Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.