Percorrer por autor "Longatto-Filho, Adhemar"
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- In vitro and in vivo evaluation of novel chromeno[2,3-d]pyrimidinones as therapeutic agents for triple negative breast cancerPublication . Carvalho, Luísa; Lima, Fábio Pedroso de; Cerqueira, Mónica; Silva, Ana; Pontes, Olívia; Oliveira-Pinto, Sofia; Guerreiro, Sara; Costa, Marta D.; Granja, Sara; Maciel, Patrícia; Longatto-Filho, Adhemar; Baltazar, Fátima; Proença, Fernanda; Costa, Marta; Granja, SaraTriple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the limited therapeutic options show poor efficacy in patients, associated to severe side effects and development of resistance. Considering that chromene-based scaffolds proved to be attractive candidates for cancer therapy, herein we prepared new chromeno[2,3-d]pyrimidinone derivatives by a simple two step procedure, starting from the reaction of cyanoacetamide and a salicylaldehyde. A cell viability screening in several breast cancer cell lines allowed to identify two promising compounds with IC50 values in the low micromolar range for TNBC cells. These chromenes inhibited cell proliferation, induced cell cycle arrest and triggered cell death through apoptosis. In vivo studies revealed a safe profile in invertebrate and vertebrate animal models and confirmed their capacity to inhibit tumor growth in the CAM model, inducing significant tumor regression after 4 days of treatment. The two compounds identified in this study are promising drug candidates for TNBC treatment and valuable hits for future optimization, using the versatile synthetic platform that was developed.
- Predictive Biomarkers of Bacillus Calmette-Gu´erin Immunotherapy Response in Bladder Cancer: Where AreWe Now?Publication . Lima, Luís; Dinis-Ribeiro, Mário; Longatto-Filho, Adhemar; Santos, LúcioThe most effective therapeutic option for managing nonmuscle invasive bladder cancer (NMIBC), over the last 30 years, consists of intravesical instillations with the attenuated strain Bacillus Calmette-Gu´erin (the BCG vaccine). This has been performed as an adjuvant therapeutic to transurethral resection of bladder tumour (TURBT) and mostly directed towards patients with highgrade tumours, T1 tumours, and in situ carcinomas. However, from 20% to 40% of the patients do not respond and frequently present tumour progression. Since BCG effectiveness is unpredictable, it is important to find consistent biomarkers that can aid either in the prediction of the outcome and/or side effects development. Accordingly, we conducted a systematic critical review to identify themost preeminent predictive molecular markers associated with BCG response. To the best of our knowledge, this is the first review exclusively focusing on predictive biomarkers for BCG treatment outcome. Using a specific query, 1324 abstracts were gathered, then inclusion/exclusion criteria were applied, and finally 87 manuscripts were included. Several molecules, including CD68 and genetic polymorphisms, have been identified as promising surrogate biomarkers. Combinatory analysis of the candidate predictive markers is a crucial step to create a predictive profile of treatment response.