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Possible pharmacotherapy for drug-induced gingival overgrowth

Research Project

Project/Area Number 25861780
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionNihon University

Principal Investigator

TAKEUCHI Reiri  日本大学, 松戸歯学部, 助教 (60419778)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywords薬物性歯肉増殖症 / 歯肉線維芽細胞 / 18α-グリチルレチン酸 / 細胞増殖 / アポトーシス / 細胞周期 / 薬物誘発性歯肉増殖症 / フェニトイン / 培養ヒト歯肉線維芽細胞 / カスパーゼ / アムロジピン / 歯肉由来線維芽細胞
Outline of Final Research Achievements

This investigation aimed to establish the basis of a pharmacotherapy for drug-induced gingival overgrowth. Gingival overgrowth has been attributed to the enhanced growth of gingival fibroblasts. In this study, we investigated the effects of 18-alpha-glycyrrhetinic acid (GA) on growth, the cell cycle, and apoptosis and on the regulators of these processes in gingival fibroblasts isolated from the patients. GA significantly decreased cell numbers and significantly increased the percentage of cells in the sub-G1 and G0/G1 phases of the cell cycle and the number of apoptotic cells. Nuclear condensation and fragmentation of the cells into small apoptotic bodies appeared in the fibroblasts treated with GA. GA significantly decreased the protein levels of cyclins A and D1, CDKs 2 and 6, phosphorylated Rb (ser780 and ser807/811), Bcl-xL and Bcl-2 and increased the protein levels of p27, cytosolic cytochrome c, pro-caspase-3, and cleaved caspase-3 and the activities of caspases 3 and 9.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (11 results)

All 2016 2015 2014 2013 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (9 results)

  • [Journal Article] Possible pharmacotherapy for nifedipine-induced gingival overgrowth: 18α-glycyrrhetinic acid inhibits human gingival fibroblast growth2016

    • Author(s)
      Reiri Takeuchi, Koichi Hiratsuka, Kazumune Arikawa, Makiko Ono, Masamichi Komiya, Yoshiaki Akimoto, Akira Fujii, Hiroko Matsumoto
    • Journal Title

      British Journal of Pharmacology

      Volume: 173 Issue: 5 Pages: 913-924

    • DOI

      10.1111/bph.13410

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Amlodipine inhibits the G1/S cell cycle transition induced by basic fibroblast growth factor in human gingival fibroblasts2013

    • Author(s)
      Reiri Takeuchi, Kazumune Arikawa, Toshikazu Uchiyama, Etsuko Aida, Michiko Takefuta, Koichi Nakakuki, Tadahiko Utsunomiya
    • Journal Title

      Journal of Oral Tissue Engineering

      Volume: Vol. 11 No. 2 Pages: 141-147

    • NAID

      130004941106

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Depressed apoptosis in cultured human gingival fibroblasts exposed to phenytoin2015

    • Author(s)
      Reiri Takeuchi, Hiroko Matsumoto, Koichi Hiratsuka
    • Organizer
      第57回歯科基礎医学会学術大会
    • Place of Presentation
      朱鷺メッセ:新潟コンベンションセンター(新潟県新潟市)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] 18-alpha-glycyrrhetinic acid has pro-apoptotic effects in fibroblasts isolated from patients with gingival overgrowth2015

    • Author(s)
      Reiri Takeuchi, Koichi Hiratsuka, Makiko Ono, Masamichi Komiya, Yoshiaki Akimoto, Hiroko Matsumoto
    • Organizer
      第35回日本歯科薬物療法学会学術大会
    • Place of Presentation
      鶴見大学大学会館(神奈川県横浜市)
    • Year and Date
      2015-06-20
    • Related Report
      2015 Annual Research Report
  • [Presentation] Induction of apoptosis in nifedipine-reactive gingival fibroblasts using 18α-glycyrrhetinic acid2015

    • Author(s)
      Reiri Takeuchi, Koichi Hiratsuka, Kazumune Arikawa, Hiroko Matsumoto
    • Organizer
      93rd General Session & Exhibition of the IADR
    • Place of Presentation
      Boston, Massachusetts, USA
    • Year and Date
      2015-03-11 – 2015-03-14
    • Related Report
      2014 Research-status Report
  • [Presentation] 培養ヒト歯肉線維芽細胞のカスパーゼ活性に対するフェニトインの影響2014

    • Author(s)
      竹内麗理、平塚浩一、松本裕子
    • Organizer
      第14回日本大学口腔科学会学術大会
    • Place of Presentation
      日本大学松戸歯学部(千葉県松戸市)
    • Year and Date
      2014-09-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 18-alpha-glycyrrhetinic acid suppresses G1/S-phase transition and induces apoptosis in gingival fibroblast isolated from a patient that presented with nifedipine-induced gingival overgrowth2014

    • Author(s)
      Reiri Takeuchi, Makiko Ono, Kazumune Arikawa, Yoshiaki Akimoto, Akira Fujii, Hiroko Matsumoto
    • Organizer
      17th World Congress of Basic & Clinical Pharmacology
    • Place of Presentation
      Cape Town, South Africa
    • Year and Date
      2014-07-13 – 2014-07-18
    • Related Report
      2014 Research-status Report
  • [Presentation] Effect of phenytoin on caspase activity in cultured human gingival fibroblasts2014

    • Author(s)
      竹内麗理、小野眞紀子、秋元芳明、藤井彰、松本裕子
    • Organizer
      第34回日本歯科薬物療法学会学術大会
    • Place of Presentation
      大阪歯科大学(大阪府大阪市)
    • Year and Date
      2014-06-21 – 2014-06-22
    • Related Report
      2014 Research-status Report
  • [Presentation] The potentiality of 18-alpha-glycyrrhetinic acid for treatment of nifedipine-induced gingival overgrowth2013

    • Author(s)
      竹内麗理,遠藤眞美
    • Organizer
      第30回日本障害者歯科学会総会および学術大会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Tentative pharmacotherapy for nifedipine-induced gingival overgrowth using 18-alpha-glycyrrhetinic acid2013

    • Author(s)
      竹内麗理,小野眞紀子,秋元芳明,藤井彰,松本裕子
    • Organizer
      第33回日本歯科薬物療法学会・学術大会
    • Place of Presentation
      東京医科歯科大学M&Dタワー2階鈴木章夫記念講堂(文京区)
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒト歯肉線維芽細胞に対するbFGFおよびIGF-Iの増殖促進効果の比較

    • Author(s)
      竹内麗理,牧村英樹,和田守康
    • Organizer
      第11回日本再生歯科医学会学術大会・総会
    • Place of Presentation
      日本大学理工学部1号館CSTホール(東京都千代田区)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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