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chemokine CXCL14 is a predictive biomarker for head and neck squamous cell carcinoma

Research Project

Project/Area Number 24792261
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Surgical dentistry
Research InstitutionKanagawa Dental College

Principal Investigator

OZAWA Shigeyuki  神奈川歯科大学, 歯学研究科(研究院), 助教 (40434394)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords頭頸部癌 / テーラーメイド医療 / メチル化 / BRAK / EGFR阻害剤 / CXCL14 / セツキシマブ / 脱メチル化剤 / 扁平上皮癌
Outline of Final Research Achievements

Cetuximab, a monoclonal antibody against the epidermal growth factor receptor, has been successfully applied in some patients with HNSCC. For effective treatment, it is essential to first identify Cetuximab-responsive patients. When we compared the expression of chemokine BRAK in HNSCC cells, both Cetuximab responsive HSC-3 and non-responsive YCU-H891 cells, we found expression of this chemokine only in the responsive HSC-3 cells. We also found that the promoter region of YCU-H891 cells were hyper methylated, and demethylation of this promoter recovered BRAK mRNA expression together with in vivo tumour-growth suppression by Cetuximab. Additionally, YCU-H891 cells were engineered to express BRAK in the presence of doxycycline in mice. Cetuximab-dependent tumour suppression was observed in vivo by doxycycline administration in the drinking water of the mice. These results indicate that BRAK expression would be a predictive biomarker for Cetuximab-dependent tumour suppression.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (6 results)

All 2014 2013 2012

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (3 results)

  • [Journal Article] Acidic extracellular microenviromental and cancer2013

    • Author(s)
      Kato Y, Ozawa S, Miyamoto C, Maehata Y, Suzuki A, Maeda T, Baba Y
    • Journal Title

      Cancer Cell International

      Volume: 13(1) Issue: 1 Pages: 89-89

    • DOI

      10.1186/1475-2867-13-89

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Calcium-calmodulin signaling induced by epithelial cell differentiation upregulates BRAK/CXCL14 expression via the binding of SP1 to the BRAK promoter region2012

    • Author(s)
      Ikoma T, Ozawa S, Suzuki K, Kondo T, Maehata Y, Lee MC, Hata R, Kubota E
    • Journal Title

      Biochemical and biophysical Research Communications

      Volume: 420(2) Issue: 2 Pages: 217-22

    • DOI

      10.1016/j.bbrc.2012.01.157

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fasudil suppresses fibrosarcoma growth by stimulating secretion of the chemokine CXCL14/BRAK.2012

    • Author(s)
      Miyamoto C, Maehata Y, Ozawa S, Ikoma T, Kubota E, Izukuri K, Kato Y, Hata R, Lee MC.
    • Journal Title

      J Pharmacol Sci.

      Volume: 120 (3) Pages: 241-249

    • NAID

      10031147570

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 口腔癌の分子標的治療:抗腫瘍性ケモカインCXCL14のエピジェネティクス異常を指標としたセツキシマブ投与前評価の基礎的研究2014

    • Author(s)
      小澤重幸
    • Organizer
      日本歯科基礎医学会
    • Place of Presentation
      福岡
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] セツキシマブによる抗腫瘍性ケモカインBRAKの発現上昇メカニズムの解明2013

    • Author(s)
      小澤重幸,近藤忠稚,生駒丈晴,鈴木健司,久保田英朗
    • Organizer
      日本口腔外科学会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] 変異したP53による抗腫瘍性ケモカインBRAKの発現調節2012

    • Author(s)
      小澤重幸,生駒丈晴,鈴木健司,久保田英朗
    • Organizer
      第66回日本口腔科学会学術集会
    • Place of Presentation
      広島
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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