Hirozane, Toru



School of Medicine, Department of Orthopaedic Surgery (Shinanomachi)




Papers 【 Display / hide

  • Feasibility of Targeting Traf2-and-Nck-Interacting Kinase in Synovial Sarcoma.

    Sekita T, Yamada T, Kobayashi E, Yoshida A, Hirozane T, Kawai A, Uno Y, Moriyama H, Sawa M, Nagakawa Y, Tsuchida A, Matsumoto M, Nakamura M, Nakayama R, Masuda M

    Cancers (Cancers)  12 ( 5 )  2020.05

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    © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Background: The treatment of patients with metastatic synovial sarcoma is still challenging, and the development of new molecular therapeutics is desirable. Dysregulation of Wnt signaling has been implicated in synovial sarcoma. Traf2-and-Nck-interacting kinase (TNIK) is an essential transcriptional co-regulator of Wnt target genes. We examined the efficacy of a small interfering RNA (siRNA) to TNIK and a small-molecule TNIK inhibitor, NCB-0846, for synovial sarcoma. Methods: The expression of TNIK was determined in 20 clinical samples of synovial sarcoma. The efficacy of NCB-0846 was evaluated in four synovial sarcoma cell lines and a mouse xenograft model. Results: We found that synovial sarcoma cell lines with Wnt activation were highly dependent upon the expression of TNIK for proliferation and survival. NCB-0846 induced apoptotic cell death in synovial sarcoma cells through blocking of Wnt target genes including MYC, and oral administration of NCB-846 induced regression of xenografts established by inoculation of synovial sarcoma cells. Discussion: It has become evident that activation of Wnt signaling is causatively involved in the pathogenesis of synovial sarcoma, but no molecular therapeutics targeting the pathway have been approved. This study revealed for the first time the therapeutic potential of TNIK inhibition in synovial sarcoma.

  • Pseudomyogenic hemangioendothelioma of bone treated with denosumab: A case report

    Otani S., Nakayama R., Sekita T., Hirozane T., Asano N., Nishimoto K., Sasaki A., Okita H., Morioka H., Nakamura M., Matsumoto M.

    BMC Cancer (BMC Cancer)  19 ( 1 )  2019.09

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    © 2019 The Author(s). Background: Pseudomyogenic hemangioendothelioma (PMHE) is a rare endothelial neoplasm that involves the bones in only 14% of all cases. The optimal treatment strategy has not been established. We herein report a case of primary PMHE in which denosumab treatment showed activity in both imaging studies and the clinical outcome. Case presentation: A 20-year-old woman presented with worsening pain in her left ankle. Imaging studies showed multifocal fluorodeoxyglucose (FDG)-avid [maximum standardized uptake value (SUVmax), 15.95] osteolytic lesions in the bones of her left lower extremity. While waiting for the definitive pathologic diagnosis of PMHE, denosumab, a human immunoglobulin G2 monoclonal antibody against RANKL, was initiated to treat progressive bone absorption after curettage of one of the lesions. Denosumab induced osteosclerosis around the lesions and pain relief and was discontinued 4 years after its initiation. Although all of the multifocal lesions remained, they all became less FDG-avid (SUVmax, 2.6), and the patient developed no signs of new lesions or distant metastasis. Conclusion: Denosumab plays a certain role in prevention of bone destruction by PMHE through suppression of osteoclast-like giant cells and would be an excellent treatment for bone absorption by PMHE of bone.

  • Preservation of the Epiphysis and Growth Plate in the Surgical Management of Femoral Osteosarcoma in a Skeletally Immature Patient by Intercalary Resection and Biological Reconstruction: A Case Report

    Yoda Y., Yamaguchi S., Hirozane T., Asano N., Seki A., Morioka H., Nakayama R., Nakamura M., Matsumoto M.

    Case Reports in Oncology (Case Reports in Oncology)  12 ( 2 ) 513 - 522 2019.05

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    © 2019 The Author(s) Published by S. Karger AG, Basel. Osteosarcoma arises most frequently in the metaphysis around the knee and its management by limb salvage surgery in skeletally immature pediatric patients is extremely challenging. Common reconstructive methods such as endoprosthetic or biological reconstruction are not fully capable of dealing with durability-related and growth-related problems and their functional outcomes are not as good as those seen in adult cases. A definitive limb salvaging procedure in children that outperforms amputation or rotationplasty has not yet been established. Herein, we report a case of stage IV osteosarcoma in the femur of a 7-year-old boy that was safely managed with intercalary resection preserving the distal femoral growth plate and epiphysis, followed by biological reconstruction using a frozen tumor-devitalized autograft. Good response to preoperative chemotherapy and the diaphyseal location of the tumor enabled us to perform a tumor resection that spared the growth plate and preserved the native knee joint structure. Plate fixation over the growth plate was terminated by removing the locking screws in the epiphysis after 44 months, which restored growth capacity to some extent. At 50 months postoperatively, no recurrence or progression of the disease was observed. The patient uses an extension shoe and reports having little discomfort in his daily life despite having a restricted range of motion and limb length discrepancy. In conclusion, limb salvage with biological reconstruction in skeletally immature patients can provide an acceptable functional outcome, including minimized limb length discrepancy, if critical damage to the growth plate and articular components can be avoided.

Papers, etc., Registered in KOARA 【 Display / hide

Research Projects of Competitive Funds, etc. 【 Display / hide

  • 骨軟部腫瘍に対するWntシグナルを標的とした治療法の探索


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 弘實 透, Grant-in-Aid for Early-Career Scientists , Principal Investigator

  • 骨肉腫に対するWntシグナルを標的とした治療法の検討


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 弘實 透, Grant-in-Aid for Early-Career Scientists , Principal Investigator


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