Glucose Metabolism in Cancer and Ischemia: Possible Therapeutic Consequences of the Warburg Effect.

The Warburg effect states that the main source of energy for cancer cells is not aerobic respiration, but glycolysis-even in normoxia. The shift from one to the other is governed by mutually counteracting enzymes: pyruvate dehydrogenase and pyruvate dehydrogenase kinase (PDK). Anaerobic metabolism of cancer cells promotes cell proliferation, local tissue immunosuppression, resistance to hypoxic conditions, and metastatic processes. By switching glucose back to oxidative metabolism, these effects might be reversed. This can be achieved using PDK inhibitors, such as dichloroacetate. Patients suffering from ischemic conditions might benefit from this effect. On the other hand, the ß-blockers (adrenergic ß-antagonists) often used in these patients appear to improve cancer-specific survival, and nonselective ß-blockers have been shown to promote glucose oxidation. Might there be a link?

Polymorphism in the GATM Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure.

The ten most statistically significant estimated glomerular filtration rate (eGFRcrea)-associated loci from genome-wide association studies (GWAs) are tested for associations with chronic kidney disease (CKD) in 208 patients, including dialysis-independent CKD and dialysis-dependent end-stage renal disease (kidney failure). The allele A of intergenic SNP rs2453533 (near GATM) is more frequent in dialysis-independent CKD patients (n = 135, adjusted p = 0.020) but not dialysis-dependent kidney failure patients (n = 73) compared to healthy controls (n = 309). The allele C of intronic SNP rs4293393 (UMOD) is more frequent in healthy controls (adjusted p = 0.042) than in CKD patients. The Allele T of intronic SNP rs9895661 (BCAS3) is associated with decreased eGFRcys (adjusted p = 0.001) and eGFRcrea (adjusted p = 0.017). Our results provide further evidence of a genetic difference between dialysis-dialysis-independent CKD and dialysis-dependent kidney failure, and add the GATM gene locus to the list of loci associated only with dialysis-independent CKD. GATM risk allele carriers in the dialysis-independent group may have a genetic susceptibility to higher creatinine production rather than increased serum creatinine due to kidney malfunction, and therefore, do not progress to dialysis-dependent kidney failure. When using eGFRcrea for CKD diagnosis, physicians might benefit from information about creatinine-increasing loci.

A Prospective Head-to-Head Comparison of 18F-Fluciclovine With 68Ga-PSMA-11 in Biochemical Recurrence of Prostate Cancer in PET/CT.

PURPOSE: One of the major challenges for all imaging modalities is accurate detection of prostate cancer (PCa) recurrence. Beyond the established Ga-PSMA, a novel promising PET tracer in PCa imaging is F-fluciclovine. For evaluating the advantages and disadvantages and the comparability, we conducted a prospective head-to-head comparison on F-fluciclovine and Ga-PSMA-11 in patients with biochemical recurrence of PCa. METHODS: 58 patients with biochemical recurrence of PCa after definitive primary therapy were included. Both scans were performed within a time window of mean 9.4 days. All scans were visually analyzed independently on a patient-, region- and lesion-based analysis. All the examinations were performed in the same medical department using identical scanners at any time. RESULTS: The overall detection rate for PCa recurrence was 79.3% in F-fluciclovine and 82.8% in Ga-PSMA-11 (P = 0.64). Local recurrence was detected in 37.9% on F-fluciclovine and in 27.6% on Ga-PSMA-11 (P = 0.03). Local pelvic lymph node recurrence was detected on F-fluciclovine versus Ga-PSMA-11 in 46.6% versus 50%, in extrapelvic lymph node metastases in 41.4% versus 51.7% and in bone metastases in 25.9% versus 36.2%. Lesion-based analysis showed identical findings in local pelvic lymph nodes in 39.7%, in extrapelvic lymph nodes in 22.4%, and in bone metastases in 13.8%. CONCLUSIONS: The advantage of F-fluciclovine is detecting curable localized disease in close anatomical relation to the urinary bladder, whereas Ga-PSMA-11 fails because of accumulation of activity in the urinary bladder. F-fluciclovine is almost equivalent to Ga-PSMA-11 in detecting distant metastases of PCa recurrence.

Medical and Dietary Uses of N-Acetylcysteine.

N-acetylcysteine (NAC), a plant antioxidant naturally found in onion, is a precursor to glutathione. It has been used as a drug since the 1960s and is listed on the World Health Organization (WHO) Model List of Essential Medicines as an antidote in poisonings. There are numerous other uses or proposed uses in medicine that are still in preclinical and clinical investigations. NAC is also used in food supplements and cosmetics. Despite its abundant use, there are projections that the NAC global market will grow in the next five years; therefore, the purpose of this work is to provide a balanced view of further uses of NAC as a dietary supplement. Although NAC is considered a safe substance, the results among clinical trials are sometimes controversial or incomplete, like for many other antioxidants. More clinical trials are underway that will improve our understanding of NAC applicability.