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2000 Fiscal Year Final Research Report Summary

Study on gene analysis and gene expresssion associated with differentiation in testicular germ cell tumor

Research Project

Project/Area Number 11470341
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKYOTO PREFECTURAL UNIVERSITY OF MEDICINE

Principal Investigator

MIKI Tsuneharu  Kyoto Prefectural University of Medicine, Urology, Professor, 医学部, 教授 (10243239)

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)
Project Period (FY) 1999 – 2000
KeywordsTesticular Tumor / Gene / WT1 / Induction of Differentiation / Apoptosis / Chemotherapy / Irinotecan / Cisplatin
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.

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Miki,T., et al.: "WT1 gene expression in human……"Molewlar Urology. 3. 357-363 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 三木恒治 ほか: "難治性精巣腫瘍に対するPBSCT併用……"泌尿器科紀要. 45. 805-809 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 三木恒治 ほか: "難治性精巣腫瘍に対する新規抗癌剤に……"泌尿器科紀要. 45. 811-814 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 三木恒治 ほか: "進行性精巣腫瘍に対する薬学的治療……"泌尿器科紀要. 45. 777-781 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] 三木恒治 ほか: "難治性精巣腫瘍の救済化学療法"癌と化学療法. 27. 542-547 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] 三木恒治,中尾昌宏 : "精巣腫瘍治療の現状と問題点"泌尿器外科. 13. 1265-1271 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] Harada Y, Nonomura N, Nishimura K, Tamaki H, Takahara S, Miki T, Sugiyama H, Okuyama A.: "WT1 gene expression in human testicular germ-cell tumors."Molecular Urology. 3. 357-363 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogata M, Takada T, Mori Y, Uchida Y, Miki T, Okuyama A, Kosugi A, Sawada M, Oh-hora M, Hamaoka T.: "Regulation of phosphorylation level and distribution of PTP36, a putative protein tyrosine phosphatase, by cell-substrate adhesion."Journal of Biological Chemistry. 274. 20717-20724 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Imazu T, Shimizu S, Tagami S, Matsushima M, Nakamura Y, Miki T, Okuyama A, Tsujimoto Y: "Bcl-2/E1B 19 kDa-interacting protein 3-like protein (Bnip3L) interacts with Bcl-2/Bcl-xL and induces apoptosis by altering mitochondrial membrane permability."Oncogene. 18. 4523-4529 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Mizutani Y, Yoshida O, Miki T: "Bonavida B : Synergistic cytotoxicity and apoptosis by Apo-2 ligand and adriamycin against bladder cancer cells."Clinical Cancer Research. 5. 2605-2612 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Mizutani Y, Yoshida O, Miki T: "Adriamycin-mediated potentiation of cytotoxicity against freshly isolated bladder cancer cells by autologous non-activated peripheral blood lymphocytes and tumor infiltrating lymphocytes."The Journal of Urology. 162. 2170-2175 (1999)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Nozawa M, Yomogida K, Kanno N, Nonomura N, Miki T, Okuyama A, Nishimune Y, Nozaki M: "Prostate-specific transcription factor hPSE is translated only in normal prostate epitherial cells"Cancer Research. 60. 1348-1352 (2000)

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  • [Publications] Kanemitsu N, Kato M, Miki T, Komatsu S, Okazaki Y, Hayashizaki Y, Sasaki T: "Characterzation of the promoter of the murine mac25 gene."Biochemical and Biophysical Research Communication.. 279. 251-257 (2000)

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  • [Publications] Nishimura K, Nonomura N, Yasunaga Y, Takaha N, Inoue H, Sugao H, Yamaguchi S, Ukimura O, Miki T, Okuyama A: "Low doses of oral dexamethasone for hormone-refractory prostate carcinoma."Cancer. 89. 2570-2576 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Kawauchi A, Tanaka Y, Soh J, Ukimura O, Kojima M, Miki T: "Cause of nocturnal urinary frequency and reasons for its increase with age in healthy older men."The Journal of Urology.. 163. 61-64 (2000)

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Published: 2002-03-26  

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