Thesis (Ph. D.)--Cornell University, August, 1999. / Vita. Includes bibliographical references (leaves 141-168).

Diss. (sammanfattning) Linköping : Univ., 2001. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Thesis (M.S.)--University of Alabama at Birmingham, 2009. / Title from first page of PDF file (viewed on June 11, 2009). Includes bibliographical references (p. 44-54).

by Chung Lung Ying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 149-157). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abbreviations --- p.ii / Abstracts --- p.v / List of figures --- p.ix / List of tables --- p.xii / Contents --- p.xiii / Contents / General Introduction --- p.1 / Chapter CHAPTER ONE --- CISPLATIN RESISTANCE MECHANISMS / Chapter 1.1 --- INTRODUCTION --- p.3 / Chapter 1.1.1 --- History of Cisplatin as An Anticancer Drug --- p.3 / Chapter 1.1.2 --- Active Mechanisms of Cisplatin --- p.8 / Chapter 1.1.3 --- Formation of DNA Adducts --- p.8 / Chapter 1.1.4 --- Cisplatin Resistance Mechanisms --- p.9 / Chapter 1.1.4.1 --- Intracellular Accumulation of Cisplatin --- p.11 / Chapter 1.1.4.2 --- Glutathione-S-transferase and Glutathion --- p.12 / Chapter 1.1.4.3 --- Metallothionein --- p.16 / Chapter 1.1.4.4 --- Cell Cycle Perturbation --- p.16 / Chapter 1.1.4.5 --- P-glycoprotein --- p.17 / Chapter 1.1.4.6 --- Multidrug Resistant Protein --- p.19 / Chapter 1.1.4.7 --- Topoisomerase II --- p.20 / Chapter 1.1.4.8 --- DNA Repair --- p.22 / Chapter 1.1.4.9 --- Induction of Programme Cell Death --- p.23 / Chapter 1.2 --- OBJECTIVES --- p.27 / Chapter 1.3 --- MATERIALS AND METHODS / Chapter 1.3.1 --- Materials --- p.28 / Chapter 1.3.2 --- Methods --- p.31 / Chapter 1.3.2.1 --- Cell Lines --- p.31 / Chapter 1.3.2.2 --- Drug Sensitivity Assay --- p.31 / Chapter 1.3.2.3 --- Platinum Uptake --- p.32 / Chapter 1.3.2.4 --- Cell Cycle Analysis --- p.32 / Chapter 1.3.2.5 --- Western Blot Analysis --- p.33 / Chapter 1.3.2.6 --- Glutathione Content Determination --- p.36 / Chapter 1.3.2.7 --- DNA Fragmentation --- p.36 / Chapter 1.3.2.8 --- JC-1 Staining --- p.37 / Chapter 1.3.2.9 --- HE and DCF Staining --- p.38 / Chapter 1.3.2.10 --- Quantitative RT-PCR --- p.38 / Chapter 1.4 --- RESULTS / Chapter 1.4.1 --- Cisplatin Sensitivity of A431 Cells by MTT Assay --- p.40 / Chapter 1.4.2 --- Cross-resistance to Anti-cancer Drugs --- p.40 / Chapter 1.4.3 --- Quantitation of Cisplatin Accumulation in A431 Cells by AAS --- p.44 / Chapter 1.4.4 --- Drug Detoxification Agent --- p.45 / Chapter 1.4.5 --- Detection of Cell Cycle Arrest by Flow Cytometer --- p.47 / Chapter 1.4.6 --- Expression of Drug Resistance Related Genes --- p.48 / Chapter 1.4.7 --- Detection of Apoptosis by DNA Fragmentation --- p.50 / Chapter 1.4.8 --- Role of Mitochondria and Reactive Oxygen Species by Flow Cytometer --- p.52 / Chapter 1.4.9 --- Detection of Apoptotic mRNA Level by Quantitative RT-PCR --- p.57 / Chapter 1.4.10 --- Detection of Apoptotic Protein Level by Western Blot Analysis --- p.57 / Chapter 1.5 --- DISCUSSIONS --- p.59 / Chapter CHAPTER TWO: --- THE INTERACTION BETWEEN DRUG RESISTANCE MECHANISMS AND GROWTH FACTOR SIGNALLING PATHWAY / Chapter 2.1 --- INTRODUCTION --- p.63 / Chapter 2.1.1 --- Structure of EGF and EGFR --- p.64 / Chapter 2.1.2 --- Growth Factor Signal Transduction Pathway --- p.69 / Chapter 2.1.3 --- Biological Effect of EGF --- p.69 / Chapter 2.1.3.1 --- Modification of Drug Sensitivity by EGF --- p.71 / Chapter 2.2 --- OBJECTIVES --- p.74 / Chapter 2.3 --- MATERIALS AND METHODS / Chapter 2.3.1 --- Materials --- p.75 / Chapter 2.3.2 --- Methods / Chapter 2.3.2.1 --- Cell Lines --- p.76 / Chapter 2.3.2.2 --- Drug Sensitivity Assay --- p.77 / Chapter 2.3.2.3 --- Northern Blot Analysis --- p.77 / Chapter 2.3.2.4 --- Southern Blot Analysis --- p.78 / Chapter 2.3.2.5 --- Others --- p.78 / Chapter 2.4 --- RESULTS / Chapter 2.4.1 --- Sensitivity to EGF --- p.79 / Chapter 2.4.2 --- EGFR Expression Levels --- p.80 / Chapter 2.4.3 --- EGF Induced Protein Phosphorylation Pattern --- p.84 / Chapter 2.4.4 --- Effect of EGF on A431 Cells --- p.86 / Chapter 2.4.5 --- Response of Cells to Agents Targeting on EGF Signalling Pathway --- p.91 / Chapter 2.4.6 --- Response of Cells to Other Growth Factors --- p.97 / Chapter 2.4.7 --- Sensitivity of Cells to Different Anti-cancer Drugs --- p.99 / Chapter 2.4.8 --- Drug Resistance Mechanisms --- p.103 / Chapter 2.4.9 --- 5-Fluorouracil Sensitivity in A431 Cells --- p.108 / Chapter 2.4.10 --- Cisplatin Sensitivity in A431 Cells --- p.113 / Chapter 2.5 --- DISCUSSIONS --- p.117 / Chapter CHAPTER THREE: --- IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENE IN A431 CELLS BY DIFFERENTIAL DISPLAY / Chapter 3.1 --- INTRODUCTION --- p.122 / Chapter 3.2 --- MATERIALS AND METHODS / Chapter 3.2.1 --- Materials --- p.128 / Chapter 3.2.2 --- Methods / Chapter 3.2.2.1 --- Identification of Differentially Expressed Genes by RT-PCR / Chapter 3.2.2.2 --- Cloning of a Differentially Expressed cDNAs --- p.129 / Chapter 3.2.2.3 --- Screening and Sequencing of cDNA Inserts --- p.130 / Chapter 3.2.2.4 --- Rapid Amplification of cDNA Ends (RACE) --- p.131 / Chapter 3.2.2.5 --- Amplifcation Reaction --- p.131 / Chapter 3.2.2.6 --- Cloning and Sequencing of the RACE Fragment --- p.132 / Chapter 3.3 --- RESULTS / Chapter 3.3.1 --- Identification of novel cDNA by mRNA differential display --- p.133 / Chapter 3.4 --- DISCUSSIONS --- p.145 / General Conclusion --- p.147 / References --- p.149

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

This thesis summarises research performed with the intent of exploring the many facets of cell death. In the first part of the thesis, the fate of the formin-homology domain containing protein FHOD1 during apoptosis is examined (research performed in the laboratory of Dr. Sophie Roy) and evidence for the cleavage of FHOD1 by caspase-3 at the SVPD616 site is demonstrated. Moreover, the C-terminal FHOD1 cleavage product is shown to translocate to the nucleolus where it inactivates RNA polymerase I transcription. / In the second part of the thesis, the role of the RNA-binding protein HuR in cancer cell migration and invasion, as well as in multidrug resistance is determined using RNA interference to knockdown the expression of HuR in HeLa and KB-V1 cells respectively (research performed in the laboratory of Dr. Imed Gallouzi). In this part of the thesis, HuR is shown to promote cancer cell migration and invasion by stabilizing the beta-actin mRNA in a U-rich-dependent manner. Moreover, evidence is shown for the potential involvement of HuR in the phenomenon of multidrug resistance possibly through the post-transcriptional regulation of the multidrug resistance 1 gene.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.