Genetic instability of stromal cells in ulcerative colitis-associated carcinogenesis

溃疡性结肠炎相关癌发生中基质细胞的遗传不稳定性

• 批准号: 14570160
• 负责人: OKAYASU Isao
• 金额: $ 2.24万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570160/
• 关键词: ulcerative colitis; carcinogenesis; genetic instability; stromal cell; microdissection; microsatellite instability; colon cancer; chronic inflammation; Microdissection

To know roles of genetic instability of stromal cells on carcinogenesis in ulcerative colitis (UC), microsatellite instability (MSI) and loss of heterozygosity (LOH) were investigated in epithelial and stromal cells separated by microdissection, by using PCR-SSCP method. In sporadic colon cancers, MSI positive results were obtained for both epithelium and stromal tissue. While MSI in epithelium correlated with differentiation and Dukes' stage, that in stroma demonstrated an inverse correlation, being particularly frequent in well differentiated adenocarcinomas and Dukes' A lesions, suggesting an alternative pathway of carcinogenesis involving stromal genetic instability in the development of colon cancers. In contrast, although chromosome 17-MSI and -LOH in epithelium correlated with histological progression, in stroma they showed a consistently high frequency throughout the different stages, indicating a distinct carcinogenesis pathway of UC.

为了解基质细胞遗传不稳定性在溃疡性结肠炎（UC）癌变中的作用，采用PCR-SSCP方法对经显微解剖分离的上皮细胞和基质细胞进行微卫星不稳定性（MSI）和杂合性缺失（LOH）的研究。在散发性结肠癌中，上皮和间质组织的MSI结果均为阳性。虽然上皮细胞的MSI与分化和Dukes分期相关，但基质细胞的MSI表现为负相关，在分化良好的腺癌和Dukes' A病变中尤为常见，这表明在结肠癌的发展中存在另一种涉及基质遗传不稳定的致癌途径。相比之下，尽管上皮细胞中的17-MSI和-LOH与组织学进展相关，但在基质中，它们在不同阶段均表现出一致的高频率，表明UC有不同的致癌途径。

项目成果

Okayasu I, 他5名: "Dysplasia and carcinoma development in a repeated dextran sulfate sodium-induced colitis model."J Gastroenterol Hepatol. 17. 1078-1083 (2002)

Okayasu I 和其他 5 人：“重复葡聚糖硫酸钠诱导的结肠炎模型中的发育不良和癌症发展。”J Gastroenterol Hepatol。17. 1078-1083 (2002)

Matumoto N, Yoshida T, Okayasu I.: "High epithelial and stromal genetic instability of chromosome 17 in ulcerative colitis-associated carcinogenesis"Cancer Res. 63. 6158-6161 (2003)

Matumoto N、Yoshida T、Okayasu I.：“溃疡性结肠炎相关癌发生中 17 号染色体的上皮和基质遗传高度不稳定性”Cancer Res。

Okayasu I, Yoshida T, 他4名: "Significant increase of colonic mutated crypts in ulcerative colitis correlatively with duration of illness."Cancer Res. 62. 2236-2238 (2002)

Okasu I、Yoshida T 和其他 4 人：“溃疡性结肠炎中结肠突变隐窝的显着增加与疾病持续时间相关。”Cancer Res. 62. 2236-2238 (2002)

Yoshida T, 他2名, Okayasu I: "Diverse p53 alterations in ulcerative colitis-associated low-grade dysplasia: full-length gene sequencing in microdissected single crypts"J. Pathol. 199(in press). (2003)

Yoshida T，其他 2 人，Okayasu I：“溃疡性结肠炎相关低度发育不良中的多种 p53 改变：显微解剖的单个隐窝中的全长基因测序”J.

Mikami T, 他4名, Okayasu I: "Apoptosis regulation differs between ulcerative colitis-associated and sporadic colonic tumors"Am J Clin Pathol. 119. 723-730 (2003)

Mikami T，其他 4 人，Okayasu I：“溃疡性结肠炎相关肿瘤和散发性结肠肿瘤之间的细胞凋亡调节不同”Am J Clin Pathol。119. 723-730 (2003)