Browsing by Author "Oliveira, Paula Alexandra"
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- Challenges with in vitro and in vivo experimental models of urinary bladder cancer for novel drug discoveryPublication . Oliveira, Paula Alexandra; Costa, Rui Gil da; Nóbrega, Carmen; Rodrigues, Regina Arantes; Leite, Rosário PintoUrinary bladder cancer (UBC) is the second most frequent malignancy of the urinary system and the ninth most common cancer worldwide, affecting individuals over the age of 65. Several investigations have embarked on advancing knowledge of the mechanisms underlying urothelial carcinogenesis, understanding the mechanisms of antineoplastic drugs resistance and discovering new antineoplastic drugs. In vitro and in vivo models are crucial for providing additional insights into the mechanisms of urothelial carcinogenesis. With these models, various molecular pathways involved in urothelial carcinogenesis have been discovered, allowing therapeutic manipulation.
- Histological classification of urothelial lesions chemically-induced in the male rat modelPublication . Faustino-Rocha, Ana Isabel; Pinto, Carla; Vala, Helena; Ferreira, Rita; Oliveira, Paula AlexandraObjective: Bladder cancer is one of the most frequent of the urinary tract. Urinary bladder tumours induced by the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) are similar to those observed in humans. This work aimed to classify, by histology, the urinary bladder tumours BBN-induced in a rat model. Methods: Procedures were made in accordance with the Directive 2010/63/EU. Eleven Wistar male rats with five weeks of age were used. BBN was administered in drinking water at a concentration of 0.05% water during the first 20 weeks of the protocol. Thirty-five weeks after the start of the protocol, animals were humanely sacrificed by the overdose of pentobarbital sodium. Results: No animals died during the protocol. In the histological analysis of the urinary bladders were identified the following lesions: simple hyperplasia (81.8%), nodular hyperplasia (54.5%), papillary hyperplasia (14%), papilloma (45.4%), papillary neoplasm of low malignant potential (36.4%), low-grade papillary carcinoma (90.9%), high-grade papillary carcinoma (72.7%), invasive carcinoma (14%) and epidermoid metaplasia with keratinization (45.4%). Conclusion: Our team has a vast experience on the bladder cancer animal models; however this is the first protocol in male rats. We concluded that the lesions identified are similar to those observed in Humans.
- Long-term treatment with chaethomellic acid A reduces glomerulosclerosis and arteriolosclerosis in a rat model of chronic kidney diseasePublication . Nogueira, António; Vala, Helena; Nóbrega, Carmen; Rocha, Ana Isabel Faustino; Pires, Carlos André; Colaço, Aura; Oliveira, Paula Alexandra; Pires, Maria JoãoThe high prevalence of end-stage renal disease emphasizes the failure to provide therapies to effectively prevent and/or reverse renal fibrosis. Therefore, the aim of this study was to evaluate the effect of long-term treatment with chaethomellic acid A (CAA), which selectively blocks Ha-Ras farnesylation, on renal mass reduction-induced renal fibrosis. Male Wistar rats were sham-operated (SO) or subjected to 5/6 renal mass reduction (RMR). One week after surgery, rats were placed in four experimental groups: SO:SO rats without treatment (n=13); SO+CAA: SO rats treated with CAA (n=13); RMR:RMR rats without treatment (n=14); and RMR+CAA:RMR rats treated with CAA (n=13). CAA was intraperitoneally administered in a dose of 0.23μg/kg three times a week for six months. Renal fibrosis was evaluated by two-dimensional ultrasonography and histopathological analysis. The kidneys of the RMR animals treated with CAA showed a significantly decrease in the medullary echogenicity (p<0.05) compared with the RMR rats that received no treatment. Glomerulosclerosis and arteriolosclerosis scores were significantly lower (p<0.001) in the RMR+CAA group when compared with the RMR group. There were no significant differences in interstitial fibrosis, interstitial inflammation and tubular dilatation scores between the RMR+CAA and RMR groups. These data suggest that CAA can be a potential future drug to attenuate the progression of chronic kidney disease.