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Study on cell fate commitment in chronic obstructive pulmonary disease

Research Project

Project/Area Number 21K08149
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionAkita University

Principal Investigator

Nakayama Katsutoshi  秋田大学, 医学系研究科, 教授 (40321989)

Co-Investigator(Kenkyū-buntansha) 荒屋 潤  東京慈恵会医科大学, 医学部, 教授 (90468679)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsCOPD / トロンボスポンジン-1 / 細胞老化 / コロナ禍での肺がん検診 / 気道上皮 / 喫煙刺激 / 肺がん検診 / コロナ禍 / 増悪 / 細胞運命 / 制御されたネクローシス
Outline of Research at the Start

COPDの肺では、喫煙刺激により細胞老化がおきている。また、ウイルスや細菌感染により急性増悪の病態を示す。COPD急性増悪では、制御されたネクローシス(細胞膜の破壊により内容が外に漏出し強い炎症をおこす)がおきていることが考えられる。これらの細胞の運命(細胞老化、制御されたネクローシス)の機序をヒト検体やマウスモデルを用いて解明し、COPDの発症と憎悪に対するリスク診断・治療戦略の確立を目指す。

Outline of Final Research Achievements

We focused on thrombospondin-1 (TS-1) as a key molecule in smoking-induced inflammatory signals in COPD and revealed that TS-1 expression was increased in the airway epithelium of COPD. We also investigated the effects of IL-1beta, IL-8, and IL-13 on smoking-induced cellular senescence, and confirmed that IL-1beta promoted cellular senescence, but the effects of IL-8 and IL-13 were unclear. During the study period, the COVID-19 pandemic caused great difficulties in sample collection, so we investigated the state of suppression of lung cancer screening in Akita Prefecture during the pandemic. It was suggested that participation in lung cancer screening decreased, especially among the elderly, and that this may have led to a decrease in lung cancer diagnoses, resulting in a decrease in the number of early lung cancer registrations.

Academic Significance and Societal Importance of the Research Achievements

COPD病態成立におけるTS-1の重要性が明らかになりつつあり、TS-1によるIL-8の誘導性や肺機能との関連も検討中である。新型コロナ禍における、肺がん検診の受診状態の検討では、高齢者が感染に対するSocial Stigmaにより集団肺がん検診を避け、早期肺がん診断の妨げになった事が示唆された。感染症罹患に対するSocial Stigmaの解消と肺がん検診の重要性の啓蒙が大切であると考えられた。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (37 results)

All 2023 2022 2021

All Journal Article (20 results) (of which Peer Reviewed: 10 results,  Open Access: 5 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Book (3 results)

  • [Journal Article] Impact of the COVID-19 pandemic on the primary lung cancer screening program in Akita Prefecture, a region with the fastest aging population in Japan.2023

    • Author(s)
      Yuji Okuda, Kazuhiro Sato, Mariko Asano, Kentaroh Kudoh, Eiki Omoto, Yuka Izumiya, Sho Sakamoto, Masahide Takeda, Tatsunori Shimizu, Hidetaka Ota, Hirokazu Kurokawa, Yoshihiro Minamiya, Katsutoshi Nakayama.
    • Journal Title

      Geriatr Gerontol Int

      Volume: 8 Issue: 8 Pages: 622-627

    • DOI

      10.1111/ggi.14637

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inferior Pulmonary Ligament Division During Left Upper Lobectomy Causes Pulmonary Dysfunction2023

    • Author(s)
      Kuriyama Shoji、Imai Kazuhiro、Saito Hajime、Takashima Shinogu、Kurihara Nobuyasu、Demura Ryo、Suzuki Haruka、Harata Yuzu、Sato Yusuke、Nakayama Katsutoshi、Nomura Kyoko、Minamiya Yoshihiro
    • Journal Title

      Interdisciplinary CardioVascular and Thoracic Surgery

      Volume: - Issue: 5

    • DOI

      10.1093/icvts/ivad035

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of polymorphisms in pregnane X receptor and ABC transporters on afatinib in Japanese patients with non-small cell lung cancer: pharmacogenomic-pharmacokinetic and exposure-response analysis.2023

    • Author(s)
      Hayato Yokota, Kazuhiro Sato, Sho Sakamoto, Yuji Okuda, Mariko Asano, Masahide Takeda, Katsutoshi Nakayama, Masatomo Miura.
    • Journal Title

      Cancer Chemother Pharmacol

      Volume: 92 Issue: 4 Pages: 315-324

    • DOI

      10.1007/s00280-023-04569-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tracheal small cell carcinoma with RB1 Splice site mutation treated by chemoradiotherapy: A case report.2023

    • Author(s)
      Sho Sakamoto, Masahide Takeda, Yuka Izumiya, Yuji Okuda, Mariko Asano, Masaaki Sano, Kazuhiro Sato, Katsutoshi Nakayama.
    • Journal Title

      Current Problems in Cancer: Case Reports

      Volume: 10 Pages: 100245-100245

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ワクチン:かかりつけ医の取り組み.2023

    • Author(s)
      中山勝敏
    • Journal Title

      Medical Practice

      Volume: 40 Pages: 439-446

    • Related Report
      2023 Annual Research Report
  • [Journal Article] COPD診療のための新ガイドラインについて.2023

    • Author(s)
      中山勝敏
    • Journal Title

      秋田県医師会雑誌

      Volume: 73 Pages: 21-30

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Tracheal Small Cell Carcinoma with RB1 Splice Site Mutation Treated by Chemoradiotherapy: A Case Report2023

    • Author(s)
      Sho Sakamoto, Katsutoshi Nakayama, Masahide Takeda, Yuka Izumiya, Yuji Okuda, Mariko Asano, Masaaki Sano, Kazuhiro Sato.
    • Journal Title

      Current Problems in Cancer: Case Reports

      Volume: -

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] 安定期のCOPDに対して,肺炎球菌ワクチンを推奨するか?2023

    • Author(s)
      中山勝敏
    • Journal Title

      呼吸器内科

      Volume: -

    • Related Report
      2022 Research-status Report
  • [Journal Article] ワクチン:かかりつけ医の取り組み2023

    • Author(s)
      中山勝敏
    • Journal Title

      Medical Practice

      Volume: 40(3) Pages: 439-446

    • Related Report
      2022 Research-status Report
  • [Journal Article] COPD診療のための新ガイドラインについて2023

    • Author(s)
      中山勝敏
    • Journal Title

      秋田県医師会雑誌

      Volume: 73(1) Pages: 21-30

    • Related Report
      2022 Research-status Report
  • [Journal Article] Improving performance and self‐efficacy of novice nurses using hybrid simulation‐based mastery learning2022

    • Author(s)
      Takashiki Rinko、Komatsu Junko、Nowicki Mari、Moritoki Yuki、Okazaki Mieko、Ohshima Shigetoshi、Hasegawa Hitoshi、Nomura Kyoko、Ouchi Gen、Berg Benjamin W.、Shirakawa Hideko、Nakayama Katsutoshi、Takahashi Naoto
    • Journal Title

      Japan Journal of Nursing Science

      Volume: 20 Issue: 2

    • DOI

      10.1111/jjns.12519

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of CYP3A4/5 and ABC transporter polymorphisms on osimertinib plasma concentrations in Japanese patients with non-small cell lung cancer2022

    • Author(s)
      Yokota Hayato、Sato Kazuhiro、Sakamoto Sho、Okuda Yuji、Fukuda Natsuki、Asano Mariko、Takeda Masahide、Nakayama Katsutoshi、Miura Masatomo
    • Journal Title

      Investigational New Drugs

      Volume: 40 Issue: 6 Pages: 1254-1262

    • DOI

      10.1007/s10637-022-01304-9

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 日本人COPDに向けた個別化医療2022

    • Author(s)
      中山勝敏
    • Journal Title

      日本臨牀

      Volume: 80(6)増刊号 Pages: 97-103

    • Related Report
      2022 Research-status Report
  • [Journal Article] COPDの遺伝的素因2022

    • Author(s)
      中山勝敏
    • Journal Title

      日本臨牀

      Volume: 80(6)増刊号 Pages: 108-119

    • Related Report
      2022 Research-status Report
  • [Journal Article] 誤嚥性肺炎の検査2022

    • Author(s)
      浅野真理子,中山勝敏
    • Journal Title

      JOHNS

      Volume: 38(5) Pages: 519-522

    • Related Report
      2022 Research-status Report
  • [Journal Article] Eosinophil extracellular traps in a patient with chronic eosinophilic pneumonia2021

    • Author(s)
      Takeda M, Sakamoto S, Ueki S, Miyabe Y, Fukuchi M, Okuda Y, Asano M, Sato K, Nakayama K.
    • Journal Title

      Asia Pac Allergy

      Volume: 11 Issue: 3 Pages: e24-e24

    • DOI

      10.5415/apallergy.2021.11.e24

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired TRIM16-Mediated Lysophagy in Chronic Obstructive Pulmonary Disease Pathogenesis2021

    • Author(s)
      J Araya, N Saito, Y Hosaka, A Ichikawa, T Kadota, Y Fujita, S Minagawa, H Hara, S Fujimoto, H Kawamoto, N Watanabe, A Ito, K Okuda, H Miyagawa, J Watanabe, D Takekoshi、H Utsumi, M Yoshida, M Hashimoto, H Wakui, S Ito, T Numata, S Mori, H Matsudaira, J Hirano, T Ohtsuka, K Nakayama, K Kuwano
    • Journal Title

      The Journal of Immunology

      Volume: 207 Issue: 1 Pages: 65-76

    • DOI

      10.4049/jimmunol.2001364

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship between Plasma Concentrations of Afatinib and the Onset of Diarrhea in Patients with Non-Small Cell Lung Cancer2021

    • Author(s)
      Yokota Hayato、Sato Kazuhiro、Sakamoto Sho、Okuda Yuji、Asano Mariko、Takeda Masahide、Nakayama Katsutoshi、Miura Masatomo
    • Journal Title

      Biology

      Volume: 10 Issue: 10 Pages: 1054-1054

    • DOI

      10.3390/biology10101054

    • NAID

      120007172095

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 誤嚥性肺炎とその他の嚥下性肺疾患の疫学2021

    • Author(s)
      中山勝敏
    • Journal Title

      日本医師会雑誌

      Volume: 149 Pages: 2130-2134

    • Related Report
      2021 Research-status Report
  • [Journal Article] 高齢者特発性間質性肺炎の治療2021

    • Author(s)
      中山勝敏
    • Journal Title

      Aging&Health

      Volume: 30 Pages: 18-22

    • Related Report
      2021 Research-status Report
  • [Presentation] COPDの分子メカニズムと臨床展開(特別講演)2023

    • Author(s)
      中山勝敏
    • Organizer
      第63回日本呼吸器学会学術講演会,4月,東京(ハイブリッド)
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 喘息の病態形成における活性化好酸球と気道上皮細胞の相互作用(シンポジウム)2023

    • Author(s)
      竹田正秀,植木重治,中山勝敏
    • Organizer
      第63回日本呼吸器学会学術講演会,4月,東京(ハイブリッド)
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 秋田県における新型コロナウイルス感染症の流行が高齢者の肺がん検診に与えた影響について.2023

    • Author(s)
      奥田佑道,浅野真理子,佐藤一洋,大本瑛己,坂本祥,竹田正秀,清水辰徳,大田秀隆,中山勝敏
    • Organizer
      第65回日本老年医学会学術集会,6月,横浜
    • Related Report
      2023 Annual Research Report
  • [Presentation] 肺区域洗浄法が奏功した自己免疫性肺胞蛋白症の一例2023

    • Author(s)
      坂本 祥,工藤健太郎,大本瑛己,泉谷有可,奥田佑道,浅野真理子,竹田正秀,佐藤一洋,佐野正明,三浦一樹,中山勝敏
    • Organizer
      第116回日本呼吸器学会東北地方会、第146回日本結核 非結核性抗酸菌症学会東北支部学会、 第17回日本サルコイドーシス/肉芽腫性疾患学会東北支部会
    • Related Report
      2022 Research-status Report
  • [Presentation] 胸膜炎を合併した肺Mycobacterium kyorinense 感染症の一例2023

    • Author(s)
      坂本 祥,工藤健太郎,大本瑛己,泉谷有可,長谷川幸保,奥田佑道,浅野真理子,竹田正秀,伊藤武史,佐藤一洋,伊藤伸朗,佐野正明,本間光信,中山勝敏
    • Organizer
      第116回日本呼吸器学会東北地方会、第146回日本結核 非結核性抗酸菌症学会東北支部学会、 第17回日本サルコイドーシス/肉芽腫性疾患学会東北支部会
    • Related Report
      2022 Research-status Report
  • [Presentation] 憎悪病態の多様性を踏まえた診療アプローチ(シンポジウム)2022

    • Author(s)
      中山勝敏
    • Organizer
      第62回日本呼吸器学会学術講演会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 非小細胞肺がんにおけるアファチニブ血中濃度と副作用である下痢との関係2022

    • Author(s)
      横田隼人,佐藤一洋,坂本 祥,奥田佑道,浅野真理子,竹田正秀,中山勝敏,三浦昌朋
    • Organizer
      第32回日本医療薬学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] 炎症性偽腫瘍からの喀血を来した常染色体優性多発性嚢胞腎の一例2022

    • Author(s)
      高橋大地,坂本 祥,五島 哲,旭ルリ子,熊谷奈保,奥田佑道,浅野真理子,竹田正秀,佐藤一洋,三浦一樹,中山勝敏
    • Organizer
      第114回日本呼吸器学会東北地方会、第144回日本結核 非結核性抗酸菌症学会東北支部学会、第16回日本サルコイドーシス/肉芽腫性疾患学会東北支部会
    • Related Report
      2022 Research-status Report
  • [Presentation] 抗結核薬の開始後に新たな多発肺陰影が出現しparadoxical response が疑われた一例2022

    • Author(s)
      坂本 祥,竹田正秀,五島 哲,旭ルリ子,熊谷奈保,長谷川幸保,浅野真理子,奥田佑道,伊藤武史,佐藤一洋,伊藤伸朗,本間光信,中山勝敏
    • Organizer
      第114回日本呼吸器学会東北地方会、第144回日本結核 非結核性抗酸菌症学会東北支部学会、第16回日本サルコイドーシス/肉芽腫性疾患学会東北支部会
    • Related Report
      2022 Research-status Report
  • [Presentation] 呼吸不全が急激に進行し死の転帰をたどった肺腫瘍血栓性微小血管症の1例2022

    • Author(s)
      泉谷有可,佐藤一洋,工藤健太郎,大本瑛己,滝田友里,坂本 祥,浅野真理子,奥田佑道,竹田正秀,佐野正明,山本洋平,中山勝敏
    • Organizer
      第115回日本呼吸器学会東北地方会、第145回日本結核 非結核性抗酸菌症学会東北支部学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Association between proton-pump inhibitors and the ABCG2 C421A polymorphism and plasma concentration of gefitinib2021

    • Author(s)
      Sakamoto,S.,Sato,K.,Goshima,S.,Asahi,R.,Takita,Y.,Omoto,E.,Izumiya,Y., Kumagai,N.,Hasegawa,Y.,Yokota,H.,Okuda,Y.,Asano,M.,Akamine,Y.,Takeda,M.,Miura,M. and Nakayama,K.
    • Organizer
      The 25th Congress of the Asian Pacific Society of Respirology, November, Hybrid (Kyoto)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 好中球性炎症(気道感染)による憎悪(シンポジウム)2021

    • Author(s)
      中山勝敏
    • Organizer
      第61回日本呼吸器学会学術講演会,4月,ハイブリッド(東京)
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] gefitinibの血中濃度と薬物動態に関する遺伝子多型との関係性についての検討2021

    • Author(s)
      坂本 祥,佐藤一洋,横田隼人,赤嶺由美子,奥田佑道,浅野真理子,竹田正秀,三浦昌朋,中山勝敏
    • Organizer
      第61回日本呼吸器学会学術講演会,4月,ハイブリッド(東京)
    • Related Report
      2021 Research-status Report
  • [Presentation] EGPAの微小血栓におけるEETs/EETosisの証明2021

    • Author(s)
      竹田正秀,植木重治,橋本哲平,上出庸介,福地峰世,宮部 結,菅野恭子,竹内啓喜,岡伸行,中山勝敏,谷口正実,松井 聖
    • Organizer
      第61回日本呼吸器学会学術講演会,4月,ハイブリッド(東京)
    • Related Report
      2021 Research-status Report
  • [Book] COPD(慢性閉塞生肺疾患) 診断と治療のためのガイドライン2022[第6版]2022

    • Author(s)
      日本呼吸器学会COPDガイドライン第6版作成委員会(編)
    • Total Pages
      279
    • Publisher
      メディカルビュー社
    • ISBN
      9784779226915
    • Related Report
      2022 Research-status Report
  • [Book] 今日の治療指針2021年度版. 第5章. 閉塞性細気管支炎2021

    • Author(s)
      中山勝敏 (総編集 福井 次矢, 高木 誠 , 小室 一成)
    • Total Pages
      2192
    • Publisher
      医学書院
    • Related Report
      2021 Research-status Report
  • [Book] 呼吸器疾患 最新の治療 2021-2022. III 呼吸器系の救急治療. 5 胸水貯留2021

    • Author(s)
      佐藤一洋, 中山勝敏 (門田淳一, 弦間昭彦, 西岡安彦)
    • Total Pages
      496
    • Publisher
      南江堂
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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