| Project/Area Number |
12470336
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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 | 一般 |
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| Research Field |
Urology
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| Research Institution | Kyoto Prefectural University of Medicine (KPUM) |
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Principal Investigator |
MIZUTANI Yoichi KPUM. Urology, Assistant Professor, 医学部, 講師 (10243031)
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| Co-Investigator(Kenkyū-buntansha) |
MIKI Tsuneharu KPUM. Urology, Professor, 医学部, 教授 (10243239)
FUJITO Akira KPUM. Urology, Assistant Professor, 医学部, 講師 (60315950)
KAWAUCHI Akihiro KPUM. Urology, Assistant Professor, 医学部, 講師 (90240952)
本郷 文弥 京都府立医科大学, 医学部, 助手 (80291798)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | Bladder cancer / Cisplatin / DNA chip / Apoptosis / Differentiotion / TRAIL |
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| Research Abstract |
We investigated the differentiation of embryonal carcinoma (EC) by cisplatin and overcoming cisplatin-resistance. The TTSC-3 human EC line heterotransplanted in nude mice was used as targets. After treatment of tumor-bearing mice with intraperitoneal injections of cisplatin, histopathological examination was assessed and various gene expressions in the tumors was determined by cDNA array technology, When cisplatin at 1 mg/kg/week was injected intraperitoneally into TTSC-3-bearing mice, the low dose cisplatin had no effect on tumor growth. However, injection of cisplatin at 5 mg/kg/week induced marked regression of the tumor. In contrast, cisplatin at 3 mg/kg/week had a modest inhibitory effect on tumor growth and induced tumor dormancy. Histological examination revealed that injection of cisplatin induced differentiation of EC. cDNA probes from reverse transcribed mRNAs of TTSC-3 treated with cisplatin or saline for 10 weeks were compared to identify genes differentially expressed in cisplatin-treated TTSC-3, Of 1176 different human cDNA transcripts in cisplatin-treated TTSC-3, three genes (tumor necrosis factor receptor 1, caspase 8 and Apaf1), which are associated with apoptosis, were found to be markedly increased, compared to saline injection. The present study demonstrates that intermediate dose of cisplatin inhibited tumor growth of EC by induction of differentiation and enhancement of the apoptosis-related gene expressions.
In the other study, we have shown that combination treatment of baldder cancer cells with TRAIL and cisplatin overcomes cisplatin-resistance. These findings support the potential application in vivo of a combination of TRAIL and cisplatin in the treatment of cisplatin-resistant bladder cancer.
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