Improving Survival Rates in Two Models of Spontaneous Postoperative Metastasis in Mice by Combined Administration of a β-Adrenergic Antagonist and a Cyclooxygenase-2 Inhibitor

摘要: Clinical practice does not consider perioperative paracrine and neuroendocrine stress responses as risk factors for cancer recurrence, although recent animal studies provided supportive evidence. Suggested mechanisms include the effects of stress-hormones on tumor cells host physiology. In this study, in mice undergoing primary excision, we tested survival-enhancing potential blockade catecholamines prostaglandins, studied mediating mechanisms. C57BL/6J were inoculated intrafootpad with syngeneic B16F10.9-melanoma or Lewis lung carcinoma, paw was amputated when a developing exceeded 100 μl. The clinically used β-adrenergic antagonist propranolol, and/or cyclooxygenase-2 inhibitor etodolac, administered once before amputation, recurrence-free survival monitored. different studies, NK cytotoxicity, leukocytes' molecular functional markers, vascular endothelial growth factor secretion by context surgery drug treatments. findings indicated that combination propranolol but neither alone, significantly markedly improved rates both models, effective established immunostimulatory agents (IL-12 polyinosinic-polycytiylic acid). Surgery reduced cytotoxicity cell expression Fas ligand CD11a, all circulating lymphocyte-subtype concentrations, increased corticosterone levels. Propranolol etodolac administration counteracted these perturbations. B16 3LL secreted vitro, affected catecholamine agonists, corticosterone, etodolac. Overall, administration, which could be applied perioperatively most patients minimal low cost, has several immunologic endocrinologic perturbations excision.