2004 Fiscal Year Final Research Report Summary
Targeting antiangiogenesis inhibitor using antiangiogenesis molecular signals
| Project/Area Number |
15390219
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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 |
General internal medicine (including Psychosomatic medicine)
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SHICHIRI Masayoshi Tokyo Medical and Dental University, Medical Hospital, Associate Professor, 医学部附属病院, 助教授 (10206097)
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| Co-Investigator(Kenkyū-buntansha) |
HIRATA Yukio Tokyo Medical and Dental University, Dept.Clinical & Molecular Endocrinology, Professor, 大学院・医歯学総合研究科, 教授 (50135787)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Antiangiogenesis signal / Endostatin / Endothelial cell migration / Endothelial cell growth / Anti-tumor effect / Endothelial apoptosis / Vascular endothelial cell / Metastasis |
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| Research Abstract |
Cancer progression and metastasis depend on recruitment of new blood vessels and are characterized by oncogene-driven tumor expression of pro-angiogenic proteins. Most pro-angiogenic factors are soluble endogenous proteins and their receptors are displayed on the surface of endothelial cells. Inhibition of tumor angiogenesis suppresses experimental tumor growth, and is considered a promising new therapeutic approach to treat human cancer. However, clinical application of anti-angiogenesis therapy for suppression of tumor progression would theoretically require long-term administration of angiogenesis inhibitors, but most of them entering clinical trials are rather large molecular weight protein and/or require intravenous administration. We have previously demonstrated that an anti-angiogenesis inhibitor, endostatin, markedly down regulates a variety of growth-, migration-, and angiogenesis-associated genes in exponentially growing human and rat microvascular endothelial cells. In the present study, we searched for compounds and peptides eliciting such anti-angiogenesis molecular signals in endothelial cells in an attempt to identify new therapeutic agents for human tumors. The results demonstrate that three ansamycin antibiotics and a fragment of vasoactive peptide induced antiangiogenesis signals similar to endostatin and that the former suppressed progression of human cancer xenografts as well.
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