2017 Fiscal Year Final Research Report
Investigation of the molecular mechanisms underlying therapeutic resistance in osteosarcoma metastasis
| Project/Area Number |
15K06845
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Hoshi University |
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Principal Investigator |
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| Research Collaborator |
SAYA Hideyuki 慶應義塾大学, 医学部・先端医科学研究所・遺伝子制御研究部門, 教授
SOGA Tomoyoshi 慶應義塾大学, 先端生命科学研究所, 教授
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 骨肉腫 / 転移 / 治療抵抗性 |
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| Outline of Final Research Achievements |
The elucidation of molecular mechanisms underlying therapeutic resistance in metastasis of osteosarcoma (OS) and development of novel therapies are urgently needed.
The changes of gene expression caused by chemotherapy suggested that macrophages or thrombosis might be involved in the therapeutic resistance in lung metastasis.
Through the screening of drugs, simvastatin and calcitriol were found to inhibit anchorage-independent growth, an important property for the establishment of metastasis. Simvastatin induced apoptosis in a manner dependent on inhibition of the mevalonate synthetic pathway. Combination of simvastatin and a fat-free diet exerted a significant antitumor effect. Calcitriol induced cell cycle arrest by activating the ER stress response. A single dose of calcitriol was sufficient to inhibit tumor growth. These findings indicated the potential of both drugs as novel therapeutic options for OS metastasis although further refinement of the optimal conditions is required.
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| Free Research Field |
腫瘍生物学
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