Estabrishment of non-clinical evaluating models in cardiotoxicities induced by a melecular targeted EGFR inhibitor for cancer
Project/Area Number |
15K08246
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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 |
General pharmacology
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Research Institution | Chiba Institute of Science (2018) Toho University (2015-2017) |
Principal Investigator |
Kentaro Ando 千葉科学大学, 薬学部, 教授 (90466904)
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Co-Investigator(Kenkyū-buntansha) |
杉山 篤 東邦大学, 医学部, 教授 (60242632)
中瀬古 寛子 東邦大学, 医学部, 講師 (80408773)
中村 裕二 東邦大学, 医学部, 助教 (10614894)
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Research Collaborator |
Wada Takeshi
Cao Xin
Chiba Koki
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Project Period (FY) |
2015-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 安全性薬理 / がん分子標的薬 / Onco-Cardiology / 心循環器毒性 / ラパチニブ / ハロセン麻酔犬モデル / 慢性房室ブロックモデル / 経胸壁心臓超音波検査 / Onco-cardiology / Lapatinib / 心毒性 / 慢性房室ブロック犬モデル / ハロセン麻酔犬 / 心臓毒性 / 左室拡張不全 / QT間隔延長 / ミトコンドリア機能 |
Outline of Final Research Achievements |
Effects of lapatinib on the cardiac electrophysiological action, contraction and relaxation, and plasma cardiac troponin I concentration were evaluated in the halothane anesthetized dog. Lapatinib-induced cardiotoxicities which first observed in clinical use can be detected in non-clinical studies by evaluation of the factors mentioned above. Furthermore, its safety in pro-arrhythmic potential can be evaluated by using the chronic atrioventricular-block dog. Implementation of precise safety pharmacology studies according to follow-up studies for the safety pharmacology core battery can change unexpected cardiac adverse events in clinical use to expect ones.
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Academic Significance and Societal Importance of the Research Achievements |
がん分子標的薬による”予期しない”心循環器毒性は、ハロセン麻酔犬モデルにおいて心臓電気生理学的検査、経胸壁心臓超音波検査、血漿中の心筋トロポニンI濃度測定の組み合わせ評価で十分に予想しうることが明らかとなった。さらに、慢性房室ブロック犬モデルにおける評価によって、催不整脈性に関する安全性も示せる事が明らかとなった。非臨床試験における心循環器毒性の適切な予測は副作用の少ないがん分子標的薬の開発につながり、がん患者を有害作用から保護して、患者のQOL向上に貢献できる。
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Report
(5 results)
Research Products
(13 results)
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[Journal Article] Sunitinib does not acutely alter left ventricular systolic function, but induces diastolic dysfunction2018
Author(s)
Wada T, Ando K, Naito AT, Nakamura Y, Goto A, Chiba K, Lubna NJ, Cao X, Hagiwara-Nagasawa M, Izumi-Nakaseko H, Nakazato Y, Sugiyama A
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Journal Title
Cancer Chemother Pharmacol.
Volume: -
Issue: 1
Pages: 65-75
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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