| Project/Area Number |
18K16910
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | Osaka Medical College |
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Principal Investigator |
Ayani Yusuke 大阪医科大学, 医学部, 助教 (80816380)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 耳下腺癌 / TRKB / 神経浸潤 / 顔面神経麻痺 / 癌治療 / 分子標的治療 / 細胞株 |
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| Outline of Final Research Achievements |
First, we showed abnormal upregulation of TRKB in human PGC. The expression was significantly high in an aggressive malignancy, SDC, comparing with a slow-growing and relentless malignancy, AdCC. Second, although high expression of TRKB was not associated with neuroinvasion in the patients with PGC (SDC and AdCC), it was significantly correlated with tumor subtype, vascular invasion, nodal metastasis, and poor prognosis. Last, BDNF-induced cell migration of PGC cells was attenuated by a TRKB specific inhibitor and an anticancer drug, larotrectinib (pan-TRK inhibitor). These findings describe the importance of the BDNF-TRKB axis in the aggressiveness of SDC and support that TRKB signaling is a therapeutic target in patients with PGC.
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| Academic Significance and Societal Importance of the Research Achievements |
耳下腺癌は希少癌であるため、有効な治療薬が確立されておらず、新たな治療薬の開発が望まれている。本研究では神経浸潤にまつわる分子としてTRKBに注目し、TRKBが耳下腺癌の予後に関連することを見出した。将来的にTRKBをターゲットとした分子標的薬が耳下腺癌の治療薬として臨床応用されれば、社会的にも意義深いと考える。
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