弘實 透 (ヒロザネ トオル)

Hirozane, Toru

写真a

所属(所属キャンパス)

医学部 整形外科学教室 (信濃町)

職名

助教(有期)

 

論文 【 表示 / 非表示

  • Malignant transformation of metastatic giant cell tumor of bone in a patient undergoing denosumab treatment: A case report.

    Yung D, Asano N, Hirozane T, Yamaguchi S, Mori T, Susa M, Okita H, Morioka H, Horiuchi K, Nakayama R

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association (Journal of Orthopaedic Science)  2021年08月

    ISSN  0949-2658

  • Sequential imaging of hyperplastic callus formation in Osteogenesis Imperfecta type V: A case report and review of the literature.

    Yung D, Arai M, Matsumoto S, Sato T, Hirozane T, Yamaguchi S, Asano N, Hasegawa T, Nakayama R

    Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association (Journal of Orthopaedic Science)  2021年06月

    ISSN  0949-2658

  • Direct conversion of osteosarcoma to adipocytes by targeting TNIK.

    Hirozane T, Masuda M, Sugano T, Sekita T, Goto N, Aoyama T, Sakagami T, Uno Y, Moriyama H, Sawa M, Asano N, Nakamura M, Matsumoto M, Nakayama R, Kondo T, Kawai A, Kobayashi E, Yamada T

    JCI insight 6 ( 3 )  2021年02月

  • Pharmacological blockage of transforming growth factor-β signalling by a Traf2- and Nck-interacting kinase inhibitor, NCB-0846.

    Sugano T, Masuda M, Takeshita F, Motoi N, Hirozane T, Goto N, Kashimoto S, Uno Y, Moriyama H, Sawa M, Nagakawa Y, Tsuchida A, Seike M, Gemma A, Yamada T

    British journal of cancer (British Journal of Cancer)  2020年11月

    ISSN  0007-0920

     概要を見る

    © 2020, The Author(s), under exclusive licence to Cancer Research UK. Background: Metastasis is the primary cause of death in cancer patients, and its management is still a major challenge. Epithelial to mesenchymal transition (EMT) has been implicated in the process of cancer metastasis, and its pharmacological interference holds therapeutic promise. Methods: Traf2- and Nck-interacting kinase (TNIK) functions as a transcriptional coregulator of Wnt target genes. Given the convergence of Wnt and transforming growth factor-β (TGFβ) signalling, we examined the effects of a small-molecule TNIK inhibitor (named NCB-0846) on the TGFβ1-induced EMT of lung cancer cells. Results: NCB-0846 inhibited the TGFβ1-induced EMT of A549 cells. This inhibition was associated with inhibition of Sma- and Mad-Related Protein-2/3 (SMAD2/3) phosphorylation and nuclear translocation. NCB-0846 abolished the lung metastasis of TGFβ1-treated A549 cells injected into the tail veins of immunodeficient mice. The inhibition of EMT was mediated by suppression of the TGFβ receptor type-I (TGFBR1) gene, at least partly through the induction of microRNAs targeting the TGFBR1 transcript [miR-320 (a, b and d) and miR-186]. Conclusions: NCB-0846 pharmacologically blocks the TGFβ/SMAD signalling and EMT induction of lung cancer cells by transcriptionally downregulating TGFBRI expression, representing a potentially promising approach for prevention of metastasis in lung cancer patients.

  • 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年05月

     概要を見る

    © 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.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

競争的資金等の研究課題 【 表示 / 非表示

  • 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

    2020年04月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 弘實 透, 若手研究, 補助金,  代表

  • 骨肉腫に対するWntシグナルを標的とした治療法の検討

    2018年04月
    -
    2020年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 弘實 透, 若手研究, 補助金,  代表

 

担当授業科目 【 表示 / 非表示

  • 整形外科学講義

    2021年度

  • 整形外科学講義

    2020年度

  • 整形外科学講義

    2019年度