Cancer chemoprevention uses noncytotoxic drugs or nutrients to prevent, retard, or delay carcinogenesis. The future of cancer chemoprevention depends on understanding key cellular growth and proliferation-controlling events, developing markers of molecular carcinogenesis, surrogate endpoint biomarkers, and targeted chemopreventive approaches.

Chiu Yuk Lan. / "December 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 160-185) / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

by Chan Pui Chung, Denise. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 119-135). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT --- p.iii / ABSTRACT (CHINESE VERSION) --- p.v / TABLE OF CONTENTS --- p.vi / LIST OF TABLES --- p.x / LIST OF FIGURES --- p.xii / LIST OF ABBREVIATIONS --- p.xiv / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Biology of Human Papillomaviruses --- p.2 / Chapter 1.1.1 --- Taxonomy --- p.2 / Chapter 1.1.2 --- Genomic organisation --- p.2 / Chapter 1.1.3 --- "Types, subtypes and variants" --- p.4 / Chapter 1.2 --- Epidemiology of cervical cancers --- p.6 / Chapter 1.2.1 --- Incidence --- p.8 / Chapter 1.2.2 --- Cervical cancers screening programme --- p.10 / Chapter 1.3 --- Association between human papillomavirus and cervical cancers --- p.11 / Chapter 1.3.1 --- Infection --- p.11 / Chapter 1.3.2 --- Multistep pathogenesis of cervical cancers --- p.13 / Chapter 1.3.3 --- Geographical distribution --- p.14 / Chapter 1.3.4 --- Age distribution of HPV infection --- p.15 / Chapter 1.3.5 --- Oncogenic property of HPV --- p.15 / Chapter 1.3.6 --- Sequence variation --- p.20 / Chapter 1.4 --- Project design --- p.23 / Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.25 / Chapter 2.1 --- Evaluation of HPV DNA extraction methods for paraffin-embedded tissues --- p.26 / Chapter 2.1.1 --- Study population --- p.26 / Chapter 2.1.2 --- Paraffin-embedded tissue collection --- p.26 / Chapter 2.1.3 --- DNA extraction --- p.26 / Chapter 2.1.3.1 --- Phenol-chloroform extraction --- p.27 / Chapter 2.1.3.2 --- Microwave extraction --- p.28 / Chapter 2.1.3.3 --- QIAGEN spin column extraction --- p.28 / Chapter 2.1.4 --- PCR amplification --- p.29 / Chapter 2.1.4.1 --- PCR amplification for human beta-globin gene --- p.29 / Chapter 2.1.4.2 --- PCR amplification for HPV DNA --- p.30 / Chapter 2.1.5 --- Optimisation of PCRs --- p.30 / Chapter 2.1.5.1 --- Optimisation of beta-globin PCRs --- p.30 / Chapter 2.1.5.2 --- Optimisation of HPV PCRs --- p.31 / Chapter 2.1.5.3 --- Analytical sensitivity of PCRs --- p.31 / Chapter 2.1.5.3.1 --- Analytical sensitivity of beta-globin PCRs --- p.31 / Chapter 2.1.5.3.2 --- Analytical sensitivity of HPV PCRs --- p.32 / Chapter 2.1.5.4 --- Detection of PCR products --- p.32 / Chapter 2.1.6 --- PCR evaluation of DNA extraction methods --- p.33 / Chapter 2.1.6.1 --- Beta-globin PCRs --- p.33 / Chapter 2.1.6.2 --- HPV PCRs --- p.33 / Chapter 2.1.6.2.1 --- MY09/MY11 PCR --- p.33 / Chapter 2.1.6.2.2 --- GP5+/GP6+ PCR --- p.34 / Chapter 2.1.6.3 --- Detection of PCR products --- p.34 / Chapter 2.2 --- Prevalence and genotype distribution of HPV --- p.35 / Chapter 2.2.1 --- Study populations --- p.35 / Chapter 2.2.1.1 --- Women with normal cervices --- p.35 / Chapter 2.2.1.2 --- Women with abnormal cervical cytologies --- p.35 / Chapter 2.2.1.3 --- Women with cervical cancer --- p.35 / Chapter 2.2.2 --- Disease classification --- p.36 / Chapter 2.2.3 --- Specimen collection and preparation --- p.36 / Chapter 2.2.3.1 --- Cervical scrape collection --- p.36 / Chapter 2.2.3.1.1 --- DNA extraction --- p.37 / Chapter 2.2.4 --- HPV DNA detection --- p.37 / Chapter 2.2.4.1 --- MY09/MY11 PCR --- p.38 / Chapter 2.2.4.2 --- GP5+/GP6+ PCR --- p.38 / Chapter 2.2.4.3 --- Detection of PCR products --- p.38 / Chapter 2.2.5 --- HPV genotyping --- p.39 / Chapter 2.3 --- Sequence variation of HPV 16 E7 gene --- p.39 / Chapter 2.3.1 --- Study population --- p.39 / Chapter 2.3.2 --- Optimisation of HPV 16 E7 nested PCR --- p.40 / Chapter 2.3.3 --- HPV 16 E7 nested PCR --- p.41 / Chapter 2.3.3.1 --- Detection of PCR products --- p.42 / Chapter 2.3.4 --- Purification of nested PCR products --- p.42 / Chapter 2.3.5 --- Direct cycle sequencing --- p.42 / Chapter 2.3.5.1 --- Cycle sequencing reaction --- p.42 / Chapter 2.3.5.2 --- Purification of cycle sequencing products --- p.43 / Chapter 2.3.5.3 --- Electrophoresis on DNA sequencer --- p.43 / Chapter 2.3.6 --- Data analysis --- p.44 / Chapter 2.4 --- Statistical methods --- p.44 / Chapter CHAPTER 3 --- RESULTS --- p.45 / Chapter 3.1 --- Evaluation of HPV DNA extraction methods for paraffin-embedded tissues --- p.46 / Chapter 3.1.1 --- Optimised conditions for beta-globin PCRs --- p.46 / Chapter 3.1.2 --- Optimised conditions for HPV PCRs --- p.47 / Chapter 3.1.3 --- Analytical sensitivity of beta-globin and HPV PCRs --- p.48 / Chapter 3.1.4 --- PCR evaluation of DNA extraction methods --- p.48 / Chapter 3.1.4.1 --- PC03/PC07 PCRs --- p.48 / Chapter 3.1.4.2 --- Beta-GPl/Beta-GP2 PCRs --- p.49 / Chapter 3.1.4.3 --- HPV PCRs --- p.49 / Chapter 3.2 --- Prevalence and genotype distribution of HPV --- p.50 / Chapter 3.2.1 --- HPV detection --- p.50 / Chapter 3.2.2 --- HPV typing --- p.50 / Chapter 3.2.3 --- Women with normal cervices --- p.51 / Chapter 3.2.4 --- Women with abnormal cervical cytologies --- p.51 / Chapter 3.2.5 --- Women with cervical cancer --- p.53 / Chapter 3.3 --- Sequence variation of HPV 16 E7 gene --- p.54 / Chapter 3.3.1 --- Optimised conditions for HPV 16 E7 nested PCR --- p.54 / Chapter 3.3.2 --- HPV 16 E7 sequencing --- p.55 / Chapter 3.3.3 --- HPV 16 E7 variants --- p.55 / Chapter 3.3.4 --- Distribution of HPV 16 E7 variants --- p.56 / Chapter CHAPTER 4 --- DISCUSSION --- p.58 / Chapter 4.1 --- Evaluation of HPV DNA extraction methods for paraffin-embedded tissues --- p.59 / Chapter 4.1.1 --- PCR evaluation of DNA extraction methods --- p.59 / Chapter 4.2 --- Prevalence and genotype distribution of HPV --- p.61 / Chapter 4.2.1 --- Women with normal cervices --- p.61 / Chapter 4.2.2 --- Women with abnormal cervical cytologies --- p.62 / Chapter 4.2.3 --- Women with cervical cancer --- p.64 / Chapter 4.3 --- Sequence variation of HPV 16 E7 gene --- p.64 / Chapter CHAPTER 5 --- CONCLUSION --- p.69 / REFERENCES --- p.119

Poon, Fan Fong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 109-124). / Abstract also in Chinese. / Abstract --- p.i / Acknowledgements --- p.v / Table of Content --- p.vi / List of Figures --- p.xi / List of Tables --- p.xiii / List of Abbreviations --- p.xiv / List of papers published during the study --- p.xvi / Chapter Chapter 1 --- Introduction and Aim of Study --- p.1 / Chapter 1.1 --- General Introduction --- p.1 / Chapter 1.2 --- Project objective and potential significances --- p.6 / Chapter Chapter 2 --- Literature Reviews --- p.8 / Chapter 2.1 --- Cancer genetics --- p.8 / Chapter 2.1.1 --- Oncogenes and TSGs --- p.8 / Chapter 2.1.2 --- Kundsońةs two-hit event of cancer gene --- p.9 / Chapter 2.2 --- Cancer Epigenetics --- p.9 / Chapter 2.2.1 --- Types of Epigenetic regulation --- p.10 / Chapter 2.2.2 --- DNA methylation in TSGs --- p.10 / Chapter 2.2.2.1 --- Promoter CpG island in DNA methylation --- p.10 / Chapter 2.2.2.2 --- Protection system in DNA methylation --- p.11 / Chapter 2.2.2.3 --- Transcriptional silencing by DNA methylation --- p.11 / Chapter 2.2.2.4 --- DNA methylation of TSG silencing in cancers --- p.13 / Chapter 2.2.3 --- Hypomethylation of the cancer genome --- p.14 / Chapter 2.2.4 --- Clinical relevance of cancer epigenetic --- p.14 / Chapter 2.3 --- EGFR/STAT/SOCS pathway --- p.15 / Chapter 2.3.1 --- General Introduction of the EGFR pathway --- p.15 / Chapter 2.3.2 --- EGFR survival signaling pathways --- p.16 / Chapter 2.3.3 --- EGFR/STAT/SOCS signaling --- p.17 / Chapter 2.3.4 --- EGFR/STAT/SOCS signaling and cancers --- p.18 / Chapter 2.3.4.1 --- EGF and cancers --- p.18 / Chapter 2.3.4.2 --- EGFR/STAT/SOCS pathway and cancers --- p.18 / Chapter 2.3.4.3 --- EGF survival signaling as a target for cancer therapy --- p.19 / Chapter 2.4 --- TSGs in the EGFR/STAT/SOCS pathway --- p.20 / Chapter 2.4.1 --- Suppressors of cytokine signaling (SOCS) family --- p.20 / Chapter 2.4.2 --- Signal transducers and activators of transcription (STATs) family --- p.22 / Chapter 2.4.3 --- Sprouty (SPRY) family --- p.23 / Chapter 2.4.4 --- Protein Inhibitor of Activated STAT (PIASs) family --- p.25 / Chapter 2.4.5 --- Ras and Rab Interactor (RIN) family --- p.26 / Chapter 2.4.6 --- Ras-association domain family (RASSF) --- p.26 / Chapter 2.4.7 --- Glycine N-methyltransferase (GNMT) --- p.28 / Chapter 2.5 --- Nasopharyngeal carcinoma (NPC) --- p.30 / Chapter 2.5.1 --- Epidemiology of NPC --- p.30 / Chapter 2.5.2 --- Histopathology of NPC --- p.30 / Chapter 2.5.3 --- Genetic and epigenetic alteration in NPC --- p.31 / Chapter 2.5.4 --- EGFR signaling in NPC --- p.32 / Chapter 2.6 --- Esophageal squamous cell carcinoma (ESCC) --- p.33 / Chapter 2.6.1 --- Epidemiology of ESCC --- p.34 / Chapter 2.6.2 --- Histopathology of ESCC --- p.34 / Chapter 2.6.3 --- Genetic and epigenetic alteration in ESCC --- p.35 / Chapter 2.6.4 --- EGFR signaling in ESCC --- p.36 / Chapter Chapter 3 --- Materials and Methods --- p.38 / Chapter 3.1 --- General Materials --- p.38 / Chapter 3.1.1 --- "Cell lines, tumor and normal tissue samples" --- p.38 / Chapter 3.1.2 --- Maintenance of cell lines --- p.38 / Chapter 3.1.3 --- Drugs treatment of cell lines --- p.39 / Chapter 3.1.4 --- Total RNA extraction --- p.39 / Chapter 3.1.5 --- Genomic DNA extraction --- p.40 / Chapter 3.2 --- General techniques --- p.40 / Chapter 3.2.1 --- Agarose gel electrophoresis of DNA --- p.40 / Chapter 3.2.2 --- TA cloning and blunt end cloning of PCR product --- p.40 / Chapter 3.2.3 --- Transformation of cloning products to E. coli competent cells --- p.41 / Chapter 3.2.4 --- Preparation of plasmid DNA --- p.41 / Chapter 3.2.4.1 --- Mini-prep plasmid DNA extraction --- p.41 / Chapter 3.2.4.2 --- Midi-prep of plasmid DNA --- p.42 / Chapter 3.2.5 --- Measurement of DNA or RNA concentrations --- p.42 / Chapter 3.2.6 --- DNA sequencing of plasmid DNA and PCR products --- p.42 / Chapter 3.3 --- Preparation of reagents and medium --- p.43 / Chapter 3.4 --- Semi-quatitative Reverse-Transcription (RT) PCR expression analysis --- p.44 / Chapter 3.4.1 --- Reverse transcriptin reaction --- p.44 / Chapter 3.4.2 --- Semi-quantitative RT-PCR --- p.44 / Chapter 3.4.2.1 --- Primers design --- p.44 / Chapter 3.4.2.2 --- PCR reaction --- p.46 / Chapter 3.5 --- Methylation analysis of candidate genes --- p.47 / Chapter 3.5.1 --- Bisulfite treatment of genomic DNA --- p.47 / Chapter 3.5.2 --- Methylation-specific PCR (MSP) --- p.48 / Chapter 3.5.2.1 --- Bioinformatics prediction of CpG island --- p.48 / Chapter 3.5.2.2 --- Primers design --- p.48 / Chapter 3.5.2.3 --- PCR reaction --- p.49 / Chapter 3.5.3 --- Bisulfite Genomic Sequencing (BGS) --- p.50 / Chapter 3.6 --- Construction of expression vectors of candidate genes --- p.51 / Chapter 3.6.1 --- Sub-cloning of expression vector of candidate genes --- p.51 / Chapter 3.6.1.1 --- Mouse Socsl expression vector --- p.51 / Chapter 3.6.1.2 --- SPRY1 expression vector --- p.51 / Chapter 3.6.1.3 --- GNMT expression vector --- p.52 / Chapter 3.6.2 --- Restriction digestion of cloning vectors and expression --- p.52 / Chapter 3.6.3 --- Ligation of cloning fragments --- p.53 / Chapter 3.6.4 --- Colony formation assay on monolayer culture --- p.53 / Chapter 3.6.5 --- Statistical analysis --- p.54 / Chapter Chapter 4 --- Screening of candidate TSGs in EGFR pathway --- p.55 / Chapter 5.3.3 --- Restoration of GNMT expression by pharmacological demethylation --- p.89 / Chapter 5.3.4 --- Confirmation of the methylation status of GNMT promoter by BGS --- p.90 / Chapter 5.3.5 --- Methylation status of GNMT in ESCC and NPC primary tumors --- p.90 / Chapter 5.3.6 --- GNMT inhibited the growth of tumor cells in-vitro --- p.90 / Chapter 5.3.7 --- Discussion --- p.95 / Chapter Chapter 6 --- General Discussion --- p.100 / Chapter Chapter 7 --- Summary --- p.105 / Chapter Chapter 8 --- Future Study --- p.107 / Reference --- p.109