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Anti-tumor effect and mechanism of combination of retinoid and histone deacetylase inhibitor against cutaneous T cell lymphoma cell

Research Project

Project/Area Number 24591636
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionTokyo Medical University

Principal Investigator

TSUBOI RYOJI  東京医科大学, 医学部, 教授 (70221421)

Research Collaborator KATO Yukihiko  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsHDAC inhibitor / MS-275 / Entinostat / レチノイド / Am80 / 抗腫瘍効果 / 皮膚リンパ腫 / エピジェネティックス / HDACi / in vivo抗腫瘍効果 / In vitro抗腫瘍効果 / 作用機序 / エピジェネティクス
Outline of Final Research Achievements

Anti-tumor effect of combination of retinoid (Am80) and histone deacetylase inhibitor MS-275(entinostat) in a cutaneous T cell lymphoma cell line (SeAx) was examined from the point of restoration of tumor suppressor gene retinoic acid receptor (RAR)β2 via histone acetylation. RARβ2 gene expression was restored only by the combination rather than by either of the agents singly. The combination treatment significantly inhibited cell growth in vitro, suppressed subcutaneously transplanted tumor growth, and prolonged survival of tumor-bearing mice in vivo. In the combination treatment, the histone H4 acetylation level in the promoter region increased after restoration of RARβ2 expression.
(Kato Y, Egusa C, Maeda T, Tsuboi R: Anti-tumor effect of combination of retinoid and histone deacetylase inhibitor in cutaneous T cell lymphoma cell is due to restoration of tumor suppressor gene retinoic acid receptor β2 via histone acetylation (Submitted).

Report

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

    (2 results)

All 2014 2013

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

  • [Journal Article] Combination of HDAC inhibitor MS-275 and IL-2 increased anti-tumor effect in a melanoma model via activated cytotoxic T cells.2014

    • Author(s)
      Kato Y, Yoshino I, Egusa C, Maeda T, Pili R, Tsuboi R
    • Journal Title

      J Dermatol Sci

      Volume: 75 Issue: 2 Pages: 140-147

    • DOI

      10.1016/j.jdermsci.2014.04.014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Histone deacetylase inhibitor MS-275 restored retinoid sensitivity and had an antitumor effect in combination with retinoic acid Am80 in human cutaneous T cell lymphoma2013

    • Author(s)
      Y Kato, C Egusa, T Maeda, RTsuboi
    • Organizer
      Epigenetics 2013
    • Place of Presentation
      Port Stephens, New South Wales, Australia
    • Related Report
      2013 Research-status Report

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

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