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The Novel and Comprehensive Screening of Genes Resistant to an Anticancer Drug and Radiation in Esophageal Squamous Cell Carcinoma

Research Project

Project/Area Number 16K07149
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor diagnostics
Research InstitutionKeio University

Principal Investigator

Kawakubo Hirofumi  慶應義塾大学, 医学部(信濃町), 准教授 (20286496)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords薬剤耐性 / 放射線耐性 / トランスポゾン / 食道癌 / 網羅的解析 / 5-FU / シスプラチン / 放射線 / 化学療法 / 薬剤耐性遺伝子 / 放射線療法 / 放射線耐性遺伝子 / 5FU / 抗癌剤耐性遺伝子 / 癌 / 遺伝子 / 薬剤反応性
Outline of Final Research Achievements

Multimodal therapies including surgery, chemotherapy, and radiotherapy are necessary for advanced esophageal cancer. However, patients with resistance to chemo or radiotherapy cannot derive benefit from the therapy but suffer side effects. Therefore, detecting resistant genes and mechanisms is essential for tailoring treatment to improve the prognosis.We used a novel method involving transposons to screen and identify drug-resistant genes and radio-resistant genes. The new gene screening technique was useful for detecting candidate of drug-resistant genes in esophageal squamous cell carcinoma. We identified 37 candidate genes responsible for CDDP resistance in the two cell lines derived from ESCC cells. TRIM16 is one of the candidate of CDDP resistant gene. We confirmed TRIM 16 overexpression cell has CDDP resistant using MTT assay and resistance is decreased by knocking down TRIM 16. We also confirmed TRIM 16 overexpression cell has CDDP resistant in vivo xenograft model.

Academic Significance and Societal Importance of the Research Achievements

現在、食道癌に対する根治的治療法は手術、化学療法、放射線療法を組み合わせた集学的治療が行われている。しかし、化学療法、放射線療法の奏効率は決して高くなく、奏効しない症例にとっては有害事象のみの無駄な治療となる。また、治療の経過中に薬剤耐性が生じることで治療不応性となることが問題である。以上より化学療法および放射線耐性のメカニズムの解明が治療戦略に非常に重要と考えられる。トランスポゾンを用いたシスプラチン、5-FU、放射線耐性遺伝子の新しい網羅的解析により、進行食道癌の新たな治療戦略の開発と治療成績の向上が可能である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Downregulation of cytochrome c oxidase 1 induced radioresistance in esophageal squamous cell carcinoma.2017

    • Author(s)
      Takesue T, Kawakubo H, Hayashida T, Tsutsui M, Miyao K, Fukuda K, Nakamura R, Takahashi, , Wada N, Takeuchi H, Kitagawa Y
    • Journal Title

      Oncology letter

      Volume: 14(4) Issue: 4 Pages: 4220-4224

    • DOI

      10.3892/ol.2017.6699

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] The novel and comprehensive screening of genes resistant to an anticancer drug and radiation in esophageal squamous cell carcinoma2016

    • Author(s)
      Hirofumi Kawakubo
    • Organizer
      2016 AACR Annual Meeting
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Transposonを用いた食道癌細胞における抗癌剤耐性遺伝子の網羅的解析2016

    • Author(s)
      林雅人
    • Organizer
      第27回日本消化器癌発生学会総会
    • Place of Presentation
      城山観光ホテル(鹿児島県鹿児島市)
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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