A5086583233- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Angiogenesis and VEGF in Cancer
- Wnt/β-catenin signaling in development and cancer
- Hippo pathway signaling and YAP/TAZ
- Chronic Myeloid Leukemia Treatments
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
- Intracranial Aneurysms: Treatment and Complications
- Microtubule and mitosis dynamics
- Hemoglobin structure and function
- Veterinary Practice and Education Studies
- Growth and nutrition in plants
- Agricultural safety and regulations
- Cutaneous Melanoma Detection and Management
- Cardiovascular Health and Disease Prevention
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Blood Coagulation and Thrombosis Mechanisms
- Plant Growth Enhancement Techniques
- Cardiomyopathy and Myosin Studies
- Veterinary Equine Medical Research
- Kruppel-like factors research
- Advanced Breast Cancer Therapies
Amsterdam University Medical Centers
2019-2020
Skyline College
2019
Amsterdam UMC Location Vrije Universiteit Amsterdam
2013-2016
Endothelial YAP/TAZ (YAP is also known as YAP1, and TAZ WWTR1) signaling crucial for sprouting angiogenesis vascular homeostasis. However, the underlying molecular mechanisms that explain how control vasculature remain unclear. This study reveals focal adhesion protein deleted-in-liver-cancer 1 (DLC1) a direct transcriptional target of activated YAP/TAZ-TEAD complex. We find substrate stiffening VEGF stimuli promote expression DLC1 in endothelial cells. In turn, levels are YAP dependent,...
Primary plasma cell leukemia (pPCL) is an aggressive subtype of multiple myeloma, which distinguished from newly diagnosed myeloma (NDMM) on the basis presence ≥ 20% circulating tumor cells (CTCs). A molecular marker for pPCL currently lacking, could help identify NDMM patients with high-risk PCL-like disease, despite not having been recognized as such clinically.
Endothelial barrier disruption and vascular leak importantly contribute to organ dysfunction mortality during inflammatory conditions like sepsis acute respiratory distress syndrome. We identified the kinase Arg/Abl2 as a mediator of endothelial disruption, but role Arg in monolayer regulation its relevance vivo remain poorly understood. Here we show that depletion cells results activation both RhoA Rac1, increased cell spreading elongation, redistribution integrin-dependent cell-matrix...
This paper describes a novel model that allows exploration of matrix-induced cardiomyocyte adaptations independent the passive effect matrix rigidity on function. Detachment adult cardiomyocytes from enables study effects cell shortening, Ca2+ handling and myofilament Cell shortening are altered in cultured for 24 h stiff matrix. Matrix stiffness-impaired contractility is reversed upon normalization extracellular stiffness. stiffness-induced reduction unloaded more pronounced isolated obese...
Typically, prognostic capability of gene expression profiling (GEP) is studied in the context clinical trials, for which 50%-80% patients are not eligible, possibly limiting generalizability findings to routine practice. Here, we evaluate GEP analysis outside aiming improve risk assessment multiple myeloma (MM) patients.A total 155 bone marrow samples from MM were collected RNA was analyzed by microarray. Sixteen previously developed GEP-based markers evaluated, combined with survival data,...
Background: Rho kinase (ROCK) is the major effector protein of RhoA and known to mediate F-actin stress fibers. ROCK activates myosin motors. Actomyosin-generated contractile forces can be transmitted cell-cell junctions, resulting in increased junctional tension, disassembly endothelial hyperpermeability. In apparent contrast, basal activity required for maintenance barrier integrity . We hypothesize that these dual roles could contributed two highly homologous expressed isoforms. Methods:...
Introduction Endothelial barrier disruption and vascular leakage during inflammation forms an important threat to the critically ill. In a recent study we demonstrated that tyrosine kinase inhibitor imatinib effectively attenuates endothelial via inhibition of Abl-related gene (ARG). Here, evaluate how ARG mediates disruption. Methods & Results was depleted from cells with various siRNAs, yielding >85% reduction in protein expression. Disruption by inflammatory mediator thrombin lower...
Introduction: Even though the majority of newly diagnosed multiple myeloma (NDMM) patients has benefited significantly from introduction novel agents, it remains an unmet need to identify best upfront treatment strategy for high-risk disease. Risk-adapted trial designs (e.g., OPTIMUM/MUKnine trial, NCT03188172, and GMMG-CONCEPT NCT03104842) aim answer this question, which in turn drive research efforts improve risk assessment NDMM. Recently, our group published two prognostic tools NDMM: (I)...
Background: In multiple myeloma (MM) patients, quality of life is a relevant outcome parameter due to the chronic nature disease. Therefore, clinical trials are now more often including as secondary measure. Multinational studies usually pool estimates without evaluating potential differences between nationalities. Although in other disease areas have shown that scores differ countries. Whether nationalities also account for variation MM still unknown. Aims: The aim this study evaluate...
Background: Many different treatment regimens are currently available for Multiple Myeloma (MM) patients. There is ongoing research to identify subgroups of patients who may benefit from specific treatments. Recently, it was found that with low‐risk MM (SKY92 standard‐risk, ISS stage I, and no del(17p)) had a better overall survival after receiving Bortezomib, Melphalan Prednisone (VMP) combination therapy compared High‐dose followed by an autologous stem cell transplantation...
Abstract YAP/TAZ signaling is crucial for sprouting angiogenesis and vascular homeostasis through the regulation of endothelial remodeling. Thus far underlying molecular mechanisms that explain how control vasculature remain unclear. We here identify Deleted-in-Liver-Cancer-1 (DLC1) as a direct transcriptional target activated YAP/TAZ-TEAD complex in endothelium. Substrate stiffening VEGF stimuli promote expression DLC1. DLC1 dependent on presence YAP TAZ, constitutive activation efficiently...