A PRODUCTIVE TRIAL OF ANTI-ANGIGENIC AGENTS BASED ON A ELUCIDATION OF A MECHANISM OF bFGF AS A FIRST TRIGGER ON ANGIOGENIC PATHWAY
| Project/Area Number |
09672343
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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 |
応用薬理学・医療系薬学
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| Research Institution | TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH |
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Principal Investigator |
ASHINO Hiromi TOKYO METROPOLITAN ORGANIZATION OF MEDICAL RESEARCH, TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE / DEPARTMENT OF MOLECULAR BIOLOGY / RESEARCH SCIENTIST, 東京都臨床医学総合研究所, 研究員 (40222608)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMAMURA Mariko TOKYO METROPOLITAN ORGANIZATION OF MEDICAL RESEARCH, TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE / DEPARTMENT OF MOLECULAR BIOLOGY / RESEARCH SCIENTIST, 東京都臨床医学総合研究所, 研究員 (00124462)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Angiogenesis / Acidic polysaccharides / bFGF / Herapan sulfate / chorioallantoic membrane / endothelial cells / bFGF / FGF |
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| Research Abstract |
In order to try the production of inhibitors of angiogenic diseases, which inhibit the activity of first angiogenic factor functioning as a trigger, we examined anti-angiogenic activities of various acidic polysaccharides using chick embryonic chorioallantoic membrane (CAM)s and bovine vascular endothelial cell culture.
We found that Dextran sulfate (DS) markedly inhibited angiogenesis of chick CAMs, that its inhibitory effect did not depend on molecular weight, but depended on sulfation, that DS inhibited cell migration unstimulated and stimulated by bFGF and that in heparitinase-treated endothelial cells the signal of bFGF to induce plasminogen activator was weakened.
These results indicate that DS may disrupt binding of bFGF or heparin / heparan sulfate(HS)-binding angiogenic factors to HS, resulting in the inhibition of angiogenesis. It is thought that functional inhibition of angiogenic factor as a trigger is important and effective to suppress the initiation of angiogenesis. Accordingly molecules like DS that modulate the activity of heparin / HS-binding growth factors by sequestering the growth factor are expected to suppress the early step of angiogenesis.
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Report
(4 results)
Research Products
(12 results)
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[Publications] Shimamura, M., Hori, H., Ashino, H., Yamamoto, Y., Hzato, T. and Inayama, S.: "Anti-angiogenic and anti-metastatic effects of new hypoxic cell radiosensitizer."I.C.C.. 20. 2369 (1997)
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[Publications] Ashino, H., Nakajima, H., Shimamura, M., Dombou, M., Kawanaka, S., Hattori, N., Iwaguchi, T. and Kawashima, S.: "Novel function of ascorbic acid as an angiogenesis inhibitor."(submitted.).
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