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The Anti-Cancer Multikinase Inhibitor Sorafenib Impairs Cardiac Contractility by Reducing Phospholamban Phosphorylation and Sarcoplasmic Calcium Transients.


ABSTRACT: Tyrosine-kinase inhibitors (TKIs) have revolutionized cancer therapy in recent years. Although more targeted than conventional chemotherapy, TKIs exhibit substantial cardiotoxicity, often manifesting as hypertension or heart failure. Here, we assessed myocyte intrinsic cardiotoxic effects of the TKI sorafenib and investigated underlying alterations of myocyte calcium homeostasis. We found that sorafenib reversibly decreased developed force in auxotonically contracting human myocardia (3?µM: -25?±?4%, 10?µM: -29?±?7%, 30?µM: -43?±?12%, p?

SUBMITTER: Schneider C 

PROVIDER: S-EPMC5871797 | biostudies-other | 2018 Mar

REPOSITORIES: biostudies-other

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The Anti-Cancer Multikinase Inhibitor Sorafenib Impairs Cardiac Contractility by Reducing Phospholamban Phosphorylation and Sarcoplasmic Calcium Transients.

Schneider Christopher C   Wallner Markus M   Kolesnik Ewald E   Herbst Viktoria V   Mächler Heinrich H   Pichler Martin M   von Lewinski Dirk D   Sedej Simon S   Rainer Peter P PP  

Scientific reports 20180328 1


Tyrosine-kinase inhibitors (TKIs) have revolutionized cancer therapy in recent years. Although more targeted than conventional chemotherapy, TKIs exhibit substantial cardiotoxicity, often manifesting as hypertension or heart failure. Here, we assessed myocyte intrinsic cardiotoxic effects of the TKI sorafenib and investigated underlying alterations of myocyte calcium homeostasis. We found that sorafenib reversibly decreased developed force in auxotonically contracting human myocardia (3 µM: -25   ...[more]

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