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The mutation effect of Ras-Raf-MAPK and PI3K/Akt pathway for chemosensitivity of cetuximab treatment in the oral cancer

Research Project

Project/Area Number 26463069
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionOkayama University

Principal Investigator

Konouchi Hironobu  岡山大学, 医歯薬学総合研究科, 准教授 (20294423)

Co-Investigator(Kenkyū-buntansha) 竹中 文章  岡山大学, 医歯薬学総合研究科, 助教 (10642522)
畦坪 輝寿  岡山大学, 医歯薬学総合研究科, 助教 (30633606)
久富 美紀  岡山大学, 大学病院, 講師 (60314704)
Co-Investigator(Renkei-kenkyūsha) MURAKAMI Jun  岡山大学, 岡山大学病院, 助教 (40362983)
Research Collaborator OKADA Shunsuke  岡山大学, 岡山大学病院, 医員 (00759681)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords口腔癌 / セツキシマブ / アービタックス / PET / BRAF / KRAS / NRAS / PIK3CA / 口腔癌細胞株 / ジルコニウム / EGFR
Outline of Final Research Achievements

Cetuximab is a monoclonal antibody targeting epidermal growth factor receptor (EGFR), and is effective for tumors with overexpression of EGFR. It was originally used for metastatic colorectal cancer, but since the overexpression of EGFR is seen in 80-100% of head and neck cancer (HNC), antitumor effect is also expected in HNC. In this study, we have assessed the antitumor effect of Cetuximab treatment using 9 oral cancer cell lines, with regard to BRAF, KRAS, NRAS, PIK3CA mutation status. We found no mutation in the mutation hot spots of BRAF gene , KRAS gene, NRAS gene. We also evaluated 5 well-known hot spots of PIK3CA gene, E542K and H1047R mutations of PIK3CA gene were observed in Ca9-22 and HSG cells. BALB/c-nu mouse transplanted with PIK3CA mutated HSG cells showed in lower sensitivity for Cetuximab. The results suggest that E542K mutation of PIK3CA could be used as a screening test to evaluate the sensitivity of HNC to Cetuximab.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (4 results)

All 2016 2015 2014

All Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Evaluation of sensitivity to Cetuximab in HNC xenograft mouse model using molecuar imaging2016

    • Author(s)
      S. Okada, J. Murakami, H.Konouchi, Y.Yanagi, M.Hisatomi, J.Asaumi
    • Organizer
      The 11th Asian Congress of Oral and Maxillo-facial Radioligy
    • Place of Presentation
      Chiang Mai, Thailand
    • Year and Date
      2016-11-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 村上 純、此内浩信、柳 文修、久富美紀、苔口進、竹中文章、畦坪輝寿、藤田麻里子、岡田俊輔、浅海淳一2015

    • Author(s)
      口腔癌マウスモデルでのセツキシマブを用いた分子イメージング解析
    • Organizer
      日本歯科放射線学会第56回学術大会
    • Place of Presentation
      仙台
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report
  • [Presentation] 口腔癌マウスモデルでの抗EGFR療法における分子イメージング解析2015

    • Author(s)
      村上 純、此内浩信、柳 文修、久富美紀、畦坪輝寿、藤田麻里子、浅海淳一
    • Organizer
      第69回日本口腔科学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2015-05-13
    • Related Report
      2015 Research-status Report
  • [Presentation] 口腔癌マウスモデルでの抗EGFR療法の検討と分子イメージング解析2014

    • Author(s)
      南原 香奈,村上 純,此内 浩信,柳 文修,久富 美紀,畦坪 輝寿,藤田 麻里子,浅海 淳一
    • Organizer
      34回歯科放射線学会 関西九州・九州関西合同地方会
    • Place of Presentation
      長崎大学
    • Year and Date
      2014-12-06
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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