| Project/Area Number |
17K16562
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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 |
Digestive surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肝癌微小環境 / 癌関連マクロファージ / 癌関連線維芽細胞 / 肝癌 / CAF / TAM / NK細胞 / マクロファージ / 線維芽細胞 / 微小環境 / 腫瘍関連マクロファージ |
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| Outline of Final Research Achievements |
Fibroblast was isolated from cancer- and non-cancerous tissue of human resected liver, and defined as cancer-associated fibroblast(CAF) and normal fibroblast(NF), respectively. Hepatoma cell line when co-cultured with exosome derived from CAF showed higher invasion. In the exosome from CAF, miR150-3p was significantly lower compared with NF. Over expression of miR150-3p showed higher invasive capacity of hepatoma cell line. Using the database, the negative target gene of miR150-3p was identified: CDH2. Knockdown of CDH2 in hepatoma cell line showed decreased invasive capacity. Immunohistochemical stain was done. Among patients who underwent hepatectomy for hepatocellular carcinoma, overall- and recurrence free survival rate was significantly worse in high CDH2 group.
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| Academic Significance and Societal Importance of the Research Achievements |
肝癌の再発には炎症性癌微小環境が大きく関わっていることが明らかになっている。また肝・脾におけるマクロファージのphenotypeの相違が肝線維化に関わっているとも考えられている。これら組織間のマクロファージや肝線維芽細胞、肝細胞との関係と各種サイトカインを詳細に検討することで、成因を超えた肝線維化と肝発癌の抑制につながる可能性が高く、かつそうした創薬はこれまでになく我が国独創的である。さらに癌微小環境は各癌腫でも注目されており、今回の検討が臓器を超えた普遍的な癌治療に結びつく可能性も秘めている。
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