| Project/Area Number |
18K07987
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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 53010:Gastroenterology-related
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| Research Institution | Kurume University |
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Principal Investigator |
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Chitinase 3-like 1 / 炎症性腸疾患 / 上皮異形成 / キサンチン誘導体 / カフェイン / ペントキシフィリン / 核局在配列 / p53 / CHI3L1 / 核内移行 / サイクリン結合部位 / 慢性炎症関連性大腸炎 / キチナーゼ3様タンパク / 大腸炎関連癌 |
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| Outline of Final Research Achievements |
Previously, our group has reported that caffeine (CAF), one of the xanthine-derivatives, suppresses inflammation by inhibiting pan-chitinases including enzymatically inactive chitinase 3-like 1 (CHI3L1), in a dextran sodium sulfate (DSS)-induced acute colitis. In this study, we have examined anti-neoplastic effect of CAF and/or PTXN in an Azoxymethane (AOM)-induced chronic colitis-associated cancer model. AOM was intraperitoneally administered to 8-week-old C57Bl/6 mice for 6 times, and these mice were sacrificed 5 weeks after the final administration of AOM. The mice were treated with CAF, PTXN or dH2O for 8 times intraperitoneally. Both CAF and PTXN administered mice cause severe adverse effects (e.g. shock death), so we suspended further experiment in this group. In an AOM-induced colonic cancer model, PTXN-treated mice significantly reduced the incidence of tumor multiplicity as well as tumor size as compared to the other two groups. PTXN may have an anti-neoplastic effect.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、日本における大腸癌と潰瘍性大腸炎やクローン病を含む炎症性腸疾患の罹患率が増加の一途をたどっている。特に大腸癌は最も予後不良な固形癌の一つである。我々のグループは、酵素活性を持たないタイプの哺乳類キチナーゼの一種であるCHI3L1が急性・慢性炎症時や大腸癌発症時に著しく増加し、その病態に深く関与することを報告してきた。興味深いことに、キサンチン誘導体の一種であるCAF とPTXNがCHI3L1の発現とその機能を抑制することがわかった。特にPTXNは、AOM誘導性の腸管上皮異形成に伴う大腸腫瘤数および腫瘤の大きさをCAFよりも有意に抑制したことから、将来的に臨床応用の可能性が期待できる。
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