Molecular-targeting chemotherapy related to p53-RB for malignant bone and soft tissue tumors

• Project/Area Number: 22591668
• 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: TSUJI Yoshiro 京都府立医科大学, 医学研究科, 客員講師 (70453123)
• Co-Investigator(Kenkyū-buntansha): MURATA Hiroaki 京都府立医科大学, 医学研究科, 客員講師 (90360031)
• Research Collaborator: KOTO Kazutaka 明治国際医療大学, 講師 (50649340)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 骨肉腫 / 線維肉腫 / スルフォラファン / 化学療法 / 放射線治療 / p53 遺伝子 / アポトーシス / 悪性骨腫瘍 / 悪性軟部腫瘍 / p53遺伝子 / P53遺伝子

Research Abstract

A MEK inhibitor suppressed cell growth and increased the population of G1/S phase cells in a dose-dependent manner for fibrosarcoma cells. The phosphorylation of ERK was inhibited and p21^WAF1/CIP1 and p27^KIP1 protein expression increased. These results indicate that it might be an attractive compound for molecular-targeting chemotherapy with the activation of the Ras-MEK-ERK pathway.Sulforaphane(SFN) enhanced the radiosensitivity of osteosarcoma cells by inducing apoptosis through G2/M-phase arrest and inhibiting ERK and Akt activation. These findings suggest that SFN can be used as a radiosensitizer for osteosarcomas.

Research Products

• [Journal Article] Effectiveness of sulforaphane as a radiosensitizer for murine osteosarcoma cells (2013)
  • Author(s): Y. Sawai, H. Murata, M. Horii, K. Koto,T. Matsui, N. Horie, Y. Tsuji, E. Ashihara, T. Maekawa, T. Kubo, S. Fushiki
  • Journal Title: Oncol Rep Volume: 29 Issue: 3 Pages: 941-945
  • DOI: 10.3892/or.2012.2195
  • Peer Reviewed
• [Journal Article] A novel MEK1/2 inhibitor induces G1/S cell cycle arrest in human fibrosarcoma cells (2010)
  • Author(s): T.A. Matsui, H. Murata, Y. Sowa, T. Sakabe, K. Koto, N. Horie, Y. Tsuji, T. Sakai, T. Kubo
  • Journal Title: Oncol Rep Volume: 24 Issue: 2 Pages: 329-333
  • DOI: 10.3892/or_00000863
  • Peer Reviewed
• [Journal Article] A novel MEK1/2 inhibitor induces G1/S cell cycle arrest in human fibro sarcoma cells (2010)
  • Author(s): Matsui TA, Murata H, Tsuji Y, et al.
  • Journal Title: Oncol Rep Volume: 24 Pages: 329-333
  • Peer Reviewed
• [Presentation] Effectiveness of sulforaphane as a radiosensitizer for murine osteosarcoma cells (2013)
  • Author(s): Y. Sawai, H. Murata, M. Horii, K. Koto,T. Matsui, N. Horie, Y. Tsuji, E. Ashihara, T. Maekawa, T. Kubo, S. Fushiki
  • Organizer: 2013 Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: San Antonio, USA
• [Presentation] マウス骨肉腫細胞株に対するsulforaphane の放射線増感作用の検討 (2012)
  • Author(s): 澤井泰志、村田博昭、小藤和孝、松井隆明、堀江直行、堀井基行、久保俊一
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋
• [Presentation] Effect of a specific MEK inhibitor against human fibrosarcoma cells (2010)
  • Author(s): T. Matsui, H. Murata, T. Sakabe, K. Koto, N. Horie, Y. Sowa, T. Sakai, T. Kubo
  • Organizer: 8th Asis Pacific Musculoskeletal Tumor Society Meeting
  • Place of Presentation: Cebu, Philippines
• [Presentation] マウス骨肉腫細胞株に対するsulforaphaneの放射線増感作用の検討
  • Author(s): 澤井泰志，村田博昭，小藤和孝，松井隆明，堀江直行，堀井基行，久保俊一(澤井泰志)
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋