| Project/Area Number |
11470341
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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 |
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Principal Investigator |
MIKI Tsuneharu Kyoto Prefectural University of Medicine, Urology, Professor, 医学部, 教授 (10243239)
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| Co-Investigator(Kenkyū-buntansha) |
NONOMURA Norio Osaka University, Urology, Assistant Professor, 医学部, 講師 (30263263)
NAKAO Masahiro Kyoto Prefectural University of Medicine, Urology, Assistant Professor, 医学部, 講師 (00188880)
SAKAI Toshiyuki Kyoto Prefectural University of Medicine, Hygiene, Professor, 医学部, 教授 (20186993)
MIZUTANI Yoichi Kyoto Prefectural University of Medicine, Urology, Assistant Professor, 医学部, 講師 (10243031)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 2000: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1999: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | Testicular Tumor / Gene / WT1 / Induction of Differentiation / Apoptosis / Chemotherapy / Irinotecan / Cisplatin / Embryonal carcinoma / Teratoma / WT1遺伝子 / VD3 / p27プロモーター / p53遺伝子 / WAF1 / Apo-2リガンド / Bnip3L |
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| Research Abstract |
We measured the expression level of WT1 mRNA in 34 testicular tumors by quantitative RT-PCR.The level of WT1 mRNA expression in high stage testicular tumors was higher than that in low stage tumors. There was no correlation between the level of WT1 mRNA expression and grade of testicular tumors.
The maturation of TTSC-3 and TTSC-5 human testicular embryonal carcinoma (EC) lines by cisplatin was examined. 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 5 weeks after injection of cisplatin ( 3 mg/kg/week), primitive mesenchymal like cells increased, and 10 weeks after cisplatin injection, cartilage and well-developed glands (teratoma) were observed. 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.
The chemotherapy with irinotecan in combination with cisplatin or nedaplatin, a derivative of cisplatin, was investigated as salvage chemotherapy for GCT.Twenty patients were entered onto the study, and 18 were assessable for response and toxicity. The response rate was 56 % (5 complete responses and 5 partial responses). Eight patients remain alive without disease. However, 5 patients died of the disease, and 1 patient died of brain glioma. The 5-year survival rate was approximately 55 %. Myelosuppression was the major toxicity, but was quite manageable. This study demonstrates that the chemotherapy with irinotecan in combination with cisplatin or nedaplatin showed a significant anticancer activity for patients with refractory GCT, without serious side effects.
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