2003 Fiscal Year Final Research Report Summary
Analysis of the mechanisms of expression and function of endostatin, a novel anti-cancer medicine derived from basement membrane collagen.
| Project/Area Number |
14571130
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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 |
General surgery
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
YAMAGUCHI Noriko Tokyo Med. & Dent. Univ., Medical Research Institute, Instructor, 難治疾患研究所, 助手 (90251553)
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| Co-Investigator(Kenkyū-buntansha) |
HORI Hisae Tokyo Med. & Dent. Univ., Medical Research Institute, Instructor, 難治疾患研究所, 助手 (80014190)
OKABE Satoshi Tokyo Med. & Dent. Univ., Graduate School, Associate Professor, 大学院・医歯学総合研究科, 講師 (60242187)
AOYAGI Masaru Tokyo Med. & Dent. Univ., Graduate School, Associate Professor, 大学院・医歯学総合研究科, 助教授 (40134704)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Angi ogenesis / Cancer / Endostatin / Rheumatoid arthritis |
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| Research Abstract |
Endostatin is an endogenous angiogenesis inhibitor and showed quite strong anti-cancer activity. In mouse tumor model, endostatin inhibits tumor progression, tumor metastasis and induces tumor regression The final goal of this research is to elucidate the functional mechanisms of endostatin on molecular level, then to contribute the development of new anti-cancer drugs. During 2002 to 2003, we achieved those progression described below.
It was reported that serum level of endostatin Was positively correlated to the progression of cancer. Therefore, we measured angiogenesis inhibitory activity of endostatin-related proteins in human serum. Four endostatin-related fragments were isolated from human serum by anti-endostatin immuno-affinity colum. Recombinant proteins for four fragments revealed inhibitory activities in endothelial cell migration assay. We detected 25kDa fragment reacted with anti-endostatin antibody in the homogenates of human glioma tissues. The levels of tissue endostatin (25kDa fragment) and malignancy grades in gliomas showed the positive correlation. Also, we discovered that endostatin has inhibitory activity against some matrix metalloproteinases through the examination of functional study of endostatin. Angiogenesis inhibitors were considered to be a potential therapy of rheumatod arthritis. We estimated the efficacy of endostatin in two different animal models of rhematoid arthritis and endostatin was proved to be a promising medicine for rhematoid arthritis.
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Research Products
(23 results)
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[Publications] Morimoto T., Aoyagi M., Tamaki M., Yoshino Y., Hon H., Duan L., Yano T., Shibata M., Ohno K., Hirakawa K., Yamaguchi N.: "Increased levels of tissue endostatin in human malignant gliomas."Clin. Cancer Res.. 8. 2933-2938 (2002)
Description
「研究成果報告書概要(欧文)」より
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