Effetti Cardiotossici Precoci e Tardivi Derivanti dal Trattamento con Chemioterapici: Sviluppo di un Modello Animale.

The combination of the anti-epidermal growth factor receptor type 2 (ErbB2) antibody Trastuzumab (Trz) with Doxorubicin (Dox) as adjuvant chemotherapy for patients with ErbB2-positive breast cancer is associated with an increased risk of myocardial disfunction. With increasing cancer survivors, the number of patients experiencing cardiotoxicity is growing. Up to 7% of patients suffer from cardiac dysfunction after receiving Trz as a monotheraphy, the incidence of this complication increases to 28% when Trz is used in combination with Dox. As result, cardio-oncology is becoming a new interdisciplinary area. We aimed to develop a rat animal model to in-vivo study cardiotoxic side effects of anti-tumoral drugs administration. Trz and Doxo were administrated alone and/or in combination to understand the contribution of each specific drug. Global heart function has been evaluated by 2D echocardiography analysis. Once assessed the reproducibility and the consistency of our model we asked whether this effects were direct consequence of cellular dysfunction. To test the latest hypothesis we isolated adult cardiomyocytes by Langendorff technology and performed analysis at “single cell” level. Molecular and functional technics such as immunofluorescence, western blotting and single cell patch-clamp have been performed.