Treatment using bisphosphonate for malignant bone and soft tissue tumors

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591764
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MURATA Hiroaki Kyoto Prefectural University of Medicine, 医学研究科, 客員講師 (90360031)
• Co-Investigator(Kenkyū-buntansha): KIMURA SHINYA 佐賀大学, 医学部, 教授 (80359794)
• Project Period (FY): 2008 – 2010
• Keywords: 悪性骨腫瘍 / 悪性軟部腫瘍 / ビスホスフォネート / 癌

Research Abstract

The lower dose of third generation bisphosphonates (BPs) significantly prevented lung metastasis for the in vivo effects of BPs, although the higher dose of BPs was required to inhibit the growth of osteosarcoma cells at the primary site. In addition, BPs inhibited the production of vascular endothelial growth factor and reduced the migration, adhesion, and invasiveness of osteosarcoma cells in vitro. Combinationtherapy using BPs and radiation augmented the antitumor effects. From the results ofantitumor effects of BPs against fibrosarcoma cells, BPs arrested the cell cycle in the S phases, inhibited cell proliferation, and induced the apoptosis of their cells. Moreover, BPs augmented the effect of antitumor agents when administered concurrently with them in human fibrosarcoma cells.

Research Products

• [Journal Article] Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis, and shows combined effects with other anticancer agents. (2010)
  • Author(s): Koto K, Murata H, Kimura S, Horie N, Matsui T, Nishigaki Y, Ryu K, Sakabe T, Itoi M, Ashihara E, Maekawa T, Fushiki S, Kubo T.
  • Journal Title: Oncol Rep 24 Pages: 233-239
  • Peer Reviewed
• [Journal Article] Combined effects of bisphosphonate and radiation on osteosarcoma cells. (2010)
  • Author(s): Ryu K, Murata H, Koto K, Horie N, Matsui T, Nishigaki Y, Sakabe T, Takeshita H, Itoi M, Kimura S, Ashihara E, Maekawa T, Fushiki S, Kubo T.
  • Journal Title: Anticancer Res 30 Pages: 2713-2720
  • Peer Reviewed
• [Journal Article] Clinically relevant dose of zoledronic acid inhibits spontaneous lung metastasis in a murine osteosarcoma model. (2009)
  • Author(s): Koto K, Horie N, Kimura S, Murata H, Sakabe T, Matsui T, Watanabe M, Adachi S, Maekawa T, Fushiki S, Kubo T.
  • Journal Title: Cancer Lett 274 Pages: 271-278
  • Peer Reviewed
• [Presentation] Combined effects of a third-generation bisphosphonate and radiation against murine osteosarcoma. (2010)
  • Author(s): 村田博昭, 劉和輝, 小藤和孝, 堀江直行, 小藤和孝, 村田博昭, 坂部智哉, 劉和輝, 西垣泰典, 松井隆明, 坂部智哉, 西垣泰典, 久保俊一
  • Organizer: 8th Asis Pacific Musculoskeletal Tumor Society Meeting
  • Year and Date: 20100224-20100227
• [Presentation] 骨軟部肉腫細胞株に対する第3世代Bisphosphonate 含有ハイドロキシアパタイトの抗腫瘍効果の検討 (2010)
  • Author(s): 小藤和孝, 村田博昭, 坂部智哉, 劉和輝, 松井隆明, 堀江直行, 澤井泰志, 芦原英司, 伏木信次, 前川平, 久保俊一
  • Organizer: 第25回日本整形外科学会基礎学術集会
  • Year and Date: 2010-10-14
• [Presentation] ヒト軟部肉腫細胞株に対する3世代Bisphosphonate と放射線の併用効果に関する検討 (2010)
  • Author(s): 小藤和孝, 村田博昭, 坂部智哉, 劉和輝, 松井隆明, 堀江直行, 澤井泰志, 久保俊一
  • Organizer: 第34回近畿肉腫研究会
  • Year and Date: 2010-07-24
• [Presentation] The third-generation bisphosphonate inhibits tumor growth and lung metastasis in murine osteosarcoma cells. (2009)
  • Author(s): 村田博昭, 小藤和孝, 堀江直行, 坂部智哉, 松井隆明, 伏木信次, 木村晋也,前川平, 久保俊一
  • Organizer: The combined meeting of International Symposium of Limb Salvage and the Musculoskeletal Tumor Society
  • Year and Date: 20090923-20090926
• [Presentation] マウス骨肉腫細胞株に対するビスフォスフォネートと放射線照射の併用効果 (2009)
  • Author(s): 劉和輝, 村田博昭, 小藤和孝, 堀江直行, 松井隆明, 西垣泰典, 坂部智哉, 久保俊一
  • Organizer: 第42回日本整形外科学会骨・軟部腫瘍学術集会
  • Year and Date: 20090716-20090717
• [Presentation] The third-generation bisphosphonates inhibit tumor proliferation in human fibrosarcoma. (2009)
  • Author(s): 小藤和孝, 村田博昭, 坂部智哉, 松井隆明, 堀江直行, 伏木信次, 前川平, 伏木信次, 久保俊一
  • Organizer: 55th Annual Meeting of the Orthopaedic Research Society
  • Year and Date: 20090222-20090225
• [Presentation] ヒト軟部肉腫細胞株に対する第3世代Bisphosphonate と放射線の併用効果に関する検討 (2009)
  • Author(s): 小藤和孝, 村田博昭, 坂部智哉, 劉和輝, 西垣泰典, 松井隆明, 堀江直行, 伏木信次, 木村晋也, 前川平, 久保俊一
  • Organizer: 第24回日本整形外科学会基礎学術集会
  • Year and Date: 2009-11-06
• [Presentation] 骨肉腫細胞に対する第3世代ビスフォスフォネートの転移抑制効果 (2009)
  • Author(s): 小藤和孝, 村田博昭, 堀江直行, 坂部智哉, 松井隆明, 木村晋也, 前川平, 伏木信次, 久保俊一
  • Organizer: 第18回がん転移学会学術集会
  • Year and Date: 2009-07-23
• [Presentation] 第3世代Bisphosphonate によるヒト線維肉腫細胞株に対する抗腫瘍効果に関する検討 (2008)
  • Author(s): 小藤和孝, 村田博昭, 木村晋也, 坂部智哉, 松井隆明, 堀江直行, 伏木信次, 前川平, 久保俊一
  • Organizer: 第23回日本整形外科学会基礎学術集会
  • Year and Date: 2008-10-24
• [Presentation] 滑膜肉腫細胞に対する第3 世代ビスホスフォネートの効果 (2008)
  • Author(s): 西垣泰典, 村田博昭, 小藤和孝, 堀江直行, 劉和輝, 竹下秀之, 木村晋也, 前川平, 伏木信次, 久保俊一
  • Organizer: 第41回日整会骨軟部腫瘍学術集会
  • Year and Date: 2008-07-18
• [Presentation] 悪性軟部腫瘍に対するビスホスフォネートを用いた治療Part 2 (2008)
  • Author(s): 小藤和孝, 村田博昭, 西垣泰典, 松井隆明, 堀江直行, 久保俊一
  • Organizer: 第30回近畿肉腫研究会
  • Year and Date: 2008-06-28