A5020708877- Glioma Diagnosis and Treatment
- Tuberous Sclerosis Complex Research
- Epilepsy research and treatment
- Neuroscience and Neuropharmacology Research
- Epigenetics and DNA Methylation
- Chromatin Remodeling and Cancer
- MicroRNA in disease regulation
- Circular RNAs in diseases
- Cerebrovascular and Carotid Artery Diseases
- Neurofibromatosis and Schwannoma Cases
- Intracerebral and Subarachnoid Hemorrhage Research
- Genetics and Neurodevelopmental Disorders
- Pharmacological Effects and Toxicity Studies
- Fetal and Pediatric Neurological Disorders
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- Amyotrophic Lateral Sclerosis Research
- Cerebrospinal fluid and hydrocephalus
- Histiocytic Disorders and Treatments
- Brain Metastases and Treatment
- Prion Diseases and Protein Misfolding
- Advanced Neuroimaging Techniques and Applications
- Advanced MRI Techniques and Applications
- Histone Deacetylase Inhibitors Research
- Dementia and Cognitive Impairment Research
University Medical Center Utrecht
2013-2022
University Medical Center Groningen
2020
University of Groningen
2020
Heidelberg University
1998-2019
University Hospital Heidelberg
1998-2019
Radboud University Nijmegen
2012-2015
Erasmus MC
2012-2015
Radboud University Medical Center
2012-2015
European Organisation for Research and Treatment of Cancer
2015
European Organisation for Research and Treatment of Cancer
2015
Increasing evidence supports the involvement of microRNAs (miRNA) in regulation inflammation human neurological disorders. In present study we investigated role miR-146a, a key regulator innate immune response, modulation astrocyte-mediated inflammation. Using Taqman PCR and situ hybridization, studied expression miR-146a epilepsy-associated glioneuronal lesions which are characterized by prominent activation response. addition, cultured astrocytes were used to response proinflammatory...
Recent evidence in experimental models of seizures and temporal lobe epilepsy support an important role high-mobility group box 1 toll-like receptor 4 signalling the mechanisms hyperexcitability leading to development perpetuation seizures. In this study, we investigated expression cellular distribution receptors 2 4, for advanced glycation end products, their endogenous ligand 1, associated with focal malformations cortical development. Immunohistochemistry showed increased products...
Cerebrovascular disease has an important role in cognitive decline and dementia. In this context, cerebral microinfarcts are attracting increasing attention, but these lesions could thus far not be detected vivo. The aim of study was to try identify possible cortical on high-resolution 7T vivo magnetic resonance imaging (MRI) perform a histopathologic validation similar appearing ex MRI postmortem brain tissue. population consisted 22 elderly subjects, who underwent MRI. fluid attenuated...
Summary: Purpose: Breast cancer resistance protein (BCRP) is a half adenosine triphosphate (ATP)‐binding cassette (ABC) transporter expressed on cellular membranes and included in the group of multidrug resistant (MDR)‐related proteins. Recently, upregulation different MDR proteins has been shown human epilepsy‐associated conditions. This study investigated expression distribution BCRP control epileptic brain, including large number both neoplastic nonneoplastic specimens from patients with...
Induction of inflammatory pathways has been reported in epileptic patients with focal malformations cortical development. In the present study we examined innate and adaptive immune responses dysplasia (FCD) different histopathologic pathogenetic features.The cell components induction major proinflammatory molecules [complement pathway, interleukin (IL)-1β, chemokine monocyte chemotactic protein-1 (MCP1)] was investigated surgical specimens sporadic type IA IIB FCD using immunocytochemical...
BackgroundHistopathological diagnosis of diffuse gliomas is subject to interobserver variation and correlates modestly with major prognostic predictive molecular abnormalities. We investigated a series patients locally diagnosed anaplastic oligodendroglial tumors included in the EORTC phase III trial 26951 on procarbazine/lomustine/vincristine (PCV) chemotherapy explore diagnostic, prognostic, value targeted next-generation sequencing (NGS) glioma assess impact FUBP1 CIC mutations.
Abstract Cortical tubers in patients with tuberous sclerosis complex are associated disabling neurological manifestations, including intractable epilepsy. While these malformations believed to result from the effects of TSC1 or TSC2 gene mutations, molecular mechanisms leading tuber formation, as well onset seizures, remain largely unknown. We used Affymetrix Gene Chip platform provide first genome‐wide investigation expression surgically resected tubers, compared histological normal...
Mutations in the RNA binding protein fused sarcoma/translated liposarcoma (FUS/TLS) cause amyotrophic lateral sclerosis (ALS). Although ALS-linked mutations FUS often lead to a cytosolic mislocalization of protein, pathogenic mechanisms underlying these remain poorly understood. To gain insight into mechanisms, we examined biochemical, cell biological and functional properties mutant neurons. Expression different mutants (R521C, R521H, P525L) neurons caused axonal defects. A interaction...
BRAF V600E mutations have been recently reported in glioneuronal tumors (GNTs). To evaluate the expression of mutated protein and its association with activation mammalian target rapamycin (mTOR) pathway, immunophenotype clinical characteristics GNTs, we investigated a cohort 174 GNTs. The presence was detected by direct DNA sequencing immunohistochemical detection. Expression BRAF-mutated 38/93 (40.8%) gangliogliomas (GGs), 2/4 (50%) desmoplastic infantile (DIGs) 23/77 (29.8%)...
The long-term follow-up results from the EORTC-26951 trial showed that addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more PCV treatment than others.We conducted genome-wide methylation profiling 115 samples included extracted CpG island hypermethylated phenotype (CIMP) MGMT promoter (MGMT-STP27) status.We first show can be on archival tissues...
Epileptogenic glioblastomas are thought to convey a favorable prognosis, either due early diagnosis or potential antitumor effects of antiepileptic drugs. We investigated the relationship between survival and epilepsy at presentation, diagnosis, drug therapy in glioblastoma patients. Multivariable Cox regression was applied data 647 consecutive patients diagnosed with de novo 2005 2013 order investigate association In addition, we quantified valproic acid (VPA) treatment. Epilepsy correlated...
To determine whether highly epileptiform electrocorticographical discharge patterns occur in patients with glioneuronal tumors (GNTs) and focal cortical dysplasia (FCD) specific histopathological features are related to such patterns.The series consists of operated pharmacoresistant epilepsy because FCD or GNT between 1992 2003. Electrocorticography was reviewed for presence continuous spiking, bursts, recruiting discharges, sporadic spikes. Surgical specimens were the balloon cells,...
Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder caused by mutations in either the TSC1 or TSC2 genes and characterized developmental brain abnormalities. In present study we discuss neuropathological findings of a 32-year-old patient with germ-line mutation gene. Post mortem MRI combined histology immunocytochemical analysis was applied to demonstrate widespread anatomical abnormalities gray white matter structure. TSC lesions were analyzed for loss...
Intrinsic glioma subtypes (IGSs) are molecularly similar tumors that can be identified based on unsupervised gene expression analysis. Here, we have evaluated the clinical relevance of these within European Organisation for Research and Treatment Cancer (EORTC) 26951, a randomized phase III trial investigating adjuvant procarbazine, lomustine, vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study includes profiles formalin-fixed, paraffin-embedded (FFPE)...
Perivascular spaces are an emerging marker of small vessel disease. in the centrum semiovale have been associated with cerebral amyloid angiopathy. However, a direct topographical relationship between dilated perivascular and angiopathy severity has not established. We examined this association using post-mortem magnetic resonance imaging five cases evidence pathology. Juxtacortical dilation was evaluated on T2 images related to overlying cortical areas 34 tissue sections stained for Amyloid...
Pediatric medulloblastomas are the most frequently diagnosed embryonal tumors of central nervous system. Current therapies cause severe neurological and cognitive side effects including secondary malignancies. Cellular immunotherapy might be key to improve survival avoid morbidity. Efficient killing tumor cells using requires overcome cancer-associated strategies evade cytotoxic immune responses. Here, we examined response evasion in pediatric medulloblastomas. Cytotoxic T-cells,...