Search results for "death"
showing 10 items of 1744 documents
Prognostic value of FEV1/FEV6 in elderly people
2010
BACKGROUND: The ratio of forced expiratory volume in 1 s and forced expiratory volume in 6 s (FEV1/FEV6) has been proposed as an alternative for FEV1/forced vital capacity (FVC) to diagnose obstructive diseases with less effort during spirometry; however, its prognostic value is unknown. We evaluated whether FEV1/FEV6 is a significant predictor of mortality in elderly subjects and compared its prognostic value with that of FEV1/FVC and FEV1. METHODS: One thousand nine hundred and seventy-one subjects, aged >65 years, participated in the population-based SA.R.A. study. During the baseline exam, a multidimensional assessment included spirometry. Vital status was determined during 6 years of f…
Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors
2013
Abstract The success in lung cancer therapy with programmed death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between EGF receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, CTL antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased CTLs and increased markers of T-cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T-cell function and lowering the levels of tumor-promoting cytokines. Expression of m…
Long-term effect of arsenic exposure: Results from an occupational cohort study
2018
Background In 1976 in Manfredonia (Italy), arsenic was released into the atmosphere due to an accident in a petrochemical plant. We aimed to analyze the mortality of workers involved in the factory for the site cleaning activities. Methods The cohort consisted of 1467 workers grouped into contract, fertilizer, and plastic workers. The outcome of interest was mortality for specific causes. Standardized mortality ratios (SMR) and 95% confidence intervals (95%CI) were computed. Results For all workers and all causes of death combined, the SMR was less than 1.0. Mortality ratios were increased for malignant neoplasms of the pleura, bone and melanoma of the skin. Contract workers, the group most…
Oestradiol or genistein rescues neurons from amyloid beta-induced cell death by inhibiting activation of p38.
2007
Oestrogenic compounds have been postulated as neuroprotective agents. This prompted us to investigate their mechanism action in neurons in primary culture. Cells were pretreated with physiological concentrations of 17-beta estradiol (0.2 nm) or with nutritionally relevant concentrations of genistein (0.5 microm), and 48 h later treated with 5 microm of amyloid beta (Abeta) for 24 h. We found that Abeta increased oxidative stress, measured as peroxide levels or oxidized glutathione/reduced glutathione ratio, which in turn, caused phosphorylation of p38 MAP kinase. Amyloid beta subsequently induced neuronal death. Inhibiting the MAP kinase pathway prevented cell death, confirming the role of …
Neuroprotection elicited by P2Y13 receptors against genotoxic stress by inducing DUSP2 expression and MAPK signaling recovery.
2014
AbstractNucleotides activating P2Y13 receptors display neuroprotective actions against different apoptotic stimuli in cerebellar granule neurons. In the present study, P2Y13 neuroprotection was analyzed in conditions of genotoxic stress. Exposure to cisplatin and UV radiation induced caspase-3-dependent apoptotic cell death, and p38 MAPK signaling de-regulation. Pre-treatment with P2Y13 nucleotide agonist, 2methyl-thio-ADP (2MeSADP), restored granule neuron survival and prevented p38 long-lasting activation induced by cytotoxic treatments. Microarray gene expression analysis in 2MeSADP-stimulated cells revealed over-representation of genes related to protein phosphatase activity. Among them…
IAPs and cell migration.
2015
Inhibitors of apoptosis (IAPs) constitute a family of cell signaling regulators controlling several fundamental biological processes such as innate immunity, inflammation, cell death, cell proliferation, and cell differentiation. Increasing evidence from in vivo and in vitro studies indicate a function for IAPs in the modulation of invasive and migratory properties of cells. Here, we present and discuss the mechanisms whereby IAPs can control cell migration.
Characteristic ERK Signaling Dynamics Distinguishes Necroptosis from Apoptosis
2021
ERK involvement in cell death remains unclear, although many studies have demonstrated the importance of ERK dynamics in determining cellular responses. To untangle ERK’s contribution in two cell death programs, we investigated ERK signaling dynamics during hFasL-induced apoptosis and TNF-induced necroptosis in L929sAhFas cells. We observed that ERK inhibition sensitizes cells to apoptosis while delaying necroptosis. By monitoring ERK activity by live-cell imaging using an improved ERK biosensor (EKAR4.0), we reported differential ERK signaling dynamics between cell survival, apoptosis, and necroptosis. We also decrypted a temporally shifted amplitude- and frequency-modulated (AM/FM) ERK ac…
The role of death effector domain (DED)-containing proteins in acute oxidative cell injury in hepatocytes
2012
Abstract Apoptosis is a mechanism that regulates hepatic tissue homeostasis and contributes to both acute and chronic injury in liver disease. The apoptotic signaling cascade involves activation of the death-inducing signaling complex (DISC) and subsequent recruitment of proteins containing death effector domains (DED), which regulate downstream effector molecules. Prominent among these are the Fas-associated death domain (FADD) and the cellular caspase 8-like inhibitory protein (cFLIP), and alterations in these proteins can lead to severe disruption of physiological processes, including acute liver failure or hepatocellular carcinoma. Their role in cell signaling events independent of the …
Trefoil factor TFF1-induced protection of conjunctival cells from apoptosis at premitochondrial and postmitochondrial levels.
2008
PURPOSE. Goblet cells of the conjunctival epithelium synthesize and secrete TFF1 (Trefoil factor 1), a small protease-resistant peptide that, together with mucins, is responsible for the rheologic properties of the tear film. This study aimed to determine whether TFF1, whose synthesis increases in inflammatory conditions such as pterygium, could protect conjunctival cells from apoptosis. METHODS. Chang conjunctival cells, either wild-type or expressing TFF1 through stable transfection, were exposed to benzalkonium chloride (BAK) and ultraviolet (UV) irradiation to trigger apoptosis. The authors used cell fractionation to detect lipid raft‐associated proteins, coimmunoprecipitation to explor…
Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1 and 2.
2006
International audience; Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family that induces cancer cell death by apoptosis with some selectivity. TRAIL-induced apoptosis is mediated by the transmembrane receptors death receptor 4 (DR4) (also known as TRAIL-R1) and DR5 (TRAIL-R2). TRAIL can also bind decoy receptor 1 (DcR1) (TRAIL-R3) and DcR2 (TRAIL-R4) that fail to induce apoptosis since they lack and have a truncated cytoplasmic death domain, respectively. In addition, DcR1 and DcR2 inhibit DR4- and DR5-mediated, TRAIL-induced apoptosis and we demonstrate here that this occurs through distinct mechanisms. While DcR1 prevents the assembly of the…