Development of new treatments against malignant bone and soft tissue tumors by using bisphosphonate and ionizing radiation
Project/Area Number |
23592196
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Orthopaedic surgery
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
MURATA Hiroaki 京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (90360031)
|
Co-Investigator(Kenkyū-buntansha) |
KOTO Kazutaka 明治国際医療大学, 公私立大学の部局等, 講師 (50649340)
|
Co-Investigator(Renkei-kenkyūsha) |
MAEKAWA Taira 京都大学, 大学院医学研究科, 教授 (80229286)
KIMURA Shinya 佐賀大学, 医学部, 教授 (80359794)
ASHIHARA Eishi 京都薬科大学, 薬学部, 教授 (70275197)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | ビスホスフォネート / 軟部肉腫 / 放射線治療 / アポトーシス / 骨肉腫 / ビスホスホネート |
Research Abstract |
Fibrosarcoma cells were treated with third-generation bisphosphonate (BPs) and/or ionizing radiation (IR), together or sequentially, and the antitumor effects were assessed. BPs significantly enhanced IR-induced apoptosis, especially when cells were treated with BPs followed by IR. We therefore assessed the detailed mechanism of sequential treatment with BPs and IR. Cells in G2 and M phases, the most radiosensitive phases of the cell cycle, were not increased by low concentrations of BPs. However, the levels of expression of Akt, ERK1/2, and NF- B proteins, all of which are related to radioadaptive resistance, were increased within a short time after irradiation with 3 Gy, and this expression was inhibited by a low concentration of BPs, which blocked the prenylation of small GTPases. This sequential treatment also increased the generation of reactive oxygen species (ROS).
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] Zoledronic acid significantly enhances radiation induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling.2013
Author(s)
8. Koto K, Murata H, Kimura S, Sawai Y, Horie N, Matsui T, Ryu K, Ashihara E, Maekawa T, Kubo T, Fushiki S.
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Journal Title
Int J Oncol
Volume: 42
Issue: 2
Pages: 525-534
DOI
Related Report
Peer Reviewed
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[Presentation] The third-generation bisphosphonate shows combined effects with anti-tumor drugs in human fibrosarcoma cells2013
Author(s)
Murata H, Koto K, Sawai Y, Matsui TA, Horie N, Fushiki S, Kimura S, Maekawa T, Horii M, Kubo T
Organizer
International Society of Limb Salvage 17th General Meeting
Place of Presentation
Bologna, Italy
Related Report
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[Presentation] Zoledronic acid significantly enhances radiation-induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling2013
Author(s)
Koto K, Murata H, Matsui TA, Horie N, Sawai Y, Ashihara E, Kimura S, Maekawa T, Fushiki S, Horii M, Kubo T
Organizer
International Society of Limb Salvage 17th General Meeting
Place of Presentation
Bologna, Italy
Related Report
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[Presentation] Combined effects of the Third-Generation Bisphosphonate and Radiation on Fibrosarcoma Cells2012
Author(s)
Koto K, Murata H, Sakabe T, Matsui TA, Horie N, Sawai Y, Ashihara E, Kimura S, Maekawa T, Fushiki S, Kubo T
Organizer
13th EFORT Congress
Place of Presentation
Berlin, Germany
Year and Date
2012-05-25
Related Report
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[Presentation] Combined effects of the Third-Generation Bisphosphonate and Radiation on Fibrosarcoma Cells
Author(s)
Koto K, Murata H, Sakabe T, Matsui TA, Horie N, Sawai Y, Ashihara E, Kimura S, Maekawa T, Fushiki S, Kubo T.
Organizer
13th EFORT Congress 2012
Place of Presentation
Berlin, Germany
Related Report
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