| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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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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