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2012 Fiscal Year Annual Research Report

タンパク質発現解析に基づいた骨軟部腫瘍バイオマーカーの大規模検証及び機能解析

Research Project

Project/Area Number 22791405
Research InstitutionJuntendo University

Principal Investigator

末原 義之  順天堂大学, 医学部, 助教 (70509405)

Project Period (FY) 2010-04-01 – 2013-03-31
Keywords骨軟部腫瘍 / プロテオミクス / GIST / Ewing肉腫 / 滑膜肉腫 / Pfetin / NPM1 / SCRN1
Research Abstract

<計画>本研究は骨軟部腫瘍の手術検体を使用したプロテオーム解析を行うことで、(i)予後予測マーカーや組織特異的マーカーの開発を行い、(ii) 各々の腫瘍にて同定された予後予測タンパク質に対しては、バイオマーカー(予後予測マーカー)としての可能性・有用性の検証を行う。(iii)バイオマーカーとして有用と判断されたタンパク質は、治療ターゲット及び機能解明のための機能解析を行う。 <結果>タンパク質発現解析を行い同定した予後予測マーカーであるPfetinとDDX39 (GIST)、Secernin-1(滑膜肉腫)、NPN1(Ewing肉腫)タンパク質等について、特異抗体を用いた免疫染色による国内海外多施設研究を行い、それぞれのタンパク質の発現が予後に有意に差があることを確認することに成功し、予後予測マーカーとして有用であることを証明した。Pfetinタンパク質(GIST)、Secernin-1タンパク質(滑膜肉腫)、NPM1(Ewing肉腫)の免疫沈降等の実験を行い、相互タンパク質(interaction protein)の同定に成功した。また、それぞれのターゲットタンパク質(遺伝子)発現の強制抑制及び強制発現を行い、その状況下における細胞増殖能の観察と制御タンパク質の網羅的タンパク質のプロファイリングを行った(現在解析中)。またGISTパラフィン固定検体より抽出したDNAを用いてメチル化修飾及び、シークエンスの行い解析を行い、Pfetinのある特定部位のORF変異がPfetinタンパク質発現及びGISTの生命予後に特異的に関与していることを同定した。

Current Status of Research Progress
Reason

24年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

24年度が最終年度であるため、記入しない。

  • Research Products

    (18 results)

All 2013 2012

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (9 results) (of which Invited: 1 results)

  • [Journal Article] Proteomic approach towards personalized sarcoma treatment: Lessons from prognostic biomarker discovery in gastrointestinal stromal tumor.2013

    • Author(s)
      Kondo T, Suehara Y et al.
    • Journal Title

      Proteomics Clinical Applications

      Volume: 7 Pages: 70-78

    • DOI

      10.1002/prca.201200085

    • Peer Reviewed
  • [Journal Article] Identification of KIF5B-RET and GOPC-ROS1 fusions in lung adenocarcinomas through a comprehensive mRNA-based screen for tyrosine kinase fusions.2012

    • Author(s)
      Suehara Y et al
    • Journal Title

      Clinical Cancer Research

      Volume: 18 Pages: 6599-6608

    • DOI

      10.1158/1078-0432. CCR-12-0838

    • Peer Reviewed
  • [Journal Article] Discovery of biomarkers for osteosarcoma by proteomics approaches2012

    • Author(s)
      Suehara Y et al.
    • Journal Title

      Sarcoma

      Volume: 1 Pages: 425636

    • DOI

      10.1155/2012/425636

    • Peer Reviewed
  • [Journal Article] Malignant granular cell tumor with unusual long clinical course. An autopsy case with review of literatures.2012

    • Author(s)
      Saito T, Suehara Y et al.
    • Journal Title

      Journal of Cancer Science and Therapy

      Volume: 4 Pages: 260-263

    • DOI

      10.4172/1948-5956.1000152

    • Peer Reviewed
  • [Journal Article] Low-grade myofibroblastic sarcoma of the distal femur2012

    • Author(s)
      Saito T, Suehara Y et al.
    • Journal Title

      International Journal of Surgery Case Reports

      Volume: 4 Pages: 195-199

    • DOI

      10.1016/j.ijscr.2012.11.017.

    • Peer Reviewed
  • [Journal Article] Validation Study on Pfetin and ATP-dependent RNA Helicase DDX39 as Prognostic Biomarkers in Gastrointestinal Stromal Tumour2012

    • Author(s)
      Kubota D, Suehara Y et al.
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 42 Pages: 730-741

    • DOI

      10.1093/jjco/hys092.

    • Peer Reviewed
  • [Journal Article] Intraneural lipomatous tumor of the median nerve: Three case reports with a review of literature2012

    • Author(s)
      Okubo T, Suehara Y et al.
    • Journal Title

      International Journal of Surgery Case Reports

      Volume: 3 Pages: 407-411

    • DOI

      10.1016/j.ijscr.2012.05.007.

    • Peer Reviewed
  • [Journal Article] Pedicle freezing with liquid nitrogen for malignant bone tumour in the radius: a new technique of osteotomy of the ulna.2012

    • Author(s)
      Torigoe T, Suehara Y et al.
    • Journal Title

      Journal of orthopaedic surgery

      Volume: 20 Pages: 98-102

    • Peer Reviewed
  • [Journal Article] Clinical proteomics identified ATP-dependent RNA helicase DDX39 as a novel biomarker to predict poor prognosis of patients with gastrointestinal stromal tumor.2012

    • Author(s)
      Kikuta K, Suehara Y et al.
    • Journal Title

      Journal of proteomic

      Volume: 75 Pages: 1089-1098

    • DOI

      10.1093/jjco/hys092.

    • Peer Reviewed
  • [Presentation] PROTEOMIC APPROACH REVEALED NOVEL PROGNOSTIC BIOMARKERS IN GASTROINTESTINAL STROMAL TUMOR (GIST)2012

    • Author(s)
      Kondo T, Suehara Y et al.
    • Organizer
      Connective Tissue Oncology Society
    • Place of Presentation
      Prague, Czech Republic
    • Year and Date
      20121114-20121117
  • [Presentation] INTEGRATION OF PROTEOMIC AND TRANSCRIPTOMIC ANALYSIS REVEALS THE DISTINCTIVE MOLECULAR BACKGROUNDS FOR GASTROINTESTINAL STROMAL TUMOR OF THE SMALL INTESTINE2012

    • Author(s)
      Ichikawa H, Suehara Y et al.
    • Organizer
      Connective Tissue Oncology Society
    • Place of Presentation
      Prague, Czech Republic
    • Year and Date
      20121114-20121117
  • [Presentation] CHEMO-RESPONSIVENESS PREDICTIVE BIOMARKER DISCOVERY FOR OSTEOSARCOMA USING MICRORNA-MICROARRAY2012

    • Author(s)
      Kubota D, Suehara Y et al.
    • Organizer
      Connective Tissue Oncology Society
    • Place of Presentation
      Prague, Czech Republic
    • Year and Date
      20121114-20121117
  • [Presentation] PROTEOMIC ANALYSIS IDENTIFIED LUNG METASTASIS-RELATED PROTEINS IN OSTEOSARCOMA2012

    • Author(s)
      Mukaihara K, Suehara Y et al.
    • Organizer
      Connective Tissue Oncology Society
    • Place of Presentation
      Prague, Czech Republic
    • Year and Date
      20121114-20121117
  • [Presentation] ROLE OF POST TRANSLATIONAL MODIFICATION OF THE RUNX2 TRANSCRIPTION FACTOR IN OSTEOSARCOMA2012

    • Author(s)
      Ito T, Suehara Y et al.
    • Organizer
      Connective Tissue Oncology Society
    • Place of Presentation
      Prague, Czech Republic
    • Year and Date
      20121114-20121117
  • [Presentation] PROTEIN EXPRESSION PROFILING OF PLEURAL EFFUSION IN MALIGNANT PLEURAL MESOTHELIOMA2012

    • Author(s)
      Sugihara Y, Suehara Y et al.
    • Organizer
      Connective Tissue Oncology Society
    • Place of Presentation
      Prague, Czech Republic
    • Year and Date
      20121114-20121117
  • [Presentation] Proteomic analysis identified lung metastasis-related proteins in osteosarcoma2012

    • Author(s)
      Daisuke Kubota, Suehara Y et al.
    • Organizer
      Human Proteome Organisation
    • Place of Presentation
      Boston, U.S.
    • Year and Date
      20120901-20120902
  • [Presentation] 基礎研究の現状と診断:骨軟部腫瘍におけるタンパク質発現解析2012

    • Author(s)
      末原義之
    • Organizer
      第45回日本整形外科学会・骨軟部腫瘍学術集会
    • Place of Presentation
      東京
    • Year and Date
      20120714-20120715
    • Invited
  • [Presentation] KIF5B-RET: Discovery of a novel fusion oncogene in lung adenocarcinomas by a systematic screen for tyrosine kinase fusions and identification of patients for a RET targeted therapy trial.2012

    • Author(s)
      Suehara Y et al.
    • Organizer
      American Society of Clinical Oncology
    • Place of Presentation
      Chicago, USA
    • Year and Date
      20120501-20120504

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Published: 2014-07-24  

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