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2013 Fiscal Year Final Research Report

Elucidation of trans-activation mechanism from TRAIL receptor to EGFR

Research Project

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Project/Area Number 23590308
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionShowa University

Principal Investigator

OHMORI Tohru  昭和大学, 腫瘍分子生物学研究所, 准教授 (10276529)

Co-Investigator(Kenkyū-buntansha) YAMAOKA Toshimitsu  昭和大学, 腫瘍分子生物学研究所, 講師 (40384359)
HIROSE Takashi  昭和大学, 内科学講座呼吸器内科学分野, 准教 (40307038)
Project Period (FY) 2011 – 2013
KeywordsEGFR / TRAIL / EGFR-TKI / 薬剤耐性 / crosstalk signal
Research Abstract

We established EGFR-TKI-resistant non-small cell lung cancer (NSCLC) cell lines and found that these cell lines acquired collateral sensitivity to Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (about 70 times) as compared with parental cell line. In parental PC-9, anti-tumor effect of TRAIL was restricted, because TRAIL activates not only apoptotic signaling but also anti-apoptotic signaling through Akt/NFkB activation by cross talk signaling from TRAIL receptor to EGFR. In case of the resistant cell lines that overexpressed c-MET, the crosstalk signaling from TRAIL receptor to c-MET was not observed, and TRAIL-mediated Akt/NFkB activation was quite diminished. From these observations, EGFR-TKI/TRAIL combination is thought to be useful therapy for NSCLC.

  • Research Products

    (51 results)

All 2014 2013 2012 2011

All Journal Article (9 results) Presentation (39 results) Book (3 results)

  • [Journal Article] Prognostic impact of the number of viable circulating cells with high telomerase activity in gastric cancer patients : A prospective study2014

    • Author(s)
      Hiroaki Ito, Tohru Ohmori, et al
    • Journal Title

      Int J Oncol

      Volume: 45 Pages: 227-234

  • [Journal Article] Relationship of circulating tumor cells to the effectiveness of cytotoxic chemotherapy in patients with metastatic non-small-cell lung cancer2012

    • Author(s)
      Hirose T, Yamaoka T, Ohmori T. et al
    • Journal Title

      Oncol Res

      Volume: 20(2-3) Pages: 131-137

  • [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 disease2012

    • Author(s)
      Okuda K, Hirose T, Yamaoka T, Ohmori T. et al
    • Journal Title

      Anticancer Res

      Volume: 32(2) Pages: 5475-5480

  • [Journal Article] Application of a qualitative and quantitative real-time polymerase chain reaction method for detecting genetically modified papaya line 55-1 in papaya products2012

    • Author(s)
      Sakai A, Ohmori T, et al
    • Journal Title

      J Thorac Oncol

      Volume: 9 Pages: 1337-1344

  • [Journal Article] Phase II trial of amrubicin and carboplatin in patients with sensitive or refractory relapsed small-cell lung cancer2011

    • Author(s)
      Hirose T, Yamaoka T, Ohmori T, et al
    • Journal Title

      Lung Cancer

      Volume: (Epub ahead of print)

  • [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, Yamaoka T, Ohmori T, et al
    • Journal Title

      Lung Cancer

      Volume: 71(2) Pages: 224-228

  • [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 cancer2011

    • Author(s)
      Oki Y, Hirose T, Yamaoka T, Ohmori T, et al
    • Journal Title

      Cancer Chemother Pharmacol

      Volume: 67(4) Pages: 791-797

  • [Journal Article] Phase II trial of the combination of carboplatin and irinotecan in elderly patients with small-cell lung cancer2011

    • Author(s)
      Murata Y, Hirose T, Yamaoka T, Ohmori T, et al
    • Journal Title

      Eur J Cancer

      Volume: 47(9) Pages: 1336-1342

  • [Journal Article] Evaluation of the efficacy and safety of the combination of gemcitabine and nedaplatin for elderly patients with advanced non-small-cell lung cancer2011

    • Author(s)
      Sugiyama T, Hirose T, Yamaoka T, Ohmori T, et al
    • Journal Title

      Oncology

      Volume: 81(3-4) Pages: 273-280

  • [Presentation] Contribution of miR-205 in gefitinib-resistant lung cancer cell lines2014

    • Author(s)
      Toshihiro Suzuki, Toshimitsu Yamaoka, Tohru Ohmori, et al
    • Organizer
      Annual Meeting 2014
    • Place of Presentation
      American Association for Cancer Research SanDiego
    • Year and Date
      20140000
  • [Presentation] TNF transactivation of EGFR protects EGFR-TKI, gefitinib induced pulmonary epithelial cell apoptosis and injury in TNF transgenic mice2014

    • Author(s)
      Toshimitsu Yamaoka, Tohru Ohmori, et al
    • Organizer
      Annual Meeting 2014
    • Place of Presentation
      American Association for Cancer Research SanDiego(#2277)
    • Year and Date
      20140000
  • [Presentation] A novel c-MET inhibitor, tivantinib, shows an additive growth-inhibitory effect with erlotinib through enhanced degradation of c-MET protein via its recycling pathway2013

    • Author(s)
      Tohru Ohmori, Toshimitsu Yamaoka, Takashi Hirose, et al
    • Organizer
      19^<th> International Charles Heidelberger Symposium on Cancer Research
    • Place of Presentation
      鹿児島(P-04)
    • Year and Date
      20130000
  • [Presentation] The characteristics of an acquired dual resistance to EGFR & MET inhibitors in non-small cell lung cancer, harboring active mutation of EGFR2013

    • Author(s)
      Toshimitsu Yamaoka, Takashi Hirose, Tohru Ohmori et al
    • Organizer
      #5648Annual Meeting 2013
    • Place of Presentation
      American Association for Cancer Research Washington
    • Year and Date
      20130000
  • [Presentation] Clinical benefit of 2nd EGFR-TKI retreatment on overall survival in patients with advanced non-small cell lung cancer2013

    • Author(s)
      Masanao Nakashima, Takashi Hirose, Toshimitsu Yamaoka, Tohru Ohmori, et al
    • Organizer
      第11回日本臨床腫瘍学会学術集会
    • Place of Presentation
      仙台(P-1413)
    • Year and Date
      20130000
  • [Presentation] MET高感受性を示すEGFR-TKI耐性PC-9細胞におけるMET阻害剤耐性細胞株の樹立/The characteristics of dual resistance to EGFR & MET inhibitors in pulmonary adenocarcinoma, PC-9 cells2013

    • Author(s)
      山岡利光, 大森亨, 他
    • Organizer
      PC-9 cells第72回日本癌学会学術総会
    • Place of Presentation
      横浜(E-2030)
    • Year and Date
      20130000
  • [Presentation] 表面増強ラマン散乱(SERS)を用いた新しいオミックス解析技術の開発/Novel methodology of integrated omics analysis by using Surface Enhanced Raman Scattering (SERS): A Preliminary Study2013

    • Author(s)
      伊藤寛晃, 大森亨, 他
    • Organizer
      A Preliminary Study第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      20130000
  • [Presentation] 循環癌細胞の個別採取と増幅抽出ゲノムDNAの次世代シークエンサーによる網羅的遺伝子解析2013

    • Author(s)
      伊藤寛晃, 大森亨, 他
    • Organizer
      第113回日本外科学会(福岡)
    • Place of Presentation
      京都(ポスターセッション(375)新規治療法開発遺伝子解析)
    • Year and Date
      2013-04-01
  • [Presentation] 進展型小細胞肺癌の生存期間に対するアムルビシンの影響に関する検討2012

    • Author(s)
      石田博雄, 大森亨, 山岡利光, 廣瀬敬, 他
    • Organizer
      (日本癌治療学会誌47巻3号Page2134)
    • Place of Presentation
      横浜
    • Year and Date
      20121000
  • [Presentation] 当院におけるCOPD合併切除不能非小細胞肺癌に関する検討2012

    • Author(s)
      杉山智英, 大森亨, 山岡利光, 廣瀬敬, 他
    • Organizer
      (肺癌52巻5号Page775)
    • Place of Presentation
      岡山
    • Year and Date
      20121000
  • [Presentation] 高齢者小細胞肺癌に対する治療成績の検討2012

    • Author(s)
      村田泰規, 大森亨, 山岡利光, 廣瀬敬, 他
    • Organizer
      (肺癌52巻5号Page637)
    • Place of Presentation
      岡山
    • Year and Date
      20121000
  • [Presentation] EGFR遺伝子変異陽性肺腺癌患者に対するゲフィチニブ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, 大森亨, 山岡利光, 廣瀬敬, 他
    • Organizer
      (肺癌52巻5号Page625)
    • Place of Presentation
      岡山
    • Year and Date
      20121000
  • [Presentation] FGFR-TKIの再投与の有効性と安全性の検討.2012

    • Author(s)
      中嶌賢尚, 大森亨, 山岡利光, 廣瀬敬, 他
    • Organizer
      (肺癌52巻5号Page621)
    • Place of Presentation
      岡山
    • Year and Date
      20121000
  • [Presentation] 進行肺大細胞神経内分泌癌と進展型小細胞肺癌に対する化学療法の有効性の比較2012

    • Author(s)
      石田博雄, 大森亨, 山岡利光, 廣瀬敬, 他
    • Organizer
      (肺癌52巻5号Page598)
    • Place of Presentation
      岡山
    • Year and Date
      20121000
  • [Presentation] 進展型小細胞肺癌の生存期間に対するアムルビシンの影響に関する検討2012

    • Author(s)
      石田博雄, 大森亨, 山岡利光, 廣瀬敬, 他
    • Organizer
      (肺癌52巻5号Page586)
    • Place of Presentation
      岡山
    • Year and Date
      20121000
  • [Presentation] 切除不能局所進行非小細胞肺癌に対する胸部放射線療法とvinorelbine, carboplatin同時併用第II相試験2012

    • Author(s)
      大森亨, 山岡利光, 廣瀬敬, 他
    • Organizer
      (肺癌52巻5号Page579)
    • Place of Presentation
      岡山
    • Year and Date
      20121000
  • [Presentation] Cancer Vaccination trial with novel multiple peptides in previously treated advanced non-small cell lung cancer2012

    • Author(s)
      Tohru Ohmori, Toshimitsu Yamaoka, Takashi Hirose, et al
    • Organizer
      Annual Meeting of American Society of Clinical Oncology
    • Place of Presentation
      Chicago
    • Year and Date
      20120600
  • [Presentation] Carboplatin+Paclitaxel+ Bevacizumabによる化学療法中にIII度房室ブロックをきたした肺腺2012

    • Author(s)
      白井崇生, 大森亨, 山岡利光, 廣瀬敬, 他
    • Organizer
      (癌症例肺癌52巻3号Page359-360)
    • Place of Presentation
      岡山
    • Year and Date
      20120600
  • [Presentation] HSP 70 may cause EGFR-TKIs-resistance due to inhibit drug binding to EGFR in the cells that expressed mutant EGFR2012

    • Author(s)
      Tohru Ohmori, Toshimitsu Yamaoka, Takashi Hirose, et al
    • Organizer
      Proceedings of American Association for Cancer Research, #1900
    • Place of Presentation
      Chicago
    • Year and Date
      20120400
  • [Presentation] Specific epidermal growth factor receptor autophosphorylation sites promote epithelial cell chemotaxis and restitution2012

    • Author(s)
      Tohru Ohmori, Toshimitsu Yamaoka, Takashi Hirose, et al
    • Organizer
      103rd Annual Meeting of American Association for Cancer Research
    • Place of Presentation
      Chicago
    • Year and Date
      20120400
  • [Presentation] 気道上皮細胞と非小細胞肺癌細胞におけるTACEを介したTNFによるEGFRのトランス活性化機序の検討2012

    • Author(s)
      山岡利光, 村廣瀬敬, 山岡利光, 大森亨, 他
    • Organizer
      (日本呼吸器学会誌1巻増刊Page323)
    • Place of Presentation
      神戸
    • Year and Date
      20120300
  • [Presentation] 高齢者進行非小細胞肺癌のnedaplatin+gemcitabine併用療法の有効性と安全性のレトロスペクティブ検討2012

    • Author(s)
      中嶌賢尚, 廣瀬敬, 山岡利光, 大森亨, 他
    • Organizer
      (日本呼吸器学会誌1巻増刊Page264)
    • Place of Presentation
      神戸
    • Year and Date
      20120300
  • [Presentation] 切除不能局所進行非小細胞肺癌に対する胸部放射線療法とvinorelbine, carboplatin同時併用第II相試験2012

    • Author(s)
      廣瀬敬, 山岡利光, 大森亨, 他
    • Organizer
      (日本呼吸器学会誌1巻増刊Page326)
    • Place of Presentation
      神戸
    • Year and Date
      20120300
  • [Presentation] 当院におけるCOPD合併肺癌手術例に関する検討2012

    • Author(s)
      杉山智英, 廣瀬敬, 山岡利光, 大森亨, 他
    • Organizer
      (日本呼吸器学会誌1巻増刊Page326)
    • Place of Presentation
      神戸
    • Year and Date
      20120300
  • [Presentation] 糖尿病合併肺癌の現状について2012

    • Author(s)
      楠本壮二郎, 廣瀬敬, 山岡利光, 大森亨, 他
    • Organizer
      (日本呼吸器学会誌1巻増刊Page319)
    • Place of Presentation
      神戸
    • Year and Date
      20120300
  • [Presentation] Micro RNAによるゲフィチニブ耐性関連因子の調節2012

    • Author(s)
      鈴木俊宏, 大森亨, 他
    • Organizer
      第16回日本がん分子標的治療学会(S2-4)
    • Place of Presentation
      福岡
    • Year and Date
      20120000
  • [Presentation] IV期非小細胞肺がんにおける末梢血中がん細胞数(CTC)と抗がん剤治療の効果と予後との関連性2011

    • Author(s)
      廣瀬敬, 山岡利光, 大森亨, 他
    • Organizer
      (肺癌51巻5号Page421)
    • Place of Presentation
      大阪
    • Year and Date
      20111000
  • [Presentation] 高齢者進行非小細胞肺癌に対するnedaplatin +gemcitabine併用療法の有効性と安全性の検討2011

    • Author(s)
      中嶌賢尚, 廣瀬敬, 山岡利光, 大森亨, 他
    • Organizer
      (肺癌51巻5号Page486)
    • Place of Presentation
      大阪
    • Year and Date
      20111000
  • [Presentation] 糖尿病合併肺癌の現状について2011

    • Author(s)
      楠本壮二郎, 廣瀬敬, 山岡利光, 大森亨, 他
    • Organizer
      (肺癌51巻5号Page495)
    • Place of Presentation
      大阪
    • Year and Date
      20111000
  • [Presentation] 当院におけるCOPD合併肺癌手術例に関する検討2011

    • Author(s)
      杉山智英, 廣瀬敬, 山岡利光, 大森亨, 他
    • Organizer
      (肺癌51巻5号Page516)
    • Place of Presentation
      大阪
    • Year and Date
      20111000
  • [Presentation] 気道上皮細胞と肺癌細胞におけるTNFによるEGFRトランス活性化に寄与するリガンドの同定とアポトーシス制御機構2011

    • Author(s)
      山岡利光, 大森亨, 廣瀬敬, 他
    • Place of Presentation
      東京(日本呼吸器学会雑誌49巻増刊Page159)
    • Year and Date
      20110300
  • [Presentation] 発熱性好中球減少症におけるプロカルシトニンの有用性の検討2011

    • Author(s)
      杉山智英, 廣瀬敬, 山岡利光, 大森亨, 他
    • Place of Presentation
      東京(日本呼吸器学会雑誌49巻増刊Page162)
    • Year and Date
      20110300
  • [Presentation] 超高齢者進行非小細胞肺癌の治療の有用性と安全性について2011

    • Author(s)
      奥田健太郎, 廣瀬敬, 山岡利光, 大森亨, 他
    • Place of Presentation
      東京(日本呼吸器学会雑誌49巻増刊Page294)
    • Year and Date
      20110300
  • [Presentation] 再発あるいは前治療無効小細胞肺癌(SCLC)に対するamrubicin, carboplatin併用第II相試験2011

    • Author(s)
      廣瀬敬, 山岡利光, 大森亨, 他
    • Place of Presentation
      東京(日本呼吸器学会雑誌49巻増刊Page295)
    • Year and Date
      20110300
  • [Presentation] HSP70 specifically binds to 15 bp deletion mutant EGFR and modulates sensitivity to EGFR-TKI2011

    • Author(s)
      Tsuyoki Kadofuku, Toshimitsu Yamaoka, Takashi Hirose, Tohru Ohmori, et al
    • Place of Presentation
      Orland FL, USA(Proceedings of American Association for Cancer Research, Vol. 52 699)
    • Year and Date
      20110000
  • [Presentation] EGFR-TKI耐性細胞に対するARQ197のMet阻害機構2011

    • Author(s)
      大森亨, 山岡利光, 廣瀬敬, 他
    • Organizer
      第15回がん分子標的治療研究会総会
    • Place of Presentation
      東京(ワークショップW6-4)
    • Year and Date
      20110000
  • [Presentation] HSP70 may cause EGFR-TKIs-resistance due to inhibit drug binding to EGFR in the cell that expressed mutant EGFR2011

    • Author(s)
      Tohru Ohmori, Toshimitsu Yamaoka, Takashi Hirose, et al
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋(English oral session E-1017)
    • Year and Date
      20110000
  • [Presentation] TNF transactivates phospho-tyrosine 1068 of EGFR through TACE/EGFR-ligand dependent mechanism2011

    • Author(s)
      Toshimitsu Yamaoka, Takashi Hirose, Tohru Ohmori, et al
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋(P-2051)
    • Year and Date
      20110000
  • [Presentation] Expression study of micro RNA in Gefitinib resistant cell lines2011

    • Author(s)
      Ai Irisawa,, Tohru Ohmori, T et al
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋(P-2095)
    • Year and Date
      20110000
  • [Book] 薬剤耐性研究-次世代シークエンサーを用いた抗がん剤感受性予測-(142)2013

    • Author(s)
      大森亨
    • Total Pages
      52
    • Publisher
      日本医師会雑誌
  • [Book] 薬剤耐性とその克服(改訂第3版)2012

    • Author(s)
      大森亨
    • Total Pages
      231-234
    • Publisher
      新臨床腫学
  • [Book] EGFR阻害剤の耐性とその克服(The mechanisms of resistance to EGFR-TKIs and challenges to overcome resistance in EGFR mutant Non-small cell lung cancer)(39巻6号)2012

    • Author(s)
      山岡利光, 大森亨
    • Total Pages
      857-862
    • Publisher
      癌と化学療法

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Published: 2015-07-16   Modified: 2015-07-29  

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