Browsing by Author "Santos, L."
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- E-Cadherin and β-Catenin Expression during Urothelial Carcinogenesis Induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in MicePublication . Vasconcelos-Nóbrega, C.; Costa, C.; Vala, Helena; Colaço, A.; Santos, L.; Lopes, C.; Oliveira, PABACKGROUND: E-cadherin and β-catenin are adhesion molecules that promote integrity and stability of the urothelium. A decrease in theirexpression is associated with more aggressive tumour phenotypes with the ability to invade and metastasize. MATERIAL AND METHODS: 45 ICR male mice were used, of which 25 received N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05%) in drinking water for a period of 12 weeks. Immunohistochemical expression was evaluated in all urinary bladder preparations for E-cadherin and for β-catenin. RESULTS: Preneoplastic lesions showed staining patterns similar to normal urothelium. In simple and nodular hyperplasia, membrane staining was dominant (66.7-78.6 and 50-100%, respectively). In dysplasia a cytoplasmic pattern was prevalent (86.7-100%). Neoplastic lesions exhibit an abnormal staining pattern (100%) with heterogeneous staining (cytoplasmic, nuclear and membrane staining). A strong correlation was observed between both adhesion molecule staining patterns (r = 0.83; p = 0.039). CONCLUSIONS: In mice, as in humans, E-cadherin and β-catenin are valuable tools to investigate cellular adhesion status of urothelium and can be considered as indicators of tumour aggressiveness and evolution.
- Experimental study of the anticancer effect of gemcitabine combined with sirolimus on chemically induced urothelial lesionsPublication . Vasconcelos-Nóbrega, C.; Colaço, A.; Santos, L.; Vala, Helena; Palomino, LF; Lopes, C.; Oliveira, PABACKGROUND: The purpose of this study was to determine the efficacy of a combination of gemcitabine and sirolimus in a mouse model of invasive bladder cancer. MATERIALS AND METHODS: Gemcitabine (50 mg/kg) and sirolimus (1.5 mg/kg) were administered to animals previously exposed to N-butyl-N-4(hydroxybutyl)nitrosamine in drinking water. Tumour development was determined by histopathological evaluation. RESULTS: Both drugs were well tolerated by animals. The incidence of lesions in mice treated with gemcitabine was lower in comparison to those not treated, however this result was not statistically significant. The incidence of invasive bladder cancer in animals treated with sirolimus was statistically lower (20%) than in animals not treated (54%) (p=0.008). The results indicate that this drug combination has no statistical significance on the development of pre-neoplastic urothelial lesions and had only a minor impact on invasive bladder cancer incidence in mice. CONCLUSION: The combination of gemcitabine and sirolimus had only a marginal impact on invasive bladder cancer in a mouse model.
- Mice: An Animal Model for Bladder CancerPublication . Vasconcelos-Nóbrega, C.; Arantes-Rodrigues, R.; Colaço, A.; Santos, L.; Vala, Helena; Palomino, L. F.; Lopes, C.; Oliveira, P. A.Background: Bladder cancer is a common malignancy and an important cause of morbidity and mortality in western world. Animal models are the centre of experimental researches aiming to elucidate our knowledge about carcinogenesis, its treatment and prevention. Mice have a lower urinary tract comparable to humans. Methods: 22 ICR male mice were randomized into two groups (I and II). Group I was the negative control drinking tap water, and group II received N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in drinking water during twelve weeks. Euthanasia was executed one week after BBN exposition. Results: All animals from Group I exhibited normal urothelium. In Group II, 100% of animals exhibited histological changes. 62.79% were preneoplastic lesions (simple hyperplasia, nodular hyperplasia, dysplasia) and 37.21% were neoplastic lesions (carcinoma in situ, invasive carcinoma, epidermoid metaplasia). Conclusions: Experimental urinary bladder tumours are useful models for the study of urinary bladder carcinogenesis and for the evaluation of new therapeutic strategies. In mice, chemically induced bladder cancer is nearly always of the invasive type and the incidence of spontaneous tumours is very rare. The similarity between human’s and mice’s bladder cancer allows the investigation of several aspects that can’t be studied under clinical conditions, such as pharmacokinetics and toxicity.
- Β cathenin in mice: expression in normal urothelium and in chemically induced pre-neoplastic and neoplastic lesionsPublication . Vasconcelos-Nóbrega C; Costa, C.; Vala, Helena; Costa, X. A.; Santos, L.; Oliveira, P. A.Background: Catenins are adhesion molecules that link cadherin molecules to cytoskeleton. The association of catenins to cadherins is a key step in the function of intact adhesion complexes, and alterations in catenin molecules can lead to the disruption of cell-cell adhesion, resulting in tumour aggressiveness and invasiveness in neoplastic disease. Material and methods: Urothelial lesions were chemically induced by BBN in ICR mice, and evaluated by immunohistochemistry to determine the staining pattern of β-cathenin. Results: In normal urothelium, 70% of β-catenin expression was at the cellular membrane level. In simple hyperplasia, the same pattern was observed in 66.67% of lesions. Nodular hyperplasia was observed only once with a membrane pattern. In dysplasia a 100% cytoplasmic pattern was seen. Invasive carcinoma showed an heterogeneous pattern with areas where the membrane, cytoplasm or nucleus were stained. On squamous metaplasia, the staining pattern was confined to the membrane, however, with heterogeneous immunoreactivity. Conclusions: β-cathenin is a good marker of the progression of bladder tumours chemically induced in mice by BBN.