Development of molecular target therapy for synovial sarcoma
| Project/Area Number |
16591487
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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 |
Orthopaedic surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
NAKAYAMA Tomitaka Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (80335273)
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| Co-Investigator(Kenkyū-buntansha) |
TOGUCHIDA Junya Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (40273502)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | synovial sarcoma / molecular target therapy / fibroblast growth factor / retinoic acid / FGF |
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| Research Abstract |
FGF receptor inhibitor SU5402 inhibited the growth of all five synovial sarcoma cell lines tested. The IC50(μmol/L) in the culture media with 1% FBS were 11.4 in YaFuSS,4.9 in HS-SYII, 8.6 in SYO-1,25.3 in Fuji, and 29.9 in 1273/99,respectively. It accompanied the hypophosphorylation of FGFR3. In YaFuSS and HS-SY-II, which was sensitive to FGFR inhibitor, SU5402 treatment completely inhibited the phosphorylation of ERK1/2 but not that of p38. An inhibitor of MAPKK, U0216 also inhibited the growth of synovial sarcoma cells and ERK1/2 phosphorylation in them. Treatment by SU5402 increased G1 and subG1 proportion in YaFuSS. SYO-1 is tumorigenic in subcutis of nude mice. 0.5mg and 0.1mg of FGFR inhibitor PD166866 given intraperitoneally inhibited the tumor growth in the dose dependent manner.
Synovial sarcoma cells and synovial sarcoma tissue expressed neuron-related genes such as neurofilament and microtubule associated protein. Synovial sarcoma cells expressed retinoic acid and retinoid X recepor and some synovial cell lines expressed cellular retinoic acid binding protein 1. All trans retinoic acid gave synovial sarcoma cells morphological change, induce the expression several neuron-related genes, and inhibits the growth.
These findings showed the potential application of FGFR inhibitor and retinoic acid for the treatment of synovial sarcoma.
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Report
(3 results)
Research Products
(8 results)
