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Novel therapeutic strategy of osteosarcoma by regulation of RANK signal pathway

Research Project

Project/Area Number 23592178
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

KAWANO Hirotaka  東京大学, 医学部附属病院, 准教授 (20345218)

Co-Investigator(Kenkyū-buntansha) KADONO Yuho  東京大学, 医学部附属病院, 講師 (70401065)
HIRATA Makoto  東京大学, 医学部附属病院, 届出診療医 (50401071)
NAKAGAWA Takumi  帝京大学, 医学部, 教授 (90338385)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords骨肉腫 / RANKLシグナル / RANKL / 骨軟部腫瘍 / 性ホルモン
Research Abstract

There has been no significant improvement in the clinical outcome of osteosarcoma and novel therapeutic strategy is required. We have focused on osteoclast differentiation factor RANKL which was reported to act directly on tumor cells and to promote proliferation and migration.
In vitro analysis, it was revealed that RANK-Fc, fusion protein consisting of the Fc chain of human IgG and RANK biding region of RANKL, had suppressive effect on differentiation, and survival and bone resorption activity of osteoclast. It was also confirmed that RANK-Fc suppressed migration, invasion ability and anchorage-independent ability in osteosarcoma cell lines.

Report

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

    (31 results)

All 2013 2012 2011

All Journal Article (25 results) (of which Peer Reviewed: 25 results) Presentation (6 results)

  • [Journal Article] Impact of hospital volume on postoperative complications and in-hospital mortality after musculoskeletal tumor surgery : analysis of a national administrative database2013

    • Author(s)
      Ogura K, Kawano H
    • Journal Title

      J Bone Joint Surg Am

      Volume: 95(18) Pages: 1684-91

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Incidence and risk factors for pulmonary embolism after primary musculoskeletal tumor surgery2013

    • Author(s)
      Ogura K, Kawano H
    • Journal Title

      Clin Orthop Relat Res

      Volume: 471(10) Pages: 3310-6

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neoadjuvant and adjuvant chemotherapy with modified mesna, adriamycin, ifosfamide, and decarbazine (MAID) regimen for adult high-grade non-small round cell soft tissue sarcomas2013

    • Author(s)
      Ogura K, Kawano H
    • Journal Title

      Int J Clin Oncol

      Volume: 18(1) Pages: 170-6

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chest wall deformity found in patientswith primary spontaneous pneumothorax2013

    • Author(s)
      Saita K, Kawano H
    • Journal Title

      Asian Cardiovascular & Thoracic Annals

      Volume: (published online) Pages: 11-11

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Incidence of, and risk factors for, postoperative venous thromboembolism in patients with benign or malignant musculoskeletal tumors2013

    • Author(s)
      Tsuda Y, Kawano H
    • Journal Title

      J Orthop Sci

      Volume: 18(4) Pages: 613-7

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vitamin D receptor in osteoblasts is a negative regulator of bone mass control2013

    • Author(s)
      Yamamoto Y, Kawano H
    • Journal Title

      Endocrinology

      Volume: 154(3) Pages: 1008-20

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of bone-resorption and sealing zone formation in osteoclasts occurs through Akt-mediated microtubule stabilization2013

    • Author(s)
      Matsumoto T, Kadono Y
    • Journal Title

      J Bone Miner Res

      Volume: 28(5) Pages: 1191-202

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Incidence of, and risk factors for, postoperative venous thromboembolism in patients with benign or malignant musculoskeletal tumors2013

    • Author(s)
      津田祐輔 河野博隆 他
    • Journal Title

      J Orthop Sci

      Volume: 18 Issue: 4 Pages: 613

    • DOI

      10.1007/s00776-013-0401-6

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Incidence and risk factors for pulmonary embolism after primary musculoskeletal tumor surgery2013

    • Author(s)
      Ogura K, Yasunaga H, Horiguchi H, Ohe K, Shinoda Y, Tanaka S, Kawano H
    • Journal Title

      CORR 2013

      Volume: 471 Issue: 10 Pages: 3310

    • DOI

      10.1007/s11999-013-3073-9

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of hospital volume on postoperative complications and in-hospital mortality after musculoskeletal tumor surgery analysis of a national administrative database2013

    • Author(s)
      小倉浩一 河野博隆 他
    • Journal Title

      J Bone Joint Surg Am

      Volume: 95 Issue: 18 Pages: 1684

    • DOI

      10.2106/jbjs.l.00913

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of PTEN tumor suppressor promotes the generation of induced pluripotent stem cells.2013

    • Author(s)
      Liao J, Marumoto T, Yamaguchi S, Okano S, Takeda N, Sakamoto C, Kawano H, Nii T, Miyamoto S, Nagai Y, Okada M, Inoue H, Kawahara K, Suzuki A, Miura Y and Tani K
    • Journal Title

      Molecular Therapy

      Volume: in press Issue: 6 Pages: 1242-1250

    • DOI

      10.1038/mt.2013.60

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neoadjuvant and adjuvant chemotherapy with modified mesna, adriamycin, ifosfamide, and dacarbazine (MAID) regimen for adult high-grade non-small round cell soft tissue sarcomas2013

    • Author(s)
      小倉浩一 河野博隆 他
    • Journal Title

      Int J Clin Oncol.

      Volume: 18 Issue: 1 Pages: 170

    • DOI

      10.1007/s10147-011-0360-x

    • NAID

      10031176251

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Alveolar soft part sarcoma : a single-center 26-patient case series and review of the literature2012

    • Author(s)
      Ogura K, Kawano H
    • Journal Title

      Sarcoma

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Extraskeletal myxoid chondrosarcoma : a review of 23 patients treated at a single referral center with long-term follow-up2012

    • Author(s)
      Ogura K, Kawano H
    • Journal Title

      Arch Orthop Trauma Surg

      Volume: 132(10) Pages: 1379-86

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bone radiofrequency ablation combined with prophylactic internal fixation for metastatic bone tumor of the femur from hepatocellular carcinoma2012

    • Author(s)
      Ogura K, Kawano H.
    • Journal Title

      Int J Clin Oncol

      Volume: 17(4) Pages: 417-21

    • NAID

      10031120988

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recurrent epithelioid hemangioma : therapeutic potential of tranilast and indomethacin2012

    • Author(s)
      Ogura K, Kawano H
    • Journal Title

      J Orthop Sci

      Volume: 17(2) Pages: 194-8

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Periosteal osteoblastoma of the distal femur : a case report and a review of the literature with special emphasison the MR features2012

    • Author(s)
      Ogura K, Kawano H
    • Journal Title

      Int Canc Conf J

      Volume: 1:103 Pages: 107-107

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Class IA phosphatidylinositol 3-kinase regulates osteoclastic bone resorption through Akt-mediated vesicle transport2012

    • Author(s)
      Shinohara M, Kadono Y
    • Journal Title

      J Bone Miner Res

      Volume: 27(12) Pages: 2464-75

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Risk factors affecting inhospital mortality after hip fracture : retrospective analysis using the Japanese Diagnosis Proc edure Combination Database2012

    • Author(s)
      Shoda N, Kadono Y
    • Journal Title

      BMJ Open

      Volume: 4 Pages: 2-2

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Alveolar soft part sarcoma: A single-center 26-patient case series and review of the literature2012

    • Author(s)
      Ogura K
    • Journal Title

      Sarcoma

      Volume: 2012 Pages: 907179-907179

    • DOI

      10.1155/2012/907179

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Extraskeletal myxoid chondrosarcoma: a review of 23 patients treated at a single referral center with long-term follow-up.2012

    • Author(s)
      小倉浩一 河野博隆 他
    • Journal Title

      Arch Orthop Trauma Surg.

      Volume: 132(10) Pages: 1379-86

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bone radiofrequency ablation combined with prophylactic internal fixation for metastatic bone tumor of the femur from hepatocellular carcinoma2012

    • Author(s)
      小倉浩一 河野博隆 他
    • Journal Title

      Int J Clin Oncol

      Volume: 17 Issue: 4 Pages: 417

    • DOI

      10.1007/s10147-011-0319-y

    • NAID

      10031120988

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recurrent epithelioid hemangioma: Therapeutic potential of tranilast and indomethacin2012

    • Author(s)
      小倉浩一 河野博隆 他
    • Journal Title

      J Orthop Sci.

      Volume: 17 Issue: 2 Pages: 194

    • DOI

      10.1007/s00776-011-0081-z

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Distinguishing the pro-apoptotic and anti-resorptive functions of risedronate in osteoclasts : Role of the Akt pathway and the Erk/Bim axis2011

    • Author(s)
      Matsumoto T, Kadono Y
    • Journal Title

      Arthritis Rheum

      Volume: 63(12) Pages: 3908-17

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of RANKL-induced osteoclastogenesis by TGF-βthrough molecular interaction between Smad3 and TRAF62011

    • Author(s)
      Yasui T, Kadono Y
    • Journal Title

      J Bone Miner Res

      Volume: 26(7) Pages: 1447-56

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] Clinical outcome of surgical treatment for tumor induced osteomalacia with phosphaturic mesenchymal tumor, mixed connective tissue variant2013

    • Author(s)
      Kawano H, Shinoda Y
    • Organizer
      International Society of Limb Salvage 17^<th> General Meeting
    • Place of Presentation
      Bologna, Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] Prediction of pathologic fracture risk in stance and fall loading configurations for metastases in the proximal femur, using CT-based finite element method2013

    • Author(s)
      Shinoda Y, Kawano H
    • Organizer
      International Society of Limb Salvage 17^<th> General Meeting
    • Place of Presentation
      Bologna, Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] A retrospective analysis of gemcitabine and docetaxel combination on neoadjuvant and adjuvant therapy compared with modified mesna, adriamycin, ifosfamide, and dacarbazine for adult soft tissue non-metastatic sarcomas2013

    • Author(s)
      Tsuda Y, Kawano H
    • Organizer
      International Society of Limb Salvage 17^<th> General Meeting
    • Place of Presentation
      Bologna, Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] Fenestration of lateral cortex at proximal femur had smaller effect on fracture risk.- The analysis by CT-based finite element method-2013

    • Author(s)
      Shinoda Y, Kawano H
    • Organizer
      18th The Connective Tissue Oncology Society Annual Meeting
    • Place of Presentation
      New York, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] A retrospective analysis of gemcitabine and docetaxel combination on neoadjuvant and adjuvant therapy compared with modified mesna, adriamycin, ifosfamide, and dacarbazine for adult soft tissue non-metastatic sarcomas2013

    • Author(s)
      Tsuda Y, Kawano H
    • Organizer
      18th The Connective Tissue Oncology Society Annual Meeting
    • Place of Presentation
      New York, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] 切除縁評価法の問題点 骨・軟部肉腫切除縁評価法の今後の課題2013

    • Author(s)
      河野博隆
    • Organizer
      日本整形外科学会骨・軟部腫瘍学術集会
    • Place of Presentation
      東京ドームホテル
    • Related Report
      2013 Annual Research Report

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

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