Leptin involvement in the survival of pancreatic adenocarcinoma patients with obesity and diabetes.

OBJECTIVE: Current molecular characterization of pancreatic ductal adenocarcinoma (PDAC) does not incorporate the host reaction to cancer cells and cannot predict the response to chemo- or immunotherapy. Leptin is an adipokine involved in regulating energy balance with a possible role in the development of obesity-associated cancers, but its relationship with other pathways in pancreatic carcinogenesis has not been established yet. The aim of this prospective study was to assess the involvement of leptin and phosphoinositide 3-kinase (PI3K) in the survival of overweight and/or diabetic patients with PDAC. PATIENTS AND METHODS: A total of 112 patients were included, 56 diagnosed with PDAC and 56 age and sex-matched healthy controls, with a maximum follow-up of 24-months. The circulating leptin, interleukin 1-beta, tumor factor necrosis-alpha, and PI3K were measured by enzyme-linked immunosorbent assay (ELISA). A multivariate Cox regression model was used to determine the factors influencing survival. RESULTS: The serum levels of leptin [38.5 (31.6-47.0) pg/ml] and other cytokines in PDAC patients were similar to controls, irrespective of the presence of diabetes. No significant correlation between the biomarkers was found. In obese and overweight patients, the leptin level and survival rate were lower than in non-obese patients. CONCLUSIONS: The leptin level was not associated with the presence of PDAC, although it was lower in obese and overweight patients who had lower survival. No association with inflammatory biomarkers or PI3K was noted. Furthermore, leptin levels had no independent role in survival, suggesting that the prognostic role of obesity in PDAC is based on a different pathway.

Mitochondrial proteomics profile points oxidative phosphorylation as main target for beauvericin and enniatin B mixture.

Beauvericin (BEA) and enniatin B (EN B) are non-legislated Fusarium mycotoxins usually found in cereal and cereal-based products all around the world. By the proteomic analysis of mitochondria enriched extracts from Jurkat cells exposed for 24 h to three concentrations of BEA:EN B (0.01-0.1-0.5 µM), a number of 1821 proteins (202 mitochondrial) were identified and relatively quantified. 340 proteins (59 mitochondrial) were statistically significant altered in our samples (Anova p-value ≤ 0.05 and fold change (FC) ≥1.5). The protein mitochondrial translational release factor 1 like (MTRF1L) was the most abundant protein in the three mycotoxin exposures studied. The mycotoxins mixture exposure induced concentration dependent changes at mitochondrial proteins levels that mainly involve inner and outer membrane complexes, Electron Transport Chain (ETC) and ribosomes. These results showed alteration of proteins levels related to oxidative phosphorylation, metabolic and neurodegenerative diseases related pathways.