Browsing by Author "Almeida, Filipe"
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- Histone deacetylase inhibitors and microtubule inhibitors induce apoptosis in feline luminal mammary carcinoma cellsPublication . Almeida, Filipe; Gameiro, Andreia; Correia, Jorge Manuel de Jesus; Ferreira, FernandoSimple Summary: Feline mammary tumors (FMT) are very common in cats, associated with very aggressive behavior and a short life expectancy. Surgery is the most used treatment but tumor recurrence is common. Currently, available therapies are insufficient, therefore, new molecular targets are needed to develop more efficient therapeutics. Histone deacetylases inhibitors (HDACis) have been developed to target tumor cells, by disrupting gene expression and leading to cell death. Microtubules inhibitors (MTIs) have also been a focus of research, to target polymerization of microtubules, and consequently disturbing the cytoskeleton and leading to cell cycle arrest and apoptosis. However, there are few studies on the use of HDACis and MTIs in cats. In this study, we addressed if these two drug classes could be used as new therapeutic options in FMTs. All HDACis and MTIs exhibited suitable and dose-dependent antitumor effects in FMT cell lines. Immunoblot analysis confirmed that the mode of action of HDACis is conserved in feline mammary tumor cell lines. Finally, flow cytometry showed that exposure with HDACis and MTIs lead to the induction of cellular apoptosis. In summary, HDACis and MTIs possess antitumor properties suggesting further studies on their use in the treatment of feline mammary tumors.
- Tyrosine kinase inhibitors are promising therapeutic tools for cats with HER2-positive mammary carcinomaPublication . Gameiro, Andreia; Almeida, Filipe; Nascimento, Catarina; Correia, Jorge Manuel de Jesus; Ferreira, FernandoABSTRACT - Feline mammary carcinoma (FMC) is a common neoplasia in cat, being HER2-positive the most prevalent subtype. In woman’s breast cancer, tyrosine kinase inhibitors (TKi) are used as a therapeutic option, by blocking the phosphorylation of the HER2 tyrosine kinase domain. Moreover, clinical trials demonstrated that TKi produce synergistic antiproliferative effects in combination with mTOR inhibitors, overcoming resistance to therapy. Thus, to uncover new chemotherapeutic strategies for cats, the antiproliferative effects of two TKi (lapatinib and neratinib), and their combination with a mTOR inhibitor (rapamycin), were evaluated in FMC cell lines (CAT-M, FMCp and FMCm) and compared with a human breast cancer cell line (SkBR-3). Results revealed that both TKi induced antiproliferative effects in all feline cell lines, by blocking the phosphorylation of EGFR members and its downstream effectors. Furthermore, combined treatments with rapamycin presented synergetic antiproliferative effects. Additionally, the DNA sequence of the her2 TK domain (exons 18 to 20) was determined in 40 FMC tissue samples, and despite several mutations were found none of them were described as inducing resistance to therapy. Altogether, our results demonstrated that TKi and combined protocols may be useful in the treatment of cats with mammary carcinomas, and that TKi-resistant FMC are rare.