Research on the mechanism and treatment of chemotherapy-induced peripheral neuropathy
Project/Area Number |
24592358
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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 |
Anesthesiology/Resuscitation studies
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Research Institution | Jikei University School of Medicine (2015-2016) Teikyo University (2012-2014) |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
下山 直人 東京慈恵会医科大学, 医学部, 教授 (40196572)
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Co-Investigator(Renkei-kenkyūsha) |
TOYAMA Satoshi 国立成育医療研究センター, 手術・集中治療部, 医長 (30318092)
ISHIDA Yasuo 帝京大学ちば総合医療センター, 病院病理部, 教授 (50151387)
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Project Period (FY) |
2012-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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Keywords | peripheral neuropathy / chemotherapy / oxaliplatin / mitochondria / オキサリプラチン / 化学療法惹起性末梢神経障害 / ミトコンドリア / 化学療法惹起性神経障害 / オレキシン / 化学療法 / 末梢神経障害 / トラマドール / 神経障害 / ミトコンドリア障害 / 急性神経障害 / 慢性神経障害 |
Outline of Final Research Achievements |
Repeated administrations of oxaliplatin at doses with anti-tumor effects with rest periods in between administrations to allow recovery from acute toxic effects, induced neuropathy that closely mimicked patients conditions. In this model, tetrapeptides that target cardiolipin of the mitochondria and improve mitochondrial bioenergetics prevented the development of the neuropathy. This suggested that mitochondrial dysfunction is involved in the pathogenesis and these compounds may be useful in preventing chemotherapy-induced peripheral neuropathy in patients. Furthermore, the results of drug tests using this model suggested that, in addition to duloxetine which is already recommended for the treatment of neuropathic pain due to chemotherapy-induced peripheral neuropathy, tramadol, pregabalin and orexin 1-receptor agonists may be effective.
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Report
(6 results)
Research Products
(19 results)
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[Journal Article] Efficacy and Safety of Sublingual Fentanyl Orally Disintegrating Tablet at Doses Determined by Titration for the Treatment of Breakthrough Pain in Japanese Cancer Patients: A Multicenter, Randomized, Placebo-controlled, Double-Blind Phase III Trial. Int.2015
Author(s)
2.Shimoyama, N., Gomyo, I., Katakami, N., Okada, M., Yukitoshi, N., Ohta, E., and Shimoyama, M.
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Journal Title
J. Clin. Oncol.
Volume: 20
Issue: 1
Pages: 198-206
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Efficacy and Safety of Sublingual Fentanyl Orally Disintegrating Tablet at Doses Determined from Oral Morphine Rescue Doses in the Treatment of Breakthrough Cancer Pain2015
Author(s)
1.Shimoyama, N., Gomyo, I., Teramoto, O., Kojima, K., Higuchi, H., Yukitoshi,Y., Ohta, E, and Shimoyama, M.
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Journal Title
Jpn. J. Clin. Oncol.
Volume: 45
Issue: 2
Pages: 189-196
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Characterization of acute and chronic neuropathies induced by oxaliplatin in mice and differential effects of a novel mitochondria-targeted antioxidant on the neuropathies.2014
Author(s)
Toyama, S., Shimoyama, N., Ishida, Y., Koyasu, T., Szeto, H.H., Shimoyama, M.
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Journal Title
Anesthesiology
Volume: 120
Issue: 2
Pages: 459-473
DOI
Related Report
Peer Reviewed
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[Journal Article] Superior analgesic effect of H-Dmt-D-Arg-Phe-Lys-NH2 ([Dmt1]DALDA), a multifunctional opioid peptide, compared to morphine in a rat model of neuropathic pain2012
Author(s)
Shimoyama, M., Schiller, P.W., Shimoyama, N. Toyama, S., Szeto, H.H.
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Journal Title
Chem. Biol. Drug Design
Volume: 80
Pages: 771-774
Related Report
Peer Reviewed
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[Presentation] A comparison of the analgesic effects of H-Dmt-D-Arg-Phe-Lys-NH2, a synthetic opioid peptide, and morphine in experimental neuropathic pain
Author(s)
Shimoyama, M., Shimoyama,N., Schiller, P.W. and Szeto, H.H.
Organizer
A,merican Pain Society Annual Scientific Meeting
Place of Presentation
Honolulu, U.S.A.
Related Report
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