Canine visceral hemangiosarcoma treated with surgery alone or surgery and doxorubicin: 37 cases (2005-2014).

The purpose of this retrospective study was to determine survival times and prognostic factors of dogs with visceral hemangiosarcoma (HSA) treated with surgery alone or surgery and doxorubicin. Medical records from 2 hospitals from 2005 to 2014 were searched for dogs with histopathologically confirmed visceral HSA. Data relevant to patient demographics, tumor characteristics, and outcomes were abstracted. The most common primary organ affected was the spleen; however, primary tumor location had no influence on prognosis. Twenty-three dogs were treated with surgery alone, while 14 dogs were treated with surgery and doxorubicin. There was a significant difference in survival times between dogs treated with surgery alone and with surgery followed by doxorubicin (66 days versus 274 days). Dogs with stage I tumors (196 days) had a longer median survival time (MST) than dogs with stage II (117 days) and stage III (23 days) disease. The overall MST was 179 days with a 1-year survival rate of 29.2%.

Hémangiosarcome viscéral canin traité par la chirurgie seule et la doxorubicine : 37 cas (2005­2014). Le but de cette étude rétrospective consistait à déterminer les temps de survie et les facteurs de pronostic des chiens atteints d'un hémangiosarcome (HSE) viscéral traités à l'aide de la chirurgie seule ou de la chirurgie et de la doxorubicine. Les dossiers médicaux de deux cliniques de 2005 à 2014 ont été fouillés pour trouver des chiens avec un HSE viscéral confirmé par histopathologie. Les données pertinentes pour les données démographiques du patient, les caractéristiques de la tumeur et les résultats ont été extraits des dossiers. L'organe primaire le plus couramment affecté était la rate. Cependant, l'emplacement primaire de la tumeur n'avait aucune influence sur le pronostic. Vingt-trois chiens ont été traités par la chirurgie seule, tandis que 14 chiens ont été traités par la chirurgie et la doxorubicine. Il y avait une différence importante dans les temps de survie entre les chiens traités par la chirurgie seule et la chirurgie suivie de la doxorubicine (66 jours contre 274 jours). Les chiens ayant des tumeurs de stade I (196 jours) avaient un temps de survie médian (TSM) plus long que les chiens atteints d'une maladie de stade II (117 jours) et de stade III (23 jours). Le TSM général était de 179 jours avec un taux de survie après 1 an de 29,2 %.(Traduit par Isabelle Vallières).

Establishment of primary mixed cell cultures from spontaneous canine mammary tumors: Characterization of classic and new cancer-associated molecules.

There are many factors which make canine cancer like cancer in humans. The occurrence of spontaneous mammary tumors in pet dogs, tumor genetics, molecular targets and exposure to the same environmental risk factors are among these factors. Therefore, the study of canine cancer can provide useful information to the oncology field. This study aimed to establish and characterize a panel of primary mixed cell cultures obtained from spontaneous canine mammary tumors. Eight established cell cultures obtained from one normal mammary gland, one complex adenoma, one mixed adenoma, two complex carcinomas and two mixed carcinomas were analyzed. The gene expression levels of classic molecular cancer players such as fibroblast growth factor receptor (FGFR) 2, breast cancer (BRCA) 1, BRCA2 and estrogen receptor (ESR) 1 were evaluated. For the first time, three orphan nuclear receptors, estrogen-related receptors (ERRs) α, ß and γ were studied in canine mammary cancer. The highest expression level of ERRα was observed in complex carcinoma-derived cell culture, while the highest levels of ERRß and γ were observed in cells derived from a mixed carcinoma. Meanwhile, complex carcinomas presented the highest levels of expression of ESR1, BRCA1 and FGFR2 among all samples. BRCA2 was found exclusively in complex adenoma. The transcription factor GATA3 had its highest levels in mixed carcinoma samples and its lowest levels in complex adenoma. Proliferation assays were also performed to evaluate the mixed cell cultures response to ER ligands, genistein and DES, both in normoxia and hypoxic conditions. Our results demonstrate that morphological and functional studies of primary mixed cell cultures derived from spontaneous canine mammary tumors are possible and provide valuable tool for the study of various stages of mammary cancer development.

Leptospira Infection Interferes with the Prothrombinase Complex Assembly during Experimental Leptospirosis.

Leptospirosis is a worldwide zoonotic and neglected infectious disease of human and veterinary concern, caused by pathogenic Leptospira species. Although bleeding is a common symptom of severe leptospirosis, the cause of hemorrhage is not completely understood. In severe infections, modulation of hemostasis by pathogens is an important virulence mechanism, and hemostatic impairments such as coagulation/fibrinolysis dysfunction are frequently observed. Here, we analyze the coagulation status of experimentally infected hamsters in an attempt to determine coagulation interferences and the origin of leptospirosis hemorrhagic symptomatology. Hamsters were experimentally infected with L. interrogans. The lungs, kidneys, and livers were collected for culture, histopathology, and coagulation assays. L. interrogans infection disturbs normal coagulation in the organs of animals. Our results suggest the presence of a thrombin-like factor or FX activator, which is able to activate FII in the leptospirosis organ extracts. The activity of those factors is accelerated in the prothrombinase complex. Additionally, we show for the first time that live leptospires act as a surface for the prothrombinase complex assembly. Our results contribute to the understanding of leptospirosis pathophysiological mechanisms and may open new routes for the discovery of novel treatments in the severe manifestations of the disease.

Leptospira Infection interferes with the prothrombinase complex assembly during experimental leptospirosis

Leptospirosis is a worldwide zoonotic and neglected infectious disease of human and veterinary concern, caused by pathogenic Leptospira species. Although bleeding is a common symptom of severe leptospirosis, the cause of hemorrhage is not completely understood. In severe infections, modulation of hemostasis by pathogens is an important virulence mechanism, and hemostatic impairments such as coagulation/fibrinolysis dysfunction are frequently observed. Here, we analyze the coagulation status of experimentally infected hamsters in an attempt to determine coagulation interferences and the origin of leptospirosis hemorrhagic symptomatology. Hamsters were experimentally infected with L. interrogans. The lungs, kidneys, and livers were collected for culture, histopathology, and coagulation assays. L. interrogans infection disturbs normal coagulation in the organs of animals. Our results suggest the presence of a thrombin-like factor or FX activator, which is able to activate FII in the leptospirosis organ extracts. The activity of those factors is accelerated in the prothrombinase complex. Additionally, we show for the first time that live leptospires act as a surface for the prothrombinase complex assembly. Our results contribute to the understanding of leptospirosis pathophysiological mechanisms and may open new routes for the discovery of novel treatments in the severe manifestations of the disease.

Pathology affects different organs in two mouse strains chronically infected by a Trypanosoma cruzi clone: a model for genetic studies of Chagas' disease.

Chagas' disease is a chronic infection caused by Trypanosoma cruzi and represents an important public health burden in Latin America. Frequently the disease evolves undetectable for decades, while in a significant fraction of the affected individuals it culminates in death by heart failure. Here, we describe a novel murine model of the chronic infection with T. cruzi using a stable clone isolated from a human patient (Sylvio X10/4). The infection in the C3H/HePAS mouse strain progresses chronically and is mainly characterized by intense cardiac inflammatory lesions that recapitulate the chronic cardiac pathology observed in the human disease. Moderate striated muscle lesions are also present in C3H/HePAS mice. Viable parasites are detected and recovered from the chronic heart lesions of C3H/HePAS mice, supporting the current notion that development of heart pathology in Chagas' disease is related to parasite persistence in the inflamed tissue. By contrast, in infected A/J mice, chronic inflammatory lesions are targeted to the liver and the skeletal muscle, while pathology and parasites are undetectable in the heart. The phenotypic analysis of F(1) (A/J x C3H/HePAS) and F(2) (A/J x C3H/HePAS) mice suggests that the genetic predisposition to develop the inflammatory lesions caused by T. cruzi (Sylvio X10/4 clone) is heterogeneous because the heart and liver pathology segregate in the F(2) generation. These findings raise the hypothesis that the pathology heterogeneity observed in humans with Chagas' disease (absence and presence of cardiac or digestive chronic lesions) may be attributable to host genetic factors.

Inhibitory effects of beta-carotene and vitamin a during the progression phase of hepatocarcinogenesis involve inhibition of cell proliferation but not alterations in DNA methylation.

The inhibitory effects of Beta-carotene and vitamin A administered to rats in the progression phase of the resistant hepatocyte model of hepatocarcinogenesis were investigated. Beta-Carotene- and vitamin A-treated animals tended to present with a lower incidence of hepatic cancers than controls at sacrifice. Vitamin A, but not Beta-carotene, administration also tended to reduce the total number of persistent hepatocyte nodules. Histological examination of sections stained with hematoxylin and eosin confirmed these results. This suggests that both compounds exhibit inhibitory effects during conversion of persistent nodules to cancers, whereas only the retinoid is also capable of inhibiting the evolution of persistent nodules or causing them to regress. Moreover, Beta-carotene- and vitamin A-treated animals showed lower hepatic bromodeoxyuridine labeling indexes in neoplastic lesions as well as in adjacent normal tissues than controls, suggesting an inhibitory action of these substances on cell proliferation. However, neither Beta-carotene nor vitamin A administration resulted in substantial alterations in the CCGG sequence methylation pattern of hydroxymethylglutaryl coenzyme A reductase, c-myc, and c-Ha-ras genes, the products of which are related to cell proliferation and carcinogenesis. Therefore, these inhibitory effects of Beta-carotene and vitamin A on progression of hepatocarcinogenesis do not seem to be related to DNA methylation.

Effects of beta-carotene and vitamin A on oval cell proliferation and connexin 43 expression during hepatic differentiation in the rat(1).

The effects of beta-carotene and vitamin A administrations were evaluated in an in vivo model of hepatic cell differentiation. For this purpose, male Wistar rats received beta-carotene (70 mg/kg of body weight), vitamin A (10 mg/kg of body weight) or corn oil (control group), by gavage and at every other day during the entire experimental period. After 4 consecutive weeks of treatment, the animals were submitted to the AAF/PH model of hepatic cell differentiation (6 x 20 mg of AAF [2-acetylaminofluorene]/kg of body weight and partial hepatectomy) and killed on different days following the surgery (until day 16 after hepatectomy). Liver samples were collected for determination of beta-carotene, retinol and retinyl palmitate concentrations, for histopathological (hematoxilin-eosin) examination, for immunohistochemical detection of glutathione S-transferase, as well as for the evaluation of connexin 43 (a structural protein of gap junctions of oval cells) expression by northern blot analysis. Compared to controls, the oval cell proliferation peaks (observed by histopathological examination and immunohistochemistry) and connexin 43 expression peaks, were postponed to later days after hepatectomy, in a similar way in beta-carotene and vitamin A treated animals. Compared to the other experimental groups, the vitamin A treated group showed an increase in connexin 43 expression. It was concluded that beta-carotene and vitamin A modulated oval cell proliferation and connexin 43 expression, delaying both events. These findings suggest that beta-carotene and vitamin A can modulate the hepatic differentiation process in vivo.