PI3K-PTEN imbalance is a potential new therapeutic target in COPD

• Project/Area Number: 15K09185
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Osaka City University
• Principal Investigator: Asai Kazuhisa 大阪市立大学, 大学院医学研究科, 講師 (10382053)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 慢性閉塞性肺疾患 / PI3K / PTEN / COPD / 気道炎症

Outline of Final Research Achievements

The PI3K (Phosphoinositide 3-kinase) -Akt signaling pathway is involved in angiogenesis,apoptosis,cell proliferation,production of inflammatory cytokines. And there is antagonistic mechanism by PTEN (Phosphatase and Tensin Homolog Deleted from Chromosome 10).
Airway epithelial cells were collected from 22 healthy non-smokers,31 healthy smokers, and 49 COPD patients.The expression of PI3K, PTEN in airway epithelial cells and its involvement in COPD pathogenesis were examined. In COPD patients, PTEN expression was significantly decreased, showing a significant inverse correlation with smoking history and significant correlation with pulmonary function testing.This suggested that PTEN was involved in COPD pathogenesis.

Research Products

• [Journal Article] Correlation between disease activity and serum ferritin in clinically amyopathic dermatomyositis with rapidly-progressive interstitial lung disease: a case report (2018)
  • Author(s): Yamada Kazuhiro、Asai Kazuhisa、Okamoto Atsuko、Watanabe Tetsuya、Kanazawa Hiroshi、Ohata Mai、Ohsawa Masahiko、Hirata Kazuto
  • Journal Title: BMC Res Notes Volume: 11 Pages: 1-2
  • DOI: 10.1186/s13104-018-3146-7
  • Peer Reviewed / Open Access
• [Journal Article] PIK3CA mutation as a distinctive genetic feature of non-small cell lung cancer with chronic obstructive pulmonary disease: a comprehensive mutational analysis from a multi-institutional cohort (2017)
  • Author(s): Sawa Kenji、Koh Yasuhiro、Kawaguchi Tomoya、Kambayashi Satoshi、Asai Kazuhisa、Mitsuoka Shigeki、Kimura Tatsuo、Yoshimura Naruo、Yoshimoto Naoki、Kubo Akihito、Saka Hideo、Matsumura Akihide、Wanibuchi Hideki、Yamamoto Nobuyuki、Nishiyama Noritoshi、Hirata Kazuto
  • Journal Title: Lung Cancer Volume: 112 Pages: 96-101
  • DOI: 10.1016/j.lungcan.2017.07.039
  • Peer Reviewed / Open Access
• [Journal Article] Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related to emphysema associated with chronic obstructive pulmonary disease. (2017)
  • Author(s): Yukari Sugiyama、Kazuhisa Asai、Kazuhiro Yamada、Yuko Kureya、Naoki Ijiri、Tetsuya Watanabe、Hiroshi Kanazawa、Kazuto Hirata
  • Journal Title: Int J Chron Obstruct Pulmon Dis. Volume: 12 Pages: 765-772
  • NAID: 120006330653
  • Peer Reviewed / Open Access
• [Journal Article] Identification of a Novel Rhizopus-specific Antigen by Screening with a Signal Sequence Trap and Evaluation as a Possible Diagnostic Marker of Mucormycosis (2017)
  • Author(s): Sato K., Oinuma K., Niki M., Yamagoe S., Miyazaki Y., Asai K., Yamada K., Hirata K., Kaneko Y. and Kakeya H.
  • Journal Title: Med Mycol Volume: 印刷中 Pages: 713-719
  • DOI: 10.1093/mmy/myw146
  • NAID: 120006533842
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Atrial natriuretic peptide protects against bleomycin-induced pulmonary fibrosis via vascular endothelial cells in mice (2017)
  • Author(s): Okamoto A, Nojiri T, Konishi K, Tokudome T, Miura K, Hosoda H, Hino J, Miyazato M, Kyomoto Y, Asai K, Hirata K, Kangawa K
  • Journal Title: Respiratory Research Volume: 18 Pages: 1-1
  • DOI: 10.1186/s12931-016-0492-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related to emphysema associated with chronic obstructive pulmonary disease. (2017)
  • Author(s): Sugiyama Y, Asai K, Yamada K, Kureya Y, Ijiri N, Watanabe T, Kanazawa H, Hirata K
  • Journal Title: International Journal of Chronic Obstructive Pulmonary Disease Volume: 12 Pages: 765-772
  • NAID: 120006330653
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An Intrinsic Strain of Colistin-resistant <i>Acinetobacter</i> Isolated from a Japanese Patient (2016)
  • Author(s): Takizawa E., Yamada K., Oinuma K., Sato K., Niki M., Namikawa H., Fujimoto H., Asai K., Kaneko Y. and Kakeya H.
  • Journal Title: Intern. Med. Volume: 55 Issue: 16 Pages: 2301-2306
  • DOI: 10.2169/internalmedicine.55.6807
  • NAID: 130005169382
  • ISSN: 0918-2918
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of indacaterol/glycopyrronium in Japanese patients with COPD: Pooled analysis of SHINE and ARISE. (2016)
  • Author(s): Asai K, Hirata K, Hashimoto S, Fukuchi Y, Kitawaki T, Ikeda K, Fogel R, Banerji D.
  • Journal Title: Respir Investig. Volume: 54 Pages: 428-435
  • DOI: 10.1016/j.resinv.2016.06.006
  • Peer Reviewed
• [Journal Article] Epidermal growth factor receptor tyrosine kinase inhibitors in previously treated advanced non-small-cell lung cancer with wild-type EGFR. (2016)
  • Author(s): Mitsuoka S, Kawaguchi T, Kubo A, Isa S, Asai K, Uji M, Watanabe T, Sawa K, Yoshimoto N, Oka T, Nakai T, Suzumura T, Tanaka H, Matsuura K, Kimura T, Yoshimura N, Kudoh S, Hirata K.
  • Journal Title: Expert Opin Pharmacother. Volume: 17 Pages: 193-203
  • DOI: 10.1517/14656566.2016.1109635
  • Peer Reviewed
• [Journal Article] Impaired nuclear factor erythroid 2-related factor 2 expression increases apoptosis of airway epithelial cells in patients with chronic obstructive pulmonary disease due to cigarette smoking. (2016)
  • Author(s): Yamada K, Asai K, Nagayasu F, Sato K, Ijiri N, Yoshii N, Imahashi Y, Watanabe T, Tochino Y, Kanazawa H, Hirata K.
  • Journal Title: BMC Pulm Med. Volume: 16 Pages: 27-27
  • DOI: 10.1186/s12890-016-0189-1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Irisin, a newly discovered myokine, is a novel biomarker associated with physical activity in patients with chronic obstructive pulmonary disease. (2015)
  • Author(s): Ijiri N, Kanazawa H, Asai K, Watanabe T, Hirata K.
  • Journal Title: Respirology Volume: 20 Pages: 612-617
  • DOI: 10.1111/resp.12513
  • Peer Reviewed
• [Journal Article] Phase II study of a combination regimen of gefitinib and pemetrexed as first-line treatment in patients with advanced non-small cell lung cancer harboring a sensitive EGFR mutation. (2015)
  • Author(s): Yoshimura N, Kudoh S, Mitsuoka S, Yoshimoto N, Oka T, Nakai T, Suzumira T, Matusura K, Tochino Y, Asai K, Kimura T, Kawaguchi T, Hirata K.
  • Journal Title: Lung Cancer Volume: 90 Pages: 65-70
  • DOI: 10.1016/j.lungcan.2015.06.002
  • Peer Reviewed
• [Journal Article] Pentraxin-3 as a Biomarker for Febrile Neutropenia in Patients with Lung Cancer. (2015)
  • Author(s): Takeda N, Asai K, Ijiri N, Yamamoto N, Watanabe T, Kamoi H, Kanazawa H, Hirata K.
  • Journal Title: Osaka City Med J. Volume: 61 Pages: 43-52
  • NAID: 120006493313
  • Peer Reviewed
• [Journal Article] Primary Pleural Synovial Sarcoma Treated with Pazopanib (2015)
  • Author(s): Sugitani A, Asai K, Kojima K, Eguchi Y, Kawaguchi T, Ohsawa M, Hirata K.
  • Journal Title: Intern. Med. Volume: 54 Issue: 16 Pages: 2051-2055
  • DOI: 10.2169/internalmedicine.54.3570
  • NAID: 130005092891
  • ISSN: 0918-2918
  • Peer Reviewed
• [Journal Article] The Macroscopic Appearance of Computed Tomography-guided Needle Biopsy Specimens Correlates with Tumor Metastasis in Non-small Cell Lung Cancer. (2015)
  • Author(s): Toshiyuki N, Kimura T, Suzumura T, Yoshimoto N, Oka T, Yamamoto N, Matsuura K, Mitsuoka S, Asai K, Tochino Y, Yoshimura N, Kawaguchi T, Kudoh S, Matsuoka T, Ohsawa M, Hirata K.
  • Journal Title: Osaka City Med J. Volume: 61 Pages: 105-112
  • NAID: 120006493307
  • Peer Reviewed
• [Presentation] Relationship between peripheral blood irisin levels and muscle mass, sarcopenia, and pulmonary function measurements in COPD subjects. (2016)
  • Author(s): Shinya Yoshida, Kazuhisa Asai, Yukari Sugiyama, Yohkoh Kyomoto, Tamaki Kawamoto, Kanako Sato, Yuko Kureya, Atsuko Okamoto, Kazuhiro Yamada, Naoko Yoshii, Tetsuya Watanabe, Masato Uji, Hiroshi Kanazawa, Kazuto Hirata
  • Organizer: 21st Congress of the Asian Pacific Society of Respirology
  • Place of Presentation: バンコク（タイ）
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Relationships between sarcopenia and pulmonary function, exercise capacity, and prognosis in patients with COPD (2016)
  • Author(s): yukari sugiyama, kazuhisa asai, shinya yoshida, yohkoh kyomoto, tamaki kawamoto, kanako sato, yuko kureya, atsuko okamoto, kazuhiro yamada, naoko yoshii, tetsuya watanabe, masato uji, kazuto hirata,
  • Organizer: ERS International Congress 2016
  • Place of Presentation: ロンドン（イギリス）
  • Year and Date: 2016-09-03
  • Int'l Joint Research
• [Presentation] Atrial Natriuretic Peptide Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice (2016)
  • Author(s): Atsuko Okamoto , Kazuhisa Konishi , Takashi Nojiri , Hiroshi Hosoda , Takeshi Tokudome , Kazuhisa Asai , Kazuto Hirata , Kenji Kangawa
  • Organizer: American Thoracic Society 2016 International Conference
  • Place of Presentation: サンフランシスコ（アメリカ合衆国）
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] Expression Levels of Developmenal Genes Distinguish Non Specific Interstitial Pneumonia from Idiopathic Pulmonary Fibrosis and Highlight Potential Diagnostic Markers (2016)
  • Author(s): Kazuhisa Konishi , Yasuhiro Kondoh , Hiroyuki Taniguchi , Atsuko Okamoto , Kathleen O. Lindell , Kazuhisa Asai , Yingze Zhang , Kevin Gibson , Naftali Kaminski , Dong Soon Kim
  • Organizer: American Thoracic Society 2016 International Conference
  • Place of Presentation: サンフランシスコ（アメリカ合衆国）
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] Decreased Nuclear Factor Erythroid 2-Related Factor 2 Expression Enhances Apoptosis of Airway Epithelial Cells in Patients with Chronic Obstructive Pulmonary Disease (2016)
  • Author(s): Kazuhiro Yamada , Kazuhisa Asai , Yuko Kubo , Yohkoh Kyomoto , Tamaki Kawamoto , Shinya Yoshida , Kanako Sato , Norio Yamamoto , Naoko Yoshii , Tetsuya Watanabe , Masato Uji , Kazuto Hirata
  • Organizer: American Thoracic Society 2016 International Conference
  • Place of Presentation: サンフランシスコ（アメリカ合衆国）
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] A case of rapidly progressed primary pleural synovial sarcoma. (2015)
  • Author(s): Kazuhisa Asai, Kanako Sato, Yuko Kubo, Atsuko Okamoto, Kazuhiro Yamada, Naoko Yoshii, Tetsuya Watanabe, Kazuhisa Konishi, Masato Uji, Kazuto Hirata
  • Organizer: Chest Annual Meeting 2015
  • Place of Presentation: モントリオール（カナダ）
  • Year and Date: 2015-10-25
  • Int'l Joint Research
• [Presentation] Global gene expression analyses highlight the role of cellular plasma remodeling as a molecular function of airway epithelium in response to interleukin-13 treatment. (2015)
  • Author(s): Yuko Kureya, Kazuhisa Konishi, Kazuhiro Yamada, Tetsuya Watanabe, Masato Uji, Kazuhisa Asai, Hiroshi Kanazawa, and Kazuto Hirata
  • Organizer: European Respiratory Society International Congress 2015
  • Place of Presentation: アムステルダム（オランダ）
  • Year and Date: 2015-09-26
  • Int'l Joint Research
• [Book] Chronic Obstructive Pulmonary Disease: A Systemic Inflammatory Disease (2016)
  • Author(s): Hiroyuki Nakamura, Kazutetsu Aoshiba, et al.
  • Total Pages: 352
  • Publisher: Springer