Leung Sau Ching. / Thesis submitted in: October 2003. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 142-165). / Abstracts in English and Chinese. / Acknowledgments --- p.ii / Abstract (English Version) --- p.iii / Abstract (Chinese Version) --- p.vi / Table of Contents --- p.viii / List of Tables --- p.xii / List of Figures --- p.xiii / List of Abbreviations --- p.xv / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Multiple Myeloma (MM) --- p.1 / Chapter 1.1.1 --- Epidemiology --- p.3 / Chapter 1.1.2 --- Clinical and Pathologic Features of MM --- p.3 / Chapter 1.1.3 --- Diagnosis and Staging --- p.4 / Chapter 1.1.4 --- Prognosis --- p.6 / Chapter 1.1.5 --- Treatment --- p.7 / Chapter 1.2 --- Molecular Abnormalities of MM --- p.8 / Chapter 1.2.1 --- Genetic Alterations: Chromosomal Aberrations --- p.8 / Chapter 1.2.2 --- Genetic Alterations: Ras Mutations --- p.11 / Chapter CHAPTER 2 --- LITERATURE REVIEW --- p.12 / Chapter 2.1 --- Epigenetic Alterations: DNA Methylation --- p.12 / Chapter 2.1.1 --- Characteristics of CpG Island --- p.14 / Chapter 2.1.2 --- Mechanism of Methylation-Related Gene Silencing --- p.14 / Chapter 2.1.3 --- DNA Methylation Is Important for Normal Cellular Functions --- p.17 / Chapter 2.1.4 --- DNA Methylation Changes in Cancer Cells --- p.17 / Chapter 2.1.5 --- Global DNA Hypomethylation --- p.18 / Chapter 2.1.6 --- Regional DNA Hypermethylation --- p.20 / Chapter 2.1.6.1 --- De Novo Methylation --- p.21 / Chapter 2.1.6.2 --- DNA Hypermethylation Acts as a Third Pathway to Loss of Function in Carcinogenesis --- p.21 / Chapter 2.1.6.3 --- DNA Hypermethylation Contributes to Tumorigenesis --- p.25 / Chapter 2.1.6.4 --- Methodologies in the Study of DNA Hypermethylation --- p.26 / Chapter 2.1.6.5 --- Single Gene Hypermethylation --- p.28 / Chapter 2.1.6.6 --- Multiple Gene Hypermethylation --- p.30 / Chapter 2.1.6.7 --- Potential Clinical Applications of DNA Hypermethylation --- p.36 / Chapter 2.1.6.7.1 --- Tumor Cells Detection by 5'CpG Island Hypermethylation --- p.37 / Chapter 2.1.6.7.2 --- Prognostic and Predictive Significances of DNA Hypermethylation --- p.39 / Chapter 2.1.6.7.3 --- Therapeutic Intervention of CpG island Hypermethylation --- p.40 / Chapter 2.2 --- DNA Hypermethylation in MM and MGUS --- p.43 / Chapter 2.3 --- Six-Genes Panel for the Hypermethylation Study --- p.45 / Chapter 2.3.1 --- Apoptotic Pathway: DAP-kinase --- p.45 / Chapter 2.3.2 --- Retinoid Signaling Pathway: RARβ --- p.50 / Chapter 2.3.3 --- Angiogenic Pathway: THBS-1 --- p.52 / Chapter 2.3.4 --- Cell cycle Regulatory Pathway: pl6 and p15 --- p.57 / Chapter 2.3.5 --- Ras Signaling Pathway: RASSF1A --- p.62 / Chapter CHAPTER 3 --- BACKGROUND OF STUDY --- p.67 / Chapter 3.1 --- Rationale --- p.67 / Chapter 3.2 --- Hypothesis --- p.69 / Chapter 3.3 --- The Objectives of Study --- p.70 / Chapter CHAPTER 4 --- MATERIALS AND METHODS --- p.71 / Chapter 4.1 --- Culture of Human Multiple Myeloma (MM)-derived Cell Lines --- p.71 / Chapter 4.2 --- Demethylation Treatment --- p.72 / Chapter 4.3 --- Patient and Control Samples --- p.72 / Chapter 4.4 --- DNA Extraction --- p.73 / Chapter 4.5 --- MS-PCR --- p.73 / Chapter 4.6 --- Plasma Cell Isolation --- p.77 / Chapter 4.7 --- RNA Extraction and RT-PCR --- p.78 / Chapter 4.8 --- Statistics --- p.82 / Chapter CHAPTER 5 --- RESULTS --- p.84 / Chapter 5.1 --- Patient Characteristics --- p.84 / Chapter 5.2 --- Single Gene Hypermethylation --- p.87 / Chapter 5.2.1 --- Normal PB Did Not Show Methylation --- p.87 / Chapter 5.2.2 --- DNA Hypermethylation in Human MM-derived Cell Lines --- p.87 / Chapter 5.2.3 --- DNA Hypermethylation in Primary MM --- p.89 / Chapter 5.3 --- Demethylation Treatment --- p.93 / Chapter 5.4 --- Concurrent Hypermethylation --- p.96 / Chapter 5.5 --- Statistical Analyses of Primary MM --- p.101 / Chapter 5.5.1 --- Statistical Analyses Between Single Gene Hypermethylation and Clinical Parameters (Categorical) --- p.101 / Chapter 5.5.2 --- Statistical Analyses Between Single Gene Hypermethylation and Clinical Parameters (Non-Categorical) --- p.101 / Chapter 5.5.3 --- Survival Analyses of Single Gene Hypermethylation --- p.105 / Chapter 5.5.4 --- Correlation Analyses of Concurrent Hypermethylation --- p.107 / Chapter 5.5.5 --- Correlation Analyses Between Concurrent Hypermethylation and Clinical Parameters --- p.107 / Chapter CHAPTER 6 --- DISCUSSION --- p.110 / Chapter 6.1 --- Involvement of Cellular Pathways by Hypermethylation --- p.111 / Chapter 6.1.1 --- Apoptotic Pathway: DAP-kinase and RARβ --- p.111 / Chapter 6.1.2 --- "Cell Cycle Regulatory Pathway: p16, p15 and RASSF1A" --- p.113 / Chapter 6.1.3 --- Angiogenic Pathway: THBS-1 --- p.117 / Chapter 6.2 --- Hypermethylation-Associated Gene Silencing --- p.119 / Chapter 6.3 --- Hypermethylation in Cell Lines and Primary MM --- p.120 / Chapter 6.4 --- Concurrent Hypermethylation --- p.122 / Chapter 6.4.1 --- DNA Hypermethylation is Common in MM --- p.122 / Chapter 6.4.2 --- Extent of Hypermethylation --- p.123 / Chapter 6.4.3 --- Involvement of Cellular Pathways by DNA Hypermethylation --- p.124 / Chapter 6.4.4 --- Concurrent p16 and DAP-kinase Hypermethylation --- p.126 / Chapter 6.5 --- Clinical Applications of DNA Hypermethylation --- p.129 / Chapter 6.5.1 --- Methylation As Tumor Markers for MM --- p.129 / Chapter 6.5.2 --- Prognostic Implications of DNA Hypermethylation in MM --- p.130 / Chapter 6.5.3 --- Correlations Between DNA Hypermethylation and Clinical Parameters --- p.131 / Chapter 6.6 --- MS-PCR --- p.136 / Chapter CHAPTER 7 --- CONCLUSION --- p.137 / Chapter CHAPTER 8 --- FURTHER STUDIES --- p.140 / References --- p.142

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

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Multiple myeloma is a bone marrow malignancy characterized by the presence of monoclonal plasma cells. In 50-75% of myeloma patients, chromosome translocations at the IgH locus are observed, which result in overexpression of oncogenes from the translocated chromosome due to linkage with the IgH enhancers. IgH enhancer activity is mediated by the B cell-specific transcription factors Bob1 and Oct2. We hypothesized that inhibiting the IgH enhancer, through inhibition of Bob1 and Oct2, is a potential therapeutic strategy for translocation-positive myeloma. The expression and prognostic value of Bob1 and Oct2 in myeloma patient samples were assayed. High Bob1 expression was associated with increased survival, whereas high Oct2 expression was associated with reduced survival. In a t(4;14) myeloma cell line, Bob1 inhibition led to decreased expression of the translocated oncogene, FGFR3; however, this did not lead to decreased proliferation or increased apoptosis. To fully understand the roles of Bob1 and Oct2 in myeloma, further research is required. / Experimental Oncology

Cheng Suk Hang. / "February 2005." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 142-160) / 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. / Abstracts in English and Chinese.

Ng Heung-ling, Margaret. / "April 2003." / Thesis (M.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 216-237). / 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.

published_or_final_version / abstract / Medicine / Doctoral / Doctor of Philosophy

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