A5080122643- Colorectal Cancer Treatments and Studies
- Pancreatic and Hepatic Oncology Research
- Lung Cancer Treatments and Mutations
- Acute Myeloid Leukemia Research
- Advanced Proteomics Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Chronic Lymphocytic Leukemia Research
- Radiomics and Machine Learning in Medical Imaging
- Cancer Genomics and Diagnostics
- Mitochondrial Function and Pathology
- Cell Adhesion Molecules Research
- Cardiomyopathy and Myosin Studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Renal cell carcinoma treatment
- Fibroblast Growth Factor Research
- Chronic Myeloid Leukemia Treatments
- HER2/EGFR in Cancer Research
- Glioma Diagnosis and Treatment
- Melanoma and MAPK Pathways
- Metabolism and Genetic Disorders
- Phosphodiesterase function and regulation
- Neurogenetic and Muscular Disorders Research
- Extracellular vesicles in disease
- PI3K/AKT/mTOR signaling in cancer
- Neurosurgical Procedures and Complications
Cancer Center Amsterdam
2023-2025
Amsterdam UMC Location Vrije Universiteit Amsterdam
2015-2025
Amsterdam University Medical Centers
2020-2023
Vrije Universiteit Amsterdam
2007-2023
University of California, San Diego
1995-2022
St. Josef-Hospital
2006
Heinrich Heine University Düsseldorf
2006
University Medical Center Freiburg
1997-2000
Exosomes are small endosome-derived extracellular vesicles implicated in cell–cell communication and secreted by living cells when multivesicular bodies (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome physiology based on isolation procedures after secretion, precluding direct dynamic insight into mechanics of biogenesis regulation their release. In this study, we propose real-time visualization MVB–PM fusion overcome these limitations. We designed...
Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. Aberrant tyrosine kinase activity influences tumor growth and regulated by phosphorylation. We investigated phosphorylated kinases as target in PDAC.Mass spectrometry-based phosphotyrosine proteomic analysis on PDAC cell lines was used to evaluate active kinases. Pathway inferred performed identify novel targets. Subsequently, we targeting of focal adhesion (FAK) vitro drug perturbations...
Bladder cancer often recurs, necessitating innovative treatments to reduce recurrence. We investigated non-thermal plasma's potential as a novel anti-cancer therapy, focusing on plasma-activated solution (PAS), created by exposing saline plasma. Our study aims elucidate the biological effects of PAS bladder cell lines in vitro, well combination with mitomycin C (MMC), using clinically relevant settings. treatment exerts potent cytotoxic effect through production intracellular reactive oxygen...
The hypoxia-inducible endothelial cell-specific mitogen vascular growth factor/vascular permeability factor (VEGF/VPF) is expressed in low amounts adult human brain, but highly upregulated the perinecrotic palisading cells of glioblastomas. We observed high VEGF expression cerebellar hemangioblastomas, which arc vascular, non-necrotic and presumably nonhypoxic tumors, hypothesized that a mechanism other than hypoxia leads to upregulation. Because hemangioblastomas develop patients with von...
Tyrosine kinase inhibitors (TKIs) have poor efficacy in patients with glioblastoma (GBM). Here, we studied whether this is predominantly due to restricted blood-brain barrier penetration or more biological characteristics of GBM.Tumor drug concentrations the TKI sunitinib after 2 weeks preoperative treatment was determined 5 GBM and compared its <em>in vitro</em> inhibitory concentration (IC50) cell lines. In addition, phosphotyrosine (pTyr) directed mass spectrometry(MS)-based proteomics...
Epidermal growth factor receptor (EGFR) is a well-exploited therapeutic target in metastatic colorectal cancer (mCRC). Unfortunately, not all patients benefit from current EGFR inhibitors. Mass spectrometry-based proteomics and phosphoproteomics were performed on 30 genomically pharmacologically characterized mCRC patient-derived xenografts (PDXs) to investigate the molecular basis of response blockade identify alternative drug targets overcome resistance. Both tyrosine global...
Diastolic dysfunction is central to diseases such as heart failure with preserved ejection fraction and hypertrophic cardiomyopathy (HCM). However, therapies that improve cardiac relaxation are scarce, partly due a limited understanding of modulators cardiomyocyte relaxation. We hypothesized regulated by multiple unidentified proteins dysregulation kinases contributes impaired in patients HCM.We optimized increased the throughput unloaded shortening measurements screened kinase inhibitor...
Phenotypic expression of hypertrophic cardiomyopathy (HCM) and disease course are associated with unfavorable metabolic health. We investigated if Western diet (WD) feeding is sufficient to trigger cardiac hypertrophy dysfunction in heterozygous (HET) Mybpc3c.772G>A knock-in mice. Wild-type (WT) HET mice (3-months-old) were fed a WD or normal chow (NC) for 8 weeks. Metabolomic analyses on serum revealed systemic derailment WD-fed WT Strikingly, only developed dysfunction, which was not...
Combined application of multiple therapeutic agents presents the possibility enhanced efficacy and reduced development resistance. Definition most appropriate combination for any given disease phenotype is challenged by vast number theoretically possible combinations drugs doses, making extensive empirical testing a virtually impossible task. We have used streamlined-feedback system control (s-FSC) technique, phenotypic approach, which converges to optimized drug (ODC) within few...
Identification of predictive biomarkers for targeted therapies requires information on drug exposure at the target site as well its effect signaling context a tumor. To obtain more insight in clinical mechanism action protein kinase inhibitors (PKIs), we studied tumor concentrations (PKIs) and their tyrosine-(pTyr)-phosphoproteome patients with advanced cancer. Tumor biopsies were obtained from 31 cancer before after 2 weeks treatment sorafenib (SOR), erlotinib (ERL), dasatinib (DAS),...
Summary Circulating cells of several lineages are thought to participate in angiogenesis and tumor growth. Experimental studies tumorbearing mice have pointed the potential importance VEGFresponding circulating (endothelial) progenitor growth.We studied CD31- and/or CD34-positive cell populations with a low moderateVEGFR2 expression human volunteers cancer patients. We recognized four populations, which were further characterized by their content major hematopoetic progenitor, monocytic,...
The etiology of Rett syndrome (RS) remains a mystery. clinical phenotype has similarities to that patients with mitochondrial defects oxidative metabolism. There is evidence lactate and pyruvate elevations in blood CSF some patients. Over the last 10 years we have studied girls RS looking for defect We present data on measurements 30 repeated performed over time many. Taken as whole means fall within control range, however, individual marked elevation both considerable fluctuation time.
Abstract The tyrosine kinase inhibitor sunitinib is an effective first-line treatment for patients with advanced renal cell carcinoma (RCC). Hypothesizing that a functional read-out by mass spectrometry-based (phospho, p- )proteomics will identify predictive biomarkers outcome of sunitinib, tumor tissues 26 RCC were analyzed. Eight had primary resistant (RES) and 18 sensitive (SENS) RCC. A 78 phosphosite signature (p < 0.05, fold-change > 2) was identified; 22 p -sites upregulated in...
e13550 Background: Increased exposure to sunitinib is associated with improved outcome. Preclinical data shows promising antitumor activity of intermittent high concentrations. In this phase 1 trial the MTD and tolerability once weekly oral administration were investigated (ClinicalTrials.gov number, NCT02058901). Methods: Key eligibility: patients (pts) advanced solid malignancies, progressive, refractory standard treatment, measurable disease WHO≤ 1. Sunitinib was administered orally...