The analysis of mechanisms of interstitial lung disease induced by epidermal growth factor receptor inhibitor.

• Project/Area Number: 19790552
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Tohoku University
• Principal Investigator: INOUE Akira Tohoku University, 病院, 助教 (70361087)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,220,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: 薬剤性肺障害 / 肺癌 / ゲフィチニブ / EGFR阻害剤 / サーファクタント蛋白

Research Abstract

EGFR阻害剤ゲフィチニブを経口投与したモデルマウスにおいて、気管支肺胞洗浄液中の炎症細胞数の増加、肺サーファクト蛋白(特にSP-A)の発現減少およびLPS追加投与時の肺組織中炎症所見の増悪が認められ、EGFR阻害剤による薬剤性肺障害の発症機序にSP-Aが関与している可能性が示唆された。それらの炎症所見はヒトSP-Aの補充投与によって改善を認め、肺障害患者への治療につながる可能性が示唆された。

Research Products

• [Journal Article] First-line Gefitinib for Advanced Non-Small Cell Lung Cancer Patients Harboring Epidermal Growth Factor Receptor Mutations without Indication for Chemotherapy. (2009)
  • Author(s): Inoue A, et al
  • Journal Title: J Clin Oncol 27 Pages: 1394-1400
  • Peer Reviewed
• [Journal Article] First-line Gefitinib for Advanced Non-Small Cell Lung Ca ncer Patients Harboring Epidermal Growth Factor Recept or Mutations without Indication for Chemotherapy (2009)
  • Author(s): Inoue A
  • Journal Title: J Clin Oncol 27 Pages: 1394-1400
  • Peer Reviewed
• [Journal Article] Suppression of surfactant protein A by an epidermal growth factor receptor tyrosine kinase inhibitor exacerbates lung inflammation. (2008)
  • Author(s): Inoue A, et al
  • Journal Title: Cancer Sci 99 Pages: 1679-1684
  • NAID: 10024010194
  • Peer Reviewed
• [Journal Article] Randomized Phase II Trial Comparing Amrubicin with Topotecan in Patients with Previously Treated Small Cell Lung Cancer: Report of North Japan Lung Cancer Study Group Trial 0402. (2008)
  • Author(s): Inoue A, et al
  • Journal Title: J Clin Oncol 26 Pages: 5401-5406
  • Peer Reviewed
• [Journal Article] Adenocarcinoma with epidermal growth factor receptor gene mutations in three siblings. (2008)
  • Author(s): Sakakibara T,・・・,Inoue A, et al
  • Journal Title: J Thorac Oncol 3 Pages: 311-313
  • Peer Reviewed
• [Journal Article] Sensitive and Specific New Enzyme-Linked Immunosorbent Assay for N-ERC/Mesothelin Increases its Potential as a Useful Serum Tumor Marker for Mesothelioma. (2008)
  • Author(s): Shiomi K, ・・・, Inoue A, et al
  • Journal Title: Clin Cancer Res 14 Pages: 1431-1437
  • Peer Reviewed
• [Journal Article] Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell lung cancer. (2008)
  • Author(s): Maruyama R, ・・・, Inoue A, et al
  • Journal Title: J Clin Oncol 26 Pages: 4244-4252
  • Peer Reviewed
• [Journal Article] siRNA targeting against EGFR, a promising candidate for a novel therapeutic application to lung adenocarcinoma. (2008)
  • Author(s): Yamanaka S, ・・・, Inoue A, et al
  • Journal Title: Pathobiology 75 Pages: 2-8
  • Peer Reviewed
• [Journal Article] Successful treatment of carcinomatous meningitis with gefitinib in a patient with lung adenocarcinoma harboring a mutated EGF receptor gene. (2008)
  • Author(s): Fukuhara T, ・・・, Inoue A, et al
  • Journal Title: Tohoku J Exp Med 214 Pages: 359-363
  • NAID: 10024167697
  • Peer Reviewed
• [Journal Article] Suppression of surfactant protein A by an epidermal grow th factor receptor tyrosine kinase inhibitor exacerbates lu ng inflammation (2008)
  • Author(s): Inoue A
  • Journal Title: Cancer Sci 99 Pages: 1679-1684
  • NAID: 10024010194
  • Peer Reviewed
• [Journal Article] Successful treatment of carcinomatous meningitis with gef itinib in a patient withlung adenocarcinoma harboring a mutated EGF receptor gene (2008)
  • Author(s): Fukuhara T
  • Journal Title: Tohoku J Exp Med 214 Pages: 359-363
  • Peer Reviewed
• [Journal Article] Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell 1 ung cancer (2008)
  • Author(s): Maruyama R
  • Journal Title: J Clin Oncol 26 Pages: 4244-4252
  • Peer Reviewed
• [Journal Article] Randomized Phase II Trial Comparing Amrubicin with To potecan in Patients with Previously Treated Small Cell L ung Cancer : Report of North Japan Lung Cancer Study G rout Trial 0402 (2008)
  • Author(s): Inoue A
  • Journal Title: J Clin Oncol 26 Pages: 5401-5406
  • Peer Reviewed
• [Journal Article] Adenocarcinoma with epidermal growth factor receptor gene mutations in three siblings (2008)
  • Author(s): Sakakibara T
  • Journal Title: J Thorac Oncol 3・3 Pages: 311-313
  • Peer Reviewed
• [Journal Article] siRNA targeting against EGFR, a promising candidate for a novel therapeutic application to lung adenocarcinoma (2008)
  • Author(s): Yamanaka S
  • Journal Title: Pathobiol. 75・1 Pages: 2-8
  • Peer Reviewed
• [Journal Article] ensitive and Specific New Enzyme-Linked Immunosorbent Assay for N-ERC/Mesothelin Increases its Potential as a Useful Serum Tumor Marker for Mesothelioma (2008)
  • Author(s): Shiomi K
  • Journal Title: Clin Cancer Res 14・5 Pages: 1431-1437
  • Peer Reviewed
• [Journal Article] Phase III Study (V-15-32) of Gefitinib (IRESSA) Versus Docetaxel in Previously Treated Japanese Patients With Non-Small-Cell Lung Cancer (2008)
  • Author(s): Ichinose Y
  • Journal Title: J Clin Oncol In press
  • Peer Reviewed
• [Presentation] I-CAMP: EGFR遺伝子変異陽性NSCLCに対するゲフィチニブ治療の統合解析 (2009)
  • Author(s): 井上彰、朝比奈肇、砂長則明、須谷顕尚、吉田公秀、岡本勇、杉尾賢二、森田智視、小林国彦、貫和敏博、福岡正博
  • Organizer: 第7回日本臨床腫瘍学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-03-20
• [Presentation] Gefitinib provides an beneficial treatment to poor PS or super-elderly patients with EGFR mutation-positive NSCLC (North-East Japan Gefitinib Study Group). (2008)
  • Author(s): Inoue A, et al
  • Organizer: 33^r^d European Society of Medical Oncology, abstract 1391
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 2008-12-09
• [Presentation] Gefitinib provides an beneficial treatment to poor PS or s uper-elderly patients with EGFR mutation-positive NSCL C (North-East Japan Gefitinib Study Group) (2008)
  • Author(s): Inoue A
  • Organizer: 33^<rd> European Society of Medical Oncology
  • Place of Presentation: Stockholm(スウェーデン)
  • Year and Date: 2008-09-15
• [Presentation] Phase II study of 1^s^t line gefitinib for > PS 3 patient with advanced NSCLC with EGFR mutations. (2007)
  • Author(s): Inoue A, et al
  • Organizer: The Meeting of Reunion Franco-Japonese on Clinical Oncology
  • Place of Presentation: Toulouse, France
  • Year and Date: 2007-09-17
• [Presentation] 肺腺癌EGFR活性型変異:基礎的意義と臨床試験での検証 (2007)
  • Author(s): 井上彰
  • Organizer: 第47回日本呼吸器学会総会教育講演
  • Place of Presentation: 東京
  • Year and Date: 2007-05-10