Correlation Between Immune-related Adverse Event (IRAE) Occurrence and Clinical Outcome in Patients With Metastatic Renal Cell Carcinoma (mRCC) Treated With Nivolumab: IRAENE Trial, an Italian Multi-institutional Retrospective Study.

BACKGROUND: Immunotherapy has brought clinical benefits to patients with metastatic renal cell cancer (mRCC). Most patients tolerate immunotherapy but serious immune-related adverse events (irAEs) have been reported. Some studies indicate a correlation between irAEs and clinical response in other cancer types (eg, lung cancer and melanoma). For patients with mRCC, the impact of irAE on clinical outcome is unknown. PATIENTS AND METHODS: A retrospective review of 167 patients with mRCC treated with nivolumab as standard of care between March 2017 and January 2018 in 16 Italian centers was performed. irAEs were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. RESULTS: Any grade and grade 3/4 irAEs occurred in 46% and 8.9% of patients, respectively. The median time to appearance of irAEs was 10 weeks; 38.8% of patients required steroid treatment. The most common irAEs were cutaneous (33.7%) and gastrointestinal (23.3%). The median overall survival and progression-free survival were 20.13 and 7.86 months, respectively. Patients with irAEs showed a greater overall survival (hazard ratio, 0.38; 95% confidence interval [CI], 0.23-0.63) and progression-free survival (hazard ratio, 0.44; 95% CI, 0.29-0.66) benefit as well as better overall response rate (27.3% vs. 13.7%; odds ratio, 2.36; 95% CI, 1.03-5.44) and disease control rate (68.8% vs. 48%; odds ratio, 2.4; 95% CI, 1.23-4.67) if compared with those without irAEs. No correlation was found between steroid use and clinical outcomes. CONCLUSIONS: Our analysis revealed that the appearance of irAEs was associated with better outcomes in patients treated with nivolumab. This data may be limited by sample size and the retrospective nature of the study.

Metabolic characterization and antioxidant activity in sweet cherry (Prunus avium L.) Campania accessions: Metabolic characterization of sweet cherry accessions.

The failure of the antioxidant scavenging system in advanced ripening stages, causing oxidative stress, is one of the most important factor of fruit decay. Production of rich antioxidant fruit could represent a way to delay fruit senescence and preserve its characteristics. We investigated the antioxidant metabolites (ascorbate, glutathione, tocopherols, and polyphenols) and enzymes (ascorbic peroxidases, peroxidases and polyphenol oxidases) involved in the antioxidant response in forty-three accessions of sweet cherry fruits from Campania region. Our results highlight accessions with high antioxidant metabolites contents but low enzymatic activities. These represent important factors in both pre- and post-harvest on the qualitative and nutritional characteristics of sweet cherry. Observed differences are probably due to endogenous characteristics making these accessions particularly interesting for breeding programs aimed to improve fruit quality and shelf-life and for addressing the cultivation of a specific characterized cultivar based on the intended use, fresh consumption or processed products.

Dataset on antioxidant metabolites and enzymes activities of freshly harvested sweet cherries (Prunus avium L.) of Campania accessions.

In this article, we reported the original data obtained by the study of metabolites and enzymes involved in sweet cherry antioxidant system. We measured hydrogen peroxide (H2O2) and malondialdehyde (MDA), which are indicator of oxidative stress. Moreover, we measured the concentration of reduced and oxidized ascorbate and glutathione that are involved in ROS detoxification together with phenolics, anthocyanins and tocopherols. Among antioxidant enzymes, we analyzed the activities of ascorbate peroxidase (APX; EC 1.11.1.11), and the soluble and bound forms of polyphenol oxidase (PPO; EC 1.10.3.1) and guaiacol peroxidase (POD; EC 1.11.1.7). The data reported in this paper are related to the research article "Metabolic characterization and antioxidant activity in sweet cherry (Prunus avium L.) Campania accessions", authored by Mirto et al. (2018) [1].

Pioppino mushroom in southern Italy: an undervalued source of nutrients and bioactive compounds.

BACKGROUND: Agrocybe aegerita (V. Brig.) Singer, commonly known as Pioppino, is a popular edible mushroom, known in the Campania Region (Italy). Despite its habitual consumption, little nutritional and biochemical information is available. Thus, nutritional values, anti-radical properties and chemical composition of the wild Pioppino were compared to those of the cultivated Agaricus bisporus (J.E. Lange) Imbach (known as Champignon), equally analysed. RESULTS: Macronutrient components (proteins, carbohydrates and lipids), free and protein amino acids and fatty acid content of poplar mushroom were achieved. Total phenol content of a defatted Pioppino alcoholic extract (PM) was determined, whereas DPPH and ABTS methods were applied to determine the radical scavenging capabilities of the extract. Ferricyanide and ORAC-fluorescein methods were also performed. Finally, LC-HRMS was used to identify and quantify the main metabolites in the extract. PM was mainly constituted of disaccharides, hexitol derivatives and malic acid. Coumaric acid isomers and C6 C1 compounds were also detected. CONCLUSION: All data revealed that wild Pioppino is an excellent functional food, by far exceeding that of the Champignon. Therefore, these data are useful to promote the consumption of this mushroom encouraging thus its biological cultivation, due to wild availability is strongly compromised by the extensive use of fungicides. © 2017 Society of Chemical Industry.

Durum wheat seedling responses to simultaneous high light and salinity involve a fine reconfiguration of amino acids and carbohydrate metabolism.

Durum wheat plants are extremely sensitive to drought and salinity during seedling and early development stages. Their responses to stresses have been extensively studied to provide new metabolic targets and improving the tolerance to adverse environments. Most of these studies have been performed in growth chambers under low light [300-350 µmol m-2 s-1 photosynthetically active radiation (PAR), LL]. However, in nature plants have to face frequent fluctuations of light intensities that often exceed their photosynthetic capacity (900-2000 µmol m-2 s-1 ). In this study we investigated the physiological and metabolic changes potentially involved in osmotic adjustment and antioxidant defense in durum wheat seedlings under high light (HL) and salinity. The combined application of the two stresses decreased the water potential and stomatal conductance without reducing the photosynthetic efficiency of the plants. Glycine betaine (GB) synthesis was inhibited, proline and glutamate content decreased, while γ-aminobutyric acid (GABA), amides and minor amino acids increased. The expression level and enzymatic activities of Δ1-pyrroline-5-carboxylate synthetase, asparagine synthetase and glutamate decarboxylase, as well as other enzymatic activities of nitrogen and carbon metabolism, were analyzed. Antioxidant enzymes and metabolites were also considered. The results showed that the complex interplay seen in durum wheat plants under salinity at LL was simplified: GB and antioxidants did not play a main role. On the contrary, the fine tuning of few specific primary metabolites (GABA, amides, minor amino acids and hexoses) remodeled metabolism and defense processes, playing a key role in the response to simultaneous stresses.

Valle Agricola lentil, an unknown lentil (Lens culinaris Medik.) seed from Southern Italy as a novel antioxidant and prebiotic source.

In order to promote 'Valle Agricola' lentil, an autochthonous lentil of the Campania Region, a thorough investigation of its biochemical and nutritional properties has been carried out. The macronutrient content (proteins, carbohydrates and lipids), free and total amino acids, and unsaturated fatty acids were determined. The antioxidant capability of raw 'Valle Agricola' lentils, as well as of boiled ones, was estimated in terms of their total phenol content (TPC), ORAC value, and free radical scavenging capacities using DPPH and ABTS assays. The data obtained evidenced that the boiling process slightly decreased Valle Agricola lentil's antioxidant power. Furthermore, when trypsin and chymotrypsin inhibitory activities were measured, a large decrease of the levels of anti-nutritional factors was estimated. In order to have a phytochemical overview of this autochthonous lentil seed, LC-ESI-MS/MS analysis was applied to raw and boiled lentil extracts. Flavonol glycosides and free flavanols, as well as typical seed prebiotic saccharides, were the most representative constituents.