Title: Cardiotoxic effects, or lack thereof, of anti‐ErbB2 immunoagents
Abstract: The FASEB JournalVolume 23, Issue 9 p. 3171-3178 Research CommunicationFree to Read Cardiotoxic effects, or lack thereof, of anti-ErbB2 immunoagents Gennaro Riccio, Gennaro Riccio Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, Naples, Italy These authors contributed equally to this work.Search for more papers by this authorGiovanni Esposito, Giovanni Esposito Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Università di Napoli Federico II, Naples, Italy These authors contributed equally to this work.Search for more papers by this authorEmanuela Leoncini, Emanuela Leoncini Dipartimento di Biochimica “G.Moruzzi,”, Università di Bologna, Bologna, ItalySearch for more papers by this authorRiccardo Contu, Riccardo Contu Istituto Ricovero e Cura a Carattere Scientifico, Multimedica, Milan, ItalySearch for more papers by this authorGianluigi Condorelli, Gianluigi Condorelli Istituto Ricovero e Cura a Carattere Scientifico, Multimedica, Milan, ItalySearch for more papers by this authorMassimo Chiariello, Massimo Chiariello Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Università di Napoli Federico II, Naples, ItalySearch for more papers by this authorPaolo Laccetti, Paolo Laccetti Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, Naples, ItalySearch for more papers by this authorSilvana Hrelia, Silvana Hrelia Dipartimento di Biochimica “G.Moruzzi,”, Università di Bologna, Bologna, ItalySearch for more papers by this authorGiuseppe D'Alessio, Giuseppe D'Alessio Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, Naples, ItalySearch for more papers by this authorClaudia De Lorenzo, Corresponding Author Claudia De Lorenzo [email protected] Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, Naples, ItalyCorrespondence. Dipartimento di Biologia Strutturale e Funzionale, Universita di Napoli Federico II, via Cinthia, 80126 Napoli, Italy. E-mail: [email protected]Search for more papers by this author Gennaro Riccio, Gennaro Riccio Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, Naples, Italy These authors contributed equally to this work.Search for more papers by this authorGiovanni Esposito, Giovanni Esposito Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Università di Napoli Federico II, Naples, Italy These authors contributed equally to this work.Search for more papers by this authorEmanuela Leoncini, Emanuela Leoncini Dipartimento di Biochimica “G.Moruzzi,”, Università di Bologna, Bologna, ItalySearch for more papers by this authorRiccardo Contu, Riccardo Contu Istituto Ricovero e Cura a Carattere Scientifico, Multimedica, Milan, ItalySearch for more papers by this authorGianluigi Condorelli, Gianluigi Condorelli Istituto Ricovero e Cura a Carattere Scientifico, Multimedica, Milan, ItalySearch for more papers by this authorMassimo Chiariello, Massimo Chiariello Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Università di Napoli Federico II, Naples, ItalySearch for more papers by this authorPaolo Laccetti, Paolo Laccetti Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, Naples, ItalySearch for more papers by this authorSilvana Hrelia, Silvana Hrelia Dipartimento di Biochimica “G.Moruzzi,”, Università di Bologna, Bologna, ItalySearch for more papers by this authorGiuseppe D'Alessio, Giuseppe D'Alessio Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, Naples, ItalySearch for more papers by this authorClaudia De Lorenzo, Corresponding Author Claudia De Lorenzo [email protected] Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, Naples, ItalyCorrespondence. Dipartimento di Biologia Strutturale e Funzionale, Universita di Napoli Federico II, via Cinthia, 80126 Napoli, Italy. E-mail: [email protected]Search for more papers by this author First published: 05 May 2009 https://doi.org/10.1096/fj.09-131383Citations: 52 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat ABSTRACT This study investigated potential cardiotoxicity as exerted by Erbicin-derived-immunoagents (EDIAs), novel human anti-ErbB2 immunoagents engineered by fusion of a human anti-ErbB2 scFv, Erbicin, with either a human RNase or the Fc region of a human IgG1. EDIAs are strongly cytotoxic on ErbB2-positive cells in vitro and in vivo and bind to an epitope different from that of Herceptin, a humanized anti-ErbB2 mAb effective in the therapy of breast carcinoma, but cardiotoxic in a high percentage of cases. Toxicity and apoptosis were tested in vitro by 3-(4,5-dimethyl-2-thizolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), DNA fragmentation, and immunoblotting analyses. Echocardiography was measured in mice after treatment with each immunoagent. Cardiac fibrosis and detection of apoptosis were examined by Sirius red staining of collagen and TUNEL assay, respectively. EDIAs were found in vitro to have no adverse effects on cardiac cells for which Herceptin is severely toxic. In vivo studies on a mouse model showed that the EDIAs did not alter cardiac function, whereas Herceptin and doxorubicin, used as positive controls, significantly reduced the fractional shortening parameter. Cardiac fibrosis and apoptosis were not significantly affected in mice treated with EDIAs. Thus, EDIAs could fulfill the therapeutic need of patients ineligible for Herceptin treatment due to cardiac dysfunction.—Riccio, G., Esposito, G., Leoncini, E., Contu, R., Condorelli, G., Chiariello, M., Laccetti, P., Hrelia, S., D'Alessio, G., De Lorenzo, C. Cardiotoxic effects, or lack thereof, of anti-ErbB2 immunoagents. FASEB J. 23, 3171–3178 (2009). www.fasebj.org REFERENCES 1Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W.J., Ullrich, A., and McGuire, W. L. (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. 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(1997) A subclass of tumor-inhibitory monoclonal antibodies to ErbB-2/HER2 blocks crosstalk with growth factor receptors. Oncogene 14, 2099–2109 Citing Literature Volume23, Issue9September 2009Pages 3171-3178 ReferencesRelatedInformation
Publication Year: 2009
Publication Date: 2009-05-05
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 69
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