Search results for " ras"

Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens?

2017

Postzygotic BRAF p.Lys601Asn Mutation in Phacomatosis Pigmentokeratotica with Woolly Hair Nevus and Focal Cortical Dysplasia

2016

International audience

A subset of flavaglines inhibits KRAS nanoclustering and activation.

2020

The RAS oncogenes are frequently mutated in human cancers and among the three isoforms (KRAS, HRAS and NRAS), KRAS is the most frequently mutated oncogene. Here, we demonstrate that a subset of flavaglines, a class of natural anti-tumour drugs and chemical ligands of prohibitins, inhibit RAS GTP loading and oncogene activation in cells at nanomolar concentrations. Treatment with rocaglamide, the first discovered flavagline, inhibited the nanoclustering of KRAS, but not HRAS and NRAS, at specific phospholipid-enriched plasma membrane domains. We further demonstrate that plasma membrane-associated prohibitins directly interact with KRAS, phosphatidylserine and phosphatidic acid, and these int…

Evaluación de la calidad de vida en personas drogodopendientes mediante el modelo de Rasch

2010

La Escala GENCAT aparece como el único instrumento que permite evaluar la calidad de vida individual de personas con drogodependencias desde una perspectiva diferente a la de calidad de vida relacionada con la salud (CVRS). Dado que las propiedades psicométricas de la mencionada escala sólo se han estudiado para la muestra general de usuarios de servicios sociales, este estudio tiene como objetivo analizar su fiabilidad y validez en un grupo específico de personas con drogodependencias. Para ello, se aplicó a 75 drogodependientes usuarios de servicios sociales en Cataluña. Los datos obtenidos permiten concluir que la escala, para este colectivo, presenta una adecuada consistencia interna (q…

Acute Effects of High-intensity Resistance Exercise on Cognitive Function

2021

The purpose of the present study was to examine the influence of an acute bout of high-intensity resistance exercise on measures of cognitive function. Ten men (Mean ± SD: age = 24.4 ± 3.2 yrs; body mass = 85.7 ± 11.8 kg; height = 1.78 ± 0.08 m; 1 repetition maximum (1RM) = 139.0 ± 24.1 kg) gave informed consent and performed a high-intensity 6 sets of 10 repetitions of barbell back squat exercise at 80% 1RM with 2 minutes rest between sets. The Automated Neuropsychological Assessment Metrics (ANAM) was completed to assess various cognitive domains during the familiarization period, immediately before, and immediately after the high-intensity resistance exercise bout. The repeated measures …

Diagnostic delay in oral squamous cell carcinoma: the role of cognitive and psychological variables

2014

This retrospective study investigated, in two cohorts of subjects living in Southern Italy and awaiting treatment for oral squamous cell carcinoma (OSCC), the variables related to diagnostic delay ascribable to the patient, with particular reference to the cognitive and psychological ones. A total of 156 patients with OSCC (mean age: 62 years, M/F: 2.39∶1) were recruited at the Universities of Palermo and Naples. Risk factors related to patient delay included: sociodemographic, health-related, cognitive and psychological variables. The analysis was conducted by considering two different delay ranges: dichotomous (≤1 month vs. >1 month) and polytomous (3 months) delay. Data were investigated…

High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice.

2008

Abstract Purpose. Several studies have suggested that KRAS somatic mutations may predict resistance to cetuximab- and panitumumab-based treatments in metastatic colorectal cancer (CRC) patients. Nevertheless, most experiences were conducted on samples from primaries. The aim of this study was to evaluate the grade of concordance in terms of KRAS status between primaries and related metastases. Patients and Methods. We analyzed KRAS codon 12 and 13 mutations from formalin-fixed sections of 107 CRC primaries and related metastases. Eight pairs were excluded from the analysis because of the low amount of tumor tissue in the available samples. The main characteristics were: 50 men, 49 women; me…

RAS mutations and cetuximab in locally advanced rectal cancer: Results of the EXPERT-C trial

2013

Background: RAS mutations predict resistance to anti-epidermal growthfactor receptor (EGFR) monoclonal antibodies in metastatic colorectal cancer. We analysed RAS mutations in 30 non-metastatic rectal cancer patients treated with or without cetuximab within the 31 EXPERT-C trial. Methods: Ninety of 149 patients with tumours available for analysis were KRAS/BRAF wild-type, and randomly assigned to capecitabine plus oxaliplatin (CAPOX) followed by chemoradiotherapy, surgery and adjuvant CAPOX or the same regimen plus cetuximab (CAPOX-C). Of these, four had a mutation of NRAS exon 3, and 84 were retrospectively analysed for additional KRAS (exon 4) and NRAS (exons 2/4) mutations by using bi-di…

Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer

2015

Abstract Tumor growth in the context of EGFR inhibitor resistance may remain EGFR-dependent and is mediated by mechanisms including compensatory ligand upregulation and de novo gene alterations. Sym004 is a two-antibody mixture targeting nonoverlapping EGFR epitopes. In preclinical models, Sym004 causes significant EGFR internalization and degradation, which translates into superior growth inhibition in the presence of ligands. In this phase I trial, we observed grade 3 skin toxicity and hypomagnesemia as mechanism-based dose-limiting events during dose escalation. In dose-expansion cohorts of 9 and 12 mg/kg of Sym004 weekly, patients with metastatic colorectal cancer and acquired EGFR inhi…

Rasch scalability of the somatosensory amplification scale: a mixture distribution approach.

2012

Abstract Objective Somatosensory amplification refers to a person's tendency to experience somatic sensations as inappropriately intense and involves hypervigilance concerning bodily sensations. We applied the Somatosensory Amplification Scale (SSAS) in an Internet sample of young adults (N = 3031) to test whether the SSAS is Rasch scalable. Methods We applied mixture distribution extensions of the partial credit and rating scale models to identify possible subgroups that use the response set of the SSAS in different ways. Results A partial credit model, with two latent classes, showed a superior fit to all other models. Still, one of the SSAS items had to be removed because it showed sever…