DEPT OF PATHOLOGY
| Researcher : Beh SL |
| Project Title: | The attitudes of doctors toward rape victims |
| Investigator(s): | Beh SL |
| Department: | Pathology |
| Source(s) of Funding: | Other Funding Scheme |
| Start Date: | 06/1993 |
| Abstract: |
| To have an objective assessment of what the prevalent attitudes are; to ascertain if there is a gender bias; to compare local data with data from other countries; to compare data with other professional groups. |
| Project Title: | A STUDY OF ANTECEDENT CLINICAL ENCOUNTERS OF VICTIMS OF DOMESTIC HOMICIDES IN HONG KONG |
| Investigator(s): | Beh SL, WONG |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 01/2006 |
| Abstract: |
| Prevention of domestic violence is one of the central tasks of family protection. In Hong Kong various tools and guidelines such as the Procedural Guidelines for Handling Battered Spouse Cases (Working group on combating violence, 2004), are researched and published to help social workers and other helping professionals to detect signs of abuse in family. Central monitoring systems, such as the Child Protection Registry and the Central Information System on Battered Spouses Cases and Sexual Violence Cases are established to record and determine the nature of suspected abuse cases. However, few efforts are paid to the understanding of domestic homicides, despite its extreme and grievous nature. The fact that fatal abuse cases were not included in the Child Protection Registry highlights well the lack of understanding and study of lethal cases (Lee& So,2005). This proposal argues that understanding domestic homicides is crucial to family protection, considering the loss of lives, the psychological damage to the surviving family and the psychological and economic impact on the whole society (Brand, Sam, Price,and Richard, 2000). Hong Kong also has a comparatively high proportion of domestic homicides amongst all homicides compared with other jurisdictions, such as the USA and Taiwan (see Appendix 1). The proportion of domestic homicides (DH) in all homicides in Hong Kong has also shown a continuous increase since the 1990s, rising from 24% of all homicides in 1990 to 41% in 2001 (see Appendix 2). One possible reason for the lack of attention to domestic homicides is that domestic homicide is widely regarded as the result of chronic abuse, or as progressing from non-lethal abuse (Browne, 1987; Goetting, 1988; Jurik and Winn, 1990; Stout, 1991; Walker, 1984). However, preliminary research findings of domestic homicides in Hong Kong between 1989 and 2001 suggests that domestic homicides cannot be adequately explained by lethal escalation of chronic abuse. In Hong Kong only 37% of all domestic homicide offenders had a prior history of using violence. This is especially evident in filicides (killing of children by parents) where only a quarter of filicide offenders had prior history of using violence and 42% were driven by non-hostile motives against the victims. Although the history of violence may be the result of under-reporting; its prevalence is unclear and these findings justify further investigations. In particular, it points to the fact that existing risk assessment tools which rely heavily on abusive history and violent records might not be as effective as they are presumed to be in predicting domestic homicides. Theoretically, the differences between lethal and non-lethal cases and the risk of victimization is intriguing. It has been widely reported that the risk of a child being murdered by his or her parents declined as the child grew older in western jurisdictions (Daly and Wilson, 1998). This pattern is also found in Hong Kong. Yet, about 68% to 83% of abused children were older than 6 years old and the highest rate of severe violence occurred around age 8 for boys and age 3 for girls (HK Council of Social Service, 1976; Tang, 1998). Most study on domestic violence in HK determined the prevalence of domestic violence and the demographics of the offenders and victims (Tang, 1998, 1999). This proposal argues that family violence, lethal or non-lethal, is the product of dynamic interactions within the family systems and it should be regarded as a process rather than a static event (Felson & Tedeschi, 1995), usually escalating from minor abuse to more severe attacks (Mouzos, 2000; Dutton, 1998). Most of the domestic homicide victims (85% in one study) had called for police intervention at least once in the 2 years before the homicides (Breedlove, 1977). It is, therefore, crucial to trace the trajectory of domestic violence and homicides for early intervention, and factors which set these two apart. Domestic violence and homicides as a public health issue has gained increasing attention since the last decade and the role of health-care and medical professionals in the prevention of domestic violence gaining more prominence. Domestic violence victims were found to be more vulnerable to a wide array of health problems, especially chronic stress-related problems, such as functional gastrointestinal disorders, appetite loss, viral infections and sexually transmitted diseases (Campbell et al. 2002). They were also more likely to suffer from frequent headaches, migraines, chronic pain syndromes, heart and blood pressures issues symptoms, arthritis, drug and alcohol intoxication, other harm and self-harm behaviors and eating disorders (Wingood, DiClemente and Raj, 2000; Ackard, Neumark-Sztainer, 2002). Research on medical records showed that a considerable proportion of domestic homicide victims had visited Emergency Departments within 2 years prior to their demise and almost all victims who had used the Emergency Department had presented with injuries on at least one encounter. They were also more likely to have injuries on head, neck, chest, abdomen, and perineum (Wadman, et al 1999). Although not necessarily killed by family members, a study on all homicide victims also reported that homicide victims paid more visits to the Emergency Department than the controls, and the frequency increased as the day of the homicide event approached (Cameron S. Crandall, et al. 2004). In view of the limited understanding of domestic homicides, in particular the killings of elderly and other family members, the research team proposes the first victim-based study of domestic homicides in Hong Kong. The objectives are: 1) to determine the epidemiology of domestic homicides, offender-victim relationship, demographics, antecedents, situational factors and post-event behaviors; 2) to trace the trajectory of domestic homicides as manifested in health problems, such as drug and alcohol intoxication, physical injuries, self-harm behaviors and other health hazards; 3) to understand the demographics, nature and frequency of visits of A & E users who died from domestic homicides and determine differences as compared with controls; 4) to increase the alertness of public health professional and facilitate early identification of potential victims who had sought help from the public health systems. |
| List of Research Outputs |
| Beh S.L., Accident & Emergency department Doctors Perceptions of Their Knowledge and Competence of Forensic Medicine - The HK Experience, The Australian New Zealand Forensic Science International Symposium - Freemantle, April 2-5, 2006. |
| Beh S.L., Chan A.C.Y. and Broadhurst R.G., Can Injury Patterns of Victims of Homicide predict the degree of intimacy of the offender?, The Australian New Zealand Forensic Science International Symposium - Freemantle, April 2-5, 2006 . 2006. |
| Beh S.L., Explaining The Autopsy - The Hong Kong Experience, 7th International Conference On Sids. 2006. |
| Beh S.L., Broadhurst R.G., Chan A.C.Y. and Lee K.W., Homicide Followed by Suicide in Hong Kong, In: R.G. Broadhurst, Homicide Followed by Suicide in Hong Kong. Hong Kong, The University of Hong Kong Centre for Criminology, 2005, 1-114. |
| Beh S.L., How to explain the need for an autopsy in a case of SIDS: the perspective of a forensic pathologist under the Hong Kong Coronial System, The 9th SIDS International Conference - Yokohama, June 1-4, 2006 . 2006. |
| Beh S.L., Keynote Address. Attitudes of Medical Students Towards Victims of Rape, International Symposium of Forensic Sciences, AMITY Institute of Advanced Forensic Sciences, Noida, INDIA. 2006. |
| Beh S.L., Overview Of Unanticipated Deaths And Psychosocial Implications, Symposium On Grief And Loss. 2005. |
| Beh S.L., Plenary Speaker. Problem Based Learning And Forensic Science Curriculum. The Ideal And Logical Step Forward, International Symposium of Forensic Sciences, AMITY Institute of Advanced Forensic Sciences, Noida, INDIA. 2006. |
| Beh S.L. and Ng I., Rape Attrition Characteristics In A Cohort Of Sexual Assault Victims Seen At A Hong Kong Rape Crisis Center (rainlily), 17th Triennial Meeting Of The International Association Of Forensic Sciences. Hong Kong, 2005. |
| Chan L.C. and Beh S.L., Monograph 2: Problem-based Learning (PBL): Everything you want to know and are not afraid to ask, Things you wish to know about PBL and are not afraid to ask. Institute of Medical and Health Scienced Education, HKU, 2006, 25-31. |
| Fatima S., Chui C.H., Tang W.K., Hui K.S., Au H.W., Li W.Y., Wong M.M., Cheung F., Tsao G.S.W., Lam K...Y., Beh S.L., Wong J., Law S.Y.K., Srivastava G., Ho K.P., Chan A.S. and Tang J.C.O., Transforming capacity of two novel genes JS-1 and JS-2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma, International Journal of Molecular Medicine. 2006, 17(1): 159-170. |
| Gibson I., Cheung L.K., Chow S.P., Cheung W.L., Beh S.L., Savalani M.M. and Lee S.H., The Use Of Rapid Prototyping To Assist Medical Applications, Rapid Prototyping Journal. UK, Emerald Group Publishing Ltd., 2006, 12: 53-58. |
| Nicholls J.M., Butany J., Poon L.L.M., Chan K.H., Beh S.L., Poutanen S., Peiris J.S.M. and Wong M.P., Time course and cellular localization of SARS-CoV nucleoprotein and RNA in lungs from fatal cases of SARS, Public Library of Science Medicine . 2006, 3(2): e27. |
| Payne-James J., Dean P., McLay W.D.S., Norfolk G.A., Robinson S.P., Stark M.M., Beh S.L., Karch S.B. and Keogh A., Associate Editor for Asia, In: Jason Payne-James, Journal of Clinical Forensic Medicine. Elsevier, 2005, 12 Number 6: 289-236. |
| Tang W.K., Fatima S., Chui C.H., Ou T.M., Hui K.S., Wong M.M., Wong J., Law S.Y.K., Tsao G.S.W., Lam A.K.Y., Beh S.L., Srivastava G., Ho K.P. and Tang J.C.O., Oncogenic properties of a novel gene located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma, Proceedings of the 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress of Biochemistry and Molecular Biology, Kyoto, Japan, June 18-23, 2006. |
| Wong J.G.W.S., Patil N.G., Beh S.L., Cheung E.P.T., Wong V., Chan L.C. and Mak-Lieh F., Cultivating psychological well-being in Hong Kong's future doctors, Medical Teacher. 2005, 27(8): 715-9. |
| Researcher : Chan ACY |
| List of Research Outputs |
| Ma E.S.K., Wong C.L., Lai K.T., Chan E.C., Yam W.C., Chan A.C. and Chan A.C.Y., Kocuria kristinae infection associated with acute cholecystitis. , BMC Infect Dis. UK, 2005, 5(1): 60. |
| Researcher : Chan ASY |
| List of Research Outputs |
| Guo D.L., Zhang J., Yuen S.T., Tsui W.Y., Chan A.S.Y., Ho C., Chen X. and Leung S.Y., Reduced Expression of EphB2 that parallels invasion and metastasis in colorectal tumors, Keystone Symposia: Stem Cells, Senescence and Cancer, 25-30 October . 2005. |
| Guo D.L., Zhang J., Yuen S.T., Tsui W.Y., Chan A.S.Y., Ho C., Ji J., Leung S.Y. and Chen X., Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumors, Carcinogenesis. 2005, 27(3): 454-464. |
| Researcher : Chan DW |
| Project Title: | Characterization of the roles of Hepatitis B virus X protein in hepatocellular carcinoma |
| Investigator(s): | Chan DW, Ng IOL |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2004 |
| Completion Date: | 04/2006 |
| Abstract: |
| To knock down the expression of HBx in an HBx-expressing HCC cell line (PLC/PRF/5), (RNAi); to investigate the expression levels of HBx-induced oncogenes in PLC/PRF/5 cells with knock-down of HBx; to evaluate the change of tumorigenicity of PLC/PRF/5 cells with knock-down of HBx using in vitro and in vivo assays. |
| List of Research Outputs |
| Chan D.W. and Ng I.O.L., Knock-down of hepatitis B virus X protein reduces the tumorigenicity of hepatocellular carcinoma cells, Journal of Pathology. 2006, 208(3): 372-80. |
| Chan D.W., Chan P.C.Y., Yam J.W.P., Ching Y.P. and Ng I.O.L., Prickle-1 promotes the degradation of Dishevelled by ubiquitination in liver cancer, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
| Researcher : Chan EYT |
| List of Research Outputs |
| Au W.Y., Kumana C.R., Lam C.W., Cheng V.C.C., Shek T.W.H., Chan E.Y.T., Liu K.Y. and Kwong Y.L., Solid tumors subsequent to arsenic trioxide treatment for acute promyelocytic leukemia, Leukemia Research. 2006. |
| Chong W.P., Ip E.W.K., Tso H.W., Ng M.W., Wong W.H.S., Law H.K.W., Yung R.W.H., Chow E.Y., Au K.L., Chan E.Y.T., Lim W., Peiris J.S.M. and Lau Y.L., The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome, BMC Infectious Diseases. 2006, 6: 82. |
| Researcher : Chan GSW |
| List of Research Outputs |
| Chan G.S.W. and Chan K.W., Images in pathology: the many faces of hepatocellular carcinoma, International Journal of Surgical Pathology. 2006, 14(1): 77. |
| Chan G.S.W., Tse K.C., Lam M.F. and Chan K.W., Thrombotic microangiopathy in an allograft kidney: a diagnostic challenge, Histopathology. 2006, 48(6): 775-6. |
| Chan K.W., Chan G.S.W. and Tang S.C.W., Glomerular pathology of allograft kidneys in Hong Kong , Transplantation Proceedings. 2005, 37(10): 4293-6. |
| Chan K.W. and Chan G.S.W., Glomerular pathology of allograft kidneys, Joint symposium on extracorporeal support for multi-organ failure organized by Hong Kong College of Physicians Scientific Symposium and Hong Kong Society of Nephrology Annual Scientific Meeting, 10-11 September 2005, Hong Kong. 2005. |
| Researcher : Chan KW |
| Project Title: | Proteomic analysis of nasal NK-cell lymphoma: understanding the oncogenic process and in search of novel tumor markers |
| Investigator(s): | Chan KW |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2003 |
| Completion Date: | 10/2005 |
| Abstract: |
| To understand the proteomic aberrations involved in the malignant transformation of normal NK cell to NL, since alterations in protein expression underlie neoplastic behavior, this proteomic analysis will provide insights into the molecular pathogenesis of NL; to identify tumor markers of NL and develop assessment methods of these tumor markers. |
| Project Title: | The significance of TWIST and DERMO-1 expressions in prostatic cancer |
| Investigator(s): | Chan KW |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 10/2005 |
| Completion Date: | 10/2006 |
| Abstract: |
| The objective of the proposed study is to investigate the expression of DERMO-1 in prostate cancer and how its inactivation may interact with changes in TWIST expression to inhibit the growth and metastasis of prostate cancer. Prostate cancer is the most commonly diagnosed cancer in American men and its incidence in Hong Kong is rising. The natural history of prostate cancer varies widely in different patients. Some prostate cancers remain latent for a long time while others grow aggressively with early metastases. TWIST is highly conserved basic helix-loop-helix transcription factor. It is highly expressed in the majority of cases of prostate cancer but only in a small percentage of benign prostate hyperplasia (Kwok et al. 2005). Our study has shown that TWIST is a critical regulator of prostate cancer cell growth. TWIST expression levels are positively correlated with Gleason grading and metastasis, indicating its role in the development and progression of prostate cancer. Down-regulation of TWIST through small interfering RNA in two androgen-independent prostate cancer cell lines, PC3 and DU145, results in increased sensitivity to the anticancer drug taxol-induced cell death which is associated with decreased Bcl/Bax ratio, leading to activation of the apoptosis pathway. More importantly, inactivation of TWIST suppresses migration and invasion abilities of androgen-independent prostate cancer cells. This is correlated with induction of E-cadherin expression as well as morphologic and molecular changes associated with mesenchymal to epithelial transition. Similar results are demonstrated on the androgen-dependent LNCaP cells ectopically expressing the TWIST protein. Based on these findings, a potential therapeutic approach to inhibit the growth and metastasis of androgen-independent prostate cancer through inactivation of the TWIST gene is suggested. DERMO-1, also known as TWIST related protein 2 (TWIST2) shows extensive similarity with TWIST in protein sequence, mesodermal expression pattern in mice and function in human bone development. I proposed to study the expression of DERMO-1 in prostate cancer and how its inactivation may interact with changes in TWIST expression to inhibit the growth and metastasis of prostate cancer. Reference: Wai Kei Kwok, Ming-Tat Ling, Tak-Wing Lee, Tracy C.M. Lau, Chun Zhou, Xiaomeng Zhang, Chee Wai Chua, Kwok W. Chan, Franky L. Chan, Carlotta Glackin, Yong-Chuan Wong, Xianghong Wang. Up-Regulation of TWIST in Prostate Cancer and Its Implication as a Therapeutic Target. Cancer Res 2005;65:5153-62. |
| List of Research Outputs |
| Chan G.S.W. and Chan K.W., Images in pathology: the many faces of hepatocellular carcinoma, International Journal of Surgical Pathology. 2006, 14(1): 77. |
| Chan G.S.W., Tse K.C., Lam M.F. and Chan K.W., Thrombotic microangiopathy in an allograft kidney: a diagnostic challenge, Histopathology. 2006, 48(6): 775-6. |
| Chan K.W., Lee P.Y., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Clinical relevance of Fas expression in oesophageal squamous cell carcinoma, Journal of Clinical Pathology . 2006, 59(1): 101-4. |
| Chan K.W., Lee P.Y., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Fas expression is a favorable prognostic factor in esophageal squamous cell carcinoma, The Fourth Asia-Pacific International Academy of Pathology Congress (IAP2005), 22-26 August 2005, Beijing, China. 2005. |
| Chan K.W., Chan G.S.W. and Tang S.C.W., Glomerular pathology of allograft kidneys in Hong Kong , Transplantation Proceedings. 2005, 37(10): 4293-6. |
| Chan K.W. and Chan G.S.W., Glomerular pathology of allograft kidneys, Joint symposium on extracorporeal support for multi-organ failure organized by Hong Kong College of Physicians Scientific Symposium and Hong Kong Society of Nephrology Annual Scientific Meeting, 10-11 September 2005, Hong Kong. 2005. |
| Chim S., Lee T.L., Chan S.Y. and Chan K.W., A case of tubulointerstitial nephritis and uveitis (TINU) syndrome treated with corticosteroid and mycophenolate mofetil, Joint Annual Scientific Meeting, The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association, 7 January 2006, Queen Elizabeth Hospital. 2006, 53. |
| Chiu P.M., Feng H., Benbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model , Journal of Clinical Pathology . 2006, 59(8): 845-50. |
| Chiu P.M., Feng H., Behbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Tissue dynamic effect of all-trans retinoic acid on choriocarcinoma an organotypic model, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Kwan H.S., Shih S.M., Xue W., Chiu P.M., Chan K.W. and Cheung A.N.Y., Differential gene expression identified in complete hydatidiform mole by combining suppression subtractive hybridization and cDNA microarray, Placenta. 2006, 27: 521-526. |
| Lee P.Y., Tong M.K., Leung P.L., Chan V.W.M., Leung S.Y.L., Tam P.C., Chan K.W., Lee C.K.F., Yeung W.S.B. and Luk J.M.C., Kidney claudin-19: Localization in distal tubules and collecting ducts and dysregulation in polycystic renal disease, FEBS Letters. 2006, 580(3): 923-31. |
| Leung J.C.K., Chan L.Y., Li F.K., Tang S.C.W., Chan K.W., Chan D.T.M., Lam M.F., Wieslander A. and Lai K.N., Glucose degradation products downregulate ZO-1 expression in human peritoneal mesothelial cells: the role of VEGF, Nephrology Dialysis Transplantation. 2005, 20(7): 1336-1349. |
| Lui S.L., Chan K.W., Tsang R.C.W., Yung S.S.Y., Lai K.N. and Chan D.T.M., Effect of rapamycin on renal ischemia reperfusion injury, Joint symposium on extracorporeal support for multi-organ failure organized by Hong Kong College of Physicians Scientific Symposium and Hong Kong Society of Nephrology Annual Scientific Meeting, 10-11 September 2005, Hong Kong. 2005. |
| Ma L., Chan K.W., Trendell-Smith N.J., Wu A.Y.Y., Tian L., Lam A.C., Lo C.K., Chik S.C.C., Ko K.H., To K.W., Kam C.S.K., Li X., Yang C., Leung S.Y., Ng M.H. and Huang F., Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains, In: Ma L, Chan KW, Trendell-Smith NJ, Wu A, Tian L, Lam AC, Chan AK, Lo CK, Chik S, Ko KH, To CK, Kam SK, Li XS, Yang CH, Leung SY, Ng MH, Stott DI, MacPherson GG, Huang FP, European Journal of Immunology (In This Issue highlight, Editorial Comments). 2005, 35(11): 3364-75. |
| Tang S., Lai F.M., Lui R.Y.H., Tang C.S.O., Kung N.N.S., Ho Y.W., Chan K.W., Leung J.C.K. and Lai K.N., Lamivudine in hepatitis B-associated membranous nephropathy, Joint symposium on extracorporeal support for multi-organ failure organized by Hong Kong College of Physicians Scientific Symposium and Hong Kong Society of Nephrology Annual Scientific Meeting, 10-11 September 2005, Hong Kong. 2005. |
| Tang S.C.W., Lai F.M., Lui Y.H., Tang C.S.O., Kung N.N., Ho Y.W., Chan K.W., Leung J.C.K. and Lai K.N., Lamivudine in hepatitis B-associated membranous nephropathy, Kidney International. 2005, 68(4): 1750-1758. |
| Xue W., Feng H., Chan Y.K., Chiu P.M., Ngan H.Y.S., Khoo U.S., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Id helix-loop-helix proteins are differentially expressed in gestational trophoblastic disease., Histopathology. 2005, 47(3): 303-9. |
| Researcher : Chan LC |
| Project Title: | Ras signaling in human leukaemia |
| Investigator(s): | Chan LC |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 01/2005 |
| Abstract: |
| N/A |
| Project Title: | ATM mutations in childhood leukaemia |
| Investigator(s): | Chan LC, Ha SY, Mizutani S., Greaves M.F., Chen S.J. |
| Department: | Pathology |
| Source(s) of Funding: | Michael Kadoorie Cancer Genetics Research Fund |
| Start Date: | 01/2005 |
| Abstract: |
| To screen for ATM gene mutations in childhood ALL samples from Hong Kong, Shanghai, Tokyo and London, UK; to determine the germline status of the ATM gene in patients whose diagnostic samples showed mutations; to determine the presence of ATM mutations or allelic variations in the normal population of samples. |
| Project Title: | Ras signaling in human leukaemia |
| Investigator(s): | Chan LC, Kong CT, So E.C.W. |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 01/2005 |
| Abstract: |
| To study: (1) Identification of the possible interaction between other MLL fusion partners and components of Ras-mediated pathways. i) design of MLL fusion partner constructs. ii) analysis of transactivation of E1K-1, a target of Ras pathway signaling. iii)soft agar transformation assay. (2) Molecular dissection of the potential functional link between Ras-signaling and MLL-AF6 fusion mediated leukaemogenesis using the ML-1 cell line. i) molecular analysis of Ras signaling pathway following suppression of MLL-AF6 expression in ML-1 cell line . ii) effects of inhibition of Ras signaling pathway on cellular growth and apotosis of ML-1 cell line . (3) Validation of the pathogenic significance of Ras-signaling pathway in MLL fusion mediated leukaemogenesis using an Mll-Een knock-in model. i) effects on suppression of Ras signaling pathway on growth and differentiation of embryonic bodies and haemopoiesis colonies derived from Mll-Een targeted ES cells. |
| List of Research Outputs |
| Au W.Y., Chan L.C., Liang R.H.S. and Kwong Y.L., Myelodysplastic syndrome and acute myeloid leukemia after treatment with fludarabine, mitoxantrone, and dexamethasone, American Journal of Hematology. 2006, 81(6): 471-3. |
| Chan A.Y., Luo H.Y., Wang W., Chui D.H., Ma E.S.K., Chan L.C. and Chong S.S., Diagnostic pitfall in PCR-based alpha-thalassemia genotyping resulting from a (G->C) polymorphism at nucleotide 71 3' to the alpha2-globin gene termination codon, Chinical Chemistry. 2006, 52(3): 536-7. |
| Chan L.C., Biological significance of MLL-EEN fusion gene in acute leukaemia., Peking University People's Hospital & Peking University Institute of Hematology. Beijing, China.. 2005. |
| Chan L.C., Diagnostic procedure of leukaemia., Peking University People's Hospital & Peking University Institute of Hematology. Beijing, China.. 2005. |
| Chan L.C. and Patil N.G., Monograph 2: Problem-Based Learning (PBL) Everything you want to know and are not afraid to ask. Hong Kong, Institue of Medical and Health Sciences Education, 2006, 1-48. |
| Chan L.C., Lee P.P.W. and Patil N.G., Monograph 2: Problem-based Learning (PBL): Everything you want to know and are not afraid to ask, PBL - Its role and place in the medical curriculum. Institute of Medical and Health Scienced Education, HKU, 2006, 7-11. |
| Chan L.C. and Lam T.H., Monograph 2: Problem-based Learning (PBL): Everything you want to know and are not afraid to ask, Problem-based learning: A new approach to medical education. Institute of Medical and Health Scienced Education, HKU, 2006, 3-6. |
| Chan L.C. and Beh S.L., Monograph 2: Problem-based Learning (PBL): Everything you want to know and are not afraid to ask, Things you wish to know about PBL and are not afraid to ask. Institute of Medical and Health Scienced Education, HKU, 2006, 25-31. |
| Chan L.C., Mouse models in human leukaemia., 4th Asia-Pacific International Academy of Pathology Congress 2005. Beijing, China.. 2005. |
| Chan L.C., Sustaining the quality of Problem Based Learning (PBL) – navigating the pitfalls, 3rd Congress of Asian Medical Education Association. Seoul, Korea. October 23-25, 2005 . 2005. |
| Chan V.S.F., Chan Y.K., Chen Y., Poon L.L.M., Cheung A.N.Y., Zheng B., Chan K.H., Mak W.W., Ngan H.Y.S., Xu X., Screaton G., Tam P.K.H., Austyn J.M., Chan L.C., Yip S.P., Peiris J.S.M., Khoo U.S. and Lin C.L., Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection. , Nature Genetics. 2006, 38: 38-46. |
| Choi C.L., Ma E.S.K. and Chan L.C., In vitro characterization of silent beta-thalassemia mutation, +8 C-to-T substitution, The 3rd Asia Hematology Association. Jeju, Korea. August 17-20, 2005. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Au W.Y., Wong M.L.Y., Shen L., Wong K.Y., Wan T.S.K., Cheung W.L., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006 . 2006. |
| Khoo U.S., Chan V.S.F., Chan Y.K., Chen Y., Poon L.L.M., Cheung A.N.Y., Zheng B., Ngan H.Y.S., Tam P.K.H., Chan L.C., Yip S.P., Peiris J.S.M., Sham P.C. and Lin C.L., The protective role of homozygous L-SIGN (CLEC4M) in SARS coronavirus infection., HUGO's 11th Human Genome Meeting, Helsinki, Finland. . 2006. |
| Kong C.T., Sham M.H. and Chan L.C., The MLL-EEN fusion gene leads to maturation arrest and self-renewal of hematopoietic progenitors in ES cells and the development of myeloid leukemia in chimeric mice, FASEB Summer Research Conferences - Hematological Malignancies, Saxtons River, USA. July 30 - August 4, 2005 . 2005. |
| Kong C.T., Sham M.H., So C.W.E., Cheah K.S.E., Chen S.J. and Chan L.C., The Mll-Een knockin fusion gene enhances proliferation of myeloid progenitors derived from mouse embryonic stem cells and causes myeloid leukaemia in chimeric mice, Leukemia. 2006, 20: 1829–1839. |
| Kwan T.F., Liang R.H.S., Verfaillie C.M., Ekker S.C., Chan L.C., Lin S. and Leung A.Y.H., Regulation of primitive hematopoiesis in zebrafish embryos by the death receptor gene, Experimental Hematology . 2006, 34(1): 27-34. |
| Li C.K., Chik K.W., Ha S.Y., Lee A.C., Yuen H.L., Ling S.C., Lee V., Chan G.C.F., Shing M.M., Chan L.C. and Ng M.H., Improved outcome of acute lymphoblastic leukaemia treated by delayed intensification in Hong Kong children: HKALL97 study, Hong Kong Medical Journal. 2006, 12(1): 33-9. |
| Ng J.M.H., Zhuang S.M. and Chan L.C., Mutation analysis of EBP, an adaptor protein, involved in MLL-EEN mediated leukaemogenesis, FASEB Summer Research Conferences – Hematological Malignancies, Saxtons River, USA. July 30 - August 4, 2005. |
| Wang W., Chan A.Y., Chan L.C., Ma E.S.K. and Chong S.S., Unusual rearrangement of the alpha-globin gene cluster containing both the -alpha3.7 and alphaalphaalphaanti-4.2 crossover junctions: clinical diagnostic implications and possible mechanisms, Clinical Chemistry. 2005, 51(11): 2167-70. |
| Wong J.G.W.S., Patil N.G., Beh S.L., Cheung E.P.T., Wong V., Chan L.C. and Mak-Lieh F., Cultivating psychological well-being in Hong Kong's future doctors, Medical Teacher. 2005, 27(8): 715-9. |
| Yip B.H., Guo T., Hu X., Au W.Y., Wong K.Y., Wan T.S.K., Chen W.Y.W., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) involving immunoglobulin heavy chain gene locus in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006. |
| Yip S.F., Wan T.S.K., Lie A.K.W., Liu H.S.Y. and Chan L.C., Monitoring of chronic myeloid leukemia (CML) imatinib response by fluorescence-in-situ-hybridization (FISH), American Society of Hematology, Atlanta, Georgia. December 10-13, 2005. Abstract No. 4837. Blood. 2005, 106(11) Part 2: 289b. |
| Yip S.F., So J.C.C., Chan A.Y.Y., Liu H.S.Y., Wan T.S.K. and Chan L.C., The lack of association between JAK2 V617F mutation and myelodysplastic syndrome with or without myelofibrosis , Leukemia. 2006, 20(6): 1165. |
| Yip S.F., Wan T.S.K., Chan L.C. and Chan G.C.F., Trisomy 4 as sole karyotypic abnormality in acute lymphoblastic leukemia: Different clinical features and treatment response between B and T phenotypes?, Cancer Genetics and Cytogenetics. 2006, 164: 94-95. |
| Researcher : Chan LK |
| List of Research Outputs |
| Chan L.K., Yam J.W.P. and Ng I.O.L., C20, a novel binding partner of DLC1 identified by yeast-2-hybrid screening, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
| Researcher : Chan PCY |
| List of Research Outputs |
| Chan D.W., Chan P.C.Y., Yam J.W.P., Ching Y.P. and Ng I.O.L., Prickle-1 promotes the degradation of Dishevelled by ubiquitination in liver cancer, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
| Ko C.F., Yam J.W.P., Chan P.C.Y., Jin D. and Ng I.O.L., Interaction of deleted in liver cancer 1 (DLC1) with tensin2 and its implications in tumor suppression, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
| Researcher : Chan QKY |
| List of Research Outputs |
| Cheung A.N.Y., Chiu P.M., Chan Q.K.Y., Chan Y.K. and Ngan H.Y.S., Expression of Stem cell related genes in normal placentas and Gestational Trophoblastic Diseases, 11th Conference of the European Placenta Group, Glasgow, 2-8th September. 2005. |
| Researcher : Chan SY |
| List of Research Outputs |
| Tse Y.T., Chan Y.K., Chan S.Y., Tsang S.T.Y., Sham P.C. and Khoo U.S., Estrogen Receptor a Gene Polymorphisms and Breast Cancer Risk in Chinese, HUGO's 11th Human Genome Meeting, Helsinki, Finland. . 2006. |
| Researcher : Chan TL |
| Project Title: | Molecular characterisation of the serrated neoplasia pathway and its role in the development of colorectal cancer with mismatch repair deficiency |
| Investigator(s): | Chan TL, Leung SY, Yuen ST |
| Department: | Pathology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 01/2005 |
| Abstract: |
| Colorectal cancer (CRC) is one of the commonest cancers world-wide with 850,000 new cases each year. Majority of CRC are known to develop through an adenoma-carcinoma sequence, with molecular genetic changes that characterize each transition step. Adenoma is considered pre-malignant and early prevention and treatment of CRC is possible through regular endoscopic surveillance and removal of tumour at the adenoma stage. However, despite regular surveillance, some patients still develop CRC. One of the possibilities is that there exists another pathway of tumour development. Recently, there are data to suggest the existence of an alternative route, the serrated neoplasia pathway, for CRC development. This latter pathway includes those serrated polyps (SP) that span a morphological spectrum from hyperplastic polyp (HP) to serrated adenoma (SA). The earliest member in this pathway, HP, is a very common lesion in aged individuals and it is a long held belief that HPs are innocent with little propensity for malignant progression. However, a small subset of HPs may progress but the criteria to distinguish the high risk versus the low risk ones are unclear. Concurrently, it is known that a subset (15%) of sporadic CRC manifest a form of genetic instability called microsatellite instability (MSI). This is due to promoter methylation leading to loss of expression of the DNA mismatch repair protein MLH1. The evolution of this subset of CRC is unclear as a preceding adenoma phase is very rarely seen. Recently, studies by us and others have provided molecular evidences to suggest that there may be a strong link between the serrated neoplasia pathway and the development of sporadic CRC with MSI. These include the identification of a high incidence of BRAF mutation in HPs and SAs, the occurrence of MSI in some SPs and the selective association of BRAF mutation with sporadic late-onset CRC with MSI. Our recent pilot study has shown that MLH1 inactivation can be detected in SPs at its very early phase and these can just involve several crypts within the lesion. With these data, we propose to perform a large scale phenotypic and molecular characterization of serrated polyps at their early phase of evolution to define the link between SPs and MSI CRC, and the temporal sequence of genetic changes in this pathway. Aims: 1. To look for evidence of MLH1 inactivation in various stages of evolution of serrated polyps, and to document its incidence and phenotypic characteristics. 2. To document the occurrence of microsatellite instability and frameshift mutation in growth regulatory genes containing microsatellite encoding region as consequences of MLH1 inactivation in various stages of serrated polyps. 3. To analyse the inter-relationship between MLH1 inactivation, BRAF/KRAS mutations and presence of the CpG Island Methylator Phenotype in SPs and their temporal sequence of occurrence. 4. To look for alteration in major molecular genetic pathways in SPs with MLH1 inactivation. 5. To look for evidence of a field effect of MLH1 inactivation in the colon in patients with sporadic late-onset MSI colorectal cancer with MLH1 promoter methylation. 6. To look for clinical, morphological or molecular markers that can distinguish SPs with high risk of progression to MSI CRC. |
| Project Title: | Allele-specific imbalance in gene expression as a cause for hereditary colorectal cancer |
| Investigator(s): | Chan TL, Leung SY, Yuen ST |
| Department: | Pathology |
| Source(s) of Funding: | Michael Kadoorie Cancer Genetics Research Fund |
| Start Date: | 01/2005 |
| Abstract: |
| To look for allele-specific imbalance in gene expression of the Adenomatous Polyposis Coli (APC), MSH2 and MLH1 genes in FAP or HNPCC patients with undetectable germline mutation; to confirm the pathological significance of the allele with a lower gene expression level by examination for co-segregation with disease and loss of the wild-type allele in cancer tissue; to look for mechanisms that can account for the reduced gene expression level in the disease allele. |
| Project Title: | Molecular characterisation of the serrated neoplasia pathway and its role in the development of colorectal cancer with mismatch repair deficiency |
| Investigator(s): | Chan TL |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 12/2005 |
| Abstract: |
| N/A |
| Project Title: | Molecular characterisation of the serrated neoplasia pathway and its role in the development of colorectal cancer with mismatch repair deficiency |
| Investigator(s): | Chan TL, Leung SY, Yuen ST |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 12/2005 |
| Abstract: |
| To look for evidence of MLH1 inactivation in various stages of evolution of serrated polyps, and to document its incidence and phenotypic characteristics; to document the occurrence of microsatellite instability and frameshift mutation in growth regulatory genes containing microsatellite encoding region as consequences of MLH1 inactivation in various stages of serrated polyps; to analyse the inter-relationship between MLH1 inactivation, BRAFIKRAS mutations and presence of the CpG Island Methylator Phenotype in SPs and their temporal sequence of occurrence; to look for alteration in major molecular genetic pathways in SPs with MLH1 inactivation; to look for evidence of a field effect of MLH1 inactivation in the colon in patients with sporadic late-onset MSI colorectal cancer with MLH1 promoter methylation; to look for clinical, morphological or molecular markers that can distinguish SPs with high risk of progression to MSI CRC. |
| Project Title: | Expression of microRNAs in various stages and pathways of colorectal carcinogenesis |
| Investigator(s): | Chan TL, Leung SY, Yuen ST |
| Department: | Pathology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 02/2006 |
| Abstract: |
| MicroRNAs (miRNAs) are a newly discovered class of non-protein coding RNAs that play important roles in embryonic development and many biological processes in diverse species. They function to regulate expression of other protein-coding genes by promoting their mRNA degradation or inhibiting their protein translation. Though the precise functions of individual miRNA and the repertoire of target genes that they each regulates are mostly unknown, emerging data suggest their involvement in regulating some major oncogenic pathways including those mediated by the RAS and the c-myc genes. miRNAs reside frequently in genomics regions involved in cancers. Deranged expression of miRNAs has been reported in several cancer types. The miRNA expression profile can distinguish histological cell lineage of cancers and can even distinguish molecular pathways of transformation for cancers derived from the same cell lineage. Colorectal cancer (CRC) is one of the most common cancers worldwide. Several major molecular pathways of CRC development is currently known, including the APC/KRAS/p53/chromosome instability pathway and the microsatellite instability/TGF pathway. Currently, little is known regarding the expression profiles of miRNAs in colon, and whether there is deregulated expression of specific miRNAs in various stages or pathways of CRC development. In this study we aim to systematically profile the expression of miRNAs, using a high-throughput quantitative RT-PCR analysis method, in various stages and pathways of CRC development, with an aim to gain a better understanding of their possible involvement in colon carcinogenesis. Aims 1) To profile the expression of miRNAs in normal mucosae, adenomas and carcinomas of the colon, and to compare the differences in miRNA expression profiles of the progenitor cells residing at the base of the crypt and the mature cells residing at the top. 2) To compare the variation in expression of miRNAs in different molecular subtypes of CRC including those with microsatellite instability, microsatellite stable or microsatellite and chromosome stable phenotype. 3) To identify specific miRNAs of interest that show altered expression in the course of CRC development, or in specific molecular subgroups of CRC 4) To investigate the function of these miRNAs by over-expression or gene silencing approach in cell culture system. 5) To delineate the putative protein-coding target(s) regulated by these miRNA(s) using bioinformatics approach and their validation by western blotting. |
| List of Research Outputs |
| Chan T.L., Molecular Genetics of Early-onset Colorectal Cancer, Frontiers in Biomedical Research, HKU. 2005. |
| Tang S.F., Chan K.H., Cheng V.C.C., Woo P.C.Y., Lau S.K.P., Lam C.C.K., Chan T.L., Wu A.K.L., Hung I.F.N., Leung S.Y. and Yuen K.Y., Comparative host gene transcription by microarray analysis early after infection of Huh7 cell line by SARS coronavirus and human coronavirus 229E., Journal of Virology. 2005, 79: 6180-6193. |
| Researcher : Chan YK |
| Project Title: | Study of metastasis suppressing genes in metastatic ovarian cancer |
| Investigator(s): | Chan YK, Ngan HYS, Cheung ANY, Khoo US |
| Department: | Obstetrics & Gynaecology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2004 |
| Completion Date: | 04/2006 |
| Abstract: |
| To investigate the role of the metastasis suppressing genes in the metastasis ovarian cancer. The epigenetic factor of promoter hypermethylation in relation to the expression of the metastasis suppressing gene will aso be investigated. |
| List of Research Outputs |
| Chan V.S.F., Chan Y.K., Chen Y., Poon L.L.M., Cheung A.N.Y., Zheng B., Chan K.H., Mak W.W., Ngan H.Y.S., Xu X., Screaton G., Tam P.K.H., Austyn J.M., Chan L.C., Yip S.P., Peiris J.S.M., Khoo U.S. and Lin C.L., Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection. , Nature Genetics. 2006, 38: 38-46. |
| Cheung A.N.Y., Chiu P.M., Chan Q.K.Y., Chan Y.K. and Ngan H.Y.S., Expression of Stem cell related genes in normal placentas and Gestational Trophoblastic Diseases, 11th Conference of the European Placenta Group, Glasgow, 2-8th September. 2005. |
| Fong P.Y., Xue W., Ngan H.Y.S., Chiu P.M., Chan Y.K., Tsao G.S.W. and Cheung A.N.Y., Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study, Journal of Clinical Pathology. 2006, 59: 179-183. |
| Khoo U.S., Chan V.S.F., Chan Y.K., Chen Y., Poon L.L.M., Cheung A.N.Y., Zheng B., Ngan H.Y.S., Tam P.K.H., Chan L.C., Yip S.P., Peiris J.S.M., Sham P.C. and Lin C.L., The protective role of homozygous L-SIGN (CLEC4M) in SARS coronavirus infection., HUGO's 11th Human Genome Meeting, Helsinki, Finland. . 2006. |
| Liu S., Chan Y.K., Leung C.Y., Law H.K.W., Leung T.W. and Ngan H.Y.S., Enhancement of the radiosensitivity of cervical cancer cells by overexpressing p73a, Molecular Cancer Therapeutics. USA, American Association of Cancer Research, 2006, 5: 1209-1215. |
| Tse Y.T., Chan Y.K., Chan S.Y., Tsang S.T.Y., Sham P.C. and Khoo U.S., Estrogen Receptor a Gene Polymorphisms and Breast Cancer Risk in Chinese, HUGO's 11th Human Genome Meeting, Helsinki, Finland. . 2006. |
| Xu M.S., Chan Y.K., Peiris J.S.M., Yip S.P., Cheung A.N.Y. and Khoo U.S., A variant in the CD209 promoter is associated with severity of Severe Acute Respiratory Syndrome (SARS), HUGO's 11th Human Genome Meeting, Helsinki, Finland. 2006. |
| Xue W., Feng H., Chan Y.K., Chiu P.M., Ngan H.Y.S., Khoo U.S., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Id helix-loop-helix proteins are differentially expressed in gestational trophoblastic disease., Histopathology. 2005, 47(3): 303-9. |
| Researcher : Chen WYW |
| List of Research Outputs |
| Chen W.Y.W., Hu X., Liang A.C.T., Au W.Y., So J.C.C., Wong M.L.Y., Shen L., Tao Q., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6 deregulating mutations, in gastric lymphoma, Blood. 2006, 108(7): 2373-83. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Wong M.L.Y., Shen L., Wong K.Y., Au W.Y., Cheung W.L., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Au W.Y., Wong M.L.Y., Shen L., Wong K.Y., Wan T.S.K., Cheung W.L., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006 . 2006. |
| Yip B.H., Guo T., Hu X., Wong K.Y., Chen W.Y.W., Au W.Y., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Yip B.H., Guo T., Hu X., Au W.Y., Wong K.Y., Wan T.S.K., Chen W.Y.W., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) involving immunoglobulin heavy chain gene locus in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006. |
| Researcher : Cheung ANY |
| Project Title: | Pi-class Glutathione-S-Transferase in endometrial carcinoma |
| Investigator(s): | Cheung ANY, Ngan HYS, Khoo US |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2003 |
| Completion Date: | 10/2005 |
| Abstract: |
| To investigate whether the genetic alteration, status of expression and methylation of GSTP1 contributes significantly to the pathogenesis and progression of endometrial cancer. |
| Project Title: | Stem cell related genes in gynaecological cancers |
| Investigator(s): | Cheung ANY, Ngan HYS |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2004 |
| Completion Date: | 10/2006 |
| Abstract: |
| To characterize the expression levels and epigenetic alterations of important stem-cell related genes in ovarian and endometrial cancers in an attempt to evaluate the roles of such genes in the their carcinogenesis; and to define useful genetic markers as predictors of clinical progression or targets for therapy. |
| Project Title: | Stem cell related genes in gestational trophoblastic diseases |
| Investigator(s): | Cheung ANY |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 01/2005 |
| Abstract: |
| N/A |
| Project Title: | Stem cell related genes in gestational trophoblastic diseases |
| Investigator(s): | Cheung ANY, Ngan HYS, Chan YK, Yeung WSB |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 01/2005 |
| Abstract: |
| To characterize the expression levels and epigenetic alterations of important stem-cell related genes in gestational trophoblastic disease (GTD) in an attempt to evaluate the roles of such genes in the pathogenesis of GTD; and to define useful genetic markers as predictors of clinical progression or targets for therapy. |
| Project Title: | Selecting most suitable students for production of best medical doctors-which criteria should we use? |
| Investigator(s): | Cheung ANY, Patil NG, Ip MSM, Chan LC, Sze D |
| Department: | Pathology |
| Source(s) of Funding: | Leung Kau Kui Research and Teaching Endowment Fund - Teaching Grants |
| Start Date: | 02/2005 |
| Abstract: |
| (a) enhancing the processes for evaluating and improving admission criteria for MBBS curriculum; and potentially; (b) improving curriculum design and (c) improving learning opportunities of students on ethical values and communication skills. |
| Project Title: | Follicle stimulating hormone receptor genetic polymorphism and susceptibility to ovarian cancer |
| Investigator(s): | Cheung ANY |
| Department: | Pathology |
| Source(s) of Funding: | Incentive Award for RGC CERG Fundable But Not Funded Projects |
| Start Date: | 07/2005 |
| Completion Date: | 06/2006 |
| Abstract: |
| N/A |
| Project Title: | RAS association domain family related genes in gynaecological cancers |
| Investigator(s): | Cheung ANY, Ngan HYS, Liu VWS, Siu KY, Ip PPC |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 01/2006 |
| Abstract: |
| The purpose of the proposed investigation are to characterize the expression levels and epigenetic alterations of RAS association domain family related genes in ovarian and endometrial cancers in an attempt to evaluate the roles of such genes in the their carcinogenesis; and to define useful genetic markers as predictors of clinical progression or targets for therapy. Key Issues and Problems being addressed: Endometrial and ovarian cancers are two common cancers in the female genital tract and the latter is responsible for the highest mortality in this group of cancers. Early detection is essential since the prognosis is significantly affected by the staging of the cancers at first diagnosis. We have earlier reported the significant roles of a few tumour suppressor genes in gynaecological malignancies (1-3) as an attempt to explore their application as potential cancer markers and to better our understanding on endometrial and ovarian cancers carcinogenesis. RASSF1 (the RAS association domain family 1) and RASSF2 are members of a new group of RAS effectors which may function as tumor suppressors genes and interact with the K-Ras oncogene affecting apoptosis and cell cycle arrest (4). Whilst mutation of RASSF1A (isoform A) occurs rarely in human cancers, RASSF1A methylation has been reported in at least 37 tumor types and is postulated to have the potential to be used as a marker for tumor diagnosis, early detection and monitoring (5). RASSF2A (isoform A) was recently reported to be frequently inactivated in colorectal cancer by CpG island promoter hypermethylation (6). The human DOC-2/DAB2 interactive protein gene (hDAB2IP) is a novel member of the Ras GTPase-activating gene family (7, 8). hDAB2IP directly interacts with the N-terminal domain of disabled-2 protein (DAB2, also known as DOC-2, differentially expressed in ovarian carcinoma 2), which appears to be a tumor suppressor in various cancers (9). Both DAB2IP and DAB2 form a unique protein complex that has a negative regulatory effect on the Ras-mediated signal pathway (8). hDAB2IP methylation was found to be associated with cancers of the prostate, breast, lung and gastrointestinal tract (10, 11). BLU gene is a candidate tumor suppressor gene immediately upstream of RASSF1 (12). Heterogenous association between methylation and expression status of BLU gene in various cancers was observed. The roles of these RAS association domain family related genes in endometrial and ovarian cancers are still unknown. References (*Publications from our group): *1. Chan KY, Ozcelik H, Cheung AN, Ngan HY, Khoo US. Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer. Cancer Res. 2002 Jul 15;62(14):4151-6. *2. Chan QK, Khoo US, Chan KY, Ngan HY, Li SS, Chiu PM, Man LS, Ip PP, Xue WC, Cheung AN. Promoter methylation and differential expression of pi-class glutathione S-transferase in endometrial carcinoma. J Mol Diagn. 2005;7:8-16. *3. Shen DH, Chan KY, Khoo US, Ngan HY, Xue WC, Chiu PM, Ip P, Cheung AN. Epigenetic and genetic alterations of p33ING1b in ovarian cancer. Carcinogenesis. 2005;26:855-63. 4. Vos MD, et al. RAS uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis. J Biol Chem 2000; 275: 35669-35672. 5. Agathanggelou A, et al. Methylation associated inactive of RASSF1A from region 3p21.3 in lung, breast and ovarian tumors. Oncogene, 2001, 20:1509-1518. 6. Hesson LB, et al. CpG island promoter hypermethylation of a novel Ras-effector gene RASSF2A is an early event in colon carcinogenesis and correlates inversely with K-ras mutations. Oncogene, 2005, 24:3987-3994. 7. Chen H, et al. Differential regulation of human gene DAB2IP in normal and malignant prostatic epithelia: cloning and characterization. Genomics 2002; 79: 573-581. 8. Wang Z, et al. The mechanism of growth-inhibitory effect of DOC-2/DAB2 in prostate cancer. Characterization of a novel GTPase-activating protein associated with N-terminal domain of DOC-2/DAB2. J Biol Chem 2002; 277: 12622-12631. 9. Zhou J, Hsieh JT. The inhibitory role of DOC-2/DAB2 in growth factor receptor-mediated signal cascade. DOC-2/DAB2-mediated inhibition of ERK phosphorylation via binding to Grb2. J Biol Chem 2001; 276: 27793-27798. 10. Dote H, et al. Aberrant promoter methylation in human BAB2 interactive protein (hDAB2IP) gene in breast cancer. Clin Cancer Res, 2004, 10: 2082-2089. 11. Yano M, et al. Aberrant promoter methylation of human DAB2 interactive protein (hDAB2IP) gene in lung cancers. Int J Cancer, 2005, 113: 59-66. 12. Agathanggelou A, et al. Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers. Oncogene. 2003, 22(10):1580-8. |
| List of Research Outputs |
| Ajonuma L.C., Ng E.H.Y., Chan L.N., Chow P.H., Kung L.S., Cheung A.N.Y., Ho L.S., Briton-Jones C., Lok I.H., Haines C.J. and Chan H.C., Ultrastructural characterization of whole hydrosalpinx from infertile Chinese women, Cell Biology International. 2005, 29: 849-856. |
| Chan V.S.F., Chan Y.K., Chen Y., Poon L.L.M., Cheung A.N.Y., Zheng B., Chan K.H., Mak W.W., Ngan H.Y.S., Xu X., Screaton G., Tam P.K.H., Austyn J.M., Chan L.C., Yip S.P., Peiris J.S.M., Khoo U.S. and Lin C.L., Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection. , Nature Genetics. 2006, 38: 38-46. |
| Cheung A.N.Y., Application of Automated Technology and HPV testing in cervical cancer screening program, Family Planning Association. July 7. 2005. |
| Cheung A.N.Y., Award for Innovative Excellence in Teaching, Learning & Technology, 17th International Conference on College Teaching and Learning. 2006. |
| Cheung A.N.Y., Cervical cancer screening in Hong Kong, Asia Oceania (research organisation on) Genital Infections & Neoplasia (AOGIN), Karambuni Sabah, Malaysia July 18-20, 2005 & Asia Pacific Cervical Cancer Prevention Round Table Meeting, Kota Kinabalu, Malaysia July 21. 2005. |
| Cheung A.N.Y., Electronic Question and Answer System: A Platform for Student Support, 17th International Conference on College Teaching and Learning, April 10-14, 2006, Jacksonville, Florida, USA. (Received Award for Innovative Excellence in Teaching, Learning & Technology). 2006. |
| Cheung A.N.Y., Chiu P.M., Chan Q.K.Y., Chan Y.K. and Ngan H.Y.S., Expression of Stem cell related genes in normal placentas and Gestational Trophoblastic Diseases, 11th Conference of the European Placenta Group, Glasgow, 2-8th September. 2005. |
| Cheung A.N.Y., Genetic indicators for development of gestational trophoblastic neoplasia, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Cheung A.N.Y., Hong Kong – cervical cancer screening, Proceedings from the First Asia-Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN) 2005. 2005. |
| Cheung A.N.Y., Pathology of Cervical Cancer and Intraepithelial neoplasia, Postgraduate Symposium on Cervical Cancer on 18-21 August 2005, Guangzhou, China. 2005. |
| Cheung A.N.Y., University Teaching Fellow, 2005. |
| Cheung W.T., Au S.C.L., Cheung A.N.Y., Ngan H.Y.S. and Wong A.S.T., Pigment Epithelium-Derived Factor, a Gene Down-Regulated by Estrogen, Mediates Growth Inhibition in Human Ovarian Surface Epithelial and Ovarian Cancer Cells, 88th Annual Meeting of the Endocrine Society, Boston, MA, p.644 (Abstract No. P3-32). 2006. |
| Cheung W.T., Au S.C., Cheung A.N.Y., Ngan H.Y.S., Tombran-Tink J., Auersperg N. and Wong A.S.T., Pigment epithelium-derived factor is estrogen sensitive and inhibits the growth of human ovarian cancer and ovarian surface epithelial cells, Endocrinology. 2006, 147(9): 4179-91. |
| Chiu P.M., Feng H., Benbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model , Journal of Clinical Pathology . 2006, 59(8): 845-50. |
| Chiu P.M., Feng H., Behbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Tissue dynamic effect of all-trans retinoic acid on choriocarcinoma an organotypic model, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M. and Cheung A.N.Y., Differential expression of insulin-like growth factor binding protein 1 and ferritin light polypeptide in gestational trophoblastic neoplasia: combined cDNA suppression subtractive hybridization and microarray study, Cancer. 2005, 104(11): 2409-2416. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Kwan H.S., Shih S.M., Xue W., Chiu P.M., Chan K.W. and Cheung A.N.Y., Differential gene expression identified in complete hydatidiform mole by combining suppression subtractive hybridization and cDNA microarray, Placenta. 2006, 27: 521-526. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate Stem Cell Antigen is a genetic indicator for development of gestational trophoblastic neoplasia, American Association for Cancer Research's 97th Annual Meeting, March 31-April 5, 2006, in Washington DC, USA. 2006. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate stem cell antigen is over-expressed in persistent hydatidiform mole, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Fong P.Y., Xue W., Ngan H.Y.S., Chiu P.M., Chan Y.K., Tsao G.S.W. and Cheung A.N.Y., Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study, Journal of Clinical Pathology. 2006, 59: 179-183. |
| Huang F.Y., Chiu P.M., Tam K.F., Kwok K.Y., Lau E.T., Tang M.H., Ng T.Y., Liu V.W.S., Cheung A.N.Y. and Ngan H.Y.S., Semi-quantitative fluorescent PCR analysis identifies PRKAA1 on chromosome 5 as a potential candidate cancer gene of cervical cancer, Gynecologic Oncology. 2006, 103(1): 219-25. |
| Ip P.P.C., Chan K.K.L., Cheung A.N.Y. and Ngan H.Y.S., Choriocarcinomas following full-term non-molar gestations, XIIIth World Congress on Gestational Trophoblastic Diseases, The International Society for the Study of Trophoblastic Diseases and The University of Hong Kong, 23-26 October, 2005. |
| Ip P.P.C. and Cheung A.N.Y., The Pathologist’s role in Gynaecological Oncology, A Management Guideline for Gynaecological Oncology. The University of Hong Kong, 2006, 20-28. |
| Khoo U.S., Chan V.S.F., Chan Y.K., Chen Y., Poon L.L.M., Cheung A.N.Y., Zheng B., Ngan H.Y.S., Tam P.K.H., Chan L.C., Yip S.P., Peiris J.S.M., Sham P.C. and Lin C.L., The protective role of homozygous L-SIGN (CLEC4M) in SARS coronavirus infection., HUGO's 11th Human Genome Meeting, Helsinki, Finland. . 2006. |
| Li H.W., Leung S.W., Cheung A.N.Y., Yu M.M., Chan L.K. and Wong Y.F., Expression of maspin in gestational trophoblastic disease – a potential prognostic marker, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Li H.W., Leung S.W., Cheung A.N.Y., Yu M.M., Chan L.K. and Wong Y.F., Expression of maspin in gestational trophoblastic disease, Gynecologic Oncology . 2005, 101(1): 76-81. |
| Siu K.Y., Woo N.W.S., Ngan H.Y.S. and Cheung A.N.Y., Differential expression of p21-activated kinases (Paks) in ovarian cancer, American Association for Cancer Research's 97th Annual Meeting, March 31-April 5, 2006, in Washington DC, USA. (Dr Siu received the Avon Foundation-AACR International Scholar-in-Training Grant). 2006. |
| Siu K.Y., Yeung C.W., Chiu P.M., Feng H., Ngan H.Y.S., Xue W. and Cheung A.N.Y., p21-activated kinases (Paks) in gestational trophoblastic disease, XIIIth World Congress on Gestational Trophoblastic Diseases. Proceedings P.103. 2005. |
| Wang Y., Liu V.W.S., Tsang P.C.K., Chiu P.M., Cheung A.N.Y., Khoo U.S., Nagley P. and Ngan H.Y.S., Microsatellite instability in mitochondrial genome of common female cancers, International Journal of Gynecological Cancer. 2006, Suppl 1: 259-266. |
| Wang Y., Liu V.W.S., Xue W., Tsang P.C.K., Cheung A.N.Y. and Ngan H.Y.S., The Increase Of Mitochondrial Dna Content In Endometrial Adenocarcinoma Cells: A Quantitative Study Using Laser-captured Microdissected Tissues, Gynecologic Oncology. 2005, 98: 104-110. |
| Xu M.S., Chan Y.K., Peiris J.S.M., Yip S.P., Cheung A.N.Y. and Khoo U.S., A variant in the CD209 promoter is associated with severity of Severe Acute Respiratory Syndrome (SARS), HUGO's 11th Human Genome Meeting, Helsinki, Finland. 2006. |
| Xue W., Feng H., Chan Y.K., Chiu P.M., Ngan H.Y.S., Khoo U.S., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Id helix-loop-helix proteins are differentially expressed in gestational trophoblastic disease., Histopathology. 2005, 47(3): 303-9. |
| Yeung M., Pun T.C., Chan K., Ngan H.Y.S., Ip P.P.C. and Cheung A.N.Y., Negative pregnancy test and trophoblastic lesions: from ectopic abortion to choriocarcinoma, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Researcher : Cheung OF |
| List of Research Outputs |
| Wong C.M., Cheung O.F. and Ng I.O.L., Epigenetic inactivation of serine protease inhibitor TFPI-2 in human HCC, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April 2006. |
| Researcher : Cheung WL |
| List of Research Outputs |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Wong M.L.Y., Shen L., Wong K.Y., Au W.Y., Cheung W.L., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Au W.Y., Wong M.L.Y., Shen L., Wong K.Y., Wan T.S.K., Cheung W.L., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006 . 2006. |
| Wong M.L.Y., Tao Q., Fu L., Wong K.Y., Qiu G.H., Law F.B.F., Tin P.C., Cheung W.L., Lee P.Y., Tang J.C.O., Tsao G.S.W., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma, International Journal of Oncology. 2006, 28(3): 767-73. |
| Researcher : Chiang AKS |
| Project Title: | Experimental immunotherapy of tumours |
| Investigator(s): | Chiang AKS |
| Department: | Paediatrics & Adolescent Med |
| Source(s) of Funding: | Research Initiation Programme |
| Start Date: | 04/2001 |
| Abstract: |
| To develop strategies in enhancing the host immune response against tumours. |
| Project Title: | Genetic studies of tubercubosis |
| Investigator(s): | Chiang AKS, Tang N., Yew W.W., Tam C.M. |
| Department: | Paediatrics & Adolescent Med |
| Source(s) of Funding: | Other Funding Scheme |
| Start Date: | 03/2002 |
| Abstract: |
| To host susceptibility genes in tubercubosis; to study pharmacogenomics in anti-tubercubosis drug metabolism. |
| Project Title: | Prospective study of virologic and immunologic parameters of primary Epstein-Barr virus infection in Chinese children |
| Investigator(s): | Chiang AKS, Chan KH |
| Department: | Paediatrics & Adolescent Med |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 10/2003 |
| Abstract: |
| An unresolved issue in EBV immunology concerns the relationship between clinical IM-like symtoms, virus DNA load and CD8+ T cell lymphocytosis; Acute IM in adolescents is associated with large expansions of EBV lytic epitope reactivities which are followed by a later expansion of latent epitope responses. The magnitude of the EBV lytic and latent epitope reactivities would be studied and compared in both IM and non-IM patients; likewise, is there a difference in the rate of emergence of latent epitope responses bewteen the IM and non -IM patients? The kinetics and evolution of the EBV epitope-specific cytotoxic T-lymphocyte (CTL) responses from primary to persistent phases of EBV infection would be compared between the two groups of children. |
| Project Title: | Prospective study of virologic and immunologic parameters of primary Epstein-Barr virus infection in Chinese children |
| Investigator(s): | Chiang AKS, Chan KH |
| Department: | Paediatrics & Adolescent Med |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 10/2003 |
| Abstract: |
| N/A |
| Project Title: | Host susceptibility genes in tuberculosis |
| Investigator(s): | Chiang AKS, Lau YL |
| Department: | Paediatrics & Adolescent Med |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2003 |
| Completion Date: | 10/2005 |
| Abstract: |
| To investigate the genetic susceptibility of the Chinese population to tuberculosis. |
| Project Title: | Prospective study of Epstein-Barr virus (EBV) strains in primary EBV infection |
| Investigator(s): | Chiang AKS |
| Department: | Paediatrics & Adolescent Med |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2004 |
| Abstract: |
| To study the occurrence of Epstein-Barr virus (EBV) diversity and coinfection in a prospective study of primary Epstein-Barr virus infection in Chinese children. |
| Project Title: | Longitudinal study of Epstein-Barr virus specific antibody responses in childhood infectious mononucleosis |
| Investigator(s): | Chiang AKS, Chan KH |
| Department: | Paediatrics & Adolescent Med |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 12/2005 |
| Abstract: |
| The purpose of the proposed study is to compare the evolution of Epstein-Barr virus (EBV) specific antibody responses in a longitudinal followup study of symptomatic and asymptomatic primary EBV infection. What is known about EBV antibody responses in the literature? Epstein-Barr virus (EBV) infects greater than 90% of all human populations and establishes a lifelong persistence within the host. Primary infections by EBV may remain silent or induce a self-limiting lymphoproliferative disorder, infectious mononucleosis (IM). EBV-encoded antigens are divided into those expressed in the viral replicative cycle, i.e., the viral capsid antigen (VCA) and the early amtigens (EA) of the diffuse (D) and the restricted (R) varieties and those expressed in the viral latent cycle, the EBV-determined nuclear antigen (EBNA). The different timing of emergence between the antibodies to VCA and EA and those to EBNA indicates that the two sets of antigens are likely expressed on separate types of cells which become available to stimulate antibody responses under different circumstances. The laboratory diagnosis of EBV infection is based on serological tests to detect both specific antibodies to EBV antigens (1, 2) and heterophile antibodies (3, 4). At the onset of symptoms of IM, the humoral response to EBV infection is characterized by the presence of VCA IgM antibodies and the concurrent rise of VCA IgG antibodies (5). Antibodies to diffuse early antigen (anti-EA-D) are transitory and are detected in about 80% of infected persons. Antibodies to EA-R may become detectable in protracted cases of the disease after the anti-D titres have subsided. Anti-EBNA IgG can usually be detected at a later stage at several weeks to months after the the onset of symptoms. The majority of adult IM patients also develop IgM heterophile antibodies of the Paul-Bunnell type but the reason for their transient emergence is unknown. However, these heterophile antibodies are absent in the majority of children under 4 years of age (6). The antibody responses in silent primary EBV infections (more frequently occurred in children than adults) largely conform to those seen in IM except that antibodies to the EA complex are directed against R instead of D (7, 8). The early EBV-specific IgG antibody response after primary infection is made up of low avidity antibodies. The avidity increases in the few weeks to several months after the infection (9, 10). This property of the humoral IgG response has been employed in serological assays to distinguish between primary and re-infection or reactivation of different viruses such as rubella, CMV and parvovirus (11, 12, 13). Key issues: The pattern of antibody responses and the antibody levels to EBV-encoded antigens are largely derived from cross sectional studies of large number of individuals. Longitudinal serology data of persons recovering from IM is seldom available and information on the humoral response in asymptomatic EBV infection is scanty. I have followed a large number of Chinese children presenting with infectious mononucleosis and some children who are found to have asymptomatic primary EBV infection from the time of onset of infection through convalescence to persistence. It offers an opportunity to compare the natural evolution of antibody responses against EBV in symptomatic and asymptomatic infections. Project objectives: 1. To define the evolution of the humoral response against a human persistent virus. 2. To study the maturation of the humoral response against a persistent virus in terms of antibody avidity. 3. To compare the magnitude and the quality of the humoral response against viral lytic and latent EBV antigens from acute phase through convalescent to persistent phase in symptomatic and asymptomatic infections. References: 1.Henle W and Henle G: Epstein-Barr virus specific serology in immunologically compromized individuals. Cancer Res 41: 4222-4225, 1981 2.Henle W and Henle G: Immunology of Epstein-Barr virus. In: B, Roizman (Ed.), The Herpsesviruses, Vol. 1. Plenum Publishing Corp., Ne York, pp 209-252, 1982 3.Paul JR and Bunnell WW: The presence of heterophile antibodies in infecetious mononucleosis. Am J Med Sci 183: 90-104, 1932 4.Davidsohn I and Lee CL: The clinical serology of infectious mononucleosis. In: RL Carter and HG Penman (Eds.), Infectious Mononucleosis. Blackwell Scientific Publications, Ltd., Oxford, pp 177-200, 1969 5.Okano M, Thiele GM, Davis JR, Grierson HL, Purtilo DT: Epstein-Barr virus and human diseases: recent advances in disgnosis. Clin Microbiol Rev 1: 300-312, 1988 6.Sumaya CV: Infectious mononucleosis and other EBV infections: diagnostic factors. Lab Manag 24: 37-45, 1986 7.Biggar RJ, Henle G, Bocker J, Lennette ET, Fleisher G, Henle W: Primary Epstein-Barr virus infections in African infacnts. II. Clinical and serological obsevations during seroconversion. Int J cancer 22: 244-250, 1978 8.Fleisher G, Henle W, Henle G, Lennette ET, Biggar RJ: Primary Epstein-Barr virus infection in American infants: clinical and serological observations. J Infect Dis 139: 553-558, 1979 9.Inouye S, Hasegawa A, MAtsuno S, Katwo S: Changes in antibody avidity after virus infections: detection by an immunosorbent assay in which a mild protein-denaturing agent is employed. J Clin Microbiol 20: 525-529, 1984 10.Kocks C and Rajewsky K: Stepwise intracloncal maturation of antibody affinity through somatic hypermutation. Proc Nat Acad Sci USA 85: 8206-8210, 1988 11.Thomas HIJ and Morgan-Capner P: Rubella-specific IgG subclass avidity and its role in differenetiation between primary rubella and rubella reinfection. Epidemiol Infect 101: 591-598, 1988 12.Lutz E, Ward KN, Gray JJ: Maturation of antibody avidity after primary human cytomegalovirus infection is delayed in immunosuppressed solid organ transplant patients. J Med Virol 44: 317-322, 1994 13.Gray JJ, Cohen BJ, Dresselberger U: Detection of human parvirus B19-specific IgM and IgG sntibodies using a recombinant viral VP1 antigen expressed in insect cells and estimation of time of infection by testing for antibody avidity. J Virol Methods 44: 11-24, 1993 |
| List of Research Outputs |
| Researcher : Ching YP |
| Project Title: | The functional characterisation of Pak5 and caspase 4 interaction- a role in apoptosis |
| Investigator(s): | Ching YP |
| Department: | Pathology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 02/2004 |
| Completion Date: | 01/2006 |
| Abstract: |
| To confirm the interaction of Pak5 and caspase 4 using three independent assays, including co-immunoprecipitation, co-immunostaining and GST affinity pull down assays; to map the minimal binding region of these two proteins and develop functional assays to assess the functional outcome of this interaction; to determine if Pak5 plays a role in apoptosis by regulating the caspase 4. |
| Project Title: | Roles and regulation of group II p21-activated protein kinases:-implications in cancer metastasis |
| Investigator(s): | Ching YP |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 01/2005 |
| Abstract: |
| N/A |
| Project Title: | Roles and regulation of group II p21-activated protein kinases:-implications in cancer metastasis |
| Investigator(s): | Ching YP, Jin D, Ng IOL |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 01/2005 |
| Abstract: |
| To study: (1) Characterisation of the interaction between Pak5 and NM23 i) co-immunoprecipitation of Pak5 adn NM23 ii) defining the binding domain between Pak 5 and NM23 iii) xploring the interaction between Pak4 adn NM23. (2) Impact of Pak5-NM23 interaction in the biochemical properties of Pak5 and NM23 i) nucleotide diphosphate kinase activity ii) GTPase activating activity iii) in vitro kinase activity iv) subcellular localisation. 3) Roles of PakII in cancer metastasis using HCC as a model i) expression profile of Pak4 in HCC ii) clinicopathological analysis iii) cell invasion assay. |
| Project Title: | Roles of p21-activated protein kinase (Pak) 1 in the pathogenesis of liver cancer |
| Investigator(s): | Ching YP |
| Department: | Pathology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 07/2005 |
| Abstract: |
| To characterize the overexpression of Pak1 protein and its activities in human HCC; to delineate the signaling pathways mediated by Pak1 in HCC; to investigate the roles of Pak1 in the metastasis of HCC. |
| Project Title: | Roles of p21-activated protein kinase (Pak) 1 in the pathogenesis of liver cancer |
| Investigator(s): | Ching YP |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 01/2006 |
| Abstract: |
| N/A |
| Project Title: | Roles of p21-activated protein kinase (Pak) 1 in the pathogenesis of liver cancer |
| Investigator(s): | Ching YP, Ng IOL, Jin D, Yau TO |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 01/2006 |
| Abstract: |
| (1) To characterize the mechanisms leading to Pak1 overexpression in human HCC; (2) to delineate the roles of Pak1 in hepatocarcinogenesis: (i) Phosphorylation of possible downstream targets of Pak1 in human HCCs. (ii) characterization of the tumorigenic activity of Pak1 in HCC cells. (iii) characterization of the anti-apoptotic activity of Pak1 in HCC cells. (3) to investigate the role of Pak1 in cancer metastasis: >(i) regulation of cell motility and cell adhesion by Pak1 in HCC cells. (ii) HGF/Rac1/Cdc42/Pak1 signaling in HCC metastasis. (iii) HGF/Pak1 mediated angiogenic activity. (iii) HGF/Pak1 mediated angiogenic activity. |
| Project Title: | Functional characterization of a putative tumour suppressor, AMP-activated protein kinase, in liver cancer |
| Investigator(s): | Ching YP |
| Department: | Pathology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 02/2006 |
| Abstract: |
| Purpose of study Liver cancer (hepatocellular carcinoma, HCC) is one of the most common cancers in the world, especially in Asia and Africa, and is the third most common fatal cancer in Hong Kong. While the risk factors are well defined, the underlying molecular mechanisms of HCC are still far from clear. Since the development of HCC is a multistep process, our long-standing interest is to identify tumour suppressor genes that play important roles in hepatocarcinogenesis. In our search, we have found that a hepatic kinase called AMP-activated protein kinase (AMPK), a key regulator for lipid and glucose metabolism in response to energy stress, is frequently downregulated in HCC cell lines and clinical samples (42%). Interestingly, recent discoveries have shown that tumour suppressors LKB1 and TSC2 lie upstream and downstream of AMPK, respectively, indicating that AMPK may be important in the regulation of cell growth, proliferation and apoptosis. Our pilot studies have also demonstrated that ectopic expression of the AMPK catalytic subunit in HepG2 cells significantly suppresses cell growth in colony formation assay. Conversely, HCC cell line with stable knockdown of AMPK catalystic subunit expression displays a much higher proliferation rate than that of the parental cell line (see research plan). These results suggest that AMPK possesses an activity to inhibit HCC cell growth. Here we propose to fully document the expression of AMPK and its effectors in HCC. We will explore the molecular basis of the underexpression of AMPK catalytic subunit in human HCC. We will also confirm the tumour suppressor activity of AMPK and delineate the molecular mechanisms by which loss of AMPK contributes to the formation of HCC. Findings derived from our work should shed important light on the pathogenesis of HCC and may provide novel targets for therapeutic intervention. Key issue and problem being address So far, the overall prognosis of HCC is unsatisfactory due to high incidence of recurrence and metastasis. It is therefore a high priority to unravel the molecular mechanisms underlying the pathogenesis of HCC so that better treatment modalities can be designed. In previous reports and our preliminary study, activation of AMPK has been demonstrated to play a role in suppressing the growth of cancer cells. These results prompt us to further address the pathogenic role of AMPK in HCC and to determine how dysregulation of AMPK leads to hepatocarcinogenesis. In this study, we will define the tumour suppressive function of AMPK in HCC and the regulatory roles of AMPK in cell signalling. Since AMPK is an important physiological regulator of cellular metabolism in response to nutrient stress and energy supply, our proposed study should advance our understanding on whether perturbation of energy metabolism can possibly linked to carcinogenesis. Results obtained in this study will derive novel insight on how the loss of AMPK function leads to the formation of cancer, aiming to provide opportunity for new molecular drug targets. |
| List of Research Outputs |
| Chan D.W., Chan P.C.Y., Yam J.W.P., Ching Y.P. and Ng I.O.L., Prickle-1 promotes the degradation of Dishevelled by ubiquitination in liver cancer, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
| Cheung H.W., Ching Y.P., Nicholls J.M., Ling M.T., Wong Y.C., Hui C.M., Cheung A., Tsao G.S.W., Wang Q., Yuen P.W., Lo K.W., Jin D. and Wang X., Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation, Molecular Carcinogenesis. 2005, 43(4): 237-245. |
| Ching Y.P., Chan S.F. and Jin D., A centrosomal target of human T-cell leukemia virus type I oncoprotein Tax on the road to genome instability, The Croucher Advanced Study Institute “Signaling in Cell Growth abd Differentiation”. The Hong Kong University of Science and Technology, Hong Kong, January 16-20, 2006. |
| Fan X.M., Jiang X., Gu Q., Ching Y.P., He H., Xia H.H.X., Lin M.C., Chan O.O., Yuen R.M.F., Kung H.F. and Wong B.C.Y., Inhibition of Akt/PKB by a COX-2 Inhibitor Induces Apoptosis in Gastric Cancer Cells, Digestion. 2006, 73(2-3): 75-83. |
| Fung K.L., Yan H., Ching Y.P., Ng I.O.L., Chung S.S.M., Sun H. and Ko B.C.B., Homodimerization of the deleted in liver cancer 2 (DLC2) is not mediated by the SAM domain, FEBS-IUBMB Conference, July 2005. |
| Hu X., Leong V.Y.L., Ng I.O.L. and Ching Y.P., Overexpression of PAK4 in hepatocellular carcinoma (HCC), 2006 American Association for Cancer Research (AACR) Annual Meeting, Washington DC., USA, April 2006 . 2006. |
| Leung H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity, Proc Natl Acad Sci U S A. 2005, 102: 15207-15212. |
| Leung T.H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in Liver Cancer 2, DLC2, Suppresses Cell Transformation via Inhibition of Rhoa Activity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
| Ng D.C.H., Chan S.F., Kok K.H., Yam J.W.P., Ching Y.P., Ng I.O.L. and Jin D., Mitochondrial targeting of growth suppressor protein DLC2 through the START domain, FEBS Letters . 2006, 580(1): 191-8. |
| Sze M.F., Ching Y.P., Jin D. and Ng I.O.L., Dysregulation of Mitotic Spindle Checkpoint Control in Hepatocellular Carcinomas , 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
| Wong C.M., Yam J.W.P., Ching Y.P., Yau T.O., Leung T.H.Y., Jin D. and Ng I.O.L., Rho GTPase-Activating Protein Deleted in Liver Cancer Suppresses Cell Proliferation and Invasion in Hepatocellular Carcinoma, Cancer Research. 2005, 65: 8861-8868. |
| Researcher : Chiu PM |
| List of Research Outputs |
| Cheung A.N.Y., Chiu P.M., Chan Q.K.Y., Chan Y.K. and Ngan H.Y.S., Expression of Stem cell related genes in normal placentas and Gestational Trophoblastic Diseases, 11th Conference of the European Placenta Group, Glasgow, 2-8th September. 2005. |
| Chiu P.M., Feng H., Benbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model , Journal of Clinical Pathology . 2006, 59(8): 845-50. |
| Chiu P.M., Feng H., Behbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Tissue dynamic effect of all-trans retinoic acid on choriocarcinoma an organotypic model, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M. and Cheung A.N.Y., Differential expression of insulin-like growth factor binding protein 1 and ferritin light polypeptide in gestational trophoblastic neoplasia: combined cDNA suppression subtractive hybridization and microarray study, Cancer. 2005, 104(11): 2409-2416. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Kwan H.S., Shih S.M., Xue W., Chiu P.M., Chan K.W. and Cheung A.N.Y., Differential gene expression identified in complete hydatidiform mole by combining suppression subtractive hybridization and cDNA microarray, Placenta. 2006, 27: 521-526. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate Stem Cell Antigen is a genetic indicator for development of gestational trophoblastic neoplasia, American Association for Cancer Research's 97th Annual Meeting, March 31-April 5, 2006, in Washington DC, USA. 2006. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate stem cell antigen is over-expressed in persistent hydatidiform mole, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Fong P.Y., Xue W., Ngan H.Y.S., Chiu P.M., Chan Y.K., Tsao G.S.W. and Cheung A.N.Y., Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study, Journal of Clinical Pathology. 2006, 59: 179-183. |
| Huang F.Y., Chiu P.M., Tam K.F., Kwok K.Y., Lau E.T., Tang M.H., Ng T.Y., Liu V.W.S., Cheung A.N.Y. and Ngan H.Y.S., Semi-quantitative fluorescent PCR analysis identifies PRKAA1 on chromosome 5 as a potential candidate cancer gene of cervical cancer, Gynecologic Oncology. 2006, 103(1): 219-25. |
| Siu K.Y., Yeung C.W., Chiu P.M., Feng H., Ngan H.Y.S., Xue W. and Cheung A.N.Y., p21-activated kinases (Paks) in gestational trophoblastic disease, XIIIth World Congress on Gestational Trophoblastic Diseases. Proceedings P.103. 2005. |
| Wang Y., Liu V.W.S., Tsang P.C.K., Chiu P.M., Cheung A.N.Y., Khoo U.S., Nagley P. and Ngan H.Y.S., Microsatellite instability in mitochondrial genome of common female cancers, International Journal of Gynecological Cancer. 2006, Suppl 1: 259-266. |
| Xue W., Feng H., Chan Y.K., Chiu P.M., Ngan H.Y.S., Khoo U.S., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Id helix-loop-helix proteins are differentially expressed in gestational trophoblastic disease., Histopathology. 2005, 47(3): 303-9. |
| Researcher : Chiu PM |
| List of Research Outputs |
| Cheung A.N.Y., Chiu P.M., Chan Q.K.Y., Chan Y.K. and Ngan H.Y.S., Expression of Stem cell related genes in normal placentas and Gestational Trophoblastic Diseases, 11th Conference of the European Placenta Group, Glasgow, 2-8th September. 2005. |
| Chiu P.M., Feng H., Benbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model , Journal of Clinical Pathology . 2006, 59(8): 845-50. |
| Chiu P.M., Feng H., Behbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Tissue dynamic effect of all-trans retinoic acid on choriocarcinoma an organotypic model, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M. and Cheung A.N.Y., Differential expression of insulin-like growth factor binding protein 1 and ferritin light polypeptide in gestational trophoblastic neoplasia: combined cDNA suppression subtractive hybridization and microarray study, Cancer. 2005, 104(11): 2409-2416. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Kwan H.S., Shih S.M., Xue W., Chiu P.M., Chan K.W. and Cheung A.N.Y., Differential gene expression identified in complete hydatidiform mole by combining suppression subtractive hybridization and cDNA microarray, Placenta. 2006, 27: 521-526. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate Stem Cell Antigen is a genetic indicator for development of gestational trophoblastic neoplasia, American Association for Cancer Research's 97th Annual Meeting, March 31-April 5, 2006, in Washington DC, USA. 2006. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate stem cell antigen is over-expressed in persistent hydatidiform mole, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Fong P.Y., Xue W., Ngan H.Y.S., Chiu P.M., Chan Y.K., Tsao G.S.W. and Cheung A.N.Y., Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study, Journal of Clinical Pathology. 2006, 59: 179-183. |
| Huang F.Y., Chiu P.M., Tam K.F., Kwok K.Y., Lau E.T., Tang M.H., Ng T.Y., Liu V.W.S., Cheung A.N.Y. and Ngan H.Y.S., Semi-quantitative fluorescent PCR analysis identifies PRKAA1 on chromosome 5 as a potential candidate cancer gene of cervical cancer, Gynecologic Oncology. 2006, 103(1): 219-25. |
| Siu K.Y., Yeung C.W., Chiu P.M., Feng H., Ngan H.Y.S., Xue W. and Cheung A.N.Y., p21-activated kinases (Paks) in gestational trophoblastic disease, XIIIth World Congress on Gestational Trophoblastic Diseases. Proceedings P.103. 2005. |
| Wang Y., Liu V.W.S., Tsang P.C.K., Chiu P.M., Cheung A.N.Y., Khoo U.S., Nagley P. and Ngan H.Y.S., Microsatellite instability in mitochondrial genome of common female cancers, International Journal of Gynecological Cancer. 2006, Suppl 1: 259-266. |
| Xue W., Feng H., Chan Y.K., Chiu P.M., Ngan H.Y.S., Khoo U.S., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Id helix-loop-helix proteins are differentially expressed in gestational trophoblastic disease., Histopathology. 2005, 47(3): 303-9. |
| Researcher : Choi CL |
| List of Research Outputs |
| Choi C.L., Ma E.S.K. and Chan L.C., In vitro characterization of silent beta-thalassemia mutation, +8 C-to-T substitution, The 3rd Asia Hematology Association. Jeju, Korea. August 17-20, 2005. |
| Researcher : Chung LP |
| List of Research Outputs |
| Au W.Y., Ma E.S.K., Choy C., Chung L.P., Fung T.K., Liang R.H.S. and Kwong Y.L., Therapy-related lymphomas in patients with autoimmune diseases after treatment with disease-modifying anti-rheumatic drugs, American Journal of Hematology. 2005, 81(1): 5-11. |
| Lam C.L., Wong M.P., Girard L., Chung L.P., Chiu W.S., Suen W.S., Lam W.K. and Minna J.D., Gene expression profiling in lung adenocarcinomas reveals molecular signatures with respect to gender, smoking, histological grading and disease-free survival. 11th World Conference on Lung Cancer, Lung Cancer. 2005, 49 (Suppl 2): S133 (P-072). |
| Lam D.C.L., Wong M.P., Girard L., Chung L.P., Suen W.S., Lam W.K. and Minna J.D., Gene expression profiling in lung adenocarcinomas reveals molecular signatures correlating with clinical significance, 11th Medical Research Conference, Department of Medicine, The University of Hong Kong. 2006, Abstract Book 090: pp. 56. |
| Tam I.Y.S., Chung L.P., Suen W.S., Wang E., Wong M.C.M., Ho K.K., Lam W.K., Chiu S.W., Girard L., Minna J.D., Gazdar A.F. and Wong M.P., Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features, Clinical Cancer Research. 2006, 12(5): 1647-53. |
| Wong M.P., Chua D.T.T., Ho J.C.M., Tam I.Y.S., Lam W.K. and Chung L.P., Mutational status of epidermal growth factor receptor is the only predictor of clinical response to gefitinib treatment in non-small cell lung cancer, 97th AACR Annual Meeting, Washington, DC, April 1-5, 2006 . 2006. |
| Zhu H., Lam D.C., Han K.C., Tin P.C., Suen W.S., Wang E., Lam W.K., Cai W.W., Chung L.P. and Wong M.P., High resolution analysis of genomic aberrations by metaphase and array comparative genomic hybridization identifies candidate tumour genes in lung cancer cell lines, Cancer Letters. 2006. |
| Researcher : Guo DL |
| List of Research Outputs |
| Aggarwal A., Guo D.L., Hoshida Y., Yuen S.T., Chu K.M., So S., Boussioutas A., Chen X., Bowtell D., Aburatani H., Leung S.Y. and Tan P., Topological and functional discovery in a gene coexpression meta-network of gastric cancer, Cancer Research. 2006, 66(1): 232-41. |
| Guo D.L., Zhang J., Yuen S.T., Tsui W.Y., Chan A.S.Y., Ho C., Chen X. and Leung S.Y., Reduced Expression of EphB2 that parallels invasion and metastasis in colorectal tumors, Keystone Symposia: Stem Cells, Senescence and Cancer, 25-30 October . 2005. |
| Guo D.L., Zhang J., Yuen S.T., Tsui W.Y., Chan A.S.Y., Ho C., Ji J., Leung S.Y. and Chen X., Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumors, Carcinogenesis. 2005, 27(3): 454-464. |
| Researcher : Guo T |
| List of Research Outputs |
| Yip B.H., Guo T., Hu X., Wong K.Y., Chen W.Y.W., Au W.Y., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Yip B.H., Guo T., Hu X., Au W.Y., Wong K.Y., Wan T.S.K., Chen W.Y.W., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) involving immunoglobulin heavy chain gene locus in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006. |
| Researcher : Ho JWY |
| Project Title: | Study on circulating endothelial progenitor cell in hepatocellular carcinoma - potential biomarker of tumor angiogenesis and target for anti-angiogenic therapy |
| Investigator(s): | Ho JWY, Poon RTP, Fan ST |
| Department: | Centre for the Study of Liver Disease |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2004 |
| Completion Date: | 04/2006 |
| Abstract: |
| To assess the levels of circulating endothelial progenitor cells in hepatocellular carcinoma (HCC). |
| List of Research Outputs |
| Researcher : Hu X |
| List of Research Outputs |
| Chen W.Y.W., Hu X., Liang A.C.T., Au W.Y., So J.C.C., Wong M.L.Y., Shen L., Tao Q., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6 deregulating mutations, in gastric lymphoma, Blood. 2006, 108(7): 2373-83. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Wong M.L.Y., Shen L., Wong K.Y., Au W.Y., Cheung W.L., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Au W.Y., Wong M.L.Y., Shen L., Wong K.Y., Wan T.S.K., Cheung W.L., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006 . 2006. |
| Hu X., Leong V.Y.L., Ng I.O.L. and Ching Y.P., Overexpression of PAK4 in hepatocellular carcinoma (HCC), 2006 American Association for Cancer Research (AACR) Annual Meeting, Washington DC., USA, April 2006 . 2006. |
| Yip B.H., Guo T., Hu X., Wong K.Y., Chen W.Y.W., Au W.Y., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Yip B.H., Guo T., Hu X., Au W.Y., Wong K.Y., Wan T.S.K., Chen W.Y.W., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) involving immunoglobulin heavy chain gene locus in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006. |
| Researcher : Huang F |
| Project Title: | The roles of regulatory dendritic cells in peripheral tolerance and autoimmunity |
| Investigator(s): | Huang F, MacPherson G.G. |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 09/2001 |
| Completion Date: | 08/2005 |
| Abstract: |
| To create in vivo models which mimic and auto- or host-reactive environment; to visualise the fate of potential self-reactive T cells in normal and in autoimmune-prone mice; to study the role of DCreg in the generation of Treg cells; to study DC functions in autoimmune models; to generate DCreg and Treg for the treatment of autoimmune diseases. |
| Project Title: | Functional conditioning of dendritic cells for DC-based tumor vaccine |
| Investigator(s): | Huang F, Tian L, Ng IOL |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 01/2003 |
| Abstract: |
| Dendritic cell (DC)-based tumor vaccine is a newly developed therapeutic approach for cancer treatment. It aims to promote specific immunity to cancer cells within tumor bearing individuals. Recent studies reveal that DC are not a homogenous population, and their ability to provide activation signals can vary significantly between different DC subtypes, lineages or maturity. The types and functional conditions, hence the immunogenic 'quality', of the DC employed are understandably essential. This project is to examine critically the roles of co-stimulatory molecules in DC-based tumor vaccines. The main objective is to develop immunologically active and programmable DC-tumor vaccines with high efficacy useful in cancer therapies. |
| Project Title: | Mechanisms for the induction and regulation of autoimmune responses by dendritic cells and T regulatory cells in systemic lupus erythematosus |
| Investigator(s): | Huang F, Wu AYY, Tian L |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 12/2003 |
| Abstract: |
| To study the mechanisms for induction and regulation of autoimmune responses; to study effects of cell death on the induction of anti-nuclear antibody production, in normal and in autoimmune-prone mice; to test the hypothesis that uptake of necrotic or apoptotic dying cells by dendritic cells may differentially regulate autoimmune responses in vivo; to determine the roles, and mechanisms for generation, of the naturally occurring T regulatory cells in autoimmune and non-autoimmune mice. |
| Project Title: | Mechanisms for the induction and regulation of autoimmune responses by dendritic cells and T regulatory cells in systemic lupus erythematosus |
| Investigator(s): | Huang F, Wu AYY, Tian L |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 12/2003 |
| Abstract: |
| N/A |
| Project Title: | Molecular characterization of dendritic cells functionally modulated by dying cells - mechanism for the induction and regulation of autoimmune responses by dendritic cells (II) |
| Investigator(s): | Huang F |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 01/2005 |
| Abstract: |
| N/A |
| Project Title: | Molecular characterization of dendritic cells functionally modulated by dying cells - mechanism for the induction and regulation of autoimmune responses by dendritic cells (II) |
| Investigator(s): | Huang F, Leung SY, Wu AYY, Tian L |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 01/2005 |
| Abstract: |
| To study the molecular mechanisms for the induction of autoimmune responses by DCs; to study the immune response profiles of DCs after uptake of dying cells; to determine how DC functional properties can be differentially modulated following uptake of apoptotic and necrotic dying cells; to determine the therapeutic potential of functionally conditioned DC for a possible long-term rectification of the autoimmune disorder. |
| List of Research Outputs |
| Chiang A.K.S., Wong O.H. and Huang F., Functional Comparison of Cord and Adult Blood-Derived Dendritic Cells, Journal of Pediatric Haematology Oncology (Abstract published in the conference proceedings for 1st Annual Fall Conference, Vancouver, Canada, 19-22 September 2005. 27(9): 463. |
| Chiang A.K.S., Wong O.H. and Huang F., Update on non-Hodgkin lymphomas, The Hong Kong Society of Haematology Monthly Scientific Meeting, Hong Kong, 15 August 2005. |
| Huang F., DC, Cell Death & Lupus Pathogenesis, The Hong Kong Society For Immunology Annual Scientific Meeting, Hong Kong, April 29. 2006. |
| Huang F., Differential Induction & Regulation Of Autoimmune Responses By Dendritic Cells Upon Interactions with Dying Cells., The Second Asia Autoimmunity Forum, Hong Kong, March 3-5, 2006.. 2006. |
| Ma L., Chan K.W., Trendell-Smith N.J., Wu A.Y.Y., Tian L., Lam A.C., Lo C.K., Chik S.C.C., Ko K.H., To K.W., Kam C.S.K., Li X., Yang C., Leung S.Y., Ng M.H. and Huang F., Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains, In: Ma L, Chan KW, Trendell-Smith NJ, Wu A, Tian L, Lam AC, Chan AK, Lo CK, Chik S, Ko KH, To CK, Kam SK, Li XS, Yang CH, Leung SY, Ng MH, Stott DI, MacPherson GG, Huang FP, European Journal of Immunology (In This Issue highlight, Editorial Comments). 2005, 35(11): 3364-75. |
| To K.W., Wong O.H., Li H.B., Chan S.F., Ma L., Cheung Y.L., Ko K.H., Chiang A.K.S. and Huang F., The effects of Bergapten in modulating dendritic cells (DC) functions for DC-based tumor vaccines, 10th Research Postgraduate Symposium, Hong Kong. December 3. 2005. |
| Wong O.H., Huang F. and Chiang A.K.S., Differential responses of cord and adult blood-derived dendritic cells to dying cells, Immunology (Cover Story). 2005, 116: 13-20. |
| Zheng B., Lee S.S., Wong K.H., Chan K.C.W., Chan C.S., Ng F., Huang F. and Yuen K.Y., Development of New Technique for Detection of HIV Specific Cytotoxic T Lymphocytes, Keystone Symposia HIV Vaccines (×6). 27 March-2 April. 2006. |
| Researcher : Ip PPC |
| List of Research Outputs |
| Ip P.P.C., Chan K.K.L., Cheung A.N.Y. and Ngan H.Y.S., Choriocarcinomas following full-term non-molar gestations, XIIIth World Congress on Gestational Trophoblastic Diseases, The International Society for the Study of Trophoblastic Diseases and The University of Hong Kong, 23-26 October, 2005. |
| Ip P.P.C. and Cheung A.N.Y., The Pathologist’s role in Gynaecological Oncology, A Management Guideline for Gynaecological Oncology. The University of Hong Kong, 2006, 20-28. |
| Yeung M., Pun T.C., Chan K., Ngan H.Y.S., Ip P.P.C. and Cheung A.N.Y., Negative pregnancy test and trophoblastic lesions: from ectopic abortion to choriocarcinoma, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Researcher : Jones BM |
| List of Research Outputs |
| Ho M.H.K., Chan G.C.F., Jones B.M., Lee T.L., Chiang A.K.S., Ha S.Y. and Lau Y.L., Juvenile Pernicious Anaemia in Association with Vitiligo, Selective IgA Deficiency, Defective Interleukin 12 Production and T Cell Dysfunction, Hong Kong Journal of Paediatrics (new series). 2006, 11: 59-63. |
| Hon C., Chui W.H., Cheng L.C., Shek T.W.H., Jones B.M. and Au W.Y., Thymoma associated with keratoconjunctivitis, lichen planus, hypogammaglobinemia, and absent circulating B cells, Journal of Clinical Oncology. 2006, 24(18): 2960-1. |
| Kwok J.S.Y., Hui K.H., Lee T.L., Wong W.H.S., Lau Y.L., Wong W.S., Kim D.L. and Jones B.M., Anti-cyclic citrullinated peptide: diagnostic and prognostic values in juvenile idiopathic arthritis and rheumatoid arthritis in a Chinese population, Scandinavian Journal of Rheumatology. 2005, 34(5): 359-366. |
| Researcher : Khoo US |
| Project Title: | Association of the pro-inflammatory and anti-inflammatory cytokine gene polymorphism to breast cancer susceptibility |
| Investigator(s): | Khoo US, Cheung ANY, Chan YK, Yip SP |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2003 |
| Abstract: |
| To determine whether the genetic variants of the pro-inflammatory and anti-inflammatory cytokines may (a) contribute towards breast cancer susceptibility or (b) influence prognosis; to investigate whether the joint effects of several of these alleles and/or in combination of specific environmental factors may contribute towards a stronger association. |
| Project Title: | Promoter polymorphisms of BRCA1: genetic association and functional study |
| Investigator(s): | Khoo US, Chan YK, Cheung ANY |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2004 |
| Abstract: |
| To perform a case-control study to investigate the promoter polymorphisms BRCA1 gene for risk association to breast cancer; to test by Luciferase report assay whether these promoter SNPs result in functional alteration of the BRCA1 gene. |
| Project Title: | Role of Polymorphisms of the Inflammatory Response Genes and DC-SIGNR in Genetic Susceptibility to SARS and other infections. |
| Investigator(s): | Khoo US, Altmeyer RM, Chu CM, Lai ST, Lin CL, Peiris JSM, Tam PKH, Wong ATY, Yam L, Yip SP |
| Department: | Pathology |
| Source(s) of Funding: | Research Fund for the Control of Infectious Diseases - Full Grants |
| Start Date: | 12/2004 |
| Abstract: |
| To determine whether (i) SNPs of the inflammatory response genes may contribute in determining susceptibilty, response to treatment and clinical outcome of SARS.(ii) Heterozygous genotypes of DC-SIGNR may influence binding affinity for viral glycopeptides, namely S1 of SARS, E2 of HCV and gp120 of HIV. |
| Project Title: | Infectious Diseases and Global Health: Genetic approach to the identification of host susceptibility factors and pathogen virulence determinants. Genetics of coronaviruses-associated acute respiratory disease |
| Investigator(s): | Khoo US |
| Department: | Pathology |
| Source(s) of Funding: | CGDN NCE Large Scale Collaborative Research Grant |
| Start Date: | 02/2005 |
| Abstract: |
| To study association of SARS-susceptibility with MHC and KIR; to carry out genetic and functional analysis of coronavirus-associated respiratory disease. |
| Project Title: | The role of L-SIGN (CD290L) in SARS coronavirus infection |
| Investigator(s): | Khoo US |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 07/2005 |
| Abstract: |
| N/A |
| Project Title: | The role of L-SIGN (CD290L) in SARS coronavirus infection |
| Investigator(s): | Khoo US, Screaton GR, Xu X, Lin CL |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 07/2005 |
| Abstract: |
| Previously we have been able to show that L_SIGN polymorphism determines the susceptibility for SARS infection. We are also to show that L-SIGN is expressed in alveolar epithelium of the healthy lung tissues, with or without co-expression of ACE2. Furthermore, L-SIGN is also expressed in the ACE2(+) alveolar epithelium of the lung of fatal SARS patients, strongly suggesting the L-SIGN may be involved in SARS pathogenesis. It has also been shown that ACE2 has been found to be expressed in the lung and small bowel enterocytes of normal individuals. In this study we intend to address specific question as below: (1) is LSIGN also expressed in the small bowel of normal individuals and SARS infected patients? (2) What is the specific role of L-SIGN in the binding and replication of SARS CoV in the setting of primary respiratory exposure/infection? - does it facilitate SARS CoV infection of permissive cells in trans or in cis, or both? (3) What is the difference in binding affinity between homozygous and heterozygous L-SIGN expression in vitro and in vivo? And how does this different account for the difference in SARS susceptibility? (4) From dbSNP (http://www.ncbi.nlm.nih.gov/SNP/), there is 12 ACE2 single nucleoride polymorphisms (SNPs) located in the coding exons, introns and promoter regions, of which four SNPs has been found with a minor allele frequency greater than 5% in our population and thus were suitable for further analysis. So we also would like to know if ACE2 SNPs is associated with different susceptibility for SARS infection. |
| Project Title: | The functional role of ICAM3 polymorphism in genetic susceptibility to SARS infection |
| Investigator(s): | Khoo US, Chan YK, Leung GM, Lin CL, Lim WWL, Peiris JSM, Sham PC, Tam PKH, Yip SP, Garcia-Barcelo MM |
| Department: | Pathology |
| Source(s) of Funding: | Research Fund for the Control of Infectious Diseases - Full Grants |
| Start Date: | 01/2006 |
| Abstract: |
| To confirm our genetic association findings by a large case-control study and a family-based association study with family members as controls; to perform functional studies to investigate the role of ICAM3 polymorphisms in influencing the initiation of immune response to SARS-CoV infection. |
| Project Title: | Gene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility |
| Investigator(s): | Khoo US, Chan YK, Cheung ANY, Garcia-Barcelo MM, Leung GM, Sham PC, Wong MY, Zheng W |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 01/2006 |
| Abstract: |
| To identify all possible risk-conferring variations within these genes by direct sequencing of the promoter region, all exons and rrelevant exon-intron junctions on 90 unrelated individuals; to examine the pattern of linkage disequilibrium (LD) between SNPs on the genes, and hence haptotype tagging SNPs (htSNP) for risk association study; to assess the combined effect of these ER-α and ER-α htSNPs on risk of breast cancer in a large Chinese case-control population of at least 2,000 case-control pairs. |
| Project Title: | Gene-based and haplotype analysis of the estrogen receptor genes for breast cancer susceptibility |
| Investigator(s): | Khoo US |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 01/2006 |
| Abstract: |
| N/A |
| Project Title: | Promoter polymorphisms of L-SIGN in relation to host genetic susceptibility to SARS. |
| Investigator(s): | Khoo US, Chan YK |
| Department: | Pathology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 02/2006 |
| Abstract: |
| Objective of study : 1. To identify the possible variants in the promoter region of L-SIGN by direct sequencing of 30 unrelated normal Chinese individuals. 2. To examine the pattern of linkage disequilibrium (LD) between all the variants identified, and hence select haptotype tagging single nucleotide polymorphism (htSNP) for risk association study. 3. To analyze these htSNPs for genetic association to SARS CoV using a large case-control study. 4. To examine for possible LD between the htSNPs and the tandem-neck repeats polymorphisms of L-SIGN previously genotyped. 5. To perform in-vitro functional studies to confirm the effect of L-SIGN promoter SNPs on the transcriptional activity of the promoter. Key issues and problems being addressed: L-SIGN or DC-SIGNR (CD209L) is a homologue of DC-SIGN (for dendritic cell-specific ICAM-3 grabbing non-integrin, CD209) and shares 77% amino acid identity with it (1). Located within 30 kb on chromosome 19p13.2-3 in a head-to-head orientation, they are thought to have arisen through a gene duplication event (2;3). The extra-cellular domain of both DC-SIGN and L-SIGN encoded by exon 4, contain tandem repeats of a highly conserved 23-amino acid sequence, followed by a C-terminal C-type carbohydrate recognition domain (CRD)(4-6). Both L-SIGN and DC-SIGN share the ability to bind to high-mannose oligosaccharides through their CRDs and serve as receptors for many viruses such as HIV, HCV and SARS Co-V. Unlike DC-SIGN, L-SIGN has considerable polymorphism in this tandem-repeat domain which encodes the extra-cellular neck region (2). This tandem-repeat segment of 3 to 9 repeats, 7 being predominant (>50%) in the general population. Homo-oligomerization through this tandem-repeat neck region is what determines its high-affinity interaction as well as ligand specificity (7). L-SIGN has been demonstrated to be a binding receptor for SARS Co-V (8). We have recently shown in a genetic association study, that individuals homozygous for L-SIGN tandem repeats are less susceptible to SARS infection, and in a series of in-vitro experiments, that L-SIGN with homozygous tandem-neck repeats had higher binding capacity for SARS-CoV, lower ability for trans infection and increased cell-association for SARS-CoV, thus playing a protective role in SARS infection (Chan et al, Nature Genetics, in press, 9). Promoter polymorphisms can cause altered binding affinity of transcription factors which may effect regulation of gene expression (10). This can give rise to differences in susceptibility to and severity of disease. A promoter polymorphism of DC-SIGN was shown to be associated with risk for parenteral acquisition of HIV-1 infection (11). This same variant was recently reported to be associated with severity of dengue disease and in-vitro study showed that it affects an Sp1-like binding site and transcriptional activity (12). We hypothesize that promoter polymorphisms may also effect the expression of L-SIGN or its association with disease. Having already shown the importance of L-SIGN as a binding receptor for SARS Co-V, and the effect of tandem-neck repeats genotype in susceptibility to SARS infection (9), it would be important to investigate whether promoter polymorphisms of L-SIGN may affect the expression of L-SIGN and thus also contribute towards disease susceptibility and/or severity for SARS. To exclude the possibility that the association with disease may be due to LD between the promoter polymorphism and the functional tandem-neck repeat homo-/heterozygosity, linkage disequilibrium (LD) between these promoter polymorphisms with tandem-neck repeat L-SIGN polymorphisms previously investigated will also be examined. Finally, in-vitro functional studies will be performed to confirm the effect of L-SIGN promoter SNPs on the promoter activity. References: 1. Soilleux EJ, Barten R, Trowsdale J. DC-SIGN; a related gene, DC-SIGNR; and CD23 form a cluster on 19p13. J Immunol 2000 September 15;165(6):2937-42. 2. Bashirova AA, et al. A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. J Exp Med 2001 March 19;193(6):671-8. 3. Pohlmann S, et al. DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and simian immunodeficiency viruses and activates infection in trans. Proc Natl Acad Sci U S A 2001 February 27;98(5):2670-5. 4. Feinberg H, Mitchell DA, Drickamer K, Weis WI. Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. Science 2001 December 7;294(5549):2163-6. 5. Guo Y, et al. Structural basis for distinct ligand-binding and targeting properties of the receptors DC-SIGN and DC-SIGNR. Nat Struct Mol Biol 2004 July;11(7):591-8. 6. Mitchell DA, Fadden AJ, Drickamer K. A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands. J Biol Chem 2001 August 3;276(31):28939-45. 7. Snyder GA, Colonna M, Sun PD. The structure of DC-SIGNR with a portion of its repeat domain lends insights to modeling of the receptor tetramer. J Mol Biol 2005 April 15;347(5):979-89. 8. Jeffers SA, Tusell SM, Gillim-Ross L, Hemmila EM, Achenbach JE, Babcock GJ et al. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc Natl Acad Sci U S A 2004 November 2;101(44):15748-53. 9. VSF Chan, KYK Chan, YX Chen, ….US Khoo* & CL Lin* Homozygous L-SIGN (CD209L) plays a protective role in SARS coronavirus infection. Nature Genetics (in press) (*co-corresponding authors) 10. Theuns J, et al. (2003) Alzheimer-associated C allele of the promoter polymorphism -22C>T causes a critical neuron-specific decrease of presenilin 1 expression. Hum Mol Genet. 12(8), 869-877. 11. Martin MP, et al. Association of DC-SIGN promoter polymorphism with increased risk for parenteral, but not mucosal, acquisition of human immunodeficiency virus type 1 infection. J Virol. 2004; 78(24):14053-6. 12. Sakuntabhai A, et al. (2005) A variant in the CD209 promoter is associated with severity of dengue disease. Nat Genet. 37(5), 507-513. 13. Lewontin RC. The interaction of selection and linkage. II. Optimum Models. Genetics. 1964;50:757-82. 14. Wei Liu,….Khoo US, et al. The functional -969C/T promoter polymorphism in BRCA1 decreases breast cancer risk in Chinese. (Submitted to JNCI) |
| Project Title: | Promoter polymorphisms of DC-SIGN in relation to host genetic susceptibility to SARS infection. |
| Investigator(s): | Khoo US, Chan YK, Leung GM, Lin CL, Lim WWL, Peiris JSM, Sham PC, Tam PKH, Yip SP, Cheung ANY |
| Department: | Pathology |
| Source(s) of Funding: | Research Fund for the Control of Infectious Diseases - Full Grants |
| Start Date: | 06/2006 |
| Abstract: |
| I. To analyze the promoter SNPs of DC-SIGN for genetic association to SARS CoV using a large case-control study and a family-based association study II. To perform in-vitro functional studies to confirm the effect of DC-SIGN promoter SNPs on promoter activity and its influence on DC-SIGN mediated transmission of SARS CoV to target cells. |
| List of Research Outputs |
| Chan V.S.F., Chan Y.K., Chen Y., Poon L.L.M., Cheung A.N.Y., Zheng B., Chan K.H., Mak W.W., Ngan H.Y.S., Xu X., Screaton G., Tam P.K.H., Austyn J.M., Chan L.C., Yip S.P., Peiris J.S.M., Khoo U.S. and Lin C.L., Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection. , Nature Genetics. 2006, 38: 38-46. |
| Chiu P.M., Feng H., Benbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model , Journal of Clinical Pathology . 2006, 59(8): 845-50. |
| Chiu P.M., Feng H., Behbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Tissue dynamic effect of all-trans retinoic acid on choriocarcinoma an organotypic model, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Khoo U.S., Fine Needle Aspiration Cytology Of The Breast: Diagnostic Issues And Controversies, 4th Asian Pacific International Academy Of Pathology. 2005. |
| Khoo U.S., Fine Needle Aspiration Cytology of the Breast: Diagnostic Issues and Controversies, Proceedings of the 4th Asian Pacific International Academy of Pathology, Beijing. Beijing, 2005. |
| Khoo U.S., Genetic Susceptibility To Diseases:application Of SNPs Analysis, 4th Asian Pacific International Academy Of Pathology Meeting. 2005. |
| Khoo U.S., Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection, Proceedings of the Croucher Foundation Advanced Study Institute on Statistical Genetics, Hong Kong. 2006. |
| Khoo U.S., Host-genetic factors in SARS , In: Chan JCK & Tam Wong VCW, Challenges of Severe Acute Respiratory Syndrome. Singapore, Elsevier, 2006, (in press). |
| Khoo U.S., Susceptitbility to diseases: Application of SNPs analysis, Proceedings of the 4th Asian Pacific International Academy of Pathology, Beijing. Beijing, 2005. |
| Khoo U.S., Chan V.S.F., Chan Y.K., Chen Y., Poon L.L.M., Cheung A.N.Y., Zheng B., Ngan H.Y.S., Tam P.K.H., Chan L.C., Yip S.P., Peiris J.S.M., Sham P.C. and Lin C.L., The protective role of homozygous L-SIGN (CLEC4M) in SARS coronavirus infection., HUGO's 11th Human Genome Meeting, Helsinki, Finland. . 2006. |
| Sy A.N., Lam T.P. and Khoo U.S., Subcutaneous panniculitislike T-cell lymphoma appearing as a breast mass: a difficult and chanllenging case appearing at an unusual site, Journal Ultrasound Medicine. 2005, 24(10): 1453-1460. |
| Tse Y.T., Chan Y.K., Chan S.Y., Tsang S.T.Y., Sham P.C. and Khoo U.S., Estrogen Receptor a Gene Polymorphisms and Breast Cancer Risk in Chinese, HUGO's 11th Human Genome Meeting, Helsinki, Finland. . 2006. |
| Wang Y., Liu V.W.S., Tsang P.C.K., Chiu P.M., Cheung A.N.Y., Khoo U.S., Nagley P. and Ngan H.Y.S., Microsatellite instability in mitochondrial genome of common female cancers, International Journal of Gynecological Cancer. 2006, Suppl 1: 259-266. |
| Xu M.S., Chan Y.K., Peiris J.S.M., Yip S.P., Cheung A.N.Y. and Khoo U.S., A variant in the CD209 promoter is associated with severity of Severe Acute Respiratory Syndrome (SARS), HUGO's 11th Human Genome Meeting, Helsinki, Finland. 2006. |
| Xue W., Feng H., Chan Y.K., Chiu P.M., Ngan H.Y.S., Khoo U.S., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Id helix-loop-helix proteins are differentially expressed in gestational trophoblastic disease., Histopathology. 2005, 47(3): 303-9. |
| Researcher : Ko CF |
| List of Research Outputs |
| Ko C.F., Yam J.W.P., Chan P.C.Y., Jin D. and Ng I.O.L., Interaction of deleted in liver cancer 1 (DLC1) with tensin2 and its implications in tumor suppression, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
| Researcher : Ko KH |
| List of Research Outputs |
| Ma L., Chan K.W., Trendell-Smith N.J., Wu A.Y.Y., Tian L., Lam A.C., Lo C.K., Chik S.C.C., Ko K.H., To K.W., Kam C.S.K., Li X., Yang C., Leung S.Y., Ng M.H. and Huang F., Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains, In: Ma L, Chan KW, Trendell-Smith NJ, Wu A, Tian L, Lam AC, Chan AK, Lo CK, Chik S, Ko KH, To CK, Kam SK, Li XS, Yang CH, Leung SY, Ng MH, Stott DI, MacPherson GG, Huang FP, European Journal of Immunology (In This Issue highlight, Editorial Comments). 2005, 35(11): 3364-75. |
| To K.W., Wong O.H., Li H.B., Chan S.F., Ma L., Cheung Y.L., Ko K.H., Chiang A.K.S. and Huang F., The effects of Bergapten in modulating dendritic cells (DC) functions for DC-based tumor vaccines, 10th Research Postgraduate Symposium, Hong Kong. December 3. 2005. |
| Zhang M., Ko K.H. and Lu L., BAFF enhances the development of autoantibody-producing plasma cells in collagen-induced arthritis mice, Annual Meeting of American Association of Immunologists, Boston, USA, May 12. 2006. |
| Zhang M., Ko K.H., Lam Q.L.K., Srivastava G., Zheng B., Lau Y.L. and Lu L., Expression and function of TNF family member B cell-activating factor in the development of autoimmune arthritis, International Immunology. 2005, 17(8): 1081-1092. |
| Researcher : Kong CT |
| List of Research Outputs |
| Kong C.T., Sham M.H. and Chan L.C., The MLL-EEN fusion gene leads to maturation arrest and self-renewal of hematopoietic progenitors in ES cells and the development of myeloid leukemia in chimeric mice, FASEB Summer Research Conferences - Hematological Malignancies, Saxtons River, USA. July 30 - August 4, 2005 . 2005. |
| Kong C.T., Sham M.H., So C.W.E., Cheah K.S.E., Chen S.J. and Chan L.C., The Mll-Een knockin fusion gene enhances proliferation of myeloid progenitors derived from mouse embryonic stem cells and causes myeloid leukaemia in chimeric mice, Leukemia. 2006, 20: 1829–1839. |
| Researcher : Kwok JSY |
| List of Research Outputs |
| Kwok J.S.Y., Hui K.H., Lee T.L., Wong W.H.S., Lau Y.L., Wong W.S., Kim D.L. and Jones B.M., Anti-cyclic citrullinated peptide: diagnostic and prognostic values in juvenile idiopathic arthritis and rheumatoid arthritis in a Chinese population, Scandinavian Journal of Rheumatology. 2005, 34(5): 359-366. |
| Ma E.S.K., Li Y.H., Kwok J.S.Y., Ling S.C., Yau P.W. and Chan G.C.F., ADAMTS13 Mutational Analysis in Chinese Patients with Chronic Relapsing Thrombotic Thrombocytopenic Purpura, Hong Kong Journal of Paediatrics (new series). 2006, 11: 22-27. |
| Researcher : Lam AC |
| List of Research Outputs |
| Ma L., Chan K.W., Trendell-Smith N.J., Wu A.Y.Y., Tian L., Lam A.C., Lo C.K., Chik S.C.C., Ko K.H., To K.W., Kam C.S.K., Li X., Yang C., Leung S.Y., Ng M.H. and Huang F., Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains, In: Ma L, Chan KW, Trendell-Smith NJ, Wu A, Tian L, Lam AC, Chan AK, Lo CK, Chik S, Ko KH, To CK, Kam SK, Li XS, Yang CH, Leung SY, Ng MH, Stott DI, MacPherson GG, Huang FP, European Journal of Immunology (In This Issue highlight, Editorial Comments). 2005, 35(11): 3364-75. |
| Researcher : Lam AKY |
| List of Research Outputs |
| Chan K.W., Lee P.Y., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Clinical relevance of Fas expression in oesophageal squamous cell carcinoma, Journal of Clinical Pathology . 2006, 59(1): 101-4. |
| Chan K.W., Lee P.Y., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Fas expression is a favorable prognostic factor in esophageal squamous cell carcinoma, The Fourth Asia-Pacific International Academy of Pathology Congress (IAP2005), 22-26 August 2005, Beijing, China. 2005. |
| Tang W.K., Fatima S., Chui C.H., Ou T.M., Hui K.S., Wong M.M., Wong J., Law S.Y.K., Tsao G.S.W., Lam A.K.Y., Beh S.L., Srivastava G., Ho K.P. and Tang J.C.O., Oncogenic properties of a novel gene located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma, Proceedings of the 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress of Biochemistry and Molecular Biology, Kyoto, Japan, June 18-23, 2006. |
| Wong M.L.Y., Tao Q., Fu L., Wong K.Y., Qiu G.H., Law F.B.F., Tin P.C., Cheung W.L., Lee P.Y., Tang J.C.O., Tsao G.S.W., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma, International Journal of Oncology. 2006, 28(3): 767-73. |
| Researcher : Lam CCK |
| List of Research Outputs |
| Au W.Y., Lam C.C.K., Chim J.C.S., Pang A.W.K. and Kwong Y.L., Alemtuzumab induced complete remission of therapy-resistant pure red cell aplasia , Leukemia Research . 2005, 29, Issue 10: 1213-1215. |
| Au W.Y., Lam C.C.K., Liu C.L. and Yuen R.M.F., Hepatitis C virus infection in adult Chinese hemophilia patients negative for the human immunodeficiency virus: treatment results with interferon and ribavirin, International Journal of Hematology. 2005, 82(3): 259-261. |
| Au W.Y., Liu C.L., Lo C.M., Fan S.T. and Lam C.C.K., Living donor liver transplantation for hepatitis C related hepatocellular carcinoma in a haemophilia A patient (Case Report), Haemophilia. 2005, 11(4): 405-407. |
| Chan V.N.Y., Ha S.Y., Au P., Lam C.C.K. and Chan T.K., A Chinese Family With Hemophilia B Leyden Due To T-->A Transition At Position +6 Of The FIX Gene, American Journal of Hematology. 2006, 81(4): 300-301. |
| Persquera-Lepatan L.M., Chan G.C.F., Lam C.C.K., Ho M.H.K., Lee T.L., Chiang A.K.S., Ha S.Y. and Lau Y.L., Cerebral Infarction in Childhood Acute Lymphoblastic Leukaemia Treated with Low Dose E. coli Asparaginase, Hong Kong Journal of Paediatrics (new series). 2006, 11: 69-72. |
| Tang S.F., Chan K.H., Cheng V.C.C., Woo P.C.Y., Lau S.K.P., Lam C.C.K., Chan T.L., Wu A.K.L., Hung I.F.N., Leung S.Y. and Yuen K.Y., Comparative host gene transcription by microarray analysis early after infection of Huh7 cell line by SARS coronavirus and human coronavirus 229E., Journal of Virology. 2005, 79: 6180-6193. |
| Researcher : Lam QLK |
| List of Research Outputs |
| Qu X., Yang M.X., Kong B.H., Qi L., Lam Q.L.K., Yan S., Li P., Zhang M. and Lu L., Hypoxia inhibits the migratory capacity of human monocyte-derived dendritic cells, Immunology and Cell Biology . 2005, 83(6): 668-73. |
| Zhang M., Ko K.H., Lam Q.L.K., Srivastava G., Zheng B., Lau Y.L. and Lu L., Expression and function of TNF family member B cell-activating factor in the development of autoimmune arthritis, International Immunology. 2005, 17(8): 1081-1092. |
| Researcher : Law FBF |
| List of Research Outputs |
| Wong M.L.Y., Tao Q., Fu L., Wong K.Y., Qiu G.H., Law F.B.F., Tin P.C., Cheung W.L., Lee P.Y., Tang J.C.O., Tsao G.S.W., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma, International Journal of Oncology. 2006, 28(3): 767-73. |
| Researcher : Lee JSK |
| List of Research Outputs |
| Ip P., Wong V.C.N., Ho M.H.K., Lee J.S.K. and Wong W.H.S., Environmental mercury exposure in children - South China's experience, DK 50th Anniversary Symposium on Paediatric Neurology and Neuro-rehabilitation (Hong Kong, 16-17 September, 2005). 2005. |
| Ip P., Wong V.C.N., Ho M.H.K., Lee J.S.K. and Wong W.H.S., Mercury Exposure in Children with Autistic Spectrum Disorder: A case-control study, DK 50th Anniversary Symposium on Paediatric Neurology and Neuro-rehabilitation (Hong Kong, 16-17 September, 2005). 2005. |
| Researcher : Lee KW |
| Project Title: | Identification of novel plasma RNA biomarkers of nasopharyngeal carcinoma for early detection of cancer |
| Investigator(s): | Lee KW, Yuen PW, Poon Tung Ping Ronnie |
| Department: | Surgery |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 09/2005 |
| Completion Date: | 08/2006 |
| Abstract: |
| Nasopharyngeal carcinoma (NPC) occurs sporadically in the west but is endemic in southern China (25 times higher than that in the western countries) with incidence rates of between 15 and 50 per 100,000 population (Ho, Int.J.Radiat.Oncol.Biol.Phys., 1978; 4:183-205). The median survival is less than 9 months for NPC patients presenting with distant metastasis (Teo et al., Cancer, 1991;67:434-439). More than half of patients are diagnosed late due to the absence of alarming early symptoms (Chan et al., Cancer, 1998; 82: 1003-1012). The diagnosis of NPC is often difficult because of the nonspecific nature of the clinical symptoms and difficulty in visualizing the nasopharynx. Obviously, there is an urgent need to develop a more sensitive and specific diagnostic method for early detection of NPC. Advances in molecular technology have provided us with many new tools for detecting small quantity of tumor-derived nucleic acid in the blood. The presence of DNA and RNA in plasma of cancer patients has been recognized since 1970s (Leon et al., Cancer Res.,1997; 37:646-650; Shapiro , et al., Cancer, 1983;51:2116-2120), but it was not until 1989 that neoplastic characteristics of plasma DNA in cancer patients were recognized. Five years later, Sorenson et al. (Sorenson et al., Cancer Epidemiol. Biomarkers Pre., 1997;3:67-71) reported the detection of tumor-derived oncogene mutation (k-ras) in pancreatic cancer, and Vasioukhin et al. (Vasioukhin et al., Br. J. Haematol., 1994; 86:774-779) reported N-ras mutations in myelodysplastic syndrome. These striking results provide an insight for the search of tumor marker in this non-invasive diagnostic approach. In tumor associated with viral infection, viral DNA has also been detected in plasma and serum (Yu et al., Clin. Cancer Res, 2004;10:1726-1732). Similar to the development of the circulating DNA field, the earliest efforts in the detection of circulating RNA focused on the detection of tumor-derived RNA in the plasma and serum of cancer patients. In 1999, two groups simultaneously achieved this goal by detection of tumor-derived RNA in patients with NPC and melanoma (Kopreski, Clin. Cancer Res., 1999; 5:1961-1965). One of the biggest surprises in the field of circulating RNA is that such RNA species are detectable at all in plasma or serum, considering the well-known instability of RNA. One may postulate that circulating RNA is probably protected from degradation through its association with apoptotic bodies (Lo et al, Ann.N.Y.Acad.Sci., 2004;1022:135-139). A number of RNA targets have been detected in the plasma and serum of cancer patients, including, RNA species associated with the various telomerase components and, CK19 and b-catenin gene (Silva et al., Clin. Cancer Res., 2001;7: 2821-2825; Wong et al., Clin. Cancer Res., 2004:10: 1613-1617). The stability of RNA in patients’ plasma has been confirmed by our lab. With modified RNA extraction protocol, we successfully amplified genes such as 18S and CK14. Diagnostically, the stability of circulating RNA has greatly enhanced its practicality as a molecular marker. Interestingly, patients suffering from NPC have increased levels of plasma RNA, when compared with healthy individuals. Therefore, we hypothesized that alterations of genes in patients’ plasma can be detected by cDNA microarray. cDNA microarray is a useful tool for studying genetic alterations in various cancers. However, gene expression profiling for NPC patients has not been reported due to absence of normal epithelial tissue as control. Based on the observation that increased levels of plasma RNA in NPC patients, array-based approach would be feasible for identification of novel biomarker in patients’ plasma for NPC. This part of project is designed to compare the genetic alterations in NPC patients’ blood plasma and normal healthy subjects by cDNA microarray. The main objective of this study is to identify novel tumor markers in clinical samples for early detection of NPC. |
| List of Research Outputs |
| Researcher : Leong VYL |
| List of Research Outputs |
| Hu X., Leong V.Y.L., Ng I.O.L. and Ching Y.P., Overexpression of PAK4 in hepatocellular carcinoma (HCC), 2006 American Association for Cancer Research (AACR) Annual Meeting, Washington DC., USA, April 2006 . 2006. |
| Researcher : Leung HY |
| List of Research Outputs |
| Leung H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity, Proc Natl Acad Sci U S A. 2005, 102: 15207-15212. |
| Researcher : Leung SY |
| Project Title: | Identification of BRAF mutation in various stages of colorectal carcinogenesis and its relationship with KRAS mutation |
| Investigator(s): | Leung SY, Yuen ST |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2002 |
| Abstract: |
| To examine the biological relationship of BRAF mutation with KRAS mutation. The association of mutations in these two genes with clinico-pathological features, molecular parameters and prognosis will be sought. |
| Project Title: | High resolution mapping of chromosomal aberrations by cDNA microarray-based comparative genomic hybridisation and their correlation with gene expression profile of gastric adenocarcinoma |
| Investigator(s): | Leung SY, Yuen ST, Chu KM, Lin MC, Chen X., So S. |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 11/2002 |
| Abstract: |
| The project attempts to achieve a high resolution mapping of the chromosomal gains and losses in primary gastric cancer samples by hybridisation of genomic DNA to a microarray containing 44,000 human cDNA clones. The changes of DNA copy number will then be correlated with gene expression profiles already available in the gastric cancer samples, generated using the same cDNA microarray. New oncogenes or tumour suppressor genes may be identified in these regions that may constitute new targets for diagnosis, prognostication and pathway specific therapeutic strategy. |
| Project Title: | Delineation of prognostic biomarkers in gastric cancer using cDNA microarray data, validation in independent dataset and their functional characterisation |
| Investigator(s): | Leung SY, Yuen ST, Chu KM, Kung H, Lin MC, Chen X., So S. |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 11/2003 |
| Abstract: |
| To identify a list of genes that significantly predict tumour behaviour and patient outcome in a cohort of 90 gastric adenocarcinoma patients studied by cDNA microarray; to validate the prognostic significance of the top 50 survival genes in a large independent cohort of gastric adenocarcinoma patients using a combination of real-time quantitative RT-PCR, in-situ hybridisation and immunohistochemistry performed in high-density tissue microarray; to carry out functional characterisation of the survival genes using various cell culture and animal models. |
| Project Title: | Detail study of relationship of BRAF and KRAS mutation with microstatellite instability in colorectal cancer |
| Investigator(s): | Leung SY, Yuen ST |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2003 |
| Abstract: |
| To examine in detail the incidence of BRAF and KRAS mutation in a large series of MSI colorectal cancer with detail characterization of germine MMR gene mutation and MLH1 promoter methylation. |
| Project Title: | Delineation of prognostic biomarkers in gastric cancer using cDNA microarray data, validation in independent dataset and their functional characterisation |
| Investigator(s): | Leung SY, Yuen ST, Chu KM, Kung H, Lin MC, Chen X., So S. |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 11/2003 |
| Abstract: |
| N/A |
| Project Title: | Genomic screening for potential tumour suppressors silenced by promoter hypermethylation in gastric adenocarcinomas using cDNA microarray |
| Investigator(s): | Leung SY, Yuen ST, Chu KM, Fung TWK, Lin MC, Chen X |
| Department: | Pathology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 01/2005 |
| Abstract: |
| Gastric cancer, being the second most common cancer worldwide, continues to present with poor prognosis and obscure cause. In view of the relatively high regional incidence in Hong Kong and certain parts of China, our group has initiated an extensive study in gastric cancer using genomics approach in order to build a solid foundation for on-going research. In collaboration with Stanford University (California, U.S.A.), we have reported the gene expression profiles of 126 gastric adenocarcinomatous and non-neoplastic mucosal samples using a cDNA microarray that contains more than 30,000 unique genes. Noted from the expression profiles were around one thousand genes that were significantly down-regulated in gastric tumours compared with the non-neoplastic mucosae. Among these are many potential tumour suppressors which may contribute to the development of gastric cancer. Recent focus on epigenetics has revealed DNA methylation at the gene promoter region as a key mechanism in silencing tumour suppressor genes and hence plays an important role in carcinogenesis. The latest development of genomics approach has also allowed the systematic profiling for genes that are silenced by methylation in tumour cell lines. The data generated can then be analysed in comparison to the gene expression profiles of tumour tissue samples. This approach will lead to the identification of a comprehensive list of genes that are down-regulated in gastric tumour tissues and at the same time, re-expressed in tumour cell lines after demethylation treatment. Aims: 1. To identify genes that are induced after demethylation treatment in a large panel of gastric cancer cell lines by cDNA microarray analysis 2. To analyse the data against the expression profile database of gastric tumour tissue samples, so as to prioritise a list of genes that are down-regulated in the largest proportion of gastric tumour tissues and at the same time, induced after demethylation treatment in the largest number of gastric cancer cell lines 3. To verify the association of promoter demethylation with gene re-expression in selected gastric cancer cell lines by bisulphite genomic sequencing/Pyrosequencing and RT-PCR 4. To systematically determine the promoter methylation pattern of these target genes in gastric tumour tissues, non-neoplastic gastric mucosae and peripheral blood leucocytes, and to correlate the extent of methylation with gene expression levels in gastric tumour tissues. 5. To correlate the promoter methylation-induced silencing of specific target genes with clinico-pathological parameters, response to treatment and patient outcome |
| List of Research Outputs |
| Aggarwal A., Guo D.L., Hoshida Y., Yuen S.T., Chu K.M., So S., Boussioutas A., Chen X., Bowtell D., Aburatani H., Leung S.Y. and Tan P., Topological and functional discovery in a gene coexpression meta-network of gastric cancer, Cancer Research. 2006, 66(1): 232-41. |
| Chan O.O., Chu K.M., Leung S.Y., Huang C., Sun Y.W., Ko S., Yuen R.M.F., Xia H.H.X., Cho C.H., Hui W.M., Lam S.K., Rashid A. and Wong B.C.Y., Helicobacter pylori infection, interleukin 1 beta polymorphism and predisposition to gastric cancer through the CpG island methylation pathway, Presented at 11th Medical Research Conference, Department of Medicine, The University of Hong Kong, Hong Kong, 14 January 2006. |
| Chan O.O., Chu K.M., Leung S.Y., Huang C., Sun Y., Ko S., Yuen R.M.F., Xia H.H.X., Cho C.H., Hui W.M., Lam S.K., Rashid A. and Wong B.C.Y., Helicobacter pylori Infection, Interleukin 1 Beta Polymorphism and Predisposition to Gastric Cancer Through the Cpg Island Methylation, Gastroenterology. 2006, 130 (4 Suppl 2): A-717. |
| Davies H., Hunter C., Smith R., Stephens P., Greenman C., Bignell G., Teague J., Butler A., Edkins S., Stevens C., Parker A., O'Meara S., Avis T., Barthorpe S., Brackenbury L., Buck G., Clements J., Cole J., Dicks E., Edwards K., Forbes S., Gorton M., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jones D., Kosmidou V., Laman R., Lugg R., Menzies A., Perry J., Petty R., Raine K., Shepherd R., Small A., Solomon H., Stephens Y., Tofts C., Varian J., Webb A., West S., Widaa S., Yates A., Brasseur F., Cooper C.S., Flanagan A.M., Green A., Knowles M., Leung S.Y., Looijenga L.H., Malkowicz B., Pierotti M.A., Teh B.T., Yuen S.T., Lakhani S.R., Easton D.F., Weber B.L., Goldstraw P., Nicholson A.G., Wooster R., Stratton M.R. and Futreal P.A., Somatic mutations of the protein kinase gene family in human lung cancer, Cancer Research. 2005, 65(17): 7591-5. |
| Fan Y.S., Yuen S.T. and Leung S.Y., Calcified fibrous nodules in the heart: a case report, Pathology. 2006, 38(3): 273-5. |
| Giacomini C.P., Leung S.Y., Chen X., Yuen S.T., Kim Y.H., Bair E. and Pollack J.R., A Gene Expression Signature of Genetic Instability in Colon Cancer, Cancer Research. 2005, 65(20): 9200-5. |
| Guo D.L., Zhang J., Yuen S.T., Tsui W.Y., Chan A.S.Y., Ho C., Chen X. and Leung S.Y., Reduced Expression of EphB2 that parallels invasion and metastasis in colorectal tumors, Keystone Symposia: Stem Cells, Senescence and Cancer, 25-30 October . 2005. |
| Guo D.L., Zhang J., Yuen S.T., Tsui W.Y., Chan A.S.Y., Ho C., Ji J., Leung S.Y. and Chen X., Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumors, Carcinogenesis. 2005, 27(3): 454-464. |
| Iacopetta B., Russo A., Bazan V., Dardanoni G., Gebbia N., Soussi T., Kerr D., Elsaleh H., Soong R., Kandioler D., Janschek E., Kappel S., Lung M., Leung C.S., Ko J.M., Yuen S.T., Ho J.W.C., Leung S.Y., Crapez E., Duffour J., Ychou M., Leahy D.T., O'donoghue D.P., Agnese V., Cascio S., Di Fede G., Chieco-Bianchi L., Bertorelle R., Belluco C., Giaretti W., Castagnola P., Ricevuto E., Ficorella C., Bosari S., Arizzi C.D., Miyaki M., Onda M., Kampman E., Diergaarde B., Royds J., Lothe R.A., Diep C.B., Meling G.I., Ostrowski J., Trzeciak L., Guzinska-Ustymowicz K., Zalewski B., Capella G.M., Moreno V., Peinado M.A., Lonnroth C., Lundholm K., Sun X.F., Jansson A., Bouzourene H., Hsieh L.L., Tang R., Smith D.R., Allen-Mersh T.G., Khan Z.A., Shorthouse A.J., Silverman M.L., Kato S. and Ishioka C., Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study, Annals of Oncology. 2006, 17(5): 842-7. |
| Lau S.K.P., Woo P.C.Y., Li S.M.K., Huang Y., Tsoi H.W., Wong H.L.B., Wong S.S.Y., Leung S.Y., Chan K.H. and Yuen K.Y., Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats., Proceedings of the National Academy of Sciences of the Unite States of America. 2005, 102: 14040–14045. |
| Leung S.Y., Ho C., Tu I.P., Li R., So S., Chu K.M., Yuen S.T. and Chen X., Comprehensive analysis of 19Q12 amplicon in human gastric cancers, Modern Pathology. 2006, 19: 854-863. |
| Leung S.Y., Use of cDNA microarray in the molecular classification and delineation of prognostic markers for gastric cancer, The fourth Asia-Pacific Internation Academy of Pathology meeting, Beijing, China, August 2005. |
| Li M., Ng S.M., Wang J., Lai L., Leung S.Y., Franco M., Peng Y., He M.L., Kung H.F. and Lin M.C., EFA6A Enhances Glioma Cell Invasion through ADP Ribosylation Factor 6/Extracellular Signal-Regulated Kinase Signaling (Li M. and Ng S.M. are equal first authors)., Cancer Research. 2006, 66(3): 1583-1590. |
| Ma L., Chan K.W., Trendell-Smith N.J., Wu A.Y.Y., Tian L., Lam A.C., Lo C.K., Chik S.C.C., Ko K.H., To K.W., Kam C.S.K., Li X., Yang C., Leung S.Y., Ng M.H. and Huang F., Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains, In: Ma L, Chan KW, Trendell-Smith NJ, Wu A, Tian L, Lam AC, Chan AK, Lo CK, Chik S, Ko KH, To CK, Kam SK, Li XS, Yang CH, Leung SY, Ng MH, Stott DI, MacPherson GG, Huang FP, European Journal of Immunology (In This Issue highlight, Editorial Comments). 2005, 35(11): 3364-75. |
| Tang S.F., Chan K.H., Cheng V.C.C., Woo P.C.Y., Lau S.K.P., Lam C.C.K., Chan T.L., Wu A.K.L., Hung I.F.N., Leung S.Y. and Yuen K.Y., Comparative host gene transcription by microarray analysis early after infection of Huh7 cell line by SARS coronavirus and human coronavirus 229E., Journal of Virology. 2005, 79: 6180-6193. |
| Researcher : Leung THY |
| List of Research Outputs |
| Leung T.H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in Liver Cancer 2, DLC2, Suppresses Cell Transformation via Inhibition of Rhoa Activity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
| Wong C.M., Yam J.W.P., Ching Y.P., Yau T.O., Leung T.H.Y., Jin D. and Ng I.O.L., Rho GTPase-Activating Protein Deleted in Liver Cancer Suppresses Cell Proliferation and Invasion in Hepatocellular Carcinoma, Cancer Research. 2005, 65: 8861-8868. |
| Researcher : Li YH |
| List of Research Outputs |
| Ma E.S.K., Li Y.H., Kwok J.S.Y., Ling S.C., Yau P.W. and Chan G.C.F., ADAMTS13 Mutational Analysis in Chinese Patients with Chronic Relapsing Thrombotic Thrombocytopenic Purpura, Hong Kong Journal of Paediatrics (new series). 2006, 11: 22-27. |
| Researcher : Liang ACT |
| List of Research Outputs |
| Chen W.Y.W., Hu X., Liang A.C.T., Au W.Y., So J.C.C., Wong M.L.Y., Shen L., Tao Q., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6 deregulating mutations, in gastric lymphoma, Blood. 2006, 108(7): 2373-83. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Wong M.L.Y., Shen L., Wong K.Y., Au W.Y., Cheung W.L., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Au W.Y., Wong M.L.Y., Shen L., Wong K.Y., Wan T.S.K., Cheung W.L., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006 . 2006. |
| Researcher : Lo CK |
| List of Research Outputs |
| Ma L., Chan K.W., Trendell-Smith N.J., Wu A.Y.Y., Tian L., Lam A.C., Lo C.K., Chik S.C.C., Ko K.H., To K.W., Kam C.S.K., Li X., Yang C., Leung S.Y., Ng M.H. and Huang F., Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains, In: Ma L, Chan KW, Trendell-Smith NJ, Wu A, Tian L, Lam AC, Chan AK, Lo CK, Chik S, Ko KH, To CK, Kam SK, Li XS, Yang CH, Leung SY, Ng MH, Stott DI, MacPherson GG, Huang FP, European Journal of Immunology (In This Issue highlight, Editorial Comments). 2005, 35(11): 3364-75. |
| Researcher : Loong F |
| List of Research Outputs |
| Chim J.C.S., Yuen W.K., Loong F., Hu H.C. and Ooi C.G.C., Primary large B-cell lymphoma of the ampulla of vater, Haematologica. 2006, 91(3): ECR06. |
| Researcher : Lu L |
| Project Title: | B cell apoptosis and its regulation in autoimmunity |
| Investigator(s): | Lu L, Kincade PW |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 09/2003 |
| Abstract: |
| To study the regulation of B cell development and survival by BLyS and APRIL in mouse bone marrow; to examine B cell apoptosis and its regulation in the development of CIA as a model of RA; to determine if BLyS and/or APRIL participate(s) in the pathogenesis of CIA. |
| Project Title: | B cell apoptosis and its regulation in autoimmunity |
| Investigator(s): | Lu L, Kincade PW |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 09/2003 |
| Abstract: |
| N/A |
| Project Title: | Effect of aging on B lymphopoiesis |
| Investigator(s): | Lu L |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2003 |
| Completion Date: | 10/2005 |
| Abstract: |
| To determine if B cell differentiation and maturation are impaired during aging process; to identify the differentiation stages at which developing B cells are susceptible to the influence of aging; to study the mechanisms underlying the change of B lymphopoiesis associated with aging. |
| Project Title: | Natural killer cells and the pathogenesis of autoimmunity |
| Investigator(s): | Lu L, Paige C.J. |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 10/2004 |
| Abstract: |
| To study : (1) NK cell development during the pathogenesis of autoimmune arthritis. (2) NK cell interaction with T and B cells under autoimmune conditions. (3) role of NK cells in the development of autoimmune arthritis. |
| Project Title: | Specific silencing of novel TNF family cytokine BAFF by small inerfering RNA as a therapeutic approach for multiple myeloma |
| Investigator(s): | Lu L, Shen L |
| Department: | Pathology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 12/2004 |
| Completion Date: | 09/2005 |
| Abstract: |
| This project aims to use human myeloma cell line(s) to study the following issues: 1) Expression profile of BAFF and its receptors in myeloma cells 2) Specific inhibition of BAFF gene by small interfering RNA |
| Project Title: | Natural killer cells and the pathogenesis of autoimmunity |
| Investigator(s): | Lu L |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 01/2005 |
| Abstract: |
| N/A |
| Project Title: | Functional interactions of dendritic cells and B cells in autoimmunity |
| Investigator(s): | Lu L, Cao X.T. |
| Department: | Pathology |
| Source(s) of Funding: | NSFC/RGC Joint Research Scheme |
| Start Date: | 03/2005 |
| Abstract: |
| To study: (1) roles of BLyS in regulating DCs and B cell functions in autoimmunity, (2) roles of heat-shock proteins in regulating functions of DCs and B cells, (3) roles of HSPs in regulating autoimmune arthritis development. |
| Project Title: | Plasma cell development and its regulation in autoimmunity |
| Investigator(s): | Lu L |
| Department: | Pathology |
| Source(s) of Funding: | Incentive Award for RGC CERG Fundable But Not Funded Projects |
| Start Date: | 07/2005 |
| Completion Date: | 06/2006 |
| Abstract: |
| N/A |
| List of Research Outputs |
| Lu L., B cells and autoimmunity, Shandong University, Jinan, July. 2005. |
| Lu L., Current Immunology. Chinese Society for Immunology, 2006. |
| Lu L., Role of B cell activating factor in autoimmunity, Annual Scientific Meeting of Hong Kong Society for Immunology, April 30. 2006. |
| Qu X., Yang M.X., Kong B.H., Qi L., Lam Q.L.K., Yan S., Li P., Zhang M. and Lu L., Hypoxia inhibits the migratory capacity of human monocyte-derived dendritic cells, Immunology and Cell Biology . 2005, 83(6): 668-73. |
| Wong P.M., Lu L. and Sham M.H., HOXB3 Mutation Generated By Gene Targeting Leads to Plasmacytoma, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
| Zhang M., Ko K.H. and Lu L., BAFF enhances the development of autoantibody-producing plasma cells in collagen-induced arthritis mice, Annual Meeting of American Association of Immunologists, Boston, USA, May 12. 2006. |
| Zhang M., Ko K.H., Lam Q.L.K., Srivastava G., Zheng B., Lau Y.L. and Lu L., Expression and function of TNF family member B cell-activating factor in the development of autoimmune arthritis, International Immunology. 2005, 17(8): 1081-1092. |
| Zheng B., Lee S.S., Wong K.H., Chan K.C.W., Zhang H. and Lu L., Ex vivo expansion of functional CD4 T cells from HIV patients., The 6th International Workshop on HIV, Cells of Macrophage/Dendritic Lineage and Other Reservoirs.. 2005, 37. |
| Zheng Y., Cao K., Ng S.P., Chua D.T.T., Sham J.S.T., Kwong D.L.W., Ng M.H., Lu L. and Zheng B., Complementary activation of peripheral natural killer cell immunity in nasopharyngeal carcinoma, Cancer Science. 2006, 97(9): 912-9. |
| Researcher : Ma ESK |
| List of Research Outputs |
| Au W.Y., Pang A.W.K., Wan T.S.K., Ma E.S.K., Cheng L.C. and Kwong Y.L., Concomitant post-transplantation lymphoproliferative disease and therapy-related myelodysplastic syndrome after lung transplantation , The Journal of Heart and Lung Transplantation . 2006, 25(2): 259-260. |
| Au W.Y., Cheung W.C., Hu H.C., Chan G.C.F., Ha S.Y., Khong P.L., Ma E.S.K. and Liang R.H.S., Hyperbilirubinaemia and cholelithiasis in Chinese patients with hemoglobin H disease., Annals of Hematology. 2005, 84(10): 671-674. |
| Au W.Y., Fung T.K., Ma E.S.K., Chan C.H., Wong K.F., Chim J.C.S., Liang R.H.S. and Kwong Y.L., Serial studies of methylation of CDKN2B and CDKN2A in relapsed acute promyelocytic leukaemia treated with arsenic trioxide, British Journal of Haematology. 2005, 131: 632. |
| Au W.Y., Hung K.N., Shek T.W.H. and Ma E.S.K., Side effects related to cancer treatment: CASE 3. Primary cerebral lymphoma after radiotherapy for recurrent meningioma, Journal of Clinical Oncology. 2005, 23(33): 8535-6. |
| Au W.Y., Ma E.S.K., Choy C., Chung L.P., Fung T.K., Liang R.H.S. and Kwong Y.L., Therapy-related lymphomas in patients with autoimmune diseases after treatment with disease-modifying anti-rheumatic drugs, American Journal of Hematology. 2005, 81(1): 5-11. |
| Chan A.Y., Luo H.Y., Wang W., Chui D.H., Ma E.S.K., Chan L.C. and Chong S.S., Diagnostic pitfall in PCR-based alpha-thalassemia genotyping resulting from a (G->C) polymorphism at nucleotide 71 3' to the alpha2-globin gene termination codon, Chinical Chemistry. 2006, 52(3): 536-7. |
| Cheung E.W.Y., Chay G.W., Ma E.S.K. and Cheung Y.F., Systemic Oxygen Saturation and Coagulation Factor Abnormalities Before and After the Fontan Procedure, The American Journal of Cardiology. 2005, 96: 1571-1575. |
| Cheung Y.F., Chay G.W. and Ma E.S.K., Ethnic Differences in Coagulation Factor Abnormalities After the Fontan Procedure, Pediatric Cardiology. 2006, 27: 96-101. |
| Chim J.C.S., Kwong Y.L., Lie A.K.W., Ma E.S.K., Chan C.C., Wong L.G., Kho B.C., Lee H.K., Sim J.P., Chan C.H., Chan J.C., Yeung Y.M., Law W. and Liang R.H.S., Long-term Outcome of 231 Patients With Essential Thrombocythemia , Archives of Internal Medicine. 2005, 165(22): 2651-8. |
| Choi C.L., Ma E.S.K. and Chan L.C., In vitro characterization of silent beta-thalassemia mutation, +8 C-to-T substitution, The 3rd Asia Hematology Association. Jeju, Korea. August 17-20, 2005. |
| Chung B.H.Y., Ma E.S.K., Khong P.L. and Chan G.C.F., Genetic thrombophilic risk factors in Chinese children with malignant illness, Joint Annual Scientific Meeting, The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association, Queen Elizabeth Hospital, 7 January 2006. 66. |
| Chung B.H.Y., Ma E.S.K., Khong P.L. and Chan G.C.F., Inherited Thrombophilia Does Not Increase Catheter Thrombosis in Chinese Children with malignancies, 1st Congress of Asian Society for Pediatric Research, Tokyo, Japan, 24-26 November 2005. 82. |
| Hon C., Ma E.S.K. and Au W.Y., A patient with anophthalmia, hemifacial microsomia, and hemoglobin anti-Lepore, Annals of Hematology. 2005, 84(9): 623-4. |
| Hon C., Chan R.T., Ma E.S.K., Shek T.W.H., Yau K. and Au W.Y., Lymphomatous proptosis as a novel featur of mantle cell lymphoma, Leukemia & Lymphoma. 2006, 47(1): 71-5. |
| Leung A.Y.H., Leung J.C.K., Chan Y.Y., Ma E.S.K., Kwan T.F., Lai K.N., Meng A. and Liang R.H.S., Proliferating cell nuclear antigen (PCNA) as a proliferative marker during embryonic and adult zebrafish hematopoiesis, Histochemistry and Cell Biology. 2005, 124(2): 105-11. |
| Leung R., Chou E.E., Au W.Y., Chow C., Kwong Y.L., Lin S.Y., Ma E.S.K., Wan T.S.K. and Wong K.F., CD4+/CD56+ hematologic malignancy with rearranged MLL gene, Human Pathology . 2006, 37(2): 247-249. |
| Ma E.S.K., Li Y.H., Kwok J.S.Y., Ling S.C., Yau P.W. and Chan G.C.F., ADAMTS13 Mutational Analysis in Chinese Patients with Chronic Relapsing Thrombotic Thrombocytopenic Purpura, Hong Kong Journal of Paediatrics (new series). 2006, 11: 22-27. |
| Ma E.S.K., Wong C.L., Lai K.T., Chan E.C., Yam W.C., Chan A.C. and Chan A.C.Y., Kocuria kristinae infection associated with acute cholecystitis. , BMC Infect Dis. UK, 2005, 5(1): 60. |
| Wang W., Chan A.Y., Chan L.C., Ma E.S.K. and Chong S.S., Unusual rearrangement of the alpha-globin gene cluster containing both the -alpha3.7 and alphaalphaalphaanti-4.2 crossover junctions: clinical diagnostic implications and possible mechanisms, Clinical Chemistry. 2005, 51(11): 2167-70. |
| Researcher : Ma L |
| List of Research Outputs |
| Ma L., Chan K.W., Trendell-Smith N.J., Wu A.Y.Y., Tian L., Lam A.C., Lo C.K., Chik S.C.C., Ko K.H., To K.W., Kam C.S.K., Li X., Yang C., Leung S.Y., Ng M.H. and Huang F., Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains, In: Ma L, Chan KW, Trendell-Smith NJ, Wu A, Tian L, Lam AC, Chan AK, Lo CK, Chik S, Ko KH, To CK, Kam SK, Li XS, Yang CH, Leung SY, Ng MH, Stott DI, MacPherson GG, Huang FP, European Journal of Immunology (In This Issue highlight, Editorial Comments). 2005, 35(11): 3364-75. |
| To K.W., Wong O.H., Li H.B., Chan S.F., Ma L., Cheung Y.L., Ko K.H., Chiang A.K.S. and Huang F., The effects of Bergapten in modulating dendritic cells (DC) functions for DC-based tumor vaccines, 10th Research Postgraduate Symposium, Hong Kong. December 3. 2005. |
| Researcher : Ma SKY |
| List of Research Outputs |
| Shen J., Ma S.K.Y., Chan P., Lee W., Fung P.C.W., Cheung R.T.F., Tong Y. and Liu K.J., Nitric oxide down-regulates caveolin-1 expression in rat brains during focal cerebral ischemia and reperfusion injury, Journal of Neurochemistry. 2006, 96(4): 1078-89. |
| Researcher : Ng IOL |
| Project Title: | Dysregulation of NF-[kappa]B signaling in liver cancer |
| Investigator(s): | Ng IOL, Yau TO, Jin D |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 09/2002 |
| Completion Date: | 08/2005 |
| Abstract: |
| The project attempts to document systematically the dyregulation of the important cellular pathway in liver cancer and identify its clinical significance in patient management. |
| Project Title: | Deciphering dysregulation of mitotic checkpoint control in liver cancer |
| Investigator(s): | Ng IOL, Jin D |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 09/2003 |
| Completion Date: | 02/2007 |
| Abstract: |
| 1) To document and characterize dysregulation of mitotic checkpoint in hepatocellular carcinoma (HCC) by evaluating; a) mitotic checkpoint competence in HCC cell lines, b) expression and alterations of mitotic checkpoint genes and proteins in HCC cells and tissues, c) epigenetic causes of mitotic checkpoint defects in HCC; 2) to investigate the roles of hepatitis B virus-encoded X protein (HBx) in mitotic checkpoint in HCC; 3) to assess the clinical, pathological and prognostic significance of mitotic checkpoint dysfunction in HCC. |
| Project Title: | Deciphering dysregulation of mitotic checkpoint control in liver cancer |
| Investigator(s): | Ng IOL, Jin D |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 09/2003 |
| Abstract: |
| N/A |
| Project Title: | Characterization of T-cadherin in hepatocellular carcinoma |
| Investigator(s): | Ng IOL, Chan DW |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2003 |
| Abstract: |
| To evaluate the expression of T-cadherin at mRNA and protein levels in human HCCs and in HCC cell lines; to investigate the factors which induce expression of T-cadherin in HCC. |
| Project Title: | Characterization of the dishevelled gene in Wnt/[beta]-catenin signaling in liver cancer |
| Investigator(s): | Ng IOL, Yam JWP, Chan DW |
| Department: | Pathology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 01/2005 |
| Abstract: |
| The main objectives of this project are to: 1) characterize the expression of Dvl, HDPR1, and Pk1 in HCC and evaluate their clinicopathological significance, 2) delineate the genetic and epignetic alterations of Dvl, HDPR1 and Pk1 in HCC, 3) assess the biochemical properties of Dvl in HCC cells, and 4) investigate the functions of Dvl, HDPR1, and Pk1 in Wnt signaling in HCC development. |
| Project Title: | Functional characterization of DLC1 gene, a novel tumour suppressor gene frequently deleted in liver cancer |
| Investigator(s): | Ng IOL |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 01/2005 |
| Abstract: |
| N/A |
| Project Title: | Genome-wide methylation screening in search for novel tumour suppressor genes in liver cancer |
| Investigator(s): | Ng IOL, Ching YP, Wong CM |
| Department: | Pathology |
| Source(s) of Funding: | Michael Kadoorie Cancer Genetics Research Fund |
| Start Date: | 01/2005 |
| Abstract: |
| To characterize HCC-specific hypermethylation profile in HCC cells using microarray approach; to identify novel tumour suppressor genes in HCC cells; to delineate epigenetic and genetic alterations of selected putative tumour suppressor genes in human HCC; to characterize tumour suppressor activities of selected novel tumour suppressor genes. |
| Project Title: | Functional characterization of DLC1 gene, a novel tumour suppressor gene frequently deleted in liver cancer |
| Investigator(s): | Ng IOL, Yau TO, Sham MH, Jin D, Ching YP |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 01/2005 |
| Abstract: |
| To develop and characterize DLC-null mice using gene targeting technology; to delineate the interaction between DLC1 and the downstream effector, ROCK in HCC cell lines and human HCCs. |
| Project Title: | Characterization of DLC1 gene, a novel tumour suppressor gene frequently deleted in liver cancer |
| Investigator(s): | Ng IOL, Jin D, Yam JWP, Ching YP |
| Department: | Pathology |
| Source(s) of Funding: | Michael Kadoorie Cancer Genetics Research Fund |
| Start Date: | 01/2005 |
| Abstract: |
| To search for binding partners of DLC1; to delineate the interaction between DLC1 and the downstream effector, ROCK, in HCC cell lines and human HCCs; to assess the clinicopathologic significance of ROCK and its relationship with DLC1 in HCCs. |
| Project Title: | A study of molecular mechanisms and characterizing novel genes in liver cancer |
| Investigator(s): | Ng IOL |
| Department: | Pathology |
| Source(s) of Funding: | Senior Medical Research Fellowships |
| Start Date: | 09/2005 |
| Abstract: |
| To investigate the genetic basis of genome instability in liver cancer in relation to competence of mitotic checkpoints, and hepatitis B virus. Different approaches will be used to study the functional aspects as well as clinicopathological and prognostic significance of these genetic changes, in order to shed light for new treatment modalities. |
| Project Title: | LRP6 coreceptor upregulation in liver cancer |
| Investigator(s): | Ng IOL, Yam W. P. |
| Department: | Pathology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 04/2006 |
| Abstract: |
| The purpose of this study is to characterize LRP6 (low-density lipoprotein receptor related protein) genetically and functionally in liver cancer, which is a major cancer in Southeast Asia and Hong Kong. Activation of Wnt/β-catenin pathways is involved in the formation and progression of various cancers. However, the role of Wnt signaling has not been extensively examined in liver cancer (hepatocellular carcinoma, HCC). Our previous studies have already documented the importance of players of this pathway, such as HDPR1 and β-catenin genes, in HCC development. Here we hypothesize that LRP6, a newly identified co-receptor of Wnt/β-catenin canonical signaling pathway, is a putative oncogene in HCC and its dysregulation plays a role in hepatocarcinogenesis. We will examine the mechanism of LRP6 upregulation in human HCC and the molecular pathways by which LRP6 exerts its effects. Our work should shed light on how LRP6 regulates the Wnt canonical signaling and how LRP6 overexpression leads to HCC formation. Objectives to be achieved are: 1. To evaluate the expression profile, genetic alterations, and clinical significance of LRP6 in HCC 2. To characterize the tumorigenic activity of LRP6 in HCC Key issues and problems being addressed: - Liver cancer is a major malignancy in the world and is particularly prevalent in this region, being the second commonest fatal cancer in Southeast Asia including Hong Kong. Despite definite improvements in the outcome of patients with HCC, so far, the overall prognosis of this cancer is still unsatisfactory because of late presentation and frequent tumor recurrence after surgical resection. New adjuvant treatment modalities for HCC are much awaited. In this regard, knowledge of the molecular and cellular targets underlying the development and progression of HCC is of importance as this can provide novel opportunities for therapeutic interventions for this cancer. - Activation of canonical Wnt signaling through β-catenin/T cell factor complexes is a key event in embryonic development and is closely linked to cancer formation. β-catenin activation is a pivotal event in this pathway. From others’ and our previous results, β-catenin overexpression in human HCC is frequent (50-68%) but somatic mutations of β-catenin occur in much lower frequencies. Evidence has shown that factors other than β-catenin mutation contribute to β-catenin activation. The Wnt signal requires two membrane receptors for the Wnt ligands, Frizzled and LRP, to form a Wnt-induced Frizzled-LRP complex. LRP5 and LRP6, identified in 1998, are essential co-receptors of Wnt and specifically function in the canonical pathway. The data derived in recent studies have suggested that LRP6 is a putative oncogene in cancers. However, the pathogenic roles of LRP5 and LRP6 have not been explored in HCC. - As part of our continual study on the role of Wnt/β-catenin in HCC, we have found in our preliminary study that LRP6 expression was frequently and significantly upregulated in human HCCs, whereas LRP5 expression was not. This significant upregulated expression in HCC suggests that dysregulation of LRP6 is implicated in hepatocarcinogenesis. However, there is minimal information available on the expression profile, tumorigenic potential and functional characteristics of LRP6. Further investigations are warranted. |
| List of Research Outputs |
| Chan D.W. and Ng I.O.L., Knock-down of hepatitis B virus X protein reduces the tumorigenicity of hepatocellular carcinoma cells, Journal of Pathology. 2006, 208(3): 372-80. |
| Chan D.W., Chan P.C.Y., Yam J.W.P., Ching Y.P. and Ng I.O.L., Prickle-1 promotes the degradation of Dishevelled by ubiquitination in liver cancer, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
| Chan L.K., Yam J.W.P. and Ng I.O.L., C20, a novel binding partner of DLC1 identified by yeast-2-hybrid screening, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
| Cheung S.T., Liu C.L., Chow J.P.H., Ng I.O.L. and Fan S.T., Preoperative blood test for prognosis of hepatocellular carcinoma (Abstract), The 4th Japan Society of Hepatology Single Topic Conference, "Hepatocellular Carcinoma: International Consensus and Controversies", Awaiji Island, Hyogo, Japan, 2-3 December 2005. |
| Chin K.T., Wong C.M., Ng I.O.L. and Jin D., Functional characterization of liver-enriched transcription factor CREB-H (poster 1989). , The American Society for Cell Biology 45th Annual Meeting, San Francisco, California, USA, December 10-14, 2005.. 2005. |
| Fung K.L., Yan H., Ching Y.P., Ng I.O.L., Chung S.S.M., Sun H. and Ko B.C.B., Homodimerization of the deleted in liver cancer 2 (DLC2) is not mediated by the SAM domain, FEBS-IUBMB Conference, July 2005. |
| Ha S.Y., Chik K.W., Ling S.C., Lee A.C.W., Luk C.W., Lam C.W.K., Ng I.O.L. and Chan G.C.F., A randomized controlled study evaluating the safety and efficacy of deferiprone treatment in thalassemia major patients from Hong Kong, Hemoglobin. 2006, 30(2): 263-274. |
| Hu X., Leong V.Y.L., Ng I.O.L. and Ching Y.P., Overexpression of PAK4 in hepatocellular carcinoma (HCC), 2006 American Association for Cancer Research (AACR) Annual Meeting, Washington DC., USA, April 2006 . 2006. |
| Ko C.F., Yam J.W.P., Chan P.C.Y., Jin D. and Ng I.O.L., Interaction of deleted in liver cancer 1 (DLC1) with tensin2 and its implications in tumor suppression, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
| Lee K.W., Man K., Ho J.W.Y., Wang X., Poon R.T.P., Xu Y., Ng T.P., Chu A.C.Y., Sun K.W., Ng I.O.L., Sun H.C., Tang Z.Y., Xu R. and Fan S.T., FTY720: a promising agent for treatment of metastatic hepatocellular carcinoma, Clinical Cancer Research. 2005, 11(23): 8458-8466. |
| Leung H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity, Proc Natl Acad Sci U S A. 2005, 102: 15207-15212. |
| Leung T.H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in Liver Cancer 2, DLC2, Suppresses Cell Transformation via Inhibition of Rhoa Activity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
| Li H., Fung K.L., Jin D., Chung S.S.M., Cing Y.P., Ng I.O.L., Sze K.H., Ko C.B. and Sun H., Solution structures and dynamics of the sterile of Motif (SAM) domain of the deleted in liver cancer 2 (DLC2): a monomeric structure with membrane-binding properties, Croucher Foundation Advanced Study Institute: Advances in Protein Sciences, Biochemistry Department, The Chinese University of Hong Kong, Hong Kong, 15-17 December 2005 . 2005, PO-17, p.33. |
| Liu C.L., Fan S.T., Cheung S.T., Lo C.M., Ng I.O.L. and Wong J., Anterior approach versus conventional approach right hepatic resection for large hepatocellular carcinoma: a prospective randomised controlled study (Abstract), The 7th Annual Scientific Meeting, Centre for the Study of Liver Disease, The University of Hong Kong, Hong Kong, 21 January 2006. |
| Luk J.M.C., Lam C.T., Siu A.F.M., Lam B.Y.H., Ng I.O.L., Hu M.Y., Che C.M. and Fan S.T., Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values, Proteomics . 2006, 6(3): 1049-1057. |
| Man K., Lo C.M., Xiao J.W., Ng T.P., Ng I.O.L., Sun K.W., Cheng Q. and Fan S.T., The significance of graft size on tumor recurrence/metastases after liver transplantation – Activation of cell invasion and migration pathways (Abstract), The 2006 Joint International Congress of the International Liver Transplantation Society (ILTS), the European Liver and Intestinal Transplant Association (ELITA), and the Liver Intensive Care Group of Europe (LICAGE), Milan, Italy, 3 - 6 May 2006. Liver Transplantation. 2006, 12: C30. |
| Ng D.C.H., Chan S.F., Kok K.H., Yam J.W.P., Ching Y.P., Ng I.O.L. and Jin D., Mitochondrial targeting of growth suppressor protein DLC2 through the START domain, FEBS Letters . 2006, 580(1): 191-8. |
| Ng I.O.L., Asian Journal of Oral and Maxillofacial Surgery. 2005. |
| Ng I.O.L., Asian Journal of Surgery. 2005. |
| Ng I.O.L., Journal of Clinical Oncology (Chinese version). 2005. |
| Ng I.O.L., Journal of Gastroenterology and Hepatology. 2005. |
| Ng I.O.L., Molecular and genetic alterations in hepatocellular carcinoma, Symposium on Advances in Cancer Biology, 18th Asia Pacific Cancer Conference, Seoul, Korea, September 2005. |
| Ng I.O.L., Multistep process of hepatocarcinogenesis, Frontiers in Biomedical Research, Faculty of Medicine, The University of Hong Kong, December 2005. 2005. |
| Ng I.O.L., Pathology and molecular genetics of liver cancer, Symposium on liver cancer: Hope for our future generations, The Hong Kong Anti-Cancer Society, Hong Kong, August. 2005. |
| Ng I.O.L., RNA interference in hepatocellular carcinoma, Fourth Asia-Pacific International Academy of Pathology Congress (IAP2005), Beijing, August. 2005. |
| Ng I.O.L., Virus to cancer - how?, World Congress of Gastroenterology 2005 Meeting “Global Goals in Gastroenterology: Expanding Horizons for the 21st Century”, Montréal, Québec, Canada, September. 2005. |
| Pawlik T.M., Delman K.A., Vauthey J.N., Nagorney D.M., Ng I.O.L., Ikai I., Yamaoka Y., Belghiti J., Lauwers G.Y., Poon R.T.P. and Abdalla E.K., Tumor size predicts vascular invasion and histologic grade: Implications for selection of surgical treatment for hepatocellular carcinoma, Liver Transplantation. 2005, 11(9): 1086-92. |
| Sze M.F., Ching Y.P., Jin D. and Ng I.O.L., Dysregulation of Mitotic Spindle Checkpoint Control in Hepatocellular Carcinomas , 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
| Tung K.K., Wong C.M. and Ng I.O.L., Underexpression of hepatocyte growth factor activator inhibitors HAI-1 and HAI-2 was assoicated with promoter hypermethylation in hepatocellular carcinoma, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April 2006. |
| Wong C.M., Cheung O.F. and Ng I.O.L., Epigenetic inactivation of serine protease inhibitor TFPI-2 in human HCC, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April 2006. |
| Wong C.M., Yam J.W.P., Ching Y.P., Yau T.O., Leung T.H.Y., Jin D. and Ng I.O.L., Rho GTPase-Activating Protein Deleted in Liver Cancer Suppresses Cell Proliferation and Invasion in Hepatocellular Carcinoma, Cancer Research. 2005, 65: 8861-8868. |
| Yuan H., Yuen R.M.F., Wong D.K.H., Sum S.M., Sablon E., Ng I.O.L. and Lai C.L., Impact of Precore and Core Promoter Mutations on Hepatic Histology in Patients with Chronic Hepatitis B, Alimentary Pharmacology and Therapeutics. 2005, 22: 301-307. |
| Yuen R.M.F., Tanaka Y., Ng I.O.L., Mizokami M., Yuen J.C.H., Wong D.K.H., Yuan H., Sum S.M., Chan O.O. and Lai C.L., Hepatic necroinflammation and fibrosis in patients with genotypes Ba and C, core-promoter and precore mutations, Journal of Viral Hepatitis . 2005, 12(5): 513-8. |
| Researcher : Ng MH |
| List of Research Outputs |
| Ng M.H., Jin D. and Chan L.C., Ras Signalling in Mll-Mediated Leukaemia, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
| Researcher : Nicholls JM |
| Project Title: | ACE and ACE 2 expression in lungs of normal patients and patients with SARS |
| Investigator(s): | Nicholls JM, Peiris JSM, Cheung CY |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 09/2005 |
| Abstract: |
| In December 2002 - June 2003 Southern China, including Hong Hong, was affected by a new coronavirus that resulted in a high mortality compared to previous coronaviral infections. The aetiological agent SARS-CoV was identified at Hong Kong University(1). In late 2003 two groups of researchers (2,3) identified a putative receptor for SARS-CoV,angiotensin converting enzyme 2 (ACE2 ) in cell lines and showed that the spike protein of SARS-CoV binds to the ACE2 receptor. Angiotensin converting enzyme (ACE) is a key enzyme in the well known rennin-angiotensin-aldosterone system (RAAS) - an endocrine cascade which is involved in blood pressure regulation. Angiotensionogen is cleaved by renin to produce a pro-hormone angiotensin I - a decapeptide. ACE removes the terminal 2 amino acids ( His-Leu) to produce an active octapeptide angiotensin 2 which is a potent vasoconstrictor and stimulator of cardiac growth (3). Whilst ACE was discovered over 50 years ago, it was only in 2000 that 2 independent groups (4,5). identified another enzyme ACE2, which though similar in many features to ACE functions by only removing a single amino acid ( Phe), converting angiotensin II to the less damaging Ang 1-7. ACE2 is therefore considered to have opposing functions to ACE(6) There is an increasing body of evidence supporting the role of an activated renin- angiotensin system (RAS) in acute lung injury/acute respiratory distress syndrome as increased ACE has been identified in the bronchoalveolar fluid of patients with ARDS together with a decrease in circulating ACE(7). Recent publications have shown that ACE2 does have an opposing function to ACE in lung injury, and that it does have a protective role - in one study mice that were given recombinant ACE2 were protected from acid-induced lung injury(8). The mechanism this appears to be a balance between the two angiotensin receptors in the lung - AT1aR and AT2R. Angiotensin II binds to both AT1aR and AT2R. Binding to AT1aR by Ang II will stimulate lung injury whilst binding toAT2R reduces lung injury. What ACE2 does is to reduce the levels of Ang II thereby reducing the binding of the AT1aR and thus reducing lung injury. The same researchers as publication (8) have also proposed that binding of SARS-CoV to ACE2 donwregulates this protective function of ACE2 by internalizing the receptor, thus allowing the angiotensin II to produce the lung damage(9). There is however some uncertainty about to what extent ACE and ACE2 are expressed in the respiratory tract. In the original reports detecting ACE2 in humans, Northern blots identified ACE2 in the heart, kidney and testis, but lungs were negative. Whilst Harmer and colleagues have recently used PCR to identify ACE2 in the gastrointestinal tract with a lower expression in the lungs(10) there seems to be a discrepancy between these findings and the widespread immunohistochemical detection of ACE2 in organ systems (11). Furthermore there is no data available concerning the ACE and ACE2 expression in the paediatric respiratory tract which would be of interest as SARS was not as fatal in this age group than in the elderly. The key issues therefore are as follows: 1. Is there a correlation between the immunohistochemical detection of ACE/ACE 2 and PCR detection in the lungs? 2. What cells of the respiratory tract contain ACE/ACE2? 3. Is there a difference in expression of ACE and ACE2 in paediatric lung tissues and adult lung tissues? 4. Do the lungs from patients who died of SARS show any change in ACE/ACE2 expression than normal patients? REFERENCES: 1. Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, Nicholls J, Yee WK, Yan WW, Cheung MT, Cheng VC, Chan KH, Tsang DN, Yung RW, Ng TK, Yuen KY; SARS study group Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet. 2003;361:1319-25 2. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.Nature. 2003;426:450-4 3. Xiao X, Chakraborti S, Dimitrov AS, Gramatikoff K, Dimitrov DS. The SARS-CoV S glycoprotein: expression and functional characterization. Biochem Biophys Res Commun. 2003 ;312:1159-64 7. Zisman LS. ACE and ACE2: a tale of two enzymes.Eur Heart J. 2005;26:322-4 4. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000 ;87:E1-9 6. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000;275:33238-43 7. Turner AJ, Hiscox JA, Hooper NM. ACE2: from vasopeptidase to SARS virus receptor. Trends Pharmacol Sci. 2004 ;25:291-4 7. Idell S, Kueppers F, Lippmann M, Rosen H, Niederman M, Fein A. Angiotensin converting enzyme in bronchoalveolar lavage in ARDS. Chest. 1987;91:52-6 8.Imai Y, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure.Nature. 2005 ;436:112-6 9.Kuba K et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury.Nat Med. 2005 Jul 10; [Epub ahead of print] 10. Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002;532:107-10 11. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004 ;203:631-7 |
| Project Title: | Sialic acid and receptor expression in normal respiratory tract, H5N1 influenza and non-avian influenza cases |
| Investigator(s): | Nicholls JM, Peiris S.M., Guan Y |
| Department: | Pathology |
| Source(s) of Funding: | Research Fund for the Control of Infectious Diseases - Full Grants |
| Start Date: | 10/2005 |
| Abstract: |
| To determine if there is a change in expression of sialic acids in the conjunctiva and respiratory tract of nornal, avian influenza and fatal non-avian influenza cases that makes infection by the H5N1 more likely in Chinese subjects. |
| Project Title: | Occult respiratory viral infections in coronial autopsies - a pilot project |
| Investigator(s): | Nicholls JM, Peiris JSM, Chan KH, Beh SL, Poon LLM |
| Department: | Pathology |
| Source(s) of Funding: | Research Fund for the Control of Infectious Diseases - Full Grants |
| Start Date: | 12/2005 |
| Abstract: |
| Analyse the presence of clinically undiagnosed respiratory viral infections in autopies performed under HK coronial system |
| List of Research Outputs |
| Chan M.C.W., Cheung C.Y., Chui W.H., Tsao G.S.W., Nicholls J.M., Chan Y.O., Chan W.Y., Long H.T., Poon L.L.M., Guan Y. and Peiris J.S.M., Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells, Respiratory Research. 2005, 6: 135. |
| Cheung H.W., Ching Y.P., Nicholls J.M., Ling M.T., Wong Y.C., Hui C.M., Cheung A., Tsao G.S.W., Wang Q., Yuen P.W., Lo K.W., Jin D. and Wang X., Epigenetic inactivation of CHFR in nasopharyngeal carcinoma through promoter methylation, Molecular Carcinogenesis. 2005, 43(4): 237-245. |
| Cheung H.W., Chun C.S., Wang Q., Deng W., Hu L., Guan X.Y., Nicholls J.M., Ling M.T., Wong Y.C., Tsao G.S.W., Jin D. and Wang X., Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to chemosensitization to DNA-damaging agents, Cancer Research. 2006, 66(8): 4357-4367. |
| Chung B.H.Y., Ip P., Wong V.C.N., Lo J., Nicholls J.M. and Khong P.L., Acute fulminant SSPE with absent measels and PCR studies in cerebrospinal fluid, DK 50th Anniversary Symposium on Paediatric Neurology and Neuro-Rehabilitation, 16-17 September 2005. |
| Nicholls J.M. and Peiris J.S.M., Good ACE, bad ACE do battle in lung injury, SARS, Nature Medicine. 2005, 11: 821-822. |
| Nicholls J.M., Butany J., Poon L.L.M., Chan K.H., Beh S.L., Poutanen S., Peiris J.S.M. and Wong M.P., Time course and cellular localization of SARS-CoV nucleoprotein and RNA in lungs from fatal cases of SARS, Public Library of Science Medicine . 2006, 3(2): e27. |
| Uiprasertkul M., Puthavathana P., Sangsiriwut K., Pooruk P., Srisook K., Peiris J.S.M., Nicholls J.M., Chokephaibulkit K., Vanprapar N. and Auewarakul P., Influenza A H5N1 replication sites in humans, Emerging Infectious Diseases. 2005, 11(7): 1036-1041. |
| Wang Q., Tsao G.S.W., Ooka T., Nicholls J.M., Cheung H.W., Fu S., Wong Y.C. and Wang X., Anti-apoptotic role of BARF1 in gastric cancer cells, Cancer Letters. 2005, xx: 1-14. |
| Researcher : Samaranayake YH |
| Project Title: | Genomic basis of fluconazole resistance in C.glabrata |
| Investigator(s): | Samaranayake YH, Samaranayake LP |
| Department: | Dental Faculty |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2004 |
| Completion Date: | 10/2006 |
| Abstract: |
| To obtain a drug resistant C. glabrata strain by sequential exposure to sub-minimal inhibitory concentrations of fluconazole; to determine cell viability (by ATP measurement) after drug exposure and observe the morphological changes by SEM. |
| List of Research Outputs |
| Researcher : Shek TWH |
| List of Research Outputs |
| Au W.Y., Pang A.W.K., Chan C., Chu K.M., Shek T.W.H. and Kwong Y.L., Epstein-barr virus-related gastric adenocarcinoma: an early secondary cancer post hemopoietic stem cell transplantation, Gastroenterology. 2005, 129(6): 2058-63. |
| Au W.Y., Hung K.N., Shek T.W.H. and Ma E.S.K., Side effects related to cancer treatment: CASE 3. Primary cerebral lymphoma after radiotherapy for recurrent meningioma, Journal of Clinical Oncology. 2005, 23(33): 8535-6. |
| Au W.Y., Kumana C.R., Lam C.W., Cheng V.C.C., Shek T.W.H., Chan E.Y.T., Liu K.Y. and Kwong Y.L., Solid tumors subsequent to arsenic trioxide treatment for acute promyelocytic leukemia, Leukemia Research. 2006. |
| Chim J.C.S. and Shek T.W.H., Primary gastrointestinal lymphoma of the colo, Haematologica. 2005, 90: Suppl:EIM01. |
| Hon C., Chan R.T., Ma E.S.K., Shek T.W.H., Yau K. and Au W.Y., Lymphomatous proptosis as a novel featur of mantle cell lymphoma, Leukemia & Lymphoma. 2006, 47(1): 71-5. |
| Hon C., Chui W.H., Cheng L.C., Shek T.W.H., Jones B.M. and Au W.Y., Thymoma associated with keratoconjunctivitis, lichen planus, hypogammaglobinemia, and absent circulating B cells, Journal of Clinical Oncology. 2006, 24(18): 2960-1. |
| Ng K.K.C., Lam C.M., Poon R.T.P., Shek T.W.H., Ho D.W.Y. and Fan S.T., Safety limit of large-volume hepatic radiofrequency ablation in a rat model, Archives of Surgery. 2006, 141(3): 252-258. |
| Researcher : Shen L |
| List of Research Outputs |
| Chen W.Y.W., Hu X., Liang A.C.T., Au W.Y., So J.C.C., Wong M.L.Y., Shen L., Tao Q., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6 deregulating mutations, in gastric lymphoma, Blood. 2006, 108(7): 2373-83. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Wong M.L.Y., Shen L., Wong K.Y., Au W.Y., Cheung W.L., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Au W.Y., Wong M.L.Y., Shen L., Wong K.Y., Wan T.S.K., Cheung W.L., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006 . 2006. |
| Researcher : Siu KY |
| Project Title: | Ectoplasmic specialization dynamics in the testis is regulated by focal adhesion complex-mediated signaling pathways |
| Investigator(s): | Siu KY, Lee WWM |
| Department: | Zoology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2004 |
| Abstract: |
| To investigate the downstream signaling pathway(s) underneath integrin and FAK that contribute to the regulation of ES dynamics. |
| Project Title: | p21-activated kinases (Paks) in ovarian and endometrial cancers |
| Investigator(s): | Siu KY, Cheung ANY |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 01/2006 |
| Abstract: |
| The purpose of the proposed investigation is to characterize the expression levels and the signaling pathways of Paks in ovarian and endometrial cancers in an attempt to explore the roles of Paks in their carcinogenesis, with potential impacts on the development of targeted anticancer therapies. Key Issues and Problems being addressed: Ovarian and endometrial cancers are two common gynecological cancers. In 2002, ovarian cancer ranked eighth among the major causes of cancer death in Hong Kong. Endometrial cancer is the most common gynecological cancer worldwide. To have a greater chance to cure, it is important to define the staging of cancers at the first diagnosis. Recent studies in our laboratories have reported several tumor suppressor genes as potential cancer markers, which play a vital role in gynecological malignancies [1-5]. The high mortality rate of cancers is related to metastasis, which is a process involving alternation in signaling pathways, increased directional cell migration and enhanced cell survival [6-8]. There is accumulating evidence that actin cytoskeleton reorganization is an essential step for cell migration, anchourage-independent growth, and invasion [7]. Members of small GTPases of the Rho family (RhoA, Rac1, and Cdc42) have been found to be an important regulator for cytoskeleton reorganization [7]. RhoA is involved in stress fiber formation, Rac1 is for lamellipodia formation and Cdc42 is for filopodia formation [6, 9]. In mammalian cells, p21-activated serine/threonine kinases (Paks) were initially identified as an effector molecules of Rac1 and Cdc42. Consequently, they were found to be activated by both GTPase-dependent and -independent manners [6, 9]. To date, six members of Paks have been found. They can be classified into two subgroups: Group 1, consisting of Pak1 (Pak), Pak2 (Pak), and Pak3 (Pak), which share >90% homology in their kinase domain and 73% overall homology in their entire sequence; and Group 2, consisting of Pak4-6, which share only ~50% homology with the Pak1 kinase domain [6, 9]. For GTPase-dependent activation manner, Paks bind with Rac1 and Cdc42 in their active, GTP bound state, inhibiting their intrinsic GTPase activity and leading to Paks autophosphorylation. Once phosphorylated, they dissociate from Rac1/Cdc42 to phosphorylate downstream effectors. Although all Paks can bind to GTPases, only Group I Paks can be activated through this binding [6, 9]. In addition, Paks can be activated through a variety of GTPase-independent mechanisms, including direct phosphorylation by other kinases, such as protein kinase B (PKB, also know as Akt) under the influence of lipid signaling involving PI 3-kinase [6, 9, 10]. Due to their complicated activation processes and the presence of multiple downstream effectors, Paks play an important role in a wide range of cellular processes, including cytoskeletal reorganization, cell motility, apoptosis, cell cycle progression, and cell transformation, all of which are required for cancer progression [6, 10, 11]. The differential expression of Paks in ovarian and endometrial cancers is poorly defined. Only Pak1 has been found to be overexpressed in ovarian cancers [12]. Worst yet, the upstream mediators and the downstream signaling pathway(s) of Paks that leads to cancer progression in ovarian and endometrial cancers are still unknown. References (Publications from our group): 1.* Chan QKY, Khoo US, Ngan HYS, Yang CQ, Xue WC, Chan KYK, Chiu PM, Ip PPC, Cheung ANY. Single Nucleotide Polymorphism of Pi-class Glutathione-S-Transferase and Susceptibility to Endometrial Carcinoma. Clin. Cancer Res. 2005; 11: 2981-2985. 2.* Chan KYK, Ozcelik H, Cheung ANY, Ngan HYS, Khoo US. Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer. Cancer Research 2002; 63: 4151-4156. 3.* Shen DH, Chan KYK, Khoo US, Ngan HYS, Xue WC, Chiu PM, Ip PPC, Cheung ANY. Epigenetic and genetic alterations of p33ING1b in ovarian cancer. Carcinogenesis 2005; 26: 855-863. 4.* Chan QKY, Khoo US, Chan KYK, Ngan HYS, Li SS, Chiu PM, Man LS, Ip PPC, Xue WC, Cheung ANY. Promoter Methylation and Differential Expression of pi-class Glutathione-S-Transferase in Endometrial Carcinoma. Journal of Molecular Diagnostics 2005; 7: 8-16. 5. The Hong Kong Cancer Registry. Department of Health Annual Report 2001/2002. Hong Kong, Department of Health, Hospital Authority. 2000. 6. Bokoch GM. Biology of the p21-activated kinases. Annu. Rev. Biochem. 2003; 72: 743-781. 7. Hall A. Rho GTPases and the actin cytoskeleton. Science 1998; 279: 509-514. 8. Vadlamudi RK, Kumar R. P21-activated kinases in human cancer. Cancer Metastasis Rev. 2003; 22: 385-393. 9. Hofmann C, Shepelev M, Chernoff J. The genetics of Pak. J. Cell Sci. 2004; 117: 4343-4354. 10.* Siu MKY, Wong CH, Lee WM, Cheng CY. Sertoli-germ cell anchoring junction dynamics in the testis are regulated by an interplay of lipid and protein kinases. J. Biol. Chem. 2005; 280: 25029-25047. 11. Kumar R, Hung MC. Signaling intricacies take center stage in cancer cells. Cancer Res. 2005; 65: 2511-2515. 12. Schraml P, Schwerdtfeger G, Burkhalter F, Raggi A, Schmidt D, Ruffalo T, King W, Wilber K, Mihatsch MJ, Moch H. Combined array comparative genomic hybridization and tissue microarray analysis suggest PAK1 at 11q13.5-q14 as a critical oncogene target in ovarian carcinoma. Am. J. Pathol. 2003; 163: 985-992. |
| List of Research Outputs |
| Siu K.Y., Avon Foundation-AACR International Scholar-in-Training Grant, American Association for Cancer Research. 2006. |
| Siu K.Y., Woo N.W.S., Ngan H.Y.S. and Cheung A.N.Y., Differential expression of p21-activated kinases (Paks) in ovarian cancer, American Association for Cancer Research's 97th Annual Meeting, March 31-April 5, 2006, in Washington DC, USA. (Dr Siu received the Avon Foundation-AACR International Scholar-in-Training Grant). 2006. |
| Siu K.Y., Yeung C.W., Chiu P.M., Feng H., Ngan H.Y.S., Xue W. and Cheung A.N.Y., p21-activated kinases (Paks) in gestational trophoblastic disease, XIIIth World Congress on Gestational Trophoblastic Diseases. Proceedings P.103. 2005. |
| Researcher : So JCC |
| List of Research Outputs |
| Chen W.Y.W., Hu X., Liang A.C.T., Au W.Y., So J.C.C., Wong M.L.Y., Shen L., Tao Q., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6 deregulating mutations, in gastric lymphoma, Blood. 2006, 108(7): 2373-83. |
| Yip S.F., So J.C.C., Chan A.Y.Y., Liu H.S.Y., Wan T.S.K. and Chan L.C., The lack of association between JAK2 V617F mutation and myelodysplastic syndrome with or without myelofibrosis , Leukemia. 2006, 20(6): 1165. |
| Researcher : Srivastava G |
| Project Title: | Study of epigenetic inactivation of ATM gene in mantle cell lymphoma |
| Investigator(s): | Srivastava G |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2003 |
| Completion Date: | 10/2005 |
| Abstract: |
| To study the importance of methylation of the ATM gene in MCL lymphomagenesis; to study the prognostic impact of ATM methylation in MCL. |
| Project Title: | Role of CD44 and protein kinase C-binding protein 1, novel translocation partners of immunoglobulin heavy chain gene, in the pathogenesis of gastric lymphoma |
| Investigator(s): | Srivastava G |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 09/2004 |
| Abstract: |
| To investigate the role of CD44 and PRKCBP1. For CD44 study: (1) to determine whether the gene amplification of CD44 represents another mechanism of CD44 upregulation in GL cases with strong CD44 expression. (2) to determine whether the hypermethylation of the promoter region of CD44 gene may be responsible for the downregulation of CD44 in GL cases lacking CD44 expression. (3) to determine whether the lack of CD44 mRNA expression detected in the pre- B-cell lines and some mature B-cell lines is due to hypermethylation of the promoter region of CD44 gene and whether the silencing of CD44 in the these cell lines could be partially reversed by the treatment of these cell lines with the demethylation agent 5-aza-2'-deoxycytidine (5-aza-dC). (4) to detect the somatic mutations in CD44 cDNA and genomic DNA in GL, as the presence of mutations at hyaluronan binding sites of CD44 may affect its normal biological function. (5) to identify different CD44 splicing variants (CD44v) in GL since a correlation between expression of CD44v and adverse prognosis has been reported in several subtypes of human carcinoma and in NHL. (6) to correlate the findings of the IGH/CD44 translocation, gene amplification of CD44, hypermethylation of CD44 promoter, CD44 expression, somatic mutations in CD44 cDNA and the different CD44 splicing variants in GL with the clinico-pathological features (CPC) to define prognostic subgroups. (7) to clone the wild-type cDNA CD44 and CDNA lacking the leader peptide, as the result of JGH/CD44 translocation in GL, and perform the transfection assays for their cellular localization and to determine whether this variant of CD44 without the leader peptide has acquired additional tumor transforming function. For PRKCBPI study: (1)to examine PRKCBP1 mRNA expression in primary B cells by in-situ hybridization in normal lymphoid tissues including reactive tonsil, lymph node and spleen. (2) to examine PRKCBP1 mRNA expression by Northern blot hybridization and RT-PCR in the normal peripheral B-lymphocytes and in human B-lineage tumor cell lines corresponding to different stages of B-cell development. (3) to determine whether the PRKCBP1 mRNA is differentially expressed in the tumor cells of GL. (4) to detect the somatic mutations in PRKCBP1 CDNA sequences are prone to mutations coding (a)8 microsatellite in PRKCBP1 mRNA. Repetitive DNA sequences are prone to mutations. (5) to correlate the findings of the IGH/PRKCBP1 translocation, differential PRKCBP1 mRNA expression and somatic mutations in PRKCBP1 cDNA in GL with the CPC to define prognostic subgroups. (6) to clone the wild-type PRKCBP1 cDNA lacking the first 11 non-coding exons, as the result of IGH/PRKCBP1 translocation in GL, and perform the transfection studies for the cellular localization of their protein to predict possible function of this gene. |
| Project Title: | Role of CD44 and protein kinase C-binding protein 1, novel translocation partners of immunoglobulin heavy chain gene, in the pathogenesis of gastric lymphoma |
| Investigator(s): | Srivastava G |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 01/2005 |
| Abstract: |
| N/A |
| Project Title: | Characterization of the role of immunoglobulin heavy and light chain [kappa] and [lambda] gene translocations in the pathogenesis of gastric lymphoma |
| Investigator(s): | Srivastava G, Liang RHS |
| Department: | Pathology |
| Source(s) of Funding: | Michael Kadoorie Cancer Genetics Research Fund |
| Start Date: | 01/2005 |
| Abstract: |
| To clone IGH-related translocations in GL at both IGHJ and 5' S[mu] region by LDI-PCR and those involving switch region sequences 3' to the S[mu], S[gamma]1-4, and S[alpha]1-2 regions by LDV-PCR; to clone IG[kappa]- and IG[lambda]-related translocations involving the joining region in GL by LDI-PCR; to determine the frequency of the known and novel IG (IGH, IG[kappa], IG[lambda])-related translocations identified by us in GL by direct PCR on genomic DNA; to study the expression of novel IG translocation partner genes in GL by immunostaining to determine whether the over expression of these genes in the tumor cells is associated with the IG translocation of these genes in GL; to determine the mRNA expression of novel IG translocation partner genes in the normal peripheral B-cells and human B-lineage tumor cell lines that correspond to different stages of B-cell development, loss of the normal control mechanisms regulating expression of these novel IG partner genes may contribute to malignant transformation in lymphomas; to analyze the mutations of incoming novel IG translocation partner genes in GL since in B cells, where the somatic hypermutation mechanism is active, mutations of the incoming gene may be observed and may contribute to the neoplastic phenotype; to determine the transforming and tumorigenic potential of each of the overexpressed novel IG translocation partner genes by in vitro growth properties and in vivo tumorigenicity assays; to determine the prevalence of all the cloned novel IG-related translocations identified by us in GL in nodal specimens (MZBCL and DLBCL) by direct PCR, for comparison of IG translocations in gastric MALT and DLBCL with their respective nodal counterparts. |
| Project Title: | Molecular mechanisms and clinicopathological significance of the aberrant nuclear BCL10 expression and constitutive NF-[kappa]B activation in EBV-associated nasal NK/T-cell lymphoma |
| Investigator(s): | Srivastava G |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 10/2005 |
| Abstract: |
| N/A |
| Project Title: | Molecular mechanisms and clinicopathological significance of the aberrant nuclear BCL10 expression and constitutive NF-[kappa]B activation in EBV-associated nasal NK/T-cell lymphoma |
| Investigator(s): | Srivastava G, Liang RHS |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 10/2005 |
| Abstract: |
| To analyze BCL10 and NF-χB expression in the cytoplasmic and nuclear protein fractions prepared from normal NK cells, NL specimens and NK tumor cell lines by Western blot analysis NF-χB transfer from cytoplasm to nucleus is the hallmark of its activation; to determine whether the nuclear localization of BCL10 in N1 is due to constitutive hyperphosphorylation of endogenous BCL10 by Western blot analysis and also by metabolic labeling experiments of NK tumor cell lines using 32P-orthophosphate; to determine whether t(1;14)(p22; q32) or t(11;18)(q21;q21), which are associated with the BCL10 nuclear expression in gastric MALT lymphoma, are also present in NL; to determine whether BCL10 nuclear expression present in NL is due to other chromosomal translocations involving the BCL10 gene locus (1p22) by 5' RACE(5' rapid amplification of cDNA ends), resulting either (i) in the upregulation of BCL10 due to promoter substitution, or (ii) in fusion gene products involving BCL10 and novel fusion partner genes; for comparison, determine the subcellular localization of BCL10 and NF-χB expression by immunohistochemistry in tumor biopsy specimens of (i) nasal-type NK/T cell lymphoma occurring in non-nasal areas, (ii) aggressive NK cell lymphoma/leukemia, and (iii) non-nasal peripheral T-cell lymphoma (PTCL); and examine the status of EBV infection in these nasal-type NK/T-cell lymphoma lymphomas & non-nasal PTCL by EBV EBER in-situ hybridization on cases with nuclear BCL10, as it is possible that BCL10 nuclear localization is related to EBV infection; to determine the usefulness of the detection of aberrant nuclear BCL10 and NF-χB expression immunohistochemistry as a potential tumor marker for the diagnosis of NL (and also in nasal-type NK/T cell lymphomas & non-nasal PTCL with nuclear BCL10 expression as detected in objective#5); to examine whether nuclear expression of BCL10 expression or NFχB activation can be used as an independent prognostic marker to indicate more advanced or more aggressive NL (and also in nasal-type NK/T-cell lymphomas & non-nasal PTCL with nuclear BCL10 expression as detected in objective#5). |
| Project Title: | To identify tumor suppressor genes in the commonly deleted region of 6q in nasal NK/T-cell lymphoma by employing array-CGH and epigenetic approach |
| Investigator(s): | Srivastava G, Liang RHS, Tao Q |
| Department: | Pathology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 03/2006 |
| Abstract: |
| Putative natural killer (NK) cell lymphoma/leukemia is a rare group of recently characterized hematolymphoid malignancies. They are highly aggressive and frequently present in extranodal sites, including the nasal area and the upper aerodigestive system, and non-nasal areas such as the skin and the gastrointestinal tract. By clinicopathological features, they can be classified into nasal NK/T-cell lymphoma (NL), nasal-type NK/T-cell lymphoma occurring in non-nasal areas, and NK cell lymphoma/leukemia. Primary NL represent the second most frequent group of extra-nodal lymphomas in Hong Kong Chinese. They are reported mostly from Asia, Mexico, and South America, but are extremely rare in Western countries. So far there have been limited data on the genetic aberrations in NL. However, preliminary results from a small number of NL cases investigated by karyotyping, metaphase-CGH and LOH studies have consistently shown a commonly deleted region of 6q21-25 in NL. Refinement of allelic loss at 6q might lead to the identification of novel TSG candidates involved in the tumorigenesis of NL. Unfortunately, owing to marked tumor necrosis and the difficulty of obtaining adequate biopsy materials from the nasal areas, procurement of the large amount of tumor tissue that are required for a comprehensive search for allelic loss at this region is not feasible. Moreover, this approach will require a laborious search for nearby genes by position cloning once the smallest altered locus is identified. The discovery of numerous hypermethylated promoters of TSG, along with a better understanding of gene-silencing mechanisms, has moved the subject of DNA methylation from obscurity to recognition of methylation as an important alternative mechanism of TSG inactivation in cancer. The incorporation of epigenetic analysis methods into microarray technology can yield quantitative and qualitative information on DNA methylation throughout the genome. This epigenetic approach to identify TSG candidates in NL is now feasible for NL due to the availability of authentic NL and aggressive NK-cell lymphoma/leukemia cell lines. The overall aim of this study is to identify TSG candidates in the commonly deleted region of 6q in NL first by array-CGH of NL cell lines and, second by employing an epigenetic approach based on subtractive, cancer genomic and microarray analyses. Clone-based array-CGH, with an average resolution of 1.3 Mb, have been previously applied successfully to gain insights into the pathogenetic mechanisms of cancer development. Major Aims: 1. To perform array-CGH to map deletions in NL and aggressive NK-cell lymphoma/leukemia cell lines for further refinement of allelic loss in the commonly deleted region of chromosome 6q in NL. 2. To identify TSG candidates in NL by the detection of upregulated transcripts after pharmacological demethylation and HDAC inhibition of TSG promoters in NL cell lines by: (1) cDNA microarray hybridization using GeneChip® expression arrays from Affymetrix® using the cDNA subtracted between mock-treated and DAC- and TSA-treated 5 NL and 4 aggressive NK-cell lymphoma/leukemia cell lines as the probe, and (2) by direct PCR screening on the subtracted cDNA for gene transcripts from the chromosome region 6q25.2-q25.3 and other specific regions deleted at 6q as identified by array-CGH in this study. 3. To determine the status of DNA hypermethylation by methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS) of the TSG promoters in 6q (identified in this study by the combination of 1 and 2 above) and correlate the methylation status of these gene promoters with the down-regulation of the expression of these genes detected by semi-quantitative RT-PCR in the NL and aggressive NK-cell lymphoma/leukemia cell lines and NL tumor biopsy specimens. 4. To perform the tumor suppressive functional assays of the selected TSG candidates in 6q (identified in this study by the combination of 1, 2 and 3) by standard transfection and colony formation assays. |
| List of Research Outputs |
| Chan K.W., Lee P.Y., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Clinical relevance of Fas expression in oesophageal squamous cell carcinoma, Journal of Clinical Pathology . 2006, 59(1): 101-4. |
| Chan K.W., Lee P.Y., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Fas expression is a favorable prognostic factor in esophageal squamous cell carcinoma, The Fourth Asia-Pacific International Academy of Pathology Congress (IAP2005), 22-26 August 2005, Beijing, China. 2005. |
| Chen W.Y.W., Hu X., Liang A.C.T., Au W.Y., So J.C.C., Wong M.L.Y., Shen L., Tao Q., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6 deregulating mutations, in gastric lymphoma, Blood. 2006, 108(7): 2373-83. |
| Fatima S., Chui C.H., Tang W.K., Hui K.S., Au H.W., Li W.Y., Wong M.M., Cheung F., Tsao G.S.W., Lam K...Y., Beh S.L., Wong J., Law S.Y.K., Srivastava G., Ho K.P., Chan A.S. and Tang J.C.O., Transforming capacity of two novel genes JS-1 and JS-2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma, International Journal of Molecular Medicine. 2006, 17(1): 159-170. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Wong M.L.Y., Shen L., Wong K.Y., Au W.Y., Cheung W.L., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Au W.Y., Wong M.L.Y., Shen L., Wong K.Y., Wan T.S.K., Cheung W.L., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006 . 2006. |
| Ko J.M.Y., Yau W.L., Chan P.L., Lung H.L., Yang L.C., Lo P.H.Y., Tang J.C.O., Srivastava G., Stanbridge E.J. and Lung M.L., Functional evidence of decreased tumorigenicity associated with monochromosome transfer of chromosome 14 in esophageal cancer and the mapping of tumor-suppressive regions to 14q32, Genes Chromosomes Cancer. 2005, 43(3): 284-293. |
| Kwong Y.L., Chow C., Kumana C.R., Srivastava G. and Au W.Y., Arsenic trioxide in mantle cell lymphoma, Blood (American Society of Hematology 2005 Annual Meeting Abstracts) . 2005, 106 (11): 283B-284B 4814 Part 2 Nov 16 2005. |
| Lo P.H., Leung A.C., Kwok C.Y., Cheung W.S., Ko J.M., Yang L.C., Law S.Y.K., Wang L.D., Li J., Stanbridge E.J., Srivastava G., Tang J.C.O., Tsao G.S.W. and Lung M.L., Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9, Oncogene. 2006. |
| Ren Y., Law S.Y.K., Huang X., Lee P.Y., Bacher M., Srivastava G. and Wong J., Macrophage migration inhibitory factor stimulates angiogenic factor expression and correlates with differentiation and lymph node status in patients with esophageal squamous cell carcinoma, Annals of Surgery. 2005, 242(1): 55-63. |
| Srivastava G., Editor of International Journal of Medical Sciences . Ivyspring International Publisher, 2005. |
| Tang W.K., Fatima S., Chui C.H., Ou T.M., Hui K.S., Wong M.M., Wong J., Law S.Y.K., Tsao G.S.W., Lam A.K.Y., Beh S.L., Srivastava G., Ho K.P. and Tang J.C.O., Oncogenic properties of a novel gene located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma, Proceedings of the 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress of Biochemistry and Molecular Biology, Kyoto, Japan, June 18-23, 2006. |
| Tsui I.F., Iqbal J., DeLeeuw R.J., Srivastava G., Shimizu N., Chan W.C. and Lam W.L., Genome-wide identification of novel regions of DNA copy number alterations in natural killer cell lymphoma by array comparative genomic hybridization, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006. |
| Wong M.L.Y., Tao Q., Fu L., Wong K.Y., Qiu G.H., Law F.B.F., Tin P.C., Cheung W.L., Lee P.Y., Tang J.C.O., Tsao G.S.W., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma, International Journal of Oncology. 2006, 28(3): 767-73. |
| Ying J., Li H., Seng T.J., Langford C., Srivastava G., Tsao G.S.W., Putti T., Murray P., Chan A.T.C. and Tao Q., Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation, Oncogene. 2006, 25(7): 1070-80. |
| Ying J., Srivastava G., Hsieh W.S., Gao Z., Murray P., Liao S.K., Ambinder R. and Tao Q., The stress-responsive gene GADD45G is a functional tumor suppressor, with its response to environmental stresses frequently disrupted epigenetically in multiple tumors, Clinical Cancer Research. 2005, 11(18): 6442-6449. |
| Yip B.H., Guo T., Hu X., Wong K.Y., Chen W.Y.W., Au W.Y., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Yip B.H., Guo T., Hu X., Au W.Y., Wong K.Y., Wan T.S.K., Chen W.Y.W., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) involving immunoglobulin heavy chain gene locus in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006. |
| Zhang M., Ko K.H., Lam Q.L.K., Srivastava G., Zheng B., Lau Y.L. and Lu L., Expression and function of TNF family member B cell-activating factor in the development of autoimmune arthritis, International Immunology. 2005, 17(8): 1081-1092. |
| Researcher : Sze MF |
| List of Research Outputs |
| Sze M.F., Ching Y.P., Jin D. and Ng I.O.L., Dysregulation of Mitotic Spindle Checkpoint Control in Hepatocellular Carcinomas , 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
| Researcher : Tam IYS |
| List of Research Outputs |
| Tam I.Y.S., Chung L.P., Suen W.S., Wang E., Wong M.C.M., Ho K.K., Lam W.K., Chiu S.W., Girard L., Minna J.D., Gazdar A.F. and Wong M.P., Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features, Clinical Cancer Research. 2006, 12(5): 1647-53. |
| Wong M.P., Chua D.T.T., Ho J.C.M., Tam I.Y.S., Lam W.K. and Chung L.P., Mutational status of epidermal growth factor receptor is the only predictor of clinical response to gefitinib treatment in non-small cell lung cancer, 97th AACR Annual Meeting, Washington, DC, April 1-5, 2006 . 2006. |
| Researcher : Tam S |
| List of Research Outputs |
| Au W.Y., Tam S., Fong B.M. and Kwong Y.L., Elemental arsenic entered the cerebrospinal fluid during oral arsenic trioxide treatment of meningeal relapse of acute promyelocytic leukemia , Blood. 2006, 107(7): 3012-3013. |
| Researcher : Tang JCO |
| List of Research Outputs |
| Fatima S., Chui C.H., Tang W.K., Hui K.S., Au H.W., Li W.Y., Wong M.M., Cheung F., Tsao G.S.W., Lam K...Y., Beh S.L., Wong J., Law S.Y.K., Srivastava G., Ho K.P., Chan A.S. and Tang J.C.O., Transforming capacity of two novel genes JS-1 and JS-2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma, International Journal of Molecular Medicine. 2006, 17(1): 159-170. |
| Ko J.M.Y., Yau W.L., Chan P.L., Lung H.L., Yang L.C., Lo P.H.Y., Tang J.C.O., Srivastava G., Stanbridge E.J. and Lung M.L., Functional evidence of decreased tumorigenicity associated with monochromosome transfer of chromosome 14 in esophageal cancer and the mapping of tumor-suppressive regions to 14q32, Genes Chromosomes Cancer. 2005, 43(3): 284-293. |
| Lo P.H., Leung A.C., Kwok C.Y., Cheung W.S., Ko J.M., Yang L.C., Law S.Y.K., Wang L.D., Li J., Stanbridge E.J., Srivastava G., Tang J.C.O., Tsao G.S.W. and Lung M.L., Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9, Oncogene. 2006. |
| Tang W.K., Fatima S., Chui C.H., Ou T.M., Hui K.S., Wong M.M., Wong J., Law S.Y.K., Tsao G.S.W., Lam A.K.Y., Beh S.L., Srivastava G., Ho K.P. and Tang J.C.O., Oncogenic properties of a novel gene located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma, Proceedings of the 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress of Biochemistry and Molecular Biology, Kyoto, Japan, June 18-23, 2006. |
| Wong M.L.Y., Tao Q., Fu L., Wong K.Y., Qiu G.H., Law F.B.F., Tin P.C., Cheung W.L., Lee P.Y., Tang J.C.O., Tsao G.S.W., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma, International Journal of Oncology. 2006, 28(3): 767-73. |
| Researcher : Tao Q |
| List of Research Outputs |
| Chen W.Y.W., Hu X., Liang A.C.T., Au W.Y., So J.C.C., Wong M.L.Y., Shen L., Tao Q., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6 deregulating mutations, in gastric lymphoma, Blood. 2006, 108(7): 2373-83. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Wong M.L.Y., Shen L., Wong K.Y., Au W.Y., Cheung W.L., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Au W.Y., Wong M.L.Y., Shen L., Wong K.Y., Wan T.S.K., Cheung W.L., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006 . 2006. |
| Wong M.L.Y., Tao Q., Fu L., Wong K.Y., Qiu G.H., Law F.B.F., Tin P.C., Cheung W.L., Lee P.Y., Tang J.C.O., Tsao G.S.W., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma, International Journal of Oncology. 2006, 28(3): 767-73. |
| Ying J., Li H., Seng T.J., Langford C., Srivastava G., Tsao G.S.W., Putti T., Murray P., Chan A.T.C. and Tao Q., Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation, Oncogene. 2006, 25(7): 1070-80. |
| Researcher : Tin PC |
| List of Research Outputs |
| Wong M.L.Y., Tao Q., Fu L., Wong K.Y., Qiu G.H., Law F.B.F., Tin P.C., Cheung W.L., Lee P.Y., Tang J.C.O., Tsao G.S.W., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma, International Journal of Oncology. 2006, 28(3): 767-73. |
| Zhu H., Lam D.C., Han K.C., Tin P.C., Suen W.S., Wang E., Lam W.K., Cai W.W., Chung L.P. and Wong M.P., High resolution analysis of genomic aberrations by metaphase and array comparative genomic hybridization identifies candidate tumour genes in lung cancer cell lines, Cancer Letters. 2006. |
| Researcher : To KW |
| List of Research Outputs |
| Ma L., Chan K.W., Trendell-Smith N.J., Wu A.Y.Y., Tian L., Lam A.C., Lo C.K., Chik S.C.C., Ko K.H., To K.W., Kam C.S.K., Li X., Yang C., Leung S.Y., Ng M.H. and Huang F., Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains, In: Ma L, Chan KW, Trendell-Smith NJ, Wu A, Tian L, Lam AC, Chan AK, Lo CK, Chik S, Ko KH, To CK, Kam SK, Li XS, Yang CH, Leung SY, Ng MH, Stott DI, MacPherson GG, Huang FP, European Journal of Immunology (In This Issue highlight, Editorial Comments). 2005, 35(11): 3364-75. |
| To K.W., Wong O.H., Li H.B., Chan S.F., Ma L., Cheung Y.L., Ko K.H., Chiang A.K.S. and Huang F., The effects of Bergapten in modulating dendritic cells (DC) functions for DC-based tumor vaccines, 10th Research Postgraduate Symposium, Hong Kong. December 3. 2005. |
| Researcher : Trendell-Smith NJ |
| List of Research Outputs |
| Ma L., Chan K.W., Trendell-Smith N.J., Wu A.Y.Y., Tian L., Lam A.C., Lo C.K., Chik S.C.C., Ko K.H., To K.W., Kam C.S.K., Li X., Yang C., Leung S.Y., Ng M.H. and Huang F., Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains, In: Ma L, Chan KW, Trendell-Smith NJ, Wu A, Tian L, Lam AC, Chan AK, Lo CK, Chik S, Ko KH, To CK, Kam SK, Li XS, Yang CH, Leung SY, Ng MH, Stott DI, MacPherson GG, Huang FP, European Journal of Immunology (In This Issue highlight, Editorial Comments). 2005, 35(11): 3364-75. |
| Researcher : Tsang STY |
| List of Research Outputs |
| Tse Y.T., Chan Y.K., Chan S.Y., Tsang S.T.Y., Sham P.C. and Khoo U.S., Estrogen Receptor a Gene Polymorphisms and Breast Cancer Risk in Chinese, HUGO's 11th Human Genome Meeting, Helsinki, Finland. . 2006. |
| Researcher : Tse YT |
| List of Research Outputs |
| Tse Y.T., Chan Y.K., Chan S.Y., Tsang S.T.Y., Sham P.C. and Khoo U.S., Estrogen Receptor a Gene Polymorphisms and Breast Cancer Risk in Chinese, HUGO's 11th Human Genome Meeting, Helsinki, Finland. . 2006. |
| Researcher : Tsui WY |
| List of Research Outputs |
| Guo D.L., Zhang J., Yuen S.T., Tsui W.Y., Chan A.S.Y., Ho C., Chen X. and Leung S.Y., Reduced Expression of EphB2 that parallels invasion and metastasis in colorectal tumors, Keystone Symposia: Stem Cells, Senescence and Cancer, 25-30 October . 2005. |
| Guo D.L., Zhang J., Yuen S.T., Tsui W.Y., Chan A.S.Y., Ho C., Ji J., Leung S.Y. and Chen X., Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumors, Carcinogenesis. 2005, 27(3): 454-464. |
| Researcher : Tung KK |
| List of Research Outputs |
| Tung K.K., Wong C.M. and Ng I.O.L., Underexpression of hepatocyte growth factor activator inhibitors HAI-1 and HAI-2 was assoicated with promoter hypermethylation in hepatocellular carcinoma, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April 2006. |
| Researcher : Wan TSK |
| List of Research Outputs |
| Au W.Y., Pang A.W.K., Wan T.S.K., Ma E.S.K., Cheng L.C. and Kwong Y.L., Concomitant post-transplantation lymphoproliferative disease and therapy-related myelodysplastic syndrome after lung transplantation , The Journal of Heart and Lung Transplantation . 2006, 25(2): 259-260. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Au W.Y., Wong M.L.Y., Shen L., Wong K.Y., Wan T.S.K., Cheung W.L., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006 . 2006. |
| Leung R., Chou E.E., Au W.Y., Chow C., Kwong Y.L., Lin S.Y., Ma E.S.K., Wan T.S.K. and Wong K.F., CD4+/CD56+ hematologic malignancy with rearranged MLL gene, Human Pathology . 2006, 37(2): 247-249. |
| Yip B.H., Guo T., Hu X., Au W.Y., Wong K.Y., Wan T.S.K., Chen W.Y.W., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) involving immunoglobulin heavy chain gene locus in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006. |
| Yip S.F., Wan T.S.K., Lie A.K.W., Liu H.S.Y. and Chan L.C., Monitoring of chronic myeloid leukemia (CML) imatinib response by fluorescence-in-situ-hybridization (FISH), American Society of Hematology, Atlanta, Georgia. December 10-13, 2005. Abstract No. 4837. Blood. 2005, 106(11) Part 2: 289b. |
| Yip S.F., So J.C.C., Chan A.Y.Y., Liu H.S.Y., Wan T.S.K. and Chan L.C., The lack of association between JAK2 V617F mutation and myelodysplastic syndrome with or without myelofibrosis , Leukemia. 2006, 20(6): 1165. |
| Yip S.F., Wan T.S.K., Chan L.C. and Chan G.C.F., Trisomy 4 as sole karyotypic abnormality in acute lymphoblastic leukemia: Different clinical features and treatment response between B and T phenotypes?, Cancer Genetics and Cytogenetics. 2006, 164: 94-95. |
| Researcher : Wang X |
| Project Title: | Downregulation of MAD2 expression and its significance in chemodrug sensitization in nasopharyngeal carcinoma cells |
| Investigator(s): | Wang X, Nicholls JM, Tsao GSW, Jin D |
| Department: | Anatomy |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 09/2003 |
| Abstract: |
| To confirm that MAD2 expression is downregulated in clinical samples of NPC; to determine the mechanism by which MAD2 is downregulated in NPC; to establish whether upregulation of MAD2 expression can sensitize NPC cells to chemotherapy. |
| Project Title: | Downregulation of MAD2 expression and its significance in chemodrug sensitization in nasopharyngeal carcinoma cells |
| Investigator(s): | Wang X, Nicholls JM, Tsao GSW, Jin D |
| Department: | Anatomy |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 09/2003 |
| Abstract: |
| N/A |
| Project Title: | The role fo MAD2 in overcoming cisplatin resistance in testicular germ cell tumors |
| Investigator(s): | Wang X, Jin D |
| Department: | Anatomy |
| Source(s) of Funding: | Lance Armstrong Foundation - General Award |
| Start Date: | 10/2003 |
| Abstract: |
| To investigate the association between decreased MAD2 protein expression and cisplatin resistance in TGCT cells; to study if exogenous expression of the MAD2 gene in TGCT cells can lead to chemosensitization to cisplatin in TGCT cells; to demonstrate that downregulation of MAD2 results in resistance ot cisplatin in TGCT cells; to characterize the role of MAD2 in cisplatin-induced cell death inTGCT cells; to identify binding partners of MAD2 in response to cisplatin-induced DNA damage. |
| Project Title: | Significance of MAD2 expression to chromosomal instability in prostate cancer |
| Investigator(s): | Wang X, Wong Y C, Jin D Y |
| Department: | Anatomy |
| Source(s) of Funding: | Association for International Cancer Research - General Award |
| Start Date: | 04/2004 |
| Abstract: |
| To correlate MAD2 expression with genomic instability in prostate cancer specimens; to show that MAD2 expression is essential for a functional mitotic checkpoint in prostate cancer cells; to demonstrate that downregulation of MAD2 leads to mitotic checkpoint defect and increased CIN in prostate cancer cells. • To investigate if promoter hypermethylation contributes to decreased MAD2 expression in prostate cancer |
| Project Title: | Role of ld-1 in the proliferation of ovarian cancer cells |
| Investigator(s): | Wang X, Wong YC |
| Department: | Anatomy |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 03/2005 |
| Completion Date: | 02/2006 |
| Abstract: |
| The main objectives of this project are: 1) To generate ovarian cancer cell lines expressing ectopic Id-1. 2) To study if ectopic Id-1 expression could promote proliferation in ovarian cancer cells. 3) To investigate if the Id-1-induced ovarian cancer cell proliferation is mediated through EGFR pathway. |
| Project Title: | Role of TWIST in prostate cancer and its implication as a novel therapeutic target |
| Investigator(s): | Wang X |
| Department: | Anatomy |
| Source(s) of Funding: | Incentive Award for RGC CERG Fundable But Not Funded Projects |
| Start Date: | 07/2005 |
| Completion Date: | 06/2006 |
| Abstract: |
| N/A |
| Project Title: | Molecular mechanisms involved in the suppressive effects of garlic derivatives on cell growth and motility in prostate cancer cells |
| Investigator(s): | Wang X, Wong Y C, Jin D Y |
| Department: | Anatomy |
| Source(s) of Funding: | American Institute for Cancer Research (AICR) - General Award |
| Start Date: | 08/2005 |
| Abstract: |
| To study the role of the mitotic checkpoint in SAC and SAMC-induced androgen independent prostate cancer cell death; to investigate if SAC and SAMC have any inhibitory effect on the invasive ability of prostate cancer cells and to determine the molecular mechanisms responsible. Specific Aim 3. To examine if SAC and SAMC can enhance the sensitivity of prostate cancer cells to chemotherapeutic drugs. |
| Project Title: | Significance of Id-1 upregulation and its association with EGFR in bladder cancer |
| Investigator(s): | Wang X |
| Department: | Anatomy |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 06/2006 |
| Abstract: |
| Background: Bladder cancer is one of the common urological cancers. Although majority of bladder cancers are superficial at presentation, 20% of the bladder cancer patients present with muscle invasive disease at diagnosis (i.e. stage T2-T4 tumours). If untreated, fewer than 15% of those patients can survive more than two years. Two main challenges remain for the treatment of this cancer which are (i) the ability to identify the small but significant number of patients with non-muscle-invasive disease who will progress to muscle-invasive disease, and (ii) to improve current treatment of the muscle invasive bladder cancer. Recently, our group identified a potential oncogene, Id-1 (inhibitor of differentiation or DNA binding), and demonstrated its significance in the development of human prostate cancer (Ouyang et al., J Urol 167: 2598, 2002), nasopharyngeal carcinoma (Wang et al., 35:42-49, 2002) and ovarian cancer (Zhang et al., Br J Cancer 91: 2042, 2004). Since then, upregulation of Id-1 has been reported in over 20 types of human cancer such as breast, pancreas, cervical, melanoma, and head and neck (Reviewed by Wong et al., 9:279-289, 2004). In addition, increased Id-1 expression levels are associated with advanced tumour stage as well as poor prognosis (Maruyama et al., Am J Pathol 155: 815, 1999; Schindl et al., Cancer Res 61: 5703, 2001; Ouyang et al., J Urol 167: 2598, 2002). Furthermore, patients with higher levels of Id-1 have much shorter overall survival than the patients with relatively lower Id-1 expression in ovarian cancer (Schindl et al., Clin Cancer Res 9:779, 2003). Recent evidence also shows that Id-1 is able to induce epidermal growth factor receptor (EGFR) expression, indicating that the oncogenic effect of Id-1 may be mediated through activation of the EGFR pathway (Ling et al., Carcinogenesis 25: 517, 2004; Zhang et al., Br J Cancer 91: 2042, 2004). In bladder cancer, upregulation of EGFR has been frequently reported in tissue samples (Neal et al., Lancet 1: 366, 1985; Mellon et al., J Urol 153: 919, 1995). Several studies have correlated EGFR positively with tumour stage, tumour progression, and poor clinical outcome in bladder cancer patients (Neal et al., Cancer 65: 1619, 1990; Mellon et al., J Urol 153: 919, 1995; Nguyen et al., Am J Clin Pathol 101: 166, 1994). Furthermore, it was recently reported that treatment of bladder cancer cells with ZD1839 (or Iressa), a highly selective EGFR inhibitor, resulted in radiosensitization to ionizing radiation (Maddineni et al., Br J Cancer 92: 125, 2005), indicating that EGFR may be a potential therapeutic target in improving treatment efficiency of bladder cancer. Based on the evidence that Id-1 is able to activate EGFR pathway, we hypothesized that activation of the EGFR pathway observed in bladder cancer may be a result of overexpression of Id-1, as indicated in other cancers (Ling et al., Carcinogenesis 25: 517, 2004; Zhang et al., Br J Cancer 91: 2042, 2004 ). Purpose of the project: The aim of this project is to study the significance of Id-1 in bladder cancer and provide an alternative target of the EGFR pathway for the treatment of bladder cancer. This will be achieved through the following objectives: 1). To study differential Id-1 protein expression between normal and malignant bladder cancer specimens and correlate its expression levels with EGFR in different stage bladder cancer specimens. 2). To study if ectopic Id-1 expression in bladder cancer cell lines could lead to upregulation of EGFR and demonstrate the significance of Id-1 overexpression in bladder cancer cell proliferation. 3). To study if inactivation of Id-1 could suppress EGFR expression and investigate if downregulation of Id-1 could lead to inhibition of bladder cancer cell growth. |
| List of Research Outputs |
| Researcher : Wong CL |
| List of Research Outputs |
| Ma E.S.K., Wong C.L., Lai K.T., Chan E.C., Yam W.C., Chan A.C. and Chan A.C.Y., Kocuria kristinae infection associated with acute cholecystitis. , BMC Infect Dis. UK, 2005, 5(1): 60. |
| Researcher : Wong CM |
| Project Title: | Genetic and epigenetic alterations of serine protease inhibitor TFPI-2 in hepatocellular carcinoma. |
| Investigator(s): | Wong CM, Ng IOL |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 10/2005 |
| Abstract: |
| Liver cancer is a major malignancy in the world and is particularly prevalent in this region, being the second most common fatal cancer in Asia including Hong Kong. Delineation of alterations or dysregulations of major cellular pathways in liver cancer is important as this can provide novel opportunities for diagnosis, clinical significance, prognosis and therapeutic interventions for patients with this cancer. As part of our long-standing effort in search for and identification of tumor suppressor genes important in liver cancer development and progression, we have used high-throughput microarray approach to screen for methylation in gene silencing in liver cancer (hepatocellular carcinoma, HCC) and have successfully selected a number of putative tumor suppressor genes (Wong et al., 2004). One of the candidate genes we identified with this technology is TFPI-2 (tissue-factor pathway inhibitor-2), which is a newly identified Kunitz-type serine protease inhibitor. TFPI-2 is abundantly expressed in umbilical vein endothelial cells, placenta, and liver. TFPI-2 inhibits gelatinolysis and caseinolysis by trypsin, plasmin, α-chymotrypsin, and pancreatic elastase (Rao et al 1995). TFPI-2 is believed to have important roles in invasive growth of tumor cells. Pervious, studies have been indicated that TFPI-2 involved in inhibiting degradation of extracellular matrix (ECM) in fibrosarcoma cell model (Rao et al., 1998). Our preliminary data have shown that this gene is frequently underexpressed and epigenetically silenced by methylation in human HCC cells and human HCC samples. In this proposal, we aim to delineate its roles in HCC and aim to 1) characterize the expression of TFPI-2 in human liver cancers and evaluate their clinicopathological and prognostic significance, 2) delineate the epigenetic and genetic alterations of TFPI-2 in liver cancer, and 3) assess the biochemical properties and anti-tumorigenic functions of TFPI-2 in liver cancer. Findings derived from this study may be of potential use for the development of effective and novel therapeutic interventions to target these genes in liver cancer. Reference Rao CN, Gomez DE, Woodley DT, Thorgeirsson UP. Novel extracellular matrix-associated serine proteinase inhibitors from human skin fibroblasts. Arch Biochem Biophys 1995; 317: 311-4. Rao CN, Cook B, Liu Y, Chilukuri K, Stack MS, Foster DC, Kisiel W, Woodley DT. HT-1080 fibrosarcoma cell matrix degradation and invasion are inhibited by the matrix-associated serine protease inhibitor TFPI-2/33 kDa MSPI. Int J Cancer 1998 ; 76: 749-56 |
| List of Research Outputs |
| Chin K.T., Wong C.M., Ng I.O.L. and Jin D., Functional characterization of liver-enriched transcription factor CREB-H (poster 1989). , The American Society for Cell Biology 45th Annual Meeting, San Francisco, California, USA, December 10-14, 2005.. 2005. |
| Leung H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity, Proc Natl Acad Sci U S A. 2005, 102: 15207-15212. |
| Tung K.K., Wong C.M. and Ng I.O.L., Underexpression of hepatocyte growth factor activator inhibitors HAI-1 and HAI-2 was assoicated with promoter hypermethylation in hepatocellular carcinoma, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April 2006. |
| Wong C.M., Cheung O.F. and Ng I.O.L., Epigenetic inactivation of serine protease inhibitor TFPI-2 in human HCC, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April 2006. |
| Wong C.M., Yam J.W.P., Ching Y.P., Yau T.O., Leung T.H.Y., Jin D. and Ng I.O.L., Rho GTPase-Activating Protein Deleted in Liver Cancer Suppresses Cell Proliferation and Invasion in Hepatocellular Carcinoma, Cancer Research. 2005, 65: 8861-8868. |
| Researcher : Wong KY |
| List of Research Outputs |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Wong M.L.Y., Shen L., Wong K.Y., Au W.Y., Cheung W.L., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Au W.Y., Wong M.L.Y., Shen L., Wong K.Y., Wan T.S.K., Cheung W.L., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006 . 2006. |
| Wong M.L.Y., Tao Q., Fu L., Wong K.Y., Qiu G.H., Law F.B.F., Tin P.C., Cheung W.L., Lee P.Y., Tang J.C.O., Tsao G.S.W., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma, International Journal of Oncology. 2006, 28(3): 767-73. |
| Yip B.H., Guo T., Hu X., Wong K.Y., Chen W.Y.W., Au W.Y., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Yip B.H., Guo T., Hu X., Au W.Y., Wong K.Y., Wan T.S.K., Chen W.Y.W., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) involving immunoglobulin heavy chain gene locus in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006. |
| Researcher : Wong MLY |
| List of Research Outputs |
| Chen W.Y.W., Hu X., Liang A.C.T., Au W.Y., So J.C.C., Wong M.L.Y., Shen L., Tao Q., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6 deregulating mutations, in gastric lymphoma, Blood. 2006, 108(7): 2373-83. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Wong M.L.Y., Shen L., Wong K.Y., Au W.Y., Cheung W.L., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Hu X., Liang A.C.T., Chen W.Y.W., Tao Q., Au W.Y., Wong M.L.Y., Shen L., Wong K.Y., Wan T.S.K., Cheung W.L., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., CD44 expression is regulated by translocation and promoter hypermethylation in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006 . 2006. |
| Wong M.L.Y., Tao Q., Fu L., Wong K.Y., Qiu G.H., Law F.B.F., Tin P.C., Cheung W.L., Lee P.Y., Tang J.C.O., Tsao G.S.W., Lam A.K.Y., Law S.Y.K., Wong J. and Srivastava G., Aberrant promoter hypermethylation and silencing of the critical 3p21 tumour suppressor gene, RASSF1A, in Chinese oesophageal squamous cell carcinoma, International Journal of Oncology. 2006, 28(3): 767-73. |
| Researcher : Wong MP |
| Project Title: | Identification of candidate cancer genes in regions of frequent chromosomal aberration in non-small cell lung cancers |
| Investigator(s): | Wong MP, Chung LP, Lam WK, Chiu S.W. |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 09/2003 |
| Abstract: |
| To define critical regions of imbalance in frequently altered chromosomal loci identified in local samples of non-small cell lung cancers (NSCLC) by microstatellite analysis; to identify target genes in the analyzed regions by comparison with genes listed in databases of the Human Genome Resources(NCBI); to study the structure and expression of the targeted genes in NSCLC of smokers and non-smokers, so as to verify their involvement and to look for genetic or epigenetic alterations. |
| Project Title: | Identification of candidate cancer genes in regions of frequent chromosomal aberration in non-small cell lung cancers |
| Investigator(s): | Wong MP, Chung LP, Lam WK, Chiu S.W. |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 09/2003 |
| Abstract: |
| N/A |
| Project Title: | Differentially expressed genes in lung cancer |
| Investigator(s): | Wong MP |
| Department: | Pathology |
| Source(s) of Funding: | Merit Award for RGC CERG Funded Projects |
| Start Date: | 01/2005 |
| Abstract: |
| N/A |
| Project Title: | Differentially expressed genes in lung cancer |
| Investigator(s): | Wong MP, Chung LP, Lam WK, Lam E.C.L., Chiu S.W. |
| Department: | Pathology |
| Source(s) of Funding: | Competitive Earmarked Research Grants (CERG) |
| Start Date: | 01/2005 |
| Abstract: |
| To verify whether molecular targets identified through expression profile microarray screening procesures truly show aberrant expressions in extended samples of lung cancers; to evaluate whether the genes encoding these verified molecular targets show alterations or mutations, so that their primary roles in carcinogenesis are supported at the genomic level. |
| Project Title: | Mutational Analysis of Epidermal Growth Factor Receptor in Non-Small Cell Lung Cancer |
| Investigator(s): | Wong MP, Chung LP, Suen WS, Chua DTT, Wang P |
| Department: | Pathology |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2005 |
| Abstract: |
| A. Purpose of study: To evaluate the incidence and patterns of EGFR mutation in NSCLC, and to correlate the findings with clinicopathological characteristics as well as clinical responses of the patients to gefitinib therapy. B. Problem being addressed and Key Issues: • Non-small cell lung cancer (NSCLC) is a common cancer in Hong Kong for both men and women. While >90% of lung cancers in men are related to tobacco, <30% of those in women are associated with cigarette smoking, but the underlying carcinogenic mechanism is still unclear. • Patients with NSCLC show poor overall survival due to late presentation defying complete surgical resection. Responses to current protocols of chemotherapy also demonstrate limited success. • Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that plays a crucial role in cell proliferation, survival and differentiation. In recent years, various forms of therapeutic agents targeting EGFR have been developed, including monoclonal antibodies or inhibitors of tyrosine kinase (TKI). Gefitinib (Iressa) is an orally administrated TKI that has been tried for NSCLC treatment. • It has recently been observed that patients with NSCLC containing EGFR mutations show better clinical responses to gefitinib, particularly women who have never smoked, or whose lung cancers show bronchioloalveolar features. However, a statistically significant benefit in survival has not been consistently demonstrated in published clinical series. The reported findings cannot be extrapolated to apply to our population, as the profile of mutation may be different and the response correlation may be population-dependent. It is thus important to evaluate the pattern of EGFR mutations and response to gefitinib in our patients with NSCLC. |
| List of Research Outputs |
| Ho J.C.M., Wong M.P. and Lam W.K., Lymphoepithelioma-like carcinoma of the lung, Respirology. 2006, 11: 539-545. |
| Ho J.C.M., Chua D.T.T., Cheng A.C., Sham J.S.T., Lam W.K. and Wong M.P., Predictive role of mutational status of epidermal growth factor receptor in clinical response to gefitinib in advanced non-small cell lung cancer, 11th Medical Research Conference, Department of Medicine, The University of Hong Kong . 2006, Abstract Book: pp. 58. |
| Lam B., Tam C.M., Lam S.Y., Wong M.P., Ooi C.G.C., Fung S.L., Lam D.C.L., Ip M.S.M. and Lam W.K., Detection of early lung cancer in high risk population: A prospective study. 11th World Conference on Lung Cancer, Lung Cancer. 2005, 49 (Suppl 2): S182 (P-257). |
| Lam B., Wong M.P., Fung S.L., Lam D.C.L., Wong P.C., Mok T.Y.W., Lam F.M., Ip M.S.M., Ooi C.G.C. and Lam W.K., The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer, 11th Medical Research Conference, Department of Medicine, The University of Hong Kong. 2006, Abstract Book 094: pp. 58. |
| Lam C.L., Wong M.P., Girard L., Chung L.P., Chiu W.S., Suen W.S., Lam W.K. and Minna J.D., Gene expression profiling in lung adenocarcinomas reveals molecular signatures with respect to gender, smoking, histological grading and disease-free survival. 11th World Conference on Lung Cancer, Lung Cancer. 2005, 49 (Suppl 2): S133 (P-072). |
| Lam D.C.L., Wong M.P., Girard L., Chung L.P., Suen W.S., Lam W.K. and Minna J.D., Gene expression profiling in lung adenocarcinomas reveals molecular signatures correlating with clinical significance, 11th Medical Research Conference, Department of Medicine, The University of Hong Kong. 2006, Abstract Book 090: pp. 56. |
| Mak J.C.W., Ho S.P., Wong M.P., Tsang K.W.T., Ip M.S.M., Lam W.K. and Chan M.M.W., Transforming growth factor (TGF)-b[sub]1[/sub] gene common polymorphisms and plasma TGF-b[sub]1[/sub] levels in patients with lung cancer, European Respiratory Journal. 2005, 26 (Suppl 49): 435S (#2797). |
| Nicholls J.M., Butany J., Poon L.L.M., Chan K.H., Beh S.L., Poutanen S., Peiris J.S.M. and Wong M.P., Time course and cellular localization of SARS-CoV nucleoprotein and RNA in lungs from fatal cases of SARS, Public Library of Science Medicine . 2006, 3(2): e27. |
| Tam I.Y.S., Chung L.P., Suen W.S., Wang E., Wong M.C.M., Ho K.K., Lam W.K., Chiu S.W., Girard L., Minna J.D., Gazdar A.F. and Wong M.P., Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features, Clinical Cancer Research. 2006, 12(5): 1647-53. |
| Wong M.P., Chua D.T.T., Ho J.C.M., Tam I.Y.S., Lam W.K. and Chung L.P., Mutational status of epidermal growth factor receptor is the only predictor of clinical response to gefitinib treatment in non-small cell lung cancer, 97th AACR Annual Meeting, Washington, DC, April 1-5, 2006 . 2006. |
| Zhu H., Lam D.C., Han K.C., Tin P.C., Suen W.S., Wang E., Lam W.K., Cai W.W., Chung L.P. and Wong M.P., High resolution analysis of genomic aberrations by metaphase and array comparative genomic hybridization identifies candidate tumour genes in lung cancer cell lines, Cancer Letters. 2006. |
| Researcher : Xu MS |
| List of Research Outputs |
| Xu M.S., Chan Y.K., Peiris J.S.M., Yip S.P., Cheung A.N.Y. and Khoo U.S., A variant in the CD209 promoter is associated with severity of Severe Acute Respiratory Syndrome (SARS), HUGO's 11th Human Genome Meeting, Helsinki, Finland. 2006. |
| Researcher : Xue W |
| List of Research Outputs |
| Chiu P.M., Feng H., Benbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model , Journal of Clinical Pathology . 2006, 59(8): 845-50. |
| Chiu P.M., Feng H., Behbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Tissue dynamic effect of all-trans retinoic acid on choriocarcinoma an organotypic model, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M. and Cheung A.N.Y., Differential expression of insulin-like growth factor binding protein 1 and ferritin light polypeptide in gestational trophoblastic neoplasia: combined cDNA suppression subtractive hybridization and microarray study, Cancer. 2005, 104(11): 2409-2416. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Kwan H.S., Shih S.M., Xue W., Chiu P.M., Chan K.W. and Cheung A.N.Y., Differential gene expression identified in complete hydatidiform mole by combining suppression subtractive hybridization and cDNA microarray, Placenta. 2006, 27: 521-526. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate Stem Cell Antigen is a genetic indicator for development of gestational trophoblastic neoplasia, American Association for Cancer Research's 97th Annual Meeting, March 31-April 5, 2006, in Washington DC, USA. 2006. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate stem cell antigen is over-expressed in persistent hydatidiform mole, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Fong P.Y., Xue W., Ngan H.Y.S., Chiu P.M., Chan Y.K., Tsao G.S.W. and Cheung A.N.Y., Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study, Journal of Clinical Pathology. 2006, 59: 179-183. |
| Siu K.Y., Yeung C.W., Chiu P.M., Feng H., Ngan H.Y.S., Xue W. and Cheung A.N.Y., p21-activated kinases (Paks) in gestational trophoblastic disease, XIIIth World Congress on Gestational Trophoblastic Diseases. Proceedings P.103. 2005. |
| Wang Y., Liu V.W.S., Xue W., Tsang P.C.K., Cheung A.N.Y. and Ngan H.Y.S., The Increase Of Mitochondrial Dna Content In Endometrial Adenocarcinoma Cells: A Quantitative Study Using Laser-captured Microdissected Tissues, Gynecologic Oncology. 2005, 98: 104-110. |
| Xue W., Feng H., Chan Y.K., Chiu P.M., Ngan H.Y.S., Khoo U.S., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Id helix-loop-helix proteins are differentially expressed in gestational trophoblastic disease., Histopathology. 2005, 47(3): 303-9. |
| Researcher : Xue W |
| List of Research Outputs |
| Chiu P.M., Feng H., Benbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model , Journal of Clinical Pathology . 2006, 59(8): 845-50. |
| Chiu P.M., Feng H., Behbrook D.M., Ngan H.Y.S., Khoo U.S., Xue W., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Tissue dynamic effect of all-trans retinoic acid on choriocarcinoma an organotypic model, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M. and Cheung A.N.Y., Differential expression of insulin-like growth factor binding protein 1 and ferritin light polypeptide in gestational trophoblastic neoplasia: combined cDNA suppression subtractive hybridization and microarray study, Cancer. 2005, 104(11): 2409-2416. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Kwan H.S., Shih S.M., Xue W., Chiu P.M., Chan K.W. and Cheung A.N.Y., Differential gene expression identified in complete hydatidiform mole by combining suppression subtractive hybridization and cDNA microarray, Placenta. 2006, 27: 521-526. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate Stem Cell Antigen is a genetic indicator for development of gestational trophoblastic neoplasia, American Association for Cancer Research's 97th Annual Meeting, March 31-April 5, 2006, in Washington DC, USA. 2006. |
| Feng H., Tsao G.S.W., Ngan H.Y.S., Xue W., Chiu P.M., Kwan H.S., Shih S.M. and Cheung A.N.Y., Prostate stem cell antigen is over-expressed in persistent hydatidiform mole, XIII World Congress On Gestational Trophoblastic Diseases, Hong Kong, October 23-26. 2005. |
| Fong P.Y., Xue W., Ngan H.Y.S., Chiu P.M., Chan Y.K., Tsao G.S.W. and Cheung A.N.Y., Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study, Journal of Clinical Pathology. 2006, 59: 179-183. |
| Siu K.Y., Yeung C.W., Chiu P.M., Feng H., Ngan H.Y.S., Xue W. and Cheung A.N.Y., p21-activated kinases (Paks) in gestational trophoblastic disease, XIIIth World Congress on Gestational Trophoblastic Diseases. Proceedings P.103. 2005. |
| Wang Y., Liu V.W.S., Xue W., Tsang P.C.K., Cheung A.N.Y. and Ngan H.Y.S., The Increase Of Mitochondrial Dna Content In Endometrial Adenocarcinoma Cells: A Quantitative Study Using Laser-captured Microdissected Tissues, Gynecologic Oncology. 2005, 98: 104-110. |
| Xue W., Feng H., Chan Y.K., Chiu P.M., Ngan H.Y.S., Khoo U.S., Tsao G.S.W., Chan K.W. and Cheung A.N.Y., Id helix-loop-helix proteins are differentially expressed in gestational trophoblastic disease., Histopathology. 2005, 47(3): 303-9. |
| Researcher : Yam JWP |
| Project Title: | Characterization of tensin2, the binding partner of DLC1 tumor suppressor in liver cancer |
| Investigator(s): | Yam JWP, Ng IOL |
| Department: | Pathology |
| Source(s) of Funding: | Seed Funding Programme for Basic Research |
| Start Date: | 12/2004 |
| Completion Date: | 11/2005 |
| Abstract: |
| The main objectives of this project are: 1) To characterize the structural determinants of DLC1-tensin2 interaction 2) To delineate the biological functions of tensin2 in HCC 3) To evaluate the clinicopathological significance of tensin2 in human HCC |
| Project Title: | Characterization of tensin2, the binding partner of DLC1 tumor suppressor in liver cancer |
| Investigator(s): | Yam JWP |
| Department: | Pathology |
| Source(s) of Funding: | Incentive Award for RGC CERG Fundable But Not Funded Projects |
| Start Date: | 07/2005 |
| Completion Date: | 06/2006 |
| Abstract: |
| N/A |
| List of Research Outputs |
| Chan D.W., Chan P.C.Y., Yam J.W.P., Ching Y.P. and Ng I.O.L., Prickle-1 promotes the degradation of Dishevelled by ubiquitination in liver cancer, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
| Chan L.K., Yam J.W.P. and Ng I.O.L., C20, a novel binding partner of DLC1 identified by yeast-2-hybrid screening, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
| Ko C.F., Yam J.W.P., Chan P.C.Y., Jin D. and Ng I.O.L., Interaction of deleted in liver cancer 1 (DLC1) with tensin2 and its implications in tumor suppression, Proceedings of the 97th Annual Meeting of American Association for Cancer Research, Washington, D.C., USA, April. 2006. |
| Leung H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity, Proc Natl Acad Sci U S A. 2005, 102: 15207-15212. |
| Leung T.H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in Liver Cancer 2, DLC2, Suppresses Cell Transformation via Inhibition of Rhoa Activity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
| Ng D.C.H., Chan S.F., Kok K.H., Yam J.W.P., Ching Y.P., Ng I.O.L. and Jin D., Mitochondrial targeting of growth suppressor protein DLC2 through the START domain, FEBS Letters . 2006, 580(1): 191-8. |
| Wong C.M., Yam J.W.P., Ching Y.P., Yau T.O., Leung T.H.Y., Jin D. and Ng I.O.L., Rho GTPase-Activating Protein Deleted in Liver Cancer Suppresses Cell Proliferation and Invasion in Hepatocellular Carcinoma, Cancer Research. 2005, 65: 8861-8868. |
| Yam J.W.P., Chan K.W., Ngan E.S.W. and Hsiao W.L., Genomic structure, alternative splicing and tissue expression of rFrp/sFRP-4, the rat frizzled related protein gene., Gene. 2005, 357: 55-62. |
| Researcher : Yang C |
| List of Research Outputs |
| Ma L., Chan K.W., Trendell-Smith N.J., Wu A.Y.Y., Tian L., Lam A.C., Lo C.K., Chik S.C.C., Ko K.H., To K.W., Kam C.S.K., Li X., Yang C., Leung S.Y., Ng M.H. and Huang F., Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains, In: Ma L, Chan KW, Trendell-Smith NJ, Wu A, Tian L, Lam AC, Chan AK, Lo CK, Chik S, Ko KH, To CK, Kam SK, Li XS, Yang CH, Leung SY, Ng MH, Stott DI, MacPherson GG, Huang FP, European Journal of Immunology (In This Issue highlight, Editorial Comments). 2005, 35(11): 3364-75. |
| Researcher : Yau TO |
| Project Title: | The role of HDPR1, a novel inhibitor of the WNT/β-catenin signalling pathway, in hepatocellular carcinoma |
| Investigator(s): | Yau TO, Fan ST, Ng IOL |
| Department: | Centre for the Study of Liver Disease |
| Source(s) of Funding: | Small Project Funding |
| Start Date: | 11/2004 |
| Completion Date: | 10/2005 |
| Abstract: |
| To study the expression of HDPR1 at mRNA levels in human HCCs and HCC cell lines; to investigate the common mechanisms, such as promoter hypermethylation and loss of heterozygosity, by which the expression of HDPR1 in HCC is downregulated; to study the function of HDPR1 in HCC cell lines. |
| List of Research Outputs |
| Leung H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity, Proc Natl Acad Sci U S A. 2005, 102: 15207-15212. |
| Leung T.H.Y., Ching Y.P., Yam J.W.P., Wong C.M., Yau T.O., Jin D. and Ng I.O.L., Deleted in Liver Cancer 2, DLC2, Suppresses Cell Transformation via Inhibition of Rhoa Activity, 10th Research Postgraduate Symposium, Faculty of Medicine, HKU, December 3, 2005 . 2005. |
| Wong C.M., Yam J.W.P., Ching Y.P., Yau T.O., Leung T.H.Y., Jin D. and Ng I.O.L., Rho GTPase-Activating Protein Deleted in Liver Cancer Suppresses Cell Proliferation and Invasion in Hepatocellular Carcinoma, Cancer Research. 2005, 65: 8861-8868. |
| Researcher : Yeung CW |
| List of Research Outputs |
| Siu K.Y., Yeung C.W., Chiu P.M., Feng H., Ngan H.Y.S., Xue W. and Cheung A.N.Y., p21-activated kinases (Paks) in gestational trophoblastic disease, XIIIth World Congress on Gestational Trophoblastic Diseases. Proceedings P.103. 2005. |
| Researcher : Yip BH |
| List of Research Outputs |
| Yip B.H., Guo T., Hu X., Wong K.Y., Chen W.Y.W., Au W.Y., Chu K.M., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) in gastric lymphoma, Proceedings of the 12th Hong Kong International Cancer Congress and 2nd Annual Meeting of Centre for Cancer Research, Hong Kong SAR, China, December 2005. |
| Yip B.H., Guo T., Hu X., Au W.Y., Wong K.Y., Wan T.S.K., Chen W.Y.W., Chu K.M., Chan L.C., Kwong Y.L., Liang R.H.S. and Srivastava G., Identification of two novel translocations t(14;20)(q32;q12) and t(2;14)(q23;q32) involving immunoglobulin heavy chain gene locus in gastric lymphoma, Proceedings of 97th Annual Meeting of American Association for Cancer Research (AACR), Washington D.C., USA, April 2006. |
| Researcher : Yip SF |
| List of Research Outputs |
| Chim J.C.S., Liang R.H.S., Leung S.M.H., Yip S.F. and Kwong Y.L., Aberrant gene promoter methylation marking disease progression in multiple myeloma, Leukemia. 2006, 20(6): 1190-2. |
| Tse E.W.C., Yip S.F., Ooi C.G.C. and Kwong Y.L., Subarachnoid haemorrhage: more than meets the eye, British Journal of Haematology. 2006, 132(4): 383. |
| Yip S.F., Wan T.S.K., Lie A.K.W., Liu H.S.Y. and Chan L.C., Monitoring of chronic myeloid leukemia (CML) imatinib response by fluorescence-in-situ-hybridization (FISH), American Society of Hematology, Atlanta, Georgia. December 10-13, 2005. Abstract No. 4837. Blood. 2005, 106(11) Part 2: 289b. |
| Yip S.F., So J.C.C., Chan A.Y.Y., Liu H.S.Y., Wan T.S.K. and Chan L.C., The lack of association between JAK2 V617F mutation and myelodysplastic syndrome with or without myelofibrosis , Leukemia. 2006, 20(6): 1165. |
| Yip S.F., Wan T.S.K., Chan L.C. and Chan G.C.F., Trisomy 4 as sole karyotypic abnormality in acute lymphoblastic leukemia: Different clinical features and treatment response between B and T phenotypes?, Cancer Genetics and Cytogenetics. 2006, 164: 94-95. |
| Researcher : Yuen ST |
| List of Research Outputs |
| Aggarwal A., Guo D.L., Hoshida Y., Yuen S.T., Chu K.M., So S., Boussioutas A., Chen X., Bowtell D., Aburatani H., Leung S.Y. and Tan P., Topological and functional discovery in a gene coexpression meta-network of gastric cancer, Cancer Research. 2006, 66(1): 232-41. |
| Davies H., Hunter C., Smith R., Stephens P., Greenman C., Bignell G., Teague J., Butler A., Edkins S., Stevens C., Parker A., O'Meara S., Avis T., Barthorpe S., Brackenbury L., Buck G., Clements J., Cole J., Dicks E., Edwards K., Forbes S., Gorton M., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jones D., Kosmidou V., Laman R., Lugg R., Menzies A., Perry J., Petty R., Raine K., Shepherd R., Small A., Solomon H., Stephens Y., Tofts C., Varian J., Webb A., West S., Widaa S., Yates A., Brasseur F., Cooper C.S., Flanagan A.M., Green A., Knowles M., Leung S.Y., Looijenga L.H., Malkowicz B., Pierotti M.A., Teh B.T., Yuen S.T., Lakhani S.R., Easton D.F., Weber B.L., Goldstraw P., Nicholson A.G., Wooster R., Stratton M.R. and Futreal P.A., Somatic mutations of the protein kinase gene family in human lung cancer, Cancer Research. 2005, 65(17): 7591-5. |
| Fan Y.S., Yuen S.T. and Leung S.Y., Calcified fibrous nodules in the heart: a case report, Pathology. 2006, 38(3): 273-5. |
| Giacomini C.P., Leung S.Y., Chen X., Yuen S.T., Kim Y.H., Bair E. and Pollack J.R., A Gene Expression Signature of Genetic Instability in Colon Cancer, Cancer Research. 2005, 65(20): 9200-5. |
| Guo D.L., Zhang J., Yuen S.T., Tsui W.Y., Chan A.S.Y., Ho C., Chen X. and Leung S.Y., Reduced Expression of EphB2 that parallels invasion and metastasis in colorectal tumors, Keystone Symposia: Stem Cells, Senescence and Cancer, 25-30 October . 2005. |
| Guo D.L., Zhang J., Yuen S.T., Tsui W.Y., Chan A.S.Y., Ho C., Ji J., Leung S.Y. and Chen X., Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumors, Carcinogenesis. 2005, 27(3): 454-464. |
| Ho J.W.C., Yuen S.T. and Lam T.H., A case-control study on environmental and familial risk factors for colorectal cancer in Hong Kong: chronic illnesses, medication and family history, Hong Kong Medical Journal. 2006, 12(suppl I): S14-16. |
| Ho J.W.C., Yuen S.T. and Lam T.H., A case-control study on environmental and familial risk factors for colorectal cancer in Hong Kong: dietary determinants of colorectal cancer risk, Hong Kong Medical Journal. 2006, 12(Suppl 1): S11-13. |
| Ho J.W.C., Yuen S.T. and Lam T.H., A case-control study on environmental and familial risk factors for colorectal cancer in Hong Kong: physical activity reduces colorectal cancer risk, Hong Kong Medical Journal. 2006, 12(suppl 1): S8-10. |
| Ho J.W.C., Yuen S.T. and Lam T.H., Smoking, drinking and colorectal cancer risk - a case-control study on environmental and familial risk factors for colorectal cancer in Hong Kong., Health Services Research Fund - Research Dissemination Report. 2005, 2 pp. |
| Iacopetta B., Russo A., Bazan V., Dardanoni G., Gebbia N., Soussi T., Kerr D., Elsaleh H., Soong R., Kandioler D., Janschek E., Kappel S., Lung M., Leung C.S., Ko J.M., Yuen S.T., Ho J.W.C., Leung S.Y., Crapez E., Duffour J., Ychou M., Leahy D.T., O'donoghue D.P., Agnese V., Cascio S., Di Fede G., Chieco-Bianchi L., Bertorelle R., Belluco C., Giaretti W., Castagnola P., Ricevuto E., Ficorella C., Bosari S., Arizzi C.D., Miyaki M., Onda M., Kampman E., Diergaarde B., Royds J., Lothe R.A., Diep C.B., Meling G.I., Ostrowski J., Trzeciak L., Guzinska-Ustymowicz K., Zalewski B., Capella G.M., Moreno V., Peinado M.A., Lonnroth C., Lundholm K., Sun X.F., Jansson A., Bouzourene H., Hsieh L.L., Tang R., Smith D.R., Allen-Mersh T.G., Khan Z.A., Shorthouse A.J., Silverman M.L., Kato S. and Ishioka C., Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study, Annals of Oncology. 2006, 17(5): 842-7. |
| Leung S.Y., Ho C., Tu I.P., Li R., So S., Chu K.M., Yuen S.T. and Chen X., Comprehensive analysis of 19Q12 amplicon in human gastric cancers, Modern Pathology. 2006, 19: 854-863. |
| Researcher : Zhang H |
| List of Research Outputs |
| Zheng B., Lee S.S., Wong K.H., Chan K.C.W., Zhang H. and Lu L., Ex vivo expansion of functional CD4 T cells from HIV patients., The 6th International Workshop on HIV, Cells of Macrophage/Dendritic Lineage and Other Reservoirs.. 2005, 37. |
| Researcher : Zhang M |
| List of Research Outputs |
| Qu X., Yang M.X., Kong B.H., Qi L., Lam Q.L.K., Yan S., Li P., Zhang M. and Lu L., Hypoxia inhibits the migratory capacity of human monocyte-derived dendritic cells, Immunology and Cell Biology . 2005, 83(6): 668-73. |
| Zhang M., Ko K.H. and Lu L., BAFF enhances the development of autoantibody-producing plasma cells in collagen-induced arthritis mice, Annual Meeting of American Association of Immunologists, Boston, USA, May 12. 2006. |
| Zhang M., Ko K.H., Lam Q.L.K., Srivastava G., Zheng B., Lau Y.L. and Lu L., Expression and function of TNF family member B cell-activating factor in the development of autoimmune arthritis, International Immunology. 2005, 17(8): 1081-1092. |
| Researcher : Zhang M |
| List of Research Outputs |
| Qu X., Yang M.X., Kong B.H., Qi L., Lam Q.L.K., Yan S., Li P., Zhang M. and Lu L., Hypoxia inhibits the migratory capacity of human monocyte-derived dendritic cells, Immunology and Cell Biology . 2005, 83(6): 668-73. |
| Zhang M., Ko K.H. and Lu L., BAFF enhances the development of autoantibody-producing plasma cells in collagen-induced arthritis mice, Annual Meeting of American Association of Immunologists, Boston, USA, May 12. 2006. |
| Zhang M., Ko K.H., Lam Q.L.K., Srivastava G., Zheng B., Lau Y.L. and Lu L., Expression and function of TNF family member B cell-activating factor in the development of autoimmune arthritis, International Immunology. 2005, 17(8): 1081-1092. |
| Researcher : Zhu H |
| List of Research Outputs |
| Zhu H., Lam D.C., Han K.C., Tin P.C., Suen W.S., Wang E., Lam W.K., Cai W.W., Chung L.P. and Wong M.P., High resolution analysis of genomic aberrations by metaphase and array comparative genomic hybridization identifies candidate tumour genes in lung cancer cell lines, Cancer Letters. 2006. |