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The action mechanism of thalidomide on the infant cancer in a culture model

Research Project

Project/Area Number 18591958
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatric surgery
Research InstitutionSaitama Medical University

Principal Investigator

FUJITA Keiko  Saitama Medical University, Faculty of Medicine, Associate Professor (80173425)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥2,370,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsCulture / Thalidomide / Infant cancer / Angiogenesis / DNA Microarray
Research Abstract

The anti-angiogenic properties of thalidomide have led to the use of the agent as a remedy for malignant tumor, e. g., multiple myeloma, prostatic cancer, hepatoma. Nevertheless, the anti-angiogenic moiety of thalidomide remains unidentified. In 2006, I confirmed anti-angiogenic effects with treatment by thalidomide using three-dimensional collagen gel-cultures of mouse aortae. The results indicated that the anti-angiogenic effects of thalidomide stem from the anti-angiogenic action of apoptosis-inducible active caspase-3. On the basis of these data, I sought in this study to investigate the effects of thalidomide using an in vitro infant cancer model (Hepatoblastoma ; HUH-6 Clone-5) in 2007. I observed morphological and molecular biological changes of hepatoblastoma cells by thalidomide.
Taken together with earlier findings, my new results indicated that the thalidomide-induced directly inhibition of proliferation of hepatoblastoma cells involved apoptosis. I demonstrated by DNA microarray that thalidomide-induced oxidative stress enhanced signaling through bone morphogenetic proteins (Bmps). This lead to up-regulation of the Bmp target gene and Wnt antagonist Dickkopf1 (DKK1) with subsequent inhibition of canonical Wnt/beta-catenin signaling and increased cell death. The apoptosis as a factor important for the mechanism of thalidomide was confirmed. From this, I conclude that perturbing of Bmp/DKK1/Wnt signaling is central to proliferation of hepatoblastoma cells of thalidomide.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (11 results)

All 2008 2007

All Journal Article (6 results) (of which Peer Reviewed: 1 results) Presentation (5 results)

  • [Journal Article] DNA micro-array gene expression profiling of angiogenesis in collagen gelculture2008

    • Author(s)
      Akita M
    • Journal Title

      Clinical Medicine:Cardiology 2

      Pages: 49-57

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 血管新生および腫瘍細胞増殖に対するサリドマイドの影響2008

    • Author(s)
      藤田 恵子
    • Journal Title

      解剖学雑誌 82巻(Suppl)

      Pages: 237-237

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] DNA micro-array gene expression profiling of angiogenesis in collagen gel culture2008

    • Author(s)
      Akita, M
    • Journal Title

      Clinical Medicine : Cardiology 2

      Pages: 49-57

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The effect of thalidomide on angiogenesis and proliferation of cancer cells2008

    • Author(s)
      Fujita, K
    • Journal Title

      Acta Anatomica Nipponica 82(Suppl)

      Pages: 237-237

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 血管新生および腫瘍細胞増殖に対するサリドアイドの影響2008

    • Author(s)
      藤田 恵子
    • Journal Title

      解剖学雑誌 82巻(Suppl)

      Pages: 237-237

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 三次元血管新生培養モデルにおける血管新生阻害実験2007

    • Author(s)
      藤田恵子
    • Journal Title

      解剖学雑誌 82(Suppl)

      Pages: 261-261

    • Related Report
      2006 Annual Research Report
  • [Presentation] 血管新生および腫瘍細胞増殖に対するサリドマイドの影響2008

    • Author(s)
      藤田 恵子
    • Organizer
      第113回日本解剖学会総会、全国学術集会
    • Place of Presentation
      大分大学医学部
    • Year and Date
      2008-03-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 血管新生および腫瘍細胞増殖に対するサリドマイドの影響2008

    • Author(s)
      藤田 恵子
    • Organizer
      第113回日本解剖学会総会・全国学術集会
    • Place of Presentation
      大分大学医学部
    • Year and Date
      2008-03-29
    • Related Report
      2007 Annual Research Report
  • [Presentation] The effect of thalidomide on angiogenesis and proliferation of cancer cells.2008

    • Author(s)
      Fujita, K
    • Organizer
      The 113th Anatomical Congress 29
    • Place of Presentation
      Oita University
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] In vitroにおける毛細血管の形成2007

    • Author(s)
      山田 久美子
    • Organizer
      第48回日本組織細胞化学会総会, 第39回日本臨床分子形態学会総会合同学術集会
    • Place of Presentation
      甲府市総合市民会館
    • Year and Date
      2007-09-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Capillary tube formation in vitro2007

    • Author(s)
      Yamada, K
    • Organizer
      The 48th Congress of Histochem & Cytochem The 39th Annual Meeting of the Japanese Society for Clinical, Molecular Morphology (Joint Meeting)29
    • Place of Presentation
      Kofu City General Auditorium
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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