Biomedical subjects

P A Oliveira

Publications and source records attributed to P A Oliveira.

4 recordsLinked to original sources

PubMed2006

Experimental bladder carcinogenesis-rodent models.

Several rodent models of bladder cancer development have been established. The aim of this review article is to provide a critical assessment of different animal models available for the study of bladder carcinogenesis, its chemoprevention and therapy. All, except for transgenic and knockout animals, require 8-12 months experimental periods in order to generate a high yield of neoplasias. Spontaneous bladder tumor models are extremely rare. The significance of the results from animal experiments is dependent upon the selection of a suitable animal model. There are no rules regarding the choice of a model, it is however very useful to have knowledge of relevant comparative medical aspects concerning this subject. We describe chemical carcinogens most commonly used to induce bladder cancer, pellet implantation and urinary calculi, agents that promote bladder cancer, and irradiation. We also evaluated other tools such as cell cultures, tumor implantation and transgenic models for bladder cancer, that have been developed to study the process. The review considers how several imaging techniques can be applied to study rodent bladder carcinogenesis.

Animals↗

PubMed2006

E-cadherin expression during urothelial carcinogenesis induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in rats.

An alteration in the expression of E-cadherin has been observed in many epithelial neoplasms. No data exist, however, for the expression of this protein in an animal model for urinary bladder cancer. The present study investigated the expression of E-cadherin in rat urothelial preneoplastic lesions and tumours induced by oral administration of N-butyl-N-(4-hydroxybutyl) nitrosamine, during 10, 15 and 20 weeks. Simple hyperplasia and squamous metaplasia showed a similar E-cadherin pattern when compared with normal urothelium, with its expression confined to cell membrane. Thirty eight percent of the nodular hyperplasia, 41.4% of the dysplasia and 100% of the papillomas showed a weak E-cadherin expression. All papillary neoplasm of low malignant potential, low-and high-grade papillary carcinoma, and invasive carcinoma revealed an abnormal staining pattern with an increase in cytoplasm reactivity and discontinuous cell membrane positivity. The loss of expression for low-grade papillary carcinoma versus simple hyperplasia, nodular hyperplasia and dysplasia was statistically significant (p = 0.0001, p = 0.007 and p=0.008, respectively). There was a similar decrease in E-cadherin expression for papillary neoplasm of low malignant potential versus simple hyperplasia, nodular hyperplasia and dysplasia (p = 0.0001; p = 0.001 and p=0.0001, respectively). These results suggest that alteration in the expression of this adhesion molecule in rat may be indicative of tumour progression in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder cancer.

Animals↗

PubMed2005

Evaluation of DNA content in preneoplastic changes of mouse urinary bladder induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.

Using image cytometry analysis we analysed the deoxyribonucleic acid content of preneoplastic lesions induced in C3H/He female mice. Female mice (n = 30) were given 0.05% BBN in their drinking water for 4, 8 and 12 weeks, and were then euthanized. At the 4th week 90% hyperplasias, 90% dysplasias and 10% papillary tumours developed selectively in the bladder, after 8 weeks mice developed 80% hyperplasias and 80% dysplasias and 12 weeks we identified 70% hyperplasias, 70% dysplasias, 10% papillary tumours and 20% squamous metaplasia. Among the ones who developed simple hyperplasia, 58.3% were diploid and 41.7% were aneuploid. In the dysplasia lesions 29.2% were diploid and 70.8% were aneuploid (p = 0.041). All papillary tumours were aneuploid and all epidermoid metaplasias were diploid. These results suggest that aneuploidization, DNA content alteration of preneoplastic lesions, might be considered as a prognostic factor.

Animals↗

PubMed2000

Cyclooxygenase inhibition reduces blood pressure elevation and vascular reactivity dysfunction caused by inhibition of nitric oxide synthase in rats.

In the present study we investigated the role of cyclooxygenase (COX)-dependent vasoconstrictors in the hypertension and altered vascular reactivity following prolonged nitric oxide (NO) synthase inhibition. Male Wistar rats (250-270 g) were divided into four groups and treated for 7 days with Placebo (control), L-NAME (48 mg/kg/day), indomethacin (4 mg/kg/day) and L-NAME in combination with indomethacin. L-NAME treatment induced arterial hypertension, in vitro aortic hyperresponsiveness to phenylephrine, impaired vasodilatory response to acetylcholine and no significant change in response to sodium nitroprusside. Indomethacin co-treatment partially prevented blood pressure elevation, restored responsiveness to phenylephrine and improved sensitivity to acetylcholine. Indomethacin treatment alone did not modify blood pressure and aortic vascular reactivity. Both enhanced phenylphrine-induced contraction and impaired acetylcholine-evoked vasodilation induced by acute NO synthase inhibition with L-NAME (10(-4) M) in normal rat aortas were not modified by indomethacin (10(-5) M). These results are consistent with the hypothesis that constricting factors, which arise from the COX pathway, contribute to hypertension and altered vascular reactivity following continued inhibition of NO synthase.

Acetylcholine↗