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Elucidation of mechanism of drug eruption due to epidermal growth factor receptor tyrosine kinase inhibitors

Research Project

Project/Area Number 20591319
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionNagoya University

Principal Investigator

SUGIURA Kazumitsu  名古屋大学, 大学院・医学系研究科, 准教授 (70335032)

Co-Investigator(Kenkyū-buntansha) MURO Yoshinao  名古屋大学, 大学院・医学系研究科, 准教授 (80270990)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords上皮成長因子受容体チロシンキナーゼ阻害薬 / 薬疹 / CCL2 / CCL5 / IL-1 / IL-1R2 / 発症メカニズム / EGFR受容体阻害薬 / ざそう様薬疹 / ケラチノサイト / 発症機序 / 小胞体ストレス応答
Research Abstract

Epidermal growth factor receptor tyrosine kinase(EGFR-TK) is a transducer of mitogenic signals, and is involved in the pathogenesis and progression of a number of cancers, including non-small cell lung cancer(NSCLC). Gefitinib is an EGFR-TK inhibitor that is clinically used to treat NSCLC ; however, this drug frequently causes adverse effects, including skin eruptions. The mechanism underlying these skin reactions is elusive, although it is assumed that they are caused by the inhibition of EGFR-TK signaling in epidermal and adnexal cells. In this study, we demonstrate that IL-1-mediated signaling is activated to induce the high expression of CCL2 and CCL5 via reduction of IL-1R2 in the skin lesions caused by gefitinib.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (46 results)

All 2010 2009 2008 Other

All Journal Article (31 results) (of which Peer Reviewed: 25 results) Presentation (13 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells which is similar to that seen in the psoriatic condition2010

    • Author(s)
      Takeichi T, Sugiura K, Muro Y, Matsumoto K, Ogawa Y, Futamura K, Kaminuma O, Hashimoto N, Shimoyama Y, Saito H, Tomita Y.
    • Journal Title

      J Invest Dermatol

      Volume: 130 Pages: 2760-2767

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epidermal growth factor receptor trosine kinase inhibitors induce CCL2 and CCL5 via reduction in IL-1R2 in keratinocytes2010

    • Author(s)
      Yamaki M, Sugiura K, Muro Y, Shimoyama Y, Tomita Y.
    • Journal Title

      Exp Dermatol

      Volume: 19(8) Pages: 730-5

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-MDA5 and anti-TIF1γantibodies have clinical significance for patients with dermatomyositis.2010

    • Author(s)
      Hoshino K, Muro Y, Sugiura K, Tomita Y, Nakashima R, Mimori T.
    • Journal Title

      Rheumatology(Oxford)

      Volume: 49(9) Pages: 1726-33

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] エトレチナートが有効であった小児膿疱性乾癬2010

    • Author(s)
      渡邉奏子, 杉浦一充, 富田靖
    • Journal Title

      皮膚病診療

      Volume: 32巻11号 Pages: 1195-1198

    • Related Report
      2010 Final Research Report
  • [Journal Article] 掻痒性皮膚疾患に対する第2世代抗ヒスタミン薬の有効性・安全性クロスオーバー法を用いた比較検討2010

    • Author(s)
      杉浦一充, 満間照之, 横田雅史, 清水真, 鈴木信吾, 新田悠紀子, 稲垣克彦, 臼田俊和, 工藤清孝, 富田靖
    • Journal Title

      Progress in Medicine

      Volume: 30巻7号 Pages: 1997-2001

    • Related Report
      2010 Final Research Report
  • [Journal Article] インフリキシマブが著効した小児膿疱性乾癬2010

    • Author(s)
      松本朋子, 杉浦一充, 富田靖
    • Journal Title

      皮膚病診療

      Volume: 32巻2号 Pages: 171-174

    • Related Report
      2010 Final Research Report
  • [Journal Article] Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in Ha CaT cells which is similar to that seen in the psoriatic condition2010

    • Author(s)
      Takeichi T, Sugiura K, et al
    • Journal Title

      J Invest Dermatol

      Volume: 130 Pages: 2760-2767

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epidermal growth factor receptor trosine kinase inhibitors induce CCL2 and CCL5 via reduction in IL-1R2 in keratinocytes2010

    • Author(s)
      Yamaki M, Sugiura K, et al
    • Journal Title

      Exp Dermatol

      Volume: 19 Pages: 730-735

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-MDA5 and anti-TIF1_Y antibodies have clinical significance for patients with dermatomyositis2010

    • Author(s)
      Hoshino K, Muro Y, Sugiura K, et al
    • Journal Title

      Rheumatology (Oxford)

      Volume: 49 Pages: 1726-1733

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Unfolded Protein Response Is Activated in Differentiating Epidermal Keratinocytes2009

    • Author(s)
      Sugiura K, Muro Y, Futamura K, Matsumoto K, Hashimoto N, Nishizawa Y, Nagasaka T, Saito H, Tomita Y, Usukura J.
    • Journal Title

      J Invest Dermatol

      Volume: 129 Pages: 2126-2135

    • Related Report
      2010 Final Research Report
  • [Journal Article] An evaluation of the efficacy of the toe brachial index measuring vascular involvement in systemic sclerosis and other connective tissue diseases2009

    • Author(s)
      Muro Y, Sugiura K, Morita Y Tomita Y
    • Journal Title

      Clin Exp Rheumatol.

      Volume: 27 Pages: 26-31

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of anti-ribosomal P protein immnoassays in Japanese patients with connective tissue diseases in comparison to indirect immunofluorescence assays2009

    • Author(s)
      Muro Y, Sugiura K, Morita Y, Tomita Y
    • Journal Title

      Scand J Rheumatol.

      Volume: 38 Pages: 460-463

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Scoring of reflux symptoms associated with scleroderma and the usefulness of rabeprazole2009

    • Author(s)
      Muro Y, Sugiura K, Nitta Y, Mitsuma T, Hoshino K, Usuda T, Hayashi K, Murase Y, Shimizu M, Matsuo H
    • Journal Title

      Clin Exp Rheumatol.

      Volume: 27 Pages: 15-21

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Successful topical hemotherapy with a new occlusive dressing for an intractable ulcer on the toe2009

    • Author(s)
      Iwayama-Hibino M, Sugiura K, Muro Y, Tomita Y.
    • Journal Title

      J Dermatol

      Volume: 36 Pages: 245-8

    • NAID

      10025200393

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] CENP-O, a protein localized at the centromere throughout the cell cycle, is a novel target antigen in systemic sclerosis.2009

    • Author(s)
      Saito A, Muro Y, Sugiura K, Ikeno M, Yoda K, Tomita Y.
    • Journal Title

      J Rheumatol.

      Volume: 36 Pages: 781-6

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sweet病関節炎を伴った症例2009

    • Author(s)
      新田悠紀子, 杉浦一充
    • Journal Title

      Visual Dermatology

      Volume: 9巻1号 Pages: 50-52

    • Related Report
      2010 Final Research Report
  • [Journal Article] SLEの経過中にStevens Johnson症候群進展型中毒性表皮壊死症を呈した1例2009

    • Author(s)
      柴田章貴, 杉浦一充, 奥田容子, 室慶直, 富田靖, 八島章仁
    • Journal Title

      臨床皮膚科

      Volume: 63巻4号 Pages: 282-285

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The unfolded potein response is activated in differentiating epidermal keratinocytes2009

    • Author(s)
      Sugiura K, et al.
    • Journal Title

      J Invest Dermatol 129

      Pages: 2126-2135

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of anti-ribosomal P protein immnoassays in Japanese patients with connective tissue diseases in comparison to indirect immunofluorescence assays2009

    • Author(s)
      Muro Y, Sugiura K, et al.
    • Journal Title

      Scand J Rheumatol 38

      Pages: 460-463

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Scoring of reflux symptoms associated with scleroderma and the usefulness of rabeprazole2009

    • Author(s)
      Muro Y, Sugiura K, et al.
    • Journal Title

      Clin Exp Rheumatol 27

      Pages: 15-21

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-SS-A/Ro antibody determination by indirect immunofluorescence and comparison of different methods of antinuclear antibody screening : Evaluation of the utility of HEp-2 cells transfected with the 60 kDa SS-A/Ro as a substrate2008

    • Author(s)
      Tanaka N., Muro Y., Sugiura K., and Tomita Y.
    • Journal Title

      Modern Rheum

      Volume: 18(6) Pages: 585-92

    • NAID

      10025111574

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-cyclic citrullinated peptide antibody in systemic sclerosis2008

    • Author(s)
      Morita Y., Muro Y., Sugiura K., Tomita Y.
    • Journal Title

      Clin Exp Rheumatol

      Volume: 26(4) Pages: 542-7

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of ELISA with CENP-A and CENP-B for the detection of anti-centromere2008

    • Author(s)
      Hoshino K., Muro Y., Sugiura K., Tomita Y.
    • Journal Title

      Clin Exp Rheumatol

      Volume: 26(3) Pages: 505-505

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of cetirizine hydrochloride-based therapeutic strategy for chronic urticaria2008

    • Author(s)
      Sugiura K, Hirai S, Suzuki T, Usuda T, KondoT, Azumi T, Masaki S, Yokoi T, Nitta Y, Kamiya S, Ando K, Mori T, Tomita Y
    • Journal Title

      Nagoya J Med Sci.

      Volume: 70(3-4) Pages: 97-106

    • NAID

      110007018350

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] High concomitance of disease marker autoantibodies in anti-DFS70/LEDGF antibody-positive. patients with autoimmune rheumatic disease.2008

    • Author(s)
      Muro Y., Sugiura K., Morita Y., Tomita Y.
    • Journal Title

      Lupus

      Volume: 17 Pages: 171-6

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] ミュンヒハウゼン症候群による自傷行為で発症した壊死性筋膜炎の1例2008

    • Author(s)
      梶田直美, 杉浦一充, 澤田昌樹, 横田憲二, 富田靖
    • Journal Title

      臨床皮膚科

      Volume: 62巻13号 Pages: 991-994

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Churg-Shtrauss症候群2008

    • Author(s)
      山崎有子, 杉浦一充, 富田靖
    • Journal Title

      皮膚病診療

      Volume: 30巻11号 Pages: 1229-1232

    • Related Report
      2010 Final Research Report
  • [Journal Article] 鞍鼻から診断された第3期梅毒の1例2008

    • Author(s)
      梶田直美, 杉浦一充, 中田誠一, 富田靖
    • Journal Title

      皮膚科の臨床

      Volume: 50巻10号 Pages: 1251-1254

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of cetirizine hydrochloride-based therapeutic strategy for chronic urticaria2008

    • Author(s)
      Sugiura K, et al.
    • Journal Title

      Nagoya J Med Sci 70

      Pages: 97-106

    • NAID

      110007018350

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High concomitance of disease marker autoantibodies in anti-DFS70/LEDGF antibody-positive-patients with autoimmune rheumatic disease2008

    • Author(s)
      Muro Y., Sugiura K., et al.
    • Journal Title

      Lupus 17

      Pages: 171-6

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-cyclic citrullinated peptide antibody, in systemic sclerosis2008

    • Author(s)
      Morita Y., Muro Y., Sugiura K., et al.
    • Journal Title

      Clin Exp Rheumatol 26

      Pages: 542-7

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells, which resembles psoriasis.2010

    • Author(s)
      Takeichi T, Sugiura K, Muro Y, Matsumoto K, Ogawa Y, Futamura K, Tomita Y
    • Organizer
      40^<th> annual ESDR meeting
    • Place of Presentation
      Helsinki
    • Related Report
      2010 Final Research Report
  • [Presentation] Epidermal growth factor receptor tyrosine kinase inhibitors induce CCL2 and CCL5 via reduction of type II interleukin-1 receptor in keratinocytes.2010

    • Author(s)
      Sugiura K, Yamaki M, Muro Y, Tomita Y
    • Organizer
      14^<th> international congress of mmunology
    • Place of Presentation
      Kobe
    • Related Report
      2010 Final Research Report
  • [Presentation] Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells which is similar to psoriatic condition2010

    • Author(s)
      Takeichi T, Sugiura K, Muro Y, Matsumoto K, Ogawa Y, Futamura K, Tomita Y
    • Organizer
      14^<th> international congress of mmunology
    • Place of Presentation
      Kobe
    • Related Report
      2010 Final Research Report
  • [Presentation] Epidemiologic study of anti-melanoma differentiation-associate gene 5(MDA-5) autoantibodies-a major autoimmune response in amyopathic dermatomyositis.2010

    • Author(s)
      Muro Y, Hoshino K, Sugiura K, Tamakoshi K
    • Organizer
      14^<th> international congress of mmunology
    • Place of Presentation
      Kobe
    • Related Report
      2010 Final Research Report
  • [Presentation] IgE class autoantibody against DFS70/LEDGF in atopic dermatitis2010

    • Author(s)
      Watanabe K, Muro Y, Sugiura K, Tomita Y
    • Organizer
      14^<th> international congress of mmunology
    • Place of Presentation
      Kobe
    • Related Report
      2010 Final Research Report
  • [Presentation] nti-DFS(dense fine speckled) 70 antibody in patients with atopic dermatitis2010

    • Author(s)
      Higashi N, Sugiura K, Muro Y
    • Organizer
      International symoposium on atopic dermatitis 2010
    • Place of Presentation
      Munchen
    • Related Report
      2010 Final Research Report
  • [Presentation] Epidermal growth factor receptor tyrosine kinase inhibitors induce CCL2 and CCL5 via reduction of type II interleukin-1 receptor in keratinocytes2010

    • Author(s)
      Sugiura K, et al
    • Organizer
      14^<th> international congress of mmunology
    • Place of Presentation
      神戸
    • Related Report
      2010 Annual Research Report
  • [Presentation] ゲフィニブによる薬疹におけるCCL2とCCL5の検討2009

    • Author(s)
      山木麻祐子, 杉浦一充, 等
    • Organizer
      第59回日本アレルギー学会秋季学術大会
    • Place of Presentation
      秋田キャッスルホテル
    • Year and Date
      2009-10-31
    • Related Report
      2009 Annual Research Report
  • [Presentation] The unfolded protein response is activated in differentiationg keratinocytes2009

    • Author(s)
      Sugiura K, Muro Y, Futamura K Matsumoto K Hashimoto N Nishizawa Y, Nagasaka T, Saito H, Usukura J Tomita Y
    • Organizer
      The 4th Joint Meeting of Japanese Dermatological Association and Australasian College of Dermatologists
    • Place of Presentation
      Sapporo
    • Year and Date
      2009-07-11
    • Related Report
      2010 Final Research Report
  • [Presentation] Examination of Gene Expression Profiles in Hair Root Tissue Provides Useful Local Information2009

    • Author(s)
      Yagami A, Matsumoto K, Futamura K, Matsuda A, Orihara K, Hashimoto N, Kojima R, Morita H, Sugiura K, Muro Y, Tomita Y, Matsunaga K, Saito H
    • Organizer
      American Academy of Allergy Asthma & Immunology
    • Related Report
      2010 Final Research Report
  • [Presentation] ゲフィチニブによる皮膚病変の免疫組織学的検討2008

    • Author(s)
      山木麻祐子, 杉浦一充等
    • Organizer
      第58回日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2008-11-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] The unfolded protein response is involved in epidermal keratinocyte differentiation2008

    • Author(s)
      Sugiura K, Muro Y, Futamura K, Matsumoto K, Hashimoto N, Nishizawa Y, Nagasaka T, Saito H, Usukura J, Tomita Y
    • Organizer
      The International Investigative Dermatology 2008
    • Place of Presentation
      Kyoto
    • Related Report
      2010 Final Research Report
  • [Presentation] LEDGF/DFS70, A Major Autoantigen of Atopic Dermatitis, Is a Component of Keratohyalin Granules 5th Georg Rajka2008

    • Author(s)
      Sugiura K
    • Organizer
      Symposium on Atopic Dermatitis
    • Place of Presentation
      Kyoto
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ

    • URL

      http://www.med.nagoya-u.ac.jp/derma/

    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] ADM抗体エピトープペプチドおよびその利用2009

    • Inventor(s)
      石井陽子、松尾克彦、丹羽幹夫、室慶直、杉浦一充
    • Industrial Property Rights Holder
      石井陽子、松尾克彦、丹羽幹夫、室慶直、杉浦一充
    • Industrial Property Number
      2009-119306
    • Filing Date
      2009-05-15
    • Related Report
      2010 Final Research Report 2009 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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