ABSTRACT
Increased glycolysis is the main source of energy supply in cancer cells that use this metabolic pathway for ATP generation. Altered energy metabolism is a biochemical fingerprint of cancer cells that represents one of the "hallmarks of cancer". The immune system can prevent tumour growth by eliminating cancer cells but this editing process ultimately results in poorly immunogenic cells remaining allowing for unchallenged tumour growth. In this review we look at the glycolysis pathway as a target for cancer treatments. We also examine the interplay between the glycolysis modulation and the immune response as an anti-cancer therapy.
Subject(s)
Glycolysis/drug effects , Immunity, Cellular/drug effects , Neoplasms/drug therapy , Adenosine Triphosphate/metabolism , Energy Metabolism/drug effects , Humans , Metabolic Networks and Pathways/drug effects , Molecular Targeted Therapy , Neoplasms/metabolism , Neoplasms/pathologyABSTRACT
BACKGROUND: Cardiopulmonary bypass results in ischemia/reperfusion (I/R)-induced endotoxemia. We conducted a prospective randomized trial to investigate the effect of taurolidine, an antiendotoxin agent with antioxidant and membrane-stabilizing properties, on patients undergoing coronary artery bypass grafting (CABG). METHODS: A total of 60 patients undergoing CABG were randomized into 4 groups. St Thomas' Hospital cold crystalloid cardioplegia was used in groups A and B, and cold blood cardioplegia in groups C and D. Groups A and C received a placebo infusion of normal saline, whereas groups B and D were administered intravenous taurolidine. Arrhythmias induced by pro- and anti-inflammatory cytokines (interleukin [IL]-6 and IL-10), and I/R were assessed perioperatively. RESULTS: Administration of taurolidine in crystalloid cardioplegia patients resulted in a significant decrease in serum IL-6 and an increase in serum IL-10 at 24 hours postaortic unclamping compared to placebo (P < .0001). Although not statistically significant, this trend in serum IL-6 decrease was mirrored in the blood cardioplegia patients (P = .068). Taurolidine treatment also significantly decreased I/R-induced arrhythmias compared to placebo in the crystalloid cardioplegia patients (P < .003). There were fewer I/R-induced arrhythmias compared to placebo in the blood cardioplegia patients; the difference, however, was marginal and not statistically significant (P = .583). CONCLUSION: This study demonstrates that administration of taurolidine in CABG patients induces a potent anti-inflammatory response that is associated with a significant decrease in arrhythmias.
