A5052179348- Cancer, Hypoxia, and Metabolism
- Cytokine Signaling Pathways and Interactions
- Angiogenesis and VEGF in Cancer
- NF-κB Signaling Pathways
- Immune Response and Inflammation
- Venous Thromboembolism Diagnosis and Management
- Rheumatoid Arthritis Research and Therapies
- Cell Adhesion Molecules Research
- Diagnosis and Treatment of Venous Diseases
- High Altitude and Hypoxia
- Cancer, Lipids, and Metabolism
- Immune cells in cancer
- Inflammatory mediators and NSAID effects
- HER2/EGFR in Cancer Research
- Cancer-related molecular mechanisms research
- CAR-T cell therapy research
- Colorectal Cancer Treatments and Studies
- Virus-based gene therapy research
- Systemic Sclerosis and Related Diseases
- Colorectal Cancer Surgical Treatments
- Immunotherapy and Immune Responses
- Autoimmune and Inflammatory Disorders Research
- Gastric Cancer Management and Outcomes
- Peptidase Inhibition and Analysis
- Phytoestrogen effects and research
University of Oxford
2012-2024
Nuffield Orthopaedic Centre
2017-2023
Imperial College London
2003-2013
University College London
2011
Hammersmith Hospital
2007
Kennedy Center
2006
Institute of Rheumatology
2006
University of Bonn
1997-2005
Charing Cross Hospital
2002
Nuclear factor κB (NF-κB) activation has been observed in human atherosclerotic plaques and is enhanced unstable coronary plaques, but whether such a protective or pathophysiological role remains to be determined. We addressed this question by developing short-term culture system of cells isolated from tissue, allowing efficient gene transfer directly investigate signaling pathways atherosclerosis. found that NF-κB activated these activity involves p65, p50, c-Rel not p52 RelB. This can...
Vascular endothelial growth factor (VEGF) is the most cell-specific angiogenic characterised to date, and it produced by a variety of cell types. In macrophages, VEGF has been shown be upregulated inflammatory mediator lipopolysaccharide (LPS) engagement CD40 ligand (CD40L). Because LPS CD40L activate nuclear factor-kappaB (NF-kappaB) in monocytes, we investigated this study whether production when stimulated with either or CD40L, NF-kappaB-dependent. We used adenoviral constructs...
Hypoxia-inducible factor-1 (HIF-1) has been reported to promote tolerance against acute myocardial ischaemia–reperfusion injury (IRI). However, the mechanism through which HIF-1 stabilization actually confers this cardioprotection is not clear. We investigated whether HIF-1α protects heart IRI by preventing opening of mitochondrial permeability transition pore (MPTP) and potential mechanisms involved. Stabilization was achieved pharmacological inhibition prolyl hydroxylase (PHD)...
Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity affects arthritis. To characterize community structure and associated functional processes driving microbial involvement arthritis, Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 diagnosed with rheumatoid ankylosing...
The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form positron emission tomography (PET), means detect and quantify inflammation vivo. However, existing literature regarding human macrophages lacking, mostly deriving from brain tissue studies, including studies malignancy, inflammatory diseases such multiple sclerosis. Here, we...
Anti-angiogenic strategies are emerging as an important tool for the treatment of cancer and inflammatory diseases. In present investigation we isolated several isoflavones from a tempeh (fermented soyabean) extract. The were identified 5,7,4′-trihydroxyisoflavone (genistein), 7,4′-dihydroxyisoflavone (daidzein), 6,7,4′-trihydroxyisoflavone (factor 2), 7,8,4′-trihydroxyisoflavone (7,8,4′-TriOH) 5,7,3′,4′-tetrahydroxyisoflavone (orobol). effects on angiogenesis these evaluated in chicken...
Abstract Background Colorectal cancer (CRC) is characterised by hypoxia, which activates gene transcription through hypoxia-inducible factors (HIF), as well expression of epidermal growth factor (EGF) and EGF receptors, targeting has been demonstrated to provide therapeutic benefit in CRC. Although induce angiogenic mediators, potential interactions CRC between EGF-mediated signalling the hypoxia/HIF pathway remain uncharacterised. Methods PCR-based profiling was applied identify genes...
During tumour progression, oxygen tension in the microenvironment surrounding cells is reduced, resulting hypoxia. It well established that cancer resist negative effects of hypoxia by inducing angiogenesis predominantly via activity transcription factor hypoxia-inducible factor-1 (HIF-1). However, more recently HIF-1α has also been linked to increased invasive potential, although molecular mechanisms remain be defined. Invasive are thought employ membrane protrusions, termed invadopodia,...
Abstract Objective Rheumatoid arthritis (RA) is characterized by hypoxia and the expression of hypoxia‐inducible transcription factors (HIFs), which coordinate cellular responses to hypoxia. The objective this study was analyze regulation prolyl hydroxylase domain (PHD) enzymes factor‐inhibiting HIF‐1α (FIH‐1), regulate HIF levels, roles these in RA fibroblast‐like synoviocytes (RA FLS). Methods PHD FIH downstream target genes assessed quantitative polymerase chain reaction Western blotting....
The inhibition of angiogenesis in vivo as a result the Ets-1 transcription factor expression by ets-1 phosphorothioate antisense oligodeoxynucleotide 5'-AGATCGACGGCCGCCTTCAT-3' has been proven experiments with chicken embryos. Thus, participation formation new blood vessels demonstrated. Furthermore, it is shown that angiostatic effect fungal metabolite and inhibitor fumagillin mainly its ability to inhibit expression.
To investigate the potential role of IkappaB kinase 1 (IKK-1) and IKK-2 in regulation nuclear factor kappaB (NF-kappaB) activation expression tumor necrosis alpha (TNFalpha), as well interleukin-1beta (IL-1beta), IL-6, IL-8, vascular endothelial growth (VEGF), matrix metalloproteinases (MMPs), rheumatoid arthritis (RA).Recombinant adenoviruses expressing beta-galactosidase, dominant-negative IKK-1 IKK-2, or IkappaBalpha were used to infect ex vivo RA synovial membrane cultures fibroblasts...