title: Immunological and angiogenic markers during metronomic temozolomide and cyclophosphamide in canine cancer patients.
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.
authors.affiliation: Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Denies
authors.affiliation: Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Cicchelero
authors.affiliation: Small Animal Hospital, Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: de Rooster
authors.affiliation: Small Animal Hospital, Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Daminet
authors.affiliation: Small Animal Hospital, Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Polis
authors.affiliation: Small Animal Hospital, Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Van de Maele
authors.affiliation: Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: N N
authors.initials: NN
authors.lastname: Sanders
mesh_terms: D059250:Administration, Metronomic / Q000662:veterinary; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D016022:Case-Control Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004283:Dog Diseases / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004285:Dogs; D018655:Lymphocyte Count / Q000662:veterinary; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000662:veterinary*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D000077204:Temozolomide; D019700:Thrombospondin 1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D003606:Dacarbazine; D003520:Cyclophosphamide; D000077204:Temozolomide
keywords: TSP-1; cyclophosphamide; regulatory T cells; temozolomide