Investigating the new strategy to suppress lung metastasis of sarcomas
| Project/Area Number |
18K09051
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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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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | 医療法人徳洲会野崎徳洲会病院(附属研究所) |
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Principal Investigator |
Sasagawa Satoru 医療法人徳洲会野崎徳洲会病院(附属研究所), 研究所, 主任研究員 (80345115)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 滑膜肉腫 / 転移 / Twist1 / MICA/B / 免疫監視 / HDAC阻害剤 / 免疫回避 / がん微小環境 / NK細胞 / 骨軟部腫瘍 / 免疫療法 |
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| Outline of Final Research Achievements |
Synovial sarcoma, classified as rare cancer, is known as one of the cancers with a poor prognosis due to its high incidence of metastasis. In this study, we demonstrated that Twist1 and metastasis-promoting environmental conditions suppress MICA/B expression, and low-dose HDAC inhibitors restore MICA/B expression. We also experimentally demonstrated that Twist1 is responsible for drug resistance to HDAC inhibitors; we identified SN38 as a drug that suppresses Twist1 expression and showed that it can be used in combination with HDAC inhibitors to improve drug efficacy. The results of this study clearly indicate the direction of novel molecular targeted therapy for synovial sarcoma metastasis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題では、滑膜肉腫の転移に対して有効な治療法として、低用量HDAC阻害剤とイリノテカン（もしくはその代謝産物SN38）を併用することで、転移巣でもMICA/Bの発現を回復させ、NK細胞による腫瘍免疫反応により細胞死を誘導することを提案した。いずれの薬剤もいくつかのがんで承認されているものであることから、滑膜肉腫治療における臨床応用へのハードルは高くないと推測される。これまでに、滑膜肉腫の転移を抑制する、転移巣に於いても有効に作用する化学療法はほとんど無いため、本研究の成果は臨床応用への重要な礎になると期待される。
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Report
(5 results)
Research Products
(11 results)
