RESUMEN
Obesity can affect the clinical course of a number of diseases, including breast cancer in women and mammary gland tumors in female dogs, via the secretion of various cytokines and hormones. The objective of this study was to examine the expression patterns of obesity-related molecules such as aromatase, leptin, and insulin-like growth factor 1 receptor (IGF-1 R) in canine mammary carcinomas (CMCs) on the basis of the body condition score (BCS). Comparative analyses of the expression of these molecules, together with prognostic factors for CMCs, including hormone receptors (HRs; estrogen and progesterone receptors), lymphatic invasion, central necrosis of the tumor, and histologic grade, were performed on 56 CMCs. The mean age of CMC onset was lower in the overweight or obese group (8.7 ± 1.9 years) than in the lean or ideal body weight group (10.4 ± 2.7 years). The proportion of poorly differentiated (grade III) tumors was significantly higher in the overweight or obese female dogs. Aromatase expression was significantly higher in the overweight or obese group and was correlated with the expression of HRs (P = .025). These findings suggest that overweight or obese status might affect the development and behavior of CMCs by tumor-adipocyte interactions and increased HR-related tumor growth.
Asunto(s)
Neoplasias de la Mama/veterinaria , Neoplasias Mamarias Animales/patología , Obesidad/veterinaria , Animales , Aromatasa/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Perros , Femenino , Leptina/metabolismo , Glándulas Mamarias Animales/metabolismo , Neoplasias Mamarias Animales/metabolismo , Receptor IGF Tipo 1/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismoRESUMEN
Canine mast cell tumours (MCTs) may be graded microscopically for prognostic purposes. Grade I (well-differentiated) and grade II (intermediate differentiation) tumours have an abundance of metachromatic granules within the cytoplasm; however, grade III (poorly differentiated) MCTs may be difficult to diagnose as they frequently have fewer discernable granules. Herein we report that a cross-reactive anti-human CD1a monoclonal antibody (clone O10) may be used in immunohistochemistry to identify canine MCTs of all grades. The antibody was applied to tissue sections from 48 canine MCTs of different histological grades. Serial sections from each tumour were stained with toluidine blue and safranin O to compare diagnostic sensitivity. All MCTs were labelled positively by the CD1a antibody, but histochemical staining was often equivocal and identification of mast cells was extremely difficult in some cases. This antibody did not label neoplastic cells in cases of canine histiocytoma, plasmacytoma or amelanotic melanoma; therefore, the reagent may be a valuable marker for the diagnosis of canine MCTs, especially those tumours of histological grade III.
Asunto(s)
Anticuerpos Monoclonales , Antígenos CD1/inmunología , Enfermedades de los Perros/diagnóstico , Mastocitosis/veterinaria , Neoplasias Cutáneas/veterinaria , Animales , Especificidad de Anticuerpos , Antígenos CD1/metabolismo , Enfermedades de los Perros/metabolismo , Enfermedades de los Perros/patología , Perros , Mastocitos/metabolismo , Mastocitos/patología , Mastocitosis/diagnóstico , Mastocitosis/metabolismo , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/metabolismoRESUMEN
The aim of the present study was to determine the distribution and characteristics of microvessels in various histological types of canine renal cell carcinoma (RCC). The study compared microvessel density (MVD) and distribution of blood vessels according to histological type and evaluated the presence of angiogenesis-related proteins. Nine archival samples of canine RCC were studied. MVD was calculated as the mean number of blood vessels per mm(2). The diameter of blood vessels was calculated by determining either the length of the long axis of blood vessels (diameter(max)) or the mean distance from the centre of each blood vessel to the tunica adventia (diameter(mean)). A significant difference in MVD was evident between RCCs and normal kidneys (46.6 ± 28.0 versus 8.4 ± 2.2 microvessels/mm(2)). Diameter(max) in canine RCCs (34.1 ± 14.7 µm) was also significantly different from normal canine kidney (23.2 ± 3.4 µm). Vascular endothelial growth factor (VEGF) was expressed by tumour cells and vascular endothelial cells and tumour necrosis factor (TNF)-α expression was observed in vascular endothelial cells in both neoplastic and normal kidney. Although VEGF is involved in angiogenesis and correlates with tumour stage of development, no correlation was found between VEGF expression and MVD. Tumour-associated macrophages expressing TNF-α and hypoxia inducible factor 1α were identified in peritumoural tissue and may play an important role in angiogenesis.
Asunto(s)
Carcinoma de Células Renales/veterinaria , Enfermedades de los Perros/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Renales/veterinaria , Neovascularización Patológica/veterinaria , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/irrigación sanguínea , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Enfermedades de los Perros/metabolismo , Perros , Femenino , Neoplasias Renales/irrigación sanguínea , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Masculino , Neovascularización Patológica/patologíaRESUMEN
Angiogenesis plays a crucial role in tumour growth, invasion and metastasis. Mast cells (MCs) release angiogenic factors that promote endothelial proliferation and differentiation. Previous studies have suggested that MCs are involved in tumour angiogenesis due to the release of various pro-angiogenic factors. This study evaluated samples from 40 canine mammary carcinomas and eight healthy non-neoplastic canine mammary glands. Toluidine blue staining was performed to characterize the MCs. Immunohistochemical labelling was performed to detect the number of tryptase-positive MCs and microvessels. MCs accumulated in tumour tissue and were closely associated with blood or lymphatic vessels in the tumour microenvironment. Angiogenesis, as measured by microvessel density, increased in direct proportion to the number of MCs. The correlation coefficient was significantly higher for tryptase-positive MCs than for toluidine blue-stained MCs. These results suggest that MCs are involved in tumour angiogenesis, which in turn influences tumour growth, invasion and metastasis. In particular, MC tryptase may be influential in mediating this function of MCs.
Asunto(s)
Enfermedades de los Perros/patología , Neoplasias Mamarias Animales/irrigación sanguínea , Mastocitos/enzimología , Neovascularización Patológica/patología , Triptasas/análisis , Inductores de la Angiogénesis/metabolismo , Animales , Estudios de Casos y Controles , Colorantes , Perros , Femenino , Neoplasias Mamarias Animales/patología , Microvasos/patología , Invasividad Neoplásica/patología , Neovascularización Patológica/veterinaria , Coloración y Etiquetado/métodos , Cloruro de Tolonio , Microambiente TumoralRESUMEN
HER-2 and HER-3 are transmembrane receptor proteins that are considered to be important but poorly understood biomarkers in canine tumors. In this study, the expression and the localization of HER-2 and HER-3 were evaluated immunohistochemically in canine mammary tumors (n=64; 12 benign, 52 malignant). HER-2 overexpression was identified in 2/12 (16.7%) benign and in 18/51 (35.3%) malignant cases. HER-3 was expressed in a non-nuclear localization in 11/12 (91.7%) benign and 18/52 (34.6%) malignant tumors. In contrast, HER-3 was expressed in the nucleus of neoplastic cells in 0/12 (0%) benign and 22/52 (42.3%) malignant tumors. Nuclear HER-3 expression was higher in neoplastic epithelial cells compared to myoepithelial cells, and positively correlated with high histological grade and lymphatic vessel invasion. These results suggest that nuclear HER-3 expression is significantly associated with tumor progression and metastasis and may serve as a useful prognostic biomarker in canine malignant mammary tumors.
Asunto(s)
Enfermedades de los Perros/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Mamarias Animales/genética , Receptor ErbB-2/genética , Receptor ErbB-3/genética , Animales , Enfermedades de los Perros/patología , Perros , Femenino , Marcadores Genéticos , Inmunohistoquímica/veterinaria , Linfocitos Infiltrantes de Tumor/patología , Neoplasias Mamarias Animales/patología , Clasificación del Tumor/veterinariaRESUMEN
CDX-2 is used as a specific cell marker for human intestinal adenocarcinoma. In human studies, HER-3 overexpression predicts poor survival for patients with various cancers including gastric cancer. Gastrointestinal adenocarcinoma is less common in dogs than in man and the expression of immunological markers by the canine tumours has not yet been extensively studied. CDX-2 and HER-3 expression was determined in 18 canine gastrointestinal adenocarcinomas: 13 were of colorectal origin and five were of gastric origin. CDX-2 expression was predominantly observed in the nuclei of normal colonic epithelium and in neoplastic epithelium and neoplastic gastric epithelial cells that which had metastasized to the gastric lymph node. CDX-2 was expressed in 11 of 13 (84.6%) colorectal adenocarcinomas and in all five (100%) gastric adenocarcinomas. HER-3 was consistently expressed in the cytoplasm of neoplastic epithelial cells. HER-3 expression was detected in 12 of 13 (92.3%) colorectal and in all five (100%) gastric adenocarcinomas. CDX-2 and HER-3 may be useful markers for canine gastrointestinal adenocarcinoma.
Asunto(s)
Adenocarcinoma/veterinaria , Neoplasias Colorrectales/veterinaria , Enfermedades de los Perros/metabolismo , Proteínas de Homeodominio/biosíntesis , Receptor ErbB-3/biosíntesis , Neoplasias Gástricas/veterinaria , Transactivadores/biosíntesis , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Animales , Biomarcadores de Tumor/análisis , Factor de Transcripción CDX2 , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Enfermedades de los Perros/genética , Perros , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Proteínas de Homeodominio/genética , Inmunohistoquímica , Masculino , Receptor ErbB-3/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Transactivadores/genéticaRESUMEN
Alzheimer's disease (AD) is the most common progressive form of dementia in aged people. Microscopical changes in the brains of AD patients include the formation of senile plaques (SPs), neurofibrillary tangles (NFTs) and granulovacuolar degeneration and the deposition of amyloid-beta (Aß). Aged dogs are known to suffer from cognitive dysfunction and this state is associated with deposition of Aß in the brain. The aim of the present study was to investigate tau phosphorylation of neurons and astrocytes in the brain of aged dogs with progressive cognitive impairment. Changes in the brain of aged dogs with cognitive dysfunction were compared with those in the brain of patients with AD of Braak stage V. Immunohistochemically, Aß deposition, phosphorylated tau Ser396 (p-tau Ser396) and ubiquitin were observed in the parietal cortex and hippocampus of aged dogs with cognitive dysfunction. Astrocytes with expression of p-tau Ser396 and neurons with co-localization of p-tau Ser396 and ubiquitin were observed. Expression of p-tau Ser396 and accumulation of ubiquitin were significantly increased in the parietal cortex and dorsal part of the hippocampus of the brain of aged dogs when compared with expression of these molecules in human AD.
Asunto(s)
Envejecimiento/patología , Enfermedad de Alzheimer/patología , Encéfalo/patología , Trastornos del Conocimiento/patología , Enfermedades de los Perros/patología , Anciano , Envejecimiento/metabolismo , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Western Blotting , Encéfalo/metabolismo , Trastornos del Conocimiento/metabolismo , Enfermedades de los Perros/metabolismo , Perros , Femenino , Humanos , Inmunohistoquímica , Masculino , Ovillos Neurofibrilares/metabolismo , Ovillos Neurofibrilares/patología , Proteínas tau/metabolismoRESUMEN
Malignant tumours are often associated with a relatively high number of tumour-infiltrating lymphocytes (TILs) and associated local cytokine production and these factors are thought to play a role in tumour progression. These aspects of tumour microenvironment have not been studied in canine mammary gland tumours (MGTs). The present study investigates TILs and the presence of related cytokines, as well as the expression of breast cancer susceptibility gene-1 (BRCA1), in canine MGTs. Immunohistochemistry, immunoblotting and reverse transcriptase-polymerase chain reaction were performed to evaluate these parameters. Three times as many T lymphocytes as B cells infiltrated canine MGTs. A correlation was found between expression of interleukin (IL)-1 and IL-6 and metastasis. There was an association between the expression of TILs, cytokines and mutation of BRCA1, suggesting that all of these factors may play a role in tumour progression.
Asunto(s)
Adenoma/metabolismo , Carcinoma/metabolismo , Enfermedades de los Perros/metabolismo , Genes BRCA1/fisiología , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Subgrupos Linfocitarios/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias Mamarias Animales/metabolismo , Adenoma/genética , Adenoma/inmunología , Análisis de Varianza , Animales , Western Blotting , Carcinoma/genética , Carcinoma/inmunología , Progresión de la Enfermedad , Enfermedades de los Perros/genética , Enfermedades de los Perros/inmunología , Perros , Femenino , Inmunohistoquímica , Subgrupos Linfocitarios/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias Mamarias Animales/genética , Neoplasias Mamarias Animales/inmunología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no Paramétricas , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
In early 2007, American pet food ingredients leading to nephrotoxic renal failure of dogs and cats raised serious concerns about the safety of pet foods. Major pet food companies recalled more than 1,000 commercial pet foods in consideration of pet safety. A similar pet food-associated outbreak of nephrotoxic renal failure occurred in Asia, in late 2003 and 2004, resulting in a similar extensive pet food recall. At that time, contamination of ingredients with a nephrotoxin-producing fungus at a pet food production facility was suspected. However, toxicologic evidence to substantiate a mycotoxicosis was lacking. Moreover, the renal lesions were not typical of those reported with fungal nephrotoxins. During 2003 and 2004, 14 dogs were presented to the Veterinary Medical Teaching Hospital of Konkuk University, Seoul, Korea, with renal failure and distinctive renal pathologic findings. Grossly, the kidneys were greenish in color with greenish uroliths in the renal pelvis or bladder. Histologically, characteristic crystals with pinwheel radiating striations were present in distal tubular segments. Toxicologic analysis identified melamine, cyanuric acid, and ammelide in deparaffinized formalin-fixed kidney samples.
Asunto(s)
Enfermedades de los Perros/inducido químicamente , Insuficiencia Renal/veterinaria , Triazinas/toxicidad , Alimentación Animal/análisis , Animales , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/patología , Perros , Femenino , Contaminación de Alimentos , Riñón/patología , Corea (Geográfico)/epidemiología , Masculino , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/patología , Estudios Retrospectivos , Triazinas/químicaRESUMEN
We describe a 10-month-old, intact female American Cocker Spaniel with pulmonary lymphomatoid granulomatosis (PLG). On clinical examination, this dog presented with nonproductive dry cough, serous nasal discharge, dyspnea, and lack of appetite. Radiography showed a consolidated lesion in the left cranial lung lobe. Histopathologic examination showed a mixed population of atypical lymphoid cells that had infiltrated into the pulmonary blood vessels angiocentrically. The lymphocytes were CD3 positive, consistent with a pan-T-cell phenotype. The lymphoid cells in the lesion were also positive for CD20cy and CD79a, indicative of the presence of B cells. We also observed large Reed-Sternberg-like cells that were positive for CD15 and CD30, similar to observations in human pulmonary Hodgkin's disease (PHD). In conclusion, canine PLG in this Cocker Spaniel was associated with B and T cells, which is first identified in a case of canine PLG. It was histopathologically similar to human lymphomatoid granulomatosis and immunophenotypically similar to human PHD.