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A study on the response of oral mucosa to reactive oxygen species and its application to the prevention against oral cancer.

Research Project

Project/Area Number 23390468
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionFukuoka Dental College

Principal Investigator

IKEBE Tetsuro  福岡歯科大学, 歯学部, 教授 (20202913)

Co-Investigator(Kenkyū-buntansha) HAYAKAWA Hiroshi  福岡歯科大学, 口腔歯学部, 教授 (70150422)
鍛治屋 浩 (鍛冶屋 浩)  福岡歯科大学, 歯学部, 講師 (80177378)
Co-Investigator(Renkei-kenkyūsha) KAJIYA Hiroshi  福岡歯科大学, 口腔歯学部, 講師 (80177378)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2011: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Keywords活性酸素 / 口腔癌 / ケラチノサイト / 細胞老化 / 癌抑制遺伝子 / エピジェネティック修飾 / 老化マーカー / EMT / TRP
Research Abstract

In order to investigate the mechanism how reactive oxygen species (ROS) induce carcinogenesis of keratinocytes, normal human kerainocytes (NHEK) and oral squamous carcinoma cells (SCCs) were treated with hydrogen peroxide, and compared for the expressions of cellular senescence-associated molecules that is thought to be one of the tumor suppressor mechanisms. Hydrogen peroxide increased the expressions of senescence associated-beta-galactosidase and p16(INK4a) and induced the growth arrest in G0/G1 phase, in NHEK, but not SCC cells. Methylation level in p16 (INK4a) promoter was reduced with hydrogen peroxide in NHEK, but not SCCs. Methylation inhibitor 5-Azac enhanced the expression of p16 (INK4a) in NHEK, but not SCCs. The expression of DNA methyltransferase DNMT1 was suppressed in NHEK, but not SCCs. The inhibition of cellular senescence through the epigenetic modification on p16 (INK4a) expression may play an important role in carcinogenesis of keratinocytes.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (17 results)

All 2014 2013 2012 2011

All Journal Article (10 results) (of which Peer Reviewed: 4 results) Presentation (7 results)

  • [Journal Article] Pathophysiology of BRONJ : Drug-related osteoclastic disease of the jaw2013

    • Author(s)
      Ikebe T
    • Journal Title

      Oral Science Int

      Volume: 10 Pages: 1-8

    • Related Report
      2013 Final Research Report
  • [Journal Article] Inhibition of extracellular signal-regulated kinase downregulates claudin-2 expression and alters paracellular permeability in mouse rectum CMT93-II cells2013

    • Author(s)
      Inai T, Kitagawa N, Hatakeyama Y, Ikebe T, Iida H, Fujita M
    • Journal Title

      Tissue and Cell

      Volume: 45(3) Pages: 175-182

    • Related Report
      2013 Final Research Report
  • [Journal Article] Inhibition of extracellular signal-regulated kinase downregulates claudin-2 expression and alters paracellular permeability in mouse rectum CMT93-II cells.2013

    • Author(s)
      Inai T, Kitagawa N, Hatakeyama Y, Ikebe T, Iida H, Fujita M.
    • Journal Title

      Tissue and Cell

      Volume: 45 Issue: 3 Pages: 175-182

    • DOI

      10.1016/j.tice.2012.11.001

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines2012

    • Author(s)
      Okamoto Y, Ohkubo T, Ikebe T, Yamazaki J
    • Journal Title

      Int J Oncol

      Volume: 40 Pages: 1431-1440

    • Related Report
      2013 Final Research Report
  • [Journal Article] Reduced expression of nuclear factor kB in oral mucosa undergoing preoperative chemoradiotherapy2012

    • Author(s)
      Ikebe T, Yamasaki K, Takamune Y, Nakayama H, Shinohara M
    • Journal Title

      Oral Science Int

      Volume: 9 Pages: 33-37

    • NAID

      10031144847

    • Related Report
      2013 Final Research Report
  • [Journal Article] Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epithelial keratinocytes via TGF-beta secretion2012

    • Author(s)
      Fukawa T, Kajiya H, Ozeki S, Ikebe T, Okabe K
    • Journal Title

      Exp Cell Res

      Volume: 318 Pages: 1926-1932

    • Related Report
      2013 Final Research Report
  • [Journal Article] Selective inhibition of nuclear factor-ĸB by nuclear factor-ĸB essential modulator-binding domain peptide suppresses the metastasis of highly metastatic oral squamous cell carcinoma2012

    • Author(s)
      Tanaka T, Nakayama H, Yoshitake Y, Irie A, Nagata M, Kawahara K, Takamune Y, Yoshida R, Nakagawa Y, Ogi H, Shinriki S, Ota K, Hiraki A, Ikebe T, Nishimura Y, Shinohara M
    • Journal Title

      Cancer Sci

      Volume: 103 Pages: 455-463

    • Related Report
      2013 Final Research Report
  • [Journal Article] Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epithelial keratinocytes via TGF-beta secretion.2012

    • Author(s)
      Fukawa T, Kajiya H, Ozeki S, Ikebe T, Okabe K.
    • Journal Title

      Exp Cell Res

      Volume: 318 Issue: 15 Pages: 1926-1932

    • DOI

      10.1016/j.yexcr.2012.05.023

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced expression of nuclear factor kB in oral mucosa undergoing preoperative chemoradiotherapy.2012

    • Author(s)
      Ikebe T, Yamasaki K, Takamune Y, Nakayama H, Shinohara M.
    • Journal Title

      Oral Science Int

      Volume: 9 Issue: 2 Pages: 33-37

    • DOI

      10.1016/s1348-8643(12)00008-0

    • NAID

      10031144847

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines2012

    • Author(s)
      Okamoto Y, et al
    • Journal Title

      International Journal of Oncology

      Volume: 40 Pages: 1431-1440

    • DOI

      10.3892/ijo.2012.1340

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 口腔扁平上皮癌細胞におけるkeratin13遺伝子のエピジェネティック制御機構2014

    • Author(s)
      永沼香織、佐々木三奈、竹山顕子、勝俣由里、府川晃久、太田信敬、岡本愛彦、橋本憲一郎、大関悟、池邉哲郎
    • Organizer
      第32回日本口腔腫瘍学会学術集会
    • Place of Presentation
      札幌市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 培養口腔癌細胞のkeratin13遺伝子プロモーター領域におけるヒストン修飾解析2014

    • Author(s)
      永沼香織、森紘一郎、佐々木三奈、田中文恵、長岡良礼、勝俣由里、永嶌勝之、太田信敬、府川晃久、岡本愛彦、内田竜司、泉喜和子、利谷幸治、橋本憲一郎、大関悟、池邉哲郎
    • Organizer
      第68回日本口腔科学会学術集会
    • Place of Presentation
      東京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 正常角化上皮細胞の上皮間葉移行におけるIKKalphaシグナルの関与2014

    • Author(s)
      佐々木三奈、森紘一郎、永嶌勝之、田中文恵、長岡良礼、永沼香織、勝俣由里、太田信敬、府川晃久、利谷幸治、橋本憲一郎、泉喜和子、内田竜司、大関悟、池邉哲郎
    • Organizer
      第68回日本口腔科学会学術集会
    • Place of Presentation
      東京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 酸化ストレスに対するがん抑制遺伝子を介した細胞老化誘導作用2013

    • Author(s)
      佐々木三奈、長岡良礼、永沼香織、太田信敬、府川晃久、中山修二、山下善弘、大関悟、池邉哲郎
    • Organizer
      第67回日本口腔科学会学術集会
    • Place of Presentation
      宇都宮市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Activation of TRPM8 channels augments invasive potential of oral carcinoma cell lines2012

    • Author(s)
      Okamoto Y, 他5名
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2012-03-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] TRPM8の選択的拮抗薬によるヒト舌癌HSC細胞における浸潤能の抑制2012

    • Author(s)
      岡本愛彦、大久保つや子、内田竜司、山崎 純、池邉哲郎
    • Organizer
      第66回日本口腔科学会学術集会
    • Place of Presentation
      広島国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] 酸化ストレスによる扁平上皮癌細胞の上皮間葉移行(EMT)作用2011

    • Author(s)
      府川晃久, 他7名
    • Organizer
      第56回日本口腔外科学会学術大会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2011-10-21
    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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