Search results for "IS Method"
showing 10 items of 730 documents
Non-small cell lung cancer (NSCLC), EGFR downstream pathway activation and TKI targeted therapies sensitivity: Effect of the plasma membrane-associat…
2017
Adenocarcinoma of Non-Small Cell Lung Cancer (NSCLC) is a severe disease. Patients carrying EGFR mutations may benefit from EGFR targeted therapies (e.g.: gefitinib). Recently, it has been shown that sialidase NEU3 directly interacts and regulates EGFR. In this work, we investigate the effect of sialidase NEU3 overexpression on EGFR pathways activation and EGFR targeted therapies sensitivity, in a series of lung cancer cell lines. NEU3 overexpression, forced after transfection, does not affect NSCLC cell viability. We demonstrate that NEU3 overexpression stimulates the ERK pathway but this activation is completely abolished by gefitinib treatment. The Akt pathway is also hyper-activated upo…
Rational Design of a Carrier Protein for the Production of Recombinant Toxic Peptides in Escherichia coli
2016
Commercial uses of bioactive peptides require low cost, effective methods for their production. We developed a new carrier protein for high yield production of recombinant peptides in Escherichia coli very well suited for the production of toxic peptides like antimicrobial peptides. GKY20, a short antimicrobial peptide derived from the C-terminus of human thrombin, was fused to the C-terminus of Onconase, a small ribonuclease (104 amino acids), which efficiently drove the peptide into inclusion bodies with very high expression levels (about 200-250 mg/L). After purification of the fusion protein by immobilized metal ion affinity chromatography, peptide was obtained by chemical cleavage in d…
Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohor…
2015
Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the i…
Mediterranean diet adherence and synergy with acute myocardial infarction and its determinants: A multicenter case-control study in Italy
2018
Background Cardiovascular diseases are the leading causes of mortality and morbidity in Western countries. The possible synergistic effect of poor adherence to a Mediterranean diet (MD) and other risk factors for acute myocardial infarction (AMI) such as hypertension, cholesterol, ever smoker, BMI> 25, diabetes, has not been deeply studied. Design Case-control study. Methods Patients with first AMI and controls from four tertiary referral Italian centers were screened for enrolment. Dietary information was collected through a questionnaire and a MD adherence score was calculated. Physical activity and smoking habits were also registered. The Synergy Index was calculated according to Rothman…
Factors influencing psychological well-being in patients with Parkinson's disease.
2017
Background Both motor and non-motor symptoms could contribute to significant deterioration of psychological well-being in patients with Parkinson's disease (PD). However, its assessment has been only indirectly evaluated using tools based on health-related quality of life (HRQoL), such as the PDQ-39 scale. Objectives To evaluate psychological well-being in PD using a specific tool of assessment, the Psychological Well-being Scale (PWS), and its clinical correlates. Methods This article reports data of patients' perception of health state, as measured by means of the PWS, from an epidemiological, cross-sectional study conducted in Italian PD patients (FORTE Study). We tested possible relatio…
Factors associated with first- versus second-generation long-acting antipsychotics prescribed under ordinary clinical practice in Italy
2018
Background For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy. Methods The STAR Network "Depot" Study is an observational, longitudinal…
In silico identification and experimental validation of hits active against KPC-2 β-lactamase
2018
Bacterial resistance has become a worldwide concern, particularly after the emergence of resistant strains overproducing carbapenemases. Among these, the KPC-2 carbapenemase represents a significant clinical challenge, being characterized by a broad substrate spectrum that includes aminothiazoleoxime and cephalosporins such as cefotaxime. Moreover, strains harboring KPC-type β-lactamases are often reported as resistant to available β-lactamase inhibitors (clavulanic acid, tazobactam and sulbactam). Therefore, the identification of novel non β-lactam KPC-2 inhibitors is strongly necessary to maintain treatment options. This study explored novel, non-covalent inhibitors active against KPC-2, …
Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens
2017
Background Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results HCV-RNA kinetics was biphasic, reflecting …
Internal limiting membrane peeling versus no peeling during primary vitrectomy for rhegmatogenous retinal detachment: A systematic review and meta-an…
2018
Background Internal limiting membrane (ILM) peeling during primary vitrectomy for rhegmatogenous retinal detachment (RRD) prevents the formation of postoperative macular epiretinal membrane (ERM). However, studies that compared vitrectomy with and without ILM peeling for RRD, have reported controversial outcomes. Objective To assess the efficacy of ILM peeling versus non-ILM peeling during vitrectomy for RRD by a systematic review and meta-analysis of published studies. Methods PubMed, Medline, Web of Science, Embase databases, and the Cochrane Library were searched up to April 2018 to identify studies that compared primary vitrectomy with and without ILM peeling for RRD with at least six m…
Oxidative stress is associated with an increased antioxidant defense in elderly subjects: a multilevel approach.
2014
© 2014 Fonseca et al. Background: Studies of associations between plasma GSH-Px activity and cardiovascular risk factors have been done in humans, and contradictory results have been reported. The aim of our study was to assess the association between the scavenger antioxidant enzyme glutathione peroxidase (GSH-Px) activity in plasma and the presence of novel and classical cardiovascular risk factors in elderly patients. Copyright: Methods: We performed a cross-sectional study with baseline data from a subsample of the PREDIMED (PREvención con DIeta MEDiterránea) study in Spain. Participants were 1,060 asymptomatic subjects at high risk for cardiovascular disease (CVD), aged 55 to 80, selec…