Search results for "WARBURG EFFECT"
showing 4 items of 14 documents
Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted
2006
Abstract Tumours ferment glucose to lactate even in the presence of oxygen (aerobic glycolysis; Warburg effect). The pentose phosphate pathway (PPP) allows glucose conversion to ribose for nucleic acid synthesis and glucose degradation to lactate. The nonoxidative part of the PPP is controlled by transketolase enzyme reactions. We have detected upregulation of a mutated transketolase transcript (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like-2 (TKTL2) transcripts were not upregulated. Strong TKTL1 protein expression was correlated to invasive colon and urothelial tumours and to poor patients outcome. TKTL1 encodes a transketolase with unusual enzymatic prop…
Inhibition of tumor lactate oxidation: consequences for the tumor microenvironment.
2011
Abstract Background and purpose Tumor cells are recognized as being highly glycolytic. However, recently it was suggested that lactate produced in hypoxic tumor areas may be taken up by the monocarboxylate transporter MCT1 and oxidized in well-oxygenated tumor parts. Furthermore, it was shown that inhibition of lactate oxidation using the MCT1 inhibitor α-cyano-hydroxycinnamate (CHC) can radio-sensitize tumors possibly by forcing a switch from lactate oxidization to glycolysis in oxygenated cells, which in turn improves tumor oxygenation and indirectly kills radio-resistant hypoxic tumor cells from glucose starvation. Material and methods To provide direct evidence for the existence of a ta…
Manipulation of glycolysis in malignant tumors: fantasy or therapy?
2009
After Warburg stated his hypothesis on tumor cell metabolism about 80 years ago, the field of carbohydrate metabolism of cancer cells and solid tumors is experiencing a boom for the past few years. Numerous studies have been focused on the characteristics of cancer metabolism and its accessibility to novel therapeutic interventions. Malignant transformation is associated with an increase in glycolytic flux, mainly caused by an upregulation of numerous glycolysis-related genes in the majority of human cancers. As a consequence of these alterations, tumor cells are producing lactate at higher levels compared to non-malignant tissue, even in the presence of oxygen, a phenomenon termed “aerobic…
Glycolytic phenotype and AMP kinase modify the pathologic response of tumor xenografts to VEGF neutralization.
2011
Abstract VEGF antagonists are now widely used cancer therapeutics, but predictive biomarkers of response or toxicity remain unavailable. In this study, we analyzed the effects of anti-VEGF therapy on tumor metabolism and therapeutic response by using an integrated set of imaging techniques, including bioluminescence metabolic imaging, 18-fluorodeoxyglucose positron emission tomography, and MRI imaging and spectroscopy. Our results revealed that anti-VEGF therapy caused a dramatic depletion of glucose and an exhaustion of ATP levels in tumors, although glucose uptake was maintained. These metabolic changes selectively accompanied the presence of large necrotic areas and partial tumor regress…