Research for esophageal carcinogenesis and differentiation induction therapy based on normal esophageal epithelial cells and esophageal stem cells

基于正常食管上皮细胞和食管干细胞的食管癌发生及分化诱导治疗研究

基本信息

批准号：
14370385
负责人：
SHIMADA Yutaka
金额：
$ 9.47万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Esophageal stem cell s1)Human esophageal keratinocyte stem cells are characterized by the expression of the low affinity neurotrophin receptor p75NTR and differentially expressed cell adhesion molecules, the β1 and β4 integrins. The candidate stem cells can be fractionated from keratinocytes as a minor cell subset by means of immunocytochemical cell sorting based on the different levels of expression of these cell surface molecules. 2)We demonstrated esophageal epithelial differentiation in vivo and detected an initial genetic alteration and abnormal cell proliferation in the p75/NTR positive putative stem cell compartment during the early stages of carcinogenesis, suggesting their role as an initial target cell population for carcinogenesis. 3)Esophageal cancer cells lines contained several levels of p75/NTR positive cells and these cells could reproduce larger colonies than p75/negative cells. p75/NTR positive cells dramatically suppressed their growth by SiRNA. These results suggest … More ed that p75/NTR may become a good therapeutic target and might be a candidate of cancer stem cell of esophageal cancer.Effect of gastroduodenal reflux and smoking on normal esophageal cell.1)COX-2 expression and prostaglandinE2 production were significantly up-regulated in normal human esophageal cells by bile acid in combination with trypsin and acid. The results suggest that duodenogastroesophageal reflux may induce cyclooxygenase-2 expression and prostaglandinE2 production in esophageal epithelial cells. Cyclooxygenase-2 specific inhibitors may have a chemopreventive effect on esophageal carcinoma. 2)We found that nicotine induced FHIT methylation via up-regulation of de novo methyltransferase Dnmt3a followed by loss of Fhit protein expression in human esophageal squamous epithelial cells. FHIT methylation was not able to be detected after cessation of nicotine exposure. Interestingly, we could not find any evidence of p16INK4a methylation. Thus, FHIT might be sensitive to nicotinic treatment rather than p16/INK4a. Our results suggest that continuous smoking may induce the risk of esophageal cancer. Less

食管干细胞S1）d差异表达的细胞粘附分子，候选干细胞可以通过这些细胞表面分子中的不同细胞表面分化的不同细胞化学细胞分类为flatinopytes作为LL子集。 p75/NTR阳离子的癌症在癌中的早期阶段，表明p75/ntr阳性细胞水平的tareal靶细胞群体可以比p75/阴性细胞更大结果表明……更多的是，p75/ntr可能成为一个很好的靶标，可能是食管癌细胞。胃二维二元回流和对正常食管的吸烟的影响。1）Cox-2表达和前列腺素2在正常的人类食管中显着上调胆汁酸与胰蛋白酶酸的结合。混合食管可能会诱导环氧酶-2的表达和前列腺素氧化酶-2的抑制剂。上皮细胞。