Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Small Animal Hospital, Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Vet Comp Oncol. 2017 Jun;15(2):594-605. doi: 10.1111/vco.12203. Epub 2016 Mar 9.
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 ), cyclophosphamide (12.5 mg m ) 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.
节拍化疗通过耗竭调节性 T 细胞(Tregs)刺激免疫反应,并通过调节血小板反应蛋白-1(TSP-1)和血管内皮生长因子(VEGF)的分泌来抑制血管生成。在这项研究中,在接受节拍替莫唑胺(6.6mg/m )、环磷酰胺(12.5mg/m )或环磷酰胺和替莫唑胺治疗前和治疗后 2 周和 4 周,从 10 只健康犬和 30 只犬癌症患者中采集血液。测量循环 CD25 Foxp3 CD4 Tregs 的百分比和 TSP-1 和 VEGF 的血浆水平。癌症患者和健康犬之间 Tregs 的百分比存在显著差异。用节拍环磷酰胺和联合治疗的患者中 Tregs 的数量明显减少。替莫唑胺治疗对 Tregs 的百分比没有影响。TSP-1 和 VEGF 水平在癌症患者中分别明显低于健康犬,但不受任何研究的节拍治疗方案的影响。