| Project/Area Number |
16406021
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 海外学術 |
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| Research Field |
Hygiene
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| Research Institution | Osaka City University |
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Principal Investigator |
WANIBUCHI Hideki Osaka City University, MEDICAL SCHOOL : DEPT. PATHOLOGY, PROFESSOR (90220970)
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| Co-Investigator(Kenkyū-buntansha) |
WEI Min OSAKA CITY UNIVERSITY MEDICAL SCHOOL, DEPT. PATHOLOGY, ASSISTANT (70336783)
福島 昭治 大阪市立大学, 大学院・医学研究科, 教授 (00137077)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥10,900,000 (Direct Cost: ¥10,900,000)
Fiscal Year 2006: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | 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 |
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| Research Abstract |
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
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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
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