Search results for "Cause"
showing 10 items of 6525 documents
The Role of ERK Signaling in Experimental Autoimmune Encephalomyelitis
2017
Extracellular signal-regulated kinase (ERK) signaling plays a crucial role in regulating immune cell function and has been implicated in autoimmune disorders. To date, all commercially available inhibitors of ERK target upstream components, such as mitogen-activated protein (MAP) kinase/ERK kinase (MEKs), but not ERK itself. Here, we directly inhibit nuclear ERK translocation by a novel pharmacological approach (Glu-Pro-Glu (EPE) peptide), leading to an increase in cytosolic ERK phosphorylation during T helper (Th)17 cell differentiation. This was accompanied by diminished secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine influencing the encephalitogenicity …
Trends of extended-spectrum β-lactamase-producing Escherichia coli sequence type 131 and its H30 subclone in a French hospital over a 15-year period.
2016
International audience; Sequence type 131 (ST131) is a predominant lineage among extraintestinal pathogenic Escherichia coli. It plays a major role in the worldwide dissemination of E. coli producing extended-spectrum β-lactamases (ESBLs). Here we describe the long-term epidemiology of this clonal group in a French university hospital, where the incidence of ESBL-producing E. coli has increased from 0.018 case per 1000 patient-days in the year 2000 to 0.50 case per 1000 patient-days in 2014. The first of the 141 ST131 isolates was recovered in 2006, and the ST131 clonal group accounted for 18.1% of total ESBL-producing E. coli over the whole period (2000-2014). Subclonal typing showed that …
Venlafaxine prevents morphine antinociceptive tolerance: The role of neuroinflammation and the l-arginine-nitric oxide pathway.
2017
Abstract Opioid-induced neuroinflammation and the nitric oxide (NO) signal-transduction pathway are involved in the development of opioid analgesic tolerance. The antidepressant venlafaxine (VLF) modulates NO in nervous tissues, and so we investigated its effect on induced tolerance to morphine, neuroinflammation, and oxidative stress in mice. Tolerance to the analgesic effects of morphine were induced by injecting mice with morphine (50 mg/kg) once a day for three consecutive days; the effect of co-administration of VLF (5 or 40 mg/kg) with morphine was similarly tested in a separate group. To determine if the NO precursor l -arginine hydrochloride ( l -arg) or NO are involved in the effec…
Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.
2019
Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…
Treatment patterns for metastatic colorectal cancer in Spain
2020
Abstract Purpose The primary aim of this retrospective study was to describe the treatment patterns according to the type of treatment received by patients with metastatic colorectal cancer (mCRC) in Spain. Methods This was a retrospective, observational, multicenter study performed by 33 sites throughout Spain that included consecutive patients aged 18 years or older who had received or were receiving treatment for mCRC. Results At the time of inclusion, of the 873 evaluable patients, 507 (58%) had received two lines, 235 (27%) had received three lines, 106 (12%) had received four lines, and the remaining patients had received up to ten lines. The most frequent chemotherapy schemes were th…
A multidimensional network approach reveals microRNAs as determinants of the mesenchymal colorectal cancer subtype
2016
Colorectal cancer (CRC) is a heterogeneous disease posing a challenge for accurate classification and treatment of this malignancy. There is no common genetic molecular feature that would allow for the identification of patients at risk for developing recurrences and thus selecting patients who would benefit from more stringent therapies still poses a major clinical challenge. Recently, an international multicenter consortium (CRC Subtyping Consortium) was established aiming at the classification of CRC patients in biologically homogeneous CRC subtypes. Four consensus molecular subtypes (CMSs) were identified, of which the mesenchymal CMS4 presented with worse prognosis signifying the impor…
Exome-wide somatic mutation characterization of small bowel adenocarcinoma
2018
Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003–2011. Paired-end exome sequencing was…
Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer
2016
Background:This single-arm phase II study investigated the EGFR monoclonal antibody necitumumab plus modified FOLFOX6 (mFOLFOX6) in first-line treatment of locally advanced or metastatic colorectal cancer (mCRC).Methods:Patients received 800-mg intravenous necitumumab (day 1; 2-week cycles), followed by oxaliplatin 85 mg m -2, folinic acid 400 mg m -2, and 5-fluorouracil (400 mg m -2 bolus then 2400 mg m -2 over 46 h). Radiographic evaluation was performed every 8 weeks until progression. Primary endpoint was objective response rate.Results:Forty-four patients were enrolled and treated. Objective response rate was 63.6% (95% confidence interval 47.8-77.6); complete response was observed in …
JC Virus and Lung Adenocarcinoma: Fact or Myth?
2017
Background/aim An association has been reported between lung cancer and John Cunningham (JC) virus infection. The aim of this study was to evaluate the prevalence of JC virus in a small cohort of patients with lung adenocarcinoma and assess its presence in nodal metastasis. Materials and methods Consecutive samples of 13 surgically-removed lung tumors and 13 surrounding normal cancer-free tissues were selected. Five cases included metastatic lymph nodes. JC virus infection was assessed through nested PCR. Results Seven out of thirteen patients with lung adenocarcinoma had a positive PCR test for JC virus. One of the five patients with nodal metastasis had a positive PCR test for JC virus. N…
Plasma heme oxygenase-1 is decreased in peripheral artery disease patients.
2016
Peripheral artery disease (PAD) is a common manifestation of atherosclerosis. A number of emerging risk factors, including oxidative stress biomarkers, free radicals and heat shock proteins, may add to the established risk factors for cardiovascular disease (CVD). The present study assessed surrogate markers of oxidative stress, including total reduced glutathione (GSH), lipid hydroperoxides (LOOH), isoprostanes, heme oxygenase‑1 (HO‑1) and metabolic biomarkers, such as adiponectin and lactate, in PAD patients (n=27). Healthy age‑matched volunteers (n=27) served as controls. GSH and LOOH were evaluated by measuring total thiol groups and iron oxidation, respectively, by spectrophotometric a…