| Project/Area Number |
17K10659
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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 | Kurume University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
角田 俊之 福岡大学, 医学部, 准教授 (70444817)
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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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 潰瘍性大腸炎 / 癌化 / ポシティブフィードバック因子 / 癌化ハイリスク症例の選別 / 潰瘍性大腸炎の癌化 / 遺伝子解析 / 炎症促進因子 / 造腫瘍機構 / 炎症性腸疾患 |
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| Outline of Final Research Achievements |
In order to select high-risk cases of cancer for patients with ulcerative colitis (UC), the expression of the cancer lesions in UC cancer-combined cases was higher than that of normal mucosa in the same cases and which was not increased in sporadic colorectal cancer patients. A cDNA microarray analysis was performed to search for those that did not exist. Claudin 2, CEACAM6, and PDE4 were extracted, and it was confirmed that CEACAM6 and E. coli-derived Lipopolysaccharide were expressed at the same site in UC cancer tissues. It was shown that PDE4 inhibitor induces apoptosis of the lumen of three-dimensional cultured mutant KRAS-positive cell mass, and that PDE4 is an important mutant KRAS signal in carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
組織を用いた今回の検討で抽出されたClaudin 2、CEACAM6、PDE4などは、接着性侵襲性大腸菌の活動に関わっていることが分かった。接着性侵襲性大腸菌はCD患者の炎症が悪化した腸管の環境下に発現が増強する蛋白質である。また、PDE4はTNFαやINFγなどの炎症性サイトカインを誘導するため、ポジティブフィードバック因子の可能性が示唆された。以上のことから、これらの発現はUC患者に対するColitic Associated Cancerの早期診断・治療など臨床応用への展開できることが期待される。
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