Li Ka Wai Kay. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references. / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT (ENGLISH/CHINESE) --- p.ii / TABLE OF CONTENTS --- p.viii / LIST OF FIGURES --- p.xii / LIST OF APPENDICES --- p.xiii / Chapter 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Gastric carcinomas --- p.1 / Chapter 1.1a --- Epidemiology --- p.1 / Chapter 1.1b --- Classification --- p.2 / Chapter 1.1c --- TNM staging --- p.3 / Chapter 1.1d --- Prognosis --- p.4 / Chapter 1.1e --- Etiology --- p.6 / Chapter 1.1f --- Genetic alteration in gastric cancer --- p.10 / Chapter 1.2 --- Treatment --- p.16 / Chapter 1.2a --- "Surgery, chemotherapy, and others" --- p.16 / Chapter 1.2b --- Response rate of treatments in previous studies --- p.18 / Chapter 1.2c --- Chemotherapeutic Drugs --- p.21 / Chapter 1.2c (1) --- 5-fluorouracil (5-FU) --- p.22 / Chapter 1.2c (2) --- cis-diamminedichloroplatinum (Cisplatin) --- p.23 / Chapter 1.2c (3) --- Doxorubicin (Adriamycin) --- p.23 / Chapter 1.2c (4) --- Daunorubicin --- p.25 / Chapter 1.2c (5) --- Epirubicin --- p.25 / Chapter 1.2d --- Toxicity of chemotherapeutic drugs --- p.26 / Chapter 1.2d (1) --- Side effects of 5-FU --- p.26 / Chapter 1.2d (2) --- "Side effects of anthracyc lines (adriamycin, daunobicin, epuirbicin)" --- p.27 / Chapter 1.2d (3) --- Side effects of cisplatin --- p.28 / Chapter 1.3 --- Mechanisms of drug resistance --- p.28 / Chapter 1.3a --- Drug resistance --- p.28 / Chapter 1.3b --- P-glycoprotein (MDR1 gene) --- p.29 / Chapter 1.3c --- p53 tumor suppressor gene --- p.35 / Chapter 1.4 --- Chemosensitivity testing --- p.40 / Chapter 1.4a --- Original of chemosensitivity testing --- p.40 / Chapter 1.4b --- Non-clonogentic assay --- p.40 / Chapter 1.4c --- Clonogenic assay --- p.42 / Chapter 2 --- AIM OF MY STUDY --- p.44 / Chapter 3 --- MATERIALS AND METHODS --- p.45 / Chapter 3.1 --- Patients --- p.45 / Chapter 3.2 --- Tumor collection and handling procedure --- p.46 / Chapter 3.2a --- Large tumor tissue from gastrectomy --- p.46 / Chapter 3.2b --- Pseudo-biopsies --- p.47 / Chapter 3.3 --- Chemosensitivity testing --- p.48 / Chapter 3.3a --- Cell Plating --- p.48 / Chapter 3.3b --- Drug testing --- p.49 / Chapter 3.4 --- Chemosensitivity analysis --- p.50 / Chapter 3.5 --- Conformational sensitive gel electrophoresis analysis (CSGE) and single strand conformational polymorphism (SSCP) --- p.51 / Chapter 3.5a --- Preparation of genomic DNA --- p.51 / Chapter 3.5b --- PCR condition for CSGE analysis --- p.51 / Chapter 3.5c --- Scanning PCR products by CSGE --- p.52 / Chapter 3.5d --- PCR condition for SSCP analysis --- p.53 / Chapter 3.5e --- Scanning PCR products by SSCP --- p.53 / Chapter 3.6 --- Reverse transcription-polymerase chain reaction (RT-PCR) for multi-drug drug resistance (MDR1) gene --- p.54 / Chapter 3.6a --- Isolation of RNA --- p.54 / Chapter 3.6b --- cDNA synthesis --- p.55 / Chapter 3.6c --- PCR primers --- p.55 / Chapter 3.6d --- Optimalization of PCR condition for MDR1 gene expression --- p.56 / Chapter 3.6e --- PCR of β2-m gene --- p.57 / Chapter 3.6f --- PCR of MDR1 gene and analysis of its expression --- p.57 / Chapter 3.7 --- Immunohistochemistry --- p.58 / Chapter 3.7a --- Immunostaining by DO-7 --- p.58 / Chapter 3.7b --- lmmunohistochemistochemical analysis of p53 protein expression --- p.59 / Chapter 3.8 --- Statistics --- p.59 / Chapter 4. --- RESULTS --- p.60 / Chapter 4.1 --- Chemosensitivity testing --- p.60 / Chapter 4.1a --- Tests completed --- p.60 / Chapter 4.1b --- Number of cases tested for each drug --- p.60 / Chapter 4.1c --- 〇D reading of the background samples --- p.60 / Chapter 4.1d --- Dose-dependent response curve --- p.61 / Chapter 4.1e --- Unique IC50 for each tumor in each drug test --- p.61 / Chapter 4.1f --- Wide distribution of ic50 for anti-tumor drugs --- p.61 / Chapter 4.1g --- Chemosensitivity and tumor histologic type --- p.63 / Chapter 4.1h --- Correlation of ic50 with tumor stage --- p.63 / Chapter 4.2 --- Immunohistochemical staining of p53 protein (DO-7) --- p.64 / Chapter 4.2a --- p53 protein accumulation in samples --- p.64 / Chapter 4.2b --- Correlation of p53 IHC expression and chemosensitivity --- p.64 / Chapter 4.3 --- SSCP and CSGE --- p.65 / Chapter 4.3a --- Detection of abnormal band movement --- p.65 / Chapter 4.3b --- Correlation of p53 mutations with chemosensitivity --- p.66 / Chapter 4.3c --- Concordance between IHC and SSCP/CSGE --- p.66 / Chapter 4.4 --- MDR1 gene expression --- p.67 / Chapter 4.4a --- MDR1 gene expression in normal and tumors --- p.67 / Chapter 4.4b --- Correlation of MDR1 expression and chemosensitivity --- p.68 / Chapter 4.5 --- Pseudobiopsies --- p.68 / Chapter 5 --- DISCUSSION --- p.70 / Chapter 5.1 --- p53 analysis of the tumors --- p.70 / Chapter 5.1a --- Immunohistochemistry versus mutational analysis --- p.70 / Chapter 5.1b --- Methods of mutational analysis --- p.73 / Chapter 5.1c --- Comparing IHC results with previous findings --- p.77 / Chapter 5.1d --- Comparing SSCP/ CSGE results with previous findings --- p.78 / Chapter 5.1e --- Correlation of IHC and SSCP/CSGE results --- p.81 / Chapter 5.2 --- MDR1 expression --- p.85 / Chapter 5.2a --- Methods for detecting MDR1 expression --- p.85 / Chapter 5.2b --- Comparing MDR1 expression results with published data --- p.88 / Chapter 5.2c --- Correlation between chemosensitivity and MDR1 gene expression --- p.92 / Chapter 5.3 --- Chemosensitivity testing --- p.94 / Chapter 5.3a --- Chemosensitivity testing method --- p.94 / Chapter 5.3b --- The chemosensitivity results --- p.102 / Chapter 5.3c --- Chemosensitivity and MDR1 expression --- p.108 / Chapter 5.3d --- Chemosensitivity and p53 immunohistochemical expression… --- p.110 / Chapter 5.3e --- Chemosensitivity and p53 mutations --- p.112 / Chapter 5.3f --- Limitation of this study --- p.115 / Chapter 5.3g --- Pseudobiopsies and large tumor samples --- p.118 / Chapter 6. --- conclusions --- p.121 / figures / appendices / references