| Grant number: | 24/17783-2 |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| Start date: | January 01, 2025 |
| End date: | December 31, 2025 |
| Field of knowledge: | Biological Sciences - Physiology - Physiology of Organs and Systems |
| Principal Investigator: | Edilamar Menezes de Oliveira |
| Grantee: | Alex Cleber Improta Caria |
| Supervisor: | Diana Esperanca dos Santos Nascimento Andre |
| Host Institution: | Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Institution abroad: | Universidade do Porto (UP), Portugal |
| Associated to the scholarship: | 22/02339-4 - Physical training-regulated microRNAs as potential biomarkers and therapeutics of doxorubicin-induced cardiotoxicity in breast cancer: in vivo study, in vitro in iPS-derived cardiomyocytes and clinical with patient analysis., BP.PD |
Abstract Breast cancer is a type of cancer with high incidence and mortality among women. Several studies investigate strategies and tools to inhibit the development of the disease or, when already diagnosed, several therapies and treatments have been used. A well-established treatment in the clinic is through chemotherapy, with anthracyclines standing out. The anthracycline most used in breast cancer and in several other types of cancer is doxorubicin, however this drug induces multiple deleterious effects on the heart, generating cardiotoxicity. Cardiotoxicity promotes an increase in reactive oxygen species, inflammation, apoptosis, cardiac fibrosis, and these continue to be a main clinical limitation in the treatment of cancer patients who use doxorubicin. These associated processes induce diastolic and/or systolic dysfunction, reducing the left ventricular ejection fraction, generating heart failure in the long term. Some in vitro studies using doxorubicin in cardiomyocyte cultures have demonstrated effects very similar to those observed in humans, since this chemotherapy agent also induced an increase in reactive oxygen species, apoptosis and fibrosis in these cells. However, the effects of doxorubicin in a co-culture model containing human cardiomyocytes together with human cardiac fibroblasts on cellular structure and molecular aspects regulated by microRNAs have not yet been observed in the literature. Also, little is known on the molecular regulation mediated by microRNAs, on the signaling pathways associated with the apoptotic process induced by this drug in this context. Herein, we propose to investigate the effects of doxorubicin on the modulation of microRNAs and regulation of apoptosis signaling pathways, to identify microRNAs differentially expressed and validate one or more signaling pathways associated with cardiotoxicity and apoptosis. Subsequently, a microRNA will be selected for in vitro validation through genetic modulation in this in vitro co-culture cardiac model towards the identification of a potential therapy to prevent and to treat cardiotoxicity in response to doxorubicin.Keywords: Breast cancer; doxorubicin; microRNAs; cardiotoxicity. | |
| News published in Agência FAPESP Newsletter about the scholarship: | |
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