Elucidation of the mechanism of bone destruction in primary bone tumors

• Project/Area Number: 17K10960
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Niigata University
• Principal Investigator: Kawashima Hiroyuki 新潟大学, 医歯学系, 准教授 (30361900)
• Co-Investigator(Kenkyū-buntansha): 有泉 高志 新潟大学, 医歯学系, 助教 (50571915)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: RANKL / デノスマブ / 骨腫瘍 / 軟部腫瘍 / 破骨細胞 / 骨破壊 / 原発性骨腫瘍

Outline of Final Research Achievements

It was found that about 70% of patients with cancer bone metastases showed sclerotic change after denosumab administration. Skeletal-related events were significantly less frequent in cases with sclerotic change than in those without. In primary bone tumors, in addition to giant cell tumor of bone, leiomyosarcoma, aneurysmal bone cyst, and fibrous dysplasia also showed sclerotic change of lesions. Furthermore, we found that RANKL-related molecules are highly expressed in soft tissue tumors such as giant cell tumor of tendon sheath, pigmented villonodular synovitis, leiomyosarcoma, and undifferentiated pleomorphic sarcoma.

Academic Significance and Societal Importance of the Research Achievements

抗RANKL抗体薬であるデノスマブは、多くのがん骨転移に対して使用されているが、どのような癌腫に有効性が高いかを示すことができ、有効な症例に対して選択的に投与することが可能になった。また現在保険適応となっていない、原発性骨腫瘍や軟部腫瘍の一部に対する治療効果も期待される結果を示すことができ、将来的な適応拡大への布石となったと考えられる。

Research Products

• [Journal Article] Prolonged Myelosuppression due to Progressive Bone Marrow Fibrosis in a Patient with Acute Promyelocytic Leukemia (2019)
  • Author(s): Inagawa Yuta、Komeno Yukiko、Saito Satoshi、Maenohara Yuji、Yamagishi Tetsuro、Kawashima Hiroyuki、Saito Taku、Abe Keiko、Iihara Kuniko、Hatada Yasumasa、Ryu Tomiko
  • Journal Title: Case Reports in Hematology Volume: 2019 Pages: 1-7
  • DOI: 10.1155/2019/1616237
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression Profiling of Receptor-Activator of Nuclear Factor-Kappa B Ligand in Soft Tissue Tumors (2019)
  • Author(s): Yamagishi T, Kawashima H, Ogose A, Ariizumi T, Oike N, Sasaki T, Hatano H, Ohashi R, Umezu H, Ajioka Y, Endo N.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 248 Issue: 2 Pages: 87-97
  • DOI: 10.1620/tjem.248.87
  • NAID: 130007662277
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Journal Article] Denosumab as a potential therapeutic option for leiomyosarcoma with osteoclast?like giant cells: A case report (2017)
  • Author(s): Sasaki Taro、Kawashima Hiroyuki、Ariizumi Takashi、Yamagishi Tetsuro、Oike Naoki、Umezu Hajime、Inagawa Shyoichi、Hotta Tetsuo、Endo Naoto、Ogose Akira
  • Journal Title: Molecular and Clinical Oncology Volume: 8 Pages: 30-33
  • DOI: 10.3892/mco.2017.1489
  • Peer Reviewed / Open Access
• [Presentation] 巨細胞腫における免疫担当細胞の浸潤状況 (2018)
  • Author(s): 大池直樹、川島寛之、生越章、堀田哲夫、有泉高志、畠野宏史、山岸哲郎、遠藤直人
  • Organizer: 第91回日本整形外科学会学術総会
• [Presentation] 転移性骨腫瘍例における原発巣別デノスマブの効果 (2017)
  • Author(s): 有泉高志、川島寛之、山岸哲郎、大池直樹、堀田哲夫、遠藤直人、生越章、畠野宏史、佐々木太郎
  • Organizer: 第90回日本整形外科学会学術総会
• [Presentation] デノスマブ投与後に脊椎全摘術を施行した腰椎骨巨細胞腫の1例 (2017)
  • Author(s): 湊圭太郎、平野徹、渡辺慶、大橋正幸、川島寛之、有泉高志、山岸哲郎、遠藤直人、生越章
  • Organizer: 第113回東北整形災害外科学会