VEGFA AND VEGFRS EXPRESSION IN CANINE APPENDICULAR OSTEOSARCOMA

Osteosarcoma is the most common primary malignant tumour of bones in dogs, occurring most frequently in the axial skeleton (75%), it is locally aggressive with a high angiogenetic and metastatic potential. VEGFRs (VEGFR1, VEGFR2 and VEGFR3) are the most important receptors regulating tumoral angiogenesis following the interaction with VEGF factor. The aim of this study was to investigate VEGFR-1, VEGFR-2 and VEGFR-3 and VEGFA expression in canine OSA tissues and cell lines to evaluate its prognostic value in relation to clinical outcome of the canine patients. Thirty-one dogs diagnosed with canine appendicular were enrolled in the study. All the animals underwent a complete clinical staging and were treated with surgery and then they were followed until the recurrence of the neoplasm or death. All the samples were histologically evaluated and immunohistochemically tested for VEGFA, VEGFR-1, VEGFR-2 and VEGFR-3. Histological and immunohistochemical results were evaluated in relation to clinic-pathological data. Total RNA was extracted from 8 canine osteosarcoma cell lines and expression of VEGFR1, VEGFR2 and VEGFR3 canine gene were evaluated by qPCR. VEGF was present in all analyzed cases and particularly was widely expressed in 33% of cases, moderately expressed in 46% of cases and poorly expressed in 20% of OSA analyzed. Regarding the expression of the receptors we found that the 64.52% of canine OSA were positive for VEGFR-1, 70.97% were positive for VEGFR-2, while 74.19% cases per positive for VEGFR-3. The positivity for VEGFR-1 was statistically associated with the positivity for VEGF (P<0.05) and VEGFR-3 (P<0.05). Statistical analyses comparing the immunohistochemical results with all clinical-pathological data revealed no statistical associations. Molecular data showed that only D22 cell lines over-expressed all three VEGFRs while VEGFR2 was expressed only by Wall and D22 cell lines and VEGFR3 by D22, Pedro, Lord and Wall cell lines if compared to osteoblastic cell line. This is the first study investigating VEGFRs and VEGFA expression in canine OSA and cell lines demonstrating that those receptors are widely expressed in this tumor. No statistical association has been found between VEGFRs expression and clinical and histopathological features while a significant association between VEGFR1 and VEGFA has been found. In human osteosarcoma the autocrine loop VEGFR-1/VEGFA is correlated to the malignant progression while VEGFR2 and VEGFR3 seem not to be involved. These preliminary data suggest that also in canine OSA this autocrine loop can be relevant in the progression of canine osteosarcoma as demonstrated in canine mammary tumors and that be considered a suitable target for innovative targeted therapies

The Italian Network of Laboratories for Veterinary Oncology (NILOV) 2.0: Improving Knowledge on Canine Tumours

Advances in tumour research are crucial, and comparative oncology can improve the knowledge in several ways. Dogs are not only models of specific naturally occurring tumours but can also be sentinels of environmental exposures to carcinogens, as they share the same environment with their owners. The purpose of this work was to describe the data collected by The Italian Network of Laboratories for Veterinary Oncology in the first 9 years of activity (2013-2021) and to evaluate their potential epidemiological significance. Frequencies of tumour topographies and main morphologies in dogs were described, analysed and compared, calculating age-adjusted proportional morbidity ratios and considering several risk factors (breed, sex, period and region of residence). These observations allowed us to highlight differences not only in morphology and topography of some tumours but also to formulate hypotheses on the potential role of some risk factors, e.g., neutering/spaying or geographical location. In our opinion, the results of this case series confirm the importance of initiating and consolidating animal cancer registration initiatives that would facilitate the possibility of conducting multicentric collaborative studies to deepen the knowledge of the epidemiology of tumours in dogs from a comparative perspective

Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs

Background Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Sources of material This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. Abstract of findings Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. Conclusion Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk