| Project/Area Number |
17K10694
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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 |
Digestive surgery
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
坂口 孝宣 浜松医科大学, 医学部, 准教授 (70313955)
平出 貴乗 浜松医科大学, 医学部, 特任助教 (70780386)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 膵癌 / 神経浸潤 / Tenascin C / DRG / EMT / Dorsal Root Ganglion / 脂質 / 脂質代謝 / 癌周囲微小環境 |
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| Outline of Final Research Achievements |
We examined immunohistochemical TNC expression in 78 resected PDAC specimens. The relationships between TNC expression and clinicopathological features were retrospectively analyzed. Interactions between cancer cells and nerves with TNC supplementation were investigated using an in vitro coculture model with PDAC cell line and DRG.
Tenascin C expression was predominant in perineural sites at the invasive tumor front. High perineural TNC expression in 30 patients (38%) was associated with perineural invasion, pathological T stage ≥3, and postoperative locoregional recurrence. High TNC expression was independently associated with postoperative, poor recurrence-free survival by multivariate analysis. In the in vitro coculture model, a TNC-rich matrix enhanced both PDAC cell colony extensions toward nerves and DRG axonal outgrowth toward cancer cell colonies, whereas TNC did not affect axonal outgrowth or cancer cell proliferation in separately cultured DRG and PDAC cells.
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| Academic Significance and Societal Importance of the Research Achievements |
今回我々は、細胞外マトリックス糖タンパク質Tenascin C (TNC)に着目し、膵がんの神経周囲浸潤における役割について検証した。膵がん神経周囲浸潤に対するTNCの役割を臨床病理学的及び分子生物学的に検証したものは過去になく、本研究は今後の詳細な膵がん神経周囲浸潤機構解明への大きな一歩になりうる。将来的にはTNCに関連する経路を治療ターゲットとした、膵癌の神経周囲浸潤抑制治療が期待できる。
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