Analysis of molecular mechanism of premalignant lesion of the stomach using genomic instability and new mucin gene.
Analysis of molecular mechanism of premalignant lesion of the stomach using genomic instability and new mucin gene.
批准号:
11557043
负责人:
IMAI Kohzoh
金额:
$6.91万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B).
财政年份:
2000
资助国家:
日本
项目状态:
已结题
起止时间:
2000 至 --
中文摘要
1)高分化胃腺癌中基因组不稳定性(微卫星不稳定性,MSI)的频率较高。在伴有高分化腺癌的肠上皮化生组织中,MSI阳性率最高,MSI阳性腺癌中hMLH 1基因启动子区甲基化程度最高。MSI与DNA修复基因及其他相关基因甲基化的关系有待进一步研究。2)新的粘蛋白基因A3D4在胃腺癌肠上皮化生组织中表达。该产物对“正常”肠化病变为阴性。3)对肠化病变中的甲基化进行了系统的研究,发现许多基因表现出异常的甲基化模式,提示甲基化在胃癌癌前状态中的重要作用。
英文摘要
1) High frequency of the genomic instability (microsatellite instability, MSI) was found in well-differentiated adenocarcinoma of the stomach. Most of the intestinal metaplasia lesion which was accompanied with well-differentiated adenocarcinoma showed positivity for MSI.Moveover, hypermethylation of the promotor lesion of hMLH1 gene was observed in MSI-positive adenocarcinoma. Further study will be needed to analyze the association between MSI status and hypermethylation of the DNA repair genes and other related genes.2) New mucin gene A3D4 was expressed in the lesion of intestinal metaplasia of the adenocarcinoma of the stomach. This product was negative for "normal" intestinal metaplasia lesion.3) Methylation has systemically been investigated in the lesion of the intestinal metaplasia and many genes were found to show abnormal pattern of methylation, suggesting the important role of methylation to the premalignant status of the stomach cancer.
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Toyota,M.,Imai,K.et al.: "Aberrant methylation in gastric cancer associated with a CpG island mathylator phenotype."Oncogene. 59. 5438-5442 (2000)
Toyota, M., Imai, K. 等人:“胃癌中的异常甲基化与 CpG 岛 mathylator 表型相关。”癌基因。
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通讯作者:
Yamamoto,H.,Imai K.et al.: "Gastric cancers of the microsatellite mutator phenotype display characteristic genetic and clinical features."Gastroenterology. 116. 1348-1357 (1999)
Yamamoto, H., Imai K.等人:“微卫星突变表型的胃癌显示出特有的遗传和临床特征。”胃肠病学。
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Naishiro Y.Imai K. et al.: "Restroration of epithelial cell polarity in a colorectal cancer cell line by suppression of β-catenin/T cell factor 4-mediated gene transactivation."Cancer Res. 61(in press). (2001)
Naishiro Y. Imai K. 等人:“通过抑制 β-连环蛋白/T 细胞因子 4 介导的基因反式激活来恢复结直肠癌细胞系中的上皮细胞极性。”Cancer Res 61(出版中)。 )
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Shirakawa K, Imai K, et al.: "gene targeting Flt-1 and Tie 2 inhibits tumor growth and metastases on WIBC-9, a human inflammatory cancer xenograft."Cancer Res. (in press). (2001)
Shirakawa K、Imai K 等人:“靶向 Flt-1 和 Tie 2 的基因可抑制 WIBC-9(一种人类炎症性癌症异种移植物)上的肿瘤生长和转移。”Cancer Res。
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Yamamoto H, Itoh F, Imai K, et al.: "Genetic and clinical features of human pancreatic ductal adenocarcinomas with widespread microsatellite instability."Cancer Res. 61 : (in press). (2001)
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