ABSTRACT
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.
Subject(s)
Aging/pathology , Alzheimer Disease/pathology , Brain/pathology , Cognition Disorders/pathology , Dog Diseases/pathology , Aged , Aging/metabolism , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Animals , Blotting, Western , Brain/metabolism , Cognition Disorders/metabolism , Dog Diseases/metabolism , Dogs , Female , Humans , Immunohistochemistry , Male , Neurofibrillary Tangles/metabolism , Neurofibrillary Tangles/pathology , tau Proteins/metabolismABSTRACT
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.
Subject(s)
Dog Diseases/pathology , Mammary Neoplasms, Animal/blood supply , Mast Cells/enzymology , Neovascularization, Pathologic/pathology , Tryptases/analysis , Angiogenesis Inducing Agents/metabolism , Animals , Case-Control Studies , Coloring Agents , Dogs , Female , Mammary Neoplasms, Animal/pathology , Microvessels/pathology , Neoplasm Invasiveness/pathology , Neovascularization, Pathologic/veterinary , Staining and Labeling/methods , Tolonium Chloride , Tumor MicroenvironmentABSTRACT
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.
Subject(s)
Dog Diseases/genetics , Gene Expression Regulation, Neoplastic , Mammary Neoplasms, Animal/genetics , Receptor, ErbB-2/genetics , Receptor, ErbB-3/genetics , Animals , Dog Diseases/pathology , Dogs , Female , Genetic Markers , Immunohistochemistry/veterinary , Lymphocytes, Tumor-Infiltrating/pathology , Mammary Neoplasms, Animal/pathology , Neoplasm Grading/veterinaryABSTRACT
An improved method for the diagnosis of canine parvovirus using in situ hybridization in standard formalin-fixed, paraffin-embedded tissue sections was developed. A digoxigenin-labeled probe complementary to DNA sequences that code for the entire sequence of the capsid protein VP-1 and the middle part of the sequence of the capsid protein VP-2 was designed. Specific histologic localization of canine parvovirus-infected cells was demonstrated in small intestine, tonsil, lymph node, thymus, spleen, heart, liver, and kidney from dogs diagnosed at necropsy with canine parvovirus infection. The in situ hybridization accurately pinpointed the specific sites of viral infection. The detection of canine parvovirus in liver, kidney, and heart tissues together in the same pups could represent an enhanced virulence of this strain of canine parvovirus and suggests a broadened tissue tropism not seen before in Korean strains of canine parvovirus.
