Development of new chemotherapy for refractory prostate cancer
| Project/Area Number |
18591774
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Keio University |
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Principal Investigator |
OHIGASHI Takashi Keio University, School of Medicine, Assistant Professor (80185371)
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| Co-Investigator(Kenkyū-buntansha) |
NAKASHIMA Jun Keio University, School of Medicine, Associate Professor (10167546)
MIYAJIMA Akira Keio University, School of Medicine, Assistant Professor (90245572)
KIKUCHI Eiji Keio University, School of Medicine, Assistant (10286552)
村井 勝 慶應義塾大学, 医学部, 教授 (90101956)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,550,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | prostate cancer / vitamin / histone / chemotherapy / アンドロゲン受容体 / 細胞周期 / ヒストン / ビタミンE |
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| Research Abstract |
Gene expression profiling using microarray analysis showed Vitamin E succinate (VES) caused a down-regulation in AR target genes. On the other hand, the expression of androgen receptor (AR) was not changed with VES. VES also down-regulated the cell cycle associated protein, microchromosome maintenance (MCM) families, Cdc-45 and Cdc-6. Reporter Gene assay using AR-negative PC-3 cells revealed VES caused reduced expression of luciferase. Immuno-precipitation analysis with androgen response element suggested that VES inhibited demethylation of histone H3 lysine 9.
The pre-incubation with VES enhanced the cytotoxic effects of paclitaxel on LNCaP and LN-AI cells. LN-AI cells implanted in nude mice showed resistance to paclitaxel alone. However, intraperitoneal injection of VES showed enhanced suppression of tumor proliferation in nude mice.
Histone deacetylase inhibitor(HDACI), FK-228, also induced G1-arrest in both LNCaP and LN-AI cells. Microaray analysis showed that HDACI downregulates AR expression. HDACI also inhibited the expression of MCM families.
These results showed the possibility of novel chemotherapeutic strategy that the agents which influences AR activity/ expression enhanced anti-tumor effects even in androgen-independent prostate cancer
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Report
(3 results)
Research Products
(28 results)
