A5031730079- Sarcoma Diagnosis and Treatment
- Alzheimer's disease research and treatments
- Bone Tumor Diagnosis and Treatments
- Oral and Maxillofacial Pathology
- Mycobacterium research and diagnosis
- Marine Invertebrate Physiology and Ecology
- Leprosy Research and Treatment
- Dementia and Cognitive Impairment Research
- Vascular Tumors and Angiosarcomas
- Infectious Diseases and Tuberculosis
- Tuberculosis Research and Epidemiology
- RNA and protein synthesis mechanisms
- Drug Transport and Resistance Mechanisms
- RNA modifications and cancer
- Marine Ecology and Invasive Species
- CRISPR and Genetic Engineering
- Cardiac tumors and thrombi
- Ubiquitin and proteasome pathways
- Insect and Pesticide Research
- Epilepsy research and treatment
- Cancer-related gene regulation
- Renal and related cancers
- Parkinson's Disease Mechanisms and Treatments
- Acute Lymphoblastic Leukemia research
- Signaling Pathways in Disease
Leiden University Medical Center
2014-2024
The Netherlands Cancer Institute
2006-2024
Oncode Institute
2006-2023
Kempenhaeghe
2018-2023
Victor Chang Cardiac Research Institute
2011-2017
ARC Centre of Excellence for Coral Reef Studies
2010
James Cook University
2005-2010
Australian National University
2001-2010
Leiden University
2009
University of Veterinary Medicine Hannover, Foundation
2008-2009
Molecular genetic studies on rare tumour entities, such as bone tumours, often require the use of decalcified, formalin-fixed, paraffin-embedded tissue (dFFPE) samples. Regardless which decalcification procedure is used, this introduces a vast breakdown DNA that precludes possibility further molecular testing. We set out to establish robust protocol would overcome these intrinsic hurdles for research.The goal our study was protocol, using modified isolation and quality controls, select...
PurposeTo define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 NPRL3 genes encoding GATOR1 complex, a negative regulator mTORC1 pathwayMethodsWe analyzed clinical genetic data 73 novel probands (familial sporadic) with epilepsy-related variants in GATOR1-encoding proposed new guidelines for interpretation variants.ResultsThe seizure phenotype consisted mostly focal seizures (e.g., hypermotor or frontal lobe 50%), mean age at onset 4.4 years, often...
Abstract High‐grade osteosarcoma is characterized by extensive genetic instability, thereby hampering the identification of causative gene mutations and understanding underlying pathological processes. It lacks a benign precursor lesion reports on associations with hereditary predisposition or germline are uncommon, despite early age onset. Here we demonstrate novel comprehensive approach for study premalignant stages development in murine mesenchymal stem cell (MSC) system that formed...
Abstract Purpose: Ewing sarcoma is an aggressive and the second most common bone in childhood. Disease-specific t(11;22) (∼85-90%), t(21;22) (∼5-10%), or rarer variant translocations with involvement of chromosome 22 (∼5%) are present. At gene level, EWSR1 fuses FLI1, ERG, other ETS transcription factor family members. Thus far, no has been identified a fusion to factors than ETS. Experimental Design: Using molecular tools such as multicolor fluorescence situ hybridization array comparative...
BackgroundThe objective of this study was to determine whether treatment with the nonselective nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows cognitive decline in patients Alzheimer's disease (AD).Methodology/Principal FindingsThis double-blind, randomized, placebo-controlled trial conducted between May 2000 and September 2005 two hospitals Netherlands. 51 mild moderate AD were enrolled into study. Patients received 100 mg or placebo daily for 12 months. Additionally, all...
Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and adolescents, being characterized by expression of genes morphological ultrastructural features sarcomeric differentiation. The spindle cell variant rhabdomyosarcoma (spindle RMS) adults has been defined as an entity, separated from embryonal (ERMS), with unfavourable clinical outcome. So far, no recurrent genetic alteration identified adult form RMS. We studied a case RMS using next-generation sequencing (NGS)...
Neurofilament (NF) proteins are major cytoskeletal constituents of neurons. Increased CSF NF levels may reflect neuronal degeneration.To investigate the diagnostic value analysis to discriminate in relatively young dementia patients between frontotemporal lobe degeneration (FTLD) and early onset Alzheimer's disease (EAD; < or = 65 years age), elderly with Lewy bodies (DLB) late AD (LAD; > age).In 28 FTLD, 37 EAD, 18 DLB 33 LAD patients, 26 control subjects, we analysed light chain (NFL),...
Abstract Clear cell, mesenchymal, and dedifferentiated chondrosarcoma are rare, cartilaginous tumors with limited treatment options other than surgery. Conventional chondrosarcomas have been extensively studied at the genetic level, but for rare subtypes, this is merely restricted to case reports. Information on genetics of may provide insight into etiology these specific disease subtypes possible alternative strategies. Therefore, aim study was genetically characterize subset tumors. Using...
Epithelioid hemangioma of bone is a locally aggressive vascular neoplasm. It can be challenging to diagnose because the wide histological spectrum, which make it difficult differentiate from other neoplasms such as epithelioid hemangioendothelioma or angiosarcoma. COBRA‐FISH karyotyping identified balanced t(3;14) translocation. Transcriptome sequencing index case and two hemangiomas revealed recurrent translocation breakpoint involving FOS gene, was fused different partners in all three...
We take a functional genomics approach to congenital heart disease mechanism. used DamID establish robust set of target genes for NKX2-5 wild type and associated mutations model loss-of-function in gene regulatory networks. mutants, including those with crippled homeodomain, bound hundreds targets unique "off-targets", retained partial functionality. NKXΔHD, which lacks the homeodomain completely, could heterodimerize its cofactors, E26 transformation-specific (ETS) family members, through...
Background. The differentiation of Alzheimer's disease (AD) from vascular dementia (VaD) is hampered by clinical diagnostic criteria with disappointing sensitivity and specificity. objective this study was to investigate whether cerebrospinal fluid (CSF) levels total tau protein (t-tau), amyloid β42 (Aβ42), phosphorylated at threonine 181 (p-tau181) are useful biomarkers distinguish AD patients VaD patients.
In humans, the defective invasion of maternal endometrium by fetal extravillous trophoblasts (EVTs) can lead to insufficient perfusion placenta, resulting in pregnancy complications that put both mother and baby at risk. To study between (W)5.5-12 weeks gestation EVTs, we combined fluorescence situ hybridization, immunofluorescence immunohistochemistry determine presence (male) EVTs vasculature decidua. We observed interstitial mononuclear directly entered decidual veins lymphatics from...
Abstract We investigated whether cerebrospinal fluid (CSF) analysis discriminates between idiopathic Parkinson's disease (PD; n = 35) and multiple system atrophy (MSA; 30). The median CSF concentration of the neurotransmitter metabolites 5‐hydroxyindolacetic acid (5‐HIAA) 3‐methoxy‐4‐hydroxyphenylethyleneglycol (MHPG) was reduced significantly (49‐70%) in MSA compared to PD. In contrast, several brain‐specific proteins (tau, neuron‐specific enolase, myelin basic protein) were elevated...
A detailed annotation of non-protein coding RNAs is typically missing in initial releases newly sequenced genomes. Here we report on a comprehensive ncRNA the genome Trichoplax adhaerens , presumably most basal metazoan whose has been published to-date. Since blast identified only small fraction best-conserved ncRNAs—in particular rRNAs, tRNAs and some snRNAs—we developed semi-global dynamic programming tool, GotohScan to increase sensitivity homology search. It successfully full complement...
Abstract Background: Cerebrospinal fluid (CSF) concentrations of amyloid β42 (Aβ42) peptides and tau proteins may serve as biomarkers for Alzheimer disease (AD). Recently, the xMAP technology has been introduced an alternative to ELISA measurement these markers. Methods: We used assays analyze CSF Aβ42, total (t-tau), phosphorylated at threonine 181 (p-tau181) in samples from 69 patients with disease, 26 vascular dementia, 55 controls without neurological disorders. Results: High CV values...
Dicer proteins are highly conserved, present in organisms ranging from plants to metazoans, and essential components of the RNA interference pathway. Although complement has been investigated many "higher" there no corresponding characterization any early-branching metazoan. We cloned partial cDNAs genes belonging family anthozoan cnidarian Nematostella vectensis two distantly related haplotypes (species lineages) Placozoa (Trichoplax adhaerens 16S haplotype 1 [H1] sp. [H2]). also identified...
Multiple osteochondromas (MO) is a hereditary skeletal disorder characterized by the presence of cartilage capped bony outgrowths at bone surface. Causative mutations in EXT1 or EXT2 genes have been described 85-90 % MO cases. However, about 10-15 cases, genomic alterations can not be detected, implying potential role other alterations. We designed custom-made Agilent oligonucleotide-based microarray, containing 44,000 probes, with tiling coverage EXT1/2 and addition 68 involved heparan...