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Elucidation of the mechanism of chemotherapy resistance relating the obese signaling pathway

Research Project

Project/Area Number 19K19171
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionGunma University

Principal Investigator

Kina Mika  群馬大学, 医学部附属病院, 医員 (80578914)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords内臓脂肪型肥満 / 口腔癌 / 組織学的分化度 / BMI / 抗がん剤感受性 / 腫瘍微小環境 / PPAR-γ / 内臓肥満
Outline of Research at the Start

過去に肥満や野菜摂取不足も癌の危険因子であることが報告され、肝臓癌や前立腺がんと内臓脂肪型肥満の関連が報告されている。いくつかの研究は癌の促進と進展においてPPARsが関与しており、一方では癌に抵抗してこれらの受容体に対して保護的な役割をする根拠を示している。しかし、肥満は癌患者の予後不良因子である理由についての科学的根拠はいまだ不明であり、口腔癌と肥満に関する報告は少ない。そこで、本研究は、①内臓肥満が口腔癌の発症に、どの様な形で関与しているのか、②脂肪組織中のPPAR-γが口腔癌の発症に関わるならば、どのような経路か、③内臓肥満患者は抗癌剤感受性に違いがあるのか、を明らかにする。

Outline of Final Research Achievements

Chemotherapy resistance is a major cause of cancer progression. To investigate the association between obesity and chemotherapy sensitivity in oral squamous cell carcinoma (OSCC), here we performed retrospective analysis in 40 patients with OSCC. We detected significantly higher frequency of pathological complete response in poorly or moderately differentiated cases than in well differentiated cases(P<0.05). Association analyses comparing the BMI with histological differentiation revealed that OSCC of male patients with 29≦BMI has significantly higher rate of poorly or moderately differentiation than those of patients with BMI<29. Cytokine expression analysis using TCGA(The Cancer Genome Atlas) indicated IL-6 is significantly enriched in poorly or moderately differentiated Head and Neck SCC. This study expands understanding of the involvement of obesity in OSCC pathogenesis and presents insights that have the potential to utilize BMI as patients screening for neoadjuvant chemotherapy.

Academic Significance and Societal Importance of the Research Achievements

研究成果の社会的意義は、口腔扁平上皮癌患者が、内臓脂肪型肥満であるかそうでないかという、簡便な基準で術前の抗癌剤治療を施行するかしないかの判断材料となりうる可能性があることである。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2023 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] EphA4 signaling is involved in the phenotype of well-differentiated oral squamous cell arcinoma with decreased tumor immunity2023

    • Author(s)
      Kina Shinichiro、Kawabata-Iwakawa Reika、Miyamoto Sho、Kato Tomoki、Kina-Tanada Mika、Arasaki Akira
    • Journal Title

      European Journal of Pharmacology

      Volume: 945 Pages: 175611-175611

    • DOI

      10.1016/j.ejphar.2023.175611

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 早期舌扁平上皮癌患者に対してUFT およびS-1 を投与した術前化学療法2019

    • Author(s)
      喜名振一郎、仁村文和、金城貴夫、砂川奈穂、喜名美香、新崎章、仲宗根敏幸
    • Organizer
      第57回日本癌治療学会 福岡国際会議場
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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