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A study of drug resistance mechanism in human carcinoma cells after hypoxia exposure.

Choi, Siu Cheong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 132-148). / Abstracts in English and Chinese. / Acknowledgement --- p.i / Abstract --- p.ii / Abbreviation --- p.v / List of Figures --- p.viii / List of Tables --- p.xii / Table of Content --- p.xiii / Chapter Chapter 1: --- General Introduction / Chapter 1.1 --- Introduction --- p.1 / Chapter 1.1.1 --- Treatment resistance in cancer --- p.1 / Chapter 1.1.1.1 --- Surgery --- p.2 / Chapter 1.1.1.2 --- Chemotherapy --- p.3 / Chapter 1.1.1.3 --- Radiotherapy --- p.3 / Chapter 1.1.1.4 --- Hormonal therapy --- p.4 / Chapter 1.1.2 --- Hypoxia/reoxygenation and its correlation with treatment resistance --- p.5 / Chapter 1.1.3 --- Aim of the study --- p.6 / Chapter Chapter 2: --- The drug sensitivity in HepG2 cells and A431 cells / Chapter 2.1 --- Introduction --- p.8 / Chapter 2.1.1 --- Treatment of cancer --- p.8 / Chapter 2.1.2 --- Drug resistance --- p.9 / Chapter 2.2 --- Materials and Methods --- p.10 / Chapter 2.2.1 --- Cell culture --- p.10 / Chapter 2.2.2 --- Drugs --- p.10 / Chapter 2.2.3 --- MTT assay --- p.11 / Chapter 2.3 --- Results --- p.12 / Chapter 2.3.1 --- The drugs to which G10HR and G20HR cells were more resistant --- p.12 / Chapter 2.3.2 --- "The drugs of which GP, G10HR and G20HR cells have similar response" --- p.12 / Chapter 2.3.3 --- The drugs to which A10HR and A20HR cells were more resistant --- p.17 / Chapter 2.3.4 --- The drugs to which A10HR and/or A20HR cells were more sensitive --- p.17 / Chapter 2.3.5 --- "The drugs which AP, A10HR and A20HR cells have similar response" --- p.18 / Chapter 2.4 --- Discussion --- p.24 / Chapter 2.4.1 --- Camptothecin and 10-hydroxy camptothecin --- p.27 / Chapter 2.4.2 --- Etoposide --- p.30 / Chapter 2.4.3 --- Hydrogen peroxide --- p.32 / Chapter 2.4.4 --- Interferons --- p.32 / Chapter 2.4.4.1 --- Interferon alpha --- p.33 / Chapter 2.4.4.2 --- Interferon gamma --- p.34 / Chapter 2.4.5 --- Methotrexate --- p.35 / Chapter 2.4.6 --- Vincristine --- p.36 / Chapter Chapter 3: --- The resistance mechanism of doxorubicin in A431 cells / Chapter 3.1 --- Introduction --- p.38 / Chapter 3.1.1 --- Chemotherapeutic resistance --- p.38 / Chapter 3.1.2 --- Tumor hypoxia --- p.39 / Chapter 3.1.3 --- Structure and function of doxorubicin --- p.39 / Chapter 3.1.4 --- Clinical use of doxorubicin --- p.40 / Chapter 3.1.5 --- Mechanisms of doxorubicin resistance --- p.41 / Chapter 3.1.6 --- Structure and function of P-glycoprotein --- p.42 / Chapter 3.1.7 --- Drug resistance contributed by P-glycoprotein and the solution --- p.43 / Chapter 3.1.8 --- Epigenetic modulation of mdr1 --- p.45 / Chapter 3.2 --- Materials and Methods --- p.47 / Chapter 3.2.1 --- Cell culture --- p.47 / Chapter 3.2.2 --- MTT assay --- p.47 / Chapter 3.2.3 --- Reverse transcription polymerase chain reaction (RT-PCR) --- p.47 / Chapter 3.2.4 --- Western blot analysis --- p.48 / Chapter 3.2.5 --- Doxorubicin efflux assay --- p.50 / Chapter 3.2.6 --- Drug sensitivity of A431 cells treated with verapamil --- p.50 / Chapter 3.2.7 --- Treatment with DNA methyltransferase inhibitor --- p.51 / Chapter 3.2.8 --- Drug sensitivity of A431 cells treated with 5-Aza-dC --- p.51 / Chapter 3.2.9 --- Methylation-specific PCR (MSP) --- p.51 / Chapter 3.2.10 --- Bisulfite genomic DNA sequencing --- p.52 / Chapter 3.3 --- Results --- p.54 / Chapter 3.3.1 --- Drug sensitivity of A431 cells to doxorubicin --- p.54 / Chapter 3.3.2 --- Expression profile of mdrl and P-glycoprotein in A431 cells --- p.54 / Chapter 3.3.3 --- Dox efflux-pump activity in A431 cells --- p.57 / Chapter 3.3.4 --- Drug sensitivity of A431 cells in the presence of verapamil --- p.59 / Chapter 3.3.5 --- Expression profile of mdrl in A431 cells in the presence of 5- Aza-dC --- p.59 / Chapter 3.3.6 --- Drug sensitivity of A431 cells in the presence of 5-Aza-dC --- p.62 / Chapter 3.3.7 --- Methylation status of mdrl promoter region --- p.64 / Chapter 3.3.8 --- Bisulfite genomic DNA sequencing of the mdrl promoter --- p.64 / Chapter 3.4 --- Discussion --- p.67 / Chapter Chapter 4: --- The resistance mechanism of cisplatin in HepG2 cells / Chapter 4.1 --- Introduction --- p.70 / Chapter 4.1.1 --- Tumor hypoxia and chemotherapeutic resistance --- p.70 / Chapter 4.1.2 --- Cisplatin and its action mechanism --- p.71 / Chapter 4.1.3 --- Mechanisms of cisplatin resistance --- p.74 / Chapter 4.1.4 --- Mismatch repair genes --- p.79 / Chapter 4.1.5 --- Epigenome and drug resistance in cancer --- p.80 / Chapter 4.2 --- Materials and Methods --- p.84 / Chapter 4.2.1 --- Cell culture --- p.84 / Chapter 4.2.2 --- MTT assay --- p.84 / Chapter 4.2.3 --- Reverse transcription polymerase chain reaction (RT-PCR) --- p.84 / Chapter 4.2.4 --- Oligonucleotide transfection --- p.85 / Chapter 4.2.5 --- Treatment with DNA methyltransferase inhibitor --- p.86 / Chapter 4.2.6 --- Drug sensitivity of HepG2 cells treated with 5-Aza-dC --- p.87 / Chapter 4.2.7 --- Treatment with histone deacetylase inhibitor --- p.87 / Chapter 4.2.8 --- Drug sensitivity of HepG2 cells treated with TSA --- p.87 / Chapter 4.3 --- Results --- p.89 / Chapter 4.3.1 --- Drug sensitivity of HepG2 cells to cisplatin --- p.89 / Chapter 4.3.2 --- Expression profile of the MMR genes in HepG2 cells --- p.89 / Chapter 4.3.3 --- Drug sensitivity of HepG2 cells to cisplatin after the knock- down of PMS2 --- p.91 / Chapter 4.3.4 --- Expression profile of MMR genes in the presence of 5-Aza-dC --- p.95 / Chapter 4.3.5 --- Drug sensitivity of HepG2 cells to cisplatin after the addition of 5-Aza-dC --- p.95 / Chapter 4.3.6 --- Expression profile of MMR genes in the presence of trichostatin A --- p.98 / Chapter 4.3.7 --- Sensitivity of HepG2 cells to cisplatin after the addition of trichostatin A --- p.98 / Chapter 4.4 --- Discussion --- p.101 / Chapter Chapter 5: --- The role of PMS2 in cisplatin-induced apoptosis / Chapter 5.1 --- Introduction --- p.105 / Chapter 5.1.1 --- Apoptosis --- p.105 / Chapter 5.1.2 --- Extrinsic pathway of apoptosis --- p.106 / Chapter 5.1.3 --- Intrinsic pathway of apoptosis --- p.106 / Chapter 5.1.4 --- Cisplatin-induced apoptosis --- p.107 / Chapter 5.1.5 --- MMR and apoptosis --- p.109 / Chapter 5.2 --- Materials and Methods --- p.111 / Chapter 5.2.1 --- Cell culture --- p.111 / Chapter 5.2.2 --- Flow cytometric analysis of apoptosis --- p.111 / Chapter 5.2.3 --- Oligonucleotide transfection --- p.111 / Chapter 5.2.4 --- Western blot analysis --- p.111 / Chapter 5.2.5 --- Drug and antibodies --- p.112 / Chapter 5.3 --- Results --- p.113 / Chapter 5.3.1 --- Cisplatin induced apoptosis --- p.113 / Chapter 5.3.2 --- Knockdown of PMS2 by siRNA --- p.113 / Chapter 5.3.3 --- Cisplatin-induced apoptosis involved caspases --- p.115 / Chapter 5.3.4 --- Protein expressions of anti-apoptotic genes --- p.119 / Chapter 5.3.5 --- Protein expressions of pro-apoptotic genes --- p.119 / Chapter 5.3.6 --- Protein expressions of apoptotic proteins after knockdown of PMS2 --- p.122 / Chapter 5.4 --- Discussion --- p.124 / Chapter Chapter 6: --- General discussion and conclusion / Chapter 6.1 --- Diverse sensitivity for hypoxia/reoxygenation treated cells to anticancer drugs --- p.128 / Chapter 6.2 --- Resistance mechanism of doxorubicin in A10HR and A20HR cells --- p.129 / Chapter 6.3 --- Resistance mechanism of cisplatin in G10HR and G20HR cells --- p.129 / Chapter 6.4 --- The role of PMS2 as a direct signaling molecule and the alteration of apoptotic proteins in cisplatin-induced apoptosis --- p.130 / Chapter 6.5 --- Future work --- p.131 / References --- p.132

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_326558
Date January 2008
ContributorsChoi, Siu Cheong., Chinese University of Hong Kong Graduate School. Division of Biochemistry.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xviii, 148 leaves : col. 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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