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Studies on the anti-tumor effects and action mechanisms of fluvastatin on murine myeloid leukemia cells.

Chin, Chi Hou. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves [165]-178). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract in Chinese (摘要) --- p.iv / Acknowledgements --- p.vi / Abbreviations --- p.vii / List of Figures and Tables --- p.xi / Publications --- p.xv / Chapter Chapter 1 --- General Introduction / Chapter 1.1. --- Hematopoiesis and Leukemia --- p.2 / Chapter 1.1.1. --- Hematopoiesis --- p.2 / Chapter 1.1.2. --- Leukemia --- p.8 / Chapter 1.1.2.1. --- Overview of leukemia --- p.8 / Chapter 1.1.2.2. --- Symptoms and diagnosis of leukemia --- p.9 / Chapter 1.1.2.3. --- Classification of leukemia --- p.9 / Chapter 1.1.2.4. --- Epidemiology of leukemia --- p.13 / Chapter 1.1.2.5. --- Conventional treatments for leukemia --- p.15 / Chapter 1.1.2.6. --- Novel approaches to leukemia treatment --- p.18 / Chapter 1.2. --- Statins --- p.22 / Chapter 1.2.1. --- Overview of statins --- p.22 / Chapter 1.2.2. --- Chemical structures of statins --- p.24 / Chapter 1.2.3. --- Pharmacokinetics of statins --- p.26 / Chapter 1.2.4. --- Pleiotropic effects of statins --- p.29 / Chapter 1.2.4.1. --- Anti-inflammatory and immunomodulatory effects of statins --- p.29 / Chapter 1.2.4.2. --- Anti-angiogenic effects of statins --- p.30 / Chapter 1.2.4.3. --- Anti-tumor effects of statins --- p.31 / Chapter 1.3. --- Objectives and scope of the present study --- p.33 / Chapter Chapter 2 --- Materials and Methods / Chapter 2.1. --- Materials --- p.36 / Chapter 2.1.1. --- Animals --- p.36 / Chapter 2.1.2. --- Cell lines --- p.36 / Chapter 2.1.3. --- "Cell culture media, buffers and other reagents" --- p.37 / Chapter 2.1.3.1. --- Cell culture media and reagents --- p.37 / Chapter 2.1.3.2. --- Drugs and chemicals --- p.40 / Chapter 2.1.3.3. --- Reagents and buffers for primary culture --- p.42 / Chapter 2.1.3.4. --- Dye solutions --- p.43 / Chapter 2.1.3.5. --- Reagents for cell proliferation assays --- p.44 / Chapter 2.1.3.6. --- Reagents and buffers for flow cytometry --- p.44 / Chapter 2.1.3.7. --- Reagents for Hoechst staining --- p.45 / Chapter 2.1.3.8. --- Reagents and buffers for DNA isolation --- p.46 / Chapter 2.1.3.9. --- Reagents and buffers for DNA agarose gel electrophoresis --- p.48 / Chapter 2.1.3.10. --- Reagents and buffers for Cell Death ELISA --- p.50 / Chapter 2.1.3.11. --- Reagents and buffers for measuring caspase activity --- p.51 / Chapter 2.1.3.12. --- Reagents and buffers for Western blotting --- p.55 / Chapter 2.1.3.13. --- Reagents for determining nitric oxide production --- p.63 / Chapter 2.2. --- Methods --- p.64 / Chapter 2.2.1. --- Culture of tumor cell lines --- p.64 / Chapter 2.2.2. --- "Isolation, preparation and culture of murine peritoneal macrophages" --- p.64 / Chapter 2.2.3. --- Cell proliferation and cytotoxicity studies --- p.66 / Chapter 2.2.4. --- In vivo tumorigenicity study --- p.68 / Chapter 2.2.5. --- Cell cycle profile and flow cytometric analysis --- p.69 / Chapter 2.2.6. --- Hoechst staining --- p.69 / Chapter 2.2.7. --- DNA fragmentation analysis --- p.70 / Chapter 2.2.8. --- Cell Death ELISA --- p.71 / Chapter 2.2.9. --- Mitochondrial membrane potential analysis --- p.73 / Chapter 2.2.10. --- Measurement of caspase activity --- p.73 / Chapter 2.2.11. --- Protein expression study --- p.75 / Chapter 2.2.12. --- Cell morphological staining --- p.80 / Chapter 2.2.13. --- Cell size and granularity analysis by flow cytometry --- p.81 / Chapter 2.2.14. --- Determination of nitric oxide production by macrophages --- p.81 / Chapter 2.2.15. --- Statistical analysis --- p.82 / Chapter Chapter 3 --- Anti-Proliferative Effect of Statins on Myeloid Leukemia Cells / Chapter 3.1. --- Introduction --- p.84 / Chapter 3.2. --- Results --- p.86 / Chapter 3.2.1. --- Anti-proliferative effect of statins on various murine and human myeloid leukemia cells --- p.86 / Chapter 3.2.2. --- Cytotoxicity of fluvastatin on murine myelomonocytic leukemia WEHI-3B JCS cells --- p.93 / Chapter 3.2.3. --- Cytotoxicity of fluvastatin on primary murine myeloid cells --- p.96 / Chapter 3.2.4. --- Kinetic and reversibility studies on the anti-proliferative effect of fluvastatin on WEHI-3B JCS cells --- p.98 / Chapter 3.2.5. --- Relationship between the anti-proliferative effect of fluvastatin and the cholesterol biosynthesis pathway in WEHI-3B JCS cells --- p.102 / Chapter 3.2.6. --- Effect of fluvastatin on the in vivo tumorigenicity of WEHI-3B JCS cells --- p.106 / Chapter 3.2.7. --- Effect of fluvastatin on the cell cycle profile of WEHI-3B JCS cells --- p.108 / Chapter 3.2.8. --- Effect of fluvastatin on the expression of cell cycle regulatory proteins inWEHI-3B JCS cells --- p.113 / Chapter 3.3. --- Discussion --- p.116 / Chapter Chapter 4 --- Apoptosis- and Differentiation-inducing Effects of Fluvastatin on Murine Myelomonocytic Leukemia WEHI-3B JCS Cells / Chapter 4.1. --- Introduction --- p.124 / Chapter 4.2. --- Results --- p.128 / Chapter 4.2.1. --- Induction of chromatin condensation in WEHI-3B JCS cells by fluvastatin --- p.128 / Chapter 4.2.2. --- Induction of DNA fragmentation in WEHI-3B JCS cells by fluvastatin --- p.130 / Chapter 4.2.3. --- Effect of fluvastatin on the mitochondrial membrane potential in WEHI-3B JCS cells --- p.134 / Chapter 4.2.4. --- Effect of fluvastatin on the caspase activities in WEHI-3B JCS cells --- p.138 / Chapter 4.2.5. --- Effect of fluvastatin on the expression of pro-apoptotic protein AIF in WEHI-3B JCS cells --- p.144 / Chapter 4.2.6. --- Effect of fluvastatin on the morphology of WEHI-3B JCS cells --- p.147 / Chapter 4.2.7. --- Effect of fluvastatin on the cell size and granularity of WEHI-3B JCS cells --- p.149 / Chapter 4.2.8. --- Immunomodulation of murine peritoneal macrophages by fluvastatin --- p.151 / Chapter 4.3. --- Discussion --- p.153 / Chapter Chapter 5 --- Conclusions and Future Perspectives --- p.160 / References --- p.165

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_327218
Date January 2010
ContributorsChin, Chi Hou., Chinese University of Hong Kong Graduate School. Division of Life Sciences.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xv, [4], 178 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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