ELUCID ATION OF MECHANISMS OF URIN ARY BLADDER CARCINOMAS ASSOCIATED WITH SCHISTOSOMIASIS IN EGYPT

埃及血吸虫病相关膀胱癌发病机制的阐明

• 批准号: 16406021
• 负责人: WANIBUCHI Hideki
• 金额: $ 6.98万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16406021/
• 关键词: Egypt; Schistosoma hematobium infection; Bladder cancer; Chronic infection; Oxidative DNA damage; Oxidative Stress; iNOS; Squamous cell carcinoma; TCC; SCC; FGFR; 増殖因子; 増殖因子受容体

To cast light on mechanisms underlying development of urothelial carcinomas of the urinary bladder (UC) associated with Schistosomiasis, we immunohistochemically analyzed the relationship between oxidative stress markers, DNA single strand breaks (ssDNA) which could also measure the levels of base damage and apoptosis in DNA, and expression of DNA repair genes with levels of nitric oxide synthases in bladder carcinomas of Egyptian patients with or without Schistosoma hematobium infection. Marked elevation of 8-hydroxy-2`-deoxyguanosine (8-OHdG) levels was found in squamous cell carcinomas (SCCs) and urothelial carcinomas (UCs) associated with Schistosomiasis as compared with non-Schistosomal carcinomas. This was accompanied by strong over expression of the DNA-repair genes, 8-oxoguanine-DNA-glycosylase (OGG1) and apurinic/apyrimidinic endonuclease (APE-1), as well as increased formation levels of ssDNA. Expression levels of inducible nitric oxide synthase (iNOS) which is known to be in … More directly related to oxidative stress was higher in Schistosomal than in the non-Schistosomal carcinomas. In conclusion, these findings suggest a strong correlation between Schistosoma haematobium infection and increased levels of oxidative stress accompanied by a continuous DNA damage and repair in UCs, all directly correlating with elevated iNOS.We also evaluated expressions of p53 and 4 types of fibroblast growth factor receptors (FGFR) in the bladder carcinomas associated with or without Schistosoma hematobium infection. Positive staining of p53 was indentified in 51% of bladder cancer associated with Schistosomiasis. Down-regulation of FGFR1, FGFR2, FGFR4 were observed in 53%, 22%, 11%, and overexpression of FGFR3 was observed in 43% of bladder cancers associated with Schistosomiasis, respectively. There were not significant differences in expression of above genes between UCs and SCC associated with Schistosomiasis. No differences in expression were evident between cancers associated with and without Schistosomiasis. These findings demonstrated the altered expression of FGFRs in bladder cancers, and suggesting the FGFRs play a role in Schistosomiasis-associated bladder carcinogenesis. Less

揭示与静脉息肉相关的尿液膀胱（UC）的尿路癌的发展。在埃及pat骨瘤的膀胱瘤癌中，在Squinomas（SCCS）中发现了8-羟基-2--脱氧藻氨酸（8-OHDG）水平的明显升高DNA修复基因的表达，8-氧气 - 瓜氨酸-DNA-糖基酶（OGG1）和肾上腺素素核酸内核酸酶（APE-1），以及ssDNA的形成水平增加。已知与氧化应激直接相关的血吸虫应比非尖锐的癌中更高。 iNOS升高还评估了与有或没有疤痕性血肿感染相关的膀胱癌中的p53和4种类型的Rowth因子受体（FGFR）。在43％的患有血吸虫病的膀胱癌中观察到53％，22％，11％和过表达的FGFR3，在上述基因UC的表达中，TERE并未明显。膀胱癌中的FGFR相关的膀胱癌发生

项目成果

Elevated oxidative stress and DNA damage and repair levels in urinary Bladder carcinomas associated with Schistomiasis

与血吸虫病相关的膀胱癌中氧化应激、DNA 损伤和修复水平升高

• 发表时间: 2008
• 期刊: International Journal of Cancer
• 影响因子: 6.4
• 作者: Salim;E.L;Wanibuchi;H.;et. al.
• 通讯作者: et. al.

Elevated oxidative stress and DNA damage and repair levels in urinary Bladder carcinomas associated with Schistomiasis.

与血吸虫病相关的膀胱癌中氧化应激、DNA 损伤和修复水平升高。

• 发表时间: 2008
• 期刊: International Journal of Cancer (in press)
• 作者: Salim;E. I.;Wanibuchi;H.;et. al.
• 通讯作者: et. al.

Increased oxidative stress associated with alterations in DNA damage and repair in urinary bladder carcinomas associated and non-associatedwith Schistosomiasis.

与血吸虫病相关和非相关的膀胱癌中 DNA 损伤和修复的改变相关的氧化应激增加。

• 发表时间: 2004
• 作者: Salim;E. I.;Wanibuchi;H.;et. al.
• 通讯作者: et. al.