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Clarification of molecular biological mechanism targeting EphA4 against the anticancer drug resistance well-differentiated oral squamous cell carcinoma

Research Project

Project/Area Number 18K09729
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionUniversity of the Ryukyus

Principal Investigator

Nakasone Toshiyuki  琉球大学, 病院, 講師 (40381214)

Co-Investigator(Kenkyū-buntansha) 金城 貴夫  琉球大学, 医学部, 教授 (30284962)
喜名 振一郎  群馬大学, 大学院医学系研究科, 講師 (40422422)
喜名 美香  群馬大学, 医学部附属病院, 医員 (80578914)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsメトロノーム化学療法 / 高分化型腫瘍 / 口腔癌 / EphA4 / 高分化型口腔癌 / 抗癌剤耐性 / 分子生学的メカニズム
Outline of Final Research Achievements

Well-differentiated tumors are intrinsically chemotherapy resistant. Receptor tyrosine kinase erythropoietin-producing human hepatocellular receptor A4 (EphA4) protein is highly expressed in the well-differentiated tumor-derived cervical cancer cell line. Reactive oxygen species-SFK-EphA4 axis is shown to be new potential drug targets for chemotherapy resistance. Patients who received S-1 were more likely than those who received UFT to have pathological complete response. Neoadjuvant S-1 significantly improved disease-free survival as compared with up-front surgery. A choice of drugs for neoadjuvant metronomic chemotherapy is needed.

Academic Significance and Societal Importance of the Research Achievements

低容量頻回投与で化学療法を行うメトロノーム化学療法において、高分化型腫瘍が低中分化型腫瘍と比較して、耐性であることを報告した。高分化型腫瘍においてはEphA4 が高発現していた。EphA4は抗癌剤耐性に関与している可能性が示唆された。メトロノーム化学療法では、抗癌剤感受性が良好なレジュメを使用することで、早期舌癌患者のdisease-free-survival が改善していた。これにより、高分化型腫瘍の抗癌剤耐性を担っているEphA4をターゲットとすることで、さらなる予後の改善が期待できることが示された。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (3 results)

All 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results)

  • [Journal Article] Oral health behavior of children and guardians’ beliefs about children’s dental caries in Vientiane, Lao People’s Democratic Republic (Lao PDR)2019

    • Author(s)
      Phanthavong Somphone、Nonaka Daisuke、Phonaphone Thongsavanh、Kanda Kyoko、Sombouaphan Phouphachanh、Wake Norie、Sayavong Sangvane、Nakasone Toshiyuki、Phongsavath Khampe、Arasaki Akira
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 1 Pages: 1-10

    • DOI

      10.1371/journal.pone.0211257

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Outcomes after up-front surgery and metronomic neoadjuvant chemotherapy with S-1 or UFT for early tongue squamous cell carcinoma2018

    • Author(s)
      Kina Shinichiro、Nakasone Toshiyuki、Kinjo Takao、Nimura Fumikazu、Sunagawa Nao、Arasaki Akira
    • Journal Title

      Clinical Oral Investigations

      Volume: - Issue: 6 Pages: 1-6

    • DOI

      10.1007/s00784-018-2689-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Targeting EphA4 abrogates intrinsic resistance to chemotherapy in well-differentiated cervical cancer cell line.2018

    • Author(s)
      Kina S, Kinjo T, Liang F, Nakasone T, Yamamoto H, Arasaki A.
    • Journal Title

      Eur J Pharmacol.

      Volume: 840 Pages: 70-78

    • DOI

      10.1016/j.ejphar.2018.09.031

    • Related Report
      2018 Research-status Report
    • Peer Reviewed

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Published: 2018-04-23   Modified: 2022-01-27  

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