Search results for "Iso"
showing 10 items of 22430 documents
MET-EGFR dimerization in lung adenocarcinoma is dependent on EGFR mtations and altered by MET kinase inhibition
2017
Advanced lung cancer has poor survival with few therapies. EGFR tyrosine kinase inhibitors (TKIs) have high response rates in patients with activating EGFR mutations, but acquired resistance is inevitable. Acquisition of the EGFR T790M mutation causes over 50% of resistance; MET amplification is also common. Preclinical data suggest synergy between MET and EGFR inhibitors. We hypothesized that EGFR-MET dimerization determines response to MET inhibition, depending on EGFR mutation status, independently of MET copy number. We tested this hypothesis by generating isogenic cell lines from NCI-H1975 cells, which co-express L858R and T790M EGFR mutations, namely H1975L858R/T790M (EGFR TKI resista…
Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy
2019
Supplemental Digital Content is available in the text.
Pharmacological basis of the anxiolytic and antidepressant properties of Silexan®, an essential oil from the flowers of lavender.
2021
Silexan®, a proprietary essential oil manufactured by steam distillation from Lavandula angustifolia flowers showed pronounced anxiolytic effects in patients with subthreshold anxiety disorders and was also efficacious in patients with Generalized Anxiety disorder (GAD). Moreover, evidences for antidepressant-like properties of Silexan® have been observed in anxious patients suffering from comorbid depressive symptoms and in patients with mixed anxiety-depression disorder (ICD-10 F41.2). In accordance with the clinical data Silexan® is active in several behavioral models in rodents at rather low concentrations indicating potent anxiolytic and antidepressive properties. As possible mechanism…
NEGR1 and FGFR2 cooperatively regulate cortical development and core behaviours related to autism disorders in mice.
2018
See Contreras and Hippenmeyer (doi:10.1093/brain/awy218) for a scientific commentary on this article. Autism spectrum disorders (ASDs) are complex conditions with diverse aetiologies. Szczurkowska et al. demonstrate that two ASD-related molecules – FGFR2 and Negr1 – physically interact to act on the same downstream pathway, and regulate cortical development and ASD-relevant behaviours in mice. Identifying common mechanisms in ASDs may reveal targets for pharmacological intervention.
Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates.
2016
Drug addiction shares brain mechanisms and molecular substrates with learning and memory processes, such as the stimulation of glutamate receptors and their downstream signalling pathways. In the present work we provide an up-to-date review of studies that have demonstrated the implication of the main memory-related calcium-dependent protein kinases in opiate and cocaine addiction. The effects of these drugs of abuse in different animal models of drug reward, dependence and addiction are altered by manipulation of the mitogen-activated protein kinase (MAPK) family, particularly extracellular signal regulated kinase (ERK), calcium/calmodulin-dependent kinase II (CaMKII), the protein kinase C…
De novo mutations in the X-linked TFE3 gene cause intellectual disability with pigmentary mosaicism and storage disorder-like features
2020
IntroductionPigmentary mosaicism (PM) manifests by pigmentation anomalies along Blaschko’s lines and represents a clue toward the molecular diagnosis of syndromic intellectual disability (ID). Together with new insights on the role for lysosomal signalling in embryonic stem cell differentiation, mutations in the X-linked transcription factor 3 (TFE3) have recently been reported in five patients. Functional analysis suggested these mutations to result in ectopic nuclear gain of functions.Materials and methodsSubsequent data sharing allowed the clustering of de novo TFE3 variants identified by exome sequencing on DNA extracted from leucocytes in patients referred for syndromic ID with or with…
Unfused Liver Segments: a Case Report of an Unknown Phenotype of the Conradi-Hünermann-Happle Syndrome
2016
Background: Since its description in 1957, Couinaud`s classification of the segmental organization of the liver has remained valid. However, recent investigations by 3-dimensional computed tomography suggest a significant variability of the vascular anatomy and segment volume. Here, we report a surprise finding during the laparoscopic cholecystectomy of a patient with Conradi-Hünermann-Happle syndrome, in whom the liver segments were not fused.
 Case report: Laparoscopic cholecystectomy was performed because of recurrent biliary pancreatitis in a 47 year-old male patient, who had been diagnosed with Conradi-Hünermann-Happle syndrome. Upon direct view, the liver parenchyma appeared norm…
Adolescent and adult mice display differential sensitivity to the effects of bupropion on the acquisition of a water maze task.
2017
Abstract Background Adolescence is characterized by major neurobiological changes, and the effects of some psychoactive drugs seem to differ between adolescents and adults. Bupropion, an antidepressant that is also used to treat nicotine addiction, induces behavioral actions in both adolescent and adult rodents. However, the effects of this drug on spatial ability have not been compared in animals at different stages of their development. The present study was conducted to assess the effects of bupropion on spatial learning and memory in adolescent and adult mice. Methods Adolescent (post-natal day: PND35-36) and adult (PND >65) NMRI mice received bupropion (10, 20 and 40 mg/kg) or saline d…
Relationship Between Body Mass Index, ApoE4 Status, and PET-Based Amyloid and Neurodegeneration Markers in Amyloid-Positive Subjects with Normal Cogn…
2018
Body weight loss in late-life is known to occur at a very early stage of Alzheimer's disease (AD). Apolipoprotein E4 (ApoE4) represents a major genetic risk factor for AD and is linked to an increased cortical amyloid-β (Aβ) accumulation. Since the relationship between body weight, ApoE4, and AD pathology is poorly investigated, we aimed to evaluate whether ApoE4 allelic status modifies the association of body mass index (BMI) with markers of AD pathology. A total of 368 Aβ-positive cognitively healthy or mild cognitive impaired subjects had undergone [18F]-AV45-PET, [18F]-FDG-PET, and T1w-MRI examinations. Composite cortical [18F]-AV45 uptake and [18F]-FDG uptake in posterior cingulate cor…
Dynamic longitudinal behavior in animals exposed to chronic social defeat stress
2020
AbstractChronic social defeat (CSD) can lead to impairments in social interaction and other behaviors that are supposed to model features of major depressive disorder (MDD). Not all animals subjected to CSD, however, develop these impairments, and maintained social interaction in some animals is widely used as a model for resilience to stress-induced mental dysfunctions. So far, animals have mainly been studied shortly (24 hours and 7 days) after CSD exposure and longitudinal development of behavioral phenotypes in individual animals has been mostly neglected. We have analyzed social interaction and novel object recognition behavior of stressed mice at different time points after CSD and ha…