Search results for " plasminogen activator"
showing 10 items of 77 documents
Immune-inflammatory markers and arterial stiffness indexes in subjects with acute ischemic stroke with and without metabolic syndrome.
2014
Objective: The aim of our study was to evaluate the associations between arterial stiffness indexes and immune-inflammatory markers in subjects with acute ischemic stroke with and without metabolic syndrome. Materials/Methods: We enrolled 130 patients with acute ischemic stroke and metabolic syndrome, 127 patients with acute ischemic stroke without metabolic syndrome and 120 control subjects without acute stroke. Applanation tonometry was used to record the augmentation index (Aix) and pulse wave velocity (PWV). We also evaluated plasma levels of C-reactive protein (CRP), Interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6) and Interleukin-10 (IL-10), E-selec…
Comparison of clot lysis activity and biochemical properties of originator tenecteplase (Metalyse®) with those of an alleged biosimilar
2014
The bioengineered tissue plasminogen activator tenecteplase is an important treatment modality of acute myocardial infarction recommended by international guidelines. Following introduction of originator tenecteplase (brand names Metalyse(®) and TNKase(®)), a "biosimilar" tenecteplase became available for commercial use in India under the brand name Elaxim(®) in the absence of Indian biosimilar guidelines which came into force from September 15th, 2012. Based on a report of biochemical and fibrinolytical differences between Metalyse and Elaxim, we have systematically compared them in a range of routine quality testing assays. As compared to Metalyse, Elaxim exhibited less clot lysis activit…
Endothelial cells and normal breast epithelial cells enhance invasion of breast carcinoma cells by CXCR-4-dependent up-regulation of urokinase-type p…
2008
Here we show the increase of invasion of three breast cancer cell lines (8701-BC, MDA-MB-231 and SKBR3) upon long-term co-incubation with culture medium of normal microvascular endothelial cells (MVEC) and normal breast epithelial cells (HB2). The enhancement of invasion relied on the interaction of microvascular endothelial cell and normal breast epithelial cell CXCL12 (SDF1) chemokine, whose expression by breast cancer cells was very low, with the cognate CXCR4 receptor of malignant cells, which resulted in over-expression of the urokinase-type plasminogen activator receptor (uPAR) on their surfaces. uPAR over-expression, showed by RT-PCR and Western blotting, was paralleled by increased …
Comparative analysis of fibrinolytic properties of Alteplase, Tenecteplase and Urokinase in an in vitro clot model of intracerebral haemorrhage.
2020
Abstract Objective Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral and intraventricular haemorrhage (ICH and IVH). However, the MISTIE III and CLEAR III trial failed to show significant improvement of favourable outcomes. Besides experimental and clinical trials revealed neurotoxic effects of rtPA. The demand for optimization of fibrinolytic therapy persists. Herein, we used our recently devised clot model of ICH to systematically analyse fibrinolytic properties of rtPA, tenecteplase and urokinase. Methods In vitro clots of human blood (size: 25 ml and 50 ml; age: 1.5 tenecteplase, 24 tenecteplase and 48…
Urokinase activates macrophage PON2 gene transcription via the PI3K/ROS/MEK/SREBP-2 signalling cascade mediated by the PDGFR-β
2009
Aims We have recently shown that urokinase plasminogen activator (uPA) increases oxidative stress (OS), cholesterol biosynthesis, and paraoxonase 2 (PON2) expression in macrophages via binding to its receptor, the uPAR. Since PON2 is regulated by both OS and cholesterol content, we hypothesized that uPA elicits a cascade of signal transduction events shared by NADPH oxidase and cholesterol biosynthesis that culminates in PON2 gene expression. Here, we investigated the signalling pathway that leads to the expression of PON2 in macrophages in response to uPA. Methods and results The increase in macrophage PON2 mRNA levels in response to uPA was shown to depend on PON2 gene promoter activation…
Anti-ETAR and suPAR as markers of disease activity in renal ANCA-associated vasculitis.
2020
Purpose In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), there is a lack of reliable biomarkers of disease activity. The aim of the study was to evaluate soluble urokinase plasminogen activator receptor (suPAR) and anti-endothelin-1 type A receptor (anti-ETAR) antibodies levels in active phase and remission of AAV. Patients and methods We enrolled 60 patients (median age 63.0 years) with renal AAV into this study. Plasma suPAR, urine suPAR (expressed as urine suPAR/creatinine ratio) and serum anti-ETAR antibodies were assayed by ELISA. Disease activity was assessed using Birmingham Vasculitis Activity Score (BVAS) and patients were divided into 2 subgroups based o…
Kondrat'eva ligation: Diels-Alder-based irreversible reaction for bioconjugation.
2014
International audience; Diversification of existing chemoselective ligations is required to efficiently access complex and well-defined biomolecular assemblies with unique and valuable properties. The development and bioconjugation applications of a novel Diels-Alder-based irreversible site-specific ligation are reported. The strategy is based on a Kondrat'eva cycloaddition between bioinert and readily functionalizable 5-alkoxyoxazoles and maleimides that readily react together under mild and easily tunable reaction conditions to afford a fully stable pyridine scaffold. The potential of this novel bioconjugation is demonstrated through the preparation of fluorescent conjugates of biomolecul…
Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Neg…
2015
BC-11 is an easily synthesized simple thiouronium-substituted phenylboronic acid, which has been shown to be cytotoxic on triple negative MDA-MB231 breast cancer cells by inducing a perturbation of cell cycle when administered at a concentration equal to its ED50 at 72 h (117 μM). Exposure of cells to BC-11, either pre-absorbed with a soluble preparation of the N-terminal fragment of urokinase-plasminogen activator (uPa), or in co-treatment with two different EGFR inhibitors, indicated that: (i) BC-11 acts via binding to the N-terminus of the enzyme where uPa- and EGF receptor-recognizing sites are present, thereby abrogating the growth-sustaining effect resulting from receptor binding
Advancing stem cells: New therapeutic strategies for treating central nervous system disorders
2018
In this special issue, we explore new methods and knowledge to improve stem cell transplantation in diseases and conditions such as stroke, PD, and depression. Advancing the conventional idea regarding cell replacement in stem cell therapy, stem cells may also transfer healthy mitochondria to diseased ischemic neurons in stroke and improve the therapeutic time window of tissue plasminogen activator (tPA) in a conjunctive therapy for stroke, and human Wharton’s Jelly-derived mesenchymal stromal cells (hWJ-MSCs) may rely mainly on trophic factor secretion to induce neuroprotective effects. In addition, trophic factors such as neurotrophin-4/5 (NT-4/5) and glial cell line-derived neurotrophic …
Interleukin 12 induces activation of fibrinolysis and coagulation in humans
2001
Interleukin 12 (IL-12) has potential efficacy in malignant, infectious and allergic diseases. Its side-effects include activation of coagulation and fibrinolysis, as documented in chimpanzees. We assessed the coagulative and fibrinolytic response in 18 patients with renal cell carcinoma after subcutaneous injection of 0.5 microg/kg recombinant human IL-12. IL-12 induced a fibrinolytic response in 17 patients (94%): plasmin-alpha2-anti-plasmin complexes (PAPc) increased from 11.8 +/- 6.6 nmol/l (mean +/- SD) to a maximum of 18.8 +/- 7.4 nmol/l at 72 h. Baseline levels of tissue plasminogen activator (tPA) and plasminogen-activator inhibitor-I (PAI) were elevated in eight and 14 patients resp…