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前立腺癌検診におけるシアリダーゼ遺伝子検査の有効性

Research Project

Project/Area Number 17659181
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Hygiene
Research InstitutionMiyagi Cancer Center Research Institute

Principal Investigator

和田 正  Miyagi Cancer Center Research Institute, 生化学部, 上席主任研究員 (50390894)

Co-Investigator(Kenkyū-buntansha) 秦 敬子  宮城県立がんセンター(研究所), 生化学部, 共同研究員 (60390895)
佐藤 郁郎  宮城県立がんセンター(研究所), 病理学部, 総括研究員 (50225918)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2007: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywords癌 / 酵素 / シアリダーゼ / 糖鎖 / 遺伝子 / 癌診断 / トランスレーショナルリサーチ / 医療・福祉 / シアル酸
Research Abstract

前立腺癌の一次検診として、現在、血清PSA(前立腺特異抗原)値によるスクリーニングが実施されている。しかし、PSA値は必ずしも癌に特異的ではない為、偽陰性あるいは偽陽性を示すことがあり、より正確な前立腺癌の鑑別診断法が望まれている。
本研究では、我々が研究を進めてきた形質膜シアリダーゼ遺伝子を利用し、癌診断の向上をめざした。我々はこれまで、シアリダーゼ遺伝子(NEU3)の単離およびモノクロナール抗体の作成に世界で初めて成功したので、これをツールとして、癌組織の免疫染色や癌患者血清のシアリダーゼ定量を試みた。
前立腺癌を疑われた患者から針生検により採取した前立腺組織、および前立腺癌患者の手術摘出標本について、mRNAレベルを解析すると、癌部では非癌部に比べて、有意にNEU3レベルが上昇していた。また、シアリダーゼモノクロナール抗体による免疫組織染色を行うと、癌組織ではグリソンスコアに比例する形で悪性度が高いほど強陽性に染色された。そこで、患者血清中にNEU3蛋白が検出されるかどうかを調べるため、ELISA法を開発した。患者血清においては健常者血清に比べて、高値を示した。今後は癌患者血清中のシアリダーゼ蛋白の同定を行い、ELISA法の検出感度の向上を試みて、癌診断への応用を図りたい。

Report

(3 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (15 results)

All 2008 2007 2006 2005 Other

All Journal Article (12 results) (of which Peer Reviewed: 3 results) Presentation (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Roles of plasma membrane-associated sialidase NEU3 in human cancers2008

    • Author(s)
      Miyagi, T., et. al.
    • Journal Title

      Biochim. Biophys. Acta 1780

      Pages: 532-537

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human sialidase as a cancer marker2008

    • Author(s)
      Miyagi, T., et. al.
    • Journal Title

      Proteomics (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acrucial role of plasma membrane-associated sialidase(NEU3)in the survival of human cancer cells2007

    • Author(s)
      Wada, T., et. al.
    • Journal Title

      Oncogene 26

      Pages: 2483-2490

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A crucial role of plasma membrane-associated sialidase (NEU3) in the survival of human cancer cells.2007

    • Author(s)
      Wada, T. et al.
    • Journal Title

      Oncogene 26

      Pages: 2483-2490

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Epidermal growth factor-induced mobilization of a ganglioside-speciflc sialidase (NEU3) to membrane ruffles.2006

    • Author(s)
      Yamaguchi, K., et al.
    • Journal Title

      Biochem Biophys Res Commun. 346

      Pages: 484-490

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Down-regulation of sialidase NEU4 may contribute to invasive properties of human colon cancers.2006

    • Author(s)
      Yamanami, T. et al.
    • Journal Title

      Cancer Sci. 98

      Pages: 299-307

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Plasma membrane-associated sialidase (NEU3) differentially regulates integrin-mediated cell proliferation through laminin- and fibronectin-derived signalling.2006

    • Author(s)
      Kato, K. et al.
    • Journal Title

      Biochem.J. 394

      Pages: 647-656

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Plasma membrane-associated sialidase is up-regulated in renal cell carcinoma and promotes the interleukin-6-induced apoptosis suppression and cell motility.2006

    • Author(s)
      Ueno, S. et al.
    • Journal Title

      J.Biol.Chem. 281

      Pages: 7756-7764

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Homology modeling of human sialidase enzymes NEU1, NEU3 and NEU4 based on the crystal structure of NEU2 : Hints for the design of selective NEU3 inhibitors.2006

    • Author(s)
      Magesha, S., et al.
    • Journal Title

      J Mol.Graphics Modelling (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Plasma membrane production of ceramide from ganglioside GM3 in human fibroblasts.2006

    • Author(s)
      Valaperta, R., et al.
    • Journal Title

      FASEB J (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A symmetric membrane ganglioside sialidase activity specifies axonal fate.2005

    • Author(s)
      Da Silva et al.
    • Journal Title

      Nat.Neurosci. 8

      Pages: 606-615

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Evidence for Mitochondrial Localization of a Novel Human Sialidase (NEU4).2005

    • Author(s)
      Yamaguchi, T. et al.
    • Journal Title

      Biochem.J. 390

      Pages: 85-93

    • Related Report
      2005 Annual Research Report
  • [Presentation] Aberrant expression and its pathological role of plasma membrane-associated sialidase in human cancer2007

    • Author(s)
      Wada, T., et. al.
    • Organizer
      第66回日本癌学会総会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.pref.miyagi.jp/mcc/htdocs/kenkyu/seikagaku.html

    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] がんまたは糖尿病治療のための医薬組成物2005

    • Inventor(s)
      宮城 妙子, 和田 正, 山口 壹範
    • Industrial Property Rights Holder
      宮城県
    • Filing Date
      2005-11-15
    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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