Search results for " Biomedical"
showing 10 items of 480 documents
β3-Adrenoceptor agonists for overactive bladder syndrome: Role of translational pharmacology in a repositioning clinical drug development project
2016
β3-Adrenoceptor agonists were originally considered as a promising drug class for the treatment of obesity and/or type 2 diabetes. When these development efforts failed, they were repositioned for the treatment of the overactive bladder syndrome. Based on the example of the β3-adrenoceptor agonist mirabegron, but also taking into consideration evidence obtained with ritobegron and solabegron, we discuss challenges facing a translational pharmacology program accompanying clinical drug development for a first-in-class molecule. Challenges included generic ones such as ligand selectivity, species differences and drug target gene polymorphisms. Challenges that are more specific included changin…
Mechanisms of the Development of Allergy (MeDALL) : Introducing novel concepts in allergy phenotypes
2017
Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non–IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Q…
Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: An international consensus statement
2018
Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management …
Targeting the Heterogeneity of Cancer with Individualized Neoepitope Vaccines
2015
Abstract Somatic mutations binding to the patient's MHC and recognized by autologous T cells (neoepitopes) are ideal cancer vaccine targets. They combine a favorable safety profile due to a lack of expression in healthy tissues with a high likelihood of immunogenicity, as T cells recognizing neoepitopes are not shaped by central immune tolerance. Proteins mutated in cancer (neoantigens) shared by patients have been explored as vaccine targets for many years. Shared (“public”) mutations, however, are rare, as the vast majority of cancer mutations in a given tumor are unique for the individual patient. Recently, the novel concept of truly individualized cancer vaccination emerged, which explo…
Immunotherapy in non-small-cell lung cancer: a bridge between research and clinical practice
2018
Lung cancer has been historically considered a poorly immunogenic disease because of the few evidence of immune responses in affected patients and the limited efficacy of immunomodulating strategies. Recent understanding of the molecular mechanisms leading to cancer immune evasion has allowed the development of a new class of drugs called immune checkpoint inhibitors, which reactivate host responses with outstanding clinical benefits in a portion of patients with non-small-cell lung cancer. In this review, we briefly summarize the basis of immunogenicity and immune escape of cancer, with specific focus on non-small-cell lung cancer, mechanisms underlying immune checkpoint inhibitors effica…
Spanish Cell Therapy Network (TerCel): 15 years of successful collaborative translational research
2019
On behalf of TerCel
Hydrodynamic IL10 Gene Transfer in Human Colon: Results from an "EX VIVO" Study with Potential Clinical Application in Crohn's Disease.
2017
Background: The aim of this work is to evaluate the efficacy of hydrodynamic venous IL10 gene delivery to "ex vivo" human colon segments and to determine its potential interest in Crohn's disease treatment. Methods: Twenty human colon segments were obtained from surgical resections. Hydrodynamic transfection through the main vein of the pedicle with 50 mL of hIL10 plasmid (20 mu g/mL) solution was performed on 13 of them. Tissue sections were cultured and DNA, RNA, and protein copies were determined after 1, 2, and 4 days. Data obtained were compared with 6 nontransfected specimens. Finally, 1 specimen was injected with gold nanoparticles, and their distribution was examined under electron …
Biophysics of high density nanometer regions extracted from super-resolution single particle trajectories: application to voltage-gated calcium chann…
2019
AbstractThe cellular membrane is very heterogenous and enriched with high-density regions forming microdomains, as revealed by single particle tracking experiments. However the organization of these regions remain unexplained. We determine here the biophysical properties of these regions, when described as a basin of attraction. We develop two methods to recover the dynamics and local potential wells (field of force and boundary). The first method is based on the local density of points distribution of trajectories, which differs inside and outside the wells. The second method focuses on recovering the drift field that is convergent inside wells and uses the transient field to determine the…
A New Frailty Score for Experimental Animals Based on the Clinical Phenotype: Inactivity as a Model of Frailty.
2016
The development of animal models to study human frailty is important to test interventions to be translated to the clinical practice. The aim of this work was to develop a score for frailty in experimental animals based in the human frailty phenotype. We also tested the effect of physical inactivity in the development of frailty as determined by our score. Male C57Bl/6J mice, individually caged, were randomly assigned to one of two groups: sedentary (inactive) or spontaneous wheel-runners. We compared the sedentary versus the active lifestyle in terms of frailty by evaluating the clinical criteria used in humans: unintentional weight loss; poor endurance (running time); slowness (running sp…
3d collagen hydrogel promotes in vitro langerhans islets vascularization through ad-mvfs angiogenic activity
2021
Adipose derived microvascular fragments (ad-MVFs) consist of effective vascularization units able to reassemble into efficient microvascular networks. Because of their content in stem cells and related angiogenic activity, ad-MVFs represent an interesting tool for applications in regenerative medicine. Here we show that gentle dissociation of rat adipose tissue provides a mixture of ad-MVFs with a length distribution ranging from 33–955 μm that are able to maintain their original morphology. The isolated units of ad-MVFs that resulted were able to activate transcriptional switching toward angiogenesis, forming tubes, branches, and entire capillary networks when cultured in 3D collagen type-…