| Project/Area Number |
12470334
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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 | Sapporo Medical University |
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Principal Investigator |
TSUKAMOTO Taiji Sapporo Medical University School of Medicine, Professor, 医学部, 教授 (50112454)
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| Co-Investigator(Kenkyū-buntansha) |
MASUMORI Naoya Sapporo Medical University School of Medicine, Assistant Professor, 医学部, 講師 (20295356)
TAKAHASHI Atsushi Sapporo Medical University School of Medicine, Assistant Professor, 医学部, 講師 (20274946)
ITOH Naoki Sapporo Medical University School of Medicine, Associate Professor, 医学部, 助教授 (60193504)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2001: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | RCC / Genestein / VEGF / PPARγ / PPAR γ / 15d-PG2 / ピオグリタゾン / 血管新生 / bFGF / アポトーシス / 前立腺癌 / LBP-Tag / トランスジェニックマウス / 神経内分泌細胞癌アログラフト / ゲニステイン / PPAPγ |
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| Research Abstract |
1) Genistein which is an isoflavone in soy beans and has inhibitory activity of tyrosine kinase, suppressed both vascular endothelial growth factor (VEGF) mRNA and basic fibroblast growth factor (bFGF) mRNA expression in human renal cell carcinoma (RCC) cell lines in vitro, and inhibited in vivo angiogenesis. Furthermore, genistein inhibited the cell growth in RCC cell line in a dose-dependent manner. These findings show that genistein has multiple antitumor functions, suggesting that it may be a novel therapeutic agent for RCC patients.
2) Elevated levels of c-src tyrosine kinase activity due to mutation of c-src genemay result in overexpression of VEGF and cell survival in RCC. To test hypothesis, we examined c-src mutation in RCC cell lines. No mutation was detected in all cell lines, suggesting that mutation of c-src gene dose not seem to be involved in these events.
3) Peroxisome proliferator-activated receptor gamma (PPAR γ) was expressed in RCC cell lines examined. PPAR γ ligand pioglitazone, a agent used in the treatment of type2 diabetes, inhibited VEGF and bFGF expression and production in RCC cells. Furthermore, it inhibited the cell growth and induced apoptosis. These findings indicate that pioglitazone may be useful in treatment RCC patients by multiple antitumor functions.
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