A5087667879- Blood Coagulation and Thrombosis Mechanisms
- Venous Thromboembolism Diagnosis and Management
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Extracellular vesicles in disease
- Platelet Disorders and Treatments
- Blood properties and coagulation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Signaling Pathways in Disease
- Cardiac tumors and thrombi
- Phagocytosis and Immune Regulation
- Hippo pathway signaling and YAP/TAZ
- Cellular Mechanics and Interactions
- Atrial Fibrillation Management and Outcomes
- Wound Healing and Treatments
- Angiogenesis and VEGF in Cancer
- Pancreatic and Hepatic Oncology Research
- Peptidase Inhibition and Analysis
- Kawasaki Disease and Coronary Complications
- Neonatal Respiratory Health Research
University of Hull
2016-2025
Hull York Medical School
2024-2025
Interactions between tissue factor (TF) and β1-integrin induce cell signals, but the molecular mechanisms are not completely understood. The extracellular domain of TF EGF4-βTD domains were hypothesised to be most likely involved in interaction. Additionally, interaction may a conformational change β1-integrin, which results changes signalling. Peptide constructs corresponding upper (residues 1-110; UED), lower 106-219; LED) or combined 1-219; TED) produced, as well peptides EGF4...
Tissue factor (TF) is the main activator of blood coagulation and associated with thrombosis tumor progression. It can be released into circulation incorporated within cancer cell-derived extracellular vesicles (EVs). In this study, we investigated influence two-dimensional (monolayer) three-dimensional (spheroid) cell culture methods, co-culture cancer-associated fibroblasts (CAF), on level EVs release TF activity. The density from spheroids monolayers Hs578t human breast CAF were measured...
Despite the association of cancer-derived circulating tissue factor (TF)-containing microvesicles and hypercoagulable state, correlations with incidence thrombosis remain unclear.In this study upregulation TF release upon activation various cancer cell lines, correlation PAR2 expression and/or activity was examined. Microvesicle induced by in seventeen lines released microvesicle density, microvesicle-associated activity, phoshpatidylserine-mediated were measured. The time-course for...
The activation of protease-activated receptor (PAR)-2 by factor Xa (fXa) promotes the release tissue factor-positive microvesicles (TF+MV), and contributes to proliferation in cancer cells. This study examined ability direct oral anticoagulants (DOACs), apixaban rivaroxaban, inhibit TF+MV from two cell lines (MDA-MB-231 AsPC-1) as well proliferation.Activation cells with fXa (10 nM) enhanced but was suppressed presence either DOAC. These MVs were found contain fVIIa, not fXa. Incubation (1.8...
Abstract The bidirectional association between coagulation and cancer has been established. However, anticoagulant therapies have reported to beneficial outcomes by influencing the vascularisation of tumours. In this study influence a set anticoagulants on tumour formation, invasion was examined. WM-266-4 melanoma AsPC-1 pancreatic cell lines were treated with LMWH (Tinzaparin Dalteparin), DOAC (Apixaban Rivaroxaban) rate growth measured in vitro . addition, these examined using...
Accumulation of tissue factor (TF) within cells leads to cellular apoptosis mediated through p38 and p53 pathways. In this study, the involvement Src1 in induction TF-mediated cell apoptosis, mechanisms activation were investigated. Human coronary artery endothelial (HCAEC) transfected with plasmids express wild-type TF (TFWt-tGFP), or a mutant (Ser253 → Ala) which is incapable being released from (TFAla253-tGFP). The then activated PAR2-agonist peptide (SLIGKV-NH) phosphorylation Src Rac,...
Abstract Tissue factor (TF)-positive microvesicles from various sources can promote cellular proliferation or alternatively induce apoptosis, but the determining factors are unknown. In this study hypothesis that ratio of fVIIa:TF within determines outcome was examined. Microvesicles were isolated HepG2, BxPC-3, 786-O, MDA-MB-231, and MCF-7 cell lines microvesicle-associated fVIIa TF antigen activity levels measured. Human coronary artery endothelial cells (HCAECs) incubated with these...
Abstract Background Tissue factor (TF) activity is stringently regulated through processes termed encryption. Post-translational modification of TF and its interactions with various protein lipid moieties allows for a multi-step de-encryption procoagulant activation. Membrane-associated guanylate kinase-with inverted configuration (MAGI) proteins are known to regulate the localisation number including cell-surface receptors. Methods The interaction MAGI1 was examined as means regulating...
Introduction Microvesicles (MV) released by endothelial cells (EC) following injury or inflammation contain tissue factor (TF) and mediate communication with the underlying smooth muscle (SMC). Ser253-phosphorylated TF co-localizes filamin A at leading edge of migrating SMC. In this study, influence endothelial-derived TF-MV, on human coronary artery SMC (HCASMC) migration was examined. Methods Results MV derived from EC (HCAEC) expressing Wt accelerated HCASMC migration, but lower...
Tissue factor (TF) possesses additional physiological functions beyond initiating the coagulation cascade. Cellular signals initiated by cellular TF or on contact with TF‑containing microvesicles, contribute to wound healing through regulating a number of properties and functions. regulates cell cycle checkpoints, however underlying signalling mechanisms have not been determined. Endothelial (human dermal blood endothelial cells human umbilical vein cells) epithelial [human telomerase...
In this study, the role of de-palmitoylation tissue factor (TF) in decryption its activity was explored. TF-tGFP constructs were prepared by mutagenesis-substitution at Cys245 to prevent or mimic palmitolyation. Additionally, reduce TF de-palmitoylation, expression palmitoyl-protein thioesterases (PPT) suppressed. Other mutants with altered flexibility, hydrophobicity length transmembrane domain. The outcome these alterations on fXa-generation, fVIIa binding, Ser253 phosphorylation and...
Procoagulant activity of tissue factor (TF) in response to injury or inflammation is accompanied with cellular signals which determine the fate cells. However, prevent excessive signalling, TF rapidly dissipated through release into microvesicles, and/or endocytosis. To elucidate mechanism by signalling may become moderated on surface cells, associations TF, fVII/fVIIa, PAR2 and caveolin-1 MDA-MB-231, BxPC-3 786-O cells were examined compared that lacking either fVII/fVIIa TF. Furthermore,...
Predicting which cancer patients are at risk of thrombosis remains a key challenge to effective thromboprophylaxis. This study was based on the hypothesis that rapid release TF-containing MV occurs in cells possess high levels TF mRNA, permitting transient but amplified TF-protein production response cellular activation. To gather preliminary clinical evidence for this correlation between tumour-associated mRNA and incidence Pulmonary Embolism (PE) Gastrointestinal (GI) assessed using...
669 Background: Premalignant pancreatic cellular genotype may remain stable for many years, but compounding conditions can produce rapid malignant transformation. This onset is rarely spontaneous and often associated with the presence of inflammation. One inflammatory modulator “tissue factor (TF),” which usually acts in complex “coagulation VIIa (fVIIa)” to initiate coagulation. The role TF malignancy its impact beyond thrombosis on cell proliferation, angiogenesis, metastasis well...
Introduction: The restriction of prolyl-protein cis/trans isomerase 1 (Pin1) activity has been shown to prevent the release tissue factor (TF) leading accumulation latter protein within cell. This study tested ability novel small molecules inhibit Pin1, suppress TF and release, induce cellular apoptosis. Methods: Four compounds were designed synthesised based on modification 5-(p-methoxyphenyl)-2-methylfuran-3-carbonyl amide outcome MDA-MB-231 primary cells examined. These contained...