Immunohistochemical investigation of cell cycle and apoptosis regulators (Survivin, beta-Catenin, P53, Caspase 3) in canine appendicular osteosarcoma

Background: Osteosarcoma (OSA) represents the most common canine primary bone tumour. Despite several pathways have been investigated so far, few molecules have been identified as prognostic tools or potential therapeutic targets, and there is still the need to find out molecular pathways with specific influence over OSA progression to facilitate earlier prognosis and treatment.Aims of the present study were to evaluate the immunohistochemical pattern and levels of expression of a panel of molecules (survivin, β-catenin, caspase 3 -inactive and active forms- and p53) involved in cell cycle and apoptosis regulation in canine OSA samples, known to be of interest in the study also of human OSA, and to detect specific relations among them and with histological tumour grade, disease free interval (DFI) and overall survival (OS).Results: Nuclear β-catenin immunostaining was detected in normal osteoblasts adjacent to the tumour, and in 47% of the cases. Cytoplasmic and/or membranous immunostaining were also observed. Nuclear survivin and p53 positive cells were found in all cases. Moderate/high cytoplasmic β-catenin expression (≥10% positive cells) was significantly associated with the development of metastasis (P = 0.014); moderate/high nuclear p53 expression (≥10% positive cells) was significantly associated with moderate/high histological grade (P = 0.017) and shorter OS (P = 0.049). Moderate/high nuclear survivin expression (≥15% positive cells) showed a tendency toward a longer OS (P = 0,088).Conclusions: The present results confirmed p53 as negative prognostic marker, while suggested survivin as a potential positive prognostic indicator, rather than indicative of a poor prognosis. The detection of nuclear β-catenin immunostaining in normal osteoblasts and the absent/low expression in most of the OSAs, suggested that this pathway could not play a major role in oncogenic transformation of canine osteoblasts. Further studies are needed to confirm these hypotheses

LINEE GUIDA NAZIONALI PER LE AUTOPSIE A SCOPO FORENSE IN MEDICINA VETERINARIA

Vedi Prefazione nel testo

Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders

Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer’s disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS) and Heat Shock Proteins (HSPs), in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging

Heat Shock Protein Expression and Implications in Spontaneous Animal Tumors: Veterinary and Comparative Aspects

Heat shock proteins (HSP) play a fundamental role in the maintenance of cellular homeostasis, under both physiological and stress conditions, by acting as molecular chaperones in protein folding, intracellular transport and degradation. HSP are also implicated in the hallmarks of cancer from proliferation, impaired apoptosis and sustained angiogenesis to invasion and metastasis. Altered HSP levels have been observed in a variety of human neoplasms and such abnormal expression may contribute to poor prognosis and drug resistance. Therefore, these molecular chaperones represent attractive targets for anti-cancer therapy. A growing number of studies in veterinary medicine have also demonstrated the presence of altered HSP expression in spontaneous animal tumors, especially canine cancer, and the study of carcinogenesis and the role of HSP in animal models represent an additional source of information for clinical cancer research. This chapter briefly reviews the current knowledge on HSP expression and implications in spontaneous animal neoplasms, and the advances in understanding of the therapeutic opportunities offered by HSP-based anti-cancer therapies in veterinary and comparative oncology