The role of ADAM17 in squamous cell lung cancer

2013 Fiscal Year Final Research Report

• Project/Area Number: 22501051
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Showa University
• Principal Investigator: SIRAI Takao 昭和大学, 医学部, 助教 (90384362)
• Co-Investigator(Kenkyū-buntansha): YAMAOKA Toshimitsu 昭和大学, 腫場分子生物学研究所, 講師 (40384359) ; OHMORI Tohru 昭和大学, 腫場分子生物学研究所, 准教授 (10276529) ; HIROSE Takashi 昭和大学, 医学部, 准教授 (40307038) ; KADOKURA Mitsutaka 昭和大学, 医学部, 教授 (60214417) ; ADACHI Mitsuru 昭和大学, 医学部, 教授 (10095870)
• Project Period (FY): 2010-10-20 – 2014-03-31
• Keywords: 喫煙者肺癌 / 扁平上皮肺癌

Research Abstract

Epidermal growth factor receptor (EGFR) overexpression and aberrant activation are frequently identified in non small cell lung carcinoma (NSCLC). Although EGFR-targeted therapies (i.e.: EGFR-TKIs, and anti-EGFR antibody) are used, the prognosis of NSCLC remains poor. ADAM17 induces activation of EGFR through EGF-like ligand cleavage. We hypothesized that the inflammatory cytokines and EGF-like ligands might up-regulate the expression of EGFR via ADAM17, leading to the resistance to EGFR-TKIs in squamous cell carcinoma of lung. These findings promisingly indicate additional therapeutic strategies and the understanding of tumorigenesis for NSCLC.

Research Products

• [Journal Article] Evaluation of the safety and efficacy of combination chemotherapy with vinorelbine and platinum agents for patients with non-small cell lung cancer with interstitial lung disease (2012)
  • Author(s): Okuda K, Hirose T, Oki Y, Murata Y, Kusumoto S, Sugiyama T, Ishida H, Shirai T, Nakashima M, Yamaoka T, Ohnishi T, Ohmori T
  • Journal Title: Anticancer Res. Volume: 32(12) Pages: 5475-80
  • URL: http://ar.iiarjournals.org/content/32/12/5475.long
  • Peer Reviewed
• [Journal Article] Relationship of circulating tumor cells to the effectiveness of cytotoxic chemotherapy in patients with metastatic non-small-cell lung cancer (2012)
  • Author(s): Hirose T, Murata Y, Oki Y, Sugiyama T, Kusumoto S, Ishida H, Shirai T, Nakashima M, Yamaoka T, Okuda K, Ohnishi T, Ohmori T
  • Journal Title: Oncol Res. Volume: 20(2-3) Pages: 131-7
  • Peer Reviewed
• [Journal Article] 進行再発非小細胞肺癌に対するセカンドライン化学療法の検討 (2012)
  • Author(s): 白井崇生, 慶瀬敬, 村田泰規, 大木康成, 楠本壮三郎, 杉山智英, 石田博雄, 中属賢尚, 大西司, 山岡利光, 大森亨, 奥田健太郎
  • Journal Title: 昭和医学会雑誌 Volume: 72巻4号 Pages: 446-452
  • Peer Reviewed
• [Journal Article] Myelosuppression induced by concurrent chemoradiotherapy as a prognostic factor for patients with locally advanced non-small cell lung cancer (2011)
  • Author(s): Kishida Y, Hirose T, Shirai T, Sugiyama T, Kusumoto S, Yamaoka T, Okuda K, Adachi M, Nakamura A
  • Journal Title: Oncol Lett. Volume: 2(5) Pages: 949-955
  • Peer Reviewed
• [Journal Article] Phase II trial of the combination of carboplatin and irinotecan in elderly patients with small -cell lung cancer (2011)
  • Author(s): Murata Y, Hirose T, Yamaoka T, Shirai T, Okuda K, Sugiyama T, Kusumoto S, Nakashima M, Ohmori T, Adachi M
  • Journal Title: Eur J Cancer Volume: 47(9) Pages: 1336-42
  • DOI: 10.1016/j.ejca.2011.03.007
  • Peer Reviewed
• [Journal Article] Phase II trial of amrubicin and carboplatin in patients with sensitive or refractory relapsed small -cell lung cancer (2011)
  • Author(s): Hirose T, Nakashima M, Shirai T, Kusumoto S, Sugiyama T, Yamaoka T, Okuda K, Ohnishi T, Ohmori T, Adachi M
  • Journal Title: Lung Cancer Volume: 73(3) Pages: 345-50
  • DOI: 10.1016/j.lungcan.2010.12.015
  • Peer Reviewed
• [Journal Article] Phase II study of S-1,a novel oral fluoropyrimidine,and biweekly administration of docetaxel for previously treated advanced non-small-cell lung cancer (2011)
  • Author(s): Oki Y, Hirose T, Yamaoka T, Kusumoto S, Shirai T, Sugiyama T, Okuda K, Nakashima M, Murata Y, Ohmori T, Adachi M
  • Journal Title: Cancer Chemother Pharmacol Volume: 67(4) Pages: 791-7
  • DOI: 10.1007/s00280-010-1382-1
  • Peer Reviewed
• [Journal Article] Are levels of pro-gastrin-releasing peptide or neuron-specific enolase at relapse prognostic factors after relapse in patients with small -cell lung cancer? (2011)
  • Author(s): Hirose T, Okuda K, Yamaoka T, Ishida K, Kusumoto S, Sugiyama T, Shirai T, Ohnshi T, Ohmori T, Adachi M
  • Journal Title: Lung Cancer Volume: 71(2) Pages: 224-8
  • DOI: 10.1016/j.lungcan.2010.05.004
  • Peer Reviewed
• [Journal Article] 急速に進展し心タンポナーデを起こした心外膜原発多形型悪性線維性組織球腫/未分化多形細胞肉腫Pleomorphic malignant fibrous histiocytoma/Undifferentiated highgrade pleomorphic sarcomaの1剖検例 (2011)
  • Author(s): 塩沢英輔, 大井正也, 慶田真規, 白井崇生, 前田朱美, 矢持淑子, 瀧本雅文, 太田秀一
  • Journal Title: 診断病理 Volume: 28巻4号 Pages: 1345-6431, 247-253
  • Peer Reviewed
• [Journal Article] The UGT1A1*28 genotype and the toxicity of low -dose irinotecan in patients with advanced lung cancer (2010)
  • Author(s): Sugiyama T, Hirose T, Kusumoto S, Shirai T, Yamaoka T, Okuda K, Ohnishi T, Ohmori T, Adachi M
  • Journal Title: Oncol Res. Volume: 18(7) Pages: 337-42
  • Peer Reviewed
• [Presentation] 小細胞肺癌患者における末梢血中がん細胞数と予後の検討 (2013)
  • Author(s): 白井崇生, 慶瀬敬, 村田泰規, 大木康成, 楠本壮三郎, 杉山智英, 石田博雄, 中属賢尚, 山岡利光, 奥田健太郎, 大西司, 大森亨, 相良博典
  • Organizer: 日本肺癌学会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-21
• [Presentation] 非小細胞肺癌におけるエルロチニプとゾレドロン酸併用療法の有用性に関する後方視的解析 (2013)
  • Author(s): 大木康成, 慶瀬敬, 白井崇生, 村田泰規, 杉山智英, 楠本壮三郎, 石田博雄, 中属賢尚, 山岡利光, 奥田健太郎, 大西司, 大森亨, 相良博典
  • Organizer: 日本肺癌学会
  • Place of Presentation: 東京
  • Year and Date: 2013-11-21
• [Presentation] 再発あるいは前治療無効小細胞肺癌に対するtopotecan、carboplatin併用第II相試験 (2013)
  • Author(s): 慶瀬敬, 白井崇生, 杉山智英, 村田泰則, 大木康成, 楠本壮三郎, 中属賢尚, 奥田健太郎, 田村厚久, 大田健
  • Organizer: 日本癌治療学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2013-10-24
• [Presentation] Carboplatin+Paclitaxel+Bevacizumabによる化学療法中にIII度房室プロックをきたした肺腺癌症例 (2012)
  • Author(s): 白井崇生, 慶瀬敬, 大木康成, 村田泰規, 楠本壮三郎, 杉山智英, 石田博雄, 中属賢尚, 奥田健太郎, 大西司, 足立満, 山岡利光, 大森亨
  • Organizer: 日本肺癌学会
  • Place of Presentation: 岡山
  • Year and Date: 2012-11-08
• [Presentation] 標準治療不応進行非小細胞肺癌に対するペプチドワクチン療法(Cancer vaccination trial with novel mult iple peptides in previously treated advanced non-small-cell lung cancer (NSCLC)) (2012)
  • Author(s): 慶瀬敬, 野田秀裕, 奥田健太郎, 阿部誠治, 大戸祐治, 杉山智英, 石田博雄, 白井崇生, 中属賢尚, 山岡利光, 大森亨, 吉田浩三, 中村祐輔
  • Organizer: 日本癌学会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-19
• [Presentation] SPC/TNFトランスジエニックマウスモデルにおけるEGFRチロシンキナーゼ阻害剤による肺組織のアポトーシス誘導機構の検討 (2012)
  • Author(s): 山岡利光, 大木康成, 村田泰規, 杉山智英, 石田博雄, 白井崇生, 中属賢尚, 奥田健太郎, 大西司, 慶瀬敬, 大森亨
  • Organizer: 日本呼吸器学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-19
• [Presentation] EGFR遺伝子変異陽性の肺腺癌患者に対する、ゲフィチニプとゾレドロン酸併用療法の有用性に関する後方視的解析 (2012)
  • Author(s): 大木康成, 村田泰規, 杉山智英, 楠本壮三郎, 石田博雄, 白井崇生, 中属賢尚, 山岡利光, 奥田健太郎, 大西司, 大森亨, 慶瀬敬
  • Organizer: 日本呼吸器学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-19
• [Presentation] 手術を回避した高齢者気胸の検討 (2012)
  • Author(s): 白井崇生, 慶瀬敬, 大木康成, 村田泰規, 杉山智英, 石田博雄, 中属賢尚, 大西司, 氷室直哉, 富田由里, 慶野素子, 片岡大輔, 野中誠, 門倉光隆
  • Organizer: 日本呼吸器学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-19
• [Presentation] 気道上皮細胞と非小細胞肺癌細胞におけるTACE/EGFR-リガンドを介したTNFによるEGFRのトランス活性化の機序検討(TNF transactivates phospho-tyrosine 1068 of EGFR through TACE/EGFR-ligand dependent mechanism) (2011)
  • Author(s): 山岡利光, 大木康成, 楠本壮三郎, 杉山智英, 白井崇生, 中属賢尚, 奥田健太郎, 慶瀬敬, 大森亨, 大西司, 足立満
  • Organizer: 日本癌学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 進行非小細胞肺癌の生存期間が延長しているのはなぜか? (2010)
  • Author(s): 白井崇生, 慶瀬敬, 楠本壮三郎, 杉山智英, 中属賢尚, 山岡利光, 奥田健太郎, 大西司, 大森亨, 足立満
  • Organizer: 日本肺癌学会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-12