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Characterization of sarcoma stem cells and development of the stem cell-targeting agents utilizing viral engineering

Research Project

Project/Area Number 20249065
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionResearch Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses

Principal Investigator

TAKAHASHI Katsuhito  Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses, 研究所, 部長 (40211338)

Co-Investigator(Kenkyū-buntansha) TOGUCHIDA Junya  京都大学, 再生医科学研究所, 教授 (40273502)
YAMAMURA Hisako  地方独立行政法人大阪府立病院機構大阪府立成人病センター(研究所), 研究所, 研究員 (50342994)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥49,790,000 (Direct Cost: ¥38,300,000、Indirect Cost: ¥11,490,000)
Fiscal Year 2010: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2009: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2008: ¥32,890,000 (Direct Cost: ¥25,300,000、Indirect Cost: ¥7,590,000)
Keywords肉腫 / 幹細胞 / 腫瘍溶解性ウイルス
Research Abstract

The purpose of this study is to concentrate the stem (tumor-initiating) cell fraction of sarcoma, and then to develop stem cell-targeted agent, utilizing cell-targeting technologies with oncolytic virus. Several lines of highly tumorigenic osateosarcoma were isolated. Tumor-initiating cells from gastrointestinal stromal tumor, sarcoma-like tumor, were concentrated into the cellular fraction characterized with the cell surface marker CD133(Low/-) in vitro. Those cells were shown to be silenced in the hypoxic region of tumor, and resistant to Imatinib treatment. Tumor-initiating cells from sarcomatous mesothelioma were concentrated into the cellular fraction with CD133 (Low/-) and CD44(+). We showed that our HSV-1 oncolytic virus d12ODDΔRR targeting hypoxic microenvironment of tumor successfully destroyed tumor-initiating cells from stromal tumor and mesothelioma.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (24 results)

All 2011 2010 2009 2008 Other

All Journal Article (10 results) (of which Peer Reviewed: 8 results) Presentation (10 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] がん遺伝子治療の可能性-標的遺伝子療法による平滑筋肉腫の治療2010

    • Author(s)
      高橋克仁
    • Journal Title

      がん治療最前線 69

      Pages: 25-27

    • Related Report
      2010 Final Research Report
  • [Journal Article] Mediastinal synovial sarcoma. Aoyama T, Okamoto T, Fukiage K, Otsuka S, Furu M, Ito K, Jin Y, Ueda M, Nagayama S, Nakayama T, Nakamura T, Toguchida J. Histone modifiers, YY1 and p300, regulate the expression of cartilage -specific gene, chondromodulin-I, in mesenchymal stem cells.2010

    • Author(s)
      Katakura H, Toguchida J, et al.
    • Journal Title

      J Biol Chem. 285

      Pages: 29842-29850

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal stem cells cultured under hypoxia escape from senescence via down-regulation of p16 and extracellular signal regulated kinase.2010

    • Author(s)
      Jin Y, Toguchida J, et al(11名/(11))
    • Journal Title

      Biochem Biophys Res Commu. 391

      Pages: 1471-1476

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel method to isolate mesenchymal stem cells from bone marrow in a closed system using a device made by non-woven fabric.2010

    • Author(s)
      Ito K, Toguchida J, et al.(18名/(18))
    • Journal Title

      Tissue Eng Part C Methods 16

      Pages: 81-91

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histone modifiers, YY1 and p300, regulate the expression of cartilage-specific gene, chondromodulin-I, in mesenchymal stem cells.2010

    • Author(s)
      Aoyama T, Okamoto T, Fukiage K, Otsuka S, Furu M, Ito K, Jin Y, Ueda M, Nagayama S, Nakayama T, Nakamura T, Toguchida J.
    • Journal Title

      J Biol Chem

      Volume: 285 Pages: 29842-29850

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel method to isolate mesenchymal stem cells from bone marrow in a closed system using a device made by nonwoven fabric.2010

    • Author(s)
      Ito K, Aoyama T, Fukiage K, Otsuka S, Furu M, Jin Y, Nasu A, Ueda M, Kasai Y, Ashihara E, Kimura S, Maekawa T, Kobayashi A, Yoshida S, Niwa H, Otsuka T, Nakamura T, Toguchida J.
    • Journal Title

      Tissue Eng Part C Methods. 16

      Pages: 81-91

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 腫瘍溶解性ウイルスによる次世代のがん遺伝子治療2009

    • Author(s)
      高橋克仁、山村倫子
    • Journal Title

      クリニックマガジン 479

      Pages: 24-25

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Journal Article] CYVADIC療法が奏功した肉腫型腹膜悪性中皮腫の1例2009

    • Author(s)
      草間俊行、山村倫子、高橋克仁, 他
    • Journal Title

      癌と化学療法 36

      Pages: 475-478

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular genetics of sarcomas : Applications to diagnoses and therapy.2009

    • Author(s)
      Toguchida J, Nakayama T.(2名/(1)
    • Journal Title

      Cancer Sci. 100

      Pages: 1573-80

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of autophagy in malignant rhabdoid tumor cells by the histone deacetylase inhibitor FK228 through AIF translocation.2008

    • Author(s)
      Watanabe M, Toguchida J, et al.(14名/(13))
    • Journal Title

      Int J Cancer 124

      Pages: 55-67

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] ウイルス工学を応用したがん細胞標的医薬の前臨床試験:腫瘍内低酸素微小環境の標的化2011

    • Author(s)
      山村倫子、高橋克仁
    • Organizer
      日本薬学会総会第131年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-30
    • Related Report
      2010 Final Research Report
  • [Presentation] ウイルス工学を応用したがん細胞標的医薬の前臨床試験;腫瘍内低酸素微小環境の標的化2011

    • Author(s)
      山村倫子
    • Organizer
      日本薬学会総会第131年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-30
    • Related Report
      2010 Annual Research Report
  • [Presentation] ウイルス工学を応用した細胞標的医薬の開発2010

    • Author(s)
      高橋克仁
    • Organizer
      第28回関東腎研究会
    • Place of Presentation
      東京
    • Year and Date
      2010-01-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] ウイルス工学を応用したがん細胞標的医薬の開発;がん幹細胞の標的化2009

    • Author(s)
      山村倫子、村井淳、玉越智樹、高橋克仁
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-01
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] カルポニン標的化腫瘍溶解性単純ヘルペスウイルスによる悪性中皮腫に対する新治療法の開発2009

    • Author(s)
      山村倫子、玉越智樹、村井淳、高橋克仁
    • Organizer
      第129回日本薬学会総会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-27
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] GIST stem cells2008

    • Author(s)
      山村倫子、高橋克仁
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2008-10-29
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] ウイルス工学を応用した肉腫標的医薬の開発2008

    • Author(s)
      高橋克仁、山村倫子
    • Organizer
      第41回日本整形外科学会 骨軟部腫瘍学術総会、シンポジウム3
    • Place of Presentation
      浜松(招待講演)
    • Year and Date
      2008-07-18
    • Related Report
      2010 Final Research Report
  • [Presentation] Insights into physiological role of calponin in smooth muscle regulation : A lesson from gene knockout2008

    • Author(s)
      K. Takahashi, H. Yamamura
    • Organizer
      Experimental Biology U. S. A. 2008
    • Place of Presentation
      Seattle
    • Year and Date
      2008-04-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] Physiological role of calponin in smooth muscle regulation:A lessonfrom knockout mice.2008

    • Author(s)
      高橋克仁, 玉越智樹, 山村倫子
    • Organizer
      Experimental Biology 2008 Symposium on Calponin and Smooth Muscle Thin Filament.
    • Place of Presentation
      San Diego, USA(Invited lecture)
    • Related Report
      2010 Final Research Report
  • [Presentation] GIST stem cells.2008

    • Author(s)
      高橋克仁, 山村倫子
    • Organizer
      The 5th Biannual Kuningas Foundation GIST Symposium
    • Place of Presentation
      Helsinki(Invited lecture)
    • Related Report
      2010 Final Research Report
  • [Book] 未来の医療遺伝子治療とは、がんを治すチカラ2009

    • Author(s)
      高橋克仁、山村倫子
    • Publisher
      大阪府立成人病センター編
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.mc.pref.osaka.jp/omc2/pathophysiology.html

    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 低酸素状態にある細胞で増殖するウイルスまたは遺伝子を発現するウイルスベクター2009

    • Inventor(s)
      高橋克仁、山村倫子
    • Industrial Property Rights Holder
      科学技術振興機構(JST)
    • Industrial Property Number
      2008-007179
    • Filing Date
      2009-01-13
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 細胞特異的発現複製ベクター2008

    • Inventor(s)
      高橋克仁、山村倫子
    • Industrial Property Rights Holder
      科学技術振興機構(JST)
    • Acquisition Date
      2008-04-11
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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