| Project/Area Number |
15390485
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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 | The University of Tokyo |
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Principal Investigator |
KITAMURA Tadaichi The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (70010551)
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| Co-Investigator(Kenkyū-buntansha) |
TOMITA Kyoichi The University of Tokyo, Faculty of Medicine, Associate professor, 医学部附属病院, 助教授 (20272578)
KUME Haruki The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (10272577)
NISHIMATSU Hiroaki The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (60251295)
鈴木 基文 東京大学, 医学部附属病院, 助手 (50401063)
太田 信隆 東京大学, 医学部附属病院, 助教授 (50160510)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | Single nucleotide polymorphism / Estramustine phosphate sodium / Prostate cancer / Tailor-made medication / 17β-hydroxysteroid dehydrogenase / Catechol-O-methyltransferase / Cytochrome P450 1A1 / Single nucleotide polymorphism / Estramustine phosphate sodium / Prostate cancer / Tailor-made medication / Cytochrome P450 1A1 / Cytochrome P450 / 17β-hydroxysteroid dehydrogenase / Catechol-O-methyltransferase / Estramustine phoshate sodium / 2-methoxyestradiol |
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| Research Abstract |
In this study, we had prompted to study the interindividual differences of efficacy and adverse effects of estramustine phosphate sodium (EMP) for the treatment of previously untreated advanced prostate cancer. At first, we evaluated clinical efficacy of a low-dose EMP therapy. A low-dose EMP therapy achieved good clinical outcome and reduced toxicities in a dose depend manner. Secondary, we analyzed single nucleotide polymorphisms (SNPs) in the 17β-hydroxysteroid dehydrogenase and the cytochrome P450 (GYP) 1A1 genes, which are involved in the metabolism of EMP. We revealed these SNPs are related with peripheral edema and gastrointestinal toxicity. Furthermore, we found that the Val158Met polymorphism of the catechol-O-methyltransferase gene is associated with the PSA-progression free survival in prostate cancer patients treated with EMP. Nowadays, prior to starting EMP therapy, we actually predict the risk of gastrointestinal toxicity by genotyping of the CYP1A1 gene to perform a tailor-made medication with EMP.
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