A5045516315- Cancer Cells and Metastasis
- MicroRNA in disease regulation
- 3D Printing in Biomedical Research
- Cell Adhesion Molecules Research
- Eicosanoids and Hypertension Pharmacology
- Barrier Structure and Function Studies
- Caveolin-1 and cellular processes
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Inflammatory mediators and NSAID effects
- Neuroinflammation and Neurodegeneration Mechanisms
- PARP inhibition in cancer therapy
- Circular RNAs in diseases
- Mesenchymal stem cell research
- Cellular Mechanics and Interactions
- Axon Guidance and Neuronal Signaling
- Immune cells in cancer
- Angiogenesis and VEGF in Cancer
- Pancreatic function and diabetes
- Cancer-related molecular mechanisms research
- Nuclear reactor physics and engineering
- Cannabis and Cannabinoid Research
- Catalytic Processes in Materials Science
- Glioma Diagnosis and Treatment
- Extracellular vesicles in disease
- Venous Thromboembolism Diagnosis and Management
King's College London
2017-2024
University of Bristol
2019-2024
European Institute of Oncology
2022-2024
Centre for Inflammation Research
2024
Brunel University of London
2024
Istituti di Ricovero e Cura a Carattere Scientifico
2023
The Open University
2014-2022
Institute of Molecular Biology and Biophysics
2015
Universidad Complutense de Madrid
2008-2010
Because metastasis is associated with the majority of cancer-related deaths, its prevention a clinical aspiration. Prostanoids are large family bioactive lipids derived from activity cyclooxygenase-1 (COX-1) and COX-2. Aspirin impairs biosynthesis all prostanoids through irreversible inhibition both COX isoforms. Long-term administration aspirin leads to reduced distant metastases in murine models trials, but isoform, downstream prostanoid, cell compartment responsible for this effect yet be...
ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond these treatments most them eventually relapse. The existence this population particularly non-responding or relapsing urges the search for novel purpose study was determine whether cannabinoids might constitute new therapeutic tool treatment tumors. We analyzed...
Pro-inflammatory cytokine-induced activation of nuclear factor, NF-κB has an important role in leukocyte adhesion to, and subsequent migration across, brain endothelial cells (BECs), which is crucial for the development neuroinflammatory disorders such as multiple sclerosis (MS). In contrast, microRNA-146a (miR-146a) emerged anti-inflammatory molecule by inhibiting activity various cell types, but its effect BECs during neuroinflammation remains to be evaluated. Here, we show that miR-146a...
Abstract Leukocyte adhesion to brain endothelial cells, the blood-brain barrier main component, is a critical step in pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). mediated mainly by selectins, cell molecules and chemokines induced pro-inflammatory cytokines TNFα IFNγ, but regulation this process not fully clear. This study investigated firm leukocyte human endothelium two different microRNAs (miRs), miR-126 miR-126*, that are downregulated IFNγ line, hCMEC/D3....
Abstract INTRODUCTION Genome‐wide association studies link susceptibility to late‐onset Alzheimer's disease (LOAD) with EphA 1. Sequencing identified a non‐synonymous substitution P460L as LOAD risk variant. Other Ephs regulate vascular permeability and immune cell recruitment. We hypothesized that dysregulates EphA1 receptor activity impacts neuroinflammation. METHODS EphA1/P460L was assayed in isogenic Human Embryonic Kidney (HEK) cells. Soluble (sEphA1/sP460L) reverse signaling brain...
Increased leukocyte adhesion to brain endothelial cells forming the blood–brain barrier (BBB) precedes extravasation into central nervous system (CNS) in neuroinflammatory diseases such as multiple sclerosis (MS). Previously, we reported that microRNA-155 (miR-155) is up-regulated MS and by inflammatory cytokines human endothelium, with consequent modulation of paracellular permeability. Here, investigated role miR-155 cerebral microvascular cell line, hCMEC/D3, under shear forces mimicking...
Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain malignancy. stem-like cells (GSCs) can migrate in vascular niches within or away from tumour mass, increasing resistance to treatments contributing relapses. To study individual GSC migration their interactions with perivasculature microenvironment, there a need develop human organotypic vitro model. Herein, we demonstrated perivascular niche-on-a-chip, serum-free condition gravity-driven flow, that...
Attachment of circulating tumor cells to the endothelial (ECs) lining blood vessels is a critical step in cancer metastatic colonization, which leads outgrowth. Breast and prostate cancers are common malignancies women men, respectively. Here, we observe that β1-integrin required for human breast cell adhesion ECs under shear-stress conditions vitro lung vessel vivo. We identify IQGAP1 neural Wiskott-Aldrich syndrome protein (NWASP) as regulators transcription expression cells. NWASP...
The human vasculature is essential in organs and tissues for the transport of nutrients, metabolic waste products, maintenance homeostasis. integration vessels vitro organs-on-chip may, therefore, improve similarity to native organ microenvironment, ensuring proper physiological functions reducing gap between experimental research clinical outcomes. This particularly evident drug testing use vascularized models may provide more realistic insights into responses drugs pre-clinical phases...
Herein, we report the synthesis and characterization of nanospheres a biodegradable zinc-imidazolate polymers (ZIPs) as proof-of-concept delivery vehicle into human brain endothelial cells, main component blood-brain barrier (BBB). The ZIP particles can readily encapsulate functional molecules such fluorophores inorganic nanoparticles at point producing stable colloidal dispersions. Our results show that these are not cytotoxic, able to penetrate release cargo species capillary cells in...
Abstract Brain metastasis from breast cancer (BCBM) are lethal tumors occurring in 10-15% of IV stage cancers against which only limited therapeutic options available. A critical hindrance to the design novel approaches is narrow set preclinical models study BCBM pathophysiology, chiefly those resembling stem-like population thought be main source dissemination and progression. We aimed isolate patient-derived metastasis-initiating cells (MICs) furnish metastatization. MICs were cultured as...
The blood-brain barrier (BBB) acquires unique properties to regulate neuronal function during development. formation of the BBB, which occurs in tandem with angiogenesis, is directed by Wnt/β-catenin signaling pathway. Yet exact molecular interplay remains elusive. Our study reveals G protein–coupled receptor GPR126 as a critical target canonical Wnt signaling, essential for development BBB's distinctive vascular characteristics and its functional integrity. Endothelial cell–specific...
<ns7:p>Adhesion between cancer cells and endothelial cells, lining the blood vessels, is a key event during tumour progression metastasis formation. However, analysis of its underlying cellular molecular mechanisms largely limited by intrinsic difficulties to study interactions circulating <ns7:italic>in vivo</ns7:italic>, vitro</ns7:italic> under conditions that mimic vivo</ns7:italic> flow. Here, we developed method cell:cell firm adhesion shear-stress coupled high-content live-cell...
Abstract Evidence from experimental studies and clinical trials has shown that aspirin reduces the incidence of distant metastases. Aspirin inhibits cyclooxygenase (COX)-1 COX-2, triggering anti-thrombotic anti-inflammatory effects, respectively. However, mechanisms underlying anti-metastatic effect are still largely unknown. By employing mouse models spontaneous metastasis, we have a selective COX-1 inhibitor dramatically reduced metastatic lung nodules, an was not replicated by inhibition...
Abstract Glioblastoma multiforme (GBM), is the most common and aggressive type of primary brain malignancy. stem- like cells (GSCs) are able to migrate in vascular niches within or away from tumour mass, increasing resistance patient treatments contributing relapses. To study individual GSCs migration their interactions with microenvironment vasculature, there a need develop model human blood vessels vitro . Herein, we report systematic on interaction between patient-derived glioma cell...
Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main source(s): British Heart Foundation Introduction Cardiovascular inflammation is associated with endothelial cell (EC) damage, resulting in leukocyte trafficking and oedema formation. Inflammation disrupts EC junctions, increasing microvascular permeability, a positive-feedback loop inflammatory events. The phosphoinositide 3-kinase pathway stimulates this response study examined the actions BYL-719, PI3K-α...
Abstract The blood–brain barrier (BBB) acquires unique properties for regulation of the neuronal function during development. genesis BBB coupled with angiogenesis is orchestrated by Wnt/β-catenin signaling pathway. Aside from importance signaling, molecular mechanisms that regulate these processes are poorly understood. Here, we identify brain endothelial adhesion G-protein–coupled receptor Gpr126 as a novel target gene required postnatal development, and its expression detrimental ischemic...