by Chan Chi Wai, Michael. / "July 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 238-272). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

by Wai-keung Leung. / Thesis (M.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 217-232). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Induction of ITF expression significantly enhanced invasion of Rat-2 (1.8-folds) without promoting proliferation. The increase in invasiveness was accompanied by an upregulation of beta-catenin (18.0%) and MMP-9 (67.8%), and downregulation of E-cadherin (29.7%) and TIMP-1 (34.7%). Silencing ITF in MKN45 markedly delayed the onset of tumor progression by Day 6 and reduced the tumor volume by 85% by Day 14. ITF siRNA significantly attenuated angiogenesis in vivo and in vitro. The effects of silencing ITF were mediated through transcriptional upregulation of the Bax (114%), Bak (89%), Ang-2 (89%) and Tie-2 (399%). Bcl-2, Bcl-xL, VEGF and Ang-1 expressions were not significantly altered. Silencing ITF in gastric cancer cells increased the effect of cisplatin-induced apoptosis in a dose-dependent manner. / Our findings suggested that ITF plays a role in invasion, proliferation and angiogenesis. The mechanisms involve regulation of catenin-cadherin complexes, balance of MMPs/TIMPs, proapoptotic Bcl-2 family members and Ang-2/Tie-2 system. Silencing ITF enhanced the chemotherapeutic response of gastric cancer cells to cisplatin. Blocking ITF expression using RNA interference may have a potential therapeutic application in gastric cancer. (Abstract shortened by UMI.) / The aim of this project was to define the role of ITF in gastric carcinogenesis. The thesis consisted of two parts of scientific studies to investigate the effects of: inducing ITF expression on the proliferation and invasion of non-tumorigenic rat fbroblast cells (Part 1); and silencing ITF on the proliferation, angiogenesis and chemotherapeutic response in gastric cancer cells (Part 2). / Chan Yik Wai. / "August 2005." / Adviser: Francis Ka Leung Chan. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3719. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 124-139). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.

by Chan Ka Lee. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 94-112). / Abstracts in English and Chinese. / Acknowledgements --- p.i / abstract(english/chinese) --- p.iii / Contents --- p.vii / List of Tables --- p.xi / List of Figures --- p.xii / Chapter I --- Introduction --- p.1 / Chapter I.1 --- Gastric Lymphoma --- p.1 / Chapter I.1.1 --- Background --- p.1 / Chapter I.1.2 --- Mucosa-Associated Lymphoid Tissue --- p.2 / Chapter I.1.3 --- Classification of Primary Gastric Lymphomas --- p.3 / Chapter I.1.3.1 --- Mucosa-Associated Lymphooid Tissue Type Lymphomas --- p.3 / Chapter I.1.3.2 --- High Grade Primary Gastric Lymphomas --- p.5 / Chapter I.1.3.3 --- Other Gastric Lymphomas --- p.7 / Chapter I.2 --- Helicobater Pylori --- p.8 / Chapter I.3 --- Epstein-Barr Virus --- p.9 / Chapter I.3.1 --- Epidemiology --- p.9 / Chapter I.3.2 --- Virus and Genome Structure --- p.9 / Chapter I.3.3 --- Latent Infection --- p.11 / Chapter I.3.4 --- Latent Membrane Protein-1 --- p.12 / Chapter I.3.5 --- "EBV-Encoded, Small Non-polydenylated RNAs (EBERs)" --- p.13 / Chapter I.3.6 --- Disease Associated with EBV --- p.13 / Chapter I.3.7 --- EBV and PGL --- p.14 / Chapter I.4 --- Genetic Alterations --- p.15 / Chapter I.4.1 --- Background --- p.15 / Chapter I.4.2 --- Tumor Suppressor Genes (TSGs) --- p.16 / Chapter I.4.2.1 --- Origin and Structure of p53 Gene and Protein --- p.16 / Chapter I.4.2.2 --- Functions of p53 Gene --- p.18 / Chapter I.4.2.3 --- Inactivation Mechanisms of p53 --- p.21 / Chapter I.4.2.4 --- p53 Mutations and Protein Expression in NHLs --- p.24 / Chapter I.4.3 --- Oncogene --- p.25 / Chapter I.4.3.1 --- Bcl-2 --- p.25 / Chapter I.4.3.2 --- Other Oncogenes --- p.27 / Chapter II --- OBJECTIVES OF STUD Y --- p.30 / Chapter III --- ma terials and methods --- p.31 / Chapter III.1 --- Materials --- p.31 / Chapter III.2 --- Detection of EB V Latent Gene Product by In-situ Hybridization --- p.33 / Chapter III.2.1 --- Pretreatment of Paraffin-embedded Tissues and Apparatus --- p.33 / Chapter III.2.2 --- In-situ Hybridization of EBERs --- p.34 / Chapter III.3 --- Detection of p53 and bcl-2 and LMP-1 Protein Expression by Immunohisiochemistry --- p.35 / Chapter III.4 --- Microdissection of Formalin-fixed Paraffin-embedded Tissues --- p.37 / Chapter III.5 --- Extraction of Genomic DNA from Formalin-fixed Paraffin-embedded Tissues --- p.38 / Chapter III.5.1 --- Phenol / Chloroform Extraction --- p.38 / Chapter III.5.2 --- Commercially Available DNA Extraction Kit --- p.40 / Chapter III.6 --- Mutational Analysis p53 --- p.41 / Chapter III.6.1 --- Polymerase Chain Reaction - Single Strand Conformation Polymorphism (PCR-SSCP) Analysis --- p.41 / Chapter III.6.1.1 --- PCR primers --- p.41 / Chapter III.6.1.2 --- PCR Amplification ofp53 gene --- p.42 / Chapter III.6.1.3 --- Non-denaturing Polyacrylamide Gel Electrophoresis --- p.42 / Chapter III.6.2 --- DNA Sequencing Analysis --- p.44 / Chapter III.6.2.1 --- Purification of DNA from Shifts on Non-denaturing Gels --- p.44 / Chapter III.6.2.2 --- 5' end Labeling of Primer --- p.45 / Chapter III.6.2.3 --- Cycle Sequencing --- p.45 / Chapter III.6.2.4 --- Denaturing Gel Electrophoresis --- p.46 / Chapter III.7 --- Loss of Heterozygosity (LOH) Analysis on Chromosome 17p --- p.47 / Chapter III.7.1 --- Microsatellite Markers --- p.49 / Chapter III.7.2 --- PCR Amplification of DNA Fragments Containing Polymorphic Microsatellites --- p.49 / Chapter III.7.3 --- Denaturing Polyacrylamide Gel Electrophoresis --- p.50 / Chapter III.7.4 --- Determination of Allelic Abnormalities --- p.51 / Chapter III. 8 --- Statistical Analysis --- p.52 / Chapter IV --- results --- p.53 / Chapter IV.1 --- Association with Helicobactor Pylori (HP) --- p.53 / Chapter IV.2 --- Detection of EBERs by ISH --- p.53 / Chapter IV.3 --- Immunohistochemical Analysis --- p.54 / Chapter IV.3.1 --- Protein Expression of EBV LMP-1 --- p.54 / Chapter IV.3.2 --- Protein Expression of p53 --- p.54 / Chapter IV.3.3 --- Protein Expression of bcl-2 --- p.55 / Chapter IV.3.4 --- Correlation between p53 and bcl-2 Protein Expression --- p.55 / Chapter IV.4 --- Mutational Analysis of p53 --- p.56 / Chapter IV.5 --- LOH Analysis on Chromosome 17p --- p.57 / Chapter V --- DISCUSSION --- p.58 / Chapter V.1 --- Helicobactor Pylori Association --- p.58 / Chapter V.2 --- Association with EE V --- p.60 / Chapter V.3 --- Protein Expression of p53 and bcl-2 --- p.61 / Chapter V.3.1 --- p53 --- p.61 / Chapter V.3.2 --- Bcl-2 --- p.62 / Chapter V.3.3 --- Correlation between p53 and bcl-2 Expression --- p.63 / Chapter V.4 --- p53 Gene Molecular Analysis --- p.65 / Chapter V.5 --- Distribution of Mutations and Molecular Fingerprinting --- p.67 / Chapter V.6 --- Possible Role of p53 Mutation in EBV+ Gastric Lymphomas --- p.69 / ILLUSTRATIONS --- p.71 / references --- p.94

Cathelicidin, a pleiotropic host defense peptide, has been shown to promote cutaneous wound repair and reaches high levels in the gastric mucosa during acute Helicobacter pylori-associated inflammation. The expression of cathelicidin, nevertheless, has also been found to be down-regulated in gastric hyperplastic polyps, tubular adenomas, and adenocarcinomas. We therefore hypothesized that cathelicidin might contribute to gastric ulcer healing and suppress gastric cancer growth. In this study, the role of this peptide in gastric tissue repair and carcinogenesis was investigated. / Collectively, this study demonstrates for the first time that cathelicidin can promote tissue repair and suppress cancer growth in stomachs by eliciting differential cellular signaling and responses in normal and cancerous gastric epithelial cells. These unique biological activities may open up a novel therapeutic avenue for the treatment of these diseases. / Concerning gastric carcinogenesis, the human cathelicidin LL-37 lowered gastric cancer cell proliferation and delayed G1-S transition in vitro and inhibited the growth of gastric cancer xenograft in vivo. Knockdown or induction of endogenous LL-37 by RNA interference or 1alpha,25-dihydroxylvitamin D3, respectively, increased or suppressed cell proliferation. In this connection, LL-37 increased bone morphogenetic protein (BMP) signaling, manifested as increases in BMP4 expression and the subsequent Smad1/5 phosphorylation and the induction of Smad6 and Smad7. Moreover, LL-37 increased the expression of p21Waf1/Cip1, whose induction was abolished by the knockdown of BMP receptor II. Knockdown of BMP receptor II or p21Waf1/Cip1 also abrogated the anti-mitogenic action of LL-37. The activation of BMP signaling by LL-37 was accompanied with the inhibition of chymotrypsin-like and caspase-like activity of proteasome. In this regard, proteasome inhibitor MG-132 mimicked the effect of LL-37 by increasing BMP4 mRNA expression and Smad1/5 phosphorylation. In addition, cyclin E 2 was down-regulated by LL-37 via a BMP-independent mechanism. Further analysis of clinical samples revealed that LL-37 and p21Waf1/Cip1 mRNA expression were both down-regulated in gastric cancer tissues and their expression were positively correlated. These findings indicate that LL-37 inhibits gastric cancer cell proliferation through activation of BMP signaling via a proteasome-dependent mechanism. / In relation to gastric ulcer healing, results revealed that ulcer induction in rats increased the expression of rat cathelicidin rCRAMP in the gastric mucosa. Further increase in expression of rCRAMP by local injection of rCRAMP-encoding plasmid promoted ulcer healing by enhancing cell proliferation and angiogenesis. rCRAMP directly stimulated proliferation of cultured rat gastric epithelial cells (RGM-1), which was abolished by inhibitors of matrix metalloproteinase (MMP), epidermal growth factor receptors (EGFR) tyrosine kinase, or mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase. rCRAMP also increased EGFR and ERK1/2 phosphorylation via an MMP-dependent mechanism. Knockdown of transforming growth factor alpha (TGFalpha), which is a ligand of EGFR, by small interfering RNA completely nullified the mitogenic signals evoked by rCRAMP in RGM-1 cells. These findings suggest that rCRAMP exhibits pro-healing activity in stomachs through TGFalpha-dependent transactivation of EGFR and its related signaling pathway to induce proliferation of gastric epithelial cells. / Wu, Ka Kei. / Adviser: Joseph J. Y. Sung. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0252. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 153-178). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.