by Anthony Tak Cheung Chan. / "March 1998." / Thesis (M.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 200-242). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstract in Chinese.

Wong Yue Hang Albert. / Thesis submitted in: December 2005. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 108-119). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.v / List of Figures --- p.x / List of Tables --- p.xi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Literature Review --- p.4 / Chapter 2.1 --- Nasopharyngeal Carcinoma (NPC) --- p.4 / Chapter 2.1.1 --- Anatomy of Nasopharynx --- p.4 / Chapter 2.1.2 --- Histopathology of Nasopharyngeal Carcinoma --- p.5 / Chapter 2.1.3 --- Epidemiology and Etiology of Nasopharyngeal Carcinoma --- p.5 / Chapter 2.1.3.1 --- Endemic Regions of Nasopharyngeal Carcinoma --- p.5 / Chapter 2.1.3.2 --- Gender and Age Bias --- p.6 / Chapter 2.1.3.3 --- Nasopharyngeal Carcinoma in Hong Kong --- p.6 / Chapter 2.1.3.4 --- Environmental Factors and Diet --- p.7 / Chapter 2.1.3.5 --- HLA Haplotypes and Nasopharyngeal Carcinoma --- p.9 / Chapter 2.1.4 --- Epstein-Barr Virus (EBV) and Nasopharyngeal Carcinoma --- p.10 / Chapter 2.1.4.1 --- EBV and Human Cacners --- p.10 / Chapter 2.1.4.2 --- EBV Infection --- p.10 / Chapter 2.1.4.3 --- "Latent, Clonal EBV Infection" --- p.11 / Chapter 2.1.4.4 --- EBV Latency Form --- p.11 / Chapter 2.1.4.5 --- Reactivation of EBV --- p.12 / Chapter 2.1.5 --- Molecular Pathogenesis of Nasopharyngeal Carcinoma --- p.13 / Chapter 2.1.5.1 --- Genetic Changes --- p.13 / Chapter 2.1.5.2 --- Epigenetic Changes --- p.13 / Chapter 2.1.6 --- Therapy of Nasopharyngeal Carcinoma and its Deficiency --- p.14 / Chapter 2.1.6.1 --- Radiotherapy --- p.14 / Chapter 2.1.6.2 --- Concurrent Chemoradiotherapy --- p.16 / Chapter 2.1.6.3 --- Adjuvant and Neo-adjuvant Chemotherapy --- p.17 / Chapter 2.1.6.4 --- Chemotherapy in Metastatic Nasopharyngeal Carcinoma --- p.18 / Chapter 2.1.6.5 --- Novel Therapeutic Agents and Approach --- p.19 / Chapter 2.2 --- Histone Modification and Cancer --- p.20 / Chapter 2.2.1 --- Histone Modification and Transcription Regulation --- p.20 / Chapter 2.2.2 --- Carcinogenic Effect of Aberrant HAT and HDAC Activities --- p.21 / Chapter 2.2.3 --- Structural Classes of HDAC Inhibitors --- p.24 / Chapter 2.2.4 --- Anti-Cancer Mechanisms of HDAC Inhibitors --- p.25 / Chapter 2.3 --- Suberoylanilide Hydroxamic Acid (SAHA) --- p.27 / Chapter 2.3.1 --- Anti-tumor Effect of SAHA in Various Cancer Cell Lines --- p.27 / Chapter 2.3.2 --- SAHA Mediated Non-apoptotic Programmed Cell Death --- p.29 / Chapter 2.3.3 --- Anti-tumor and Preventive Effect of SAHA in Animal Model --- p.29 / Chapter 2.3.4 --- Clinical Trials of SAHA --- p.30 / Chapter 2.4 --- FK228 (Depsipeptide or FR901228) --- p.31 / Chapter 2.4.1 --- Anti-malignancy mechanism of FK228 --- p.31 / Chapter 2.4.2 --- Anti-angiogenesis --- p.32 / Chapter 2.4.3 --- Drug Resistance and FK228 --- p.33 / Chapter 2.4.4 --- Studies of FK228 on Animal Models --- p.33 / Chapter 2.4.5 --- Clinical Trials --- p.34 / Chapter 2.5 --- Histone Modification and Nasopharyngeal Carcinoma --- p.34 / Chapter Chapter 3 --- Materials and Methods --- p.36 / Chapter 3.1 --- Cell Lines --- p.36 / Chapter 3.2 --- EBER ish Hybridization (EBER ISH) --- p.37 / Chapter 3.3 --- HDAC Inhibitors --- p.38 / Chapter 3.4 --- Cellular Sensitivity of NPC Cell Lines to HDAC Inhibitors --- p.38 / Chapter 3.4.1 --- Drug Treatment --- p.38 / Chapter 3.4.2 --- Determining Relative Amount of Survival Cells (WST-1 Assay) --- p.39 / Chapter 3.5 --- Flow Cytometry Analysis --- p.40 / Chapter 3.5.1 --- Collecting Cells and Fixation --- p.40 / Chapter 3.5.2 --- Staining --- p.41 / Chapter 3.5.3 --- Flow Cytometry Analysis --- p.41 / Chapter 3.6 --- Protein Extraction --- p.41 / Chapter 3.6.1 --- Harvesting Samples --- p.41 / Chapter 3.6.2 --- Protein Extraction --- p.42 / Chapter 3.6.3 --- Protein Quantification --- p.42 / Chapter 3.7 --- Western Blotting --- p.43 / Chapter 3.7.1 --- SDS-Polyarcylamide Gel Electrophoresis (PAGE) (SDS-PAGE) --- p.43 / Chapter 3.7.2 --- Wet Transfer of Proteins --- p.43 / Chapter 3.7.3 --- Immunoblotting --- p.44 / Chapter 3.7.4 --- Signal Detection --- p.44 / Chapter 3.8 --- CodeLin´kёØ Oligonucleotide Microarray --- p.45 / Chapter 3.8.1 --- HDAC Inhibitor Treatment --- p.45 / Chapter 3.8.2 --- RNA Extraction --- p.45 / Chapter 3.8.3 --- Quality and Quantity Assessment of Total RNA Extracted --- p.46 / Chapter 3.8.4 --- CodeLinkIM Expression Bioarray System --- p.46 / Chapter 3.8.5 --- Data Analysis --- p.48 / Chapter 3.9 --- Real-time Reverse Transcription PCR (Real-time RT-PCR) --- p.48 / Chapter Chapter 4 --- Results --- p.50 / Chapter 4.1 --- Presence of EBV --- p.50 / Chapter 4.2 --- Anti-prolirative Effect of HDAC Inhibitors --- p.52 / Chapter 4.3 --- Histone Acetylation --- p.56 / Chapter 4.4 --- Induction of p21 Expression in NPC Cell Lines --- p.58 / Chapter 4.5 --- HDAC Inhibitors Induced Cell Cycle Arrest and Polyploidy Formation --- p.60 / Chapter 4.5.1 --- Trichostatin A Induced G2/M Arrest --- p.60 / Chapter 4.5.2 --- Suberoylanilide Hydroxamic Acid Induced G1 Arrest --- p.62 / Chapter 4.5.3 --- FK228 Mediated G2/M Arrest --- p.64 / Chapter 4.6 --- HDAC Inhibitors Altered the Expression of Cell Cycle Regulatory Proteins --- p.66 / Chapter 4.6.1 --- TSA Down-regulated Cyclin A and B --- p.66 / Chapter 4.6.2 --- Suppressed Expression of Cyclin D1 and B by SAHA --- p.69 / Chapter 4.6.3 --- Effect of FK228 on Expression of Different Cyclins in NPC Cell Lines --- p.71 / Chapter 4.7 --- Effect of HDAC Inhibitors on EBV Proteins --- p.73 / Chapter 4.8 --- HDAC Inhibitors Modulated Gene Expression Profile --- p.76 / Chapter 4.8.1 --- SAHA and FK228-Induced Gene Expression Profile --- p.76 / Chapter 4.8.2 --- Validation of Expression Profile of Selected Genes by Real-time RT-PCR --- p.83 / Chapter Chapter 5 --- Discussion --- p.87 / Chapter 5.1 --- Anti-proliferative Effect of SAHA and FK228 on NPC Cell Lines --- p.88 / Chapter 5.2 --- Resistance of SAHA or FK228 in NPC --- p.93 / Chapter 5.3 --- Growth Inhibitory Mechanism of SAHA and FK228 in NPC Cells --- p.94 / Chapter 5.4 --- Induction of Polyploidy Cells in NPC Cell Lines --- p.98 / Chapter 5.5 --- Does EBV play a Role in HDAC Inhibiotrs Induced Growth Arrest in NPC Cell Lines? --- p.99 / Chapter 5.6 --- Transcriptional Signature of SAHA and FK228 in NPC Cell Lines --- p.100 / Chapter 5.7 --- Combining SAHA or FK228 with other Anti-tumor Agents --- p.104 / Chapter 5.8 --- Future Prospectus --- p.105 / Chapter Chapter 6 --- Summary --- p.106 / References --- p.108 / Appendix 1 --- p.120 / Appendix 2 --- p.121