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Molecular pathological study on the expression of apoptosis-related genes and regulating factors in human gastrointestinal carcinomas :

人胃肠道癌凋亡相关基因及调控因子表达的分子病理学研究：

基本信息

批准号：
09670185
负责人：
ITO Hisao
金额：
$ 1.98万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670185/
关键词：
Gastrointestinal carcinoma apoptosis p53 gene cell cycle dThdPase Anticancer agent Hyperthermia Fas エタノール熱ショック FAS

项目摘要

1) Adenovirus-mediated transfer of wild type p53 gene of 50 MCI into the human gastric and colonic carcinoma cell lines resulted in apoptotic cell death , growth arrest, or non-effectiveness. After infection with AxCA-p53, the expression levels of bax or bcl-XL protein changed in the cell lines showing apoptosis.2) Human gastric and colonic carcinoma cell lines showed Fas expression variably. Anti-Fas antibody induced apoptosis of the gastric cell lines, regardless of p53 gene status, while the antibody induced apoptosis only in LoVo carrying wild type p53 gene of the colonic cell lines. AxCA-p53 transfection resulted in up-regulation of Fas.3) Hyperthermia for 30 min. resulted in apoptosis in human gastric carcinoma cell lines, while necrosis was induced by the treatment for 60 min. The former showed up-regulation of P53.4) The progression of gastric carcinoma was defined by a gradual increase of proliferative activity and constant occurrence of apoptosis and naturally occurring apoptosis is induced predominantly via a p53 gene-independent pathway.5) Preoperative treatment with tegafur suppository significantlyenhanced apoptotic cell death and abated intratumoral microvessel density (IMVD) in human colorectal carcinomas.6) IMVD was significantly higher in gastric and colonic carcinomas with dThdPase expression than in those without the expression, regardless the tumor stage. dThdPase expression was correlated with decrease of apoptos is.

1)腺病毒介导的50mCI野生型P53基因导入人胃、结肠癌细胞系，可导致细胞死亡、生长停滞或无效。感染AxCA-P53后，bax和bclxl蛋白的表达水平在出现凋亡的细胞系中发生改变。2)人胃、结肠癌细胞系均有不同程度的Fas表达。抗Fas抗体诱导胃癌细胞发生凋亡，与P53基因状态无关，而仅诱导携带野生型P53基因的LoVo结肠癌细胞发生凋亡。AxCA-P53基因表达上调。3)热疗30min。可诱导人胃癌细胞系发生凋亡，60min可引起细胞坏死。前者显示P53.4表达上调)胃癌的进展是由逐渐增加的增殖活性和持续的细胞凋亡决定的，自然发生的细胞凋亡主要是通过P53基因无关的途径诱导的。5)术前使用替加氟栓剂显著增加人结直肠癌的凋亡细胞死亡和肿瘤内微血管密度(IMVD)。6)无论肿瘤分期，有dThdPase表达的胃和结肠癌的IMVD均显著高于未表达dThdPase的胃癌和结肠癌。DThdPase的表达与细胞凋亡率的减少相关。