Co-Investigator(Kenkyū-buntansha) |
MORIMURA Keiichirou OSAKA CITY UNIVERSITY MEDICAL SCHOOL, DEPT.PATHOLOGY, ASSISTANT PROFESSOR, 大学院・医学研究科, 講師 (30315999)
WANIBUCHI Hideki OSAKA CITY UNIVERSITY MEDICAL SCHOOL, DEPT.PATHOLOGY, ASSOCIATE PROFESSOR, 大学院・医学研究科, 助教授 (90220970)
ALINA M Romanenko INSTITUTE OF UROLOGY AND NEPHROLOGY ACADEMY OF MEDICAL SCIENCE OF UKRAINE, DEPT.PATHOLOGY, PROFESSOR AND DIRECTRATE
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Research Abstract |
After the Chernobyl accident, the incidence of urinary bladder cancers in Ukrainian is reported to increase 1.6 times within 15 years. Low level but persistent contamination of radioactive ^<137> Cs in the soil may be one of the main reasons for this increasing bladder cancer incidence. In this research project, we found out the increased incidence of dysplasia and/or bladder cancer including carcinoma in situ, was accompanied with increased ^<137> Cs level in urine among the people living in the radio-contaminated area, who showed no clinical symptoms of bladder cancer. Also we detected that a very specific chronic proliferative atypical cystitis with displastic lesions and/or carcinoma in situ was ubiquitously seen in the inhabitant of this radio-contaninated area. We defined this lesion as "Chernobyl cystitis". In this bladder lesion, several cancer related genes such as p53, p21 and Cyclin D1, were aberrantly expressed and iNOS and COX2 were over-expressed. These results point out
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to the great contribution of oxidative stress to the occurrence of cancer prone bladder lesions seen in this area. Moreover, we detected the difference in the incidences of p53 gene mutations in bladder cancers before and after Chernobyl accident, to be the possible distinct molecular carcinogenic pathway of bladder cancer formation in this area. To further investigate the mechanism underlying bladder carcinogenesis with this specific etiology, we investigated the expression level of growth factor receptor immunohistochemically. High expressions of FGF-R3, EGE-R1 and EGF-R2 were detected in bladder epithelia of radio-contaminated area, compared with those in clean area, and these growth factor receptors were suggested to play an important role in the bladder carcinogenesis after in the Chernobyl accident. From the sequence of the studies in this project, we demonstrated that people living in this radio-contaminated area were in peril of bladder cancer, and that a distinct molecular pathway might exist in the genesis of bladder cancer, based on this specific etiology. Less
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