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尿膀胱（UC）的尿路上皮癌的发展机制，我们在免疫组织化学分析了氧化物应激标记之间的关系，DNA单链断裂（SSDNA）之间的关系，这也可以测量与DNA和DNA级别的水平相结合的DNA的水平，并在DNA的水平上进行了含量，并在DNA中的表达水平以及DNA的表达水平。有或没有血吸虫血吸虫感染的埃及患者的癌。与非智囊癌相比，在鳞状细胞癌（SCC）和尿路上皮癌（UCS）中发现了8-羟基-2--脱氧鸟苷（8-OHDG）水平的升高。这是通过强烈表达DNA-REPAIR基因，8-氧气甘氨酸-DNA-糖基化酶（OGG1）和磷灰酮/apyrimidinic核酸酶（APE-1）的强烈表达来实现的，并增加了ssDNA的地层水平。已知在……与非尖刺癌中更直接相关的诱导型一氧化氮合酶（INOS）的表达水平更高。总之，这些发现表明血吸虫感染血吸虫与UCS的连续DNA损伤和修复达到的氧化应激水平之间存在很强的相关性，所有这些都与iNOS的升高直接相关。我们还评估了与bladder cotobs cotob carcinob cactos nont Innonicob carcinob coctos nont Innonicob carcinob cotob cotob cotob coction nont Ints SCHNOS p53和4种类型的表达。 p53的阳性染色在与血吸虫病相关的51％的膀胱癌中被确定。在与血吸虫病相关的43％的膀胱癌中观察到了53％，22％，11％的FGFR1，FGFR2，FGFR4的下调。与血吸虫病相关的UCS和SCC之间的上述基因表达没有显着差异。表达没有差异是与血吸虫病相关的癌症之间的证据。这些发现表明，膀胱癌中FGFR的表达改变，并表明FGFR在与血吸虫病相关的膀胱癌发生中起作用。较少的

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.