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

为了阐明与血吸虫病相关的膀胱尿路上皮癌（UC）发生的潜在机制，我们化学分析了氧化应激标志物、DNA单链断裂（ssDNA）（也可以测量DNA中碱基损伤和凋亡水平）和埃及患者膀胱癌中一氧化氮合酶水平的DNA修复基因的表达与血吸虫感染或无血吸虫感染。与非血吸虫癌相比，血吸虫病相关的鳞状细胞癌（SCC）和尿路上皮癌（UC）中8-羟基-2 `-脱氧鸟苷（8-OHdG）水平显著升高。这伴随着DNA修复基因，8-氧代鸟嘌呤-DNA-糖基化酶（OGG 1）和脱嘌呤/脱嘧啶核酸内切酶（APE-1）的强烈过度表达，以及ssDNA形成水平的增加。诱导型一氧化氮合酶（iNOS）的表达水平是已知的， ...更多信息 与氧化应激直接相关的血吸虫癌高于非血吸虫癌。总之，这些研究结果表明，血吸虫感染和氧化应激水平的增加，伴随着一个连续的DNA损伤和修复的UC之间有很强的相关性，所有直接相关的升高iNOS.We还评估了表达p53和4种类型的成纤维细胞生长因子受体（FGFR）在膀胱癌与或不与血吸虫感染。51%的血吸虫病相关膀胱癌p53蛋白表达阳性。血吸虫病相关膀胱癌中FGFR 1、FGFR 2、FGFR 4表达下调分别为53%、22%、11%，FGFR 3表达过度为43%。上述基因在血吸虫病相关的UC和SCC中的表达无显著性差异。与血吸虫病相关和不相关的癌症之间的表达没有明显差异。这些发现表明膀胱癌中FGFRs的表达改变，并表明FGFRs在血吸虫病相关的膀胱癌发生中起作用。少

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.