Wong Pak Cheung Ronald. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 121-142). / Abstracts in English and Chinese. / Acknowledgement --- p.I / Abstract --- p.II / Abbreviation --- p.VI / List of figures --- p.IX / List of tables --- p.XI / Content --- p.XII / Content / Chapter Chapter 1: --- General Introduction --- p.1 / Chapter 1.1 --- The p53 tumor suppressor gene --- p.2 / Chapter 1.1.1 --- Structure and function --- p.2 / Chapter 1.1.2 --- Regulation of p53 stability and activity --- p.3 / Chapter 1.1.3 --- p53 and cell cycle arrest --- p.4 / Chapter 1.1.4 --- p53 and apoptosis --- p.4 / Chapter 1.2 --- Mutation in p53 gene --- p.9 / Chapter 1.2.1 --- Loss of function through dominant negative effect --- p.9 / Chapter 1.2.2 --- Gain-of-function through transactivation by mutant p53 --- p.10 / Chapter 1.2.3 --- Mutation in p53 and resistance to cancer therapy --- p.10 / Chapter 1.3 --- Objective of the study --- p.14 / Chapter Chapter 2: --- Mutant p53 induced interferon resistance and its regulation of the Jak/Stat pathway --- p.15 / Chapter 2.1 --- Introduction --- p.16 / Chapter 2.1.1 --- IFN classification and biological activities --- p.16 / Chapter 2.1.2 --- IFN signaling --- p.17 / Chapter 2.1.3 --- IFN direct antitumor effect: cell cycle arrest and apoptosis --- p.18 / Chapter 2.1.4 --- IFN in immunotherapy --- p.20 / Chapter 2.1.5 --- Resistance to IFN therapy --- p.21 / Chapter 2.2 --- Materials and Methods --- p.24 / Chapter 2.2.1 --- Cell lines --- p.24 / Chapter 2.2.2 --- Drugs and antibodies --- p.24 / Chapter 2.2.3 --- Cell Proliferation assay- MTT assay --- p.24 / Chapter 2.2.4 --- Cell cycle analysis --- p.25 / Chapter 2.2.5 --- DNA fragmentation assay --- p.25 / Chapter 2.2.6 --- Western blot analysis --- p.26 / Chapter 2.2.7 --- "Combined treatment of IFNs and Jak inhibitors in MTT assay, DNA fragmentation assay and Western blot analysis" --- p.26 / Chapter 2.3 --- Results --- p.27 / Chapter 2.3.1 --- Mutant p53-V143A and p53-R273H induced IFN resistance: the role of IFN induced apoptosis and cell cycle arrest --- p.27 / Chapter 2.3.2 --- IFN induction of apoptosis: a p53-independent and caspase-dependent pathway --- p.28 / Chapter 2.3.3 --- Mutant p53 regulation of Jak/Stat pathway --- p.36 / Chapter 2.3.4 --- Janus kinases (Jaks) and IFN-alpha sensitivity in Saos-2 cells --- p.41 / Chapter 2.3.5 --- Janus kinases (Jaks) and IFN-gamma sensitivity --- p.49 / Chapter 2.4 --- Discussion --- p.56 / Chapter 2.4.1 --- Mutant p53-V143 and p53-R273H induced IFN resistance in Saos-2 cells --- p.56 / Chapter 2.4.2 --- Role of Jaks in IFN sensitivity in Saos-2 cells --- p.57 / Chapter 2.4.3 --- IFN signaling in Saos-2 cells --- p.57 / Chapter 2.4.4 --- Jak2 and IFN induced apoptosis --- p.58 / Chapter Chapter 3: --- Mutant p53 induced drug resistance --- p.60 / Chapter 3.1 --- Introduction --- p.61 / Chapter 3.1.1 --- The multidrug resistance (MDR) --- p.61 / Chapter 3.1.2 --- Anticancer drugs used in the study: action mechanisms and resistance --- p.67 / Chapter 3.1.3 --- Jak/Stat pathway and MDR --- p.68 / Chapter 3 .2 --- Materials and Methods --- p.72 / Chapter 3.2.1 --- Cell lines --- p.72 / Chapter 3.2.2 --- Drugs and antibodies --- p.72 / Chapter 3.2.3 --- Caspase 3 activity assay --- p.72 / Chapter 3.2.4 --- Cell Proliferation assay- MTT assay --- p.73 / Chapter 3.2.5 --- Cell cycle analysis --- p.73 / Chapter 3.2.6 --- DNA fragmentation assay --- p.73 / Chapter 3.2.7 --- Reverse transcription polymerase chain reaction --- p.73 / Chapter 3.2.8 --- Western blot analysis --- p.74 / Chapter 3.2.9 --- "Combined treatment of IFNs and Jak inhibitors in MTT assay, DNA fragmentation assay and Western blot analysis" --- p.74 / Chapter 3.3 --- Results --- p.75 / Chapter 3.3.1 --- Mutant p53 and drug sensitivity --- p.75 / Chapter 3.3.2 --- Mutant p53 and drug induced apoptosis and cell cycle arrest --- p.75 / Chapter 3.3.3 --- Classical drug resistance factors in mutant p53 induced drug resistance --- p.87 / Chapter 3.3.4 --- The role of Jaks in drug sensitivity of Saos-2 cells --- p.89 / Chapter 3.3.5 --- The role of Jaks in drug induced DNA fragmentationin Saos-2 cells --- p.89 / Chapter 3.3.6 --- Jak signaling and caspase activation in MTX induced apoptosis in Saos-2 cells --- p.100 / Chapter 3.3 --- Discussion --- p.108 / Chapter 3.3.1 --- Mutant p53-V143A and p53-R273H induced drug resistance in Saos-2 cells --- p.108 / Chapter 3.3.2 --- Role of Jaks in drug sensitivity in Saos-2 cells --- p.109 / Chapter 3.3.3 --- Jak/Stat signaling in Saos-2 cells --- p.109 / Chapter 3.3.4 --- Jak2 and MTX induced apoptosis --- p.110 / Chapter Chapter 4: --- General discussion --- p.112 / Chapter 4.1 --- Mutant p53 induced immunotherapy and chemotherapy resistance --- p.113 / Chapter 4.2 --- Gain of new function of mutant p53-V143A and p53-R273H in regulating Jak/Stat pathway leading to resistance to IFN and chemotherapeutic drugs --- p.114 / Chapter 4.3 --- The role of Jaks in MTX sensitivity --- p.114 / Chapter 4.4 --- Future work --- p.115 / Chapter 4.5 --- Perspective --- p.120 / References --- p.121
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_324609 |
| Date | January 2004 |
| Contributors | Wong, Pak Cheung Ronald., 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, xiv, 142 leaves : ill. ; 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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