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Hedgehog signal inhibitors suppress the invasion of human rhabdomyosarcoma cells

Research Project

Project/Area Number 23592629
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatric surgery
Research InstitutionOsaka University

Principal Investigator

OUE Takaharu  大阪大学, 医学(系)研究科(研究院), 講師 (50314315)

Co-Investigator(Kenkyū-buntansha) FUKUZAWA Masahiro  大阪大学, 医学部, 名誉教授 (60165272)
UEHARA Shuichiro  大阪大学, 医学部, 助教 (00448060)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsヘッジホグ / Gli-1 / 阻害剤 / cyclopamine / forskolin / 細胞増殖 / 横紋筋肉腫 / 分子標的治療 / ヘッジホッグシグナル / 阻害 / Cyclopamine / Forskolin / ヘッジホグシグナル / Cyclipamine
Research Abstract

The objective of this study was to determine whether Hedgehog signaling plays a role in the invasion of RMS. Two kinds of specific Hh signaling inhibitors, cyclopamine and forskolin, were used to suppress activated Hh signals in three RMS cell lines. The effects of the Hh signaling inhibitors on tumor cell invasion and motility were investigated using Matrigel Invasion assays and wound closure assays, respectively. The number of invaded cells in the Matrigel chambers was significantly decreased. The wound closure assays revealed that a blockade of the Hh signaling pathway impairs RMS cell motility. Both the invasive capacity and motility of RMS cells are significantly suppressed by Hh signaling inhibitors, demonstrating that the Hh pathway plays an important role in the invasion of RMS. Hh inhibitors may provide a new paradigm for the treatment of RMS.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (44 results)

All 2014 2013 2012 2011

All Journal Article (17 results) (of which Peer Reviewed: 15 results) Presentation (22 results) (of which Invited: 3 results) Book (5 results)

  • [Journal Article] Bilateral Wilms tumors treated according to the Japan Wilms Tumor Study Group protocol2014

    • Author(s)
      Oue T, Koshinaga T, Okita H, Kaneko Y, Hinotsu S, Fukuzawa M
    • Journal Title

      Pediatr Blood Cancer

      Volume: (Epub ahead of print)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hedgehog signal inhibitors suppress the invasion of human rhabdomyosarcoma cells2014

    • Author(s)
      Oue T, Uehara S, Yamanaka H, Nomura M, Usui N
    • Journal Title

      Pediatric Surgery International

      Volume: 29 Issue: 11 Pages: 1153-1158

    • DOI

      10.1007/s00383-013-3369-6

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low serum concentrations of anti-Mullerian hormone are common in 53 female childhood cancer survivors2014

    • Author(s)
      Miyoshi Y, Ohta H, Namba N, Tachibana M, Miyamura T, Miyashita E, Hashii Y, Oue T, Isobe A, Tsutsui T, Kimura T, Ozono K
    • Journal Title

      Hormone Research in Paediatrics

      Volume: 79 Issue: 1 Pages: 17-21

    • DOI

      10.1159/000346139

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hedgehog signal inhibitors suppress the invasion of human rhabdomyosarcoma cells2013

    • Author(s)
      Oue T, Uehara S, Yamanaka H, Nomura M, Usui N
    • Journal Title

      Pediatr Surg Int

      Volume: 29 Pages: 1153-8

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Low serum concentrations of anti-Mullerian hormone are common in 53 female childhood cancer survivors2013

    • Author(s)
      Miyoshi Y, Ohta H, Namba N, Tachibana M, Miyamura T, Miyashita E, Hashii Y, Oue T, Isobe A, Tsutsui T, Kimura T, Ozono K
    • Journal Title

      Horm Res Paediatr

      Volume: 79 Pages: 17-21

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 頬部横紋筋肉腫に対する集学的治療後4年で発生した耳下腺悪性腫瘍の1例2013

    • Author(s)
      上原秀一郎, 太田秀明, 山本佳史, 橋井佳子, 大植孝治, 福澤正洋
    • Journal Title

      日本小児血液・がん学会雑誌

      Volume: 50 Pages: 232-236

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased expression of survivin in hepatoblastoma after chemotherapy.2013

    • Author(s)
      Uehara S, Oue T, Kawatsu M, Nara K, Fukuzawa M.
    • Journal Title

      Eur J Pediatr Surg

      Volume: 46 Issue: 05 Pages: 326-331

    • DOI

      10.1055/s-0033-1333637

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 頭蓋外胚細胞腫瘍の病態と診断・治療2013

    • Author(s)
      大植孝治
    • Journal Title

      日本小児血液・がん学会雑誌

      Volume: 50 Pages: 426-432

    • Related Report
      2013 Annual Research Report
  • [Journal Article] ncreased Expression of Survivin in Hepatoblastoma after Chemotherapy2013

    • Author(s)
      Uehara S, Oue T, Fukuzawa M, et al
    • Journal Title

      Eur J Pediatr Surg

      Volume: 26

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Methylation of the RASSF1A promoter is predictive of poor outcome among patients with Wilms tumor2012

    • Author(s)
      Ohshima J, Haruta M, Fujiwara W, Watanabe N, Arai Y, Ariga T, Okita H, Koshinaga T, Oue T, Hinotsu S, Nakadate H, Horie H, Fukuzawa M, Kaneko Y
    • Journal Title

      Pediatr Blood Cancer

      Volume: 59 Issue: 3 Pages: 499-505

    • DOI

      10.1002/pbc.24093

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of Wilms tumor 1 gene in a variety of pediatric tumors2011

    • Author(s)
      Oue T, Uehara S, Yamanaka H, Takama Y, Oji Y, Fukuzawa M
    • Journal Title

      J Pediatr Surg

      Volume: 46 Pages: 2233-8

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of WT1 gene in neuroblastoma2011

    • Author(s)
      Wang J, Oue T, Uehara S, Yamanaka H, Oji Y, Fukuzawa M
    • Journal Title

      J Pediatr Surg

      Volume: 46 Pages: 326-31

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hedgehog signal inhibitor forskolin suppresses cell proliferation and tumor growth of human rhabdomyosarcoma xenograft2011

    • Author(s)
      Yamanaka H, Oue T, Uehara S, Fukuzawa M
    • Journal Title

      J Pediatr Surg

      Volume: 46 Pages: 320-5

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of Wilms tumor 1 gene in a variety of pediatric tumors.2011

    • Author(s)
      Oue T, et al
    • Journal Title

      Journal of Pediatric Surgery

      Volume: 46 Pages: 2233-2238

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 【小児腫瘍における多施設共同臨床試験の背景と進捗】 日本ウィルムス腫瘍スタディグループの成果2011

    • Author(s)
      大植孝治、他
    • Journal Title

      小児外科

      Volume: 47 Pages: 1203-1206

    • Related Report
      2011 Research-status Report
  • [Journal Article] A case of childhood dermatofibrosarcoma protuberans of the face2011

    • Author(s)
      Nara K, Oue T, et al
    • Journal Title

      Journal of Pediatric Surgery

      Volume: 46 Pages: 1438-1441

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of WT1 gene in neuroblastoma2011

    • Author(s)
      Wang J, Oue T, et al
    • Journal Title

      Journal of Pediatric Surgery

      Volume: 46 Pages: 326-331

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Bilateral Wilms'tumors treated according to the Japan Wilms Tumor Study Group protocol2013

    • Author(s)
      Oue T, Fukuzawa M, Okita H, HorieH, Saito M, Nozaki M, Chin M, Nakadate N, Hinotsu S, Koshinaga T, Kaneko Y, Tanaka Y
    • Organizer
      45^<th> Congress of the International Society of Paediatric Oncology
    • Place of Presentation
      Hong Kong, China
    • Related Report
      2013 Final Research Report
  • [Presentation] Novel strategy for neuroblastoma with the combination of 13-cis-retinoic acid and inactivated Sendai virus particle2013

    • Author(s)
      Nomura M, Uehara S, Oue T, Usui N
    • Organizer
      14^<th> Congress of the European Paediatric Surgeons' Association
    • Place of Presentation
      Leipzig, Germany
    • Related Report
      2013 Final Research Report
  • [Presentation] 無血清培養から抽出した胞巣型横紋筋肉腫幹細胞の生物学的特徴2013

    • Author(s)
      上原秀一郎, 中畠賢吾, 川津美代子, 大植孝治, 臼井規朗
    • Organizer
      第55回日本小児血液・がん学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] 無血清培養より抽出した胞巣型横紋筋肉腫幹細胞様細胞の生物学的特徴2013

    • Author(s)
      上原秀一郎, 川津美代子, 野村元成, 奈良啓吾, 上野豪久, 曹英樹, 大植孝治, 臼井規朗
    • Organizer
      第113回日本外科学会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] 横紋筋肉腫細胞の浸潤能におけるHedgehogシグナル系の関与2013

    • Author(s)
      大植孝治, 上原秀一郎, 野村元成, 上野豪久, 奈良啓吾, 曹英樹, 臼井規朗, 山中宏晃, 福澤正洋
    • Organizer
      第50回日本小児外科学会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] 頬部横紋筋肉腫に対する集学的治療後4年で発生した耳下腺悪性腫瘍の1例2013

    • Author(s)
      上原秀一郎, 太田秀明, 山本佳史, 橋井佳子, 大植孝治, 福澤正洋
    • Organizer
      第55回日本小児血液・がん学会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] 横紋筋肉腫細胞の浸潤能におけるHedgehogシグナル系の関与2013

    • Author(s)
      大植孝治、上原秀一郎、山中宏晃、野村元成、臼井規朗
    • Organizer
      第50回日本小児外科学会学術集会
    • Place of Presentation
      新宿区
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 無血清培養より抽出した胞巣型横紋筋肉腫幹細胞様細胞の生物学的特徴2013

    • Author(s)
      上原秀一郎、川津美代子、野村元成、奈良啓悟、上野豪久、曺 英樹、大植孝治、臼井規朗
    • Organizer
      第113回日本外科学会定期学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 無血清培養から抽出した胞巣型横紋筋肉腫幹細胞の生物学的特徴2013

    • Author(s)
      上原秀一郎、中畠賢吾、川津美代子、大植孝治、臼井規朗
    • Organizer
      第55回日本小児血液・がん学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Problema of Childhood Cancer Survivers in Pediatric Surgical Clinic2012

    • Author(s)
      OueT, Uehara S, Fukuzawa M, Miyoshi Y, Ohta H, Hashii Y
    • Organizer
      44^<th> Congress of the International Society of Paediatric Oncology
    • Place of Presentation
      London, UK
    • Related Report
      2013 Final Research Report
  • [Presentation] Hedgehog Signal Inhibitors Supress the Invasion of Human Rhabdomyosarcoma Cells2012

    • Author(s)
      OueT, Uehara S, Yamanaka H, Takama Y, Fukuzawa M
    • Organizer
      59^<th> Cogress of the British Association of Paediatric Surgeons
    • Place of Presentation
      Rome, Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] The expression of survivin and its increased expression after chemotherapy in hepatoblastoma2012

    • Author(s)
      Uehara S, Kawatsu M, Oue T, Fukuzawa M
    • Organizer
      XXV International Symposium on Paediatric Surgical Research
    • Place of Presentation
      London, UK
    • Related Report
      2013 Final Research Report
  • [Presentation] The use of tissue expanders to prevent the side effect of preoperative radiotherapy in pediatric malignant pelvic tumors2012

    • Author(s)
      Uehara S, Oue T, Takenaka S, Hashimoto N, Adachi K, Matsumura R, Yoshida H, Hashii Y, Fukuzawa M
    • Organizer
      44^<th> Congress of the International Society of Paediatric Oncology
    • Place of Presentation
      London, UK
    • Related Report
      2013 Final Research Report
  • [Presentation] 小児悪性固形腫瘍に対する新たな治療標的分子の検討2012

    • Author(s)
      大植孝治, 奈良啓吾, 山中宏晃, 野村元成, 上原秀一郎, 福澤正洋
    • Organizer
      第112回日本外科学会
    • Place of Presentation
      幕張
    • Related Report
      2013 Final Research Report
  • [Presentation] 小児悪性固形腫瘍に対する新たな治療標的分子の検討2012

    • Author(s)
      大植孝治, 上原秀一郎, 福澤正洋,他
    • Organizer
      第112回日本外科学会定期学術集会
    • Place of Presentation
      幕張
    • Related Report
      2012 Research-status Report
  • [Presentation] 小児固形悪性腫瘍治療後長期生存患者(childhood cancer survivors)における晩期障害の実情2012

    • Author(s)
      大植孝治, 上原秀一郎, 野村元成,他
    • Organizer
      第49回日本小児外科学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] HEDGEHOG SIGNAL INHIBITORS SUPPRESS THE INVASION OF HUMAN RHABDOMYOSARCOMA CELLS2012

    • Author(s)
      Oue T, Uehara S, Fukuzawa M, et al
    • Organizer
      59th British Association of Paediatric Surgeons Congress
    • Place of Presentation
      イタリア・ローマ
    • Related Report
      2012 Research-status Report
  • [Presentation] Rhabdomyosarcoma alveolar typeの成分を持つMalignant Ectomesenchymomaの1例2012

    • Author(s)
      大植孝治、他
    • Organizer
      第10回JRSG研究会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] 当院における横紋筋肉腫22症例の臨床病理学的検討特に再発・転移症例と大量化学療法について2011

    • Author(s)
      上原秀一郎, 野村元成, 山中宏晃, 大植孝治, 橋井佳子, 太田秀明, 福澤正洋
    • Organizer
      第48回日本小児外科学会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] 横紋筋肉腫細胞株に対するヘッジホッグシグナル伝達経路阻害剤フォルスコリンの浸潤抑制効果の検討2011

    • Author(s)
      山中宏晃, 大植孝治, 上原秀一郎, 福澤正洋
    • Organizer
      第53回日本小児血液がん学会
    • Place of Presentation
      前橋
    • Related Report
      2013 Final Research Report
  • [Presentation] 小児悪性固形腫瘍におけるWT1遺伝子の発現2011

    • Author(s)
      大植孝治、他
    • Organizer
      第48回日本小児外科学会
    • Place of Presentation
      東京都江東区
    • Related Report
      2011 Research-status Report
  • [Presentation] 神経芽腫におけるWT1遺伝子の発現と腫瘍増殖への関与2011

    • Author(s)
      大植孝治、他
    • Organizer
      第111回日本外科学会
    • Place of Presentation
      紙上掲載
    • Related Report
      2011 Research-status Report
  • [Book] 小児外科診療ハンドブック(福澤正洋監修)超音波検査, 腫瘍生検, 肝芽腫, 腎芽腫, 横紋筋肉腫, 精巣腫瘍2014

    • Author(s)
      大植孝治
    • Publisher
      医薬ジャーナル社
    • Related Report
      2013 Final Research Report
  • [Book] スタンダード小児外科手術(田口智章、岩中督監修)腫瘍生検、縦隔腫瘍の手術2013

    • Author(s)
      大植孝治
    • Publisher
      メジカルビュー社
    • Related Report
      2013 Final Research Report
  • [Book] 系統小児外科学第3版(福澤正洋、中村哲郎、窪田昭男編),病理組織検査法, 分子標的治療, 再生医療, 腎芽腫, 肝腫瘍, 横紋筋肉腫, 膵腫瘍, 悪性リンパ腫2013

    • Author(s)
      大植孝治
    • Publisher
      永井書店
    • Related Report
      2013 Final Research Report
  • [Book] 系統小児外科2013

    • Author(s)
      大植孝治
    • Total Pages
      38
    • Publisher
      永井書店
    • Related Report
      2013 Annual Research Report
  • [Book] スタンダード小児外科手術2013

    • Author(s)
      大植孝治
    • Total Pages
      7
    • Publisher
      メジカルビュー社
    • Related Report
      2013 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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