No description available.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

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.

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

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Made available in DSpace on 2015-07-22T20:50:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-04-28 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Introdução: A infecção por Helicobacter pylori está associada ao câncer gástrico (CG) não localizado na região da cárdia, no entanto, apenas uma pequena proporção das pessoas infectadas desenvolvem esta neoplasia. Estudos sobre cepas específicas dessa bactéria demonstram que os fatores genéticos e ambientais estão associados a esta carcinogênese. A Interleucina-8 (IL-8) desempenha um papel importante na inflamação da mucosa do estômago após a infecção por H. pylori. Estudos têm demonstrado que o polimorfismo da IL-8 pode aumentar o risco de CG. Objetivo: Investigar a associação entre o polimorfismo da IL-8, infecção por H. pylori, hábitos de vida e risco de CG. Casuística e métodos: Estudo caso-controle feito em pacientes com CG não-cárdia em comparação com indivíduos saudáveis na proporção de 1:2, respectivamente. O DNA foi extraído de leucócitos, purificado e a análise do polimorfismo foi feita pela técnica de PCR-RFLP e visualizado por eletroforese em gel de agarose a 5%. Infecção por H. pylori foi investigada pelos níveis séricos de anticorpos anti-H.pylori. Aspectos ambientais como tabagismo, etilismo e dieta foram investigados por questionário. Resultados: Um total de 312 indivíduos foi estudado, sendo 208 controles e 104 pacientes com câncer. Não houve diferença significante entre sexo ou idade, entre o grupo controle e os pacientes com CG. A proporção de pacientes infectados pelo H. pylori foi semelhante (p=0,15) entre os grupos controle (53,8%) e caso (45,2%). Menor frequência do genótipo AA foi encontrada no grupo com câncer (p = 0,01), sem diferença entre os alelos A e T. O tabagismo (p=0,001), acentuada ingestão de gordura (p=0,003) e baixa ingestão de legumes (p=0,02), foram mais frequentes no grupo caso. A análise de regressão logística multivariada demonstrou maior risco de CG em indivíduos com o genótipo heterozigoto AT (OR: 2,28 95%IC 1,16-4,49; p=0,02) e consumo excessivo de gordura (OR: 1,77 95%IC 1,12-2,92; p=0,03). Fumantes e ex-fumantes também demonstraram maior risco de CG quando comparados ao grupo controle (OR: 1,89 95%IC 1,41-3,11; p=0,01). Conclusões: A presença do genótipo AT está associada à elevação do risco de CG em aproximadamente duas vezes. O percentual de pacientes com CG infectados pelo H. pylori, diagnosticado pelos níveis de anticorpos séricos, não foi diferente do grupo controle na população estudada. Não observamos correlação entre a frequência alélica e o risco de CG. Indivíduos que consomem gorduras em excesso, ex-fumantes e fumantes têm maior risco de CG. / Background: Helicobacter pylori infection is associated with gastric cancer (GC) non-cardia, however, only a small proportion of infected people develop this cancer. Studies on specific strains of bacteria showed that the genetic and environmental factors are associated with this carcinogenesis. Interleukin-8 (IL-8) plays an important role in inflammation of the stomach mucosa after infection with H. pylori. Studies have shown that the polymorphism of IL-8 may increase the risk of GC. Objective: To investigate the association between polymorphism of IL-8, infection with H. pylori, lifestyle and risk of GC. Patients and methods: Case-control study done in patients with non-cardia GC compared with healthy subjects in the ratio 1:2, respectively. DNA was extracted from white blood cells, purified and polymorphism analysis was performed by PCR-RFLP and visualized by agarose gel electrophoresis to 5%. Infection with H. pylori was investigated by serum antibodies to H. pylori. Environmental issues such as smoking, alcohol consumption and diet were investigated by questionnaire. Results: A total of 312 individuals was studied, and 208 controls and 104 cancer patients. No significant differences between sex or age between the control group and patients with CG. The proportion of patients infected by H. pylori was similar (p=0.15) between the control group (53.8%) and case (45.2%). Lower frequency of AA genotype was found in the cancer group (p=0.01), however, no difference between alleles A and T. Cigarette smoking (p=0.001), sharp intake of fat (p=0.003) and low intake of vegetables (p=0.02) were more frequent in case group. A multivariate logistic regression analysis demonstrated a higher risk of GC in subjects with the heterozygous genotype AT (OR: 2.28 95% IC 1,16-4,49, p=0.02) and excessive consumption of fat (OR: 1 77 95% CI 1,12-2,92, p = 0.03). Smokers and former smokers also showed increased risk of GC compared to the control group (OR: 1.89 95% CI 1,41-3,11, p=0.01). Conclusions: The presence of the AT genotype is associated with increased risk of GC in about two times. The percentage of patients with GC infected with H. pylori, diagnosed by serum antibody levels was not different from the control group in the population. No correlations between allele frequency and risk of GC. Individuals who consume too much fat, ex-smokers and smokers have a higher risk of GC. / FAPESP: 08/05763 / TEDE / BV UNIFESP: Teses e dissertações