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GLI2-targeted gene therapy for musculoskeletal tumors

Research Project

Project/Area Number 24592237
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionKagoshima University

Principal Investigator

NAGANO Satoshi  鹿児島大学, 医歯(薬)学総合研究科, 講師 (50373139)

Co-Investigator(Kenkyū-buntansha) KOMIYA Setsuro  鹿児島大学, 医歯学総合研究科, 教授 (30178371)
SETOGUCHI Takao  鹿児島大学, 医歯学総合研究科, 特任准教授 (40423727)
KOSAI Kenichiro  鹿児島大学, 医歯学総合研究科, 教授 (90258418)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords遺伝子治療 / ヘッジホッグシグナル / 骨軟部腫瘍 / GLI2 / Adenovirus / Hedgehog / RPS3 / ヘッジホッグ経路 / サバイビン / がん幹細胞 / 骨肉腫
Outline of Final Research Achievements

We showed arsenic trioxide targets GLI2, a crucial factor for intracellular signaling of musculoskeletal tumors, and suppressed growth of osteosarcoma cells. ATO is already approved for leukemia, therefore translation into clinical usage for osteosarcoma is anticipated. We also showed that Surv.m-CRA, a survivin-responsive conditionally-replicative adenovirus (CRA), exhibit strong antitumor activity to rhabdomyosarcoma stem cells. We found that ribosomal protein S3 is a target gene of GLI2 and its knockdown suppressed invasion and motility of osteosarcoma cells. We are preparing for clinical trial of Surv.m-CRA for musculoskeletal tumor patients, which is expected to further advance the research of gene therapy for musculoskeletal tumors.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (31 results)

All 2015 2014 2013 2012

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (20 results) (of which Invited: 1 results)

  • [Journal Article] GLI2 is a novel therapeutic target for metastasis of osteosarcoma.2015

    • Author(s)
      Nagao-Kitamoto H, Nagata M, Nagano S, Kitamoto S, Ishidou Y, Yamamoto T, Nakamura S, Tsuru A, Abematsu M, Fujimoto Y, Yokouchi M, Kitajima S, Yoshioka T, Maeda S, Yonezawa S, Komiya S, Setoguchi T.
    • Journal Title

      Int J Cancer.

      Volume: 136 Issue: 6 Pages: 1276-1284

    • DOI

      10.1002/ijc.29107

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ribosomal protein S3 regulates GLI2-mediated osteosarcoma invasion.2015

    • Author(s)
      Nagao-Kitamoto H, Setoguchi T, Kitamoto S, Nakamura S, Tsuru A, Nagata M, Nagano S, Ishidou Y, Yokouchi M, Kitajima S, Yoshioka T, Maeda S, Yonezawa S, Komiya S.
    • Journal Title

      Cancer Lett.

      Volume: 356 Issue: 2 Pages: 855-861

    • DOI

      10.1016/j.canlet.2014.10.042

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differentiation of lipoma and atypical lipomatous tumor by a scoring system: implication of increased vascularity on pathogenesis of liposarcoma.2015

    • Author(s)
      Nagano S, Yokouchi M, Setoguchi T, Ishidou Y, Sasaki H, Shimada H, Komiya S.
    • Journal Title

      BMC Musculoskelet Disord.

      Volume: 16 Issue: 1 Pages: 36-36

    • DOI

      10.1186/s12891-015-0491-8

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hairy/enhancer-of-split related with YRPW motif protein 1 promotes osteosarcoma metastasis via matrix metallopeptidase 9 expression.2015

    • Author(s)
      Tsuru A, Setoguchi T, Matsunoshita Y, Nagao-Kitamoto H, Nagano S, Yokouchi M, Maeda S, Ishidou Y, Yamamoto T, Komiya S.
    • Journal Title

      Br J Cancer.

      Volume: 112 Issue: 7 Pages: 1232-40

    • DOI

      10.1038/bjc.2015.84

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elastofibroma dorsi: Surgical indications and complications of a rare soft tissue tumor.2014

    • Author(s)
      Nagano S, Yokouchi M, Setoyama T, Sasaki H, Shimada H, Kawamura I, Ishidou Y, Setoguchi T, Komiya S
    • Journal Title

      Mol Clin Oncol.

      Volume: 2 Issue: 3 Pages: 421-424

    • DOI

      10.3892/mco.2014.257

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human Immunodeficiency Virus Type I Enhancer Binding Protein 3 is Essential for the Expression of Asparagine-linked Glycosylation 2 in the Regulation of Osteoblast and Chondrocyte Differentiation.2014

    • Author(s)
      Imamura K, Maeda S, Kawamura I, Matsuyama K, Shinohara N, Yahiro Y, Nagano S, Setoguchi T, Yokouchi M, Ishidou Y, Komiya S.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 289 Issue: 14 Pages: 9865-9879

    • DOI

      10.1074/jbc.m113.520585

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metastatic bone tumors: Analysis of factors affecting prognosis and efficacy of CT and 18F-FDG PET-CT in identifying primary lesions.2014

    • Author(s)
      Shimada H, Setoguchi T, Yokouchi M, Sasaki H, Ishidou Y, Kawamura I, Abematsu M, Nagano S, Komiya S.
    • Journal Title

      Mol Clin Oncol.

      Volume: 2 Pages: 875-881

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Survivin-responsive conditionally replicating adenovirus kills rhabdomyosarcoma stem cells more efficiently than their progeny2014

    • Author(s)
      Tanoue K, Wang Y, Ikeda M , Mitsui K, Irie R , Setoguchi T, Komiya S, Natsugoe S, Kosai K
    • Journal Title

      J Trans Med

      Volume: 12 Issue: 1 Pages: 27-27

    • DOI

      10.1186/1479-5876-12-27

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Arsenic trioxide prevents osteosarcoma growth by inhibition of GLI transcription via DNA damage accumulation.2013

    • Author(s)
      Nakamura S, Nagano S, Nagao H, Ishidou Y, Yokouchi M, Abematsu M, Yamamoto T, Komiya S, Setoguchi T.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 7 Pages: e69466-e69466

    • DOI

      10.1371/journal.pone.0069466

    • NAID

      120005324788

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] RBPJ Is a Novel Target for Rhabdomyosarcoma Therapy.2012

    • Author(s)
      Hiroko Nagao, Takao Setoguchi, Sho Kitamoto, Yasuhiro Ishidou, Satoshi Nagano, Masahiro Yokouchi, Masahiko Abematsu, Naoya Kawabata, Shingo Maeda, Suguru Yonezawa, Setsuro Komiya
    • Journal Title

      PLoS ONE

      Volume: 7(7) Issue: 7 Pages: e39268-e39268

    • DOI

      10.1371/journal.pone.0039268

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pathological femoral fractures due to osteomalacia associated with adefovir dipivoxil treatment for hepatitis B: a case report.2012

    • Author(s)
      Tanaka M, Setoguchi T, Ishidou Y, Arishima Y, Hirotsu M, Saitoh Y, Nakamura S, Kakoi H, Nagano S, Yokouchi M, Kamizono J, Komiya S.
    • Journal Title

      Diagn Pathol

      Volume: 7 Issue: 1

    • DOI

      10.1186/1746-1596-7-108

    • NAID

      120005342565

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 革新的癌治療薬を目指した増殖制御型アデノウイルスの独自開発から医師主導治験へ2014

    • Author(s)
      永野 聡,小戝健一郎,小宮節郎
    • Organizer
      第29回日本整形外科学会基礎学術集会
    • Place of Presentation
      鹿児島市、城山観光ホテル
    • Year and Date
      2014-10-09 – 2014-10-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] GLI2によるRPS3発現を介した骨肉腫転移解析と臨床薬剤による阻害2014

    • Author(s)
      永田政仁,永野 聡,中村俊介,北本宗子,棈松昌彦,横内雅博,石堂康弘,小宮節郎,瀬戸口啓夫
    • Organizer
      第29回日本整形外科学会基礎学術集会
    • Place of Presentation
      鹿児島市、城山観光ホテル
    • Year and Date
      2014-10-09 – 2014-10-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] GLI2とSMO制御による骨肉腫転移能抑制の相乗効果解析2014

    • Author(s)
      永田政仁,鶴亜里紗,小宮節郎,瀬戸口啓夫
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜市、パシフィコ横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] GLI転写を抑制する三酸化ヒ素と抗がん剤併用による骨肉腫増殖抑制効果2014

    • Author(s)
      永田政仁,瀬戸口啓夫,北本宗子,棈松昌彦,永野 聡,中村俊介,北本宗子,横内雅博,石堂康弘,小宮節郎
    • Organizer
      第47回日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      大阪市、大阪国際会議場
    • Year and Date
      2014-07-17 – 2014-07-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] GLI2阻害による骨肉腫増殖・転移抑制メカニズム解析2014

    • Author(s)
      瀬戸口啓夫,永尾宗子,中村俊介,永野 聡,横内雅博,棈松昌彦,石堂康弘,小宮節郎
    • Organizer
      第87回日本整形外科学会学術総会
    • Place of Presentation
      神戸市、神戸国際会議場
    • Year and Date
      2014-05-22 – 2014-05-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 骨・軟部肉腫に対する分子標的治療研究2014

    • Author(s)
      瀬戸口啓夫、小宮節郎
    • Organizer
      第87回日本整形外科学会学術総会
    • Place of Presentation
      神戸市、神戸国際会議場
    • Year and Date
      2014-05-22 – 2014-05-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 骨軟部肉腫に対する分子標的治療研究2013

    • Author(s)
      瀬戸口 啓夫
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] GLI2によるRPS3発現を介した骨肉腫転移能亢進2013

    • Author(s)
      瀬戸口啓夫, 永尾宗子, 永野聡, 中村俊介, 横内雅博, 棈松雅彦, 石堂康弘, 小宮節郎
    • Organizer
      第28回日本整形外科学会基礎学術集会
    • Place of Presentation
      千葉市幕張
    • Related Report
      2013 Research-status Report
  • [Presentation] 三酸化ヒ素はGLIの転写を抑制しDNA損傷を介して骨肉腫の増殖を阻害する2013

    • Author(s)
      中村俊介, 瀬戸口啓夫, 永尾宗子, 永野聡, 棈松昌彦, 小宮節郎
    • Organizer
      第28回日本整形外科学会基礎学術集会
    • Place of Presentation
      千葉市幕張
    • Related Report
      2013 Research-status Report
  • [Presentation] Arsenic trioxide prevents osteosarcoma growth by inhibition of GLI transcription via DNA damage accumulation2013

    • Author(s)
      S Nakamura, S Nagano, H Nagao, M Abematsu, M Yokouchi, Y Ishidou, S Komiya, T Setoguchi
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸市
    • Related Report
      2013 Research-status Report
  • [Presentation] Arsenic trioxide prevents osteosarcoma growth by inhibition of GLI transcription via DNA damage accumulation2013

    • Author(s)
      S Nakamura, S Nagano, H Nagao, A Tsuru , Y Ishidou, M Yokouchi, M Abematsu, T Yamamoto, S Komiya, T Setoguchi
    • Organizer
      Orthopedic Research Society 2013 Annual Meeting
    • Place of Presentation
      San Antonio, TX, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] GLI2の骨肉腫転移・浸潤への機能の解析2012

    • Author(s)
      瀬戸口 啓夫, 永尾 宗子, 永野 聡, 横内 雅博, あべ松 昌彦, 小宮 節郎
    • Organizer
      第45回日本整形外科学会骨軟部腫瘍学会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] 当科を受診した転移性骨腫瘍患者の解析-原発巣診断に影響する因子2012

    • Author(s)
      嶋田博文、永野 聡、横内雅博、佐々木裕美、吉井理一郎、有島善也、小宮節郎
    • Organizer
      第45回日本整形外科学会骨軟部腫瘍学会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] Hedgehog pathwayの薬理学的抑制によるヒト骨肉腫の増殖抑制効果2012

    • Author(s)
      中村俊介, 永尾宗子、永野聡、横内雅博、あべ松昌彦、小宮節郎、瀬戸口啓夫
    • Organizer
      第45回日本整形外科学会骨軟部腫瘍学会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] 骨肉腫転移におけるHEY1の役割について2012

    • Author(s)
      鶴 亜里紗、松野下 幸弘、永尾宗子、永野 聡、横内雅博、棈松昌彦、石堂康弘、小宮節郎、瀬戸口啓夫
    • Organizer
      第45回日本整形外科学会骨軟部腫瘍学会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] Functional analysis of HEY1 in osteosarcoma metastasis2012

    • Author(s)
      Setoguchi T., Nagano S., and Komiya S.
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 転移性骨腫瘍患者の予後に関する因子の解析 ~骨関連事象の重要性~2012

    • Author(s)
      嶋田博文, 永野 聡, 横内雅博, 佐々木裕美, 佐久間大輔, 瀬戸口 啓夫, 小宮 節郎
    • Organizer
      第124回西日本整形・災害外科学会学術集会
    • Place of Presentation
      別府市
    • Related Report
      2012 Research-status Report
  • [Presentation] A new method for determining surgical margin in soft tissue sarcoma using a combination of CT and FDG-positron emission tomography2012

    • Author(s)
      S Nagano, M Yokouchi, M Terahara, H Sasaki, H Shimada, R Hidaka, H Tokumoto, S Komiya
    • Organizer
      22nd Japan-Korean Combined Orthopaedic Symposium
    • Place of Presentation
      日光市
    • Related Report
      2012 Research-status Report
  • [Presentation] Pharmacological inhibition of GLI transcription prevents human osteosarcoma growth2012

    • Author(s)
      Setoguchi T., Nakamura S., Nagao H., Nagano S., Abematsu M., Komiya S.
    • Organizer
      22nd Japan-Korean Combined Orthopaedic Symposium
    • Place of Presentation
      日光市
    • Related Report
      2012 Research-status Report
  • [Presentation] Arsenic trioxide prevents osteosarcoma growth by inhibition of GLI transcription via DNA damage accumulation2012

    • Author(s)
      S Nakamura, S Nagano, H Nagao, A Tsuru, Y Ishidou, M Yokouchi, M Abematsu, T Yamamoto, S Komiya, and T Setoguchi
    • Organizer
      第35回 日本分子生物学会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2021-12-22  

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