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Immunological and angiogenic markers during metronomic temozolomide and cyclophosphamide in canine cancer patients
Authors:S Denies  L Cicchelero  H de Rooster  S Daminet  I Polis  I Van de Maele  N N Sanders
Institution:1. Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium;2. Small Animal Hospital, Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
Abstract:Metronomic chemotherapy stimulates the immune response via depletion of regulatory T cells (Tregs) and suppresses angiogenesis by modulating the secretion of thrombospondin‐1 (TSP‐1) and vascular endothelial growth factor (VEGF). In this study, blood was collected from 10 healthy dogs and from 30 canine cancer patients before and 2 and 4 weeks after treatment with metronomic temozolomide (6.6 mg m?2), cyclophosphamide (12.5 mg m?2) or cyclophosphamide and temozolomide. The percentage of circulating CD25+Foxp3+CD4+ Tregs and the plasma levels of TSP‐1 and VEGF were measured. There was a significant difference in the percentage of Tregs between cancer patients and healthy dogs. A significant decrease in Tregs was noted in patients treated with metronomic cyclophosphamide and the combination. Treatment with temozolomide had no effect on the percentage of Tregs. TSP‐1 and VEGF levels were, respectively, significantly lower and higher in cancer patients than in healthy dogs, but they were not influenced by any of the studied metronomic treatment regimens.
Keywords:cyclophosphamide  regulatory T cells  temozolomide  TSP‐1
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