Novel adjuvant therapy for malignant primary bone tumor using combination of anti-angiogenic reagent and bisphosphonate
| Project/Area Number |
17591596
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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 | Kyorin University (2006)
Keio University (2005) |
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Principal Investigator |
MORII Takeshi Kyorin Univ., School of Medicine, Assistant Professor, 医学部・高 (70255496)
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| Co-Investigator(Kenkyū-buntansha) |
TOYAMA Yoshiaki Keio Univ., School of Medicine, Assistant Professor, 医学部, 教授 (40129549)
YABE Hiroo Keio Univ., School of Medicine, Assistant Professor, 医学部, 講師 (70119030)
MORIOKA Hideo Keio Univ., School of Medicine, Assistant Professor, 医学部, 講師 (10230096)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Osteosarcoma / Chondrosarcoma / Angiogenesis / Bisphosphonate / 原発性悪性骨腫瘍 |
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| Research Abstract |
In vitro direct inhibition effect of alendronate on chondrosarcoma and osteosarcoma growth was confirmed. This effect was through the inhibition of ras-mevalonate pathway. By using proteome analysis with confirmation by Western blot, intracellular mechanism of this phenomenon was by apoptosis induction, cell cycle arrest and inhibition of phosphorylation on cytoskeleton proteins. Inhibition of migration of tumor cells was induced by bisphosphonate. Direct inhibition effect of endothelial cell growth in vitro was shown, also through the mevalonate pathway. Co-culture system of endothelial cells and fibroblast was established. Inhibition effect by alendronate on endothelial growth, migration, tube formation and branching was confirmed in this system without harming normal fibroblasts, suggesting the safety application of this reagent on human. Novel antiangiogenic protein, plasminogen related protein B was generated by cloning plasminogen related gene B and confirmed its antiangiogenic effect in vitro and in vivo. This effect was through the inhibition of phosphorylation of MAPK. Possible receptor of this protein was shown to be alpha VbetaII integrin on the cell surface.
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Report
(3 results)
Research Products
(28 results)
