2004 Fiscal Year Final Research Report Summary
Analysis of tumor suppressor gene in refractory or relapsed germ cell tumors and its therapeutic application
| Project/Area Number |
14370519
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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, Professor, 医学研究科, 教授 (10243239)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Toshiyuki Kyoto Prefectural University of Medicine, Professor, 医学研究科, 教授 (20186993)
KAWAUCHI Akihiro Kyoto Prefectural University of Medicine, Associate professor, 医学研究科, 助教授 (90240952)
MIZUTANI Yoichi Kyoto Prefectural University of Medicine, Associate professor, 医学研究科, 助教授 (10243031)
NOMOTO Takeshi Kyoto Prefectural University of Medicine, Lecturer, 医学研究科, 助手 (20301426)
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| Project Period (FY) |
2002 – 2004
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| Keywords | refractory or relapsed GCTs / retinoblastoma gene / promoter / tumor suppressor gene / E4TF1 / NALP7 / irinotecan / cisplatin |
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| Research Abstract |
The overall response rate of cisplatin-based combination chemotherapy for 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.
The tumor suppressor retinoblastoma gene (RB) is a well known regulator of cell cycle progression, differentiation and apoptosis. Inactivation of this gene is closely associated with the development of many human malignancies. Previous studies revealed lower levels of RB mRNA and protein in GCTs compared with normal testis tissue. Therefore, we investigated the mechanisms of the inactivation of the RB gene in, GCTs and planned to develop its therapeutic application for GCTs.
In this study, we showed that the hGABP/E4TF1 site did not act as a positive regulatory element and the RB gene might be down-regulated at the transcriptional level in human seminoma cells (Oncol Rep, 2005). Moreover, 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). In clinical study, we demonstrated that the chemotherapy with irinotecan in combination with cisplatin showed significant anticancer activity for patients with refractory or relapsed GCTs (Cancer, 2002).
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