Leung Po-Ki. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 204-235). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABBREVIATIONS --- p.ii / ABSTRACT --- p.vi / 撮要 --- p.x / TABLE OF CONTENTS --- p.xiii / Chapter CHAPTER 1: --- GENERAL INTRODUCTION / Chapter 1.1 --- Hematopoiesis & Leukemia --- p.1 / Chapter 1.1.1 --- An Overview on Hematopoiesis --- p.1 / Chapter 1.1.2 --- Leukemia - Aberrant Hematopoiesis --- p.4 / Chapter 1.1.2.1 --- Classification and Epidemiology of Leukemia --- p.4 / Chapter 1.1.2.2 --- Pathophysiology and Etiology of Leukemia --- p.7 / Chapter 1.1.2.3 --- Conventional Treatments for Leukemia --- p.9 / Chapter 1.1.2.4 --- New Avenues for Leukemia Therapy --- p.11 / Chapter 1.2 --- Coumarins: General Properties and Pharmacological Activities --- p.13 / Chapter 1.2.1 --- Introduction to Coumarins --- p.13 / Chapter 1.2.1.1 --- Historical Development of Coumarins --- p.13 / Chapter 1.2.1.2 --- Occurrence and Functions of Coumarins in Plants --- p.13 / Chapter 1.2.2 --- Phytochemistry and Metabolism of Coumarins --- p.14 / Chapter 1.2.2.1 --- Chemical Structures of Coumarins --- p.14 / Chapter 1.2.2.2 --- Biosynthesis of Coumarins --- p.18 / Chapter 1.2.2.3 --- Toxicology of Coumarins --- p.18 / Chapter 1.2.2.4 --- Metabolic Pathways and Pharmacokinetics of Coumarins --- p.19 / Chapter 1.2.3 --- Pharmacological Activities of Coumarins --- p.22 / Chapter 1.2.3.1 --- Anti-edema and Anti-inflammatory Activities --- p.22 / Chapter 1.2.3.2 --- Immunomodulatory Activity --- p.23 / Chapter 1.2.3.3 --- Anti-tumor Activity --- p.23 / Chapter 1.2.3.3.1 --- Mode of Entry of Coumarins into Tumor Cells --- p.23 / Chapter 1.2.3.3.2 --- Anti-carcinogenic Effect --- p.24 / Chapter 1.2.3.3.3 --- Anti-proliferative Activity --- p.25 / Chapter 1.2.3.3.4 --- Induction of Cell Differentiation --- p.26 / Chapter 1.2.3.3.5 --- Other Biological Activities --- p.26 / Chapter 1.2.4 --- Clinical Applications of Coumarins --- p.27 / Chapter 1.2.4.1 --- Treatment of Lymphoedema and Other High-protein Edemas --- p.27 / Chapter 1.2.4.2 --- Treatment of Thermal Injuries --- p.27 / Chapter 1.2.4.3 --- Therapeutic Agent for Renal Cell Carcinoma --- p.28 / Chapter 1.2.4.4 --- Therapy of Prostate Cancer --- p.29 / Chapter 1.3 --- Tumor Models Used in This Study --- p.30 / Chapter 1.3.1 --- Myeloid Leukemias --- p.30 / Chapter 1.3.1.1 --- HL-60 --- p.30 / Chapter 1.3.1.2 --- K562 --- p.30 / Chapter 1.3.1.3 --- EoL-1 --- p.30 / Chapter 1.3.1.4 --- WEHI-3B JCS --- p.31 / Chapter 1.3.2 --- Neuroblastoma - Neuro-2a BU-1 --- p.31 / Chapter 1.4 --- Aims and Scopes of This Investigation --- 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 Medium, Buffers and Other Reagents" --- p.37 / Chapter 2.1.4 --- [methyl-3H] Thymidine (3H-TdR) --- p.40 / Chapter 2.1.5 --- Methylthiazoletetrazolium (MTT) --- p.41 / Chapter 2.1.6 --- Nitro Blue Tetrazolium (NBT) --- p.41 / Chapter 2.1.7 --- Liquid Scintillation Cocktail --- p.42 / Chapter 2.1.8 --- Reagents and Buffers for Flow Cytometry --- p.42 / Chapter 2.1.9 --- Mouse Anti-MAP-2 Monoclonal Antibody --- p.44 / Chapter 2.1.10 --- Reagents for DNA Extraction --- p.44 / Chapter 2.1.11 --- Reagents for Total RNA Isolation --- p.45 / Chapter 2.1.12 --- Reagents and Buffers for RT-PCR --- p.46 / Chapter 2.1.13 --- Reagents and Buffers for Gel Electrophoresis --- p.49 / Chapter 2.1.14 --- Reagents and Buffers for Western Blot Analysis --- p.50 / Chapter 2.1.15 --- Reagents for Measuring Caspase Activity --- p.58 / Chapter 2.2 --- Methods / Chapter 2.2.1 --- Culture of the Tumor Cell Lines --- p.61 / Chapter 2.2.2 --- "Isolation, Preparation and Culture of Mouse Peritoneal Macrophages" --- p.61 / Chapter 2.2.3 --- Determination of Cell Proliferation by [3H]-TdR Incorporation Assay --- p.62 / Chapter 2.2.4 --- Determination of Cell Viability --- p.62 / Chapter 2.2.5 --- Cell Morphology Study --- p.63 / Chapter 2.2.6 --- Immunocytochemistry --- p.64 / Chapter 2.2.7 --- Confocal Microscopy --- p.64 / Chapter 2.2.8 --- NBT Reduction Assay --- p.65 / Chapter 2.2.9 --- In vivo Tumorigenicity Assay --- p.65 / Chapter 2.2.10 --- In vivo Anti-tumor Study --- p.65 / Chapter 2.2.11 --- Measurement of In vivo Macrophage Migration --- p.66 / Chapter 2.2.12 --- Measurement of Cytokine Production by ELISA --- p.66 / Chapter 2.2.13 --- Measurement of Apoptosis by DNA Fragmentation Analysis --- p.67 / Chapter 2.2.14 --- Determination of the Mitochondrial Membrane Potential --- p.67 / Chapter 2.2.15 --- Cell Cycle/DNA Content Evaluation --- p.68 / Chapter 2.2.16 --- Nitric oxide/Annexin V-PE Dual Sensor Assay --- p.68 / Chapter 2.2.17 --- Gene Expression Study --- p.68 / Chapter 2.2.18 --- Protein Expression Study --- p.71 / Chapter 2.2.19 --- Measurement of Caspase Activity --- p.74 / Chapter 2.2.20 --- Statistical Analysis --- p.75 / Chapter CHAPTER 3: --- STUDIES ON THE ANTI-TUMOR ACTIVITIES OF COUMARINS ON MYELOID LEUKEMIA CELLS / Chapter 3.1 --- Introduction --- p.76 / Chapter 3.2 --- Results --- p.18 / Chapter 3.2.1 --- Differential Anti-proliferative Effect of Coumarins on Various Leukemic Cell Lines In Vitro --- p.78 / Chapter 3.2.2 --- Cytotoxic Effect of Coumarins on Various Leukemic Cell Lines In Vitro --- p.91 / Chapter 3.2.3 --- "Kinetic, Reversibility and Stability Studies of the Anti- proliferative Effect of Coumarins on the Leukemia JCS cells" --- p.94 / Chapter 3.2.4 --- Induction of DNA Fragmentation in Myeloid Leukemia Cells by Coumarins --- p.100 / Chapter 3.2.5 --- Effect of Coumarins on the Cell Cycle Kinetics of the Leukemia JCS Cells In Vitro --- p.107 / Chapter 3.2.6 --- Effect of Coumarins on the In Vivo Tumorigenicity of the Leukemia JCS Cells --- p.112 / Chapter 3.2.7 --- Effect of Esculetin on the In Vivo Growth of the Leukemia JCS cells in Syngeneic Mice --- p.115 / Chapter 3.3 --- Discussion --- p.117 / Chapter CHAPTER 4: --- AN INVESTIGATION ON THE DIFFERENTIATION- INDUCING EFFECT OF COUMARINS / Chapter 4.1 --- Introduction --- p.122 / Chapter 4.2 --- Results --- p.124 / Chapter 4.2.1 --- The Differentiation-inducing Effect of Coumarins on Myeloid Leukemia Cells --- p.124 / Chapter 4.2.1.1 --- Morphological Changes in Coumarin-treated HL-60 Cells --- p.124 / Chapter 4.2.1.2 --- NBT Reduction of HL-60 Cells --- p.127 / Chapter 4.2.1.3 --- Effects of Coumarins on the Cell Size and Granularity of HL-60 Cells --- p.129 / Chapter 4.2.2 --- The Anti-proliferative and Differentiation-inducing Effects of Coumarins on Neuroblastoma Cells --- p.131 / Chapter 4.2.2.1 --- Anti-proliferative Effect of Coumarins on the BU-1 Cell Line In Vitro --- p.131 / Chapter 4.2.2.2 --- Morphological Changes in Coumarin-treated BU-1 Cells --- p.134 / Chapter 4.2.2.3 --- Immunocytochemistry of Coumarin-treated BU-1 Cells --- p.137 / Chapter 4.3 --- Discussion --- p.139 / Chapter CHAPTER 5: --- MECHANISTIC STUDIES ON THE ANTI-LEUKEMIC ACTIVITIES OF COUMARINS / Chapter 5.1 --- Introduction --- p.142 / Chapter 5.2 --- Results --- p.147 / Chapter 5.2.1 --- Modulatory Effects of Coumarins on the Expression of Apoptosis-regulatory Genes in the Leukemia JCS Cells --- p.147 / Chapter 5.2.2 --- Modulatory Effects of Coumarins on the Expression of Growth-related Genes in the Leukemia JCS Cells --- p.151 / Chapter 5.2.3 --- Modulatory Effects of Coumarins on the Expression of Apoptosis-regulatory Proteins in Leukemia JCS Cells --- p.157 / Chapter 5.2.4 --- Modulatory Effects of Coumarins on the Expression of Growth-related Proteins in Leukemia JCS Cells --- p.162 / Chapter 5.2.5 --- Effect of Coumarins on the Mitochondrial Membrane Depolarization of the Leukemia JCS cells --- p.165 / Chapter 5.2.6 --- Induction of Apoptosis and Nitric Oxide Production in Leukemia JCS Cells by Coumarins --- p.168 / Chapter 5.2.7 --- Effects of Coumarins on the Caspase Activity in the Leukemia JCS cells --- p.172 / Chapter 5.3 --- Discussion --- p.177 / Chapter CHAPTER 6: --- STUDIES ON THE IMMUNOMODULATORY EFFECT OF COUMARINS ON MURINE MACROPHAGES / Chapter 6.1 --- Introduction --- p.185 / Chapter 6.2 --- Results --- p.188 / Chapter 6.2.1 --- Effect of Coumarins on the Viability of Macrophages In vitro --- p.188 / Chapter 6.2.2 --- Effect of Coumarins on the In vivo Migration of Macrophages --- p.190 / Chapter 6.2.3 --- Effect of Coumarins on Cytokine Production by Macrophages --- p.192 / Chapter 6.3 --- Discussion --- p.194 / Chapter CHAPTER 7: --- CONCLUSIONS AND FUTURE PERSPECTIVES --- p.197 / REFERENCES --- p.204
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_324060 |
| Date | January 2002 |
| Contributors | Leung, Po-Ki., Chinese University of Hong Kong Graduate School. Division of Biochemistry. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography |
| Format | print, xvii, 235 leaves : ill. (some col.) ; 30 cm. |
| Rights | Use 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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