Gene analysis of aberrant crypt foci in patients with ulcerative colitis

溃疡性结肠炎患者隐窝异常病灶基因分析

• 批准号: 13670536
• 负责人: TAKAYAMA Tetsuji
• 金额: $ 2.62万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670536/
• 关键词: ACF; Ulcerative colitis; Colorectal cancer

Aim : To investigate the significance of aberrant crypt foci (ACF), which could be identified by magnifying endoscopy, as a biomarker in colitic cancer, and to analyze gene alterations in order to demonstrate it is a precursor lesion in colorectal carcinogenesis of the patients with ulcerative colitis (UC).Methods and Results : ACF was identified using magnifying endoscope (Fujinon 485, ZW) with the aid of methylene blue. The mean number of ACF in patients with UC was 8.7±3.7, being significantly higher than that of normal subjects. In particular, it was significantly higher in UC patients with dysplasia than that without dysplasia. The number of ACF was significantly correlated with the positivity of dysplasia (p<0.01). There were few mutations of K-ras in ACF and dysplasia of UC patients. No APC and beta-catenin abnormality was detected in ACF or dysplasia. No p53 abnormality was detected in ACF, but was in dysplasia. Hypermethylation of p16 gene promoter was frequently detected in ACF and dysplasia in UC patients. Now gene analysis with microarray in ACF and dysplasia are underway.Conclusion : It was demonstrated that ACF could serve as a useful biomarker for surveillance of colorectal cancer in UC patients, and that ACF might be a precursor lesion of dysplasia in colitc carcinogensis.

目的：探讨异常隐窝灶(ACF)作为结肠癌生物标志物的意义，并分析其基因改变，以证实ACF是溃疡性结肠炎(UC)患者结直肠癌发生的前驱病变。UC患者平均ACF数为8.7±3.7，显著高于正常对照组。尤其是UC伴异型增生患者显著高于无异型增生患者。ACF的数量与异型增生的阳性率显著相关(p&lt；0.01)。UC患者ACF和异型增生组织中K-ras基因突变较少。ACF和异型增生均未检测到APC和β-连环素异常。ACF组织中未见P53异常表达，异型增生组织中P53蛋白表达异常。P16基因启动子高甲基化多见于ACF和UC异型增生。结论：ACF可作为监测UC患者结直肠癌的有用生物标志物，ACF可能是结肠癌发生过程中不典型增生的前驱病变。

项目成果

Sagawa T, Takayama T, Niitsu Y, et al.: "Argon Plasma Coagulation for Successful Treatment of Early Gastric Cancer with Intramucosal Invasion"GUT. 52. 334-339 (2003)

Sakawa T、Takayama T、Niitsu Y 等人：“氩离子凝固成功治疗粘膜内浸润的早期胃癌”GUT。

Koike K, Kogawa K, Takayama T, Yoshizaki N, Muramatsu H, Nakamura K, Sakamaki S and Niitsu Y: "Enhanced expression of typeIV collagen binding protein (p29) in fyn-transfected murine fibrosarcoma cells"Jpn J Cancer Res. 93. 1090-1099 (2002)

Koike K、Kokawa K、Takayama T、Yoshizaki N、Muramatsu H、Nakamura K、Sakamaki S 和 Niitsu Y：“fyn 转染的小鼠纤维肉瘤细胞中 IV 型胶原结合蛋白 (p29) 的表达增强”Jpn J Cancer Res。

Kato J, Niitsu Y, et al.: "Ratio of transferrin (Tf) to Tf-receptor complex in circulation differs depending on Tf iron saturation"Clin Chem.. 48. 181-183 (2002)

Kato J、Niitsu Y 等人：“循环中转铁蛋白 (Tf) 与 Tf 受体复合物的比率根据 Tf 铁饱和度而不同”Clin Chem.. 48. 181-183 (2002)

Sasaki H, Takayama T, Niitsu Y, et al.: "Induction of heat shock protein 47 synthesis by TGF-β and IL-1β via enhancement of the heat shock element binding activity of heat shock transcription factor 1"J. Immunol. 168. 5178-5183 (2002)

Sasaki H、Takayama T、Niitsu Y 等人：“TGF-β 和 IL-1β 通过增强热休克转录因子 168 的热休克元件结合活性诱导热休克蛋白 47 合成”。 .5178-5183 (2002)

Sasaki H, Takayama T, et al.: "Induction of heat shock protein 47 synthesis by TGF-β and IL-1β via enhancement of the heat shock element binding activity of heat shock transcription factor 1"J.Immunol. 168. 5178-5183 (2002)

Sasaki H、Takayama T 等人：“TGF-β 和 IL-1β 通过增强热休克转录因子 1 的热休克元件结合活性诱导热休克蛋白 47 合成”J.Immunol. 168。 5183 (2002)