Apoptotic intrinsic pathway proteins predict survival in canine cutaneous mast cell tumours.

Mast cell tumours (MCTs) are the most frequent canine round cell neoplasms and show variable biological behaviours with high metastatic and recurrence rates. The disease is treated surgically and wide margins are recommended. Adjuvant chemotherapy and radiotherapy used in this disease cause DNA damage in neoplastic cells, which is aimed to induce apoptotic cell death. Resisting cell death is a hallmark of cancer, which contributes to the development and progression of tumours. The aim of this study was to investigate the expression of the proteins involved in the apoptotic intrinsic pathway and to evaluate their potential use as prognostic markers for canine cutaneous MCTs. Immunohistochemistry for BAX, BCL2, APAF1, Caspase-9, and Caspase-3 was performed in 50 canine cases of MCTs. High BAX expression was associated with higher mortality rate and shorter survival. BCL2 and APAF1 expressions offered additional prognostic information to the histopathological grading systems. The present results indicate that variations in the expression of apoptotic proteins are related to malignancy of cutaneous MCTs in dogs.

Increased expression of tissue inhibitor of metalloproteinase-1 correlates with improved outcome in canine cutaneous mast cell tumours.

Canine mast cell tumour (MCT) is a biologically heterogeneous disease. The extracellular matrix degradation promoted by matrix metalloproteinases (MMPs) has been studied in an attempt to elucidate the mechanisms involved in the biological behaviour of tumours. The aim of this study was to characterize the expression of MMP-2 and -9 and tissue inhibitors of metalloproteinase (TIMP)-1 and -2 in canine cutaneous MCTs and to evaluate their prognostic values. Immunohistochemical staining for MMP-2, MMP-9, TIMP-2 and TIMP-1 was performed in 46 canine cases of MCTs. TIMP-1 expression showed an independent prognostic value for post-surgical survival and disease-related mortality. Dogs with MCTs showing less than 22.9% mast cell TIMP-1 positivity were more prone to die because of the disease and had a shorter post-surgical survival. This article suggests the involvement of TIMP-1 in MCT progression, by contributing to a good outcome in patients with MCTs.

Immunohistochemical Expression of the Pluripotency Factor OCT4 in Canine Mast Cell Tumours.

Cancer stem cells (CSCs) are related to malignancy and resistance to chemotherapy in several tumours. OCT4 is a 'pluripotency factor' that is expressed by these cells. The aim of the present study was to investigate OCT4 expression in canine cutaneous mast cell tumours (MCTs) by means of immunohistochemistry. Twenty-eight cases were evaluated and showed variable immunolabelling patterns. The dogs were treated by surgery alone and followed up for a minimum of 180 days. No significant difference was found between histopathological grades and similar results were obtained for mortality due to the disease and post-surgical survival. These preliminary results suggest that OCT4 expression is not a precise prognostic indicator for canine MCT.

Uranium deposition in bones of Wistar rats associated with skeleton development.

Sixty female Wistar rats were submitted to a daily intake of ration doped with uranium from weaning to adulthood. Uranium in bone was quantified by the SSNTD (solid state nuclear track detection) technique, and bone mineral density (BMD) analysis performed. Uranium concentration as a function of age exhibited a sharp rise during the first week of the experiment and a drastic drop of 70% in the following weeks. Data interpretation indicates that uranium mimics calcium. Results from BMD suggest that radiation emitted by the incorporated Uranium could induce death of bone cells.

Gross and histopathological findings in magellanic penguins (Spheniscus magellanicus Forster, 1781) / Achados necroscópicos e histopatológicos em pinguins-de-Magalhães (Spheniscus magellanicus Forster, 1781)

Durante os movimentos migratórios os Pinguins-de-Magalhães chegam às águas da costa brasileira, especialmente nos estados do sul do Brasil até o estado do Rio de Janeiro. Muitos chegam desidratados, hipotérmicos, com lesões traumáticas ou coberto de óleo, exigindo cuidados especiais em centros de reabilitação. Vinte e quatro pinguins juvenis, que chegaram para a reabilitação e posteriormente vieram a óbito apresentaram caquexia, incapacidade de ficar ereto e manter a temperatura do corpo, média de 33ºC ou menos, apresentando desidratação, bradicardia e letargia. Durante a necrópsia, amostras histológicas foram coletadas de fígado, pulmão e rim. Um importante achado histopatológico foi a congestão hepática passiva, encontrada em 50% dos espécimes e a congestão pulmonar foi a lesão histopatológico mais frequente, ocorrendo em 75% dos casos. Anorexia pode acarretar a perda de massa muscular e isso inclui o coração, fazendo com que ocorra uma diminuição da pressão cardíaca, resultando em uma respiração mais lenta e uma bradicardia. Os principais achados anatomopatológicos neste trabalho foram relacionados a lesões vasculares nos pulmões e no fígado, sendo estes encontrados em aves que experimentam uma sobrecarga metabólica associada à adversidade ambiental.

The value of immunohistochemical expression of BAX in formulating a prognosis for canine cutaneous mast cell tumours.

Immunohistochemical expression of BAX was evaluated in 24 canine cutaneous mast cell tumours in order to verify the relationship of this expression to the histopathological grade of the lesions and its prognostic value for clinical outcome. BAX expression increased with higher histopathological grades (P=0.0148; P<0.05 between grades I and III). Animals with high levels of BAX expression were 4.25 times more likely to die from the disease and had shorter post-surgical survival times (P=0.0009). These results suggest that alterations in BAX expression may be related to the aggressiveness of canine cutaneous mast cell tumours, indicating that immunohistochemical detection of BAX may be predictive of clinical outcome.

Haloperidol increases spreading and nitric oxide production in macrophages from tumor-bearing mice: a possible mechanism for its antitumoral effect.

Subcutaneous treatment with haloperidol (2.0 mg/kg) was found to increase both the percent of macrophage spreading and nitric oxide (NO) release in peritoneal macrophage from animals inoculated intraperitoneally with 5.0 x 10(6) Ehrlich ascites cells. This haloperidol-induced macrophage activation seems to be involved in its antitumoral effect since cotreatment with the iNOS inhibitor aminoguanidine was able to reverse the inhibitory effect of haloperidol on the development of the Ehrlich solid carcinoma.

Effect of haloperidol on the development of the solid Ehrlich tumor in mice.

We determined the effect of 13 days of treatment with 2.0 mg/kg haloperidol (s.c) on the development of the Ehrlich solid carcinoma, after inoculation of 1.5 x 10(6) Ehrlich ascites tumor cells into the left footpad of mice. The footpad thickness of haloperidol treated animals was significantly smaller than control from day two after tumor inoculation, to the end of the experiment. Histopathological examination showed that haloperidol treated mice apparently presented less necrotic areas within the tumor mass as well as less invasion of subepithelial connective tissue and other adjacent structures. In particular, in comparison with the control group, no nerve bundles were invaded by neoplastic cells in experimental mice. The possible mechanism underlying these results is discussed in light of the specific pharmacological properties of this neuroleptics drug.