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2013 Fiscal Year Annual Research Report

軟部肉腫における転移関連バイオマーカーの同定と分子標的治療への応用

Research Project

Project/Area Number 23590434
Research InstitutionJuntendo University

Principal Investigator

齋藤 剛  順天堂大学, 医学部, 准教授 (80439736)

Keywords骨軟部腫瘍 / 浸潤・転移 / 原発不明癌骨転移 / GIST / 骨巨細胞腫
Research Abstract

1)骨巨細胞腫(GCTB)は良性腫瘍だが、再発率が高く治療に難渋する。また、経過中に2%程度が悪性転化するが、その詳細なメカニズムは不明である。GCTBにおけるp53遺伝子変異の悪性転化への関与の可能性を検討した。悪性転化例3例では、悪性転化と診断された病変ではp53遺伝子変異あるいはLOHが確認され免疫染色でもp53過剰発現を認めた。通常型病変ではp53遺伝子変異を7例に認めたが、p53過剰発現は認めなかった。また、他臓器転移例2例のうち1例にはp53領域のLOHを認めたが、p53の遺伝子変異・過剰発現は認めなかった。glutathione peroxidase1(GPX-1)免疫染色では、悪性転化例3例および他臓器転移例2例では過剰発現を認めた。GCTB全体でもGPX-1の過剰発現は早期再発と有意な相関を認めた。また、p53過剰発現とGPX-1の過剰発現の間には正の相関を認めた。蛋白過剰発現に結びつくp53遺伝子変異がGCTBの悪性転化に重要な役割を果たし、この過程にp53によるGPX-1の転写制御による過剰発現が関与している可能性が示唆された(Okubo et al. Virchows Arch, 2013)
2)胃腸管間質腫瘍(GIST)におけるpfetinの予後予測因子としての検討を多施設共同研究にて行い、有効な予後予測因子としての価値を確認した(Kuboda et al. Jpn J Clin Oncol, 2013)。また、プロテオミクスを用いてその発現が予後不良因子として働くDDX39を 新規予後予測マーカー同定した(Kikuta et al. J Proteomics, 2012)。さらに、プロテオミクスと遺伝子発現解析を組み合わせることで、GISTにおける新規予後予測マーカーKCTD10を同定した(Kubota et al. PLoS One, 2013)

  • Research Products

    (23 results)

All 2014 2013

All Journal Article (23 results) (of which Peer Reviewed: 23 results)

  • [Journal Article] Distinct Wnt/-catenin signaling activation in the serrated neoplasia pathway and the adenoma-carcinoma sequence of the colorectum.2014

    • Author(s)
      Murakami T, Mitomi H, Saito T, Takahashi M, Sakamoto N, Fukui N, Yao T, Watanabe S.
    • Journal Title

      Modern Pathology

      Volume: in press Pages: in press

    • Peer Reviewed
  • [Journal Article] A case of Krukenberg carcinoma metastasized from colon cancer resembling mucinous cystadenocarcinoma of the ovary.2014

    • Author(s)
      Shiono S, Saito T, Fujii H, Arakawa A, Nakamura T, Yao T.
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 7 Pages: 394-401

    • Peer Reviewed
  • [Journal Article] Review: Proteomic technologies to develop biomarkers and functional analyses in the bone and soft tissue tumors.2014

    • Author(s)
      Suehara Y, Kohsaka S, Kubota D, Mukaihara K, Akaike K, Mineki R, Fujimura T, Ladanyi M, Saito T, Kondo T.
    • Journal Title

      J Proteo Bioinf

      Volume: in press Pages: in press

    • Peer Reviewed
  • [Journal Article] A case of dedifferentiated solitary fibrous tumor of thoracic cavity.2014

    • Author(s)
      Masuda Y, Kurisaki-Arakawa A, Hara K, Arakawa A, Oh S, Suzuki K, Yao T, Saito T.
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 7 Pages: 386-393

    • Peer Reviewed
  • [Journal Article] An outpatient-based survey about the recognition of locomotive syndrome and the results of the loco-check at a university hospital in Tokyo.2014

    • Author(s)
      Okubo T, Suehara Y, Kawasaki T, Akaike K, Toda M, Okubo N, Kubota D, Mukaihara K, Kim Y, Kaketa T, Homma Y, Shimanouchi N, Saito T, Takagi T, Kaneko K.
    • Journal Title

      Brit J Med Med Res

      Volume: 4 Pages: 3268-3268

    • Peer Reviewed
  • [Journal Article] Desmoplastic fibroma of the rib with cystic change : a case report and literature review.2014

    • Author(s)
      Okubo T, Saito T, Takagi T, Suehara Y, Kaneko K.
    • Journal Title

      Skeletal Radiol

      Volume: 43 Pages: 703-708

    • Peer Reviewed
  • [Journal Article] Giant-cell tumor of bone arising in the anterior chest wall with positive expressions of GPX-1: a case report with review of literature.2014

    • Author(s)
      Toda M, Suehara Y, Akaike K, Okubo T, Kubota D, Mukaihara K, Kaneko K, Yao T, Takagi T, Saito T.
    • Journal Title

      Int Canc Conf J

      Volume: in press Pages: in pres

    • Peer Reviewed
  • [Journal Article] Downregulation of sFRP-2 by epigenetic silencing activates the -catenin/Wnt signaling pathway in esophageal basaloid squamous cell carcinoma.2014

    • Author(s)
      Saito T, Mitomi H, Imamhasan A, Hayashi T, Mitani K, Takahashi M, Kajiyama Y, Yao T.
    • Journal Title

      Virchows Arch

      Volume: 464 Pages: 135-143

    • Peer Reviewed
  • [Journal Article] Distinct profile of HIF1α, PTCH, EphB2 or DNA repair protein expression and BRAF mutation in colorectal serrated adenomas.2014

    • Author(s)
      Morimoto T, Murakami T, Sakamoto N, Watanabe S, Saito T, Takahashi M, Yao T, Mitomi H.
    • Journal Title

      J Gastroenterology and Hepatology

      Volume: in press Pages: in press

    • Peer Reviewed
  • [Journal Article] Review: SYT-SSX fusion protein and histological epithelial differentiation in synovial sarcoma: relationship with extracellular matrix remodeling.2013

    • Author(s)
      Saito T.
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 6 Pages: 2272-2279

    • Peer Reviewed
  • [Journal Article] A case of bilateral renal cell carcinoma associated with long-term dialysis showing false-positive immunoreactivity for TFE3.2013

    • Author(s)
      Kurisaki-Arakawa A, Saito T, Takahashi M, Mitani K, Fukumura Y, Nagashima Y, Argani P, Yao T.
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 6 Pages: 2585-2590

    • Peer Reviewed
  • [Journal Article] Desmoplastic fibroma of the scapula with uptake of FDG-PET: A case report with review of literature.2013

    • Author(s)
      Okubo T, Saito T, Takagi T, Torigoe T, Suehara Y, Akaike K, Yao T, Kaneko K.
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 6 Pages: 2230-2236

    • Peer Reviewed
  • [Journal Article] A case of myxoid liposarcoma of the breast.2013

    • Author(s)
      Saito T, Ryu M, Fukumura Y, Asahina M, Arakawa A, Nakai K, Miura H, Saito M, Yao T.
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 6 Pages: 1432-1436

    • Peer Reviewed
  • [Journal Article] The prognostic value of pfetin: a validation study in gastrointestinal stromal tumors using a commercially available antibody.2013

    • Author(s)
      Kubota D, Mukaihara K, Yoshida A, Suehara Y, Saito T, Okubo T, Gotoh M, Orita H, Tsuda H, Kaneko K, Kawai A, Kondo T, Sato K, Yao T.
    • Journal Title

      Jpn J Clin Oncol

      Volume: 43 Pages: 669-675

    • Peer Reviewed
  • [Journal Article] Gene expression network analysis of ETV1 reveals KCTD10 as a novel prognostic biomarker in gastrointestinal stromal tumor.2013

    • Author(s)
      Kubota D, Yoshida A, Tsuda H, Suehara Y, Okubo T, Saito T, Orita H, Sato K, Taguchi T, Yao T, Kaneko K, Katai H, Kawai A, Kondo T.
    • Journal Title

      PLoS One

      Volume: 8 Pages: e73896

    • Peer Reviewed
  • [Journal Article] A combined integrated genomics / functional genomics strategy to dissect the biology of a cancer-associated, aberrant transcription factor, the ASPSCR1-TFE3 fusion oncoprotein.2013

    • Author(s)
      Kobos R, Nagai M, Tsuda M, Lui MY, Saito T, Laé M, Mo Q, Olshen A, Lianoglou S, Leslie C, Shao Y, Antczak C, Djaballah H, Ladanyi M.
    • Journal Title

      J Pathol

      Volume: 229 Pages: 743-754

    • Peer Reviewed
  • [Journal Article] Low-grade myofibroblastic sarcoma of the distal femur.2013

    • Author(s)
      Saito T, Mitomi H, Kurisaki A, Torigoe T, Takagi T, Suehara Y, Okubo T, Kaneko K, Yao T.
    • Journal Title

      Int J Surg Case Rep

      Volume: 4 Pages: 195-199

    • Peer Reviewed
  • [Journal Article] Infiltrative angiolipoma of the thoracic wall: A case report.2013

    • Author(s)
      Hamano A, Suzuki T, Saito T, Kuwatsuru R, Oh S, Suzuki K.
    • Journal Title

      Open J Clin Diag

      Volume: 3 Pages: 19-22

    • Peer Reviewed
  • [Journal Article] Galectin-4, a novel predictor for lymph node metastasis in lung adenocarcinoma: A proteomic study.2013

    • Author(s)
      Hayashi T, Saito T, Fujimura T, Hara K, Takamochi K, Mitani K, Mineki R, Kazuno S, Oh S, Suzuki K, Ueno T, Suzuki K, Yao T.
    • Journal Title

      PLoS One

      Volume: 82013 Pages: e81883

    • Peer Reviewed
  • [Journal Article] Alteration in the Wnt/β-catenin signaling pathway in gastric neoplasias of fundic gland (chief cell predominant) type.2013

    • Author(s)
      Hidaka Y, Mitomi H, Saito T, Takahashi M, Lee SY, Matsumoto K, Yao T, Watanabe S.
    • Journal Title

      Human Pathol

      Volume: 44 Pages: 2438-2448

    • Peer Reviewed
  • [Journal Article] Protein expression and methylation of DNA repair genes hMLH1, hMSH2, MGMT and BRCA1 and their correlation with clinicopathological parameters and prognosis in basal-like breast cancer.2013

    • Author(s)
      Alkam Y, Mitomi H, Nakai K, Himuro T, Saito T, Takahashi M, Arakawa A, Yao T, Saito M.
    • Journal Title

      Histopathology

      Volume: 63 Pages: 713-725

    • Peer Reviewed
  • [Journal Article] Tissue Sample Preparation for Biomarker Discovery.2013

    • Author(s)
      Suehara Y, Kubota D, Saito T.
    • Journal Title

      Methods Mol Biol

      Volume: 1002 Pages: 13-23

    • Peer Reviewed
  • [Journal Article] Possible involvement of p53 genetic alteration associated with protein overexpression in malignant transformation of giant-cell tumor of bone.2013

    • Author(s)
      Okubo T, Saito T, Mitomi H, Takagi T, Torigoe T, Suehara Y, Yao T, Kaneko K.
    • Journal Title

      Virchows Arch

      Volume: 63 Pages: 67-77

    • DOI

      doi: 10.1007/s00428-013-1435-z

    • Peer Reviewed

URL: 

Published: 2015-05-28  

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