Search results for "blas"

showing 10 items of 2217 documents

Cabozantinib targets bone microenvironment modulating human osteoclast and osteoblast functions

2016

Cabozantinib, a c-MET and vascular endothelial growth factor receptor 2 inhibitor, demonstrated to prolong progression free survival and improve skeletal disease-related endpoints in castration-resistant prostate cancer and in metastatic renal carcinoma. Our purpose is to investigate the direct effect of cabozantinib on bone microenvironment using a total human model of primary osteoclasts and osteoblasts.Osteoclasts were differentiated from monocytes isolated from healthy donors; osteoblasts were derived from human mesenchymal stem cells obtained from bone fragments of orthopedic surgery patients. Osteoclast activity was evaluated by tartrate resistant acid phosphatase (TRAP) staining and …

0301 basic medicinePyridines -- pharmacologyPyridinesPyridineImmunoenzyme TechniqueOsteoclastsApoptosisRANK Ligand -- genetics -- metabolismImmunoenzyme Techniqueschemistry.chemical_compoundBone Resorption -- drug therapy -- metabolism -- pathology0302 clinical medicineOsteogenesisCathepsin KMedicineAnilidesAnilides -- pharmacologyOsteoprotegerin -- genetics -- metabolismOsteoclasts -- cytology -- drug effects -- physiologyHuman primary cellCells CulturedTartrate-resistant acid phosphataseReceptor Activator of Nuclear Factor-kappa B -- genetics -- metabolismbiologyProto-Oncogene Proteins c-met -- genetics -- metabolismReceptor Activator of Nuclear Factor-kappa BReverse Transcriptase Polymerase Chain ReactionOsteoblastOsteogenesiOsteoblastCell DifferentiationSciences bio-médicales et agricolesProto-Oncogene Proteins c-metOsteoblasts -- cytology -- drug effects -- physiologymedicine.anatomical_structureCell Differentiation -- drug effectsOncologyRANKL030220 oncology & carcinogenesishuman primary cellsOsteoclastosteoprotegerin (OPG)bone microenvironmentHumanResearch Papermusculoskeletal diseasesmedicine.medical_specialtyCabozantinibBlotting WesternOsteogenesis -- drug effects -- physiologyReal-Time Polymerase Chain ReactionBone resorption03 medical and health sciencesOsteoprotegerinOsteoclastcabozantinibInternal medicineHumansRNA MessengerBone ResorptionCell ProliferationOsteoblastsbusiness.industryRANK LigandAnilideOsteoprotegerinApoptosiBone microenvironment; Cabozantinib; Human primary cells; Osteoprotegerin (OPG); Receptor activator of nuclear factor-kb ligand (RANKL); Anilides; Apoptosis; Blotting Western; Bone Resorption; Cell Differentiation; Cell Proliferation; Cells Cultured; Humans; Immunoenzyme Techniques; Osteoblasts; Osteoclasts; Osteogenesis; Osteoprotegerin; Proto-Oncogene Proteins c-met; Pyridines; RANK Ligand; RNA Messenger; Real-Time Polymerase Chain Reaction; Receptor Activator of Nuclear Factor-kappa B; Reverse Transcriptase Polymerase Chain Reaction; Oncology030104 developmental biologyEndocrinologychemistrybiology.proteinbusinessRNA Messenger -- geneticsreceptor activator of nuclear factor-kb ligand (RANKL)
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Metabolic and inflammatory reprogramming of macrophages by ONC201 translates in a pro-inflammatory environment even in presence of glioblastoma cells

2020

Tumor-associated macrophages facilitate tumor progression and resistance to therapy. Their capacity for metabolic and inflammatory reprogramming represents an attractive therapeutic target. ONC201/TIC10 is an anticancer molecule that antagonizes the dopamine receptor D2 and affects mitochondria integrity in tumor cells. We examined whether ONC201 induces a metabolic and pro-inflammatory switch in primary human monocyte-derived macrophages that reactivates their antitumor activities, thus enhancing the onco-toxicity of ONC201. Contrary to glioblastoma cells, macrophages exhibited a low ratio of dopamine receptors D2/D5 gene expression and were resistant to ONC201 cytotoxicity. Macrophages re…

0301 basic medicinePyridinesImmunology610 MedizinGlutamic AcidAntineoplastic AgentsMitochondrionBiology570 Life sciences03 medical and health sciences0302 clinical medicineImmune systemCell Line TumorDopamine receptor D2610 Medical sciencesTumor MicroenvironmentHumansImmunology and AllergyMacrophageReceptors Dopamine D5Tumor microenvironmentReceptors Dopamine D2MacrophagesImidazolesMitochondriaCell biologyGene Expression Regulation NeoplasticPyrimidines030104 developmental biologyDrug Resistance NeoplasmTumor progressionDopamine receptorEnergy MetabolismGlioblastomaReprogrammingTranscription Factor CHOPSignal Transduction030215 immunology570 Biowissenschaften
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Generation of three human iPSC lines from PLAN (PLA2G6-associated neurodegeneration) patients

2021

© 2021 The Authors.

0301 basic medicineQH301-705.5Cellular differentiationInduced Pluripotent Stem CellsNeuroaxonal Dystrophies:Cells::Stem Cells::Adult Stem Cells::Induced Pluripotent Stem Cells [ANATOMY]Biologymedicine.disease_cause:células::células madre::células madre adultas::células madre pluripotentes inducidas [ANATOMÍA]Sistema nerviós - DegeneracióCell LineDermal fibroblastGroup VI Phospholipases A203 medical and health sciencesKruppel-Like Factor 40302 clinical medicineSOX2medicineHumans:enfermedades del sistema nervioso::enfermedades neurodegenerativas [ENFERMEDADES]Biology (General)Induced pluripotent stem cellMutationNeurodegenerationCell DifferentiationCell BiologyGeneral Medicinemedicine.diseaseCellular Reprogramming030104 developmental biologyKLF4:Nervous System Diseases::Neurodegenerative Diseases [DISEASES]MutationCancer researchMalalties raresReprogramming030217 neurology & neurosurgeryGenèticaDevelopmental BiologyStem Cell Research
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Radial Glial Fibers Promote Neuronal Migration and Functional Recovery after Neonatal Brain Injury.

2018

Radial glia (RG) are embryonic neural stem cells (NSCs) that produce neuroblasts and provide fibers that act as a scaffold for neuroblast migration during embryonic development. Although they normally disappear soon after birth, here we found that RG fibers can persist in injured neonatal mouse brains and act as a scaffold for postnatal ventricular-subventricular zone (V-SVZ)-derived neuroblasts that migrate to the lesion site. This injury-induced maintenance of RG fibers has a limited time window during post-natal development and promotes directional saltatory movement of neuroblasts via N-cadherin-mediated cell-cell contacts that promote RhoA activation. Transplanting an N-cadherin-contai…

0301 basic medicineRHOAanimal structuresventricular-subventricular zoneBiology03 medical and health sciences0302 clinical medicinegait behaviorNeuroblastCell MovementNeuroblast migrationLateral VentriclesGeneticsmedicineAnimalsreproductive and urinary physiologyN-cadherinNeuronsneuronal migrationneuronal regenerationneonatal brain injuryCadherinEmbryogenesisfungiCell Biologypostnatal neurogenesisRecovery of FunctionCadherinsEmbryonic stem cellNeural stem cellRadial glial cell030104 developmental biologymedicine.anatomical_structurenervous systemAnimals NewbornBrain Injuriesbiology.proteinMolecular MedicinerhoA GTP-Binding ProteinNeuroscienceNeuroglia030217 neurology & neurosurgeryradial glial cellCell stem cell
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The RAB GTPase RAB18 modulates macroautophagy and proteostasis

2017

Macroautophagy is a conserved degradative pathway and its deterioration is linked to disturbances in cellular proteostasis and multiple diseases. Here, we show that the RAB GTPase RAB18 modulates autophagy in primary human fibroblasts. The knockdown of RAB18 results in a decreased autophagic activity, while its overexpression enhances the degradative pathway. Importantly, this function of RAB18 is dependent on RAB3GAP1 and RAB3GAP2, which might act as RAB GEFs and stimulate the activity of the RAB GTPase. Moreover, the knockdown of RAB18 deteriorates proteostasis and results in the intracellular accumulation of ubiquitinated degradation-prone proteins. Thus, the RAB GTPase RAB18 is a positi…

0301 basic medicineRecombinant Fusion Proteinsrab3 GTP-Binding ProteinsPrimary Cell CultureBiophysicsGTPaseBiochemistry03 medical and health sciencesUbiquitinGenes ReporterAutophagyHumansRNA Small InterferingMolecular BiologyGene knockdownbiologyProtein StabilityChemistryfungiAutophagyCell BiologyFibroblastsCell biologyLuminescent Proteins030104 developmental biologyProteostasisGene Expression Regulationrab GTP-Binding ProteinsProteolysisbiology.proteinCancer researchRabSignal transductionRAB18Signal TransductionBiochemical and Biophysical Research Communications
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Innovations in assisted reproductive technologies: impact on contemporary donor egg practice and future advances.

2018

Innovations in assisted reproductive technologies (ART) have driven progress in the donor egg field since the birth of the first baby derived from a donor egg in 1983. Over time, donor oocytes have become an increasingly used option for patients unable to conceive with autologous oocytes. In donor egg, the unique separation of the oocyte source and recipient uterus has created a model that has propelled advances in ART. Progressive ART innovations that have optimized the oocyte donor and resulting embryo include the following: evaluation of ovarian reserve, controlled ovarian hyperstimulation regimens that reduce the risk of ovarian hyperstimulation syndrome, blastocyst culture, oocyte cryo…

0301 basic medicineReproductive Techniques Assistedmedicine.medical_treatmentOvarian hyperstimulation syndromeReproductive technologyControlled ovarian hyperstimulationAndrologyEmbryo Culture Techniques03 medical and health sciences0302 clinical medicineInventionsMedicineHumansBlastocystOvarian reserveOvarian Reserve030219 obstetrics & reproductive medicineAssisted reproductive technologyOocyte Donationbusiness.industryObstetrics and GynecologyOocyte cryopreservationmedicine.diseaseOocyte030104 developmental biologymedicine.anatomical_structureReproductive MedicineFemalebusinessForecastingFertility and sterility
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A stiff extracellular matrix is associated with malignancy in peripheral neuroblastic tumors

2017

Purpose and objective Improved prognosis for patients with peripheral neuroblastic tumors (PNB) depends on enhanced pretreatment risk stratification combined with research into new therapeutic targets. This study investigated the potential contribution of extracellular matrix (ECM) elements toward this endeavor. Methods We characterized certain elements such as reticulin fibers, collagen type I fibers, and elastic fibers by digital pathology in almost 400 untreated PNB. Results A reticular and poorly porous ECM was identified in neuroblastomas (NBs) from patients with clinical and biological features associated with poor prognosis compared with a loose and permeable matrix found in NBs of t…

0301 basic medicineReticular fiberPathologymedicine.medical_specialtybusiness.industryHematologyMatrix (biology)Malignancymedicine.diseaseNeuroblastic TumorPeripheralExtracellular matrix03 medical and health sciences030104 developmental biology0302 clinical medicineOncology030220 oncology & carcinogenesisNeuroblastomaPediatrics Perinatology and Child HealthReticular connective tissuemedicinebusinessPediatric Blood & Cancer
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PEX6 is Expressed in Photoreceptor Cilia and Mutated in Deafblindness with Enamel Dysplasia and Microcephaly

2015

Deafblindness is part of several genetic disorders. We investigated a consanguineous Egyptian family with two siblings affected by congenital hearing loss and retinal degeneration, initially diagnosed as Usher syndrome type 1. At teenage, severe enamel dysplasia, developmental delay, and microcephaly became apparent. Genome-wide homozygosity mapping and whole-exome sequencing detected a homozygous missense mutation, c.1238G>T (p.Gly413Val), affecting a highly conserved residue of peroxisomal biogenesis factor 6, PEX6. Biochemical profiling of the siblings revealed abnormal and borderline plasma phytanic acid concentration, and cerebral imaging revealed white matter disease in both. We show …

0301 basic medicineRetinal degenerationGeneticsMicrocephalyPathologymedicine.medical_specialtyCiliumUsher Syndrome Type 1Biologymedicine.diseaseCiliopathies03 medical and health sciences030104 developmental biologystomatognathic systemGeneticsmedicineMissense mutationAmeloblastGenetics (clinical)PEX6Human Mutation
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Serotonin Heteroreceptor Complexes and Their Integration of Signals in Neurons and Astroglia—Relevance for Mental Diseases

2021

The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor–receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical antipsychotic drugs not only based on blockade of 5-HT2AR and of D2R in higher doses but also based on blocking the allosteric enhancement of D2R protomer signaling by 5-HT2AR protomer activation. This research opens a new understanding of the integration of DA and 5-HT signals released from DA and 5-HT nerve terminal networks. The biologica…

0301 basic medicineReviewheteroreceptor complexesTropomyosin receptor kinase BReceptor tyrosine kinasechemistry.chemical_compound0302 clinical medicineG protein-coupled receptorsserotonin receptorsReceptor Serotonin 5-HT2ABiology (General)astrogliabiologyChemistryMental DisordersBrainGeneral MedicineAntidepressive AgentsdepressionG protein-coupled receptors; astroglia; depression; heteroreceptor complexes; rapid antidepressant drugs; receptor tyrosine kinase; serotonin receptors.medicine.symptomAntipsychotic AgentsSerotonergic NeuronsSignal TransductionProto-oncogene tyrosine-protein kinase Srcserotonin receptorheteroreceptor complexeQH301-705.5Astroglia; Depression; G protein-coupled receptors; Heteroreceptor complexes; Rapid antidepressant drugs; Receptor tyrosine kinase; Serotonin receptors;Allosteric regulationserotonin receptors heteroreceptor complexes depression astroglia receptor tyrosine kinase rapid antidepressant drugs G protein-coupled receptors.depression astroglia receptor tyrosine kinase rapid antidepressant drugs G protein-coupled receptorsHeteroreceptorNO03 medical and health sciencesmedicineAnimalsHumansReceptor Fibroblast Growth Factor Type 1rapid antidepressant drugsG protein-coupled receptorReceptors Dopamine D2Dopaminergic NeuronsTyrosine phosphorylationReceptor Cross-TalkReceptor Galanin Type 1Receptor Galanin Type 2030104 developmental biologyMechanism of actionAstrocytesreceptor tyrosine kinasebiology.proteinReceptors Serotonin 5-HT1Neuroscience030217 neurology & neurosurgeryCells
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Extracellular matrix composition defines an ultra-high-risk group of neuroblastoma within the high-risk patient cohort

2016

Background: Although survival for neuroblastoma patients has dramatically improved in recent years, a substantial number of children in the high-risk subgroup still die. Methods: We aimed to define a subgroup of ultra-high-risk patients from within the high-risk cohort. We used advanced morphometric approaches to quantify and characterise blood vessels, reticulin fibre networks, collagen type I bundles, elastic fibres and glycosaminoglycans in 102 high-risk neuroblastomas specimens. The Kaplan-Meier method was used to correlate the analysed elements with survival. Results: The organisation of blood vessels and reticulin fibres in neuroblastic tumours defined an ultra-high-risk patient subgr…

0301 basic medicineRiskCancer ResearchPathologymedicine.medical_specialtyblood vascularisationColorectal cancerKaplan-Meier EstimateRisk AssessmentCollagen Type IExtracellular matrix03 medical and health sciencesProstate cancerNeuroblastomaneuroblastoma0302 clinical medicineNeuroblastomamedicineHumansSurvival rateMolecular Diagnosticscollagen type I fibresbusiness.industryBrain Neoplasmsultra-high-risk neuroblastomaInfantExtracellular matrixelastic fibresmedicine.diseaseElastic TissuePrognosisSurvival RateReticulin030104 developmental biologymedicine.anatomical_structureOncologyglycosaminoglycans030220 oncology & carcinogenesisBlood Vesselsreticulin fibresBone marrowSkin cancerLiver cancerbusiness
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