Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.
PD-L1 does not appear to be a prognostic marker or influence survival in GBC patients. However, PD-L1 expression occurs in one of four GBCs, supporting the future possibility of immune-modulation therapy to improve the dismal overall survival.
Gall bladder Carcinoma (GBC) is the fifth most common cancer of the digestive tract and frequently diagnosed in late stage of disease. Estimation of circulating free DNA (cfDNA) in serum has been applied as a "liquid biopsy" in several deep seated malignancies. Its value in diagnosis of gall bladder carcinoma has not been studied. The present study was designed to assess the role of cfDNA in the diagnosis of GBC and correlate levels with the TNM stage. Serum was collected from 34 patients with GBC and 39 age and sex matched controls including 22 cholecystitis and 17 healthy individuals. Serum cfDNA levels were measured through quantitative polymerase chain reaction (qPCR) by amplification of β-globin gene. Performance of the assay was calculated through the receiver operating characteristic (ROC) curve. The cfDNA level was significantly lower in healthy controls and cholecystitis (89.32 ± 59.76 ng/ml, 174.21 ± 99.93 ng/ml) compared to GBC (1245.91 ± 892.46 ng/ml, p = <0.001). The cfDNA level was significantly associated with TNM stage, lymph node involvement and jaundice (0.002, 0.027, and 0.041, respectively). Area under curve of ROC analysis for cancer group versus healthy and cholecystitis group was 1.00 and 0.983 with sensitivity of 100 %, 88.24 % and specificity of 100 % respectively. Quantitative analysis of cfDNA may distinguish cholecystitis and gall bladder carcinoma and may serve as new diagnostic, noninvasive marker adjunct to imaging for the diagnosis of GBC.
The current study investigates the role of circulating free DNA (cfDNA) as a liquid biopsy in diagnosis gall bladder carcinoma (GBC) utilizing levels of long DNA fragments (ALU247) derived from tumor necrosis, short apoptotic fragments (ALU115) denoting total cfDNA and cfDNA integrity denoting ratio of ALU247 and ALU115. The global methylation status of cfDNA was also estimated with the hypothesis that these parameters provide a diagnostic distinction between cancer and non-cancer subjects, with higher or altered values favoring presence of malignancy. Study group included 60 cases of GBC and 36 controls including diseased controls (cholecystitis) and healthy subjects. Median levels of ALU115, ALU247 and cfDNA integrity were significantly different in GBC at 1790.88, 673.75, 0.4718 vs. controls at 840.73, 165.03, 0.1989 ng/ml respectively. Global DNA methylation was not significantly different between GBC at 0.679% and controls at 0.695%. The sensitivity and specificity of ALU 247 in discriminating GBC from controls was highest with a sensitivity, specificity and diagnostic accuracy of 80.0%, 86.1% and 82.2% respectively. Global DNA methylation showed lowest sensitivity of 55.0% and specificity of 50.0%. Clinico-pathological parameters showing significant association with cfDNA integrity, on ROC curve analysis, showed significant diagnostic discrimination of the tumor stage, lymphovascular invasion, disease stage and grade histology. This is a first time analysis of ALU115, ALU247 and cfDNA integrity in the diagnosis of GBC and confirms that the combination of ALU247 and cfDNA integrity provides good sensitivity, specificity and diagnostic accuracy in discriminating GBC from controls as well correlates with aggressive disease parameters.
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