SPARC is a new myeloid-derived suppressor cell marker licensing suppressive activities

Myeloid-derived suppressor cells (MDSC) are well-known key negative regulators of the immune response during tumor growth, however scattered is the knowledge of their capacity to influence and adapt to the different tumor microenvironments and of the markers that identify those capacities. Here we show that the secreted protein acidic and rich in cysteine (SPARC) identifies in both human and mouse MDSC with immune suppressive capacity and pro-tumoral activities including the induction of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In mice the genetic deletion of SPARC reduced MDSC immune suppression and reverted EMT. Sparc−/− MDSC were less suppressive overall and the granulocytic fraction was more prone to extrude neutrophil extracellular traps (NET). Surprisingly, arginase-I and NOS2, whose expression can be controlled by STAT3, were not down-regulated in Sparc−/− MDSC, although less suppressive than wild type (WT) counterpart. Flow cytometry analysis showed equal phosphorylation of STAT3 but reduced ROS production that was associated with reduced nuclear translocation of the NF-kB p50 subunit in Sparc−/− than WT MDSC. The limited p50 in nuclei reduce the formation of the immunosuppressive p50:p50 homodimers in favor of the p65:p50 inflammatory heterodimers. Supporting this hypothesis, the production of TNF by Sparc−/− MDSC was significantly higher than by WT MDSC. Although associated with tumor-induced chronic inflammation, TNF, if produced at high doses, becomes a key factor in mediating tumor rejection. Therefore, it is foreseeable that an unbalance in TNF production could skew MDSC toward an inflammatory, anti-tumor phenotype. Notably, TNF is also required for inflammation-driven NETosis. The high level of TNF in Sparc−/− MDSC might explain their increased spontaneous NET formation as that we detected both in vitro and in vivo, in association with signs of endothelial damage. We propose SPARC as a new potential marker of MDSC, in both human and mouse, with the additional feature of controlling MDSC suppressive activity while preventing an excessive inflammatory state through the control of NF-kB signaling pathway

Sinonasal cancer and occupational exposure in a population-based registry.

We examined occupational exposures among subjects with sinonasal cancer (SNC) recorded in a population-based registry in the Lombardy Region, the most populated and industrialized Italian region. The registry collects complete clinical information and exposure to carcinogens regarding all SNC cases occurring in the population of the region. In the period 2008-2011, we recorded 210 SNC cases (137 men, 73 women). The most frequent occupational exposures were to wood (44 cases, 21.0%) and leather dust (29 cases, 13.8%), especially among men: 39 cases (28.5%) to wood and 23 cases (16.8%) to leather dust. Exposure to other agents was infrequent (<2%). Among 62 subjects with adenocarcinoma, 50% had been exposed to wood dust and 30.7% to leather dust. The proportions were around 10% in subjects with squamous cell carcinoma and about 20% for tumors with another histology. The age-standardized rates (×100,000 person-years) were 0.7 in men and 0.3 in women. Complete collection of cases and their occupational history through a specialized cancer registry is fundamental to accurately monitor SNC occurrence in a population and to uncover exposure to carcinogens in different industrial sectors, even those not considered as posing a high risk of SNC, and also in extraoccupational settings

Amyotrophic lateral sclerosis: a comparison of two staging systems in a population-based study

Background and purpose: To compare two recently developed staging systems for amyotrophic lateral sclerosis (ALS) [King's College and Milano-Torino staging (MITOS) systems] in an incident, population-based cohort of patients with ALS. Methods: Since 2009, a prospective registry has been recording all incident cases of ALS in the Emilia Romagna region in Italy. For each patient, detailed clinical information, including the ALS functional rating scale score, is collected at each follow-up. Results: Our study on 545 incident cases confirmed that King's College stages occurred at predictable times and were quite evenly spaced out throughout the disease course (occurring at approximately 40%, 60% and 80% of the disease course), whereas MITOS stages were mostly skewed towards later phases of the disease. In the King's College system there was a decrease in survival and an increase in deaths with escalating stages, whereas in the MITOS system survival curves pertaining to intermediate stages overlapped and the number of deaths was fairly homogenous throughout most stages. Conclusions: The King's College staging system had a higher homogeneity (i.e. smaller differences in survival among patients in the same stage) and a higher discriminatory ability (i.e. greater differences in survival among patients in different stages), being more suitable for individualized prognosis and for measuring efficacy of therapeutic interventions

Electron scattering mechanisms in fluorine-doped SnO2 thin films

Polycrystalline fluorine-doped SnO2 (FTO) thin films have been grown by ultrasonic spray pyrolysis on glass substrate. By varying growth conditions, several FTO specimens have been deposited and the study of their structural, electrical, and optical properties has been carried out. By systematically investigating the mobility as a function of carrier density, grain size, and crystallite size, the contribution of each physical mechanism involved in the electron scattering has been derived. A thorough comparison of experimental data and calculations allows to disentangle these different mechanisms and to deduce their relative importance. In particular, the roles of extended structural defects such as grain or twin boundaries as revealed by electron microscopy or x-ray diffraction along with ionized impurities are discussed. As a consequence, based on the quantitative analysis presented here, an experimental methodology leading to the improvement of the electro-optical properties of FTO thin films is reported. FTO thin films assuming an electrical resistivity as low as 3.7 center dot 10(-4)Omega cm (square sheet resistance of 8 Omega/square) while retaining good transmittance up to 86% (including substrate effect) in the visible range have been obtained. (c) 2013 AIP Publishing LLC

A semi-parametric approach to estimate risk functions associated with multi-dimensional exposure profiles: application to smoking and lung cancer

A common characteristic of environmental epidemiology is the multi-dimensional aspect of exposure patterns, frequently reduced to a cumulative exposure for simplicity of analysis. By adopting a flexible Bayesian clustering approach, we explore the risk function linking exposure history to disease. This approach is applied here to study the relationship between different smoking characteristics and lung cancer in the framework of a population based case control study

Exposure to benzene at work and the risk of leukemia: a systematic review and meta-analysis

Background A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have been heterogeneous. To bridge this gap in knowledge, we synthesized the existing epidemiologic evidence on the relation between occupational exposure to benzene and the risk of leukemia, including all types combined and the four main subgroups acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). Methods A systematic literature review was carried out using two databases 'Medline' and 'Embase' from 1950 through to July 2009. We selected articles which provided information that can be used to estimate the relation between benzene exposure and cancer risk (effect size). Results In total 15 studies were identified in the search, providing 16 effect estimates for the main analysis. The summary effect size for any leukemia from the fixed-effects model was 1.40 (95% CI, 1.23-1.57), but the study-specific estimates were strongly heterogeneous (I2 = 56.5%, Q stat = 34.47, p = 0.003). The random-effects model yielded a summary- effect size estimate of 1.72 (95% CI, 1.37-2.17). Effect estimates from 9 studies were based on cumulative exposures. In these studies the risk of leukemia increased with a dose-response pattern with a summary-effect estimate of 1.64 (95% CI, 1.13-2.39) for low (< 40 ppm-years), 1.90 (95% CI, 1.26-2.89) for medium (40-99.9 ppm-years), and 2.62 (95% CI, 1.57-4.39) for high exposure category (> 100 ppm-years). In a meta-regression, the trend was statistically significant (P = 0.015). Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95), medium (2.32, 95% CI, 0.91-5.94) to high exposure category (3.20, 95% CI, 1.09-9.45), but the trend was not statistically significant. Conclusions Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an increased risk of AML and CLL. The meta-analysis indicated a lack of association between benzene exposure and the risk of CML

Monolithically integrated DBR waveguidelaser and intensity modulator in erbiumdoped LiNbO3

For the first time, a DBR laser has been integrated with a Mach Zehnder intensity modulator in Er diffusion doped, Z cut LiNbO,, with Ti indiffused waveguides and dry etched Bragg gratings. The monolithically integrated device has a threshold of 54.8mW incident pump power (hp = 1480nm) and emits, in a single longitudinal mode, up to 0.65 mW CW output power at hs = 1561nm. The Mach-Zehnder type intensity modulator has an optical bandwidth > 3GHz

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde