Vet. Sci., Volume 2, Issue 3 (September 2015) – 12 articles , Pages 111-292

Human angiosarcomas and canine hemangiosarcomas are highly aggressive cancers thought to arise from cells of vascular origin. The pathological features, morphological organization, and clinical behavior of canine hemangiosarcomas are virtually indistinct from those of human angiosarcomas. Overall survival with current standard-of-care approaches remains dismal for both humans and dogs, and each is likely to succumb to their disease within a short duration. While angiosarcomas in humans are extremely rare, limiting their study and treatment options, canine hemangiosarcomas occur frequently. Therefore, studies of these sarcomas in dogs can be used to advance treatment approaches for both patient groups. Emerging data suggest that angiosarcomas and hemangiosarcomas utilize beta adrenergic signaling to drive their progression by regulating the tumor cell niche and fine-tuning cellular responses within the tumor microenvironment. These discoveries indicate that inhibition of beta adrenergic signaling could serve as an Achilles heel for these tumors and emphasize the need to design therapeutic strategies that target tumor cell and stromal cell constituents. In this review, we summarize recent discoveries and present new hypotheses regarding the roles of beta adrenergic signaling in angiosarcomas and hemangiosarcomas. Because the use of beta adrenergic receptor antagonists is well established in human and veterinary medicine, beta blockade could provide an immediate adjunct therapy for treatment along with a tangible opportunity to improve upon the outcomes of both humans and dogs with these diseases. Full article

Necrotizing scleritis is uncommon in dogs and presumed to be immune-mediated. Its clinical pattern and histopathology are similar to ocular lesions observed in humans suffering from granulomatosis with polyangiitis (GPA), formerly named Wegener’s granulomatosis, where the pathogenesis revolves around anti-neutrophil antibodies (e.g., anti-myeloperoxidase). These antibodies are used to diagnose and follow-up the disease in humans, but variants that only affect the eyes often test negative. Here, we present the first case of canine necrotizing scleritis where measurement of anti-myeloperoxidase antibodies was attempted. A 1.5 year-old female Scottish Terrier was presented with bilateral deep multifocal scleromalacia, severe inflammation of corneal/uveal/retrobulbar tissues, perilimbal corneal oedema and neovascularization, hypotony, and mild exophthalmos. Corticosteroids and antibiotics had been administrated (topically and orally) without success. Due to painful multifocal scleral perforation with vitreal haemorrhage, the left eye underwent enucleation, so did the right eye one week later. The histopathology of the left eye revealed a neutrophilic and histiocytic scleral infiltration with extension of pyogranulomatous inflammation to the cornea, choroid, ciliary body, and orbital fat. Levels of plasma anti-myeloperoxidase antibodies were not statistically significant to those of 13 healthy dogs. Further research is warranted to investigate the presence and role of anti-neutrophil antibodies in canine necrotizing scleritis. Full article

Relative to the dog, integration of the cat into the “One Health” concept has been more restricted, particularly in the field of molecular oncology. Beyond the continual need to enhance the sophistication of feline healthcare per se, the unique spectrum of naturally-occurring cancers in the cat offers tremendous opportunities for comparative and translational advances that may have mutual benefit for human and veterinary medicine. The study of feline cancers additionally may generate new insight into underexplored aspects of tumor biology that are less accessible in other species, such as the relationship between chronic inflammation and neoplasia, and the role of viruses in malignant transformation. Several factors that have hindered molecular studies of feline cancers have now been surmounted, with the most fundamental step forward coming from the development of a high-quality reference genome sequence assembly for the cat. This article reviews landmark studies that have led to our current appreciation of feline genome architecture, and outlines techniques used in cancer cytogenomics, from conventional karyotyping analysis through to the development of genomic microarrays and beyond. A summary of progress in the identification and characterization of chromosomal aberrations in feline cancers is provided using examples from studies of injection-site sarcomas, lymphomas and mammary tumors. Full article

Activating mutations of the BRAF gene lead to constitutive activation of the MAPK pathway. The characterization and discovery of BRAF mutations in a variety of human cancers has led to the development of specific inhibitors targeting the BRAF/MAPK pathway and dramatically changed clinical outcomes in BRAF-mutant melanoma patients. Recent discovery of BRAF mutation in canine cancers underscores the importance of MAPK pathway activation as an oncogenic molecular alteration evolutionarily conserved between species. A comparative approach using the domestic dog as a spontaneous cancer model will provide new insights into the dysregulation of BRAF/MAPK pathway in carcinogenesis and facilitate in vivo studies to evaluate therapeutic strategies targeting this pathway’s molecules for cancer therapy. The BRAF mutation in canine cancers may also represent a molecular marker and therapeutic target in veterinary oncology. This review article summarizes the current knowledge on BRAF mutations in human and canine cancers and discusses the potential applications of this abnormality in veterinary oncology. Full article

Osteosarcoma (OS) is a primary and aggressive bone sarcoma affecting the skeleton of two principal species, human beings and canines. The biologic behavior of OS is conserved between people and dogs, and evidence suggests that fundamental discoveries in OS biology can be facilitated through detailed and comparative studies. In particular, the relative genetic homogeneity associated with specific dog breeds can provide opportunities to facilitate the discovery of key genetic drivers involved in OS pathogenesis, which, to-date, remain elusive. In this review, known causative factors that predispose to the development OS in human beings and dogs are summarized in detail. Based upon the commonalities shared in OS pathogenesis, it is likely that foundational discoveries in one species will be translationally relevant to the other and emphasizes the unique opportunities that might be gained through comparative scientific approaches. Full article

The aim of this study was to compare the bacterial load of unclipped gluteal skin in dairy cows following either no treatment or treatment with a standard 70% isopropyl alcohol-based skin treatment protocol. Twenty Holstein-Friesian dairy cows from a commercial dairy herd in Cambridgeshire, England, were used in this randomised, blinded, controlled study. On each of the experimental cows an area of unclipped gluteal skin on one side of the pelvis was treated with swabs soaked in 70% isopropyl alcohol-based using a standard protocol and a contra-lateral area of skin was left untreated as a control. All the experimental skin sites were sampled using a swab followed by bacterial culture and quantitative analysis of bacterial load. There was a statistically significant decrease in the bacterial colony forming units per mL for the isopropyl-alcohol treatment group when compared to the control group (p ≤ 0.01). There was a 58% reduction in the median bacterial load of the treated sites when compared to the bacterial load of the untreated sites. This study has demonstrated that the treatment protocol will reduce the skin bacterial load. Full article

The most important causes of treatment failure in canine lymphoma include intrinsic or acquired drug resistance. Thus, elucidation of molecular mechanisms of drug resistance is essential for the establishment of better treatment alternatives for lymphoma patients. The overexpression of drug transporters is one of the most intensively studied mechanisms of drug resistance in many tumors. In canine lymphoma, it has also been shown that the overexpression of drug efflux pumps such as P-glycoprotein is associated with drug-resistant phenotypes. Canine lymphoma has many pathological similarities to human non-Hodgkin’s lymphoma, and they also share similar molecular mechanisms of drug resistance. We have previously demonstrated the association of the overexpression of drug transporters with drug resistance and indicated some molecular mechanisms of the regulation of these transporters’ expressions in canine and human lymphoid tumor cells. However, it has also been indicated that other known or novel drug resistance factors should be explored to overcome drug resistance in lymphoma. In this review, we summarize the recent findings on the molecular mechanisms of drug resistance and possible strategies to develop better treatment modalities for canine lymphoma from the comparative aspects with human lymphoid tumors. Full article

Drug resistance (DR) is the major limiting factor in the successful treatment of systemic neoplasia with cytotoxic chemotherapy. DR can be either intrinsic or acquired, and although the development and clinical implications are different, the underlying mechanisms are likely to be similar. Most causes for DR are pharmacodynamic in nature, result from adaptations within the tumor cell and include reduced drug uptake, increased drug efflux, changes in drug metabolism or drug target, increased capacity to repair drug‐induced DNA damage or increased resistance to apoptosis. The role of active drug efflux transporters, and those of the ABC‐transporter family in particular, have been studied extensively in human oncology and to a lesser extent in veterinary medicine. Methods reported to assess ABC‐transporter status include detection of the actual protein (Western blot, immunohistochemistry), mRNA or ABC‐transporter function. The three major ABC‐transporters associated with DR in human oncology are ABCB1 or P‐gp, ABCC1 or MRP1, and ABCG2 or BCRP, and have been demonstrated in canine cell lines, healthy dogs and dogs with cancer. Although this supports a causative role for these ABC‐transporters in DR cytotoxic agents in the dog, the relative contribution to the clinical phenotype of DR in canine cancer remains an area of debate and requires further prospective studies. Full article

Despite the fact that health communication is a discipline developed only recently, its importance in human medicine is well recognized. However, it is less considered in veterinary medicine, even if it has the potential to improve public health because of the role of veterinary medicine in public health. For this reason, an One Health approach is useful for communication as well. This approach leads to a “One Communication” concept, which is the result of the synergy in communicative efforts both in human and in veterinary medicine. Our analysis explores the potential of communication in several veterinary fields: institutions, food safety, companion animal and food-producing animal practice, pharmacology and drugs, wildlife fauna and environment. In almost all the areas of veterinary activity communication can contribute to human health. It takes many forms and use several channels, and this variety of communicative opportunities represent a challenge for veterinarians. For this reason, the communication course should be included in the curricula of Veterinary Medicine Schools. As One Health, One Communication is a strategy for expanding collaborations in health communication and it will enhance public health. Full article

The purpose of this study was to investigate the proportion of twins carried to term and the sex ratio of twin calves at birth in Holstein-Friesian dairy cattle kept on commercial farms in Devon and Cornwall, England. Ten farms were used in the study. Fifty four cows with twin pregnancies were identified using trans-rectal ultra-sonographic examination between 30 and 70 days of gestation. The farm records were subsequently used to derive the number of calves born. Farm records of 66 additional sets of twin births with the sex of the calves recorded were also identified. Of the 54 cows diagnosed with twin pregnancies, 16 cows (29.6%) aborted or absorbed both fetuses, 11 cows (20.4%) carried one calf to term and 27 cows (50%) carried both calves to term. In the calf sex analysis of the additional 66 sets of twins: 13♂♂ calves (19.7%), 18 ♀♀ calves (27.3%) and 35 ♂♀ calves (53.0%). There was no statistically significant difference from an expected ratio of 1♂♂:2♂♀:1♀♀ (p = 0.61). This study provides bench marks for the expected abortion/absorption rates following the early ultra-sonographic diagnosis of twin pregnancies in comparable populations and supports earlier observations that the expected sex ratio for twinning approximates to1♂♂:2♂♀:1♀♀. Full article

Naturally occurring tumors in dogs are well-established models for several human cancers. Domestic cats share many of the benefits of dogs as a model (spontaneous cancers developing in an immunocompetent animal sharing the same environment as humans, shorter lifespan allowing more rapid trial completion and data collection, lack of standard of care for many cancers allowing evaluation of therapies in treatment-naïve populations), but have not been utilized to the same degree in the One Medicine approach to cancer. There are both challenges and opportunities in feline compared to canine models. This review will discuss three specific tumor types where cats may offer insights into human cancers. Feline oral squamous cell carcinoma is common, shares both clinical and molecular features with human head and neck cancer and is an attractive model for evaluating new therapies. Feline mammary tumors are usually malignant and aggressive, with the ‘triple-negative’ phenotype being more common than in humans, offering an enriched population in which to examine potential targets and treatments. Finally, although there is not an exact corollary in humans, feline injection site sarcoma may be a model for inflammation-driven tumorigenesis, offering opportunities for studying variations in individual susceptibility as well as preventative and therapeutic strategies. Full article