Tumor size, stage and grade alterations of urinary peptidome in RCC

Background: Several promising biomarkers have been found for RCC, but none of them has been used in clinical practice for predicting tumour progression. The most widely used features for predicting tumour aggressiveness still remain the cancer stage, size and grade. Therefore, the aim of our study is to investigate the urinary peptidome to search and identify peptides whose concentrations in urine are linked to tumour growth measure and clinical data. Methods: A proteomic approach applied to ccRCC urinary peptidome (n = 117) based on prefractionation with activated magnetic beads followed by MALDI-TOF profiling was used. A systematic correlation study was performed on urinary peptide profiles obtained from MS analysis. Peptide identity was obtained by LC-ESI-MS/MS. Results: Fifteen, twenty-six and five peptides showed a statistically significant alteration of their urinary concentration according to tumour size, pT and grade, respectively. Furthermore, 15 and 9 signals were observed to have urinary levels statistically modified in patients at different pT or grade values, even at very early stages. Among them, C1RL, A1AGx, ZAG2G, PGBM, MMP23, GP162, ADA19, G3P, RSPH3, DREB, NOTC2 SAFB2 and CC168 were identified. Conclusions: We identified several peptides whose urinary abundance varied according to tumour size, stage and grade. Among them, several play a possible role in tumorigenesis, progression and aggressiveness. These results could be a useful starting point for future studies aimed at verifying their possible use in the managements of RCC patients

Minimally-invasive treatments for benign thyroid nodules: a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group

Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS 643) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and 6580% nodule volume ablation is expected (LoE = 3)

The AGILE Mission

AGILE is an Italian Space Agency mission dedicated to observing the gamma-ray Universe. The AGILE's very innovative instrumentation for the first time combines a gamma-ray imager (sensitive in the energy range 30 MeV-50 GeV), a hard X-ray imager (sensitive in the range 18-60 keV), a calorimeter (sensitive in the range 350 keV-100 MeV), and an anticoincidence system. AGILE was successfully launched on 2007 April 23 from the Indian base of Sriharikota and was inserted in an equatorial orbit with very low particle background. Aims. AGILE provides crucial data for the study of active galactic nuclei, gamma-ray bursts, pulsars, unidentified gamma-ray sources, galactic compact objects, supernova remnants, TeV sources, and fundamental physics by microsecond timing. Methods. An optimal sky angular positioning (reaching 0.1 degrees in gamma- rays and 1-2 arcmin in hard X-rays) and very large fields of view (2.5 sr and 1 sr, respectively) are obtained by the use of Silicon detectors integrated in a very compact instrument. Results. AGILE surveyed the gamma- ray sky and detected many Galactic and extragalactic sources during the first months of observations. Particular emphasis is given to multifrequency observation programs of extragalactic and galactic objects. Conclusions. AGILE is a successful high-energy gamma-ray mission that reached its nominal scientific performance. The AGILE Cycle-1 pointing program started on 2007 December 1, and is open to the international community through a Guest Observer Program

Identification by MS/MS of disulfides produced by a functional redox transition.

Among posttranslational modifications of proteins entailed with signal transduction, the redox transition is today brought to the focus as a major biochemical event accounting for the signaling functions of reactive oxygen species. Thermodynamic and kinetic criteria highlight hydroperoxides and protein disulfides as signaling and transducer elements, respectively, and growing biochemical evidence supports this notion. The protein Cys residue involved in this function must react fast and specifically with the oxidant and then with a second accessible Cys yielding the disulfide. These kinetic and structural constraints are shared with peroxidases and peroxiredoxins, which are competitors for the signaling hydroperoxide. In this chapter, a procedure based on MS/MS analysis for inter- and intrachain disulfide assignment in proteins undergoing redox-switch is presented. While the sensitivity of the modern MS/MS instruments permits the sequencing of double peptides linked by a disulfide bond, the major pitfall of the proteomic procedure is the thiol disulfide scrambling taking place at the alkaline pH needed for the proteolytic reaction of trypsin. Instead, the use of pepsin at acidic pH prevents the disulfide scrambling, but the specificity of the proteolytic reaction is low and thus the complexity of fragmentation increases. We succeeded to limit this problem by heuristically assuming a conserved pepsin cleavage pattern of the protein both in the oxidized and the reduced form. Asymmetric cleavage of the disulfide by collisional fragmentation further corroborated the identification. In conclusion, the use of pepsin, integrated by a minimal computation, appears suitable for positively assigning inter- and intrachain disulfides generated by a functional redox-switch