2024/10/13 更新

写真a

サカモト コウジ
阪本 考司
SAKAMOTO Koji
所属
医学部附属病院 呼吸器内科 病院講師
職名
病院講師
連絡先
メールアドレス

学位 1

  1. 博士(医学) ( 2012年7月   名古屋大学 ) 

研究分野 1

  1. ライフサイエンス / 呼吸器内科学

現在の研究課題とSDGs 2

  1. 肺線維症の病態解明と新規治療開発

  2. 細胞外微粒子の呼吸器への影響

経歴 1

  1. 名古屋大学   医学部附属病院 呼吸器内科   病院講師

    2022年12月 - 現在

学歴 2

  1. 名古屋大学   医学系研究科   病態内科学

    - 2012年3月

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    国名: 日本国

  2. 名古屋大学   医学系研究科   病態内科学

    - 2012年3月

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    国名: 日本国

所属学協会 5

  1. 日本呼吸器学会

  2. 日本アレルギー学会

  3. American Thoracic Society

  4. 日本内科学会

  5. American Thoracic Society

受賞 4

  1. Young Innovator Award

    2022年   JST-CREST[細胞外微粒子]   呼吸中の細胞外小胞を利用した新しい診断指標の開発

    阪本考司

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    受賞区分:国内学会・会議・シンポジウム等の賞  受賞国:日本国

  2. International Session Award

    2017年  

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    受賞区分:国際学会・会議・シンポジウム等の賞  受賞国:日本国

  3. The I.M. Rosenzweig Junior Investigator Award

    2016年   Pulmonary Fibrosis Foundation  

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    受賞区分:出版社・新聞社・財団等の賞  受賞国:アメリカ合衆国

  4. Scientific Abstract Award

    2014年   American Thoracic Society  

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    受賞区分:国際学会・会議・シンポジウム等の賞  受賞国:アメリカ合衆国

 

論文 85

  1. BMP3b Is a Novel Antifibrotic Molecule Regulated by Meflin in Lung Fibroblasts 国際誌

    Suzuki, A; Sakamoto, K; Nakahara, Y; Enomoto, A; Hino, J; Ando, A; Inoue, M; Shiraki, Y; Omote, N; Kusaka, M; Fukihara, J; Hashimoto, N

    AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY   67 巻 ( 4 ) 頁: 446 - 458   2022年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American journal of respiratory cell and molecular biology  

    Fibroblasts play a central role in the lung fibrotic process. Our recent study identified a novel subpopulation of lung fibroblasts expressing meflin (mesenchymal stromal cell- and fibroblast-expressing Linx paralogue), antifibrotic properties of which were confirmed by murine lung fibrosis model. Meflin-expressing fibroblasts were resistant to fibrogenesis induced by TGF-β (transforming growth factor-β), but its underlying mechanisms remain unknown. In this study, evaluation of a silica-nanoparticle-induced lung fibrosis model confirmed the antifibrotic effect of meflin via the regulation of TGF-β signaling. We conducted comparative gene expression profiling in lung fibroblasts, which identified growth differentiation factor 10 (Gdf10) encoding bone morphogenic protein 3b (BMP3b) as the most downregulated gene in meflin-deficient cells under the profibrotic condition with TGF-β. We hypothesized that BMP3b can be an effector molecule playing an antifibrotic role downstream of meflin. As suggested by single-cell transcriptomic data, restricted expressions of Gdf10 (Bmp3b) in stromal cells including fibroblasts were confirmed. We examined possible antifibrotic properties of BMP3b in lung fibroblasts and demonstrated that Bmp3b-null fibroblasts were more susceptible to TGF-β-induced fibrogenic changes. Furthermore, Bmp3b-null mice exhibited exaggerated lung fibrosis induced by silica-nanoparticles in vivo. We also demonstrated that treatment with recombinant BMP3B was effective against TGF-β-induced fibrogenesis in fibroblasts, especially in the suppression of excessive extracellular matrix production. These lines of evidence suggested that BMP3b is a novel humoral effector molecule regulated by meflin which exerts antifibrotic properties in lung fibroblasts. Supplementation of BMP3B could be a novel therapeutic strategy for fibrotic lung diseases.

    DOI: 10.1165/rcmb.2021-0484OC

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  2. Fibroblasts positive for meflin have anti-fibrotic properties in pulmonary fibrosis 国際共著 国際誌

    Nakahara, Y; Hashimoto, N; Sakamoto, K; Enomoto, A; Adams, TS; Yokoi, T; Omote, N; Poli, S; Ando, A; Wakahara, K; Suzuki, A; Inoue, M; Hara, A; Mizutani, Y; Imaizumi, K; Kawabe, T; Rosas, IO; Takahashi, M; Kaminski, N; Hasegawa, Y

    EUROPEAN RESPIRATORY JOURNAL   58 巻 ( 6 )   2021年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:European Respiratory Journal  

    The prognosis of elderly individuals with idiopathic pulmonary fibrosis (IPF) remains poor. Fibroblastic foci, in which aggregates of proliferating fibroblasts and myofibroblasts are involved, are the pathological hallmark lesions in IPF to represent focal areas of active fibrogenesis. Fibroblast heterogeneity in fibrotic lesions hampers the discovery of the pathogenesis of pulmonary fibrosis. Therefore, to determine of the pathogenesis of IPF, identification of functional fibroblasts is warranted. This study was aimed to determine the role of fibroblasts positive for meflin, identified as a potential marker for mesenchymal stromal cells, during the development of pulmonary fibrosis. We characterized meflin-positive cells in a single cell atlas established by single-cell RNA sequencing (scRNA-seq)-based profiling of 243,472 cells from 32 IPF lungs and 29 normal lung samples. scRNA-seq combined with in situ RNA hybridization identified proliferating fibroblasts positive for meflin in fibroblastic foci, not dense fibrosis, of fibrotic lungs in IPF patients. We determined the role of fibroblasts positive for meflin using bleomycin (BLM)-induced pulmonary fibrosis. A BLM-induced lung fibrosis model for meflin-deficient mice showed that fibroblasts positive for meflin had anti-fibrotic property to prevent pulmonary fibrosis. Although transforming growth factor-β-induced fibrogenesis and cell senescence with senescence-associated secretory phenotype were exacerbated in fibroblasts via the repression or lack of meflin, these were inhibited in meflin-deficient fibroblasts with meflin reconstitution. These findings provide evidence to show the biological importance of meflin expression on fibroblasts and myofibroblasts in the active fibrotic region of pulmonary fibrosis.

    DOI: 10.1183/13993003.03397-2020

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  3. Serum mitochondrial DNA predicts the risk of acute exacerbation and progression of idiopathic pulmonary fibrosis 査読有り 国際共著 国際誌

    Sakamoto Koji, Furukawa Taiki, Yamano Yasuhiko, Kataoka Kensuke, Teramachi Ryo, Walia Anjali, Suzuki Atsushi, Inoue Masahide, Nakahara Yoshio, Ryu Changwan, Hashimoto Naozumi, Kondoh Yasuhiro

    EUROPEAN RESPIRATORY JOURNAL   57 巻 ( 1 )   2021年1月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:European Respiratory Journal  

    DOI: 10.1183/13993003.01346-2020

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  4. Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non-Small-Cell Lung Cancer Who Received Programmed Death 1 Inhibitors 査読有り 国際誌

    Fukihara Jun, Sakamoto Koji, Koyama Junji, Ito Takayasu, Iwano Shingo, Morise Masahiro, Ogawa Masahiro, Kondoh Yasuhiro, Kimura Tomoki, Hashimoto Naozumi, Hasegawa Yoshinori

    CLINICAL LUNG CANCER   20 巻 ( 6 ) 頁: 442 - +   2019年11月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Clinical Lung Cancer  

    DOI: 10.1016/j.cllc.2019.07.006

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  5. Mitochondrial DNA in bronchoalveolar lavage fluid is associated with the prognosis of idiopathic pulmonary fibrosis: a single cohort study 査読有り

    Fukihara J, Sakamoto K, Ikeyama Y, Furukawa T, Teramachi R, Kataoka K, Kondoh Y, Hashimoto N, Ishii M.

    Respiratory Research   25 巻 ( 1 ) 頁: 202   2024年5月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s12931-024-02828-9.

  6. Mild elevation of pulmonary vascular resistance predicts mortality regardless of mean pulmonary artery pressure in mild interstitial lung disease. 査読有り

    Sato T, Furukawa T, Teramachi R, Fukihara J, Yamano Y, Yokoyama T, Matsuda T, Kataoka K, Kimura T, Sakamoto K, Ishii M, Kondoh Y.

    Thorax     2024年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1136/thorax-2023-220179

  7. Rapidly progressive interstitial lung disease with positive anti-MDA5 antibody as an immune-related complication of nivolumab: A case report. 査読有り

    Kato S, Sakamoto K, Sato T, Kobayashi T, Shindo Y, Morise M, Iwama S, Arima H, Ishii M.

    Respiratory Investigation   62 巻 ( 2 ) 頁: 313 - 316   2024年2月

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    担当区分:筆頭著者, 責任著者   記述言語:英語  

    DOI: 10.1016/j.resinv.2024.01.009.

  8. Cohort study to evaluate prognostic factors in idiopathic pulmonary fibrosis patients introduced to oxygen therapy. 査読有り

    Kataoka K, Oda K, Takizawa H, Ogura T, Miyamoto A, Inoue Y, Akagawa S, Hashimoto S, Kishaba T, Sakamoto K, Hamada N, Kuwano K, Nakayama M, Ebina M, Enomoto N, Miyazaki Y, Atsumi K, Izumi S, Tanino Y, Ishii H, Ohnishi H, Suda T, Kondoh Y.

    Scientific Reports   13 巻 ( 1 ) 頁: 13664   2023年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-023-40508-8

  9. Inhalation adherence for asthma and COPD improved during the COVID-19 pandemic: a questionnaire survey at a university hospital in Japan 国際誌

    Fukutani Eriko, Wakahara Keiko, Nakamura Saya, Yokoi Eito, Yoshimi Akira, Miyazaki Masayuki, Nakamura Mariko, Shindo Yuichiro, Sakamoto Koji, Okachi Shotaro, Tanaka Ichidai, Hamajima Nobuyuki, Noda Yukihiro, Hashimoto Naozumi, Ishii Makoto

    JOURNAL OF ASTHMA     頁: 1 - 12   2023年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Journal of Asthma  

    Background: Good adherence to an inhaled medication protocol is necessary for the management of asthma and chronic obstructive pulmonary disease (COPD), and several interventions to improve adherence have been reported. However, the impact of patient life changes and psychological aspects on treatment motivation is obscure. Here, we investigated changes in inhaler adherence during the COVID-19 pandemic and how lifestyle and psychological changes affected it. Methods: Seven-hundred sixteen adult patients with asthma and COPD who had visited Nagoya University Hospital between 2015 and 2020 were selected. Among them, 311 patients had received instruction at a pharmacist-managed clinic (PMC). We distributed one-time cross-sectional questionnaires from January 12 to March 31, 2021. The questionnaire covered the status of hospital visits, inhalation adherence before and during the COVID-19 pandemic, lifestyles, medical conditions, and psychological stress. The Adherence Starts with Knowledge-12 (ASK-12) was used to assess adherence barriers. Results: Four-hundred thirty-three patients answered the questionnaire. Inhalation adherence was significantly improved in both diseases during the COVID-19 pandemic. The most common reason for improved adherence was fear of infection. Patients with improved adherence were more likely to believe that controller inhalers could prevent COVID-19 from becoming more severe. Improved adherence was more common in patients with asthma, those not receiving counseling at PMC, and those with poor baseline adherence. Conclusions: Inhalation adherence for asthma and COPD improved in the COVID-19 pandemic. The patients seemed to realize the necessity and benefits of the medication more strongly than before the pandemic, which motivated them to improve adherence.

    DOI: 10.1080/02770903.2023.2209173

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  10. Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease triggered by COVID-19: What is the best practice for treatment? 査読有り

    Yonezawa T, Suzuki A, Fukumitsu K, Katano T, Kako H, Ishii M, Niimi A, Imaizumi K, Sakamoto K, Omote N, Yamaguchi E.

    Respiratory Medicine Case Report   43 巻   頁: 101857   2023年4月

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    記述言語:英語  

    DOI: 10.1016/j.rmcr.2023.101857.

  11. Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial. 査読有り 国際誌

    Kataoka K, Nishiyama O, Ogura T, Mori Y, Kozu R, Arizono S, Tsuda T, Tomioka H, Tomii K, Sakamoto K, Ishimoto H, Kagajo M, Ito H, Ichikado K, Sasano H, Eda S, Arita M, Goto Y, Hataji O, Fuke S, Shintani R, Hasegawa H, Ando M, Ogawa T, Shiraishi M, Watanabe F, Nishimura K, Sasaki T, Miyazaki S, Saka H, Kondoh Y, FITNESS study Collaborators

    Thorax   78 巻 ( 8 ) 頁: 784 - 791   2023年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1136/thorax-2022-219792

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  12. <i>DOCK2</i> is involved in the host genetics and biology of severe COVID-19 国際誌

    Namkoong, H; Edahiro, R; Takano, T; Nishihara, H; Shirai, Y; Sonehara, K; Tanaka, H; Azekawa, S; Mikami, Y; Lee, H; Hasegawa, T; Okudela, K; Okuzaki, D; Motooka, D; Kanai, M; Naito, T; Yamamoto, K; Wang, QBS; Saiki, R; Ishihara, R; Matsubara, Y; Hamamoto, J; Hayashi, H; Yoshimura, Y; Tachikawa, N; Yanagita, E; Hyugaji, T; Shimizu, E; Katayama, K; Kato, Y; Morita, T; Takahashi, K; Harada, N; Naito, T; Hiki, M; Matsushita, Y; Takagi, H; Aoki, R; Nakamura, A; Harada, S; Sasano, H; Kabata, H; Masaki, K; Kamata, H; Ikemura, S; Chubachi, S; Okamori, S; Terai, H; Morita, A; Asakura, T; Sasaki, J; Morisaki, H; Uwamino, Y; Nanki, K; Uchida, S; Uno, S; Nishimura, T; Ishiguro, T; Isono, T; Shibata, S; Matsui, Y; Hosoda, C; Takano, K; Nishida, T; Kobayashi, Y; Takaku, Y; Takayanagi, N; Ueda, S; Tada, A; Miyawaki, M; Yamamoto, M; Yoshida, E; Hayashi, R; Nagasaka, T; Arai, S; Kaneko, Y; Sasaki, K; Tagaya, E; Kawana, M; Arimura, K; Takahashi, K; Anzai, T; Ito, S; Endo, A; Uchimura, Y; Miyazaki, Y; Honda, T; Tateishi, T; Tohda, S; Ichimura, N; Sonobe, K; Sassa, CT; Nakajima, J; Nakano, Y; Nakajima, Y; Anan, R; Arai, R; Kurihara, Y; Harada, Y; Nishio, K; Ueda, T; Azuma, M; Saito, R; Sado, T; Miyazaki, Y; Sato, R; Haruta, Y; Nagasaki, T; Yasui, Y; Hasegawa, Y; Mutoh, Y; Kimura, T; Sato, T; Takei, R; Hagimoto, S; Noguchi, Y; Yamano, Y; Sasano, H; Ota, S; Nakamori, Y; Yoshiya, K; Saito, F; Yoshihara, T; Wada, D; Iwamura, H; Kanayama, S; Maruyama, S; Yoshiyama, T; Ohta, K; Kokuto, H; Ogata, H; Tanaka, Y; Arakawa, K; Shimoda, M; Osawa, T; Tateno, H; Hase, I; Yoshida, S; Suzuki, S; Kawada, M; Horinouchi, H; Saito, F; Mitamura, K; Hagihara, M; Ochi, J; Uchida, T; Baba, R; Arai, D; Ogura, T; Takahashi, H; Hagiwara, S; Nagao, G; Konishi, S; Nakachi, I; Murakami, K; Yamada, M; Sugiura, H; Sano, H; Matsumoto, S; Kimura, N; Ono, Y; Baba, H; Suzuki, Y; Nakayama, S; Masuzawa, K; Namba, S; Suzuki, K; Naito, Y; Liu, YC; Takuwa, A; Sugihara, F; Wing, JB; Sakakibara, S; Hizawa, N; Shiroyama, T; Miyawaki, S; Kawamura, Y; Nakayama, A; Matsuo, H; Maeda, Y; Nii, T; Noda, Y; Niitsu, T; Adachi, Y; Enomoto, T; Amiya, S; Hara, R; Yamaguchi, Y; Murakami, T; Kuge, T; Matsumoto, K; Yamamoto, Y; Yamamoto, M; Yoneda, M; Kishikawa, T; Yamada, S; Kawabata, S; Kijima, N; Takagaki, M; Sasa, N; Ueno, Y; Suzuki, M; Takemoto, N; Eguchi, H; Fukusumi, T; Imai, T; Fukushima, M; Kishima, H; Inohara, H; Tomono, K; Kato, K; Takahashi, M; Matsuda, F; Hirata, H; Takeda, Y; Koh, H; Manabe, T; Funatsu, Y; Ito, F; Fukui, T; Shinozuka, K; Kohashi, S; Miyazaki, M; Shoko, T; Kojima, M; Adachi, T; Ishikawa, M; Takahashi, K; Inoue, T; Hirano, T; Kobayashi, K; Takaoka, H; Watanabe, K; Miyazawa, N; Kimura, Y; Sado, R; Sugimoto, H; Kamiya, A; Kuwahara, N; Fujiwara, A; Matsunaga, T; Sato, Y; Okada, T; Hirai, Y; Kawashima, H; Narita, A; Niwa, K; Sekikawa, Y; Nishi, K; Nishitsuji, M; Tani, M; Suzuki, J; Nakatsumi, H; Ogura, T; Kitamura, H; Hagiwara, E; Murohashi, K; Okabayashi, H; Mochimaru, T; Nukaga, S; Satomi, R; Oyamada, Y; Mori, N; Baba, T; Fukui, Y; Odate, M; Mashimo, S; Makino, Y; Yagi, K; Hashiguchi, M; Kagyo, J; Shiomi, T; Fuke, S; Saito, H; Tsuchida, T; Fujitani, S; Takita, M; Morikawa, D; Yoshida, T; Izumo, T; Inomata, M; Kuse, N; Awano, N; Tone, M; Ito, A; Nakamura, Y; Hoshino, K; Maruyama, J; Ishikura, H; Takata, T; Odani, T; Amishima, M; Hattori, T; Shichinohe, Y; Kagaya, T; Kita, T; Ohta, K; Sakagami, S; Koshida, K; Hayashi, K; Shimizu, T; Kozu, Y; Hiranuma, H; Gon, Y; Izumi, N; Nagata, K; Ueda, K; Taki, R; Hanada, S; Kawamura, K; Ichikado, K; Nishiyama, K; Muranaka, H; Nakamura, K; Hashimoto, N; Wakahara, K; Sakamoto, K; Omote, N; Ando, A; Kodama, N; Kaneyama, Y; Maeda, S; Kuraki, T; Matsumoto, T; Yokote, K; Nakada, TA; Abe, R; Oshima, T; Shimada, T; Harada, M; Takahashi, T; Ono, H; Sakurai, T; Shibusawa, T; Kimizuka, Y; Kawana, A; Sano, T; Watanabe, C; Suematsu, R; Sageshima, H; Yoshifuji, A; Ito, K; Takahashi, S; Ishioka, K; Nakamura, M; Masuda, M; Wakabayashi, A; Watanabe, H; Ueda, S; Nishikawa, M; Chihara, Y; Takeuchi, M; Onoi, K; Shinozuka, J; Sueyoshi, A; Nagasaki, Y; Okamoto, M; Ishihara, S; Shimo, M; Tokunaga, Y; Kusaka, Y; Ohba, T; Isogai, S; Ogawa, A; Inoue, T; Fukuyama, S; Eriguchi, Y; Yonekawa, A; Kan-o, K; Matsumoto, K; Kanaoka, K; Ihara, S; Komuta, K; Inoue, Y; Chiba, S; Yamagata, K; Hiramatsu, Y; Kai, H; Asano, K; Oguma, T; Ito, Y; Hashimoto, S; Yamasaki, M; Kasamatsu, Y; Komase, Y; Hida, N; Tsuburai, T; Oyama, B; Takada, M; Kanda, H; Kitagawa, Y; Fukuta, T; Miyake, T; Yoshida, S; Ogura, S; Abe, S; Kono, Y; Togashi, Y; Takoi, H; Kikuchi, R; Ogawa, S; Ogata, T; Ishihara, S; Kanehiro, A; Ozaki, S; Fuchimoto, Y; Wada, S; Fujimoto, N; Nishiyama, K; Terashima, M; Beppu, S; Yoshida, K; Narumoto, O; Nagai, H; Ooshima, N; Motegi, M; Umeda, A; Miyagawa, K; Shimada, H; Endo, M; Ohira, Y; Watanabe, M; Inoue, S; Igarashi, A; Sato, M; Sagara, H; Tanaka, A; Ohta, S; Kimura, T; Shibata, Y; Tanino, Y; Nikaido, T; Minemura, H; Sato, Y; Yamada, Y; Hashino, T; Shinoki, M; Iwagoe, H; Takahashi, H; Fujii, K; Kishi, H; Kanai, M; Imamura, T; Yamashita, T; Yatomi, M; Maeno, T; Hayashi, S; Takahashi, M; Kuramochi, M; Kamimaki, I; Tominaga, Y; Ishii, T; Utsugi, M; Ono, A; Tanaka, T; Kashiwada, T; Fujita, K; Saito, Y; Seike, M; Watanabe, H; Matsuse, H; Kodaka, N; Nakano, C; Oshio, T; Hirouchi, T; Makino, S; Egi, M; Omae, Y; Nannya, Y; Ueno, T; Katayama, K; Ai, M; Fukui, Y; Kumanogoh, A; Sato, T; Hasegawa, N; Tokunaga, K; Ishii, M; Koike, R; Kitagawa, Y; Kimura, A; Imoto, S; Miyano, S; Ogawa, S; Kanai, T; Fukunaga, K; Okada, Y

    NATURE   609 巻 ( 7928 ) 頁: 754 - +   2022年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature  

    Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

    DOI: 10.1038/s41586-022-05163-5

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  13. A comprehensible machine learning tool to differentially diagnose idiopathic pulmonary fibrosis from other chronic interstitial lung diseases

    Furukawa, T; Oyama, S; Yokota, H; Kondoh, Y; Kataoka, K; Johkoh, T; Fukuoka, J; Hashimoto, N; Sakamoto, K; Shiratori, Y; Hasegawa, Y

    RESPIROLOGY   27 巻 ( 9 ) 頁: 739 - 746   2022年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Respirology  

    Background and objective: Idiopathic pulmonary fibrosis (IPF) has poor prognosis, and the multidisciplinary diagnostic agreement is low. Moreover, surgical lung biopsies pose comorbidity risks. Therefore, using data from non-invasive tests usually employed to assess interstitial lung diseases (ILDs), we aimed to develop an automated algorithm combining deep learning and machine learning that would be capable of detecting and differentiating IPF from other ILDs. Methods: We retrospectively analysed consecutive patients presenting with ILD between April 2007 and July 2017. Deep learning was used for semantic image segmentation of HRCT based on the corresponding labelled images. A diagnostic algorithm was then trained using the semantic results and non-invasive findings. Diagnostic accuracy was assessed using five-fold cross-validation. Results: In total, 646,800 HRCT images and the corresponding labelled images were acquired from 1068 patients with ILD, of whom 42.7% had IPF. The average segmentation accuracy was 96.1%. The machine learning algorithm had an average diagnostic accuracy of 83.6%, with high sensitivity, specificity and kappa coefficient values (80.7%, 85.8% and 0.665, respectively). Using Cox hazard analysis, IPF diagnosed using this algorithm was a significant prognostic factor (hazard ratio, 2.593; 95% CI, 2.069–3.250; p < 0.001). Diagnostic accuracy was good even in patients with usual interstitial pneumonia patterns on HRCT and those with surgical lung biopsies. Conclusion: Using data from non-invasive examinations, the combined deep learning and machine learning algorithm accurately, easily and quickly diagnosed IPF in a population with various ILDs.

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/resp.14310

  14. CINS: Cell Interaction Network inference from Single cell expression data. 査読有り 国際共著 国際誌

    Ye Yuan, Carlos Cosme Jr, Taylor Sterling Adams, Jonas Schupp, Koji Sakamoto, Nikos Xylourgidis, Matthew Ruffalo, Jiachen Li, Naftali Kaminski, Ziv Bar-Joseph

    PLoS computational biology   18 巻 ( 9 ) 頁: e1010468   2022年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Studies comparing single cell RNA-Seq (scRNA-Seq) data between conditions mainly focus on differences in the proportion of cell types or on differentially expressed genes. In many cases these differences are driven by changes in cell interactions which are challenging to infer without spatial information. To determine cell-cell interactions that differ between conditions we developed the Cell Interaction Network Inference (CINS) pipeline. CINS combines Bayesian network analysis with regression-based modeling to identify differential cell type interactions and the proteins that underlie them. We tested CINS on a disease case control and on an aging mouse dataset. In both cases CINS correctly identifies cell type interactions and the ligands involved in these interactions improving on prior methods suggested for cell interaction predictions. We performed additional mouse aging scRNA-Seq experiments which further support the interactions identified by CINS.

    DOI: 10.1371/journal.pcbi.1010468

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  15. The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force. 査読有り 国際誌

    Wang QS, Edahiro R, Namkoong H, Hasegawa T, Shirai Y, Sonehara K, Tanaka H, Lee H, Saiki R, Hyugaji T, Shimizu E, Katayama K, Kanai M, Naito T, Sasa N, Yamamoto K, Kato Y, Morita T, Takahashi K, Harada N, Naito T, Hiki M, Matsushita Y, Takagi H, Ichikawa M, Nakamura A, Harada S, Sandhu Y, Kabata H, Masaki K, Kamata H, Ikemura S, Chubachi S, Okamori S, Terai H, Morita A, Asakura T, Sasaki J, Morisaki H, Uwamino Y, Nanki K, Uchida S, Uno S, Nishimura T, Ishiguro T, Isono T, Shibata S, Matsui Y, Hosoda C, Takano K, Nishida T, Kobayashi Y, Takaku Y, Takayanagi N, Ueda S, Tada A, Miyawaki M, Yamamoto M, Yoshida E, Hayashi R, Nagasaka T, Arai S, Kaneko Y, Sasaki K, Tagaya E, Kawana M, Arimura K, Takahashi K, Anzai T, Ito S, Endo A, Uchimura Y, Miyazaki Y, Honda T, Tateishi T, Tohda S, Ichimura N, Sonobe K, Sassa CT, Nakajima J, Nakano Y, Nakajima Y, Anan R, Arai R, Kurihara Y, Harada Y, Nishio K, Ueda T, Azuma M, Saito R, Sado T, Miyazaki Y, Sato R, Haruta Y, Nagasaki T, Yasui Y, Hasegawa Y, Mutoh Y, Kimura T, Sato T, Takei R, Hagimoto S, Noguchi Y, Yamano Y, Sasano H, Ota S, Nakamori Y, Yoshiya K, Saito F, Yoshihara T, Wada D, Iwamura H, Kanayama S, Maruyama S, Yoshiyama T, Ohta K, Kokuto H, Ogata H, Tanaka Y, Arakawa K, Shimoda M, Osawa T, Tateno H, Hase I, Yoshida S, Suzuki S, Kawada M, Horinouchi H, Saito F, Mitamura K, Hagihara M, Ochi J, Uchida T, Baba R, Arai D, Ogura T, Takahashi H, Hagiwara S, Nagao G, Konishi S, Nakachi I, Murakami K, Yamada M, Sugiura H, Sano H, Matsumoto S, Kimura N, Ono Y, Baba H, Suzuki Y, Nakayama S, Masuzawa K, Namba S, Shiroyama T, Noda Y, Niitsu T, Adachi Y, Enomoto T, Amiya S, Hara R, Yamaguchi Y, Murakami T, Kuge T, Matsumoto K, Yamamoto Y, Yamamoto M, Yoneda M, Tomono K, Kato K, Hirata H, Takeda Y, Koh H, Manabe T, Funatsu Y, Ito F, Fukui T, Shinozuka K, Kohashi S, Miyazaki M, Shoko T, Kojima M, Adachi T, Ishikawa M, Takahashi K, Inoue T, Hirano T, Kobayashi K, Takaoka H, Watanabe K, Miyazawa N, Kimura Y, Sado R, Sugimoto H, Kamiya A, Kuwahara N, Fujiwara A, Matsunaga T, Sato Y, Okada T, Hirai Y, Kawashima H, Narita A, Niwa K, Sekikawa Y, Nishi K, Nishitsuji M, Tani M, Suzuki J, Nakatsumi H, Ogura T, Kitamura H, Hagiwara E, Murohashi K, Okabayashi H, Mochimaru T, Nukaga S, Satomi R, Oyamada Y, Mori N, Baba T, Fukui Y, Odate M, Mashimo S, Makino Y, Yagi K, Hashiguchi M, Kagyo J, Shiomi T, Fuke S, Saito H, Tsuchida T, Fujitani S, Takita M, Morikawa D, Yoshida T, Izumo T, Inomata M, Kuse N, Awano N, Tone M, Ito A, Nakamura Y, Hoshino K, Maruyama J, Ishikura H, Takata T, Odani T, Amishima M, Hattori T, Shichinohe Y, Kagaya T, Kita T, Ohta K, Sakagami S, Koshida K, Hayashi K, Shimizu T, Kozu Y, Hiranuma H, Gon Y, Izumi N, Nagata K, Ueda K, Taki R, Hanada S, Kawamura K, Ichikado K, Nishiyama K, Muranaka H, Nakamura K, Hashimoto N, Wakahara K, Koji S, Omote N, Ando A, Kodama N, Kaneyama Y, Maeda S, Kuraki T, Matsumoto T, Yokote K, Nakada TA, Abe R, Oshima T, Shimada T, Harada M, Takahashi T, Ono H, Sakurai T, Shibusawa T, Kimizuka Y, Kawana A, Sano T, Watanabe C, Suematsu R, Sageshima H, Yoshifuji A, Ito K, Takahashi S, Ishioka K, Nakamura M, Masuda M, Wakabayashi A, Watanabe H, Ueda S, Nishikawa M, Chihara Y, Takeuchi M, Onoi K, Shinozuka J, Sueyoshi A, Nagasaki Y, Okamoto M, Ishihara S, Shimo M, Tokunaga Y, Kusaka Y, Ohba T, Isogai S, Ogawa A, Inoue T, Fukuyama S, Eriguchi Y, Yonekawa A, Kan-O K, Matsumoto K, Kanaoka K, Ihara S, Komuta K, Inoue Y, Chiba S, Yamagata K, Hiramatsu Y, Kai H, Asano K, Oguma T, Ito Y, Hashimoto S, Yamasaki M, Kasamatsu Y, Komase Y, Hida N, Tsuburai T, Oyama B, Takada M, Kanda H, Kitagawa Y, Fukuta T, Miyake T, Yoshida S, Ogura S, Abe S, Kono Y, Togashi Y, Takoi H, Kikuchi R, Ogawa S, Ogata T, Ishihara S, Kanehiro A, Ozaki S, Fuchimoto Y, Wada S, Fujimoto N, Nishiyama K, Terashima M, Beppu S, Yoshida K, Narumoto O, Nagai H, Ooshima N, Motegi M, Umeda A, Miyagawa K, Shimada H, Endo M, Ohira Y, Watanabe M, Inoue S, Igarashi A, Sato M, Sagara H, Tanaka A, Ohta S, Kimura T, Shibata Y, Tanino Y, Nikaido T, Minemura H, Sato Y, Yamada Y, Hashino T, Shinoki M, Iwagoe H, Takahashi H, Fujii K, Kishi H, Kanai M, Imamura T, Yamashita T, Yatomi M, Maeno T, Hayashi S, Takahashi M, Kuramochi M, Kamimaki I, Tominaga Y, Ishii T, Utsugi M, Ono A, Tanaka T, Kashiwada T, Fujita K, Saito Y, Seike M, Watanabe H, Matsuse H, Kodaka N, Nakano C, Oshio T, Hirouchi T, Makino S, Egi M, Omae Y, Nannya Y, Ueno T, Takano T, Katayama K, Ai M, Kumanogoh A, Sato T, Hasegawa N, Tokunaga K, Ishii M, Koike R, Kitagawa Y, Kimura A, Imoto S, Miyano S, Ogawa S, Kanai T, Fukunaga K, Okada Y

    Nature communications   13 巻 ( 1 ) 頁: 4830 - 4830   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41467-022-32276-2

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  16. COVID-19-Triggered Acute Exacerbation of IPF, an Underdiagnosed Clinical Entity With Two-Peaked Respiratory Failure: A Case Report and Literature Review 査読有り 国際誌

    Goto Yosuke, Sakamoto Koji, Fukihara Jun, Suzuki Atsushi, Omote Norihito, Ando Akira, Shindo Yuichiro, Hashimoto Naozumi

    FRONTIERS IN MEDICINE   9 巻   頁: 815924   2022年2月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers in Medicine  

    Because severe coronavirus disease 2019 (COVID-19) affects the respiratory system and develops into respiratory failure, patients with pre-existing chronic lung disorders, such as idiopathic pulmonary fibrosis (IPF), are thought to be at high risk of death. Patients with IPF often suffer from a lethal complication, acute exacerbation (AE), a significant part of which is assumed to be triggered by respiratory viral infection. However, whether mild to moderate COVID-19 can trigger AE in patients with IPF remains unknown. This is the case report of a 60-year-old man with a 4-year history of IPF who successfully recovered from moderate COVID-19 but subsequently developed more severe respiratory failure, which was considered to be a COVID-19-triggered acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). It is important to be aware of the risk of AE-IPF after COVID-19 and to properly manage this deadly complication of IPF. Recent literature reporting cases with chronic interstitial lung diseases which developed respiratory failure by complications with COVID-19 is also reviewed and discussed.

    DOI: 10.3389/fmed.2022.815924

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  17. 肺線維症の病態に関連する2つの新規マーカー分子:メフリンとミトコンドリアDNA

    阪本 考司, 橋本 直純, 中原 義夫, 古川 大記

    呼吸器内科   41 巻 ( 2 ) 頁: 197 - 201   2022年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:(有)科学評論社  

  18. Overexpression of bone morphogenetic protein receptor type 2 suppresses transforming growth factor beta-induced profibrotic responses in lung fibroblasts 査読有り 国際共著 国際誌

    Fukihara Jun, Maiolo Suzanne, Kovac Jessica, Sakamoto Koji, Wakahara Keiko, Hashimoto Naozumi, Reynolds Paul N.

    EXPERIMENTAL LUNG RESEARCH   48 巻 ( 1 ) 頁: 35 - 51   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Experimental Lung Research  

    Purpose of the study: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. As the efficacy of currently available antifibrotics is limited, development of new therapies is warranted. Transforming growth factor (TGF)-β plays a central role in the pathogenesis of IPF through mechanisms such as promoting the production of extracellular matrix by fibroblasts. Conversely, bone morphogenetic proteins (BMPs) are known to be antifibrotic and may counterbalance TGF-β signaling via BMP receptor type 2 (BMPR2). However, little is known about the expression status of BMPR2 and its function in pulmonary fibrosis, and manipulation of BMPR2 expression has never been attempted. In this study, we aimed at evaluating the effectiveness of BMPR2 upregulation for modulating the imbalance of the TGF-β/BMP axis and reduce the profibrotic changes in lung fibroblasts. Materials and Methods: We investigated BMPR2 expression in pulmonary fibrosis and TGF-β/BMP signaling in lung fibroblasts. Then we evaluated the impact of BMPR2 upregulation using adenoviral transduction on TGF-β-induced Smad2/3 phosphorylation and fibronectin production in lung fibroblasts. Results: BMPR2 was distributed in airway epithelium and alveolar walls in rat lungs. BMPR2 expression was decreased in fibrotic lesions in the lungs of rats with bleomycin-induced pulmonary fibrosis and in human lung fibroblasts (HLFs) stimulated with TGF-β. Although Smad2/3 phosphorylation and fibronectin production were not suppressed solely by BMPs, phosphorylated Smad2/3 was decreased in BMPR2-transduced cells even without BMP stimulation. Fibronectin was decreased only when BMPR2-transduced HLFs were stimulated with BMP7 (but not BMP4). Similar results were also observed in IPF patient HLFs and rat lung fibroblasts. Conclusions: BMPR2 expression was reduced in fibrotic lungs and lung fibroblasts stimulated with TGF-β. BMPR2 transduction to lung fibroblasts reduced Smad2/3 phosphorylation, and reduced fibronectin production when treated with BMP7. Upregulation of BMPR2 may be a possible strategy for treating pulmonary fibrosis.

    DOI: 10.1080/01902148.2021.2024301

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  19. Successful Treatment with High-dose Steroids for Acute Exacerbation of Idiopathic Pulmonary Fibrosis Triggered by COVID-19

    Omote Norihito, Kanemitsu Yoshihiro, Inoue Takahiro, Yonezawa Toshiyuki, Ichihashi Takuji, Shindo Yuichiro, Sakamoto Koji, Ando Akira, Suzuki Atsushi, Niimi Akio, Ito Satoru, Imaizumi Kazuyoshi, Hashimoto Naozumi

    INTERNAL MEDICINE   61 巻 ( 2 ) 頁: 233 - 236   2022年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:一般社団法人 日本内科学会  

    We herein report a case of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) triggered by COVID-19. An 87-year-old woman tested positive for COVID-19 on a polymerase chain reaction test, and computed tomography revealed ground-glass opacity (GGO) superimposed on a background pattern consistent with usual interstitial pneumonia. Considering these data, we diagnosed her with AE-IPF. She experienced worsening of dyspnea and expansion of the GGO. Therefore, we introduced high-dose steroids (methylprednisolone 250 mg/day for 3 days). After the treatment, the pulmonary infiltrates improved. She was discharged from our hospital without severe disability. High-dose steroids can be a viable treatment option for AE-IPF triggered by COVID-19.

    DOI: 10.2169/internalmedicine.8163-21

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  20. The Effect of Pirfenidone on the Prescription of Antibiotics and Antitussive Drugs in Patients With Idiopathic Pulmonary Fibrosis: A Post Hoc Exploratory Analysis of Phase III Clinical Trial. 査読有り 国際誌

    Suzuki A, Sakaguchi H, Sakamoto K, Ebina M, Azuma A, Ogura T, Taguchi Y, Suga M, Takahashi H, Sugiyama Y, Kudoh S, Nukiwa T, Miyazawa S, Kondoh Y

    Chest   160 巻 ( 4 ) 頁: 1372 - 1376   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Chest  

    DOI: 10.1016/j.chest.2021.05.058

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  21. Size and surface modification of silica nanoparticles affect the severity of lung toxicity by modulating endosomal ROS generation in macrophages 国際誌

    Inoue Masahide, Sakamoto Koji, Suzuki Atsushi, Nakai Shinya, Ando Akira, Shiraki Yukihiko, Nakahara Yoshio, Omura Mika, Enomoto Atsushi, Nakase Ikuhiko, Sawada Makoto, Hashimoto Naozumi

    PARTICLE AND FIBRE TOXICOLOGY   18 巻 ( 1 ) 頁: 21 - 21   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Particle and Fibre Toxicology  

    Background: As the application of silica nanomaterials continues to expand, increasing chances of its exposure to the human body and potential harm are anticipated. Although the toxicity of silica nanomaterials is assumed to be affected by their physio-chemical properties, including size and surface functionalization, its molecular mechanisms remain unclear. We hypothesized that analysis of intracellular localization of the particles and subsequent intracellular signaling could reveal a novel determinant of inflammatory response against silica particles with different physico-chemical properties. Results: We employed a murine intratracheal instillation model of amorphous silica nanoparticles (NPs) exposure to compare their in vivo toxicities in the respiratory system. Pristine silica-NPs of 50 nm diameters (50 nm-plain) induced airway-centered lung injury with marked neutrophilic infiltration. By contrast, instillation of pristine silica particles of a larger diameter (3 μm; 3 μm-plain) significantly reduced the severity of lung injury and neutrophilic infiltration, possibly through attenuated induction of neutrophil chemotactic chemokines including MIP2. Ex vivo analysis of alveolar macrophages as well as in vitro assessment using RAW264.7 cells revealed a remarkably lower cellular uptake of 3 μm-plain particles compared with 50 nm-plain, which is assumed to be the underlying mechanism of attenuated immune response. The severity of lung injury and neutrophilic infiltration was also significantly reduced after intratracheal instillation of silica NPs with an amine surface modification (50 nm-NH2) when compared with 50 nm-plain. Despite unchanged efficacy in cellular uptake, treatment with 50 nm-NH2 induced a significantly attenuated immune response in RAW264.7 cells. Assessment of intracellular redox signaling revealed increased reactive oxygen species (ROS) in endosomal compartments of RAW264.7 cells treated with 50 nm-plain when compared with vehicle-treated control. In contrast, augmentation of endosomal ROS signals in cells treated with 50 nm-NH2 was significantly lower. Moreover, selective inhibition of NADPH oxidase 2 (NOX2) was sufficient to inhibit endosomal ROS bursts and induction of chemokine expressions in cells treated with silica NPs, suggesting the central role of endosomal ROS generated by NOX2 in the regulation of the inflammatory response in macrophages that endocytosed silica NPs. Conclusions: Our murine model suggested that the pulmonary toxicity of silica NPs depended on their physico-chemical properties through distinct mechanisms. Cellular uptake of larger particles by macrophages decreased, while surface amine modification modulated endosomal ROS signaling via NOX2, both of which are assumed to be involved in mitigating immune response in macrophages and resulting lung injury.

    DOI: 10.1186/s12989-021-00415-0

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  22. Impact of post-capillary pulmonary hypertension on mortality in interstitial lung disease 査読有り 国際誌

    Teramachi Ryo, Taniguchi Hiroyuki, Kondoh Yasuhiro, Kimura Tomoki, Kataoka Kensuke, Yokoyama Toshiki, Furukawa Taiki, Yagi Mitsuaki, Sakamoto Koji, Hashimoto Naozumi, Hasegawa Yoshinori

    RESPIRATORY INVESTIGATION   59 巻 ( 3 ) 頁: 342 - 349   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Respiratory Investigation  

    Background: Pulmonary hypertension (PH) influences mortality in patients with interstitial lung disease (ILD). Almost all studies on patients with ILD, have focused on the clinical impact of pre-capillary PH on survival. Therefore, little is known about the influence of post-capillary PH. We aimed to assess the prevalence of post-capillary PH and its clinical impact on survival in patients with ILD, followed by comparison with pre-capillary PH. Methods: This retrospective study enrolled 1152 patients with ILD who were diagnosed with PH using right heart catheterization between May 2007 and December 2015. We analyzed the demographics and composite outcomes (defined as death from any cause or lung transplantation) of patients with post-capillary PH and compared them with patients with pre-capillary PH. Results: Thirty-two (20%) of the 157 patients with ILD-PH were diagnosed with post-capillary PH. Patients with post-capillary PH had significantly lower modified Medical Research Council scores, higher diffusion capacity for carbon monoxide, higher resting PaO2, lower pulmonary vascular resistance (PVR), and higher lowest oxygen saturation during the 6-min walk test compared to those with pre-capillary PH. Cardiovascular diseases were associated with a higher risk of mortality in patients with post-capillary PH. Multivariate Cox proportional hazards analysis demonstrated no significant difference between the composite outcomes in pre-capillary and post-capillary PH, while PVR and the ILD Gender-Age-Physiology Index were significantly associated with the composite outcome. Conclusions: We found that approximately one-fifth of patients with ILD-PH were diagnosed with post-capillary PH, and that PVR and not post-capillary PH was associated with mortality.

    DOI: 10.1016/j.resinv.2020.12.010

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  23. The Importance of Appropriate Diagnosis in the Practical Management of Chronic Obstructive Pulmonary Disease 国際誌

    Hashimoto Naozumi, Wakahara Keiko, Sakamoto Koji

    DIAGNOSTICS   11 巻 ( 4 )   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Diagnostics  

    Chronic obstructive pulmonary disease (COPD) is projected to continue to contribute to an increase in the overall worldwide burden of disease until 2030. Therefore, an accurate assessment of the risk of airway obstruction in patients with COPD has become vitally important. Although the Global Initiative for Chronic Obstructive Lung Disease (GOLD), the American Thoracic Society (ATS) and European Respiratory Society (ERS), and the Japanese Respiratory Society (JRS) provide the criteria by which to diagnose COPD, many studies suggest that it is in fact underdiagnosed. Its prevalence increases, while the impact of COPD-related systemic comorbidities is also increasingly recognized in clinical aspects of COPD. Although a recent report suggests that spirometry should not be used to screen for airflow limitation in individuals without respiratory symptoms, the early detection of COPD in patients with no, or few, symptoms is an opportunity to provide appropriate management based on COPD guidelines. Clinical advances have been made in pharmacotherapeutic approaches to COPD. This article provides a current understanding of the importance of an appropriate diagnosis in the real-world management of COPD.

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  24. Long noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state 査読有り 国際共著 国際誌

    Omote Norihito, Sakamoto Koji, Li Qin, Schupp Jonas C., Adams Taylor, Ahangari Farida, Chioccioli Maurizio, DeIuliis Giuseppe, Hashimoto Naozumi, Hasegawa Yoshinori, Kaminski Naftali

    PHYSIOLOGICAL REPORTS   9 巻 ( 3 ) 頁: e14727   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Physiological Reports  

    DOI: 10.14814/phy2.14727

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  25. Supplemental oxygen improves exercise capacity in IPF patients with exertional desaturation 査読有り 国際誌

    Arizono Shinichi, Furukawa Taiki, Taniguchi Hiroyuki, Sakamoto Koji, Kimura Tomoki, Kataoka Kensuke, Ogawa Tomoya, Watanabe Fumiko, Kondoh Yasuhiro

    RESPIROLOGY   25 巻 ( 11 ) 頁: 1152 - 1159   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Respirology  

    Background and objective: The efficacy of supplemental oxygen during exercise remains unclear for patients with IPF, as there have been conflicting results from recent prospective studies with small sample sizes. Methods: This prospective, single-blind, randomized, crossover trial evaluated the efficacy of supplemental oxygen compared with placebo air during exercise in consecutive patients with IPF without resting hypoxaemia at initial evaluation. Patients with <90% SpO2 in a 6MWT using room air were randomly assigned to a CWRET at 80% of peak work rate with oxygen or placebo air gas via nasal cannula at 4 L/min. The primary endpoint was the effect of supplemental oxygen on endurance time. Results: We recruited 72 consecutive patients (median age: 66.5 years, % FVC: 84.6%, % DLCO: 61.4%). Supplemental oxygen significantly increased the endurance time (340–424 s; P < 0.001) and minimum SpO2 (88.0–94.0%; P < 0.001) compared with placebo air. Furthermore, supplemental oxygen significantly improved dyspnoea and leg fatigue. In a multivariate linear regression analysis, the endurance time on air was an independent explanatory variable of the improvement rate of endurance time (P = 0.02). Conclusion: In mild–moderate IPF with exercise-induced hypoxaemia even without resting hypoxaemia, supplemental oxygen during exercise improved the endurance time, desaturation and subjective symptoms. Patients with shorter endurance times with placebo air showed better improvement with supplemental oxygen.

    DOI: 10.1111/resp.13829

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  26. Clinical burden of immune checkpoint inhibitor-induced pneumonitis 査読有り 国際誌

    Sakamoto Koji, Fukihara Jun, Morise Masahiro, Hashimoto Naozumi

    RESPIRATORY INVESTIGATION   58 巻 ( 5 ) 頁: 305 - 319   2020年9月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Respiratory Investigation  

    Immune checkpoint inhibitors (ICIs) have been a breakthrough in medical oncology. However, many patients experience a novel type of adverse drug reaction that has a unique clinical presentation, called immune-related adverse events (irAEs). A breakdown of self-tolerance and an exaggerated autoimmune reaction by the host are assumed to be the underlying mechanisms. Therefore, special attention to the optimal diagnosis and management is required. Among the various effects of irAE, pneumonitis has been recognized as an important manifestation because of its high morbidity and mortality. As the application of ICIs is expanding to a wider variety of tumor types, as well as its use with cytotoxic agents and radiation, clinicians are highly likely to encounter this complication. In this review, we will summarize the current understanding of the underlying mechanisms, incidence, risk factors, optimal diagnostic workup, and management of ICI-related pneumonitis (IRP). We will also review fundamental information on drug-induced lung toxicity in the oncology setting. In addition, research perspectives focused on better risk stratification and management to avoid serious complications in the future are presented.

    DOI: 10.1016/j.resinv.2020.05.008

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  27. 肺線維症 新規治療に関する基礎研究 肺線維症の病態形成におけるメフリンの役割

    中原 義夫, 橋本 直純, 阪本 考司, 榎本 篤

    日本呼吸器学会誌   9 巻 ( 増刊 ) 頁: 139 - 139   2020年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:(一社)日本呼吸器学会  

  28. Acute Exacerbation of Pleuroparenchymal Fibroelastosis Secondary to Allogenic Hematopoietic Stem Cell Transplantation.

    Murakami Y, Sakamoto K, Okumura Y, Suzuki A, Mii S, Sato M, Yokoi T, Hashimoto N, Hasegawa Y

    Internal medicine (Tokyo, Japan)     2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.4995-20

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  29. High-flow nasal cannula therapy for acute respiratory failure in patients with interstitial Pneumonia: A retrospective observational study 査読有り 国際誌

    Omote N.

    Nagoya Journal of Medical Science   82 巻 ( 2 ) 頁: 301 - 313   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nagoya Journal of Medical Science  

    DOI: 10.18999/nagjms.82.2.301

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  30. Reply to "Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With NoneSmall-Cell Lung Cancer Who Received Programmed Death-1 Inhibitors" 査読有り 国際誌

    Fukihara Jun, Sakamoto Koji, Koyama Junji, Ito Takayasu, Iwano Shingo, Morise Masahiro, Ogawa Masahiro, Kondoh Yasuhiro, Kimura Tomoki, Hashimoto Naozumi, Hasegawa Yoshinori

    CLINICAL LUNG CANCER   21 巻 ( 3 ) 頁: E205 - E205   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Clinical Lung Cancer  

    DOI: 10.1016/j.cllc.2019.11.013

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  31. Acute exacerbations of fibrotic interstitial lung diseases 査読有り 国際誌

    Suzuki Atsushi, Kondoh Yasuhiro, Brown Kevin K., Johkoh Takeshi, Kataoka Kensuke, Fukuoka Junya, Kimura Tomoki, Matsuda Toshiaki, Yokoyama Toshiki, Fukihara Jun, Ando Masahiko, Tanaka Tomonori, Hashimoto Naozumi, Sakamoto Koji, Hasegawa Yoshinori

    RESPIROLOGY   25 巻 ( 5 ) 頁: 525 - 534   2020年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Respirology  

    DOI: 10.1111/resp.13682

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  32. Renewed Japanese spirometric reference variables and risk stratification for postoperative outcomes in COPD patients with resected lung cancer 査読有り 国際誌

    Okada Yu, Hashimoto Naozumi, Iwano Shingo, Kawaguchi Koji, Fukui Takayuki, Sakamoto Koji, Wakai Kenji, Yokoi Kohei, Hasegawa Yoshinori

    NAGOYA JOURNAL OF MEDICAL SCIENCE   81 巻 ( 3 ) 頁: 427 - 438   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nagoya Journal of Medical Science  

    DOI: 10.18999/nagjms.81.3.427

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  33. Repressive role of stabilized hypoxia inducible factor 1 alpha expression on transforming growth factor beta-induced extracellular matrix production in lung cancer cells 査読有り 国際誌

    Ando Akira, Hashimoto Naozumi, Sakamoto Koji, Omote Norihito, Miyazaki Shinichi, Nakahara Yoshio, Imaizumi Kazuyoshi, Kawabe Tsutomu, Hasegawa Yoshinori

    CANCER SCIENCE   110 巻 ( 6 ) 頁: 1959 - 1973   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Cancer Science  

    Activation of transforming growth factor β (TGF-β) combined with persistent hypoxia often affects the tumor microenvironment. Disruption of cadherin/catenin complexes induced by these stimulations yields aberrant extracellular matrix (ECM) production, characteristics of epithelial-mesenchymal transition (EMT). Hypoxia-inducible factors (HIF), the hallmark of the response to hypoxia, play differential roles during development of diseases. Recent studies show that localization of cadherin/catenin complexes at the cell membrane might be tightly regulated by protein phosphatase activity. We aimed to investigate the role of stabilized HIF-1α expression by protein phosphatase activity on dissociation of the E-cadherin/β-catenin complex and aberrant ECM expression in lung cancer cells under stimulation by TGF-β. By using lung cancer cells treated with HIF-1α stabilizers or carrying doxycycline-dependent HIF-1α deletion or point mutants, we investigated the role of stabilized HIF-1α expression on TGF-β-induced EMT in lung cancer cells. Furthermore, the underlying mechanisms were determined by inhibition of protein phosphatase activity. Persistent stimulation by TGF-β and hypoxia induced EMT phenotypes in H358 cells in which stabilized HIF-1α expression was inhibited. Stabilized HIF-1α protein expression inhibited the TGF-β-stimulated appearance of EMT phenotypes across cell types and species, independent of de novo vascular endothelial growth factor A (VEGFA) expression. Inhibition of protein phosphatase 2A activity abrogated the HIF-1α-induced repression of the TGF-β-stimulated appearance of EMT phenotypes. This is the first study to show a direct role of stabilized HIF-1α expression on inhibition of TGF-β-induced EMT phenotypes in lung cancer cells, in part, through protein phosphatase activity.

    DOI: 10.1111/cas.14027

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  34. Performance of the COPD Assessment Test in patients with connective tissue disease-associated interstitial lung disease

    Suzuki Atsushi, Kondoh Yasuhiro, Swigris Jeffrey James, Matsuda Toshiaki, Kimura Tomoki, Kataoka Kensuke, Ando Masahiko, Hashimoto Naozumi, Sakamoto Koji, Hasegawa Yoshinori

    RESPIRATORY MEDICINE   150 巻   頁: 15-20   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.rmed.2019.01.017

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  35. Multidimensional improvement in connective tissue disease-associated interstitial lung disease: Two courses of pulse dose methylprednisolone followed by low-dose prednisone and tacrolimus 査読有り 国際誌

    Yamano Yasuhiko, Taniguchi Hiroyuki, Kondoh Yasuhiro, Ando Masahiko, Kataoka Kensuke, Furukawa Taiki, Johkoh Takeshi, Fukuoka Junya, Sakamoto Koji, Hasegawa Yoshinori

    RESPIROLOGY   23 巻 ( 11 ) 頁: 1041 - 1048   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Respirology  

    DOI: 10.1111/resp.13365

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  36. Outcomes with newly proposed classification of acute respiratory deterioration in idiopathic pulmonary fibrosis

    Teramachi Ryo, Kondoh Yasuhiro, Kataoka Kensuke, Taniguchi Hiroyuki, Matsuda Toshiaki, Kimura Tomoki, Yokoyama Toshiki, Yamano Yasuhiko, Furukawa Taiki, Sakamoto Koji, Hashimoto Naozumi, Hasegawa Yoshinori

    RESPIRATORY MEDICINE   143 巻   頁: 147-152   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.rmed.2018.09.011

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  37. Performance of the St George's Respiratory Questionnaire in patients with connective tissue disease-associated interstitial lung disease 査読有り 国際誌

    Suzuki Atsushi, Kondoh Yasuhiro, Swigris Jeffrey J., Ando Masahiko, Kimura Tomoki, Kataoka Kensuke, Yamano Yasuhiko, Furukawa Taiki, Numata Mari, Sakamoto Koji, Hasegawa Yoshinori

    RESPIROLOGY   23 巻 ( 9 ) 頁: 851 - 859   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Respirology  

    DOI: 10.1111/resp.13293

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  38. Prognostic evaluation by oxygenation with positive end-expiratory pressure in acute exacerbation of idiopathic pulmonary fibrosis: A retrospective cohort study

    Suzuki Atsushi, Taniguchi Hiroyuki, Ando Masahiko, Kondoh Yasuhiro, Kimura Tomoki, Kataoka Kensuke, Matsuda Toshiaki, Yokoyama Toshiki, Sakamoto Koji, Hasegawa Yoshinori

    CLINICAL RESPIRATORY JOURNAL   12 巻 ( 3 ) 頁: 895 - 903   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/crj.12602

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  39. Thin-section computed tomography-determined usual interstitial pneumonia pattern affects the decision-making process for resection in newly diagnosed lung cancer patients: a retrospective study 査読有り

    Hashimoto Naozumi, Ando Akira, Iwano Shingo, Sakamoto Koji, Okachi Shotaro, Matsuzaki Asuka, Okada Yu, Wakai Kenji, Yokoi Kohei, Hasegawa Yoshinori

    BMC PULMONARY MEDICINE   18 巻 ( 1 ) 頁: 2   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC Pulmonary Medicine  

    DOI: 10.1186/s12890-017-0565-5

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  40. A scoring system to predict the elevation of mean pulmonary arterial pressure in idiopathic pulmonary fibrosis

    Furukawa Taiki, Kondoh Yasuhiro, Taniguchi Hiroyuki, Yagi Mitsuaki, Matsuda Toshiaki, Kimura Tomoki, Kataoka Kensuke, Johkoh Takeshi, Ando Masahiko, Hashimoto Naozumi, Sakamoto Koji, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL   51 巻 ( 1 )   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1183/13993003.01311-2017

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  41. Pirfenidone as salvage treatment for refractory bleomycin-induced lung injury: a case report of seminoma 査読有り 国際誌

    Sakamoto Koji, Ito Satoru, Hashimoto Naozumi, Hasegawa Yoshinori

    BMC CANCER   17 巻 ( 1 ) 頁: 526   2017年8月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC Cancer  

    DOI: 10.1186/s12885-017-3521-0

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  42. Aging Impairs Alveolar Macrophage Phagocytosis and Increases Influenza-Induced Mortality in Mice. 査読有り 国際誌

    Wong CK, Smith CA, Sakamoto K, Kaminski N, Koff JL, Goldstein DR

    Journal of immunology (Baltimore, Md. : 1950)   199 巻 ( 3 ) 頁: 1060 - 1068   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4049/jimmunol.1700397

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  43. Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model. 査読有り 国際誌

    Huleihel L, Sellares J, Cardenes N, Álvarez D, Faner R, Sakamoto K, Yu G, Kapetanaki MG, Kaminski N, Rojas M

    American journal of physiology. Lung cellular and molecular physiology   313 巻 ( 1 ) 頁: L92 - L103   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1152/ajplung.00323.2016

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  44. Progression of mean pulmonary arterial pressure in idiopathic pulmonary fibrosis with mild to moderate restriction 査読有り 国際誌

    Teramachi Ryo, Taniguchi Hiroyuki, Kondoh Yasuhiro, Ando Masahiko, Kimura Tomoki, Kataoka Kensuke, Suzuki Atsushi, Furukawa Taiki, Sakamoto Koji, Hasegawa Yoshinori

    RESPIROLOGY   22 巻 ( 5 ) 頁: 986 - 990   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Respirology  

    DOI: 10.1111/resp.12986

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  45. COPD Assessment Test for measurement of health status in patients with idiopathic pulmonary fibrosis: A cross-sectional study. 査読有り

    Matsuda T, Taniguchi H, Ando M, Kondoh Y, Kimura T, Kataoka K, Sakamoto K, Suzuki A, Furukawa T, Hasegawa Y

    Respirology (Carlton, Vic.)   22 巻 ( 4 ) 頁: 721-727   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/resp.12936

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  46. Soluble thrombomodulin in bronchoalveolar lavage fluid is an independent predictor of severe drug-induced lung injury 査読有り 国際誌

    Suzuki Atsushi, Taniguchi Hiroyuki, Kondoh Yasuhiro, Ando Masahiko, Watanabe Naohiro, Kimura Tomoki, Kataoka Kensuke, Yokoyama Toshiki, Sakamoto Koji, Hasegawa Yoshinori

    RESPIROLOGY   22 巻 ( 4 ) 頁: 744 - 749   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Respirology  

    DOI: 10.1111/resp.12965

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  47. Validation of the prognostic value of MMP-7 in idiopathic pulmonary fibrosis. 査読有り 国際誌

    Tzouvelekis A, Herazo-Maya JD, Slade M, Chu JH, Deiuliis G, Ryu C, Li Q, Sakamoto K, Ibarra G, Pan H, Gulati M, Antin-Ozerkis D, Herzog EL, Kaminski N

    Respirology (Carlton, Vic.)   22 巻 ( 3 ) 頁: 486 - 493   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/resp.12920

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  48. Hemosiderin-laden macrophages are an independent factor correlated with pulmonary vascular resistance in idiopathic pulmonary fibrosis: a case control study 査読有り 国際誌

    Fukihara Jun, Taniguchi Hiroyuki, Ando Masahiko, Kondoh Yasuhiro, Kimura Tomoki, Kataoka Kensuke, Furukawa Taiki, Johkoh Takeshi, Fukuoka Junya, Sakamoto Koji, Hasegawa Yoshinori

    BMC PULMONARY MEDICINE   17 巻 ( 1 ) 頁: 30   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC Pulmonary Medicine  

    DOI: 10.1186/s12890-017-0376-8

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  49. SH2 Domain-Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis. 査読有り 国際共著 国際誌

    Tzouvelekis A, Yu G, Lino Cardenas CL, Herazo-Maya JD, Wang R, Woolard T, Zhang Y, Sakamoto K, Lee H, Yi JS, DeIuliis G, Xylourgidis N, Ahangari F, Lee PJ, Aidinis V, Herzog EL, Homer R, Bennett AM, Kaminski N

    American journal of respiratory and critical care medicine   195 巻 ( 4 ) 頁: 500 - 514   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1164/rccm.201602-0329OC

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  50. The St. George's Respiratory Questionnaire as a prognostic factor in IPF 査読有り 国際誌

    Furukawa Taiki, Taniguchi Hiroyuki, Ando Masahiko, Kondoh Yasuhiro, Kataoka Kensuke, Nishiyama Osamu, Johkoh Takeshi, Fukuoka Junya, Sakamoto Koji, Hasegawa Yoshinori

    RESPIRATORY RESEARCH   18 巻 ( 1 ) 頁: 18   2017年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Respiratory Research  

    Background: It is unclear whether health related quality of life (HRQL) may have a predictive value for mortality in idiopathic pulmonary fibrosis (IPF). We investigated the relationship between HRQL assessed using the St. George's Respiratory Questionnaire (SGRQ) and survival time in patients with IPF, and tried to determine a clinical meaningful cut off value to predict poorer survival rates. Methods: We retrospectively analyzed consecutive patients with IPF who underwent an initial evaluation from May 2007 to December 2012. The diagnosis of IPF was made according to the 2011 international consensus guidelines. We used Cox proportional hazard models to identify independent predictors for mortality rate in patients with IPF. Results: We examined 182 eligible cases, average age was 66years old, and 86% were male. Mean levels of percent predicted FVC, DLco, six-minute-walk test distance, and the SGRQ total score were around 80%, 58%, 580m, and 34 points. On multivariate analysis, the SGRQ total score (hazard ratio [HR], 1.012; 95% confidence interval [CI] 1.001-1.023; P=<.029) and percent predicted FVC (HR, 0.957; 95% CI 0.944-0.971, P<.001) were independent predictors for mortality rate. Moreover, a score higher than 30 points in the SGRQ total score showed higher mortality rate (HR, 2.047; 95% CI, 1.329-3.153; P=<.001). Conclusions: The SGRQ total score was one of independent prognostic factors in patients with IPF. Total scores higher than 30 points were associated with higher mortality rates. Trial registration: This study was retrospective, observational study, so it is not applicable.

    DOI: 10.1186/s12931-017-0503-3

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  51. Exercise hypoxaemia as a predictor of pulmonary hypertension in COPD patients without severe resting hypoxaemia. 査読有り

    Nakahara Y, Taniguchi H, Kimura T, Kondoh Y, Arizono S, Nishimura K, Sakamoto K, Ito S, Ando M, Hasegawa Y

    Respirology (Carlton, Vic.)   22 巻 ( 1 ) 頁: 120-125   2017年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/resp.12863

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  52. Exogenous induction of unphosphorylated PTEN reduces TGFβ-induced extracellular matrix expressions in lung fibroblasts. 査読有り

      25 巻 ( 1 ) 頁: 86-97   2017年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/wrr.12506

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  53. Depression Is Significantly Associated with the Health Status in Patients with Idiopathic Pulmonary Fibrosis. 査読有り

    Matsuda T, Taniguchi H, Ando M, Kondoh Y, Kimura T, Kataoka K, Nishimura K, Nishiyama O, Sakamoto K, Hasegawa Y

    Internal medicine (Tokyo, Japan)   56 巻 ( 13 ) 頁: 1637-1644   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2169/internalmedicine.56.7019

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  54. Impact of mild to moderate COPD on feasibility and prognosis in non-small cell lung cancer patients who received chemotherapy

    Omote Norihito, Hashimoto Naozumi, Morise Masahiro, Sakamoto Koji, Miyazaki Shinichi, Ando Akira, Nakahara Yoshio, Hasegawa Yoshinori

    INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE   12 巻   頁: 3541 - 3547   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2147/COPD.S149456

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  55. PULMONARY REHABILITATION IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS: COMPARISON WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE 査読有り

    Arizono Shinichi, Taniguchi Hiroyuki, Sakamoto Koji, Kondoh Yasuhiro, Kimura Tomoki, Kataoka Kensuke, Ogawa Tomoya, Watanabe Fumiko, Tabira Kazuyuki, Kozu Ryo

    SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES   34 巻 ( 4 ) 頁: 283 - 289   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  56. Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis: comparison with chronic obstructive pulmonary disease. 査読有り 国際誌

    Arizono S, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, Ogawa T, Watanabe F, Tabira K, Kozu R

    Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG   34 巻 ( 4 ) 頁: 283 - 289   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.36141/svdld.v34i4.5549

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  57. Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis: Comparison with chronic obstructive pulmonary disease

    Arizono S., Taniguchi H., Sakamoto K., Kondoh Y., Kimura T., Kataoka K., Ogawa T., Watanabe F., Tabira K., Kozu R.

    Sarcoidosis Vasculitis and Diffuse Lung Diseases   34 巻 ( 4 ) 頁: 283 - 289   2017年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Sarcoidosis Vasculitis and Diffuse Lung Diseases  

    Background: While the efficacy of pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) has been well established, emerging evidence also suggests its benefit in idiopathic pulmonary fibrosis (IPF). However, the differences and similarities between how PR affects diseases with different physiologies remain unknown. Objective: This study aimed to compare the efficacy of PR in COPD and IPF patients by performing multifactorial evaluation with various exercise capacity measurements, and dyspnea and health-related quality of life (QoL) assessment. Methods: Twenty-two IPF patients (%vital capacity: 72%) and 27 COPD patients (%forced expiratory volume1: 43%) were recruited. Subjects who completed a 10-week outpatient PR program were analyzed. We assessed five exercise capacity indicators (6-minute walking distance, incremental shuttle walking distance, endurance time, peak work rate, and peak values for oxygen uptake [peak VO2]), dyspnea (Baseline Dyspnea Index: BDI), and health-related QoL (St. George's Respiratory Questionnaire: SGRQ) at baseline and immediately following completion of the PR program. Results: After 10 weeks of PR, all exercise capacity measurements, except VO2, as well as BDI and SGRQ score improved significantly (p<0.05) in both disease groups. The magnitude of the observed changes in each outcome, assessed by the effect size, was comparable between IPF and COPD patients. This was also true for endurance time, the measurement most responsive to PR, with a large effect size. Conclusions: PR can result in comparable improvements in exercise capacity, including endurance time, and dyspnea and HRQoL in both IPF and COPD patients after 10 weeks of exercise training.

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  58. Impact of Thin-Section Computed Tomography-Determined Combined Pulmonary Fibrosis and Emphysema on Outcomes Among Patients With Resected Lung Cancer. 査読有り

    Hashimoto N, Iwano S, Kawaguchi K, Fukui T, Fukumoto K, Nakamura S, Mori S, Sakamoto K, Wakai K, Yokoi K, Hasegawa Y

    The Annals of thoracic surgery   102 巻 ( 2 ) 頁: 440-7   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.athoracsur.2016.03.014

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  59. Mean pulmonary arterial pressure as a prognostic indicator in connective tissue disease associated with interstitial lung disease: a retrospective cohort study. 査読有り

    Takahashi K, Taniguchi H, Ando M, Sakamoto K, Kondoh Y, Watanabe N, Kimura T, Kataoka K, Suzuki A, Ito S, Hasegawa Y

    BMC pulmonary medicine   16 巻 ( 1 ) 頁: 55   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s12890-016-0207-3

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  60. Biomarkers in the Evaluation and Management of Idiopathic Pulmonary Fibrosis. 査読有り

    Tzouvelekis A, Herazo-Maya J, Sakamoto K, Bouros D

    Current topics in medicinal chemistry   16 巻 ( 14 ) 頁: 1587-98   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PubMed

  61. Hypoxia-induced modulation of PTEN activity and EMT phenotypes in lung cancers. 査読有り

    Kohnoh T, Hashimoto N, Ando A, Sakamoto K, Miyazaki S, Aoyama D, Kusunose M, Kimura M, Omote N, Imaizumi K, Kawabe T, Hasegawa Y

    Cancer cell international   16 巻   頁: 33   2016年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s12935-016-0308-3

    PubMed

  62. Lung-Dominant Connective Tissue Disease: Clinical, Radiologic, and Histologic Features. 査読有り

    Omote N, Taniguchi H, Kondoh Y, Watanabe N, Sakamoto K, Kimura T, Kataoka K, Johkoh T, Fujimoto K, Fukuoka J, Otani K, Nishiyama O, Hasegawa Y

    Chest   148 巻 ( 6 ) 頁: 1438-1446   2015年12月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1378/chest.14-3174

    PubMed

  63. Direct regulation of transforming growth factor β-induced epithelial-mesenchymal transition by the protein phosphatase activity of unphosphorylated PTEN in lung cancer cells. 査読有り

      106 巻 ( 12 ) 頁: 1693-704   2015年12月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/cas.12831

    PubMed

  64. Recombinant Human Thrombomodulin in Acute Exacerbation of Idiopathic Pulmonary Fibrosis. 査読有り

    Kataoka K, Taniguchi H, Kondoh Y, Nishiyama O, Kimura T, Matsuda T, Yokoyama T, Sakamoto K, Ando M

    Chest   148 巻 ( 2 ) 頁: 436-443   2015年8月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1378/chest.14-2746

    PubMed

  65. Risk stratification by the lower limit of normal of FEV1/FVC for postoperative outcomes in patients with COPD undergoing thoracic surgery. 査読有り

    Osuka S, Hashimoto N, Sakamoto K, Wakai K, Yokoi K, Hasegawa Y

    Respiratory investigation   53 巻 ( 3 ) 頁: 117-23   2015年5月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.resinv.2015.01.005

    PubMed

  66. Broader criteria of undifferentiated connective tissue disease in idiopathic interstitial pneumonias. 査読有り

    Kondoh Y, Johkoh T, Fukuoka J, Arakawa H, Tanaka T, Watanabe N, Sakamoto K, Kataoka K, Kimura T, Taniguchi H

    Respiratory medicine   109 巻 ( 3 ) 頁: 389-96   2015年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.rmed.2015.01.009

    PubMed

  67. Endurance time is the most responsive exercise measurement in idiopathic pulmonary fibrosis. 査読有り

    Arizono S, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, Ogawa T, Watanabe F, Nishiyama O, Nishimura K, Kozu R, Tabira K

    Respiratory care   59 巻 ( 7 ) 頁: 1108-15   2014年7月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.4187/respcare.02674

    PubMed

  68. Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts. 査読有り

    Huleihel L, Ben-Yehudah A, Milosevic J, Yu G, Pandit K, Sakamoto K, Yousef H, LeJeune M, Coon TA, Redinger CJ, Chensny L, Manor E, Schatten G, Kaminski N

    American journal of physiology. Lung cellular and molecular physiology   306 巻 ( 6 ) 頁: L534-42   2014年3月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1152/ajplung.00149.2013

    PubMed

  69. Crizotinib-induced acute interstitial lung disease in a patient with EML4-ALK positive non-small cell lung cancer and chronic interstitial pneumonia. 査読有り

    Watanabe N, Nakahara Y, Taniguchi H, Kimura T, Kondoh Y, Kataoka K, Sakamoto K

    Acta oncologica (Stockholm, Sweden)   53 巻 ( 1 ) 頁: 158-60   2014年1月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3109/0284186X.2013.802838

    PubMed

  70. Efficacy of combined therapy with cyclosporin and low-dose prednisolone in interstitial pneumonia associated with connective tissue disease. 査読有り

    Watanabe N, Sakamoto K, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Ono K, Fukuoka J, Nishiyama O, Hasegawa Y

    Respiration; international review of thoracic diseases   87 巻 ( 6 ) 頁: 469-77   2014年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000358098

    PubMed

  71. Significance of pulmonary arterial pressure as a prognostic indicator in lung-dominant connective tissue disease. 査読有り

    Suzuki A, Taniguchi H, Watanabe N, Kondoh Y, Kimura T, Kataoka K, Matsuda T, Yokoyama T, Sakamoto K, Nishiyama O, Hasegawa Y

    PloS one   9 巻 ( 9 ) 頁: e108339   2014年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0108339

    PubMed

  72. Endobronchial ultrasound transbronchial needle aspiration in older people. 査読有り

    Okachi S, Imai N, Imaizumi K, Hase T, Shindo Y, Sakamoto K, Aso H, Wakahara K, Hashimoto I, Ito S, Hashimoto N, Sato M, Kondo M, Hasegawa Y

    Geriatrics & gerontology international   13 巻 ( 4 ) 頁: 986-92   2013年10月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/ggi.12043

    PubMed

  73. Quadriceps weakness contributes to exercise capacity in nonspecific interstitial pneumonia. 査読有り

    Watanabe F, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, Ogawa T, Arizono S, Nishiyama O, Hasegawa Y

    Respiratory medicine   107 巻 ( 4 ) 頁: 622-8   2013年4月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.rmed.2012.12.013

    PubMed

  74. Pulmonary hypertension as a prognostic indicator at the initial evaluation in idiopathic pulmonary fibrosis. 査読有り

    Kimura M, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Nishiyama O, Aso H, Sakamoto K, Hasegawa Y

    Respiration; international review of thoracic diseases   85 巻 ( 6 ) 頁: 456-63   2013年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000345221

    PubMed

  75. Involvement of TGFβ-induced phosphorylation of the PTEN C-terminus on TGFβ-induced acquisition of malignant phenotypes in lung cancer cells. 査読有り

      8 巻 ( 11 ) 頁: e81133   2013年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0081133

    PubMed

  76. Predictors of the need to initiate noninvasive ventilation in stable outpatients with acute exacerbation of chronic obstructive pulmonary disease. 査読有り

    Taga S, Taniguchi H, Watanabe N, Kondoh Y, Kimura T, Kataoka K, Aso H, Sakamoto K, Hasegawa Y

    Internal medicine (Tokyo, Japan)   52 巻 ( 16 ) 頁: 1781-6   2013年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PubMed

  77. Differential modulation of surfactant protein D under acute and persistent hypoxia in acute lung injury. 査読有り

    Sakamoto K, Hashimoto N, Kondoh Y, Imaizumi K, Aoyama D, Kohnoh T, Kusunose M, Kimura M, Kawabe T, Taniguchi H, Hasegawa Y

    Am J Physiol Lung Cell Mol Physiol.   303 巻 ( 1 ) 頁: L43-53   2012年7月

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

  78. Acute exacerbation of IPF following diagnostic bronchoalveolar lavage procedures.

    Sakamoto K, Taniguchi H, Kondoh Y, Wakai K, Kimura T, Kataoka K, Hashimoto N, Nishiyama O, Hasegawa Y.

    Respir Med   106 巻 ( 3 ) 頁: 436-42   2012年

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

  79. Involvement of the transcription factor twist in phenotype alteration through epithelial-mesenchymal transition in lung cancer cells.

    Nakashima H, Hashimoto N, Aoyama D, Kohnoh T, Sakamoto K, Kusunose M, Imaizumi K, Takeyama Y, Sato M, Kawabe T, Hasegawa Y.

    Mol Carcinog   51 巻   頁: 400-410   2012年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  80. Risk factors of acute exacerbation of idiopathic pulmonary fibrosis. 査読有り

    Kondoh Y, Taniguchi H, Katsuta T, Kataoka K, Kimura T, Nishiyama O, Sakamoto K, Johkoh T, Nishimura M, Ono K, Kitaichi M.

    Sarcoidosis Vasc Diffuse Lung Dis   27 巻   頁: 103-110   2010年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  81. Serum KL-6 in fibrotic NSIP: Correlations with physiologic and radiologic parameters.

    Sakamoto K, Taniguchi H, Kondoh Y, Johkoh T, Sumikawa H, Kimura T, Nishiyama O, Kato K, Kataoka K, Ono K, Kitaichi M, Hasegawa Y.

    Respir Med   104 巻   頁: 127-133   2009年

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

  82. Acute exacerbation of idiopathic pulmonary fibrosis as the initial presentation of the disease.

    Sakamoto K, Taniguchi H, Kondoh Y, Ono K, Hasegawa Y, Kitaichi M.

    Eur Respir Rev   18 巻   頁: 129-132.   2009年

     詳細を見る

    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

  83. 原発性肺クリプトコッカス症の臨床的検討 査読有り

    阪本 考司, 麻生 裕紀, 横山 俊樹, 加藤 景介, 西山 理, 木村 智樹, 近藤 康博, 谷口 博之

    感染症学雑誌   4 巻   頁: 403-407   2007年7月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

  84. びまん性肺疾患に対する外科的肺生検の検討 合併症、診断効率と早期死亡について

    阪本 考司, 横山 俊樹, 麻生 裕紀, 岩木 舞, 野間 聖, 加藤 景介, 西山 理, 木村 智樹, 近藤 康博, 谷口 博之

    日本呼吸器学会雑誌   44 巻 ( 10 ) 頁: 675-680   2006年10月

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  85. 化学療法を施行したIV期非小細胞肺癌におけるQuality of Life

    西山 理, 谷口 博之, 近藤 康博, 木村 智樹, 加藤 景介, 野間 聖, 岩木 舞, 麻生 裕紀, 阪本 考司, 清水 淳市

    日本呼吸器学会雑誌   44 巻 ( 5 ) 頁: 368-373   2006年5月

     詳細を見る

    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

▼全件表示

MISC 18

  1. 喘息・COPDにおける吸入デバイスとアドヒアランスの検討

    福谷 衣里子, 若原 恵子, 中村 さや, 横井 英人, 吉見 陽, 宮崎 雅之, 進藤 有一郎, 阪本 考司, 岡地 祥太郎, 田中 一大, 浜島 信之, 野田 幸裕, 橋本 直純  

    日本呼吸器学会誌11 巻 ( 増刊 ) 頁: 213 - 213   2022年4月

     詳細を見る

    記述言語:日本語   掲載種別:研究発表ペーパー・要旨(全国大会,その他学術会議)   出版者・発行元:(一社)日本呼吸器学会  

  2. Supplemental oxygen improves exercise capacity in IPF patients with exertional desaturation 査読有り

    Arizono S, Furukawa T, Taniguchi H, Sakamoto K, Kimura T, Kataoka K, Ogawa T, Watanabe F, Kondoh Y  

    Respirology (Carlton, Vic.)   2020年5月

     詳細を見る

    記述言語:英語  

    DOI: 10.1111/resp.13829

    PubMed

  3. High-flow nasal cannula therapy for acute respiratory failure in patients with interstitial pneumonia: a retrospective observational study 査読有り

    Omote N, Matsuda N, Hashimoto N, Nishida K, Sakamoto K, Ando A, Nakahara Y, Nishikimi M, Higashi M, Matsui S, Hasegawa Y  

    Nagoya journal of medical science82 巻 ( 2 ) 頁: 301-313   2020年5月

     詳細を見る

    記述言語:英語  

    DOI: 10.18999/nagjms.82.2.301

    PubMed

  4. Silica Nanoparticle Induced Lung Injury in Mice: Dissecting Relative Contribution of Its Size and Surface Modification

    Inoue M., Sakamoto K., Suzuki A., Nakahara Y., Hashimoto N., Hasegawa Y., Sawada M.  

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE201 巻   2020年

     詳細を見る

  5. Single-Cell RNAseq of Aging Mouse Lungs Reveals Global and Cell-Specific Inflammatory Aberrations

    Cosme C. Jr., McDonough J. E., Adams T., Schupp J. C., Omote N., Ahangari F., Deluliis G., Sakamoto K., Kaminski N.  

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE201 巻   2020年

     詳細を見る

  6. The Role of Meflin Expression in Fibroblasts During Development of Pulmonary Fibrosis

    Hashimoto N., Nakahara Y., Sakamoto K., Enomoto A., Yokoi T., Suzuki A., Inoue M., Wakahara K., Hasegawa Y.  

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE201 巻   2020年

     詳細を見る

  7. Serum CRP Decrease Has Predictive Value for LongTerm Disease Control by PD-1/ PD-L1 Inhibitors in Patients with NSCLC

    Matsuzawa R., Morise M., Tanaka I., Koyama J., Kimura T., Kondoh Y., Hase T., Sakamoto K., Hashimoto N., Hasegawa Y.  

    JOURNAL OF THORACIC ONCOLOGY14 巻 ( 10 ) 頁: S716 - S716   2019年10月

     詳細を見る

  8. The new-defined mesenchymal stromal/stem cell marker has a protective role in the development of acute lung injury

    Nakahara Yoshio, Hashimoto Naozumi, Sakamoto Koji, Ando Akira, Inoue Masahide, Suzuki Atsushi, Enomoto Atsushi, Hasegawa Yoshinori  

    EUROPEAN RESPIRATORY JOURNAL54 巻   2019年9月

  9. Renewed Japanese spirometric reference variables and risk stratification for postoperative outcomes in COPD patients with resected lung cancer 査読有り

    Okada Y, Hashimoto N, Iwano S, Kawaguchi K, Fukui T, Sakamoto K, Wakai K, Yokoi K, Hasegawa Y  

    Nagoya journal of medical science81 巻 ( 3 ) 頁: 427-438   2019年8月

     詳細を見る

    記述言語:英語  

    DOI: 10.18999/nagjms.81.3.427

    PubMed

  10. Repressive role of stabilized hypoxia inducible factor 1α expression on transforming growth factor β-induced extracellular matrix production in lung cancer cells 査読有り

    Ando A, Hashimoto N, Sakamoto K, Omote N, Miyazaki S, Nakahara Y, Imaizumi K, Kawabe T, Hasegawa Y  

    Cancer science110 巻 ( 6 ) 頁: 1959-1973   2019年6月

     詳細を見る

    記述言語:英語  

    DOI: 10.1111/cas.14027

    PubMed

  11. Recurrent Acute Exacerbations of Fibrotic Interstitial Lung Diseases

    Suzuki A., Kondoh Y., Brown K. K., Kimura T., Kataoka K., Matsuda T., Yokoyama T., Ando M., Hashimoto N., Sakamoto K., Hasegawa Y.  

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE199 巻   2019年

     詳細を見る

  12. TINCR, a Long Intergenic Noncoding RNA Decreased in IPF, Is a Novel Regulator of Airway Epithelial Cell Differentiation

    Omote N., Sakamoto K., Li Q., Schupp J. C., Adams T., Ahangari F., Chioccioli M., Xylourgidis N., DeIuliis G., Hashimoto N., Hasegawa Y., Kaminski N.  

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE199 巻   2019年

     詳細を見る

  13. Risk Factor Evaluation of Programmed Death 1 Inhibitor Related Pneumonitis in Patients with Non-Small Cell Lung Cancer

    Fukihara J., Sakamoto K., Iwano S., Morise M., Hashimoto N., Hasegawa Y.  

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE197 巻   2018年

     詳細を見る

  14. 閉塞性細気管支炎(GVHDを含めて) (特集 稀な呼吸器疾患 : 診断と治療の最前線)

    阪本 考司, 橋本 直純, 長谷川 好規  

    呼吸器内科 = Respiratory medicine31 巻 ( 5 ) 頁: 436 - 442   2017年5月

     詳細を見る

    記述言語:日本語   出版者・発行元:科学評論社  

    CiNii Books

    その他リンク: http://search.jamas.or.jp/link/ui/2017262989

  15. Single Cell Rna-Sequencing Reveals Distinct Effects Of Inhibition Of Fendrr, A Long Non-Coding Rna Implicated In Fibroblast To Myofibroblast Differentiation

    Adams T., Sakamoto K., Ahangari F., Munivar A., Kaminski N.  

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE195 巻   2017年

     詳細を見る

  16. Risk Stratification For Airflow Obstruction-Related Outcomes Based On A Renewed Japanese Spirometric Reference By Using The Lambda-Mu-Sigma Method

    Hashimoto N., Okada Y., Sakamoto K., Hasegawa Y.  

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE195 巻   2017年

     詳細を見る

  17. The Impact Of CT-Detected Usual Interstitial Pneumonia Pattern As The Decision-Making Factor For Treatment Of Lung Cancer

    Ando A., Hashimoto N., Sakamoto K., Hasegawa Y.  

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE195 巻   2017年

     詳細を見る

  18. Unphosphorylated Pten Inhibits Tgf beta-Induced Aberrant Cell Motility In Epithelial Cells Via Differential Phosphatase Activities

    Hashimoto N., Sakamoto K., Miyazaki S., Hasegawa Y.  

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE195 巻   2017年

     詳細を見る

▼全件表示

講演・口頭発表等 33

  1. Late Breaking Abstract - Long-term Effect of Pulmonary Rehabilitation under Nintedanib treatment in Idiopathic Pulmonary Fibrosis (FITNESS study) 国際会議

    Ogura, T; Mori, Y; Kataoka, K; Nishiyama, O; Ando, M; Arizono, S; Ogawa, T; Shiraki, A; Ichikado, K; Ishimoto, H; Ito, H; Sakamoto, K; Tomii, K; Tomioka, H; Tsuda, T; Kozu, R; Kondoh, Y

    EUROPEAN RESPIRATORY JOURNAL  2021年9月5日 

     詳細を見る

    開催年月日: 2021年9月

    記述言語:英語   会議種別:口頭発表(一般)  

    DOI: 10.1183/13993003.congress-2021.RCT2905

  2. Assessment of Circulating Mitochondrial DNA as a Liquid Biomarker in Acute Exacerbation of Idiopathic Pulmonary Fibrosis 国際会議

    Sakamoto K., Furukawa T., Yamano Y., Teramachi R., Kataoka K., Hashimoto N., Kondoh Y., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 

     詳細を見る

    開催年月日: 2019年

    記述言語:英語   会議種別:ポスター発表  

  3. Possible UIP Pattern with Traction Bronchiectasis on HRCT: Prognostic Impact in IIP 国際会議

    Fukihara J., Kondoh Y., Kimura T., Kataoka K., Matsuda T., Yokoyama T., Furukawa T., Johkoh T., Fukuoka J., Sakamoto K., Hashimoto N., Hasegawa Y., Brown K. K.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 

     詳細を見る

    開催年月日: 2018年

    記述言語:英語   会議種別:ポスター発表  

  4. Lung Epithelium Overexpressed Noncoding Rna (leon): A Potential Regulator Of Epithelial Gene Expression In Idiopathic Pulmonary Fibrosis 国際会議

    Guardela B. Juan, Herazo-Maya J. D., Sakamoto K., Li Q., Deluliis G., Yan X., Prasse A., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 

     詳細を見る

    開催年月日: 2017年

    記述言語:英語   会議種別:ポスター発表  

  5. Performance Of The Saint George's Respiratory Questionnaire (sgrq) In Patients With Connective Tissue Disease-Associated Interstitial Lung Disease (ctd-Ild) 国際会議

    Suzuki A., Taniguchi H., Kondoh Y., Swigris J. J., Yamano Y., Furukawa T., Numata-Nakamura M., Sakamoto K., Ando M., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 

     詳細を見る

    開催年月日: 2017年

    記述言語:英語   会議種別:ポスター発表  

  6. Transduction of PTEN with mutated its C-terminal phosphorylation sites inhibits TGFb- induced phe notype alterations through epithelial-mesenchymal transition 国際会議

    K. Sakamoto, N. Hashimoto, D. Aoyama, M. Kusunose, M. Kimura, T. Kohnoh, K. Imaizumi, Y. Hasegawa.

    American Thoracic Society 2012 International Conference 

     詳細を見る

    開催年月日: 2012年

    記述言語:英語   会議種別:ポスター発表  

    国名:アメリカ合衆国  

  7. Acute Exacerbation of IPF Following Bronchoalveolar Lavage Procedures 国際会議

    K. Sakamoto, H. Taniguchi, Y. Kondoh, K. Wakai, T. Kimura, K. Kataoka, N. Hashimoto, O. Nishiyama, Y. Hasegawa.

    Chest 2011 Annual Congress 

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    開催年月日: 2011年

    記述言語:英語   会議種別:口頭発表(一般)  

    国名:アメリカ合衆国  

  8. Modulated Expression Of Surfactant Protein D In Acute Lung Injury Might Be Associated With Epithelial-Mesenchymal Transition In Epithelial Cells 国際会議

    K. Sakamoto, N. Hashimoto, K. Imaizumi, H. Taniguchi, Y. Kondoh, T. Kohnoh, D. Aoyama, T. Ogawa, Y. Hasegawa.

    American Thoracic Society 2011 International Conference 

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    開催年月日: 2011年

    記述言語:英語   会議種別:ポスター発表  

    国名:日本国  

  9. Modulated expression of surfactant protein D in acute lung injury might be associated with epithelial-mesenchymal transition in epithelial cells. 国際会議

    K. Sakamoto, N. Hashimoto, Y. Hasegawa.

    FASEB Summer Research Conferences 2010 

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    開催年月日: 2010年

    記述言語:英語   会議種別:ポスター発表  

    国名:アメリカ合衆国  

  10. EMT-Related Gene, Twist, for Phenotype Change in Lung Cancer Cells 国際会議

    K. Sakamoto, N. Hashimoto, K. Imaizumi, H. Nakashima, T. Kohnoh, D. Aoyama, T. Ogawa, Y. Hasegawa.

    American Thoracic Society 2010 International Conference 

     詳細を見る

    開催年月日: 2010年

    記述言語:英語   会議種別:ポスター発表  

    国名:アメリカ合衆国  

  11. Assessment of Circulating Mitochondrial DNA as a Liquid Biomarker in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

    Sakamoto K, Furukawa T, Yamano Y, Teramachi R, Kataoka K, Hashimoto N, Kondoh Y, Hasegawa Y

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2019年 

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    記述言語:英語   会議種別:ポスター発表  

  12. TINCR, a Long Intergenic Noncoding RNA Decreased in IPF, Is a Novel Regulator of Airway Epithelial Cell Differentiation 国際共著 国際会議

    Omote N., Sakamoto K., Li Q., Schupp J. C., Adams T., Ahangari F., Chioccioli M., Xylourgidis N., DeIuliis G., Hashimoto N., Hasegawa Y., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2019年 

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    記述言語:英語   会議種別:口頭発表(一般)  

  13. The Role of Meflin Expression in Fibroblasts During Development of Pulmonary Fibrosis 国際会議

    Hashimoto N., Nakahara Y., Sakamoto K., Enomoto A., Yokoi T., Suzuki A., Inoue M., Wakahara K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020年 

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    記述言語:英語   会議種別:ポスター発表  

  14. The new-defined mesenchymal stromal/stem cell marker has a protective role in the development of acute lung injury 国際会議

    Nakahara Yoshio, Hashimoto Naozumi, Sakamoto Koji, Ando Akira, Inoue Masahide, Suzuki Atsushi, Enomoto Atsushi, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL  2019年9月28日 

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    記述言語:英語   会議種別:ポスター発表  

  15. The hypoxia-inducible factor 1a protein stabilizers inhibit transforming growth factor beta-induced extracellular matrix proteins in epithelial cells and fibroblasts 国際会議

    Ando Akira, Hashimoto Naozumi, Sakamoto Koji, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL  2018年9月15日 

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    会議種別:ポスター発表  

  16. Single-Cell RNAseq of Aging Mouse Lungs Reveals Global and Cell-Specific Inflammatory Aberrations 国際共著 国際会議

    Cosme C. Jr., McDonough J. E., Adams T., Schupp J. C., Omote N., Ahangari F., Deluliis G., Sakamoto K., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020年 

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    記述言語:英語   会議種別:ポスター発表  

  17. Silica Nanoparticle Induced Lung Injury in Mice: Dissecting Relative Contribution of Its Size and Surface Modification 国際共著 国際会議

    Inoue M., Sakamoto K., Suzuki A., Nakahara Y., Hashimoto N., Hasegawa Y., Sawada M.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020年 

     詳細を見る

    記述言語:英語   会議種別:ポスター発表  

  18. Serum CRP Decrease Has Predictive Value for LongTerm Disease Control by PD-1/ PD-L1 Inhibitors in Patients with NSCLC 国際会議

    Matsuzawa R., Morise M., Tanaka I., Koyama J., Kimura T., Kondoh Y., Hase T., Sakamoto K., Hashimoto N., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY  2019年10月 

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    記述言語:英語   会議種別:ポスター発表  

  19. Recurrent Acute Exacerbations of Fibrotic Interstitial Lung Diseases 国際会議

    Suzuki A., Kondoh Y., Brown K. K., Kimura T., Kataoka K., Matsuda T., Yokoyama T., Ando M., Hashimoto N., Sakamoto K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2019年 

     詳細を見る

    記述言語:英語   会議種別:口頭発表(一般)  

  20. Possible UIP Pattern with Traction Bronchiectasis on HRCT: Prognostic Impact in IIP 国際共著 国際会議

    Fukihara J, Kondoh Y, Kimura T, Kataoka K, Matsuda T, Yokoyama T, Furukawa T, Johkoh T, Fukuoka J, Sakamoto K, Hashimoto N, Hasegawa Y, Brown K. K

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2018年 

     詳細を見る

    記述言語:英語   会議種別:口頭発表(一般)  

  21. Pirfenidone Delays the Prescription of Concomitant Drugs in Patients with Idiopathic Pulmonary Fibrosis: Post-Hoc Analysis of Japanese Phase III Clinical Trial 国際会議

    Suzuki A., Sakaguchi H., Ebina M., Azuma A., Ogura T., Taguchi Y., Suga M., Takahashi H., Sugiyama Y., Kudoh S., Nukiwa T., Miyazawa S., Sakamoto K., Kondoh Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020年 

     詳細を見る

    記述言語:英語   会議種別:口頭発表(一般)  

  22. Performance Of The Saint George's Respiratory Questionnaire (sgrq) In Patients With Connective Tissue Disease-Associated Interstitial Lung Disease (ctd-Ild) 国際会議

    Suzuki A, Taniguchi H, Kondoh Y, Swigris J. J, Yamano Y, Furukawa T, Numata-Nakamura M, Sakamoto K, Ando M, Hasegawa Y

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2017年 

     詳細を見る

    記述言語:英語   会議種別:ポスター発表  

  23. Lung Epithelium Overexpressed Noncoding Rna (leon): A Potential Regulator Of Epithelial Gene Expression In Idiopathic Pulmonary Fibrosis 国際会議

    Guardela B. Juan, Herazo-Maya J. D, Sakamoto K, Li Q, Deluliis G, Yan X, Prasse A, Kaminski N

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2017年 

     詳細を見る

    記述言語:英語   会議種別:ポスター発表  

  24. Loss of lncRNA FENDRR Induces Senescence in Adult Mouse Lungs 国際共著 国際会議

    Xylourgidis N., Sakamoto K., Schupp J. C., Adams T., DeIuliis G., Omote N., Hashimoto N., Hasegawa Y., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2019年 

     詳細を見る

    記述言語:英語   会議種別:ポスター発表  

  25. Long Non-Coding RNA TINCR Is a Novel Regulator of Human Bronchial Epithelial Cell Differentiation 国際共著 国際会議

    Omote N., Sakamoto K., Li Q., Schupp J. C., Adams T., Ahangari F., Chioccioli M., Hashimoto N., Hasegawa Y., Kaminski N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020年 

     詳細を見る

    記述言語:英語   会議種別:ポスター発表  

  26. Increased Circulating Mitochondrial DNA Content Predicts Fatal Complication and Worse Prognosis in Idiopathic Pulmonary Fibrosis 国際会議

    Sakamoto K., Furukawa T., Yamano Y., Teramachi R., Suzuki A., Nakahara Y., Inoue M., Kataoka K., Hashimoto N., Kondoh Y., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2020年 

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    記述言語:英語   会議種別:口頭発表(一般)  

  27. Exogenous Induction Of Unphosphorylated Tumor Suppressor Phosphatase And Tensin Homolog Deleted On Chromosome 10 Modulates Transforming Growth Factor beta-Induced Extracellular Matrix Expression In Lung Fibroblasts 国際会議

    Omote N., Hashimoto N., Kimura M., Miyazaki S., Ando A., Sakamoto K., Hasegawa Y.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2017年 

     詳細を見る

    会議種別:ポスター発表  

  28. Exogenous induction of unphosphorylated PTEN reduces TGF beta-induced extracellular matrix expressions in lung fibroblasts 国際会議

    Kimura Motohiro, Hashimoto Naozumi, Kusunose Masaaki, Aoyama Daisuke, Sakamoto Koji, Miyazaki Shinichi, Ando Akira, Omote Norihiro, Imaizumi Kazuyoshi, Kawabe Tsutomu, Hasegawa Yoshinori

    WOUND REPAIR AND REGENERATION  2017年  Wound Repair and Regeneration

     詳細を見る

    会議種別:ポスター発表  

    Scopus

    PubMed

  29. The new-defined mesenchymal stromal/stem cell marker has a protective role in the development of acute lung injury 国際会議

    Nakahara Yoshio, Hashimoto Naozumi, Sakamoto Koji, Ando Akira, Inoue Masahide, Suzuki Atsushi, Enomoto Atsushi, Hasegawa Yoshinori

    EUROPEAN RESPIRATORY JOURNAL  2019年9月28日 

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    記述言語:英語   会議種別:口頭発表(一般)  

  30. Immune checkpoint inhibitor for advanced or recurrent non-small cell lung cancer patients with poor performance status 国際会議

    Koyama Junji, Kimura Tomoki, Oi Hajime, Yamano Yasuhiko, Yokoyama Toshiki, Matsuda Toshiaki, Kataoka Kensuke, Matsuzawa Reiko, Fukihara Jun, Sakamoto Koji, Morise Masahiro, Hashimoto Naozumi, Kondoh Yasuhiro, Hasegawa Yoshinori

    ANNALS OF ONCOLOGY  2019年10月 

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    記述言語:英語   会議種別:ポスター発表  

    DOI: 10.1093/annonc/mdz343.108

  31. EVALUATING THE BONE MORPHOGENETIC PROTEIN PATHWAY IN PULMONARY FIBROSIS 国際会議

    Fukihara J., Maiolo S., Savaglia J., Sakamoto K., Hashimoto N., Hasegawa Y., Reynolds P.

    RESPIROLOGY  2020年6月 

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    記述言語:英語   会議種別:口頭発表(一般)  

  32. The Critical Role of Meflin-Positive Fibroblasts Against Acute Lung Injury

    Hashimoto N., Sakamoto K., Nakahara Y., Omote N., Ando A., Inoue M., Suzuki A., Fukihara J., Kusaka M., Wakahara K., Enomoto A.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2022年5月1日 

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    記述言語:英語   会議種別:口頭発表(一般)  

  33. Meflin-BMP3b Axis Is a Novel Anti-Fibrotic Pathway Against TGF-beta-Induced Lung Fibrogenesis 国際会議

    Suzuki A., Sakamoto K., Nakahara Y., Enomoto A., Hino J., Ando A., Inoue M., Omote N., Kusaka M., Fukihara J., Hashimoto N.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE  2022年5月1日 

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    記述言語:英語   会議種別:シンポジウム・ワークショップ パネル(公募)  

▼全件表示

共同研究・競争的資金等の研究課題 5

  1. 標的分子Xに対する急性肺傷害治療ペプチドの探索

    2024年10月 - 2026年9月

    国立研究開発法人日本医療研究開発機構  創薬ブースター(創薬支援ネットワーク) 

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    担当区分:研究代表者 

  2. 急性肺傷害及び続発性肺線維化を標的とした新規ペプチド薬吸入療法の開発

    2024年4月 - 2025年3月

    先端研究支援経費 

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    担当区分:研究代表者  資金種別:競争的資金

  3. 呼気に含まれる微粒子解析による革新的非侵襲呼吸器疾患診断技術の検証

    2024年4月 - 2025年3月

    橋渡し研究プログラム 

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    資金種別:競争的資金

  4. 異常上皮細胞から再考した肺線維症の病態形成と二次発癌の機序の解明

    2021年12月

    GSK ジャパン  2021年度 GSK ジャパン研究助成 

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    担当区分:研究代表者  資金種別:その他

    配分額:2000000円

  5. 新規内因性抗線維化因子メフリンを用いた肺線維症新規治療開発

    2021年4月 - 2023年3月

    ベーリンガーインゲルハイム研究助成プログラム 

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    担当区分:研究代表者  資金種別:競争的資金

科研費 7

  1. 新規肺線維化防御性細胞集団の起源と細胞運命および抗線維化機序の解明

    研究課題/研究課題番号:24K02457  2024年4月 - 2027年3月

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    阪本 考司, 榎本 篤, 石井 誠, 橋本 直純

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:18460000円 ( 直接経費:14200000円 、 間接経費:4260000円 )

    原因不明の難病である肺線維症や重症新型コロナウイルス肺炎の後遺症に共通する肺の状態である「線維化」は、死亡や永続的な呼吸障害の原因となっているため、病態の早期解明が必要です。近年、肺線維化の主な悪役と考えられて来た線維芽細胞の中にも多彩な機能を持つ亜集団が含まれることが明らかになりつつあります。その一つ、ユニークな線維化防御機能をもつ“メフリン陽性細胞”の生態は未解明である。この研究では、線維化肺に出現する“メフリン陽性細胞”が何処から来て、どのような運命をたどるのか、またどのような仕組みで肺を線維化から防御するのかの解明に挑戦します。

  2. 転写因子による効率的な肺上皮細胞直接誘導法の開発

    研究課題/研究課題番号:24K02113  2024年4月 - 2028年3月

    科学研究費助成事業  基盤研究(B)

    石井 誠, 阪本 考司

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    担当区分:研究分担者  資金種別:競争的資金

    本研究は、研究代表者がマウスで成功し特許取得した、特異的遺伝子の複数導入による直接リプログラミングで、II型肺胞上皮細胞の誘導を、ヒト細胞で目指す研究である。予備実験では、マウスのリプログラミング2因子に新たに4因子を加えることでヒト肺線維芽細胞からII型肺胞上皮細胞を誘導できる可能性を示す有望な結果を得ており、誘導効率を高めるべく、条件設定を行い、最適なリプログラミング法の確立を目指す。本研究により、肺線維症や慢性閉塞性肺疾患などの難治性肺疾患の細胞治療、再生医療の実臨床応用に向けた重要な基礎的分子基盤が確立されると考える。

  3. 間質性肺炎急性増悪病態における新規病的微小環境因子・ミトコンドリアDNAの役割

    研究課題/研究課題番号:21K08202  2021年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    阪本 考司, 芳川 豊史, 若原 恵子, 橋本 直純, 猪股 弥生

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    特発性肺線維症(IPF)は中高年に発症する進行性難治性の肺疾患である。急性増悪はIPF患者の約4割に突然発症する死亡率の高い合併症であるが、原因が分かっておらず発症の予測や治療法の開発が進んでいない。我々は最近、IPF患者さんの体液中のミトコンドリアDNAの増加が急性増悪の発症を予測しうることを発見した。これにヒントを得た本研究は、急性増悪発症のメカニズムとして肺に存在するマクロファージの異常活性化とミトコンドリアの代謝異常が関与していると仮定して、新たに急性増悪の動物モデルを作成し治療標的と診断法の開発を目指します。

  4. 好塩基球を介した2型炎症調節機構の解明ーアレルギー性・好酸球性肺疾患と肺恒常性

    研究課題/研究課題番号:21K08456  2021年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    若原 恵子, 阪本 考司, 橋本 直純

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    担当区分:研究分担者 

    本研究では、2型炎症が創傷治癒と恒常性維持、アレルギー・好酸球性疾患の正・負の両面に関わっていることに注目し、そのコントロールを行っている細胞が好塩基球であるという仮説のもと、好塩基球のフェノタイプ(病原性・非病原性)を探索すること、フェノタイプを調節する因子を探ることを目的としている。特に呼吸器疾患に注目し、肺・気道における好塩基球の役割について検討を行う。

  5. 線維芽細胞巣特異的造影マイクロCTによる肺線維症の免疫病理学診断人工知能開発研究

    研究課題/研究課題番号:20K21599  2020年7月 - 2022年3月

    日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽)

    橋本 直純, 若原 恵子, 阪本 考司, 中村 彰太, 古川 大記

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    担当区分:研究分担者  資金種別:競争的資金

    本研究課題は、病理診断が極めて重要な特発性肺線維症の肺に対して線維芽細胞巣特異的分子meflinに対するX線造影物質の金ナノ粒子標識抗体を用いた造影マイクロCTスキャンを行い線維芽細胞巣に特異的な形態学的所見と分子学的所見を放射線画像として同時に捉えることにチャレンジして、マイクロCTに免疫病理学的診断能を付与する線維芽細胞巣の画像診断アルゴリズムを確立して非侵襲的で高精度な【造影マイクロCTによる特発性肺線維症の診断と治療予測人工知能(AI)開発】につなげる革新的技術基盤の構築を行い、患者のunmetニーズを解決する挑戦的研究目的を持つものである。
    特発性肺線維症(IPF)の「線維芽細胞巣」は疾患活動性と高い相関性を示すが通常胸部computed tomography (CT)では描出できないため、IPFの治療機会を逃すとともに治療反応性を予測できない。CTで検出しうる金ナノ粒子を標識したIPF特異的分子抗体をもちいてCTで検出することにより,免疫病理学的診断能を付与する線維芽細胞巣のCT画像診断アルゴリズムを確立することを本研究課題の目的としている.
    我々は特発性肺線維症患者10例の肺組織を用いて線維芽細胞特異的分子としてmeflinの発現をIn situ hybridization(ISH)法によって局在を評価した.ISH法ではmeflin mRNAは線維芽細胞巣に限局して発現していることを同定し得た.一方, コマーシャルベースのmeflin特異的抗体を用いた免疫染色では,正常肺におけるmeflin発現の特異性を同定しえなかった.本研究の実現に抗体の調整が必要であることを把握できた.
    抗体に標識された金ナノ粒子の検出を行う適正化のために,肺線維症特異的分子に対する抗体を用いて免疫染色を行い,金ナノ粒子の検出を評価した.暗視野顕微鏡を用いて肺線維症特異的分子に対する抗体に標識された金ナノ粒子を評価した.今回,肺組織内平滑筋に発現し筋線維芽細胞特異的分子であるα-smooth muscle actin(α-SMA)に対する一次抗体に金ナノ粒子標識二次抗体を用いて免疫染色を行い,暗視野顕微鏡で金ナノ粒子発現を観察したところ検出可能であった.
    現在,マウス動物実験において,金ナノ粒子標識抗体を生体内静脈投与し,肺線維症特異的分子に結合した抗体の金ナノ粒子を検出する病理学的評価を行うとともに,CTでの検出条件の設定を進めている.よって,当初計画における研究課題1と研究課題2のデータ収集をしており,概ね順調であると考えられる.
    ・我々は特発性肺線維症患者10例の肺組織を用いてmeflinの発現をISH法で評価したところmeflin mRNAは線維芽細胞巣に限局して発現していることを同定し得たが,市販のmeflin特異的抗体を用いた免疫染色では,正常肺におけるmeflin発現の特異性を同定しえなかった.本研究の実現に抗体の調整が必要であることを把握できた.
    ・抗体に標識された金ナノ粒子の検出を行う適正化のために,肺線維症特異的分子に対する抗体を用いて免疫染色を行い,金ナノ粒子の検出を評価した.暗視野顕微鏡を用いて肺線維症特異的分子に対する抗体に標識された金ナノ粒子を評価した.今回,肺組織内平滑筋に発現し筋線維芽細胞特異的分子であるα-smooth muscle actin(α-SMA)に対する一次抗体に金ナノ粒子標識二次抗体を用いて免疫染色を行い,暗視野顕微鏡で金ナノ粒子発現を観察したところ検出可能であった.
    ・暗視野顕微鏡を用いて肺線維症特異的分子に対する抗体に標識された金ナノ粒子を評価した.今回,肺組織内平滑筋に発現し筋線維芽細胞特異的分子であるα-smooth muscle actin(α-SMA)に対する一次抗体に金ナノ粒子標識二次抗体を用いて免疫染色を行い,暗視野顕微鏡で金ナノ粒子発現を観察したところ検出可能であった.
    新型コロナウイルス感染症パンデミックの影響により,移動制限と物流の停滞が再三起こったため,計画していた実験の実施が困難であったが,マウス動物実験において金ナノ粒子標識抗体を生体内静脈投与し,肺線維症特異的分子に結合した抗体の金ナノ粒子を検出する病理学的評価を行うとともに,CTでの検出条件の設定を進めている.
    よって,当初計画における研究課題1と研究課題2のデータ収集をしており,概ね順調であると考えられる.
    ・マウス肺線維症モデルにおける金ナノ粒子を同定する研究課題の達成を目指して,ヒト肺線維症検体を用いた金ナノ粒子の同定を同時に達成する.その一方で,暗視野顕微鏡とマイクロCTでの金ナノ粒子の検出の感度の相違が想定されるため,最適化した金ナノ粒子の標識が重要な課題と考えている.
    ・金ナノ粒子をマイクロCTで検出して免疫病理学的診断能を付与することは,対象疾患に疾患特異的病理所見・疾患特異的抗原・その特異的抗体がある場合に応用できるものであり、既存の学術の体系や方向を大きく変革・転換させる潜在性を有する.
    ・「線維芽細胞巣」の同定は本研究において重要な課題目標であるが,「線維芽細胞巣」特異的抗体が樹立・確立できない場合やマイクロCTでの検出感度以下の発現であった場合には,肺線維症特異的分子に対する金ナノ粒子標識抗体を用いて,マイクロCTでの免疫病理学的診断能付与の確立を先行させる.

  6. 呼吸器疾患患者に対するリハビリテーション方策(振動刺激療法)の新規開拓

    研究課題/研究課題番号:20K10709  2020年4月 - 2024年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    井上 貴行

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    担当区分:研究分担者  資金種別:競争的資金

    従来のリハビリテーション(リハ)の主要な方策は運動療法であるが、呼吸器疾患患者には軽労作でも重度の低酸素症状を来す患者や循環動態の不安定な患者など積極的な運動療法が行えない症例が数多く存在するため、運動療法の代替手段の開発が必要となっている。一方、振動刺激(VS)には筋萎縮の抑制や筋力の増大などの効果があることが報告されており、運動療法の代替手段となり得ることが実証されつつある。そこで本研究は、呼吸器疾患患者に対してVSを用いたリハを行うことで、筋萎縮や筋力、体力、日常生活動作、生活の質の低下を予防および抑制、さらには改善する効果が得られるかを網羅的に無作為化比較対照試験により検証する。

  7. 老化関連長鎖ノンコーディングRNAの制御による肺線維症難治性の克服

    研究課題/研究課題番号:18K15948  2018年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業  若手研究

    阪本 考司

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    加齢関連難治肺疾患である肺線維症において、線維化誘導性の細胞老化に陥った線維芽細胞が難治性の病態形成に寄与するとの仮説から、新規の細胞運命決定である長鎖ノンコーディングRNA(lncRNA)に注目し、同病態の線維芽細胞の細胞老化を制御するlncRNA群を同定することで疾患の新たな治療介入標的や疾患のバイオマーカーにすることを目指している。R2年度は以下の研究を進めた。
    lncRNAの発現調節による細胞表現型制御:昨年度に同定したIPF関連lncRNAの一つXを線維芽細胞に形質導入し、向線維化性や細胞老化の表現型を評価したところ、lncRNA-Xの発現回復はIPF由来の老化線維芽細胞においてp16/p21などの老化関連制御因子の発現抑制を誘導することが分かった。さらに、lncRNA-Xの遺伝子欠損マウスを作成し、その肺の表現型を評価した。lncRNA-X欠失細胞の肺組織では老化関連βガラクトシダーゼ染色陽性の老化細胞の増多が認められた。さらにlncRNA-X欠失マウスにブレオマイシンを用いて肺線維症を誘導し、線維化の程度を検討している。
    さらにIPFの病態形成に関わる新たな機能性lncRNA候補を同定したため、予備的な機能解析を開始した。
    また細胞老化により病態形成を媒介するミトコンドリアDNAの肺線維症へ寄与を解析した。ミトコンドリア代謝異常を反映して、IPFの患者由来の血清ではミトコンドリアDNAの濃度が上昇しており、その増多がIPF患者の不良な予後、および急性増悪の発症と相関することを発見した。
    バイオマーカーの検索のための臨床検体収集は、コロナウイルスの蔓延による受診抑制、臨床検体への取り扱いの制限などで遅れている。
    研究計画を一年延長して最終年度は血清からのlncRNA定量検出を進める。マウスモデルについては新たに細胞老化に関わる経路を制御する因子の欠損マウスでの解析を進める。

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担当経験のある科目 (本学) 10

  1. 臓器別臨床講義 呼吸器

    2024

  2. 臓器別臨床講義 呼吸器

    2023

  3. 現代医学入門

    2023

  4. 臓器別臨床講義 呼吸器

    2022

  5. 臓器別臨床講義 呼吸器

    2021

  6. 生涯健康と医学「大気環境と呼吸器疾患」

    2020

  7. 臓器別臨床講義 呼吸器

    2020

  8. 臓器別臨床講義 呼吸器

    2019

  9. 臓器別臨床講義 呼吸器

    2018

  10. 臓器別臨床講義 呼吸器

    2017

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社会貢献活動 1

  1. 特発性間質性肺炎~最新の治療と日常生活の注意点について~

    役割:講師

    名古屋市瑞穗保健センター  難病講演会  2018年7月

メディア報道 4

  1. The cells combating a deadly lung disease インターネットメディア

    American Association for the Advancement of Science (AAAS)  EurekAlert  https://www.eurekalert.org/news-releases/773991  2021年7月

  2. ナノ素材による健康被害のメカニズムが明らかに インターネットメディア

    名古屋大学 学術研究・産学官連携推進本部  名大研究フロントライン  https://www.youtube.com/watch?v=QKIcuDphFQc&t=1s  2021年7月

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    執筆者:本人以外 

  3. 人工微粒子、細胞に有害活性酸素 肺の炎症原因に、名古屋大 インターネットメディア

    共同通信  地方紙と共同通信のよんななニュース  https://nordot.app/778048216281759744?c=39546741839462401  2021年6月

  4. 名古屋大、指定難病「特発性肺線維症」の疾患進行の運命を握る線維芽細胞を世界で初めて同定~特発性肺線維症克服へ向けての新展開~ インターネットメディア

    日経バイオテク  https://bio.nikkeibp.co.jp/atcl/release/21/05/31/10796/  2021年5月

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    執筆者:本人以外