Elucidation of epigenetic mechanism for new therapeutic strategies against COPD
Project/Area Number |
16J07163
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Research Category |
Grant-in-Aid for JSPS Fellows
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Allocation Type | Single-year Grants |
Section | 国内 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Keio University |
Principal Investigator |
朝倉 崇徳 慶應義塾大学, 医学研究科, 特別研究員(DC2)
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Project Period (FY) |
2016-04-22 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2017: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2016: ¥1,000,000 (Direct Cost: ¥1,000,000)
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Keywords | 慢性閉塞性肺疾患 / エピジェネティクス |
Outline of Annual Research Achievements |
既にDZNepおよびEzh2コンディショナルノックアウト(cKO)マウスを用いて、エラスターゼ誘導肺気腫モデルで気腫が増悪する結果を得ている。Ezh2 cKOマウスを用いたエラスターゼ誘導肺気腫モデルにおいて、投与7日後の全肺細胞をFACSで解析したところ、NK細胞お よびCD11b陽性マクロファージがEzh2 cKOマウス群でEzh2 cKO群で有意に上昇していた。同様に、DZNepを用いたエラスターゼ誘導肺気 腫モデルにおいてもNK細胞およびCD11b陽性マクロファージがDZNep投与群で有意に上昇していることを確認した。また、CD11b陽性細胞もしくはNK細胞に対するアンタゴニストを用いた実験ではDZNep投与による気腫増悪が相殺された。また、Ezh2 cKOマウスを用いて長期喫煙曝露モデルで検討した。喫煙開始12週間後の肺組織において、Ezh2 cKOマウス群で有意に気腫が増悪した。また、FACSではNK細胞およびCD11b陽性マクロファージが上昇していることを確認した。さらにEzh2 cKOマウスにおいて、タモキシフェン誘導性にEzh2をノックアウトし6ヶ月の長期観察を行ったところ、一部のマウスに腫瘍発生がみられることを確認した。また、肺組織を固定したところ、気腫形成がコントロール群に比較して増悪した可能性が示唆された。今後さらに、Ezh2 cKOマウス群での気腫増悪の機序およびヒト肺組織における検討を行う予定である。
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Research Progress Status |
29年度が最終年度であるため、記入しない。
|
Strategy for Future Research Activity |
29年度が最終年度であるため、記入しない。
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Report
(2 results)
Research Products
(41 results)
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[Journal Article] Health-related QOL of elderly patients with pulmonary M. avium complex disease in a university hospital2018
Author(s)
Asakura T, Ishii M, Ishii K, Suzuki S, Namkoong H, Okamori S, Kamata H, Yagi K, Funatsu Y, Betsuyaku T, Hasegawa N
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Journal Title
Int J Tuberc Lung Dis
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Aspergillus precipitating antibody in patients with Mycobacterium avium complex lung disease: a cross-sectional study. Aspergillus precipitating antibody in patients with Mycobacterium avium complex lung disease: a cross-sectional study.2018
Author(s)
Suzuki S, Asakura T, Namkoong H, Okamori S, Yagi K, Kamata H, Uwamino Y, Funatsu Y, Yasushi Nakano, Tomoyasu Nishimura, Ishii M, Ebihara T, Betsuyaku T, Hasegawa N.
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Journal Title
Respir Med
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Clarithromycin Expands CD11b+Gr-1+ Cells via the STAT3/Bv8 Axis to Ameliorate Lethal Endotoxic Shock and Post-influenza Bacterial Pneumonia.2018
Author(s)
Namkoong H, Ishii M, Fujii H, Yagi K, Asami T, Asakura T, Suzuki S, Hegab AE, Kamata H, Tasaka S, Atarashi K, Nakamoto N, Iwata S, Honda K, Kanai T, Naoki H, Koyasu S, Betsuyaku T.
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Journal Title
PloS Pathog
Volume: in press
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mycobacterium triplex Pulmonary Disease with Acquired Macrolide Resistance inImmunocompetent Patients.2018
Author(s)
Matsuda S, Suzuki S, Morimoto K, Aono A, Nishio K, Asakura T, Sasaki Y, Namkoong H, Nishimura T, Ogata H, Hasegawa N, Kurashima A, Ishii M, Tatsumi K, Mitarai S, Goto H.
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Journal Title
Clin Microbiol Infect
Volume: in press
Issue: 6
Pages: 671-672
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical characteristics of pulmonary Mycobacterium lentiflavum disease in adult patients.2018
Author(s)
Yagi K, Morimoto K, Ishii M, Namkoong H, Okamori S, Asakura T, Suzuki S, Asami T, Uwamino Y, Funatsu Y, Fujiwara H, Kamata H, Nishimura T, Betsuyaku T, Kurashima A, Hasegawa N.
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Journal Title
International Journal of Infectious Diseases
Volume: 67
Pages: 65-69
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impact of Cavity and Infiltration on Pulmonary Function and Health-Related Quality of Life in Mycobacterium avium complex Pulmonary Disease: A 3-Dimensional Computed Tomographic Analysis2017
Author(s)
Asakura T, Yamada Y, Namkoong H, Suzuki S, Niijima Y, Kamata H, Funatsu Y, Yagi K, Okamori S, Sugiura H, Ishii M, Jinzaki M, Betsuyaku T, Hasegawa N
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Journal Title
Respir Med
Volume: 126
Pages: 9-16
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impact of chronic Pseudomonas aeruginosa infection on health-related quality of life in Mycobacterium avium complex lung disease.2017
Author(s)
Kamata H1, Asakura T1,2, Suzuki S1,2, Namkoong H1, Yagi K1, Funatsu Y1, Okamori S1, Uno S3, Uwamino Y4, Fujiwara H3, Nishimura T5, Ishii M1, Betsuyaku T1, Hasegawa N6.
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Journal Title
BMC Pulmonary Medicine
Volume: 17(1)
Issue: 1
Pages: 198-198
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The efficacy, safety, and feasibility of inhaled amikacin for the treatment of difficult-to-treat non-tuberculous mycobacterial lung diseases.2017
Author(s)
Yagi K, Ishii M, Namkoong H, Asami T, Iketani O, Asakura T, Suzuki S, Sugiura H, Yamada Y, Nishimura T, Fujiwara H, Funatsu Y, Uwamino Y, Kamo T, Tasaka S, Betsuyaku T, Hasegawa N
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Journal Title
BMC Infectious Diseases
Volume: 17(1)
Issue: 1
Pages: 558-558
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical Efficacy and Safety of Multidrug Therapy including Thrice Weekly Intravenous Amikacin Administration for Mycobacterium abscessus Pulmonary Disease in Outpatient Settings: A Case Series2016
Author(s)
Namkoong H, Morimoto K, Nishimura T, Tanaka H, Sugiura H, Yamada Y, Kurosaki A, Asakura T, Suzuki S, Fujiwara H, Yagi K, Ishii M, Tasaka S, Betsuyaku T, Hoshino Y, Kurashima A, Hasegawa N
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Journal Title
BMC Infect Dis
Volume: 16
Issue: 1
Pages: 396-396
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical characteristics of pulmonary Mycobacterium scrofulaceum disease in 2001-2011: a case series and literature review2016
Author(s)
Suzuki S, Morino E, Ishii M, Namkoong H, Yagi K, Asakura T, Asami T, Fujiwara H, Uwamino Y, Nishimura T, Tasaka S, Betsuyaku T, Takasaki J, Iwata S, Hasegawa N
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Journal Title
J Infect Chemother
Volume: 22
Issue: 9
Pages: 611-616
DOI
Related Report
Peer Reviewed
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[Journal Article] Finger fractures as an early manifestation of primary hyperparathyroidism among young patients: a case report of a 30-year-old male with recurrent osteoporotic fractures2016
Author(s)
Ozaki A, Tanimoto T, Yamagishi E, Sato S, Tsukada M, Sawano T, Leppold C, Tsuda K, Asakura T, Tsubokura M, Kato S, Kami M, Ohira H
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Journal Title
Medicine (Baltimore)
Volume: 95
Issue: 20
Pages: e3683-e3683
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Successful treatment of a non-small-cell lung cancer patient with afatinib and a glucocorticoid after both gefitinib- and erlotinib- induced interstitial lung disease2016
Author(s)
Tani T, Naoki K, Asakura T, Hirano T, Suzuki S, Masuzawa K, Hasegawa H, Kuroda A, Yasuda H, Ishii M, Soejima K, Betsuyaku T
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Journal Title
Mol Clin Oncol
Volume: 4
Issue: 4
Pages: 488-490
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] S1P Receptor Modulation Expands CD11b+Gr-1+ Cells and Inhibits Lymphocyte Infiltration to Ameliorate Murine Pulmonary Emphysema.2018
Author(s)
Asakura T, Ishii M, Namkoong H, Suzuki S, Kagawa S, Kamata H, Komiya T, Yagi K, Okamori S, Hasegawa N, Betsuyaku T.
Organizer
The 57th Japanese Respiratory Society Meeting
Related Report
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[Presentation] S1P Receptor Modulation Expands CD11b+Gr-1+ Cells and Inhibits Lymphocyte in the Lungs Infiltration to Ameliorate Murine Pulmonary Emphysema.2018
Author(s)
Asakura T, Ishii M, Namkoong H, Suzuki S, Kagawa S, Kamata H, Komiya T, Yagi K, Okamori S, Hasegawa N, Betsuyaku T.
Organizer
ATS International Conference
Related Report
Int'l Joint Research
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[Presentation] 3-Deazaneplanocin A, an inhibitor of histone methyltransferase EZH2, exacerbates elastase-induced emphysema in mice2016
Author(s)
Asakura T, Ishii M, Namkoong H, Yagi K, Tanosaki T, Suzuki S, Kamo T, Tasaka S, Hasegawa N, Betsuyaku T
Organizer
he 56th Japanese Respiratory Society Meeting
Place of Presentation
東京国際フォーラム(東京都千代田区)
Year and Date
2016-04-08
Related Report
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