that the FA-BRCA pathway may play a clear etiologic role in inherited cancers. Fig. 2 shows the mutations identified in patients with familial breast cancer, Fanconi anemia, or familial pancreatic cancer (Jones et al., 2009). Inherited breast cancer is associated with germline mutations in ten genes including both BRCA2 and PALB2 (Walsh and King, 2007). Similar to inherited breast cancer, BRCA2 mutations were found in 12% Chinese, 15% Indian, and 7.6% Turkmen familial ESCC cases in high-risk areas from different ethnic groups (Akbari et al., 2008; Hu et al., 2002; Hu et al., 2003; Hu et al., 2004; Kaushal et al., 2009). The DNA damage response proteins, including BRCA2 and PALB2, function downstream of FANCD2 and are breast cancer susceptibility genes. It is of interest to study the role of PALB2 in ESCC susceptibility as BRCA2 germline mutations have been detected in familial ESCC in different regions with high risk EC. Purpose: This current proposal aims to determine if PALB2 is an esophageal cancer susceptibility gene contributing ESCC development in Henan, a high-risk area in Northern China. This is a pilot study to investigate the contribution of PALB2 germline mutations in inherited EC in China. It aims to: 1) determine the prevalence of PALB2 germline mutations in inherited EC and 2) identify high penetrance genetic variants of PALB2 that may be associated with aggressive tumor phenotype as well as founder mutations, such as PALB2 1592delT occurring in Finnish cancer families, in Chinese ESCC families. Key issues and problems addressed ESCC is often a deadly cancer diagnosed at late stage with a 5-year survival rate less than 10% in advanced cancers. It is important to elucidate the molecular genetic basis for this deadly cancer to achieve the ultimate goal of early cancer detection and improved clinical management. One key issue addressed by this current study is to understand the genetic basis of inherited ESCC by deciphering PALB2 mutation status in high risk northern China. Blood was collected from high-risk Henan familial history-positive (FH+) individuals. Blood DNAs were extracted for sequence analysis. By investigation of PALB2 germline mutations and variants, as compared to healthy individuals, the genetic basis and genomic risk factor associations with inherited EC will be clarified. Fundings for the proposed research should improve detection of individuals genetically susceptibility to ESCC development. Earlier detection translates into improved survival. Elucidates the role of the FA-BRCA pathway in ESCC will also provide more molecular targeted therapy options for this deadly cancer. Fig. 1: Please see uploaded file in the “SectionVI: Significance of the research proposal”. References: Please see attached file in the attachment list.


Project Title:AACR 101st Annual Meeting 2010 Tumor suppressive and angiogenic role of THSD1 in esophageal squamous cell carcinoma and nasopharyngeal carcinoma
Investigator(s):Ko JMY
Department:Clinical Oncology
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

Chan K.C., Ko J.M.Y., Lung H.L., Sedlacek R. and Lung M.L., Importance of zinc-binding domain of matrix metalloproteinase 19 (MMP19) in tumor suppression and anti-angiogenesis of nasopharyngeal carcinoma , the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21. 2010.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Cheng Y., Stanbridge E.J., Zabarovsky E.R., Nicholls J.M., Chua D.T.T., Tsao G.S.W., Guan X.Y. and Lung M.L., Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, mirror image polydactyly 1, in nasopharyngeal carcinoma., In: George Klein, Proc Natl Acad Sci. 2009, 106: 14478-14483.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Cheng Y., Stanbridge E.J., Zabarovsky E.R., Nicholls J.M., Chua D.T.T., Tsao G.S.W., Guan X.Y. and Lung M.L., Functional Studies of a Cell Cycle and Angiogenesis-related Candidate Tumor Suppressor Gene, Mirror Image Polydactyly 1 , in Nasopharyngeal Carcinoma, 16th Hong Kong International Cancer Congress. 2009.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Stanbridge E.J., Zabarovsky E.R. and Lung M.L., Functional studies of a cell cycle and angiogenesis-related candidate tumor suppressor gene, Mirror image polydactyly 1, in nasopharyngeal carcinoma , The 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21. 2010.
Ko J.M.Y., Cheung A.K.L. and Lung M.L., Tumor suppressive and angiogenic role of THSD1 in esophageal squamous cell carcinoma and nasopharyngeal carcinoma, In: Josephine Mun Yee Ko, Arthur KL Cheung, Maria Li Lung., AACR 101st Annual Meeting 2010. Washington, DC, U.S.A., 2010 Apr 17-21: 1.
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.


Researcher : Kwan PS

List of Research Outputs

Ma S.K.Y., Chan Y.P., Kwan P.S., Tang K.H., Vielkind J.V., Guan X.Y. and Chan K.W., microRNA-616 induces androgen-independent growth of prostate cancer cells through suppression of TFPI-2 expression , American Association for Cancer Research. 2010.


Researcher : Kwong DLW

Project Title:The use of PET-CT in target delineation for dose escalation in locally advanced nasopharyngeal carcinoma
Investigator(s):Kwong DLW, Khong PL
Department:Clinical Oncology
Source(s) of Funding:Small Project Funding
Start Date:12/2007
Completion Date:12/2009
Abstract:
- To identify the metabolically active tumor with PET-CT and to refine the delineation of target in intensity modulated radiotherapy (IMRT) planning so that the highest radiation dose will conform to the most active part of the tumor. - To test out the efficacy and safety of dose escalation to the part of tumor that is metabolically active for locally advanced disease.


Project Title:The 51st ASTRO Annual Meeting Prognostic significance of parapharyngeal extension in nasapharyngeal carcinoma treated with intensity modulated radiotherapy
Investigator(s):Kwong DLW
Department:Clinical Oncology
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:11/2009
Completion Date:11/2009
Abstract:
N/A


Project Title:Delineating PET active target in radiotherapy of nasopharyngeal carcinoma
Investigator(s):Kwong DLW, Khong PL
Department:Clinical Oncology
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:02/2010
Abstract:
Purpose of project: To develop and validate an automatic contouring algorithm in delineating PET positive tumor so that biological targets are also incorporated in radiotherapy treatment of nasopharyngeal carcinoma. Key Issues and problems being addressed: Radiotherapy (RT) is the backbone of primary treatment for all stages of NPC. Advance in RT will translate into improved outcome, both in terms of survival and reduced toxicity in survivors. Advancement of RT comes from 2 directions: the RT technique and imaging. For RT technique, it is important to precisely control the radiation dose distribution so that the maximum radiation is deposited in the tumor while the unaffected tissue receives minimal radiation. As surgery is not the primary treatment for NPC, radiation oncologists have to rely heavily on imaging to guide them in localizing the tumor for RT. To know the exact boundaries of tumor(s) is of utmost importance in RT planning. It is especially true as we now adopt conformal RT for NPC using intensity modulated radiotherapy (IMRT). IMRT allows a tight margin around tumor with rapid dose fall-off beyond the target to protect normal tissue from unnecessary irradiation. In IMRT planning, the purpose is to match the high dose area to the tumor(s) and keep down the radiation dose to normal tissue especially sensitive critical structures. The standard imaging employed in localizing tumor for IMRT planning for NPC are computer tomography (CT) scan and magnetic resonance imaging (MRI). Both CT and MRI are anatomical imaging. Anatomical imaging has good resolution and both tumors and normal organs can be clearly seen and delineated for IMRT. However, anatomic imaging only tells us where the tumors are but provides no information on the tumor biological activity. Tumor is in fact a heterogeneous mass with different areas of varying proliferative, metabolic activity and oxygenation. The biologically more active part of tumor would require higher radiation dose for control. Fluorodeoxyglucose (FDG) positron emission tomography (PET) scan is the commonly used biological imaging. Actively metabolizing and proliferative tumor tends to be FDG avid. FDG-PET scan is now well accepted for diagnosis and staging of cancers. However, it is still uncertain how PET scan can be integrated into RT treatment of cancers. The main problem is PET scan has poor structural resolution. FDG avid area has indistinct border which makes it difficult to delineate the extent of active tumor which is essential for IMRT treatment. In this project, we shall investigate how to make use of the information from PET scan to delineate the active tumor in NPC so radiation dose can be deposited right where it is needed. Accurate tumor localization will not only improve tumor control but also minimize radiation toxicity and improve quality of life of survivors. We plan to develop an algorithm for contouring the FDG avid area on PET scan to facilitate IMRT plan. Tumor localization is the most labor-intensive part of IMRT planning since radiation oncologists have to visually localize tumor in every images and spend hours in delineating tumor on every 2.5mm CT slides from head to neck. Auto-contouring device will not only make IMRT more efficient but also less user-dependent, and more reliable. Although IMRT is considered the standard of care for NPC, some centres still cannot provide IMRT to all patients because of manpower limitation. Improving efficiency of IMRT planning by auto-contouring will help to reduce manpower requirement, thus, more patient will be able to receive and benefit from IMRT.


List of Research Outputs

Chan K.S., Mak H.K.F., Huang B., Yeung D.W.C., Kwong D.L.W. and Khong P.L., Nasopharyngeal carcinoma: relationship between 18F-FDG PET-CT maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis, and TNM classification, Nuclear Medicine Communication . 2010, 31: 206-210.
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.
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.
Kan M.W., Leung L.H., Kwong D.L.W., Wong W. and Lam N., Peripheral doses from noncoplanar IMRT for pediatric radiation therapy, Medical Dosimetry. 2009.
Kwong D.L.W., Death - from a Medical, Legal Perspective, International Workshop on Death: Philosophy, Therapy, Medicine, 23 April 2010, Centre for the Humanities and Medicine, The University of Hong Kong, Hong Kong. 2010.
Kwong D.L.W., Palliative Radiotherapy; Palliative Chemotherapy, Head and Neck Course 2010: Palliative Therapy for Head and Neck Cancer, 3-4 June 2010. 2010.
Kwong D.L.W., Panel Speaker: 1. Lymphoma in H&N - Radiotherapy for Head and Neck Lymphoma 2. Precision Radiation Therapy for H&N Cancer - the Potential of Integrating Biological Imaging in Radiotherapy. Chairman for proffered paper session: Chemoradiation, 4th World Congress of International Federation of Head and Neck Oncologic Societies, 15-19 June 2010, Seoul, Korea. 2010.
Kwong D.L.W., Prognostic significance of parapharyngeal extension in nasopharyngeal carcinoma treated with intensity modulated radiotherapy, American Society for Therapeutic Radiology and Oncology 51st Annual Meeting, 2009, Chicago, USA. 2009.
Kwong D.L.W., Use of PET in head and neck cancer, National Symposium on Head and Neck Tumors and Reconstruction - Basic to Advance, 17-20 August 2009, Kuala Lumpur, Malaysia. 2009.
Lai T.L., Yung S.T., Chua D.T.T., Au G.K.H., Kwong D.L.W. and Tsang J.W.H., Body Mass Index Is Associated With Breast Cancer Of Large Size And Positive Lymph Nodes In Pre-menopausal Women But Not Post-menopausal Women, 2010.
Lai T.L., Yung S.T., Chua D.T.T., Au G.K.H., Kwong D.L.W. and Tsang J.W.H., Body Mass Index Is Associated With Breast Cancer Of Large Size And Positive Lymph Nodes In Pre-menopausal Women But Not Post-menopausal Women, In: John Smyth, Jeap Verweij, Lilian Siu et al., European Journal of Cancer. Oxford, UK, ElsevierO, 2010, Volume 8 (Supplements): 98.
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 Metastases after Tumour Removal and Whole-brain Irradiation. , American Society of Clinical Oncology. USA, ASCO, American Society of Clinical Oncology (ASCO), 2010.
Lee V.H.F., Kwong D.L.W., Khong P.L., Chua D.T.T., Ng C.Y., Wong G.K.W., Chan K.S., Leung T.W. and Au G.K.H., Co-registration and application of positron emission tomography (PET), computed tomography (CT) as compared with magnetic resonance imaging (MRI) in target localization for undifferentiated carcinoma of the nasopharynx (NPC), ASTRO 2009 Annual Meeting, Chicago, USA, 1-5 November 2009.
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 V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Leung T.W. and Au G.K.H., Dosimetric Predictors of Radiation-induced Acute Nausea and Vomiting in Intensity Modulated Radiation Therapy for Undifferentiated Carcinoma of the Nasopharynx, 10th Biennial ESTRO Conference on Physics and Radiation Technology for Clinical Radiotherapy 2009.
Lee V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Ng T.M.C., Leung T.W. and Au G.K.H., Shrinkage of Volumes of Parotid and Submandibular Glands but Elevated Radiation Doses during Intensity Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma., 4th World Congress of International Federation of Head and Neck Oncologic Societies 2010. Seoul, South Korea, International Federation of Head and Neck Oncologic Societie.
Lee V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Khong P.L., Ng T.M.C., Leung T.W. and Au G.K.H., Shrinkage of Volumes of Parotid and Submandibular Glands but Elevated Radiation Doses during Intensity Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma., Hong Kong International Cancer Congress. Hong Kong, 16th Hong Kong International Cancer Congress, 2009.
Lee V.H.F., Kwong D.L.W., Khong P.L., Chua D.T.T., Ng C.Y., Wong G.K.W., Chan K.S., Leung T.W. and Au G.K.H., The optimal window-setting of Positron Emission Tomography when co-registered with Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) in Target Localization For Undifferentiated Carcinoma of the Nasopharynx (NPC). , European Society of Therapeutic Radiology and Oncology. The Netherlands, ESTRO, European Society of Therapeutic Radiology and Oncology, 2010.
Pow E.H.N., Shan J.J.W., Tsang P.C.S., McMillan A.S. and Kwong D.L.W., A comparison of laboratory extraction techniques for the detection of Epstein-Barr virus in saliva of nasopharyngeal carcinoma patients., Oral Oncology. 2009, 3: 200.
Pow E.H.N., Shan J.J.W., Tsang P.C.S., McMillan A.S. and Kwong D.L.W., Detection of Epstein-Barr virus in saliva of nasopharyngeal carcinoma patients: a comparison of two laboratory extraction techniques, Conjoint Scientific Sessions Faculty of Dentistry, The University of Hong Kong - Peking University School of Stomatology. 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 (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.
Tsang J.W.H., Lau T.T.S., Lee V.K.H., Yung S.T., Li V.W.K., Cheung T.K., Lam W.W.T., Lee V.H.F., Au G.K.H. and Kwong D.L.W., Higher Education And Younger Age Are Associated With Better Understanding Of Clinical Trials Among Hong Kong Cancer Patients, 16th Hong Kong International Cancer Congress & 6th Annual Meeting Centre For Cancer Researach. 2009.
Tsang J.W.H., Li V.W.K., Lai T.L., Au G.K.H., Chua D.T.T. and Kwong D.L.W., Triple Negative Breast Cancer Patients With Brain Metastasis Are Associated With More Concurrent Lung Metastasis., 32 Annual CTRC-AACR San Antonio Breast Cancer Symposium. 2009.
Tsang J.W.H., Lau T.T.S., Lee V.K.H., Yung S.T., Li V.W.K., Cheung T.K., Lam W.W.T., Lee V.H.F., Au G.K.H. and Kwong D.L.W., Young Investigator Award In Psychosocial Oncology : Higher Education And Younger Age Are Associated With Better Understanding Of Clinical Trials Among Hong Kong Cancer Patients, 16th Hong Kong International Cancer Congress & 6th Annual Meeting Centre For Cancer Research. 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. 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.


Researcher : Kwong FM

List of Research Outputs

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.
Lung H.L., Cheung A.K.L., Cheng Y., Kwong F.M., Lo P.H.Y., Law W.L., Chua D.T.T., Zabarovsky E.R., Wang N., Tsao G.S.W., Stanbridge E.J. and Lung M.L., Functional characterization of THY1 as a tumor suppressor gene with anti-invasive activity in nasopharyngeal carcinoma, International Journal of Cancer. 2009, 127: 304-312.


Researcher : Lai TL

List of Research Outputs

Lai T.L., Yung S.T., Chua D.T.T., Au G.K.H., Kwong D.L.W. and Tsang J.W.H., Body Mass Index Is Associated With Breast Cancer Of Large Size And Positive Lymph Nodes In Pre-menopausal Women But Not Post-menopausal Women, 2010.
Lai T.L., Yung S.T., Chua D.T.T., Au G.K.H., Kwong D.L.W. and Tsang J.W.H., Body Mass Index Is Associated With Breast Cancer Of Large Size And Positive Lymph Nodes In Pre-menopausal Women But Not Post-menopausal Women, In: John Smyth, Jeap Verweij, Lilian Siu et al., European Journal of Cancer. Oxford, UK, ElsevierO, 2010, Volume 8 (Supplements): 98.
Tsang J.W.H., Li V.W.K., Lai T.L., Au G.K.H., Chua D.T.T. and Kwong D.L.W., Triple Negative Breast Cancer Patients With Brain Metastasis Are Associated With More Concurrent Lung Metastasis., 32 Annual CTRC-AACR San Antonio Breast Cancer Symposium. 2009.


Researcher : Lau BSH

List of Research Outputs

Bi J., Lau B.S.H., Lv Z.L., Xie D., Li W., Lai Y.R., Zhong J.M., Wu H.Q., Su Q., He Y.L., Zhan W.H., Wen J.M. and Guan X.Y., Overexpression of YKL-40 is an independent prognostic marker in gastric cancer., Human Pathology. 2009, 40: 1790-7.
Bi J., Guo A., Lai Y.R., Li B., Zhong J.M., Wu H.Q., Xie Z., He Y.L., Lv Z.L., Lau B.S.H., Wang Q., Huang X.H., Zhang L.J., Wen J.M. and Guan X.Y., Overexpression of clusterin correlates with tumor progression, metastasis in gastric cancer: a study on tissue microarrays, Neoplasma. 2010, 57: 191-197.


Researcher : Law WL

List of Research Outputs

Lung H.L., Cheung A.K.L., Cheng Y., Kwong F.M., Lo P.H.Y., Law W.L., Chua D.T.T., Zabarovsky E.R., Wang N., Tsao G.S.W., Stanbridge E.J. and Lung M.L., Functional characterization of THY1 as a tumor suppressor gene with anti-invasive activity in nasopharyngeal carcinoma, International Journal of Cancer. 2009, 127: 304-312.


Researcher : Lee VHF

Project Title:A retrospective analysis of genetic aberrations as predictors of relapse and survival outcomes in completely resected stage III adenocarcinoma of colon after the use of oxaliplatin-based regimen as adjuvant chemotherapy
Investigator(s):Lee VHF, Chua DTT, Kwong DLW
Department:Clinical Oncology
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:02/2009
Abstract:
To retrospectively review the presence of K-ras mutations and microsatellite instability of completely resected stage III adenocarcinoma of the colon and identify any genetic aberrations which can predict improvement of disease-free and overall survival by the addition of oxaliplatin in adjuvant chemotherapy.


Project Title:51st American Society For Radiation Oncology (ASTRO) Annual Meeting 2009 Co-registration And Application Of Positron Emission Tomography (PET), Computed Tomography (CT) As Compared With Magnetic Resonance Imaging (MRI) In Target Localization For Undifferentiated Carcinoma of the Nasopharynx (NPC)
Investigator(s):Lee VHF
Department:Clinical Oncology
Source(s) of Funding:URC/CRCG - Conference Grants for Teaching Staff
Start Date:11/2009
Completion Date:11/2009
Abstract:
N/A


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 Metastases after Tumour Removal and Whole-brain Irradiation. , American Society of Clinical Oncology. USA, ASCO, American Society of Clinical Oncology (ASCO), 2010.
Lee V.H.F., Brain Tumour: Presentation, Investigation and Management for the Elderly., Hong Kong Anti-Cancer Society on 26th October 2009, Hong Kong Anti-Cancer Society. 2009.
Lee V.H.F., Brain tumour: presentation, investigation and management, Hong Kong Anti-Cancer Society. Hong Kong, Hong Kong Anti-Cancer Society, 2010.
Lee V.H.F., Kwong D.L.W., Khong P.L., Chua D.T.T., Ng C.Y., Wong G.K.W., Chan K.S., Leung T.W. and Au G.K.H., Co-registration and application of positron emission tomography (PET), computed tomography (CT) as compared with magnetic resonance imaging (MRI) in target localization for undifferentiated carcinoma of the nasopharynx (NPC), ASTRO 2009 Annual Meeting, Chicago, USA, 1-5 November 2009.
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 V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Leung T.W. and Au G.K.H., Dosimetric Predictors of Radiation-induced Acute Nausea and Vomiting in Intensity Modulated Radiation Therapy for Undifferentiated Carcinoma of the Nasopharynx, 10th Biennial ESTRO Conference on Physics and Radiation Technology for Clinical Radiotherapy 2009.
Lee V.H.F., Management of Cancers of the Retromolar Trigone, Oropharynx and Tonsils- an oncologist’s perspective, Symposium on Head and Neck Tumours and Reconstruction, Ministry of Health, Hospital Kuala Lumpur, Malaysia. Malaysia, Ministry of Health, Hospital Kuala Lumpur, Malaysia, 2009.
Lee V.H.F., Radiotherapy for Head and Neck Cancer – Principles and Techniques, Symposium on Head and Neck Tumours and Reconstruction, Ministry of Health, Hospital Kuala Lumpur, Malaysia. Malaysia, Ministry of Health, Hospital Kuala Lumpur, Malaysia, 2009.
Lee V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Ng T.M.C., Leung T.W. and Au G.K.H., Shrinkage of Volumes of Parotid and Submandibular Glands but Elevated Radiation Doses during Intensity Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma., 4th World Congress of International Federation of Head and Neck Oncologic Societies 2010. Seoul, South Korea, International Federation of Head and Neck Oncologic Societie.
Lee V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Khong P.L., Ng T.M.C., Leung T.W. and Au G.K.H., Shrinkage of Volumes of Parotid and Submandibular Glands but Elevated Radiation Doses during Intensity Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma., Hong Kong International Cancer Congress. Hong Kong, 16th Hong Kong International Cancer Congress, 2009.
Lee V.H.F., Kwong D.L.W., Khong P.L., Chua D.T.T., Ng C.Y., Wong G.K.W., Chan K.S., Leung T.W. and Au G.K.H., The optimal window-setting of Positron Emission Tomography when co-registered with Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) in Target Localization For Undifferentiated Carcinoma of the Nasopharynx (NPC). , European Society of Therapeutic Radiology and Oncology. The Netherlands, ESTRO, European Society of Therapeutic Radiology and Oncology, 2010.
Tsang J.W.H., Lau T.T.S., Lee V.K.H., Yung S.T., Li V.W.K., Cheung T.K., Lam W.W.T., Lee V.H.F., Au G.K.H. and Kwong D.L.W., Higher Education And Younger Age Are Associated With Better Understanding Of Clinical Trials Among Hong Kong Cancer Patients, 16th Hong Kong International Cancer Congress & 6th Annual Meeting Centre For Cancer Researach. 2009.
Tsang J.W.H., Lau T.T.S., Lee V.K.H., Yung S.T., Li V.W.K., Cheung T.K., Lam W.W.T., Lee V.H.F., Au G.K.H. and Kwong D.L.W., Young Investigator Award In Psychosocial Oncology : Higher Education And Younger Age Are Associated With Better Understanding Of Clinical Trials Among Hong Kong Cancer Patients, 16th Hong Kong International Cancer Congress & 6th Annual Meeting Centre For Cancer Research. 2009.
Wong F.C.S., Ng A.W.Y., Lee V.H.F., Yuen K.K., Lui C.M.M., Sze W.K., Leung T.W. and Tung S.Y., Whole-field Simultaneous Integrated-boost Intensity-modulated Radiotherapy for Patients with Nasopharyngeal Carcinoma, International Journal of Radiation Oncology Biology and Physics. The United States of America, International Journal of Radiation Oncology Biology Physics, 2009, available online: available online.


Researcher : Leung TW

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 Metastases after Tumour Removal and Whole-brain Irradiation. , American Society of Clinical Oncology. USA, ASCO, American Society of Clinical Oncology (ASCO), 2010.
Lee V.H.F., Kwong D.L.W., Khong P.L., Chua D.T.T., Ng C.Y., Wong G.K.W., Chan K.S., Leung T.W. and Au G.K.H., Co-registration and application of positron emission tomography (PET), computed tomography (CT) as compared with magnetic resonance imaging (MRI) in target localization for undifferentiated carcinoma of the nasopharynx (NPC), ASTRO 2009 Annual Meeting, Chicago, USA, 1-5 November 2009.
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 V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Leung T.W. and Au G.K.H., Dosimetric Predictors of Radiation-induced Acute Nausea and Vomiting in Intensity Modulated Radiation Therapy for Undifferentiated Carcinoma of the Nasopharynx, 10th Biennial ESTRO Conference on Physics and Radiation Technology for Clinical Radiotherapy 2009.
Lee V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Ng T.M.C., Leung T.W. and Au G.K.H., Shrinkage of Volumes of Parotid and Submandibular Glands but Elevated Radiation Doses during Intensity Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma., 4th World Congress of International Federation of Head and Neck Oncologic Societies 2010. Seoul, South Korea, International Federation of Head and Neck Oncologic Societie.
Lee V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Khong P.L., Ng T.M.C., Leung T.W. and Au G.K.H., Shrinkage of Volumes of Parotid and Submandibular Glands but Elevated Radiation Doses during Intensity Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma., Hong Kong International Cancer Congress. Hong Kong, 16th Hong Kong International Cancer Congress, 2009.
Lee V.H.F., Kwong D.L.W., Khong P.L., Chua D.T.T., Ng C.Y., Wong G.K.W., Chan K.S., Leung T.W. and Au G.K.H., The optimal window-setting of Positron Emission Tomography when co-registered with Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) in Target Localization For Undifferentiated Carcinoma of the Nasopharynx (NPC). , European Society of Therapeutic Radiology and Oncology. The Netherlands, ESTRO, European Society of Therapeutic Radiology and Oncology, 2010.
Wong F.C.S., Ng A.W.Y., Lee V.H.F., Yuen K.K., Lui C.M.M., Sze W.K., Leung T.W. and Tung S.Y., Whole-field Simultaneous Integrated-boost Intensity-modulated Radiotherapy for Patients with Nasopharyngeal Carcinoma, International Journal of Radiation Oncology Biology and Physics. The United States of America, International Journal of Radiation Oncology Biology Physics, 2009, available online: available online.


Researcher : Li VWK

List of Research Outputs

Tsang J.W.H., Lau T.T.S., Lee V.K.H., Yung S.T., Li V.W.K., Cheung T.K., Lam W.W.T., Lee V.H.F., Au G.K.H. and Kwong D.L.W., Higher Education And Younger Age Are Associated With Better Understanding Of Clinical Trials Among Hong Kong Cancer Patients, 16th Hong Kong International Cancer Congress & 6th Annual Meeting Centre For Cancer Researach. 2009.
Tsang J.W.H., Li V.W.K., Lai T.L., Au G.K.H., Chua D.T.T. and Kwong D.L.W., Triple Negative Breast Cancer Patients With Brain Metastasis Are Associated With More Concurrent Lung Metastasis., 32 Annual CTRC-AACR San Antonio Breast Cancer Symposium. 2009.
Tsang J.W.H., Lau T.T.S., Lee V.K.H., Yung S.T., Li V.W.K., Cheung T.K., Lam W.W.T., Lee V.H.F., Au G.K.H. and Kwong D.L.W., Young Investigator Award In Psychosocial Oncology : Higher Education And Younger Age Are Associated With Better Understanding Of Clinical Trials Among Hong Kong Cancer Patients, 16th Hong Kong International Cancer Congress & 6th Annual Meeting Centre For Cancer Research. 2009.


Researcher : Li Y

List of Research Outputs

Tang D., Dong S., Ma N.F., Xie D., Chen L., Fu L., Lau S.H., Li Y., Li Y. and Guan X.Y., Overexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma, Hepatology. 2010, 51: 1255-63.


Researcher : Liu KY

List of Research Outputs

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., Chan Q., Law W.L., Liu K.Y. and Zhang J., Dynamic Contrast-enhanced MRI of Primary Rectal Cancer at 3T: Correlation with Positron Emission Tomography, Joint ISMRM-ESMRMB Annual Scientific Meeting, Stockholm, Sweden, 1-7 May 2010.
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.
Gu J., Khong P.L., Wang S., Chan Q., Law W.L., Liu K.Y. and Zhang J., Quantitative analysis of indexes from DWI and PET/CT in primary rectal cancer, Joint ISMRM-ESMRMB Annual Scientific Meeting, Stockholm, Sweden, 1-7 May 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.


Researcher : Lo PHY

List of Research Outputs

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.
Lung H.L., Lo P.H.Y., Cheung A.K.L., Apte S.S. and Lung M.L., ADAMTS9 inhibits angiogenesis and induces apoptosis in nasopharyngeal carcinoma , The 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21. 2010.
Lung H.L., Cheung A.K.L., Cheng Y., Kwong F.M., Lo P.H.Y., Law W.L., Chua D.T.T., Zabarovsky E.R., Wang N., Tsao G.S.W., Stanbridge E.J. and Lung M.L., Functional characterization of THY1 as a tumor suppressor gene with anti-invasive activity in nasopharyngeal carcinoma, International Journal of Cancer. 2009, 127: 304-312.


Researcher : Lung HL

Project Title:The involvement of hypoxic tumor micro-environment in nasopharyngeal carcinoma (NPC) tumorigenesis
Investigator(s):Lung HL, Lung ML
Department:Clinical Oncology
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:08/2009
Abstract:
Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and Southeast Asia but is rare in most Western countries. Numerous molecular alterations have been detected in this cancer (Lung et al., 2001). This tumor is highly sensitive to radiation and chemotherapy. The current treatment strategy in non-metastatic NPC is a course of radical radiotherapy in early stage disease, and concurrent chemotherapy and radiotherapy in locally advanced stage. Despite an aggressive approach combining both chemotherapy and radiotherapy, about 25-30% of patients still fail with local recurrence and/or distant metastases and which are due to poor prognosis for those patients (Wei and Sham, 2005). Hypoxia is a reduction in the normal level of tissue oxygen (O2) tension and is usually defined as ≤2% O2 (Bertout et al., 2008). Tumors become hypoxic because newly developed blood vessels are abnormal and have poor blood flow. Tissue hypoxia is thought to occur very early during tumor development, beginning at a tumor diameter of a few millimeters (Kunz and Ibrahim, 2003). Although hypoxia is toxic to both cancer cells and normal cells, cancer cells undergo genetic and adaptive changes that allow them to survive and even proliferate in a hypoxic environment. Tumors contain cancer cells that have been differentially exposed to acute hypoxia for minutes to hours and then reoxygenated. This can reoccur and result in “cycling hypoxia”. Cells can also be exposed to a more prolonged chronic hypoxia for hours to days before undergoing cell death or reoxygenation (Bristow and Hill, 2008). These processes contribute to resistance to radiotherapy and chemotherapy, as well as to a more malignant tumor phenotype with increased invasiveness, metastasis, and poorer survival (Harris, 2001). In many cancer types, patients with hypoxic primary tumors at diagnosis are more likely to develop recurrence, locally as well as at metastatic sites, regardless of whether initial treatment is by surgery or radiotherapy (Bristow and Hill, 2008). Several studies have shown that hypoxia can alter chromosome metabolism, leading to gene amplification, fragile site induction, and increased frequencies of point mutations in vitro and in vivo (Rice et al., 1986; Coquelle et al., 1998; Reynolds et al., 1996; Wilkinson et al., 1995; Reynolds et al., 1996), pointing to a deleterious effect of the tumor microenvironment on genome integrity. One of the problems of studying hypoxia in cancer progression is whether exposure to acute, chronic, or cycling hypoxia has a more important role in the induction of the increased metastatic potential of cancer cells and whether this is also dependent on the severity of hypoxia. Exposure to cycling hypoxia can lead to increased levels of reactive oxygen species (ROS) in the cells, which are capable of causing DNA damage and might drive malignant progression of tumor cells (Bristow and Hill, 2008). In NPC, most of the hypoxia studies are epidemiological studies of the hypoxia protein markers in tumor tissues. For example, in one of those studies, the hypoxia protein markers, hypoxia-inducible factor-1 (HIF-1, carbonic anhydrase IX (CA IX), and vascular endothelial growth factor (VEGF), were found frequently over-expressed in patients’ tumor samples. Co-expression of these three proteins in tumors is associated with poor survival after radiotherapy (Hui et al., 2002). In later studies, by using genome-wide expression profiling, 222 differentially expressed genes in the NPC cell lines under hypoxia treatment for 16 hrs were identified. Responsive genes were involved in diverse biological processes in NPC cells (Sung et al., 2007). Problems with this study are that the functions of those genes in response to hypoxia in NPC are not known. Their global gene expression study was based on a single time point (16 hrs) of the hypoxia treatment, and the phenotypic change of their NPC cell lines during the hypoxic conditions were not studied. Moreover, the cell lines (HONE1 and CNE2 cells) chosen for their global gene expression analysis are already tumorigenic. In our previous study, suppression of tumorigenicity in the NPC HONE1 cells was observed after the transfer of additional intact human chromosomes (Cheng et al., 1998, 2000). NPC tumor segregants derived from those HONE1 microcell hybrids (MCHs) exhibited delayed latency periods in tumor formation compared with the parental HONE1 cells. The delayed tumor appearance may be associated with loss or inactivation of wild type tumor suppressor genes (TSGs) from the normal donor chromosomes. Based on this hypothesis, we have successfully identified candidate NPC TSGs such as THY1, CADM1 (formerly called TSLC1), and ADAMTS9 (Lung et al., 2004, 2005, 2008). We also observed loss of THY1 and CADM1 expression in the single gene stable transfectants after in vivo inoculation in nude mice (Lung et al., 2006, 2009). Those losses are presumably due to in vivo selective pressure that results in functional inactivation of TSGs, but the actually cause of those events is still unknown. We previously showed that the allelic loss of tumor suppressive regions and inactivation of TSGs in the tumor segregants result in more aggressive phenotypes of cancer cell lines (Ko et al., 2005, 2008; Cheung et al., 2009). Interestingly, TSGs such as MLH1, p16, RUNX3, are reported to be down-regulated by chronic hypoxia in a variety of mammalian and cancer cells (Mihaylova et al., 2003; Box and Demetrick, 2004; Lee et al. 2009). Our unpublished observations also demonstrated that the ADAMTS9 gene expression is lost in the esophageal squamous cell carcinoma (ESCC) stable ADAMTS9 transfectants when treated with the hypoxia mimicking drug, cobalt chloride (CoCl2). Taken together, these interesting findings suggest that, during the in vivo inoculation, hypoxia might be one of the possible conditions to initiate the down-regulation of TSGs. Thus, the basic objectives of this proposal are to: 1. Investigate whether the more aggressive/metastatic phenotype of NPC cell lines is associated with acute, chronic, and cycling hypoxia, or severity of hypoxia. 2. Determine whether the increased invasiveness of NPC cell lines is due to the inactivation of THY1 initiated by hypoxia.


Project Title:The role of serum amyloid A1 (SAA1) in nasopharyngeal carcinoma
Investigator(s):Lung HL, Chua DTT
Department:Clinical Oncology
Source(s) of Funding:General Research Fund (GRF)
Start Date:09/2009
Abstract:
1) Determine whether SAA1 polymorphisms are significantly related to risk for NPC development ; 2) Investigate the anti-tumorigenic activities of SAA1.1, 1.3, and 1.5 variants using relevant physiological concentrations of recombinant SAA variant proteins by in vitro assays and determine whether they can be used as potential therapeutic targets in cancer; 3) Determine the usefulness of SAA1.1, 1.3, or 1.5 variants as a biomarker for NPC diagnosis; 4) Investigate the functional roles of ectopically-expressed SAA1.1, 1.3, and 1.5 variants in cancer development, angiogenesis, and metastasis in the NPC cell lines and tissues: 5) Validate the clinical relevance of SAA1 in serum and tumor tissues of NPC patients.


Project Title:AACR 101st Annual Meeting 2010 ADAMTS9 inhibits angiogenesis and induces apoptosis in nasopharyngeal carcinoma
Investigator(s):Lung HL
Department:Clinical Oncology
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

Chan K.C., Ko J.M.Y., Lung H.L., Sedlacek R. and Lung M.L., Importance of zinc-binding domain of matrix metalloproteinase 19 (MMP19) in tumor suppression and anti-angiogenesis of nasopharyngeal carcinoma , the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21. 2010.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Cheng Y., Stanbridge E.J., Zabarovsky E.R., Nicholls J.M., Chua D.T.T., Tsao G.S.W., Guan X.Y. and Lung M.L., Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, mirror image polydactyly 1, in nasopharyngeal carcinoma., In: George Klein, Proc Natl Acad Sci. 2009, 106: 14478-14483.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Cheng Y., Stanbridge E.J., Zabarovsky E.R., Nicholls J.M., Chua D.T.T., Tsao G.S.W., Guan X.Y. and Lung M.L., Functional Studies of a Cell Cycle and Angiogenesis-related Candidate Tumor Suppressor Gene, Mirror Image Polydactyly 1 , in Nasopharyngeal Carcinoma, 16th Hong Kong International Cancer Congress. 2009.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Stanbridge E.J., Zabarovsky E.R. and Lung M.L., Functional studies of a cell cycle and angiogenesis-related candidate tumor suppressor gene, Mirror image polydactyly 1, in nasopharyngeal carcinoma , The 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21. 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.
Lung H.L., Lo P.H.Y., Cheung A.K.L., Apte S.S. and Lung M.L., ADAMTS9 inhibits angiogenesis and induces apoptosis in nasopharyngeal carcinoma , The 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21. 2010.
Lung H.L., CRCG Conference Grants for Teaching Staff, The Committee on Research and Conference Grants, HKU. 2010.
Lung H.L., Cheung A.K.L., Cheng Y., Kwong F.M., Lo P.H.Y., Law W.L., Chua D.T.T., Zabarovsky E.R., Wang N., Tsao G.S.W., Stanbridge E.J. and Lung M.L., Functional characterization of THY1 as a tumor suppressor gene with anti-invasive activity in nasopharyngeal carcinoma, International Journal of Cancer. 2009, 127: 304-312.
Lung H.L., Invited lecture-as a guest speaker for the departmental seminar , Department of Chemical Pathology, The Chinese University of Hong Kong . 2010.
Lung H.L., Reviewer, Cancer Letter for manuscript 1. 2009.
Lung H.L., Reviewer, Cancer Letter for manuscript 2. 2009.
Lung H.L. and Lung M.L., The involvement of hypoxic tumor micro-environment in nasopharyngeal carcinoma (NPC) tumorigenesis, Seed Funding Programme for Basic Research, HKU. 2009.
Ting C.M., Lee Y.M., Wong C.K., Wong A.S.T., Lung H.L., Lung M.L., Lo K.W., Wong R.N. and Mak N.K., 2-Methoxyestradiol induces endoreduplication through the induction of mitochondrial oxidative stress and the activation of MAPK signaling pathways, Biochem Pharmacol. 2009, 79: 825-841.


Researcher : Lung ML

Project Title:Molecular and functional investigation of two thrombospondin type 1 repeat candidate tumor suppressor genes mapping to critical regions involved in esophageal carcinoma
Investigator(s):Lung ML
Department:Clinical Oncology
Source(s) of Funding:General Research Fund (GRF)
Start Date:08/2006
Abstract:
1) Determine the expression levels of ADAMTS9 and THSD1 in Hong Kong and Henan ESC tumor tissues to evaluate their clinical relevance; 2) Establish TMA for IHC staining to determine expression level of ADAMTS9 in pre-neoplastic lesions to determine usefulness as cancer marker; 3) Engineer the ESC SLMT1 cell line to express the tetracycline-inducible transactivator for th pETE tet-off system; 4) Clone the THSD1 gene into the pETE-bsd vector for functional studies; 5) Determine the functional roles of ADAMTS9 and THSD1 in ESC in in vitro colony forming, soft agar, and invasion assays; 6) Determine the functional roles of ADAMTS9 and THSD1 in ESC in animal assays for tumorigenicity


Project Title:Esophageal Carcinoma Research Center
Investigator(s):Lung ML, Cheung A, Guan XY, Kwong DLW, Law SYK, Luk JMC, Tao Q, Tsao GSW
Department:Clinical Oncology
Source(s) of Funding:Collaborative Research Fund (CRF) - Group Research Project
Start Date:04/2007
Completion Date:03/2010
Abstract:
1) Investigate and functionally characterize candidate TSGs identified by MMCT approaches; 2) Define chromosome 3p MDRs for primary EC specimens by SMSG analysis and functional analysis of candidate TSGs identified by this approach; 3) Perform genome-wide epigenetic screening to identify novel candidate TSGs by aCGH and further epigenetic profiling and functional analyses; 4) Identify and characterize the novel candidate oncogene(s) within the chromosome 17p HSR of esophageal cancer using 17p11.2-17p12 region-specific expressed sequences from the microdissected DNA by hybrid selection, and to study their overexpression in EC cases; 5) Constuct TMAs to determine clinical relevance and temporal sequence of genetic alterations in EC; 6) Establish telomerase immortalized esophageal cell lines for SKY characterization, and perform CGH and gene expression microarray studies to identify candidate genes essential for immortalization and tumorigenic transformation for functional studies; 7) Perform comparative CGH and LOH analysis of family history-positive and negative specimens to determine MDR; 8) Identify high-risk families and obtain specimens from family history-positive (FH+) individuals for SNP IBD analysis to determine MDR and perform a pilot study of tumor and blood DNAs from FH+/- specimens form Henan vs HK on oligonucleotide microarrays; 9) Recruit patients and collect specimens of responders and non-responders for CRT, comparative proteomic analysis, and generation of predictive model for discriminating CR and NR; 10) Perform functional studies of proteins associated with CRT resistance by immunostaining, immunoblotting, and RNAi approaches (depends on when target proteins are identified as to how far we can progress with this part of the project); 11) Recruit patients to evaluate the efficacy, toxicity, tolerance and molecular response of COX-2 inhibition and preoperative CRT for EC


Project Title:Molecular and functional studies of the role of chromosome 14q candidate genes, CRIP2 and MIPOL1, in nasopharyngeal and esophageal carcinomas
Investigator(s):Lung ML
Department:Clinical Oncology
Source(s) of Funding:General Research Fund (GRF)
Start Date:09/2007
Abstract:
Initial validation studies to: Examine the levels of CRIP2 and MIPOL1 gene expression directly in paired normal and tumor tissues and of protein expression in cell line panels to determine clinical relevance; perform in vitro cell growth and in vivo tumorigenicity assays to identify genes contributing to tumor suppression in NPC and EC.


Project Title:Molecular and Functional Investigation of the Role of Two Metalloproteinases in Nasopharyngeal Carcinoma Tumorigenesis
Investigator(s):Lung ML
Department:Clinical Oncology
Source(s) of Funding:General Research Fund (GRF)
Start Date:01/2009
Abstract:
1) Investigate the clinical relevance of MMP19 and ADAMTS9 and mechanisms of inactivation in NPC and determine whether they play coordinated non-redundant tumor suppressive roles in NPC pathogenesis; 2) Investigate the functional and mechanistic roles of MMP19 and ADAMTS9 in NPC; 3) Identify interacting proteins associated with ADAMTS9 to determine their contribution to NPC tumorigenesis


Project Title:Candidate tumor suppressor gene, DUSP6, involvement in esophageal and nasopharyngeal carcinomas
Investigator(s):Lung ML
Department:Clinical Oncology
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:05/2009
Abstract:
Objectives of research proposal Cancers remain one of the leading causes of mortality in Hong Kong. Understanding the molecular genetic basis of cancers will aid in its earlier detection and improved treatment. We have previously identified a gene, Deleted in Esophageal Cancer 1 (DEC1), which maps to chromosome 9q32 and appears to play an important functional role in esophageal squamous cell carcinoma (ESCC). Its expression is reduced in esophageal carcinoma and the gene is able to suppress cancer cell growth in vitro and tumor growth in vivo in nude mice. In in vitro cell migration, invasion, and soft agar assays of DEC1 transfectants, only the soft agar assay showed statistically significant differences in colony numbers with the vector-alone controls, indicating that DEC1 may be involved in anchorage-independent cell growth. In addition, the global gene expression affected by DEC1 in tumor suppressive stable transfectants was investigated using cDNA oligonucleotide microarray hybridization. One candidate gene identified through this approach, Dual specificity phosphatase 6 (DUSP6), is down-regulated in tumor segregants of DEC1 stable transfectants, ESCC cell lines, and esophageal tumors and has a potential role in tumor growth and progression. We would now like to elucidate the role of DUSP6 in ESCC tumor development. DUSP6 is a member of the subfamily of protein tyrosine phosphatases known as dual specificity phosphatases. They are frequently down-regulated in some cancers such as pancreatic and ovarian cancers. Two common cancers amongst the Chinese in Hong Kong include nasopharygngeal carcinoma (NPC) and ESCC. DUSP6 appears to be downstream of the DEC1 gene, known to be important in ESCC. Its role, if any, in both ESCC and NPC will be studied. Purpose The purpose of these studies is to evaluate the clinical and functional importance of a candidate tumor suppressor gene (TSG), DUSP6, in ESCC and NPC. We propose to study the frequency of involvement of DUSP6 down-regulation in ESCC and NPC cell line panels and tumor tissues. We also intend to elucidate the mechanism involved in its decreased expression in tumors and to determine the functional importance of this gene in cell growth, tumor formation, cell migration and invasion assays. Key issues and problems addressed Determining what key genes are involved in the development of tumors such as ESCC and NPC will allow a greater understanding of the molecular genetic basis for these two important cancers amongst the Hong Kong Chinese. Identifying key biomarkers that will allow early detection of cancer and its prognostication will be useful in improving control of these deadly cancers.


Project Title:Centre for Nasopharyngeal Carcinoma Research
Investigator(s):Lung ML, Chen H, Chiang AKS, Chua DTT, Khong PL, Kwong DLW, Guan XY, Tsao GSW, Wu EX
Department:Clinical Oncology
Source(s) of Funding:Areas of Excellence Scheme
Start Date:01/2010
Abstract:
n/a


List of Research Outputs

Chan K.C., Ko J.M.Y., Lung H.L., Sedlacek R. and Lung M.L., Importance of zinc-binding domain of matrix metalloproteinase 19 (MMP19) in tumor suppression and anti-angiogenesis of nasopharyngeal carcinoma , the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21. 2010.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Cheng Y., Stanbridge E.J., Zabarovsky E.R., Nicholls J.M., Chua D.T.T., Tsao G.S.W., Guan X.Y. and Lung M.L., Chromosome 14 transfer and functional studies identify a candidate tumor suppressor gene, mirror image polydactyly 1, in nasopharyngeal carcinoma., In: George Klein, Proc Natl Acad Sci. 2009, 106: 14478-14483.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Cheng Y., Stanbridge E.J., Zabarovsky E.R., Nicholls J.M., Chua D.T.T., Tsao G.S.W., Guan X.Y. and Lung M.L., Functional Studies of a Cell Cycle and Angiogenesis-related Candidate Tumor Suppressor Gene, Mirror Image Polydactyly 1 , in Nasopharyngeal Carcinoma, 16th Hong Kong International Cancer Congress. 2009.
Cheung A.K.L., Lung H.L., Ko J.M.Y., Stanbridge E.J., Zabarovsky E.R. and Lung M.L., Functional studies of a cell cycle and angiogenesis-related candidate tumor suppressor gene, Mirror image polydactyly 1, in nasopharyngeal carcinoma , The 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21. 2010.
Ko J.M.Y., Cheung A.K.L. and Lung M.L., Tumor suppressive and angiogenic role of THSD1 in esophageal squamous cell carcinoma and nasopharyngeal carcinoma, In: Josephine Mun Yee Ko, Arthur KL Cheung, Maria Li Lung., AACR 101st Annual Meeting 2010. Washington, DC, U.S.A., 2010 Apr 17-21: 1.
Koon H.K., Chan P.S., Wong R.N., Wu Z.G., Chang C.K., Mak N.K. and Lung M.L., Targeted inhibition of the EGFR pathways enhances Zn-BC-AM PDT-induced apoptosis in well-differentiated nasopharyngeal carcinoma cells., J Cellular Biochem. 2009, 108: 1356-63.
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.
Lung H.L., Lo P.H.Y., Cheung A.K.L., Apte S.S. and Lung M.L., ADAMTS9 inhibits angiogenesis and induces apoptosis in nasopharyngeal carcinoma , The 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21. 2010.
Lung H.L., Cheung A.K.L., Cheng Y., Kwong F.M., Lo P.H.Y., Law W.L., Chua D.T.T., Zabarovsky E.R., Wang N., Tsao G.S.W., Stanbridge E.J. and Lung M.L., Functional characterization of THY1 as a tumor suppressor gene with anti-invasive activity in nasopharyngeal carcinoma, International Journal of Cancer. 2009, 127: 304-312.
Lung H.L. and Lung M.L., The involvement of hypoxic tumor micro-environment in nasopharyngeal carcinoma (NPC) tumorigenesis, Seed Funding Programme for Basic Research, HKU. 2009.
Ting C.M., Lee Y.M., Wong C.K., Wong A.S.T., Lung H.L., Lung M.L., Lo K.W., Wong R.N. and Mak N.K., 2-Methoxyestradiol induces endoreduplication through the induction of mitochondrial oxidative stress and the activation of MAPK signaling pathways, Biochem Pharmacol. 2009, 79: 825-841.


Researcher : Ng CY

List of Research Outputs

Lee V.H.F., Kwong D.L.W., Khong P.L., Chua D.T.T., Ng C.Y., Wong G.K.W., Chan K.S., Leung T.W. and Au G.K.H., Co-registration and application of positron emission tomography (PET), computed tomography (CT) as compared with magnetic resonance imaging (MRI) in target localization for undifferentiated carcinoma of the nasopharynx (NPC), ASTRO 2009 Annual Meeting, Chicago, USA, 1-5 November 2009.
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 V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Leung T.W. and Au G.K.H., Dosimetric Predictors of Radiation-induced Acute Nausea and Vomiting in Intensity Modulated Radiation Therapy for Undifferentiated Carcinoma of the Nasopharynx, 10th Biennial ESTRO Conference on Physics and Radiation Technology for Clinical Radiotherapy 2009.
Lee V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Ng T.M.C., Leung T.W. and Au G.K.H., Shrinkage of Volumes of Parotid and Submandibular Glands but Elevated Radiation Doses during Intensity Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma., 4th World Congress of International Federation of Head and Neck Oncologic Societies 2010. Seoul, South Korea, International Federation of Head and Neck Oncologic Societie.
Lee V.H.F., Ng C.Y., Chua D.T.T., Kwong D.L.W., Khong P.L., Ng T.M.C., Leung T.W. and Au G.K.H., Shrinkage of Volumes of Parotid and Submandibular Glands but Elevated Radiation Doses during Intensity Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma., Hong Kong International Cancer Congress. Hong Kong, 16th Hong Kong International Cancer Congress, 2009.
Lee V.H.F., Kwong D.L.W., Khong P.L., Chua D.T.T., Ng C.Y., Wong G.K.W., Chan K.S., Leung T.W. and Au G.K.H., The optimal window-setting of Positron Emission Tomography when co-registered with Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) in Target Localization For Undifferentiated Carcinoma of the Nasopharynx (NPC). , European Society of Therapeutic Radiology and Oncology. The Netherlands, ESTRO, European Society of Therapeutic Radiology and Oncology, 2010.


Researcher : Tsang JWH

Project Title:Breast Cancer Awareness, Spectrum of Breast Cancer with Particular Reference to Triple Negative Breast Cancer in the Hong Kong Chinese Population
Investigator(s):Tsang JWH, Chua DTT, Kwong A, Khoo US, Lam WWT
Department:Clinical Oncology
Source(s) of Funding:Seed Funding Programme for Basic Research
Start Date:10/2008
Abstract:
Background Breast cancer is the most common female cancer in the world with a worldwide yearly estimate of 1 150 000 new cases and 410 000 deaths from the disease.1 It is also the leading cause of cancer-related deaths and the most common female cancer in Asia.2 The rising incidence of breast cancer in Hong Kong tops virtually all other East Asian populations except Singapore.3 Breast cancer is now the most common cancer among Hong Kong Chinese women with 1 in 22 cumulative life-time risk.4 There has been data showing that breast cancer is a disease which should be assessed separately in different populations, as it differs substantially between Chinese and Caucasian women.3 Few studies have demonstrated differences in certain biological breast cancer characteristics associated with survival, including hormone receptor status and histology, among women of different racial and ethnic groups.5 A recent local review has revealed that Hong Kong Chinese women present with breast cancer at an earlier age than their Western counterparts with its incidence peaks at the age of 40.6 However, population-based study on the trend and characteristics of breast cancer in Hong Kong is not available. The clinical awareness, understanding and approach to breast cancer patients among oncologist, surgeons and primary care physicians are not known. Furthermore, breast cancer is a heterogeneous group of disease consisting of different tumour subtypes as evidenced by molecular and gene expression profiling. These tumour subtypes include: the luminal subtype (hormone receptor positive), the human epidermal growth factor receptor 2 (HER-2)-positive subtype (cerbB-2 positive), and the basal subtype (the majority lacking hormone receptor and HER-2 receptor expression). 7-9 Currently, targeted adjuvant therapy for breast cancer is guided in large part by the status of oestrogen receptor (ER), progesterone receptor (PgR), and HER-2 neu (HER-2) receptor.10 Triple-negative (ER negative, PgR negative, HER-2 negative) breast cancer, which accounts for about 15% of all newly diagnosed breast cancers,7 is a discrete subclass of biologically more aggressive breast cancer, carrying a poor prognosis. It is associated with younger age at presentation, higher grade of tumour with larger tumour size, shorter disease-free survival and overall survival.11 There are also positive associations with pushing margins, poorer Nottingham Prognostic Index with development of recurrence and distant metastasis.12 As triple negative breast cancers are insensitive to most available hormonal or targeted therapeutic agents thus far developed, a better understanding of its pathophysiology, epidemiology, natural history and currently available treatment options is necessary to improve outcomes of patients with triple negative breast cancer. Triple negative breast cancer in Hong Kong warrants further attention and study in order to improve the overall outcome of this particular subset of the population. On the other hand, there is recent suggestion that the biological characteristics and prognostic outlook of Chinese triple negative breast cancers might be more favourable and somewhat different from those in Western populations.13 The data in Asia is limited while those for Hong Kong Chinese population is lacking. Objectives of the Research Proposal 1) To study and understand the epidemiology, clinical features and natural progression of breast cancer in Hong Kong Chinese population with particular reference to triple-negative breast cancer. 2) To study the pathological features of Hong Kong Chinese breast cancer with particular reference to triple-negative breast cancer, and attempt to identify potential protein markers of this subset of breast cancer, including studying the role of stanniocalcin-1 (STC-1) and stanniocalcin-2 (STC-2). 3) To explore any radiological features associated with Hong Kong Chinese breast cancer and explore the role of PET- CT in the diagnosis and follow-up of breast cancer women, especially its role in the diagnosis and follow-up of triple-negative breast cancer. 4) To better understand the genetic make-up and pattern of mutation of triple-negative breast cancer in the Hong Kong Chinese population and study the relationship of the BRCA mutation in this population. 5) To further understand the psycho-social needs of Hong Kong Chinese breast cancer patients, especially those who belong to sub-group of triple-negative breast cancer and their quality of life related to their disease. 6) To better understand the clinical awareness, views, understanding and approach to breast cancer patients among oncologists, surgeons and primary care physicians with particular reference to triple-negative breast cancer


List of Research Outputs

Chan K.H., Tsang J.W.H., Mak W., Liu H.H.W., Ho S.L. and Cheung R.T.F., Thymomatous myasthenia gravis among Hong Kong Chinese, 20th Meeting of the European Neurological Society, Berlin, 2010. Journal of Neurology. 2010, 257 (Supplement 1): S170.
Lai T.L., Yung S.T., Chua D.T.T., Au G.K.H., Kwong D.L.W. and Tsang J.W.H., Body Mass Index Is Associated With Breast Cancer Of Large Size And Positive Lymph Nodes In Pre-menopausal Women But Not Post-menopausal Women, 2010.
Lai T.L., Yung S.T., Chua D.T.T., Au G.K.H., Kwong D.L.W. and Tsang J.W.H., Body Mass Index Is Associated With Breast Cancer Of Large Size And Positive Lymph Nodes In Pre-menopausal Women But Not Post-menopausal Women, In: John Smyth, Jeap Verweij, Lilian Siu et al., European Journal of Cancer. Oxford, UK, ElsevierO, 2010, Volume 8 (Supplements): 98.
Liu H.H.W., Tsang J.W.H., Pang S.Y.Y., Ho S.L., Cheung R.T.F., Chu A.C.Y., Tse M.M.Y., Mak W., Ho W.L. and Chan K.H., Thymomatous myasthenia gravis, 15th Medical Research Conference, Faculty of Medicine, The University of Hong Kong. 2010.
Tsang J.W.H., Adjuvant Hormonal Thearpy for Breast Cancer, Multidisciplinary Approach for Breast Cancer Symposium 2010. 2010.
Tsang J.W.H., Advances in Breast Cancer Treatment, Macau Surgical Association Scientific Symposium - Advances in Breast Cancer Treatment. 2009.
Tsang J.W.H., Breast Cancer Treatment Trends, Health Action. 2009.
Tsang J.W.H., Cancer And Stress, Health Information, Metro Daily. 2009.
Tsang J.W.H., Carcinogens and Risk Factors for Common Cancers, Health Information, Ming Pao Daily. 2009.
Tsang J.W.H., Clinical Update on Breast Cancer, Hong Kong Pharmacy Conference 2010 . 2010.
Tsang J.W.H., Editorial Board , In: Lara Siobhan Doyle et al. , Asia-Pacific Oncology & Haematology. Touch Briefings, 2010.
Tsang J.W.H., HER-2 Positive Breast Cancer, Health Expert Column, Wedding Message. 2009.
Tsang J.W.H., Lau T.T.S., Lee V.K.H., Yung S.T., Li V.W.K., Cheung T.K., Lam W.W.T., Lee V.H.F., Au G.K.H. and Kwong D.L.W., Higher Education And Younger Age Are Associated With Better Understanding Of Clinical Trials Among Hong Kong Cancer Patients, 16th Hong Kong International Cancer Congress & 6th Annual Meeting Centre For Cancer Researach. 2009.
Tsang J.W.H., Improving Chemotherapy-related Side Effects With Diet, 改變飲食紓緩化療副作用, Oriental Daily. 2009.
Tsang J.W.H., Management Of Newly Diagnosed Resected GBM –What Is The Standard And Anything New?, The Hong Kong Anti-Cancer Society Professional Symposium – Multidisciplinary Approach in Glioblastoma Multiforme (GBM). 2010.
Tsang J.W.H., Metastatic Breast Cancer: Where Are We Now?, Haven of Hope Staff Training CME Workshop . 2010.
Tsang J.W.H., Overview of Targeted Therapies & New Targets, Hong Kong College of Radiology Training Workshop . 2010.
Tsang J.W.H., Practical Aspects Of Anti—VEGF Therapy On Breast Cancer : Case Sharing, Hong Kong Society of Clinical Oncology Scientific Symposium. 2009.
Tsang J.W.H., Salvage Therapy for Refractory ErbB2+ MBC, CUHK Breast Cancer Pre-Conference Workshop- State-of-the-Art Treatment Strategy in Managing ErbB2+ Metastatic Breast Cancer. 2009.
Tsang J.W.H., Targeted Therapy in Breast Cancer, 16th Hong Kong International Cancer Congress & 6th Annual Meeting of Centre for Cancer Research. 2009.
Tsang J.W.H., Techniques for Nurse Specialists in Managing Breast Cancer Patients Workshop 2010, Post-Multidisciplinary Symposium Workshop. 2010.
Tsang J.W.H., Treating Her-2 Positive Breast Cancer: Recent Advances In The Use Of Lapatinib, HAHO Chief Pharmacist's Office (CPO) Training Workshop. 2009.
Tsang J.W.H., Li V.W.K., Lai T.L., Au G.K.H., Chua D.T.T. and Kwong D.L.W., Triple Negative Breast Cancer Patients With Brain Metastasis Are Associated With More Concurrent Lung Metastasis., 32 Annual CTRC-AACR San Antonio Breast Cancer Symposium. 2009.
Tsang J.W.H., Lau T.T.S., Lee V.K.H., Yung S.T., Li V.W.K., Cheung T.K., Lam W.W.T., Lee V.H.F., Au G.K.H. and Kwong D.L.W., Young Investigator Award In Psychosocial Oncology : Higher Education And Younger Age Are Associated With Better Understanding Of Clinical Trials Among Hong Kong Cancer Patients, 16th Hong Kong International Cancer Congress & 6th Annual Meeting Centre For Cancer Research. 2009.


Researcher : Wang J

List of Research Outputs

Chen L., Chan H.M., Yuan Y.F., Hu L., Huang J., Ma S.K.Y., Wang J., Dong S., Tang K.H., Xie D., Li Y. and Guan X.Y., CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients, Journal of Clinical Investigation. 2010, 120: 1178-1191.


Researcher : Yung ST

List of Research Outputs

Lai T.L., Yung S.T., Chua D.T.T., Au G.K.H., Kwong D.L.W. and Tsang J.W.H., Body Mass Index Is Associated With Breast Cancer Of Large Size And Positive Lymph Nodes In Pre-menopausal Women But Not Post-menopausal Women, 2010.
Lai T.L., Yung S.T., Chua D.T.T., Au G.K.H., Kwong D.L.W. and Tsang J.W.H., Body Mass Index Is Associated With Breast Cancer Of Large Size And Positive Lymph Nodes In Pre-menopausal Women But Not Post-menopausal Women, In: John Smyth, Jeap Verweij, Lilian Siu et al., European Journal of Cancer. Oxford, UK, ElsevierO, 2010, Volume 8 (Supplements): 98.
Tsang J.W.H., Lau T.T.S., Lee V.K.H., Yung S.T., Li V.W.K., Cheung T.K., Lam W.W.T., Lee V.H.F., Au G.K.H. and Kwong D.L.W., Higher Education And Younger Age Are Associated With Better Understanding Of Clinical Trials Among Hong Kong Cancer Patients, 16th Hong Kong International Cancer Congress & 6th Annual Meeting Centre For Cancer Researach. 2009.
Tsang J.W.H., Lau T.T.S., Lee V.K.H., Yung S.T., Li V.W.K., Cheung T.K., Lam W.W.T., Lee V.H.F., Au G.K.H. and Kwong D.L.W., Young Investigator Award In Psychosocial Oncology : Higher Education And Younger Age Are Associated With Better Understanding Of Clinical Trials Among Hong Kong Cancer Patients, 16th Hong Kong International Cancer Congress & 6th Annual Meeting Centre For Cancer Research. 2009.


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