A5038974602- Glioma Diagnosis and Treatment
- Cancer Research and Treatments
- Nanoplatforms for cancer theranostics
- Photodynamic Therapy Research Studies
- Cancer Genomics and Diagnostics
- Extracellular vesicles in disease
- Immune cells in cancer
- Cancer Cells and Metastasis
- Neuroblastoma Research and Treatments
- Cardiovascular Disease and Adiposity
- Adipokines, Inflammation, and Metabolic Diseases
- Chemical Reactions and Isotopes
- Single-cell and spatial transcriptomics
- Ferroptosis and cancer prognosis
- Pancreatic and Hepatic Oncology Research
- Nuclear Structure and Function
- Testicular diseases and treatments
- Peroxisome Proliferator-Activated Receptors
- Genetic factors in colorectal cancer
- Meningioma and schwannoma management
- Vascular Malformations Diagnosis and Treatment
- Renal and related cancers
- Advanced Electron Microscopy Techniques and Applications
- Chromatin Remodeling and Cancer
- Immunotherapy and Immune Responses
Princess Máxima Center
2020-2025
University Medical Center Utrecht
2013-2025
Heidelberg University
2020-2025
University Hospital Heidelberg
2020-2025
Utrecht University
2013-2024
University Medical Center Groningen
2024
University of Groningen
2024
National Institute for Public Health and the Environment
2024
University of Zurich
2023
Cancer Genomics Centre
2013
The intestinal epithelium is maintained by a population of rapidly cycling ( Lgr5 + ) stem cells (ISCs). It has been postulated, however, that slowly ISCs must also be present in the intestine to protect genome from accumulating deleterious mutations and allow for response tissue injury. Here, we identify subpopulation marked mouse telomerase reverse transcriptase mTert expression can give rise cells. -expressing distribute pattern along crypt–villus axis similar long-term label-retaining...
Purpose: To provide proof of principle safety, breast tumor-specific uptake, and positive tumor margin assessment the systemically administered near-infrared fluorescent tracer bevacizumab-IRDye800CW targeting VEGF-A in patients with cancer.Experimental Design: Twenty primary invasive cancer eligible for surgery received 4.5 mg as intravenous bolus injection. Safety aspects were assessed well uptake delineation during ex vivo surgical specimens using an optical imaging system. Ex multiplexed...
Abstract Central nervous system tumours represent one of the most lethal cancer types, particularly among children 1 . Primary treatment includes neurosurgical resection tumour, in which a delicate balance must be struck between maximizing extent and minimizing risk neurological damage comorbidity 2,3 However, surgeons have limited knowledge precise tumour type prior to surgery. Current standard practice relies on preoperative imaging intraoperative histological analysis, but these are not...
SUMMARY Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (hereafter, GB), is an aggressive brain malignancy associated with a dismal prognosis and poor quality of life. Single-cell RNA sequencing has helped to grasp the complexity cell states dynamic changes in GB. Large-scale data integration can help uncover unexplored tumor pathobiology. Here, we resolved composition milieu created cellular map GB (‘GBmap’), curated resource that harmonizes 26 datasets gathering 240 patients spanning...
Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain stem tumor and the leading cause of pediatric cancer-related death. To date, these tumors remain incurable, underscoring need for efficacious therapies. In this study, we demonstrate that immune checkpoint TIM-3 (HAVCR2) highly expressed in both cells microenvironmental cells, mainly microglia macrophages, DIPG. We show inhibition syngeneic models DIPG prolongs survival produces long-term survivors free disease harbor memory....
Extracellular vesicles (EVs) released by human adipocytes or adipose tissue (AT)-explants play a role in the paracrine interaction between and macrophages, key mechanism AT inflammation, leading to metabolic complications like insulin resistance (IR) were determined.EVs from vitro differentiated AT-explants ex vivo characterized electron microscopy, Western blot, multiplex adipokine-profiling, quantified flow cytometry. Primary monocytes stimulated with EVs adipocytes, subcutaneous (SCAT)...
Objective Insulin resistance (IR) is a key mechanism in obesity-induced cardiovascular disease. To unravel mechanisms whereby human adipose tissue (AT) contributes to systemic IR, the effect of AT-extracellular vesicles (EVs) on insulin signaling liver and muscle cells was determined. Methods EVs released from subcutaneous (SAT) omental AT (OAT)-explants ex vivo were used for stimulation hepatocytes myotubes vitro. Subsequently, insulin-induced Akt phosphorylation expression gluconeogenic...
Alterations in extracellular vesicles (EVs), including exosomes and microparticles, contribute to cardiovascular disease. We hypothesized that obesity could favour enhanced release of EVs from adipose tissue, thereby risk via obesity-induced metabolic complications. The objectives this study were: 1) investigate the relation between quantity, distribution (dys) function tissue plasma concentrations atherothrombotic EV-markers; 2) determine these EV-markers prevalence syndrome; 3) assess...
Whole genome sequencing (WGS) using fresh-frozen tissue and matched blood samples from cancer patients may become the most complete genetic tumor test. With increasing availability of small biopsies need to screen more number biomarkers, use a single all-inclusive test is preferable over multiple consecutive assays. To meet high-quality diagnostics standards, we optimized clinically validated WGS sample data processing procedures, resulting in technical success rate 95.6% for with sufficient...
Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation has emerged as useful tool for robust tumor classification, providing new insights into these heterogeneous classes. This is particularly true rare CNS with broad morphological spectrum, which are not possible...
Abstract Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups ependymoma are characterized by distinct alterations and/or patterns. Based on unsupervised visualization large cohort genome-wide DNA methylation data, we highly pediatric-type tumors ( n = 40) forming cluster separate from all established CNS tumor types,...
iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 2021, 302 samples from 253 patients were included. Comprehensive profiling including low-coverage whole genome sequencing (lcWGS), exome (WES), RNA (RNA-seq), Affymetrix, and/or 850k methylation was successfully performed for 226 at least 20% content. Germline...
Gene fusions play a significant role in cancer etiology, making their detection crucial for accurate diagnosis, prognosis, and determining therapeutic targets. Current diagnostic methods largely focus on either targeted or low-resolution genome-wide techniques, which may be unable to capture rare events both fusion partners. We investigate if RNA sequencing can overcome current limitations with traditional techniques identify gene events.
Aims Tumour-associated macrophages (TAMs) and regulatory T cells (Tregs) form a special niche supporting tumour progression, both correlate with worse survival in head neck cancers. However, the prognostic role of TAM Tregs nasopharyngeal carcinoma (NPC) is still unknown. Therefore, we determined differences TAMs different NPC subtypes, their significance. Methods Tissue 91 NPCs was assessed for by determination CD68, CD163, CD206 FOXP3 expression microenvironment. Clinicopathological...
In vivo tumor labeling with fluorescent agents may assist endoscopic and surgical guidance for cancer therapy as well create opportunities to directly observe biology in patients. However, malignant nonmalignant tissues are usually distinguished on fluorescence images by applying empirically determined intensity thresholds. Here, we report the development of fSTREAM, a set analytic methods designed streamline analysis surgically excised breast collecting statistically processing hybrid...
Abstract Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification combination with copy number, RNA-seq, ChIP-seq analysis to characterize newly identified type. In addition,...
Abstract Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4 . ATRTs can be further classified different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that have distinct clinical features, subgroup-specific treatment regimens not been developed thus far. This is hampered lack of...
Abstract Lynch syndrome (LS) predisposes to cancer in adulthood and is caused by heterozygous germline variants a mismatch repair (MMR) gene. Recent studies show an increased prevalence of LS among children with cancer, suggesting causal relationship. For LS‐spectrum (LSS) cancers, including high‐grade gliomas colorectal causality has been supported typical MMR‐related tumor characteristics, but for non‐LSS unclear. We characterized 20 malignant tumors 18 LS, 16 tumors. investigated second...
ABSTRACT Aims Embryonal tumours with PLAGL1 or PLAGL2 amplification (ET, PLAGL) show substantial heterogeneity regarding their clinical characteristics and have been treated inconsistently, resulting in diverse outcomes. In this study, we aimed to evaluate the behaviour of ET, PLAGL elucidate response pattern across different applied treatment regimens. Methods We conducted an in‐depth retrospective analysis serial imaging data 18 patients (nine each amplified). Results Patients ‐amplified...
Abstract Background Glioblastoma (GB), particularly IDH-wildtype, is the most aggressive brain malignancy with a dismal prognosis. Despite advances in molecular profiling, complexity of its tumor microenvironment and spatial organization remains poorly understood. This study aimed to create comprehensive single-cell atlas GB unravel cellular heterogeneity, architecture, clinical relevance. Methods We integrated RNA sequencing data from 26 datasets, encompassing over 1.1 million cells 240...
Abstract We determined the dynamics of CD8+ T cells specific for influenza virus and respiratory syncytial in blood tracheostoma aspirates children during course infections. showed that localized infections ratio activated effector to resting memory/naive peripheral increased significantly. Furthermore, number effector/memory viruses declined airways, suggesting these redistributed from airways. infecting were present airways longer periods at levels than nonspecifically recruited bystander...
Familial partial lipodystrophy (FPLD) is a rare metabolic disorder with clinical features that may not be readily recognised. As FPLD patients require specific therapeutic approach, early identification warranted. In the present study we aimed to identify cases of among non-obese type 2 diabetes mellitus and marked insulin resistance. We searched databases three diabetic outpatient clinics for resistance, arbitrarily defined as use ≥100 U insulin/day, BMI ≤ 27 kg/m2. all patients, variables...