| Project/Area Number |
17K16063
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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 |
Respiratory organ internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
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| Research Collaborator |
Kaymeyama Naofumi
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | COPD / 肺気腫 / 肺癌 / マウス / 癌 |
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| Outline of Final Research Achievements |
The mechanisms involved in smoke-induced tumorigenesis and emphysema are not fully understood, attributable to a lack of appropriate animal models. Here, we optimized a model of intermittent cigarette smoke induced lung cancer and emphysema in A/J mice treated with NNK, a potent carcinogen. Intermittent CS exposure increased the severity of emphysema and resulted in a higher incidence of adenocarcinomas. Furthermore, intermittent CS exposure elicited a marked increase in M2-polarized macrophages within and near the developed tumors.
This model is also suitable for screening putative chemo-preventive agents, and serves as a therapeutic intervention that mimics progressive human lung cancer with emphysema in smokers.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の意義は、肺がん発現に至るまでの経時的な遺伝子変化、慢性炎症、酸化ストレスを評価可能なことである。また連続喫煙群と、禁煙群の肺に与える影響の差を明らかにできることである。肺がんの発症予防は臨床的に非常に重要な分野であり、ヒトを対象にしたphase Ⅲ試験も複数行われている。しかしこうした臨床研究で効果の確立したChemopreventionの薬剤は未だないのが現状である。本研究の結果により、肺癌のchemopreventionの薬剤開発のためのpreclinical modelの提唱、chemopreventionが有効である対象の選択、マーカーの探索の開発につながると考えている。
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