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Analyses of signal network of bone metabolism through giant cell-rich lesions of bone

Research Project

Project/Area Number 16K19085
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionYokohama City University

Principal Investigator

Kato Ikuma  横浜市立大学, 医学部, 助教 (80644939)

Research Collaborator FURUYA Mitsuko  
KAWABATA Yusuke  
MATSUO Kosuke  
TANAKA Reiko  
OHASHI Kenichi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords骨巨細胞腫 / 骨腫瘍 / RANK / RANKL / 遺伝子変異 / 病理組織 / 免疫組織化学 / 分子標的治療 / 病理学
Outline of Final Research Achievements

Denosumab, a human monoclonal antibody directed against the receptor activator of nuclear factor-kappa B ligand (RANKL), was introduced as a therapeutic agentis for giant cell tumor of bone (GCTB). To understand the complete mechanism of denosumab, we compared the histologic and immunohistochemical features of GCTBs before and after denosumab therapy. In all cases, the osteoclast-like giant cells disappeared. However, all post-therapeutic lesions still contained many H3.3 G34W(+) cells. Immunofluorescent double-staining revealed that RUNX2(+) mononuclear cells co-expressed H3.3 G34W in pre- and post-denosumab lesions. In conclusion, the neoplastic cells survive denosumab therapy and make woven bones in respond to the new environment free from osteoclastic cells.

Academic Significance and Societal Importance of the Research Achievements

近年発見された特異的遺伝子異常の視点を加えたことで、骨巨細胞腫は、非腫瘍細胞(破骨細胞系細胞)との相互作用によって成立している腫瘍性病変であることが明らかとなった。また抗RANKL抗体による治療は、一見すると劇的な治療効果があるように思われていたが、根本的な治療とは言い難いことが明らかとなった。病理組織像と遺伝子異常を統合的に解析することが、疾患の本質的な理解につながることが示された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2019 2018 2017

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (7 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Myoepithelioma‐like tumor of the vulvar region showing infiltrative growth and harboring only a few estrogen receptor‐positive cells: A case report2019

    • Author(s)
      Kojima Yui、Tanabe Mikiko、Kato Ikuma、Motoi Toru、Kimura Mariko、Sawazumi Tomoe、Tanaka Reiko、Chiba Sawako、Otani Masako、Inayama Yoshiaki
    • Journal Title

      Pathology International

      Volume: 69 Issue: 3 Pages: 172-176

    • DOI

      10.1111/pin.12765

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Rare Solitary Fibrous Tumor Originating From the Distal Aortic Arch2019

    • Author(s)
      Kotani Sohsyu、Inoue Yoshito、Haida Hirofumi、Dehari Reiko、Kato Ikuma
    • Journal Title

      The Annals of Thoracic Surgery

      Volume: 107 Issue: 3 Pages: e195-e197

    • DOI

      10.1016/j.athoracsur.2018.07.063

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Giant cell tumours of bone treated with denosumab: histological, immunohistochemical and H3F3A mutation analyses2018

    • Author(s)
      Kato Ikuma、Furuya Mitsuko、Matsuo Kosuke、Kawabata Yusuke、Tanaka Reiko、Ohashi Kenichi
    • Journal Title

      Histopathology

      Volume: 72 Issue: 6 Pages: 914-922

    • DOI

      10.1111/his.13448

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel partner of TFE3 in the Xp11 translocation renal cell carcinoma: clinicopathological analyses and detection of EWSR1-TFE3 fusion2018

    • Author(s)
      Fukuda Hironori、Kato Ikuma、Furuya Mitsuko、Tanaka Reiko、Takagi Toshio、Kondo Tsunenori、Nagashima Yoji
    • Journal Title

      Virchows Archiv

      Volume: 474 Issue: 3 Pages: 389-393

    • DOI

      10.1007/s00428-018-2509-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hereditary leiomyomatosis and renal cell cancer without cutaneous manifestations in two Japanese siblings2018

    • Author(s)
      Noguchi Go、Furuya Mitsuko、Okubo Yoichiro、Nagashima Yoji、Kato Ikuma、Matsumoto Kana、Tanaka Reiko、Hisasue Shin-ichi、Yao Masahiro、Kishida Takeshi
    • Journal Title

      International Journal of Urology

      Volume: 25 Issue: 9 Pages: 832-835

    • DOI

      10.1111/iju.13760

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intracranial epidermoid cyst with proliferative folliculosebaceous epithelium: Report of a rare case and discussion on pathogenesis2018

    • Author(s)
      Okada Tomu、Fujitsu Kazuhiko、Ichikawa Teruo、Miyahara Kousuke、Tanino Shin、Uriu Yasuhiro、Hataoka Synsuke、Tanaka Yuusuke、Suzuki Kouji、Niino Hitosi、Yagishita Saburou、Kato Ikuma
    • Journal Title

      Neuropathology

      Volume: 38 Issue: 5 Pages: 510-515

    • DOI

      10.1111/neup.12481

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histopathological analysis of aggressive renal cell carcinoma harboring a unique germline mutation in fumarate hydratase2018

    • Author(s)
      Matsumoto Kana、Udaka Naoko、Hasumi Hisashi、Nakaigawa Noboru、Nagashima Yoji、Tanaka Reiko、Kato Ikuma、Yao Masahiro、Furuya Mitsuko
    • Journal Title

      Pathology International

      Volume: 68 Issue: 8 Pages: 473-478

    • DOI

      10.1111/pin.12684

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 3-I-11 デノスマブ投与後の骨巨細胞腫:蛍光免疫二重染色を含めた統合的解析2018

    • Author(s)
      加藤生真、古屋充子、川端佑介、田中玲子、大橋健一
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] J-3028 骨巨細胞腫における真の腫瘍細胞は、破骨細胞系ではなく骨芽細胞系である2018

    • Author(s)
      加藤生真、古屋充子、大橋健一
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] True Neoplastic Cells in Giant Cell Tumor of Bone are Osteoblast Lineage Cells.2018

    • Author(s)
      Kato I, Furuya M, Kawabata Y, Tanaka R, Ohashi K.
    • Organizer
      Global Academic Programs GAP 2018 conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Denosumab Induces the Disappearance of Osteoclastic Lineage Cells, but Failed to Eliminate the Tumor Cells of Giant Cell Tumor of Bone.2017

    • Author(s)
      Kato I., Furuya M., Matsuo K., Tanaka R., Ohashi K., Aoki I.
    • Organizer
      103rd The United States Canadian Academy of Pathology Annual meeting
    • Place of Presentation
      米国, San Antonio
    • Year and Date
      2017-03-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] デノスマブ投与後の骨巨細胞腫:組織像の劇的な変化は腫瘍細胞の消失を意味しない2017

    • Author(s)
      加藤 生真、古屋 充子、松尾 光祐、田中 玲子、大橋 健一、青木 一郎
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Giant cell tumor of bone after denosumab therapy: histologic changes do not mean disappearance of the tumor cells2017

    • Author(s)
      加藤生真、古屋充子、大橋健一
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] True Neoplastic Cells in Giant Cell Tumor of Bone Potentially Have Osteogenic Nature and Reveal their Osteogenic Histology After Denosumab Therapy: Integrated Analyses Including Immunofluorescent Double Staining.2017

    • Author(s)
      Kato I, Furuya M, Kawabata Y, Tanaka R, Ohashi K.
    • Organizer
      107th The United States Canadian Academy of Pathology Annual meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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