RESUMEN
The endocannabinoid system is increasingly being implicated in the pathogenesis and progression of various human cancers. Specifically, increased levels of 2-arachidonoylglycerol (2-AG) and oleoythanolamide (OEA) have been demonstrated in human diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL) patients, respectively. The objectives of this paper were to compare 2-AG, OEA, N-arachidonoylethanolamine (AEA), and palmitoylethanolamide (PEA) levels between dogs with multicentric lymphoma and healthy control dogs. In addition, evaluate 2-AG, OEA, AEA, and PEA levels as biomarkers for progression free interval (PFI) and overall survival time (OST) in the dogs with lymphoma. The study consisted of 26 dogs with multicentric B cell lymphoma, 14 dogs with multicentric T cell lymphoma, and 12 healthy control dogs. Serum 2-AG, OEA, AEA, and PEA levels were measured using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) in dogs with lymphoma and in healthy dogs. OEA, AEA, and PEA levels were significantly elevated in dogs with lymphoma compared to healthy controls (p < 0.05). Total AG was significantly higher in healthy control dogs (p = 0.049). There was no significant difference between dogs with B cell and T cell lymphoma for any of the measured endocannabinoids. Elevated PEA was significantly associated with decreased PFI (p = 0.04) in dogs with lymphoma with a hazards ratio of 1.816 [95% Confidence Interval (CI): 1.020-3.232]. Overall, dogs with lymphoma have elevated levels of OEA, AEA, and PEA. PEA levels have the potential to be a prognostic biomarker.
RESUMEN
The efficacy and toxicity of lomustine and prednisone for treating high-grade completely excised mast cell tumors (MCTs) was evaluated in a retrospective study of 15 dogs. Dogs were treated with lomustine (CCNU) at 70 mg/m2 every 4 weeks and prednisone at 0.5 to 1 mg/kg body weight PO daily. Eight dogs had treatment failures due to recurrence at the site of the initial surgery (2/15), de novo cutaneous MCT (4/15), or metastatic disease (2/15). The median overall survival time was 904 days, with 9 dogs alive at 1 year and 6 dogs alive after 2 years. All but 2 of the dogs had toxicity throughout their treatment protocol, with neutropenia (67%) and elevations in ALT (60%) being the most common; however, no dogs required hospitalization. The protocol was overall well-tolerated and lomustine/prednisone should be considered in the adjunctive treatment of high-grade mast cell tumors.
Chimiothérapie avec lomustine (CCNU) et prednisone pour le traitement de tumeurs mastocytaires de grade élevé complètement excisées. L'efficacité et la toxicité de la lomustine et de la prednisone pour traiter des tumeurs mastocytaires (MCTs) de grade élevé complètement excisées furent évaluées dans une étude rétrospective de 15 chiens. Les chiens furent traités avec la lomustine (CCNU) à un dosage de 70 mg/m2 aux 4 semaines et avec de la prednisone à un dosage de 0,5 à 1 mg/kg de poids corporel PO quotidiennement. Un échec de traitement est survenu chez huit chiens étant donné la récurrence au site de la chirurgie initiale (2/15), une MCT cutanée de novo (4/15), ou une maladie métastasique (2/15). Globalement, la médiane du temps de survie était de 904 jours, avec neuf chiens toujours vivants après 1 an et 6 chiens toujours vivants après 2 ans. À l'exception de deux chiens, tous les chiens présentèrent des signes de toxicité durant toute la durée de leur protocole de traitement, la neutropénie (67 %) et une augmentation de l'ALT (60 %) étant les plus communes; toutefois, aucun chien ne nécessita d'être hospitalisé. Le protocole était généralement bien toléré et la combinaison lomustine/prednisone devrait être considérée dans le traitement complémentaire des tumeurs mastocytaires de grade élevé.(Traduit par Dr Serge Messier).
