The expression of Ki67, BCL-2, and COX-2 was investigated in 53 canine cutaneous mast cell tumors (MCTs) by immunohistochemistry and quantitative real time polymerase chain reaction (qPCR) to evaluate their prognostic significance and the association with the histologic grading and the mitotic index (MI). MCTs were graded according to the Patnaik grading system and the novel 2-tier grading system proposed by Kiupel. The numbers of mitotic figures/10 high-power fields (MI) were counted. Both grading systems were significantly associated with prognosis. The Patnaik grading was of limited prognostic value for grade 2 MCTs, with 23% being associated with mortality. The concordance among pathologists was strongly improved by the application of the 2-tier grading system, and 71% of high-grade MCTs were associated with a high mortality rate. MI and Ki67 protein expression were significantly associated with grading and survival. No significant association between BCL-2 protein expression and either grading system or health status was observed. BCL-2 mRNA expression was significantly higher in grade 2 than in grade 1 MCTs, while no statistically significant differences were detected between low- and high-grade MCTs. The increased BCL-2 mRNA level was significantly associated with increased mortality rate. The COX-2 protein expression was detected in 78% of the MCTs investigated. However, neither association with the tumor grade nor with the health status was observed. COX-2 mRNA was significantly up-regulated in MCTs compared to surgical margins and control skin tissue, but it was neither associated with tumor grade nor with survival.

No abstract

Currently, there is no satisfactory treatment for stage IV cMCT. Asymptomatic dogs with tumor diameter <3 cm and a low tumor burden, without bone marrow infiltration may be candidates for multimodal treatment. Stage IV dogs without lymph node metastasis may enjoy a surprisingly prolonged survival. The achievement of local tumor control seems to predict a better outcome in dogs with stage IV cMCT.

To complete a studyaimed at investigating the pattern of the basal activities of liver xenobioticmetabolizing enzymes in major and minor species intended for meat production, microsomal carboxylesterases and some conjugating enzyme activities were determined and compared in liver preparations from horses, cattle, pigs, rabbits and broiler chicks, using the rat as a reference species. Horses and broiler chicks exhibited a lower microsomal carboxylesterase activity towards indophenyl or p-nitrophenyl acetate than that measured in cattle or pig subfractions. Among food-producing species, the rate of glucuronidation of either 1-naphthol or p-nitrophenol was in the order pigs approximately rabbits > horses >> cattle > broiler chicks. The widest variations were observed in the acetylation capacity towards p-aminobenzoic acid or isoniazid, which in rabbits was 3-fold to 11-fold greater than that displayed by any other examined species; low but measurable activities were found in equine and bovine cytosols. The activity of cytosolic glutathione S-transferase (GST) accepting the general substrate 1-chloro-2,4-dinitrobenzene was significantly higher in rabbits, horses and pigs than in rat, broiler chicks and cattle. Finally, an uneven pattern of activity towards the other tested GST substrates - 3,4-dichloronitrobenzene, ethacrinic acid or 1,2-epoxybutane - was observed, possibly reflecting the species-related expression of different GST classes; in this respect, the conjugative capacity displayed by horses was higher than or comparable to that found in the other food-producing species.

Aflatoxins, and particularly aflatoxin B1 (AFB1), are toxic mycotoxins to humans and farm animal species, resulting in acute and chronic toxicities. At present, AFB1 is still considered a global concern with negative impacts on health, the economy, and social life. In farm animals, exposure to AFB1-contaminated feed may cause several untoward effects, liver damage being one of the most devastating ones. In the present study, we assessed in vitro the transcriptional changes caused by AFB1 in a bovine fetal hepatocyte-derived cell line (BFH12). To boost the cellular response to AFB1, cells were pre-treated with the co-planar PCB 3,3′,4,4′,5-pentachlorobiphenyl (PCB126), a known aryl hydrocarbon receptor agonist. Three experimental groups were considered: cells exposed to the vehicle only, to PCB126, and to PCB126 and AFB1. A total of nine RNA-seq libraries (three replicates/group) were constructed and sequenced. The differential expression analysis showed that PCB126 induced only small transcriptional changes. On the contrary, AFB1 deeply affected the cell transcriptome, the majority of significant genes being associated with cancer, cellular damage and apoptosis, inflammation, bioactivation, and detoxification pathways. Investigating mRNA perturbations induced by AFB1 in cattle BFH12 cells will help us to better understand AFB1 toxicodynamics in this susceptible and economically important food-producing species.

Aflatoxin B1 (AFB1) toxicity in livestock and human beings is a major economic and health concern. Natural polyphenolic substances with antioxidant properties have proven to be effective in ameliorating AFB1-induced toxicity. Here we assessed the potential anti-AFB1 activity of curcumin (pure curcumin, C, and curcumin from Curcuma longa, CL) in a bovine fetal hepatocyte-derived cell line (BFH12). First, we measured viability of cells exposed to AFB1 in presence or absence of curcumin treatment. Then, we explored all the transcriptional changes occurring in AFB1-exposed cells cotreated with curcumin. Results demonstrated that curcumin is effective in reducing AFB1-induced toxicity, decreasing cells mortality by approximately 30%. C and CL induced similar transcriptional changes in BFH12 exposed to AFB1, yet C treatment resulted in a larger number of significant genes compared to CL. The mitigating effects of curcuminoids towards AFB1 toxicity were mainly related to molecular pathways associated with antioxidant and anti-inflammatory response, cancer, and drug metabolism. Investigating mRNA changes induced by curcumin in cattle BFH12 cells exposed to AFB1 will help us to better characterize possible tools to reduce its consequences in this susceptible and economically important food-producing species.

No abstract

No abstract