Molecular analysis of bile duct cancer associated with PBM

与 PBM 相关的胆管癌的分子分析

• 批准号: 13671309
• 负责人: YAMAGUCHI Koji
• 金额: $ 2.3万
• 依托单位: Kyushu 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-13671309/
• 关键词: pancreaticobiliary maljunction; oxidative stress; inflammation and carcinoma; gallbladder carcinoma; 膵胆管合流異常症; 炎症性サイトカイン; エイコサイド; 細胞回転; DNA傷害

Pancreaticobiliary maljunction, an anomalous union of the pancreatic duct with the common bile duct, is a risk factor for biliary carcinoma. We hypothesized that, in patients with pancreaticobiliary maljunction, persistent regurgitation of pancreatic juice into the biliary tract induces oxidative DNA damage. We assessed the expression of an oxidative DNA base-modified product, 8-hydroxy-2'-deoxyguanosine, in gallbladder. Stronger cytoplasmic staining of 4-hydroxy-2-nonenal-modified protein was observed in the gallbladder epithelium from patients with pancreaticobiliary maljunction than in epithelium from gallbladder cancer patients or from control subjects with normal gallbladders. Clear, strong nuclear staining of 8-hydroxy-2'-deoxyguanosine was observed in the gallbladder epithelial cells from patients with pancreaticobiliary maljunction. Positivity of p53 was more frequent and stronger in gallbladder carcinoma and in gallbladder epithelium associated with pancreaticobiliary maljunction. These results suggest that reactive oxygen species are produced in the gallbladder of patients with pancreaticobilary maljunction and that oxidative DNA injury is related to carcinogenesis of gallbladder carcinoma in patients with pancreaticobiliary maljunction.

胰胆管合流异常是胰管与胆总管的异常连接，是胆道癌的危险因素。我们假设，在胰胆管合流异常的患者中，持续的胰液反流进入胆道会诱导氧化性DNA损伤。我们评估了胆囊中氧化DNA碱基修饰产物8-羟基-2 '-脱氧鸟苷的表达。胰胆管连接异常患者胆囊上皮细胞中4-羟基-2-壬烯醛修饰蛋白质的胞质染色较胆囊癌患者或正常胆囊对照组上皮细胞更强。在胰胆管合流异常患者的胆囊上皮细胞中观察到清晰、强烈的8-羟基-2 '-脱氧鸟苷核染色。p53蛋白在胆囊癌和伴胰胆管合流异常的胆囊上皮中表达更频繁、更强。这些结果表明，活性氧在胰胆合流异常患者的胆囊中产生，氧化性DNA损伤与胰胆合流异常患者胆囊癌的发生有关。