A5009637222- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- Angiogenesis and VEGF in Cancer
- Cell Adhesion Molecules Research
- Wnt/β-catenin signaling in development and cancer
- Hippo pathway signaling and YAP/TAZ
- Hematopoietic Stem Cell Transplantation
- Cellular Mechanics and Interactions
- Protein Kinase Regulation and GTPase Signaling
- Protease and Inhibitor Mechanisms
- Mesenchymal stem cell research
- Adrenal and Paraganglionic Tumors
- Lung Cancer Research Studies
- Epigenetics and DNA Methylation
- Erythrocyte Function and Pathophysiology
- Kruppel-like factors research
- Cancer-related molecular mechanisms research
- NF-κB Signaling Pathways
- Blood Coagulation and Thrombosis Mechanisms
- Cytokine Signaling Pathways and Interactions
- Galectins and Cancer Biology
- Neonatal Respiratory Health Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Protein Tyrosine Phosphatases
University of Amsterdam
2010-2025
Sanquin
2012-2025
Princess Máxima Center
2019-2025
Amsterdam University Medical Centers
2020-2025
Max Planck Institute for Molecular Biomedicine
2024
Radboud University Nijmegen
2024
Radboud University Medical Center
2024
Amsterdam UMC Location University of Amsterdam
2012-2018
Amsterdam UMC Location Vrije Universiteit Amsterdam
2009
Endothelial cell-cell junctions maintain a restrictive barrier that is tightly regulated to allow dynamic responses permeability-inducing angiogenic factors as well inflammatory agents and adherent leukocytes. The ability of these stimuli transiently remodel adherens (AJs) depends on Rho-GTPase-controlled cytoskeletal rearrangements. How activity Rho-GTPases spatio-temporally controlled at endothelial AJs by guanine-nucleotide exchange (GEFs) incompletely understood. Here, we identify...
We recently identified MAL (T-lymphocyte maturation associated protein) as the most down-regulated gene in cervical oncogenesis. Here, we examined mechanism underlying silencing, its functional role carcinogenesis, and relevance of detecting alterations for risk assessment hrHPV-positive women. mRNA expression promoter methylation were analysed primary keratinocytes, hrHPV-immortalized cancer cell lines, biopsies, scrapings by quantitative (methylation-specific) PCR. SiHa cells transfected...
Impaired endothelial barrier function results in a persistent increase permeability and vascular leakage. Repair of dysfunctional requires controlled restoration adherens junctions, comprising (VE)-cadherin associated β-, γ-, α-, p120-catenins. Little is known about the mechanisms by which recovery VE-cadherin–mediated cell–cell junctions regulated. Using inflammatory mediator thrombin, we demonstrate an important role for Src homology 2-domain containing tyrosine phosphatase (SHP2)...
VE-cadherin-based cell-cell junctions form the major restrictive barrier of endothelium to plasma proteins and blood cells. The function VE-cadherin actin cytoskeleton are intimately linked. Vascular permeability factors adherent leukocytes signal through small Rho GTPases tightly regulate cytoskeletal rearrangements in order open re-assemble endothelial a rapid controlled manner. activated by guanine nucleotide exchange (GEFs), conferring specificity context-dependent control junctions....
Autologous hematopoietic stem cell transplantation is used to restore bone marrow function after high-dose chemotherapy. For apheresis, granulocyte colony-stimulating factor (G-CSF) standard of care, but obtaining sufficient cells can be challenging. Other mobilization agents include plerixafor and PEGylated G-CSF (PEG-G-CSF). While efficacy these established in adults, limited data for their use pediatric patients are available. Here, we compare Good versus Poor Mobilizers study success...
PURPOSE Patients with neuroblastoma in molecular remission remain at considerable risk for disease recurrence. Studies have found that tissue contains adrenergic (ADRN) and mesenchymal (MES) cells; the latter express low levels of commonly used markers minimal residual (MRD). We identified MES-specific MRD studied dynamics these during treatment. PATIENTS AND METHODS Microarray data were to identify genes differentially expressed between ADRN MES cell lines. Candidate then using real-time...
Current immunotherapy for patients with high-risk neuroblastoma involves the therapeutic antibody dinutuximab that targets GD2, a ganglioside expressed on majority of tumors. Opsonized tumor cells are killed through antibody-dependent cellular cytotoxicity (ADCC), process mediated by various immune cells, including neutrophils. The capacity neutrophils to kill dinutuximab-opsonized can be further enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF), which has been shown in past...
Inflammation is characterized by endothelium that highly expresses numerous adhesion molecules to trigger leukocyte extravasation. Central this event increased gene transcription. Small Rho-GTPases not only control the actin cytoskeleton, but are also implicated in regulation. However, inflammation, it clear how regulated. Here, we show guanine-nucleotide exchange factor Trio expression upon inflammatory stimuli endothelium. Additionally, was found vessel wall of rheumatoid arthritis...
Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, is expressed and secreted by endothelial cells. Patients with PAI-1 deficiency show mild to moderate bleeding diathesis, which has been exclusively ascribed the function of in down-regulating fibrinolysis. We tested hypothesis that plays direct role controlling vascular integrity permeability keeping cell-cell junctions intact.
Background: The bone marrow (BM) is the main site of metastases and relapse in patients with neuroblastoma (NB). BM-residing mesenchymal stromal cells (MSCs) were shown to promote tumor cell survival chemoresistance. Here we characterize MSC compartment metastatic NB BM niche. Methods: Fresh 62 (all stages), control fetal adult studied by flow cytometry using well-established MSC-markers (CD34−, CD45−, CD90+, CD105+), CD146 CD271 subtype-markers. FACS-sorted MSCs validated qPCR. Moreover,...
Abstract Background Patient participation is fundamental in nursing care and has yielded benefits for patient outcomes. However, despite their compassionate approach, nurses do not always incorporate patients' needs wish into evidence‐based practice, quality improvement or learning activities. Therefore, a shift to continuous based on practice necessary enhance the of care. The patient's opinion an essential part this process. To establish more sustainable culture improvement, it crucial...
Despite their indisputable importance in neuroblastoma (NB) pathology, knowledge of the bases NB plasticity and heterogeneity remains incomplete. They may be rooted developmental trajectories lineage origin, sympatho-adrenal neural crest. We find that implanting human cells crest avian embryo allows recapitulating metastatic sequence until bone marrow involvement. Using deep single cell RNA sequencing, we characterize transcriptome states dynamics over time space, compare them to those fetal...
Targeted radiotherapy with 131iodine-meta-iodobenzylguanidine (131I-MIBG) is effective for neuroblastoma (NBL), although optimal scheduling during high-risk (HR) treatment being investigated. We aimed to evaluate the feasibility of stem cell apheresis and study hematologic reconstitution after autologous transplantation (ASCT) in patients HR-NBL treated upfront 131I-MIBG-therapy.In two prospective multicenter cohort studies, newly diagnosed were courses 131I-MIBG-therapy, followed by an...
Endothelial cell-cell junctions maintain a restrictive barrier that is tightly regulated to allow dynamic responses permeability-inducing angiogenic factors, as well inflammatory agents and adherent leukocytes. The ability of these stimuli transiently remodel adherens depends on Rho-GTPase-controlled cytoskeletal rearrangements. How the activity Rho-GTPases spatio-temporally controlled at endothelial by guanine-nucleotide exchange factors (GEFs) incompletely understood. Here, we identify...
Abstract: Endothelial cell–cell junctions are strictly regulated in order to control the barrier function of endothelium. Vascular endothelial (VE)-cadherin is one proteins that crucial this process. It has been reported phosphorylation events VE-cadherin. This review summarizes role VE-cadherin regulation and highlights how affects vascular permeability leukocyte extravasation. Keywords: endothelium, VE-cadherin, junctions, barrier,
Abstract Bone marrow (BM) is a common site for solid tumor metastasis, often causing poor outcome. Here, we define the characteristics of BM-disseminated cells (DTCs) using neuroblastoma as model. We combined single-cell RNA-sequencing (scRNA-seq) and cell-surface protein analysis 7 paired BM primary (PT) samples found that DTCs contain higher percentage cycling expression neurodevelopmental genes compared to corresponding PT cells. In 6 patients, copy number variation profile differed...
C-terminal Src kinase (Csk) targets family kinases (SFKs) and thereby inactivates them. We have previously shown that Csk binds to phosphorylated tyrosine 685 of VE-cadherin, an adhesion molecule major importance for the regulation endothelial junctions. This residue is SFK target, its mutation (VE-cadherin-Y685F) inhibits induction vascular permeability in various inflammation models. Nevertheless, surprisingly, it increases leukocyte extravasation. Here, we investigated whether involved...
<p>S1: Neutrophil recovery post ASCT S2: Clonogenic capacity harvested stem cells</p>
<p>Legends</p>
<p>CD34+cell harvest yield and quality</p>