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Resistance to drug-induced apoptosis in T-cell acute lymphoblastic leukemia.

Leung Kam Tong. / Thesis submitted in: September 2006. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 79-95). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract (Chinese) --- p.iii / Acknowledgements --- p.v / Table of contents --- p.vi / List of figures --- p.ix / List of abbreviations --- p.xii / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Acute lymphoblastic leukemia --- p.1 / Chapter 1.2 --- T-cell acute lymphoblastic leukemia --- p.2 / Chapter 1.2.1 --- Chemotherapy --- p.2 / Chapter 1.2.1.1 --- Induction therapy --- p.2 / Chapter 1.2.1.2 --- Intensification therapy --- p.3 / Chapter 1.2.1.3 --- Maintenance therapy --- p.3 / Chapter 1.2.2 --- Chemoresistance in T-ALL --- p.3 / Chapter 1.3 --- Apoptosis and chemoresistance --- p.5 / Chapter 1.3.1 --- "Initiation, execution and regulation of apoptosis" --- p.5 / Chapter 1.3.1.1 --- Initiation of apoptosis --- p.5 / Chapter 1.3.1.2 --- Execution of apoptosis --- p.7 / Chapter 1.3.1.3 --- Regulation of apoptosis --- p.7 / Chapter 1.3.2 --- Mechanisms of resistance to apoptosis --- p.9 / Chapter 1.3.2.1 --- Overexpression of pro-survival proteins --- p.9 / Chapter 1.3.2.2 --- Downregulation and mutation of pro-apoptotic proteins --- p.11 / Chapter 1.3.2.3 --- Other mechanisms --- p.13 / Chapter 1.4 --- Bcl-2 interating mediator of cell death --- p.14 / Chapter 1.4.1 --- Role of Bim in apoptosis --- p.16 / Chapter 1.4.2 --- Regulation of Bim --- p.17 / Chapter 1.4.2.1 --- Transcriptional regulation of Bim --- p.18 / Chapter 1.4.2.2 --- Post-transcriptional regulation of Bim --- p.18 / Chapter 1.5 --- c-Jun N-terminal kinase --- p.20 / Chapter 1.5.1 --- Pro-apoptotic role of JNK --- p.21 / Chapter 1.5.2 --- Anti-apoptotic role of JNK --- p.21 / Chapter 1.6 --- Hypotheses --- p.22 / Chapter Chapter 2 --- Materials and Methods --- p.23 / Chapter 2.1 --- Cell culture --- p.23 / Chapter 2.2 --- Induction of quantification of apoptosis --- p.24 / Chapter 2.3 --- Determination of caspase activities --- p.24 / Chapter 2.4 --- Western blotting --- p.25 / Chapter 2.4.1 --- Protein extraction and determination of protein concentration --- p.25 / Chapter 2.4.2 --- SDS-PAGE and immunodetection --- p.26 / Chapter 2.5 --- Cell-free apoptosis reactions --- p.27 / Chapter 2.6 --- Analysis of mitochondrial membrane potential --- p.27 / Chapter 2.7 --- Transient transfection of Sup-Tl cells --- p.28 / Chapter 2.8 --- Reverse transcription-polymerase chain reaction (RT-PCR) --- p.28 / Chapter 2.8.1 --- RNA isolation --- p.28 / Chapter 2.8.2 --- Synthesis of first-strand cDNA --- p.29 / Chapter 2.8.3 --- Polymerase chain reaction --- p.29 / Chapter 2.9 --- Alkaline phosphatase digestion of Bim --- p.30 / Chapter Chapter 3 --- Results --- p.31 / Chapter 3.1 --- The T-ALL cell line Sup-Tl is resistant to etoposide-induced apoptosis --- p.31 / Chapter 3.2 --- Sup-Tl cells are resistant to etoposide-induced caspase activation --- p.40 / Chapter 3.3 --- Sup-Tl cells are insusceptible to etoposide-induced mitochondrial alterations --- p.46 / Chapter 3.4 --- BimEL is required for etoposide-induced apoptosis in Sup-Tl cells --- p.51 / Chapter 3.5 --- The reduced level of BimEL in Sup-Tl cells is owing to the presence of constitutively active JNK --- p.58 / Chapter Chapter 4 --- Discussion --- p.67 / References --- p.79

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_325838
Date January 2007
ContributorsLeung, Kam Tong., Chinese University of Hong Kong Graduate School. Division of Biology.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xiii, 95 leaves : ill. ; 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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