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The effect of arsenic trioxide on acute megakaryocytic leukemia : signaling, cell cycle arrest, and apoptosis.

Lam Kin Bong Hubert. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 139-161). / Abstracts in English and Chinese. / Abstract (in English) --- p.i / (in chinese) --- p.iv / Acknowledgements --- p.vi / Publications --- p.ix / Table of Contents --- p.x / List of Tables --- p.xiii / List of Figures --- p.xiv / List of Abbreviations --- p.xvi / Chapter CHAPTER1: --- General Introduction --- p.1 / Chapter Section 1.1 --- Historical Background and Application of Arsenic Trioxide as an Anti-cancer Agent --- p.1 / Chapter Section 1.2 --- Arsenic Trioxide Induces Apoptosis in Cancer Cells --- p.3 / Chapter 1.2.1 --- The Intrinsic and Extrinsic Pathways of Apoptosis Initiation --- p.4 / Chapter 1.2.2 --- The Convergence of Pathways --- p.8 / Chapter 1.2.3 --- Induction of Apoptosis by Arsenic Trioxide --- p.9 / Chapter 1.2.3.1 --- Controversies in the Involvement of the Extrinsic Pathway --- p.9 / Chapter 1.2.3.2 --- "Arsenic Trioxide, Oxidative Stress and the Mitochondria" --- p.10 / Chapter 1.2.3.3 --- Caspase-3 Activation in Arsenic Trioxide-mediated Apoptosis --- p.12 / Chapter Section 1.3 --- Arsenic Trioxide Perturbs the Cell Division Cycle --- p.13 / Chapter 1.3.1 --- The Cell Cycle Oscillator --- p.14 / Chapter 1.3.2 --- DNADamage and Cell Cycle Checkpoints --- p.15 / Chapter 1.3.3 --- Induction of Cell Cycle Arrest by Arsenic Trioxide and its Association with Apoptosis --- p.17 / Chapter Section 1.4 --- Acute Megakaryocytic Leukemia and Arsenic Trioxide --- p.20 / Chapter CHAPTER 2: --- Objectives --- p.28 / Chapter CHAPTER 3: --- Methodology --- p.30 / Chapter Section 3.1 --- Materials --- p.30 / Chapter Section 3.2 --- Methods --- p.39 / Chapter 3.2.1 --- Culture of Megakaryocytic Cells and Their Treatment with Arsenic Trioxide --- p.39 / Chapter 3.2.1.1 --- Maintenance of Cell Lines --- p.39 / Chapter 3.2.1.2 --- Treatment with Arsenic Trioxide --- p.39 / Chapter 3.2.2 --- "Effects of Arsenic Trioxide on Cell Proliferation, Apoptosis, Mitochondrial Integrity and Cell Division Cycle Profiles of Human Megakaryocytic Leukemia Cell Lines" --- p.40 / Chapter 3.2.2.1 --- Trypan Blue Exclusion Assay --- p.40 / Chapter 3.2.2.2 --- Quantitation of Externalized Phosphatidylserine --- p.41 / Chapter 3.2.2.3 --- Quantitation of Active Caspase-3 Expression --- p.42 / Chapter 3.2.2.4 --- Assessment of Mitochondrial Intensity --- p.42 / Chapter 3.2.2.5 --- Analysis of Cell Division Cycle Profile --- p.43 / Chapter 3.2.2.6 --- Analysis of Cell Cycle Kinetics by BrdU Labeling --- p.43 / Chapter 3.2.2.7 --- Identification of Cell Cycle Specificity of Caspase-3 Expression --- p.45 / Chapter 3.2.3 --- Effects of Arsenic Trioxide on the Expression of Apoptotic Signals in Human Megakaryocytic Leukemia Cell Lines --- p.45 / Chapter 3.2.3.1 --- Effects of Arsenic Trioxide on mRNA Expression Levels of Apoptotic Regulators --- p.45 / Chapter 3.2.3.2 --- Effects of Arsenic Trioxide on Protein Expression Levels of Apoptotic Regulators --- p.50 / Chapter 3.2.3.2.1 --- Flow Cytometric Analysis --- p.50 / Chapter 3.2.3.2.2 --- Western Blot Analysis --- p.51 / Chapter 3.2.4 --- Effects of Arsenic Trioxide on Gene Expression Profiles of Human Megakaryocytic Leukemia Cell Lines By Microarray Analysis --- p.54 / Chapter 3.2.5 --- Statistical Analysis --- p.57 / Chapter CHAPTER 4: --- "Effects of Arsenic Trioxide on Cell Proliferation, Apoptosis, Mitochondrial Integrity and Cell Division Cycle Profiles of Human Megakaryocytic Leukemia Cell Lines" --- p.62 / Chapter Section 4.1 --- Introduction --- p.62 / Chapter Section 4.2 --- Results --- p.63 / Chapter 4.2.1 --- Effects of Arsenic Trioxide on Proliferation Kinetics --- p.63 / Chapter 4.2.2 --- Effects of Arsenic Trioxide on Cell Viability --- p.64 / Chapter 4.2.3 --- Apoptosis-inducing Capability of Arsenic Trioxide --- p.65 / Chapter 4.2.3.1 --- Quantitation of Externalized Phosphatidylserine --- p.65 / Chapter 4.2.3.2 --- Quantitation of Active Caspase-3 Expression --- p.66 / Chapter 4.2.4 --- Effects of Arsenic Trioxide on Mitochondrial Integrity --- p.67 / Chapter 4.2.5 --- Effects of Arsenic Trioxide on Cell Division Cycle Profiles --- p.69 / Chapter 4.2.6 --- Effects of Arsenic Trioxide on Cell Cycle Kinetics by Bromodeoxyuridine Labeling --- p.69 / Chapter 4.2.7 --- Identification of Cell Cycle Specificity of Arsenic Trioxide-Induced Caspase-3 Activation --- p.71 / Chapter Section 4.3 --- Discussion --- p.72 / Chapter CHAPTER 5: --- Effects of Arsenic Trioxide on Apoptotic Signal Expression in Human Megakaryocytic Leukemia Cell Lines --- p.91 / Chapter Section 5.1 --- Introduction --- p.91 / Chapter Section 5.2 --- Results --- p.92 / Chapter 5.2.1 --- Effects of Arsenic Trioxide on mRNA Expression Levels of Apoptotic Regulators --- p.92 / Chapter 5.2.2 --- Effects of Arsenic Trioxide on Protein Expression Levels of Apoptotic Regulators --- p.94 / Chapter 5.2.2.1 --- Flow Cytometric Analysis --- p.94 / Chapter 5.2.2.2 --- Western Blot Analysis --- p.96 / Chapter Section 5.3 --- Discussion --- p.96 / Chapter CHAPTER 6: --- Effects of Arsenic Trioxide on Gene Expression Profiles of Human Megakaryocytic Leukemia Cell Lines by Microarray Analysis --- p.119 / Chapter Section 6.1 --- Introduction --- p.119 / Chapter Section 6.2 --- Results --- p.119 / Chapter Section 6.3 --- Discussion --- p.122 / Chapter CHAPTER 7: --- General Discussion and Conclusions --- p.135 / BIblography --- p.139

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_324628
Date January 2004
ContributorsLam, Kin Bong Hubert., Chinese University of Hong Kong Graduate School. Division of Medical Sciences.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xviii, 161 leaves : ill. (some col.) ; 30 cm.
RightsUse of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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