No description available.

Previous research has indicated two distinctive characteristics of flavour-aversion learning in rats: (1) rats very readily associate flavors with an internal malaise (toxicosis) , as evidenced by their subsequent aversion to the flavor, but they do not readily associate flafors with peripherally-applied electric shock. In contrast, rats readily associate auditory and visual stimuli with shock but not with toxicosis; (2) rats associate flavors with a subsequent toxicosis even when the gustatory stimulus is removed hours prior to onset of toxicosis. However, associations are formed between audio/visual cues and shock only if the offset of the signal does not precede onset of shock by more than one or two minutes. It has been suggested that the unique features of flavour-aversionn learning result from the fact that toxicosis is primarily a visceral experience while shock is applied to somesthetic receptors. However, toxicosis differs from shock along a number of dimensions in addition to receptor site. Most notably, toxicosis typically rises to a peak intensity over a period of many minutes and lasts for hours while shock is usually applied with a rapid onset (milliseconds) and short duration (seconds or milliseconds). Inasmuch as aversion learning experiments have confounded the receptor site of the aversive stimulus with its distinctive temporal features, it is not clear whether receptor site or temporal features is the functionally important characteristic of toxicosis as an aversive stimulus in the taste-aversion learning preparation. To determine the role played by the temporal features of the aversive stimulus in taste-aversion learning, rats were prepared with a stomach balloon and stomach balloon inflation was paired with ingestion of a flavored solution. In contrast to toxicosis, the onset/offset rate and duration of balloon inflation may be directly manipulated thus permitting application of a relatively discrete internal stimulus (in comparison to toxicosis) to visceral receptors. Experiments presented here found: (a) rats associated a flavor with a stomach balloon inflation as indicated by an aversion to the flavor during a two-solution preference test. In contrast to toxicosis, the stomach balloon inflation had a rapid onset (seconds) and short duration (minutes). Control groups demonstrated that the rapid onset, short duration balloon inflation did not produce the long lasting malaise characteristic of toxicosis. (b) Rats associated a flavor with a rapid onset, short duration balloon inflation even when exposure to the flavor was terminated many minutes prior to onset of balloon inflation. (c) Rats readily associated a flavor with balloon inflation but not with shock, and an auditory stimulus with shock but not with balloon inflation, even though balloon inflation and shock were equated in terms of their temporal parameters. These findings clearly indicate that the very slow onset and long duration characteristics of toxicosis are not the functionally important features of toxicosis as the aversive stimulus in the taste-aversion learning preparation. Furthermore, the unique temporal features of toxicosis and shock do not appear responsible for the distinctive characteristics of flavor-aversion learning in rats. / Thesis / Doctor of Philosophy (PhD)

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.

Wang, Ruizhi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 109-134). / Abstracts in English and Chinese. / Acknowledgement --- p.i / Publications --- p.ii / Abstract --- p.iv / 中文摘要 --- p.viii / Abbreviations --- p.xi / List of tables --- p.xiv / List of figures --- p.xv / Contents --- p.xvii / Chapter Chapter One: --- Introduction --- p.1 / Chapter 1.1 --- Epidemiology of gastric cancer --- p.2 / Chapter 1.2 --- Risk factors of gastric cancer --- p.3 / Chapter 1.3 --- Treatment of gastric cancer --- p.4 / Chapter 1.3.1 --- Surgical treatment --- p.4 / Chapter 1.3.2 --- Chemotherapy --- p.4 / Chapter 1.3.3 --- Targeted therapy --- p.5 / Chapter 1.4 --- "Phenotypes of cell death: apoptosis, oncosis and autophagy" --- p.9 / Chapter 1.4.1 --- Cell death --- p.9 / Chapter 1.4.2 --- Apoptosis --- p.10 / Chapter 1.4.2 --- Oncosis --- p.11 / Chapter 1.4.3 --- Autophagy --- p.12 / Chapter 1.4.4 --- p53 --- p.13 / Chapter 1.5 --- Heme oxygenase-1 --- p.14 / Chapter 1.5.1 --- General introduction of Heme oxygenase --- p.14 / Chapter 1.5.2 --- Anti-oxidant function of HO-1 --- p.15 / Chapter 1.5.3 --- Anti-inflammation function of HO-1 --- p.17 / Chapter 1.5.4 --- Pro-angiogenesis role of HO-1 --- p.18 / Chapter 1.5.5 --- HO-1 and cell proliferation --- p.19 / Chapter 1.5.6 --- HO-1 as a therapeutic target for tumors --- p.20 / Chapter 1.6 --- Objectives of study --- p.22 / Chapter Chapter Two: --- Methods and materials --- p.26 / Chapter 2.1 --- Gastric cancer cell lines --- p.27 / Chapter 2.2 --- Cell proliferation detection --- p.27 / Chapter 2.2.1 --- "MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)assay" --- p.27 / Chapter 2.2.1.1 --- Introduction of MTT assay --- p.27 / Chapter 2.2.1.2 --- Processes of MTT assay --- p.27 / Chapter 2.2.1.3 --- Cell proliferation and cytotoxicity of drugs --- p.28 / Chapter 2.2.2 --- Detection of apoptosis by TUNEL assay --- p.29 / Chapter 2.2.2.1 --- TUNEL (Terminal uridine deoxynucleotidyl transferase dUTP nick end labeling) --- p.29 / Chapter 2.2.2.2 --- Sample preparation --- p.29 / Chapter 2.3 --- Detection of cell cycle by flow cytometry --- p.32 / Chapter 2.3.1 --- Cell cycle --- p.32 / Chapter 2.3.2 --- Sample preparation --- p.33 / Chapter 2.3.3 --- Flow cytometry analysis --- p.34 / Chapter 2.4 --- Detection of mitochondrial membrane potential(ΔΨm) --- p.35 / Chapter 2.4.1 --- Sample preparation --- p.35 / Chapter 2.4.2 --- Mitochondrial membrane potential(ΔΨm) analysis by flow cytometry --- p.36 / Chapter 2.5 --- Detection of proteins investigated in the project --- p.37 / Chapter 2.5.1 --- Antibodies --- p.37 / Chapter 2.5.2 --- Sample Preparation --- p.39 / Chapter 2.5.2.1 --- Cell culture --- p.39 / Chapter 2.5.2.2 --- Protein extraction --- p.39 / Chapter 2.5.2.3 --- Protein assay --- p.41 / Chapter 2.5.2.4 --- Final loading protein --- p.42 / Chapter 2.5.3 --- Western blotting --- p.43 / Chapter 2.6 --- Statistical analysis --- p.45 / Chapter Chapter three: --- Roles of HO-1 in 5-FU treatment for gastric cancer cell lines --- p.47 / Chapter 3.1 --- Cell proliferations with drug treatments --- p.48 / Chapter 3.1.1 --- MTT assay --- p.48 / Chapter 3.1.1.1 --- Introduction --- p.48 / Chapter 3.1.1.2 --- Method and results --- p.49 / Chapter 3.1.2 --- TUNEL assay --- p.58 / Chapter 3.1.2.1 --- Introduction --- p.58 / Chapter 3.1.2.2 --- Method and results --- p.59 / Chapter 3.2 --- HO-1 expression with drug treatments --- p.63 / Chapter 3.2.1 --- Introduction --- p.63 / Chapter 3.2.2 --- Method and results --- p.64 / Chapter 3.3 --- Discussion --- p.72 / Chapter Chapter Four: --- Mechanism responsible for the additive effect of 5-FU and ZnPP --- p.77 / Chapter 4.1 --- Cell cycle arrest after drug treatments --- p.78 / Chapter 4.1.1 --- Introduction --- p.78 / Chapter 4.1.2 --- Method and results --- p.79 / Chapter 4.2 --- Mitochondrial dependent and independent pathway --- p.85 / Chapter 4.2.1 --- Introduction --- p.85 / Chapter 4.2.2 --- Method and results --- p.87 / Chapter 4.3 --- Alteration of apoptotic proteins in gastric cancer cell death after drug treatments --- p.91 / Chapter 4.3.1 --- Introduction --- p.91 / Chapter 4.3.2 --- Method and results --- p.94 / Chapter 4.4 --- Discussion --- p.101 / Chapter Chapter Five: --- Summary and future prospects --- p.107 / Chapter 5.1 --- Summary --- p.108 / Chapter 5.1.1. --- The inhibition of HO-1 enhances the sensitivity of gastric cancer cells to 5-FU --- p.108 / Chapter 5.1.2 --- Apoptosis induced by 5-FU plus HO-1 inhibitor ZnPP is through a mitochondrial-related pathway in MKN28 and MKN45 --- p.109 / Chapter 5.1.3 --- 5-FU plus ZnPP induces apoptosis in a caspase-dependent pathway in MKN45 while in both caspase-dependent and caspase-independent pathway in MKN28 --- p.110 / Chapter 5.2 --- Future prospects --- p.111 / References --- p.113

Thesis (M.S.)--University of Michigan, 1982.

Thesis (M.S.)--University of Michigan, 1982.

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy

No description available.

No description available.