2006 Fiscal Year Final Research Report Summary
Analysis of mechanisms of the resistance of cisplatin in refractory or relapsed germ cell tumors
Project/Area Number |
16591611
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Urology
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
NOMOTO Takeshi Kyoto Prefectural University of Medicine, Graduate School of Medicine, Assistant Professor, 医学研究科, 助教 (20301426)
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Co-Investigator(Kenkyū-buntansha) |
MIKI Tsuneharu Kyoto Prefectural University of Medicine, Graduate School of Medicine, Professor, 医学研究科, 教授 (10243239)
MIZUTANI Yoichi Kyoto Prefectural University of Medicine, Graduate School of Medicine, Associate professor, 医学研究科, 准教授 (10243031)
KAWAUCHI Akihiro Kyoto Prefectural University of Medicine, Graduate School of Medicine, Associate professor, 医学研究科, 准教授 (90240952)
OKIHARA Koji Kyoto Prefectural University of Medicine, Graduate School of Medicine, Associate professor, 医学研究科, 講師 (80285270)
MIKAMI Kazuya Kyoto Prefectural University of Medicine, Graduate School of Medicine, Assistant Professor, 医学研究科, 助教 (10291585)
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Project Period (FY) |
2004 – 2006
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Keywords | refractory testicular tumor / Salvage chemotherapy / NALP7 / cisplatin / Paclitaxel |
Research Abstract |
The overall response rate of cisplatin-based combination chemotherapy of patients with germ cell tumors (GCTs) has improved. Despite the high cure rate, 20-30 percent of patients with advanced GCTs failed to achieve a durable complete response. These refractory or relapsed GCTs remain a major problem in current treatment. In clinical study, we investigated the chemotherapy with paclitaxel in combination with nedaplatin, which is a derivative of cisplatin, and ifosphamide as salvage chemotherapy for cisplatin refractory germ cell cancer. Fourteen patients were evaluated for response and toxicity. Response rate was 57.1 % (CR / PR^<m.> : 8 cases, NC : 5 cases、 PD : 1 cases ).Seven patients remain alive without disease. This study demonstrates that the chemotherapy with paclitaxel in combination with nedaplatin and ifosphamide showed a significant anticancer activity for patients with cisplatin refractory or relapsed germ cell cancer. These findings suggest that the combination chemotherapy may be one of the options of salvage chemotherapy for cisplatin refractory or relapsed germ cell cancer. In this study, to investigate new diagnostic markers and potential therapeutic targets for GCTs, we identified 347 genes that were commonly up-regulated in GCTs by using a cDNA microarray (Int J Oncol, 2003). Furthermore, we identified NALP7 that was significantly transactivated in GCTs and showed that NALP7 may be a promising candidate for development of targeted therapy for GCTs (Cancer Sci, 2004).
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