Search results for "Amide"
showing 10 items of 3119 documents
Targeting brain and peripheral plasticity of the lipidome in acute kainic acid-induced epileptic seizures in mice via quantitative mass spectrometry.
2017
Epilepsy is a highly common chronic neurological disorder, manifested in many different types, affecting ~1% of the worldwide human population. The molecular mechanisms of epileptogenesis have not yet been clarified, and pharmacoresistance exhibited by 30-40% of epilepsy patients remains a major obstacle in medical care. Growing evidence indicates a role of lipid signalling pathways in epileptogenesis, thus lipid signals emerge as potential biomarkers for the onset and evolving course of the epileptic disorder, as well as potential therapeutic agents and targets. For this purpose, we applied a lipidomic strategy to unravel lipid alterations in brain regions, periphery tissues and plasma tha…
Moving Towards Precision Urologic Oncology: Targeting Enzalutamide-resistant Prostate Cancer and Mutated Forms of the Androgen Receptor Using the Nov…
2017
Abstract Darolutamide (ODM-201) is a novel androgen receptor (AR) antagonist with a chemical structure distinctly different from currently approved AR antagonists that targets both wild-type and mutated ligand binding domain variants to inhibit AR nuclear translocation. Here, we evaluate the activity of darolutamide in enzalutamide-resistant castration resistant prostate cancer (CRPC) as well as in AR mutants detected in patients after treatment with enzalutamide, abiraterone, or bicalutamide. Darolutamide significantly inhibited cell growth and AR transcriptional activity in enzalutamide-resistant MR49F cells in vitro, and led to decreased tumor volume and serum prostate-specific antigen l…
Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial.
2020
Abstract Ibrutinib, obinutuzumab, and venetoclax demonstrate synergy in preclinical models of mantle cell lymphoma (MCL). OAsIs (NCT02558816), a single-arm multicenter prospective phase 1/2 trial, aimed to determine the maximum tolerated dose of venetoclax in combination with fixed doses of ibrutinib and obinutuzumab, in relapsed MCL patients. At the venetoclax MTD, extension cohorts were opened for relapsed and untreated patients. Safety and efficacy were secondary objectives. Minimal residual disease (MRD) was assessed by allele-specific oligonucleotide quantitative polymerase chain reaction. Between 14 October 2015 and 29 May 2018, 48 patients were enrolled. No dose-limiting toxicity was…
Characterization of the porcine seminal plasma proteome comparing ejaculate portions.
2016
Full identification of boar seminal plasma (SP) proteins remains challenging. This study aims to provide an extensive proteomic analysis of boar SP and to generate an accessible database of boar SP-proteome. A SP-pool (33 entire ejaculates/11 boars; 3 ejaculates/boar) was analyzed to characterize the boar SP-proteome. Twenty ejaculates (5 boars, 4 ejaculates/boar) collected in portions (P1: first 10 mL of sperm rich ejaculate fraction (SRF), P2: rest of SRF and P3: post-SRF) were analyzed to evaluate differentially expressed SP-proteins among portions. SP-samples were analyzed using a combination of SEC, 1-D SDS PAGE and NanoLC-ESI-MS/MS followed by functional bioinformatics. The identified…
Association between taste perception and adiposity in overweight or obese older subjects with metabolic syndrome and identification of novel taste-re…
2019
BACKGROUND The relation between taste perception, diet, and adiposity remains controversial. Additionally, there is a lack of knowledge on the polymorphisms influencing taste given the scarcity of genome-wide association studies (GWASs) published. OBJECTIVES We studied the relation between perception of the basic tastes, i.e., sweet, salty, bitter, sour, and umami (separately and jointly in a "taste score"), and anthropometric measurements in older subjects with metabolic syndrome (MetS). GWASs were undertaken to identify genes associated with basic tastes and their score. METHODS Taste perception was cross-sectionally determined by challenging subjects (381 older individuals with MetS) wit…
Blocking CD248 molecules in perivascular stromal cells of patients with systemic sclerosis strongly inhibits their differentiation toward myofibrobla…
2018
Abstract Background Fibrosis may be considered the hallmark of systemic sclerosis (SSc), the end stage triggered by different pathological events. Transforming growth factor-β (TGF-β) and platelet-derived growth factor BB (PDGF-BB) are profibrotic molecules modulating myofibroblast differentiation and proliferation, respectively. There is evidence linking CD248 with these two molecules, both highly expressed in patients with SSc, and suggesting that CD248 may be a therapeutic target for several diseases. The aim of this work was to evaluate the expression of CD248 in SSc skin and its ability to modulate SSc fibrotic process. Methods After ethical approval was obtained, skin biopsies were co…
Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial.
2019
Abstract Background Fabry disease is a rare, X-linked, lifelong progressive lysosomal storage disorder. Severely deficient α-galactosidase A activity in males is associated with the classic phenotype with early-onset, multisystem manifestations evolving to vital organ complications during adulthood. We assessed the ability of 2 low-dose agalsidase beta regimens to lower skin, plasma, and urine globotriaosylceramide (GL-3) levels, and influence clinical manifestations in male pediatric Fabry patients. Methods In this multicenter, open-label, parallel-group, phase 3b study, male patients aged 5–18 years were randomized to receive agalsidase beta at 0.5 mg/kg 2-weekly (n = 16) or 1.0 mg/kg 4-w…
Mechanisms involved in the increased sensitivity of the rabbit basilar artery to atrial natriuretic peptide in diabetes.
2017
Atrial natriuretic peptide (ANP) is a vasodilator with significant regional differences and controversial effects in the cerebral circulation, a vascular bed particularly prone to diabetes-induced complications. The present study has investigated how alloxan-induced diabetes modifies the mechanisms involved in the response of the rabbit basilar artery to ANP. ANP (10(-12) -10(-7) M) relaxed precontracted basilar arteries, with higher potency in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal reduced ANP-induced relaxations. Inhibition of NO-synthesis attenuated ANP-induced relaxation but this attenuation was lower in diabetic than in control ra…
Pazopanib for treatment of typical solitary fibrous tumours: a multicentre, single-arm, phase 2 trial
2020
[Background] Solitary fibrous tumour is an ultra-rare sarcoma, which encompasses different clinicopathological subgroups. The dedifferentiated subgroup shows an aggressive course with resistance to pazopanib, whereas in the malignant subgroup, pazopanib shows higher activity than in previous studies with chemotherapy. We designed a trial to test pazopanib activity in two different cohorts of solitary fibrous tumour: the malignant-dedifferentiated cohort, which was previously published, and the typical cohort, which is presented here.
Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomis…
2020
Background Venetoclax is a highly selective, potent, oral BCL-2 inhibitor, which induces apoptosis in multiple myeloma cells. Venetoclax plus bortezomib and dexamethasone has shown encouraging clinical efficacy with acceptable safety and tolerability in a phase 1 trial. The aim of this study was to evaluate venetoclax plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods In this randomised, double-blind, multicentre, phase 3 trial, patients aged 18 years or older with relapsed or refractory multiple myeloma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received one to three previous therapies were enrolled from …