the pathogenic mechanisms of EGFR inhibitor-induced rash and establishment of system for constructing medical treatment

• Project/Area Number: 25461666
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Shinshu University
• Principal Investigator: UHARA Hisashi 信州大学, 学術研究院医学系, 准教授 (40201355)
• Co-Investigator(Kenkyū-buntansha): ASHIDA Atsuko 信州大学, 学術研究院医学系, 助教 (00596786) ; OKUYAMA Ryuhei 信州大学, 学術研究院医学系, 教授 (80292332)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: EGFR阻害剤 / ざ瘡様皮疹 / 脂腺細胞 / SEB-1 / PPARγ / NFkappaB / COX-2 / エルロチニブ / NFκB / ゲフィチニブ / 皮疹 / 痤瘡様皮疹 / サイトカイン / PPAR

Outline of Final Research Achievements

We investigated the pathogenic mechanisms of EGFR inhibitor-induced papulopustular rash development, using cultured human sebocytes, SEB-1. Blockade of EGFR led to TNFα induction, which was associated with sebaceous differentiation. EGFR inhibitor-induced TNFα　expression was involves with PPARγ, COX-2 and NFκB; thus, inhibition of these molecules may attenuate inflammation of papulopustular rash.

Research Products

• [Journal Article] Inhibition of epidermal growth factor receptor sinduces tumor necrosis factor-a via activation of peroxisome proliferator-activated receptor-g and nuclear factor-kB in sebocytes: A possible pathogenesis of papulopustular rash (2016)
  • Author(s): Atsuko Ashida, Eisaku Ogawa,, Hisashi Uhara, Tomonobu Koizumi, Ryuhei Okuyama
  • Journal Title: J Dermatol Sci Volume: 82 Issue: 1 Pages: 53-56
  • DOI: 10.1016/j.jdermsci.2015.12.004
  • Peer Reviewed / Open Access
• [Presentation] Epidermal growth factor receptor inhibitor induces tumor necrosis factor-α via activation of the PPARκ and NF-kappa B from sebocytes. (2015)
  • Author(s): Atsuko Ashida, Eisaku Ogawa, Ryuhei Uchiyama, Hisashi Uhara, Ryuhei Okuyama
  • Organizer: 第40回日本研究皮膚科学会学術大会総会
  • Place of Presentation: 岡山コンベンションセンター（岡山県岡山市）
  • Year and Date: 2015-12-11
• [Presentation] Analysis of EGF receptor(EGFR) inhibitor-induced inflammation in sebaceous cells (2013)
  • Author(s): 芦田敦子、木庭幸子、高沢裕子、内山龍平、宇原久、小川英作、奥山隆平
  • Organizer: 第4回最新医療研究会
  • Place of Presentation: 松本市
• [Book] 抗EGFR抗体薬により皮膚障害とその予防・対策、最新臨床 大腸癌学 (2015)
  • Author(s): 御子柴飛鳥、芦田敦子、奥山隆平
  • Total Pages: 715
  • Publisher: 日本臨床