1574P - Differential regulation of profibrotic genes responsible for cardiotoxicity after experimental anticancer treatments

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Translational Research
Presenter Mariann Gyongyosi
Citation Annals of Oncology (2016) 27 (6): 526-544. 10.1093/annonc/mdw392
Authors M. Gyongyosi, K. Zlabinger, D. Lukovic, A. Spannbauer, G. Maurer, J. Bergler-Klein
  • Cardiology, Medizinische Universitaet Wien (Medical University of Vienna), A-1090 - Vienna/AT

Abstract

Background

Transcriptomic analysis of the myocardial samples aimed to search genes responsible for myocardial fibrosis and development of heart failure induced by anticancer therapy under experimental setting.

Methods

Domestic pigs (38 ± 3 kg) received 3 cycles of cytostatic treatment of human dose with either doxorubicin (DOX, n = 6) or liposomal encapsulation of doxorubicin-citrat complex (Myocet® MYO, n = 9), or epirubicin (EPI, n = 9) or physiologic saline (Controls, CO, n = 6). Left (LV) and right ventricular (RV) ejection fraction (EF) was assessed after the application of the last dose by cardiac magnetic resonance imaging. LV and RV myocardial fibrosis was quantified by picrosorius-red staining. mRNAs of myocardial samples from the LV and RV were isolated. The gene expression profile was analyzed by next generation sequencing (NGS) followed by post-hoc RT-PCR of selected genes.

Results

Five, 6 and 2 animals survived the treatment in DOX, MYO and EPI groups, respectively, thus EPI was excluded from the functional analysis. Both MYO and DOX resulted in decrease of LV EF (56.4 ± 5.6% vs 41.9 ± 13.5%, p 

Conclusions

Myocet® proved to be less cardiotoxic as compared with DOX, resulting in better cardiac function and less fibrosis. However, both cytostatic treatments led to overexpression of collagen-associated genes and proto-oncogenes, which might explain the development of myocardial fibrosis and secondary malignancies.

Clinical trial identification

Legal entity responsible for the study

Mariann Gyongyosi

Funding

TEVA ratiopharm provided the Department of Cardiology, Medical University of Vienna, with NPL-doxorubicin and an unrestricted grant, but was not involved in the study protocol, data acquisition, data analysis or the writing of the abstract.

Disclosure

M. Gyongyosi: Funding: TEVA ratiopharm provided the Department of Cardiology, Medical University of Vienna, with NPL-doxorubicin and an unrestricted grant, but was not involved in the study protocol, data acquisition, data analysis or the writing of the abstract. All other authors have declared no conflicts of interest.