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We have investigated whether chromogranin A (CgA), a cardioregulatory protein released in the blood by the neuroendocrine system and by the heart itself, may contribute to regulation of the cardiotoxic and antitumor activities of Doxo. The effects of a physiologic dose of full\u2010length recombinant CgA on Doxo\u2010induced cardiotoxicity and antitumor activity were investigated in rats using\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    models and in murine models of melanoma, fibrosarcoma, lymphoma, and lung cancer, respectively. The effect of Doxo on circulating levels of CgA was also investigated.\n                    <jats:italic>In vivo<\/jats:italic>\n                    and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    mechanistic studies showed that CgA can prevent Doxo\u2010induced heart inflammation, oxidative stress, apoptosis, fibrosis, and ischemic injury. On the other hand, CgA did not impair the anticancer activity of Doxo in all the murine models investigated. Furthermore, we observed that Doxo can reduce the intracardiac expression and release of CgA in the blood (\n                    <jats:italic>i.e<\/jats:italic>\n                    ., an important cardioprotective agent). These findings suggest that administration of low\u2010dose CgA to patients with low levels of endogenous CgA might represent a novel approach to prevent Doxo\u2010induced adverse events without impairing antitumor effects.\u2014Rocca, C., Scavello, F., Colombo, B., Gasparri, A. M., Dallatomasina, A., Granieri, M. C., Amelio, D., Pasqua, T., Cerra, M. C., Tota, B., Corti, A., Angelone, T. Physiological levels of chromogranin A prevent doxorubicin\u2010induced cardiotoxicity without impairing its anticancer activity. FASEB J. 33, 7734\u20137747 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201802707r","type":"journal-article","created":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T14:05:26Z","timestamp":1554991526000},"page":"7734-7747","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Physiological levels of chromogranin A prevent doxorubicin\u2010induced cardiotoxicity without impairing its anticancer activity"],"prefix":"10.1096","volume":"33","author":[{"given":"Carmine","family":"Rocca","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Cardiac Pathophysiology Department of Biology, Ecology, and Earth Science University of Calabria Rende (Cosenza) 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