183 research outputs found
Kinetic and thermodynamic study of beta-Boswellic acid interaction with Tau protein investigated by surface plasmon resonance and molecular modeling methods
Introduction: Beta-Boswellic acid (BBA) is a pentacyclic terpene which has been obtained from frankincense and its beneficial effects on neurodegenerative disorders such as Alzheimer’s disease (AD) have been addressed. Methods: In the present study, thermodynamic and kinetic aspects of BBA interaction with Tau protein as one of the important proteins involved in AD in the absence and presence of glucose has been investigated using surface plasmon resonance (SPR) method. Tau protein was immobilized onto the carboxy methyl dextran chip and its binding interactions with BBA were studied at physiological pH at various temperatures. Glucose interference with these interactions was also investigated. Results: Results showed that BBA forms a stable complex with Tau (KD=8.45×10-7 M) at 298 K. Molecular modeling analysis showed a hydrophobic interaction between BBA and HVPGGG segment of R2 and R4 repeated domains of Tau. Conclusion: The binding affinity increased by temperature enhancement, while it decreased significantly in the presence of glucose. Both association and dissociation of the BBA-Tau complex were accompanied with an entropic activation barrier; however, positive enthalpy and entropy changes revealed that hydrophobic bonding is the main force involved in the interaction
Anaplastic oligodendrogliomas with 1p19q codeletion have a proneural gene expression profile
<p>Abstract</p> <p>Background</p> <p>In high grade gliomas, 1p19q codeletion and <it>EGFR </it>amplification are mutually exclusive and predictive of dramatically different outcomes. We performed a microarray gene expression study of four high grade gliomas with 1p19q codeletion and nine with <it>EGFR </it>amplification, identified by CGH-array.</p> <p>Results</p> <p>The two groups of gliomas exhibited very different gene expression profiles and were consistently distinguished by unsupervised clustering analysis. One of the most striking differences was the expression of normal brain genes by oligodendrogliomas with 1p19q codeletion. These gliomas harbored a gene expression profile that partially resembled the gene expression of normal brain samples, whereas gliomas with <it>EGFR </it>amplification expressed many genes in common with glioblastoma cancer stem cells. The differences between the two types of gliomas and the expression of neuronal genes in gliomas with 1p19q codeletion were both validated in an independent series of 16 gliomas using real-time RT-PCR with a set of 22 genes differentiating the two groups of gliomas (<it>AKR1C3</it>, <it>ATOH8</it>, <it>BMP2</it>, <it>C20orf42</it>, <it>CCNB1</it>, <it>CDK2</it>, <it>CHI3L1</it>, <it>CTTNBP2</it>, <it>DCX, EGFR, GALNT13, GBP1, IGFBP2, IQGAP1, L1CAM, NCAM1, NOG, OLIG2, PDPN, PLAT, POSTN, RNF135</it>). Immunohistochemical study of the most differentially expressed neuronal gene, alpha-internexin, clearly differentiated the two groups of gliomas, with 1p19q codeletion gliomas showing specific staining in tumor cells.</p> <p>Conclusion</p> <p>These findings provide evidence for neuronal differentiation in oligodendrogliomas with 1p19q codeletion and support the hypothesis that the cell of origin for gliomas with 1p19q codeletion could be a bi-potential progenitor cell, able to give rise to both neurons and oligodendrocytes.</p
Efficacy of vinblastine in central nervous system Langerhans cell histiocytosis: a nationwide retrospective study
<p>Abstract</p> <p>Background</p> <p>Vinblastine (VBL) is the standard treatment for systemic Langerhans cell histiocytosis (LCH), but little is known about its efficacy in central nervous system (CNS) mass lesions.</p> <p>Methods</p> <p>A retrospective chart review was conducted. Twenty patients from the French LCH Study Group register met the inclusion criteria. In brief, they had CNS mass lesions, had been treated with VBL, and were evaluable for radiologic response.</p> <p>Results</p> <p>The median age at diagnosis of LCH was 11.5 years (range: 1-50). Intravenous VBL 6 mg/m<sup>2 </sup>was given in a 6-week induction treatment, followed by a maintenance treatment. The median total duration was 12 months (range: 3-30). Eleven patients received steroids concomitantly. Fifteen patients achieved an objective response; five had a complete response (CR: 25%), ten had a partial response (PR: 50%), four had stable disease (SD: 20%) and one patient progressed (PD: 5%). Of interest, four out of the six patients who received VBL without concomitant steroids achieved an objective response. With a median follow-up of 6.8 years, the 5-year event-free and overall survival was 61% and 84%, respectively. VBL was well-tolerated and there were no patient withdrawals due to adverse events.</p> <p>Conclusion</p> <p>VBL, with or without steroids, could potentially be a useful therapeutic option in LCH with CNS mass lesions, especially for those with inoperable lesions or multiple lesions. Prospective clinical trials are warranted for the evaluation of VBL in this indication.</p
Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951
Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization. The data were processed using a binary tree method. Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis (p < 0.0001). Type I tumors (25%) were characterized by: (1) an EGFR amplification, (2) a poor prognosis, (3) a higher rate of necrosis, and (4) an older age of patients. Type II tumors (21.7%) had: (1) loss of prognostic BACs located on 1p tightly associated with 19q deletion, (2) a longer survival, (3) an oligodendroglioma phenotype, and (4) a frontal location in brain. Type III AOTs (11.7%) exhibited: (1) a deletion of prognostic BACs located on 21q, and (2) a short survival. Finally, type IV tumors (41.7%) had different genomic patterns and prognosis than type I, II and III AOTs. Multivariate analysis showed that genomic type provides additional prognostic data to clinical, imaging and pathological features. Similar results were obtained in the cohort of 45 centrally reviewed–validated cases of AOTs. Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs
Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas
Peer reviewe
Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study
Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1–3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were much younger (median age 1.3–1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age
Regionalisation et emergence industrielle au Maroc
<p><span>Aujourd'hui, nous assistons à la faillite du modèle de développement économique et social<span> </span>établi<span> </span>dans<span> </span>une<span> </span>perspective<span> </span>macroéconomique,<span> </span>qui<span> </span>s'est<span> </span>élaboré<span> </span>autour<span> </span>de<span> </span>l'État-nation.<span> </span>C'est<span> </span>principalement parce qu'ils ne peuvent pas surmonter les défis et les problèmes liés à la nouvelle ère<span> </span>économique qui désormais, se manifeste par des inégalités criantes et croissantes dans ses aspects<span> </span>économiques, sociaux et spatiaux. Face à ces nouvelles considérations, nous avons fait émerger dans<span> </span>les cercles scientifiques et politiques un nouveau consensus autour du rôle des régions infranationales<span> </span>en tant qu'entités territoriales dans les connexions globales et locales. Les travaux portant sur les questions stratégiques de développement socio-économique s'inscrivent dans cette direction1. Il s'agit d'interpréter et de décrire les déterminants de la compétitivité régionale. À cet égard, nous pensons que celles-ci peuvent être intégrées dans un cadre unifié, en l'occurrence la localisation, la concentration, l'agglomération et le maillage régional des entreprises opérant dans les bassins de production locaux.</span></p>
<p><span>La recherche est basée sur une étude économétrique. L'objectif est de vérifier que le modèle conceptuel reposait à l'origine sur un corpus théorique, dans lequel le travail de la nouvelle économie géographique et le travail de l’économie industrielle et de l’organisation territoriale constituent les principales composantes.</span></p>
<p><span>Les<span> </span>résultats<span> </span>de<span> </span>nos<span> </span>recherches<span> </span>montrent<span> </span>que<span> </span>l'ancrage<span> </span>géographique<span> </span>des<span> </span>activités<span> </span>de<span> </span>production<span> </span>est<span> </span>primordial. Ainsi,<span> </span>la<span> </span>politique<span> </span>de<span> </span>développement<span> </span>adoptée<span> </span>au<span> </span>niveau<span> </span>régional<span> </span>doit<span> </span>s'appuyer<span> </span>sur<span> </span>une<span> </span>approche<span> </span>spatiale,<span> </span>voire<span> </span>régionale,<span> </span>pour<span> </span>diviser<span> </span>l'interactivité<span> </span>des<span> </span>différents<span> </span>territoires<span> </span>de<span> </span>la<span> </span>région,<span> </span>à<span> </span>savoir<span> </span>:<span> </span>territoire<span> </span>de<span> </span>production,<span> </span>territoire<span> </span>administratif<span> </span>et<span> </span>territoire<span> </span>de<span> </span>sciences et de savoir. Il s’agit d’une approche régionale où la participation active, collaborative et<span> </span>constructive de tous les acteurs dans un contexte de proximité diversifiée sera mieux stimulée et très<span> </span>demandée.</span></p>
<p><span>Ainsi, le renforcement du processus de mise en réseau des entreprises locales à travers une<span> </span>gouvernance<span> </span>territoriale<span> </span>tripartite,<span> </span>faisant<span> </span>écho<span> </span>à<span> </span>la<span> </span>coexistence<span> </span>des<span> </span>acteurs<span> </span>locaux<span> </span>(systèmes<span> </span>d'administration publique, collectivités locales et opérateurs économiques privés) et à la convergence<span> </span>d'intérêts autour des enjeux de développement local et régional, aura certainement un impact sur la<span> </span>compétitivité<span> </span>régionale<span> </span>et<span> </span>nationale.</span></p>
Increasing the diagnostic yield of stereotactic brain biopsy using intraoperative histological smear
Intracranial solitary fibrous tumors/hemangiopericytomas: first report of malignant progression
International audienceOBJECTIVE: Meningeal solitary fibrous tumors/hemangiopericytomas (MSFTs/HPCs) are rare intracranial tumors resembling meningiomas. Their classification was redefined in 2016 by the World Health Organization (WHO) as benign Grade I fibrohyaline type, intermediate Grade II hypercellular type, and malignant highly mitotic Grade III. This grouping is based on common histological features and identification of a common NAB2-STAT6 fusion.METHODS: The authors retrospectively identified 49 cases of MSFT/HPC. Clinical data were obtained from the medical records, and all cases were analyzed according to this new 2016 WHO grading classification in order to identify malignant transformations.RESULTS: Recurrent surgery was performed in 18 (37%) of 49 patients. Malignant progression was identified in 5 (28%) of these 18 cases, with 3 Grade I and 2 Grade II tumors progressing to Grade III, 3-13 years after the initial surgery. Of 31 Grade III tumors treated in this case series, 16% (5/31) were proved to be malignant progressions from lower-grade tumors.CONCLUSIONS: Low-grade MSFTs/HPCs can transform into higher grades as shown in this first report of such progression. This is a decisive argument in favor of a common identity for MSFT and meningeal HPC. High-grade MSFTs/HPCs tend to recur more often and be associated with reduced overall survival. Malignant progression could be one mechanism explaining some recurrences or metastases, and justifying long-term follow-up, even for patients with Grade I tumors
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