Browsing by Author "Oliveira, PA"
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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.
- Effects of intense pulsed light on skin carcinogenesisPublication . Faustino-Rocha, AI; Gama, A.; Rodrigues, D.; Colaço, B.; Vala, Helena; Pires, MJ; Oliveira, PAObjective: Intense pulsed light (IPL) is a non-laser high intensity light that has been used to the treatment of several skin conditions. This work intended to evaluate the effects of IPL on a mouse model of two-stage skin carcinogenesis. Methods: Procedures were made in accordance with the Directive 2010/63/EU. Sixteen DBA/2JRccHsd mice were divided into two groups: IPL-exposed and non-exposed. The carcinogen agent DMBA was topically applied once and TPA was applied twice a week during 22 weeks. Animals IPL-exposed received IPL applications twice a week, at an intensity of 2J/cm2 during 22 weeks. Animals were sacrificed and skin samples were histologically evaluated. Results: Animals IPL-exposed developed 44 skin lesions (5.5 lesions per animal) while non-exposed animals developed 63 lesions (7.9 lesions per animal) (p=0.066). The animals IPL-exposed developed 20 skin neoplastic lesions while non-exposed animals developed 38 lesions (p=0.018), however the number of malignant lesions was higher in IPL-exposed animals (3 lesions) than in non-exposed animals (1 lesion) (p>0.05). Conclusion: The animals IPL-exposed developed lower number of skin lesions and neoplastic lesions, but the number of malignant lesions was higher. IPL inhibits the development of skin lesions but may have a promoting effect on the malignant conversion.
- 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.
- Implementation of humane endpoints on bladder cancer researchPublication . Oliveira, MC; Faustino-Rocha, AI; Vala, Helena; Oliveira, PAObjective: Pain, distress, or discomfort should be minimized during experimental procedures using animals. The goal of this work was to establish humane endpoints for a model of bladder cancer chemically-induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Methods: Procedures were made in accordance with the European Directive 2010/63/EU. Twelve Wistar rats were used. The carcinogen agent BBN was administered in drinking water during 20 weeks. After this, they consumed only water until 35 weeks of the experimental protocol. During the protocol was used a scoring sheet where biological variables were registered daily to monitor animal welfare. Results: No animals died during the experimental protocol. Four animals showed signs of haematuria since the fifteenth week after the beginning of the experiment, these animals also exhibited moderate anemia in the last week of the protocol that was evident through the mucosal observations. All animals exhibited a mental status, eyes, ears and whiskers position, response to handling, breathing and hydration within the parameters considered normal for the specie. Conclusion: The animals did not show clinical signs compatible to suffering that justified their sacrifice before the end of the study. The endpoints established for this model are adequate to bladder cancer studies once no endpoints were reached.
- Urinary bladder cancer - Old models, new opportunitiesPublication . Oliveira, PA; Vala, Helena; Gil da Costa, RM; Pinto-Leite, MR; Arantes-Rodrigues, R; Vasconcelos-Nóbrega, CUrinary bladder cancer remains as one of most frequent tumours. To elucidate the reasons for the development of tumours, to find out which factors determine the tumour progression and to develop new and better treatments with fewer side effects, intensive research, with the combination of in vitro and in vivo studies is mandatory. So, in this manuscript we performed a revision concerning the different methodologies to study this disease. In authors’ opinion, the best strategy to improve scientific knowledge for UBC should always rely in the association of in vivo and in vitro results. Currently, there are still many challenges in UBC diagnosis and therapy. These challenges must be faced as new opportunities. The molecular diagnostics and genomic revolution will be fundamental to develop new therapeutic modalities, and also to promote personalized therapies.