Does spironolactone ameliorate trastuzumab-induced cardiac toxicity?

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dc.contributor.authorYavas, Guler
dc.contributor.authorElsurer, Rengin
dc.contributor.authorYavas, Cagdas
dc.contributor.authorElsurer, Cagdas
dc.contributor.authorAta, Ozlem
dc.date.accessioned2020-03-26T18:41:33Z
dc.date.available2020-03-26T18:41:33Z
dc.date.issued2013
dc.departmentSelçuk Üniversitesien_US
dc.description.abstractThe ErbB2 receptor is a proto-oncogene associated with a poor prognosis in breast cancer. Trastuzumab, a humanized anti-ErbB2 antibody currently in clinical use, has proven to be an essential tool in the immunotherapy of breast carcinoma. Additionally, ErbB2 is involved in the growth and survival pathway of adult cardiomyocytes which accounts for the trastuzumab-induced cardiotoxicity. Moreover, in metastatic breast cancer patients treated with trastuzumab, endomyocardial biopsy documented focal vacuolar changes, pleomorphic mitochondria, myocardial cell hypertrophy, and mild interstitial fibrosis on electron microscopy without accompanying light microscopic abnormalities, a finding consistent with a reversible pattern of cardiac injury. On the other hand, aldosterone and mineralocorticoid receptor (MR) researches have experienced a revival after the discovery that aldosterone and MR are not only involved in the electrolyte and volume balance but also in the pathophysiological processes of the reno-cardiovascular system. Aldosterone has both genomic and nongenotropic effects on epidermal growth factor receptor (EGFR) expression. Genomic effect induces genomic up-regulation of the EGFR protein expression via EGFR promoter, whereas nongenotropic effect leads to the EGFR transactivation resulting in persistent pathophysiological effects including formation of extracellular matrix and myocardial hypertrophy. Spironolactone, an aldosterone receptor antagonist, is known to ameliorate the cardiac damage. The underlying mechanism for the genomic interactions seem to be the stimulation of the EGFR promoter by aldosterone-bound MR, which then dose-dependently enhances the EGFR protein levels, which may be successively inhibited by spironolactone. By the light of these findings, we hypothesize that spironolactone may ameliorate trastuzumab-induced cardiotoxicity via inhibition of transactivation of the EGFR by aldosterone and reversing myocardial hypertrophy. This issue warrants further studies. (C) 2013 Elsevier Ltd. All rights reserved.en_US
dc.identifier.doi10.1016/j.mehy.2013.04.042en_US
dc.identifier.endpage234en_US
dc.identifier.issn0306-9877en_US
dc.identifier.issue2en_US
dc.identifier.pmid23688742en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage231en_US
dc.identifier.urihttps://dx.doi.org/10.1016/j.mehy.2013.04.042
dc.identifier.urihttps://hdl.handle.net/20.500.12395/29392
dc.identifier.volume81en_US
dc.identifier.wosWOS:000322348900024en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherCHURCHILL LIVINGSTONEen_US
dc.relation.ispartofMEDICAL HYPOTHESESen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.selcuk20240510_oaigen_US
dc.titleDoes spironolactone ameliorate trastuzumab-induced cardiac toxicity?en_US
dc.typeArticleen_US

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