The Development of Novel Therapy Targeting Metabolic Pathway Dysregulation in Doxorubicin-resistant Bone and Soft Tissue Sarcomas
| Project/Area Number |
26861218
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Kobayashi Eisuke 国立研究開発法人国立がん研究センター, 中央病院, 医員 (40365292)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肉腫 / メタボリックエラー / アルギニン / オートファジー / 骨軟部肉腫 / ドキソルビシン耐性 / 新規治療開発 |
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| Outline of Final Research Achievements |
We focused on the arginosuccinate synthetase 1 (ASS1), which is essential for generation of arginine with non-essential amino acids in metabolic error of cancer cell metabolism. The expression of ASS1 was reduced in Dox-resistant sarcoma cells. Interestingly, there was an inverse relationship between the expression of ASS1 and the expression of P-gp. Furthermore, the inhibition of cellular proliferation, with G1-arrest, was shown to lead to autophagy with arginine deprivation. The combination of chloroquine plus arginine deprivation was more effective than arginine deprivation alone. In ASS1 reduced cells, the expression of P-gp was upregulated in comparison to negative controls. These results indicate that the reduced expression of ASS1 expression in Dox-resistant sarcomas may contribute to drug resistance. ASS1 deficiency is a potential target for novel drug therapies.
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Report
(3 results)
Research Products
(10 results)
