Mechanism of lung tumorigenesis in smoke exposure mouse model.
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 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Keio University |
Principal Investigator |
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Research Collaborator |
Kaymeyama Naofumi
|
Project Period (FY) |
2017-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
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)
|
Keywords | COPD / 肺気腫 / 肺癌 / マウス / 癌 |
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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Report
(3 results)
Research Products
(3 results)
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[Journal Article] Intermittent Exposure to Cigarette Smoke Increases Lung Tumors and the Severity of Emphysema More Than Continuous Exposure.2018
Author(s)
Kameyama N, Chubachi S, Hegab AE, Yasuda H, Kagawa S, Tsutsumi A, Fukunaga K, Shimoda M, Kanai Y, Soejima K, Betsuyaku T.
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Journal Title
Am J Respir Cell Mol Biol.
Volume: Epub ahead of print
Issue: 2
Pages: 179-188
DOI
Related Report
Peer Reviewed
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