Novel therapeutic strategy of osteosarcoma by regulation of RANK signal pathway

• Project/Area Number: 23592178
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The 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: ¥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.

Research Products

• [Journal Article] Impact of hospital volume on postoperative complications and in-hospital mortality after musculoskeletal tumor surgery : analysis of a national administrative database (2013)
  • Author(s): Ogura K, Kawano H
  • Journal Title: J Bone Joint Surg Am Volume: 95(18) Pages: 1684-91
  • Peer Reviewed
• [Journal Article] Incidence and risk factors for pulmonary embolism after primary musculoskeletal tumor surgery (2013)
  • Author(s): Ogura K, Kawano H
  • Journal Title: Clin Orthop Relat Res Volume: 471(10) Pages: 3310-6
  • 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 sarcomas (2013)
  • Author(s): Ogura K, Kawano H
  • Journal Title: Int J Clin Oncol Volume: 18(1) Pages: 170-6
  • Peer Reviewed
• [Journal Article] Chest wall deformity found in patientswith primary spontaneous pneumothorax (2013)
  • Author(s): Saita K, Kawano H
  • Journal Title: Asian Cardiovascular & Thoracic Annals Volume: (published online) Pages: 11-11
  • Peer Reviewed
• [Journal Article] Incidence of, and risk factors for, postoperative venous thromboembolism in patients with benign or malignant musculoskeletal tumors (2013)
  • Author(s): Tsuda Y, Kawano H
  • Journal Title: J Orthop Sci Volume: 18(4) Pages: 613-7
  • Peer Reviewed
• [Journal Article] Vitamin D receptor in osteoblasts is a negative regulator of bone mass control (2013)
  • Author(s): Yamamoto Y, Kawano H
  • Journal Title: Endocrinology Volume: 154(3) Pages: 1008-20
  • Peer Reviewed
• [Journal Article] Regulation of bone-resorption and sealing zone formation in osteoclasts occurs through Akt-mediated microtubule stabilization (2013)
  • Author(s): Matsumoto T, Kadono Y
  • Journal Title: J Bone Miner Res Volume: 28(5) Pages: 1191-202
  • Peer Reviewed
• [Journal Article] Incidence of, and risk factors for, postoperative venous thromboembolism in patients with benign or malignant musculoskeletal tumors. (2013)
  • Author(s): 津田祐輔 河野博隆 他
  • Journal Title: J Orthop Sci Volume: 18(4) Issue: 4 Pages: 613-617
  • DOI: 10.1007/s00776-013-0401-6
  • Peer Reviewed
• [Journal Article] Incidence and risk factors for postoperative pulmonary embolism following primary musculoskeletal tumor surgery: Analysis of a national administrative database. (2013)
  • Author(s): Ogura K, Yasunaga H, Horiguchi H, Ohe K, Shinoda Y, Tanaka S, Kawano H
  • Journal Title: CORR 2013 Volume: 471(10) Issue: 10 Pages: 3310-3316
  • DOI: 10.1007/s11999-013-3073-9
  • Peer Reviewed
• [Journal Article] Impact of hospital volume on postoperative complications and in-hospital mortality after musculoskeletal tumor surgery: analysis of a national administrative database. (2013)
  • Author(s): 小倉浩一 河野博隆 他
  • Journal Title: J Bone Joint Surg Am Volume: 95(18) Issue: 18 Pages: 1684-91
  • DOI: 10.2106/jbjs.l.00913
  • 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
  • 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 sarcomas. (2013)
  • Author(s): 小倉浩一 河野博隆 他
  • Journal Title: Int J Clin Oncol. Volume: 18(1) Issue: 1 Pages: 170-6
  • DOI: 10.1007/s10147-011-0360-x
  • Peer Reviewed
• [Journal Article] Alveolar soft part sarcoma : a single-center 26-patient case series and review of the literature (2012)
  • Author(s): Ogura K, Kawano H
  • Journal Title: Sarcoma
  • 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): Ogura K, Kawano H
  • Journal Title: Arch Orthop Trauma Surg Volume: 132(10) Pages: 1379-86
  • Peer Reviewed
• [Journal Article] Bone radiofrequency ablation combined with prophylactic internal fixation for metastatic bone tumor of the femur from hepatocellular carcinoma (2012)
  • Author(s): Ogura K, Kawano H.
  • Journal Title: Int J Clin Oncol Volume: 17(4) Pages: 417-21
  • NAID: 10031120988
  • Peer Reviewed
• [Journal Article] Recurrent epithelioid hemangioma : therapeutic potential of tranilast and indomethacin (2012)
  • Author(s): Ogura K, Kawano H
  • Journal Title: J Orthop Sci Volume: 17(2) Pages: 194-8
  • Peer Reviewed
• [Journal Article] Periosteal osteoblastoma of the distal femur : a case report and a review of the literature with special emphasison the MR features (2012)
  • Author(s): Ogura K, Kawano H
  • Journal Title: Int Canc Conf J Volume: 1:103 Pages: 107-107
  • Peer Reviewed
• [Journal Article] Class IA phosphatidylinositol 3-kinase regulates osteoclastic bone resorption through Akt-mediated vesicle transport (2012)
  • Author(s): Shinohara M, Kadono Y
  • Journal Title: J Bone Miner Res Volume: 27(12) Pages: 2464-75
  • Peer Reviewed
• [Journal Article] Risk factors affecting inhospital mortality after hip fracture : retrospective analysis using the Japanese Diagnosis Proc edure Combination Database (2012)
  • Author(s): Shoda N, Kadono Y
  • Journal Title: BMJ Open Volume: 4 Pages: 2-2
  • Peer Reviewed
• [Journal Article] Alveolar soft part sarcoma: a single-center 26-patient case series and review of the literature. (2012)
  • Author(s): Ogura K
  • Journal Title: Sarcoma Volume: 2012 Pages: 907179-907179
  • DOI: 10.1155/2012/907179
  • 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
  • Peer Reviewed
• [Journal Article] Bone radiofrequency ablation combined with prophylactic internal fixation for metastatic bone tumor of the femur from hepatocellular carcinoma. (2012)
  • Author(s): 小倉浩一 河野博隆 他
  • Journal Title: Int J Clin Oncol Volume: 17(4) Issue: 4 Pages: 417-21
  • DOI: 10.1007/s10147-011-0319-y
  • NAID: 10031120988
  • Peer Reviewed
• [Journal Article] Recurrent epithelioid hemangioma: therapeutic potential of tranilast and indomethacin. (2012)
  • Author(s): 小倉浩一 河野博隆 他
  • Journal Title: J Orthop Sci. Volume: 17(2) Issue: 2 Pages: 194-8
  • DOI: 10.1007/s00776-011-0081-z
  • 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 axis (2011)
  • Author(s): Matsumoto T, Kadono Y
  • Journal Title: Arthritis Rheum Volume: 63(12) Pages: 3908-17
  • Peer Reviewed
• [Journal Article] Regulation of RANKL-induced osteoclastogenesis by TGF-βthrough molecular interaction between Smad3 and TRAF6 (2011)
  • Author(s): Yasui T, Kadono Y
  • Journal Title: J Bone Miner Res Volume: 26(7) Pages: 1447-56
  • Peer Reviewed
• [Presentation] Clinical outcome of surgical treatment for tumor induced osteomalacia with phosphaturic mesenchymal tumor, mixed connective tissue variant (2013)
  • Author(s): Kawano H, Shinoda Y
  • Organizer: International Society of Limb Salvage 17^<th> General Meeting
  • Place of Presentation: Bologna, Italy
• [Presentation] Prediction of pathologic fracture risk in stance and fall loading configurations for metastases in the proximal femur, using CT-based finite element method (2013)
  • Author(s): Shinoda Y, Kawano H
  • Organizer: International Society of Limb Salvage 17^<th> General Meeting
  • Place of Presentation: Bologna, Italy
• [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 sarcomas (2013)
  • Author(s): Tsuda Y, Kawano H
  • Organizer: International Society of Limb Salvage 17^<th> General Meeting
  • Place of Presentation: Bologna, Italy
• [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
• [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 sarcomas (2013)
  • Author(s): Tsuda Y, Kawano H
  • Organizer: 18th The Connective Tissue Oncology Society Annual Meeting
  • Place of Presentation: New York, USA
• [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