Role of human papillomavirus (HPV) infection in human esophageal squamous cell carcinoma

• Objectives:
  To examine evidences for a pathological role of HPV infection in esophageal carcinoma by studying HPV DNA integration using in situ hybridization and analyzing the pattern of loss of heterozygosity in both HPV -positive and -negative esophageal cancers.
  
• Techniques:
  In situ hybridization, PCR, loss of heterozygosity analysis
  
• Investigators:
  Dr. Annie L. M. Cheung, Professor. George S. W. Tsao, Dr. Cycles Suet-Ping Poon

Mechanism of down-regulation of E-cadherin in human esophageal carcinoma

• Objectives:
  To examine the molecular mechanisms regulating the expression of E-cadherin, a cell adhesion molecular, in esophageal cancer specimens and cell lines.
  
• Techniques:
  Methylation specific PCR, immunocytochemistry, Western blot, RT-PCR
  
• Investigators:
  Dr. Annie L. M. Cheung, Professor. George S. W. Tsao

• Objectives:
  Specific gene expression and suppression, mapping of genetic alteration, telomerase activation, cell cycle checkpoint regulation and signaling pathway, establishment of immortal human cell lines.
  
• Techniques:
  Cell culture, gene transfection and expression, microarray and proteomic approach, subtractive library, cell cycle analysis, western blotting, quantitative PCR, flow cytometry etc.
  
• Investigator:
  Professor. George S. W. Tsao

• Objectives:
  To define the pathological role of EBV genes in nasopharyngeal carcinoma
  
• Techniques:
  Gene cloning, site-directed mutagenesis, mapping of functional domains, in vitro models of invasion, anchorage independence growth, proliferation and cell cycle analysis etc.
  
• Investigators:
  Professor. George S. W. Tsao, Dr. P. W. Yuen (Surgery), Dr. L. Cao (Microbiology)

• Objectives:
  To define the profile of genetic alterations and specific gene expression in human trophoblastic disease
  
• Techniques:
  Cell culture, gene transfection and expression, microarray and proteomic approach, subtractive library, western blotting, quantitative PCR, immunocytochemistry
  
• Investigators:
  Professor. George S. W. Tsao, Dr. A. N. Y. Cheung (Pathology)

• Objectives:
  To examine the changes of stromal smooth muscle differentiation in the Noble rat during the process of sex hormone-induced prostate carcinogenesis and to examine the expression of E-cadherin and related molecules in the epithelium during this process.
  
• Techniques:
  Tissue culture, tissue recombination, one and two dimensional electrophoresis, PCR, microarray technique, immunohistochemistry, in situ hybridization, flow cytometry, fluorescent microscopy and confocal microscopy
  
• Investigators:
  Principal Investigator: Professor Y. C. Wong
  Co-investigators: Professor George S. W. Tsao, Dr. X. H. Wang
  Technician: Mr. Davy Lee

• Objectives:

The objectives of the current proposal are:
1) To establish the mechanism of androgen actions by examine the expression of several factors involved in the cross talk between the epithelium and stroma during the process of mammary carcinogenesis
2) To further refine and characterize these factors at protein and mRNA levels to substantiate our hypothesis of a paracrine regulation between epithelium and stroma in breast carcinogenesis
3) To examine changes in expression patterns of several oncogenes and tumour suppressor genes as well as the role of apoptosis in hormonal carcinogenesis
4) To examine the genes affected during the early process of hormonal carcinogenesis.
By doing so, we hope to demonstrate the roles played by androgens in mammary carcinogenesis. The study aims to shed new light on the role of androgens on breast carcinogenesis.

• Techniques:
  Eliza assay, differential gene expression, PCR, microarray, electrophoresis, flow cytometry, confocal microscopy, tissue culture, fluorescent microscopy, immunohistochemistry and in situ hybridization
  
• Investigators:
  Principal Investigator: Professor Y. C. Wong
  Co-Investigators: Dr. Y. Q. Ke (Liverpool), Professor George S. W. Tsao, Dr. X. H. Wang
  Technician: Mr. Davy Lee

The role of ID-1 gene in prostate carcinogenesis and its relationship to invasiveness of prostate cancer

• Objectives:
  The project has the following specific aims:

1. To determine the Id-1 status in human prostate cancer and its value as a prognostic marker.
2. To examine the functional role of Id-1 in prostate cancer cells as well as its regulation under in vitro conditions.

The findings from these studies may have prognostic value in predicting the metastatic potentials of prostate cancer; thus improvement in prostate cancer management.

• Techniques:
  Eliza assay, differential gene expression, PCR, microarray, transfection study, electrophoresis, flow cytometry, confocal microscopy, tissue culture, fluorescent microscopy, immunohistochemistry and in situ hybridization.
  
• Investigators:
  Principal investigator: Professor Y. C. Wong
  Co-Investigators: Professor. George S. W. Tsao, Dr. P. T. Tam (Surgery), Dr. X. H. Wang
  Technician: Mr. Davy Lee

• Recently, a mitotic checkpoint defect is shown to be a common phenotype in human cancer cells. We have identified alterations of several key factors of the mitotic checkpoint in several types of human cancer such as nasopharyngeal carcinoma, ovarian carcinoma and prostate cancer. As several groups of anticancer drugs function through the disruption of mitosis, we are currently studying the role of mitotic checkpoint regulators in the sensitivity to chemotherapeutic drugs. We are also investigating whether restoration of the mitotic checkpoint control could lead to chemosensitization in human cancer cells.
  
• Techniques:
  Variety of molecular and cell biology techniques from cell culture, gene expression analysis, to chromosomal analysis and protein-protein interaction.
  
• Investigators:
  Principal investigators: Dr. X. H. Wang, Professor Y. C. Wong & Professor. George S. W. Tsao

• Recently, during the development of acquired drug resistant cell lines, we identified a novel function of the bHLH protein, TWIST, in the resistance to an anticancer drug, taxol. We are currently, we studying the molecular mechanisms responsible for TWIST-induced chemodrug resistance. In addition, we are investigating if inactivation of TWIST through RNAi technology could lead to the reversal of taxol resistant phenotypes in human cancer cells.
  
• Techniques:
  Variety of molecular and cell biology techniques from cell culture, gene expression analysis, to chromosomal analysis and protein-protein interaction.
  
• Investigators:
  Principal investigators: Dr. X. H. Wang, Professor Y. C. Wong & Professor George S. W. Tsao

• Currently, we are continuing to identify novel factors/pathways that are involved in the development of chemodrug resistance using human nasopharyngeal carcinoma, ovarian carcinoma and prostate cancer cells as models.
  
• Techniques:
  Variety of molecular and cell biology techniques from cell culture, gene expression analysis, to chromosomal analysis and protein-protein interaction.
  
• Investigators:
  Principal investigators: Dr. X. H. Wang, Professor Y. C. Wong & Professor George S. W. Tsao

• Using in vivo established human androgen independent prostate cancer models, we are in the process of demonstrating several potential anticancer agents for the treatment of advanced prostate cancer.
  
• Techniques:
  Variety of molecular and cell biology techniques from cell culture, gene expression analysis, to chromosomal analysis and protein-protein interaction.
  
• Investigators:
  Principal investigators: Dr. X. H. Wang, Professor Y. C. Wong & Professor George S. W. Tsao