enerated by combining 2 molecules of DCA with one of cisplatin showed clear synergism PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19844759 in terms of cell death in several cancer cell lines, including induction of apoptosis in cell lines resistant to cisplatin. The interest in DCA by the general public has led to unique issues in its development as an antineoplastic. Cancer patients have frequently gone to websites which have touted benefits of DCA that are not clearly supported by medical literature. During the conduct of this trial, the investigators received countless calls and e-mails from cancer patients around the world requesting additional information on DCA. Since DCA is commercially available and accessible, patients can obtained DCA for treatment of cancer. We received several calls from outside hospitals inquiring about toxicity, particularly neurologic, of DCA. On further investigation, these patients were frequently self-administering doses that are larger than what has been shown to be safe in cancer patients. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript Conclusion We acknowledge the difficulty in drawing solid conclusions about efficacy and safety of DCA in patients with advanced cancer, based on our data. However, we feel it is important to publish our experience and stress the danger of using DCA in patients with advanced and rapidly progressing disease, where DCA may not reach adequate drug levels to have the potential for therapeutic effect. Desperate and unfortunate patients may self-medicate with DCA given its wide availability on the internet and the potential for exploitation by forprofit suppliers. Proper regulation of lymphocyte function is critical to allow normal immune responses while preventing autoimmunity or immunodeficiency. Lymphocyte Piclidenoson biological activity metabolism is now appreciated to play a key role in cellular function and homeostasis. In T lymphocytes activation through the TCR along with CD28-mediated co-stimulation leads to a rapid increase in expression of the glucose transporter, Glut1, to support increased glucose uptake and metabolism. Simultaneously, glutamine oxidation increases and beta-oxidation of fatty acids decreases. Overall, glycolysis becomes predominant over oxidative metabolism in activated T cells, leading to a reliance on aerobic glycolysis and glutaminolysis in a metabolic phenotype that resembles that of cancer cells. Stimulated dendritic cells and inflammatory macrophages induced similar metabolic programs. Metabolic reprogramming in T cells is mediated through the induction of cMyc, a well-described regulator of glycolysis, glutaminolysis, and cell growth, together with the phosphatidyl-inositol-3 kinase /Akt pathway. As in T cells, the PI3K/Akt pathway can increase B cell expression of Glut1 and metabolism upon antigenic stimulation. There can be significant metabolic heterogeneity in distinct lymphocyte subsets and it is now of significant interest to establish mechanisms of metabolic reprogramming to better understand lymphocyte physiology and identify metabolic targets that could be exploited to treat disease. However, the metabolic phenotype of stimulated B cells and the requirements for antibody production are poorly understood. Metabolic 
reprogramming to induce glycolysis may dictate the inflammatory potential of activated lymphocytes. Glucose deprivation, or treatment with the glycolytic inhibitor, 2-deoxyglucose , suppresses T cell activation, proliferation, and production of IFN. In contrast, increased glu