Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A tightly controlled increase in extracellular proteolysis, restricted both in time and space, is an important component of the angiogenic process, while anti-proteolysis is effective in inhibiting angiogenesis. By focussing on the plasminogen activator (PA)-plasmin system, the objective of the present studies was to assess whether previously described inhibitors of angiogenesis modify bovine microvascular endothelial cell proteolytic properties. We demonstrate that although synthetic angiostatic steroids (U-24067 and U-42129), heparin, suramin, interferon alpha-2a, and retinoic acid are all inhibitors of in vitro angiogenesis, each of these agents has distinct effects on the plasminogen-dependent proteolytic system. Specifically, angiostatic steroids and interferon alpha-2a reduce urokinase-type PA (u-PA) and PA inhibitor-1 activity, while heparin and retinoic acid increase u-PA activity. Suramin reduces cell-associated u-PA activity and greatly increases PAI-1 production at doses which induce monolayer disruption. These findings demonstrate that a spectrum of alterations in extracellular proteolysis is associated with anti-angiogenesis, and that anti-angiogenesis and anti-proteolysis are not necessarily correlated. A reduction in extracellular proteolysis would be expected to reduce invasion, whereas an increase in proteolysis might modulate the activity of inhibitory cytokines, which in turn could reduce endothelial cell proliferation and migration and inhibit angiogenesis. The spectrum of effects on different elements of the PA system observed in response to the agents assessed suggests that the role of modulations in extracellular proteolytic activity in anti-angiogenesis is likely to be varied and complex.
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PMID:Modulation of bovine microvascular endothelial cell proteolytic properties by inhibitors of angiogenesis. 752 17

The differentiation of A549, a human tumour cell line from type II pneumocytes, can be induced by a crude fibroblast-derived factor (FDF) isolated from the conditioned medium of glucocorticoid-treated lung fibroblasts. In the present report, we have used alkaline phosphatase as a differentiation marker to investigate the activity of a number of growth factors as potential candidates for this paracrine activity. This showed that insulin, interleukin 6 (IL-6), and interferon alpha (IFN-alpha) could simulate the activity of conditioned medium. Their effects were dexamethasone (DX) dependent, additive and reversible with a half-life of 1 week. Transforming growth factor alpha and beta, IL-1 alpha and epidermal growth factor, were all inhibitory, and inhibition was opposed, partially or completely, by DX. The most potent inducer was IL-6, but as DX was shown to decrease the concentration of IL-6 in lung fibroblast-conditioned medium it seems an unlikely candidate for FDF. Unlike FDF, all of the positive-acting factors were shown to induce plasminogen activator. FDF has also been shown to be active in the absence of DX. This suggests that differentiation-inducing activity may be present in several paracrine factors, but that so far a candidate for FDF has not been identified.
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PMID:Activity of interferon alpha, interleukin 6 and insulin in the regulation of differentiation in A549 alveolar carcinoma cells. 784 Oct 35

Human ovarian adenocarcinoma cells N.1 secrete an autocrine activity that stimulates active cell death under serum-reduced conditions. To substitute the autocrine activity by a single physiological component, 28 cytokines, growth factors and biomodulators were tested [interleukin 1alpha (IL-1alpha), IL-1beta, IL-2, IL-3, IL-4, IL-6, IL-10, IL-11, stem cell factor (SCF), platelet-derived growth factor (PDGF), acid fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-1), IGF-2, insulin, macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), oncostatin, RANTES (regulated on activation normal T cell expressed and secreted), angiogenin, leukaemia inhibitory factor (LIF), erythropoietin (EPO), interferon alpha (INF-alpha), INF-gamma, transferrin, tumour necrosis factor alpha (TNF-alpha, TNF-beta and bovine serum albumin for control reasons]. In these experiments, only TNF-alpha and TNF-beta rapidly induced apoptosis. TNF-alpha and TNF-receptor 1 were expressed by N.1 cells, and the secretion of TNF-alpha was verified by enzyme-linked immunosorbent assay (ELISA). Autocrine factor-triggered apoptosis was inhibited when conditioned supernatant was preincubated with anti-TNF-alpha antibody. These findings suggested that the apoptosis-inducing component of the N.1 autocrine activity was TNF-alpha. In the presence of antisense c-myc oligonucleotides, induction of cell death by autocrine factor was partly inhibited. Autocrine factor and TNF-alpha stimulated transcription of the invasiveness-related protease plasminogen activator/urokinase mRNA (upa) with similar kinetics. When N.1 cells were exposed to purified plasminogen activator/urokinase protein (uPA), cell matrix contact was disrupted. Thus, uPA might serve a physiological role during TNF-induced apoptosis by affecting the interactions between cells and the basal membrane, thereby facilitating anoikis. This mechanistic study, which was restricted to a single human ovarian carcinoma model cell line (N.1), provides evidence that N.1 maintains the capacity to undergo c-myc-dependent apoptosis by the TNF-TNF-receptor pathway, and no additional pharmacological stimuli for induction of apoptosis are required.
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PMID:Autocrine self-elimination of cultured ovarian cancer cells by tumour necrosis factor alpha (TNF-alpha). 976 76

Biotechnology is a rapidly developing area of drug development which has great growth potential. Development of genetically engineered drugs is very expensive and as these products become available the impact on healthcare costs could be vast. The cost-benefit ratio of biotechnology products needs to be established, but few relevant pharmacoeconomic studies are available. Issues in pharmacoeconomic analysis of genetically engineered drugs can be exemplified by the data available for alteplase, epoetin and interferon alpha-2b. One study concluded that thrombolysis with streptokinase rather than alteplase would substantially reduce the percentage of total hospital costs that were not reimbursed. However, differences in efficacy were not accounted for. Based on the superior efficacy of alteplase, a more extensive pharmacoeconomic analysis found that alteplase was more cost-effective than streptokinase when the agents were combined with aggressive reocclusion management. However, this conclusion may be altered by the finding of a more recent study that streptokinase may be at least as effective as alteplase. Economic factors involved in epoetin treatment of anaemia associated with chronic renal disease have been studied thoroughly. However, cost-effectiveness or cost-benefit analysis was not attempted, and improvement in quality of life with epoetin therapy also needs to be considered, to facilitate cost-utility analysis. Compared with chlorambucil, the use of interferon alpha-2b for hairy cell leukaemia resulted in significant direct and indirect cost savings, in a retrospective cost-benefit analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacoeconomics of genetically engineered drugs. 1017 57

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate, nevirapine, nifedipine, NSC-683864; Oral heparin; Paclitaxel, peginterferon alfa-2b, phenytoin, pimecrolimus, piperacillin, pleconaril, pramipexole hydrochloride, prednisone, pregabalin, progesterone; Rasburicase, ravuconazole, reteplase, ribavirin, rituximab, rizatriptan, rosiglitazone maleate, rotigotine; Semaxanib, sildenafil citrate, simvastatin, stavudine, sumatriptan; Tacrolimus, tamoxifen citrate, tanomastat, tazobactam, telithromycin, tenecteplase, tolafentrine, tolterodine tartrate, triamcinolone acetonide, trimetazidine, troxacitabine; Valproic acid, vancomycin hydrochloride, vincristine, voriconazole, Warfarin sodium; Ximelagatran, Zidovudine, zolmitriptan.
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PMID:Gateways to Clinical Trials. 1208 78

In this work, magnetite (Fe(3)O(4)) nanoparticles with an average size 10 nm modified by sodium oleate were prepared by the modified controlled chemical coprecipitation method, which can be well dispersed in water and linked well with protein molecules because of the presence of -COOH on their surface. Then magnetic poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microspheres containing interferon alpha-2b (IFN-a-2b) were prepared by the modified water-in-oil-in-water solvent evaporation procedure. X-ray powder diffraction analysis, particle size analysis, transmission electron microscopy, scanning electron microscopy, and vibrating-sample magnetometer (VSM) analysis were carried out to examine phase composition, surface and interior morphology, size and size distribution, and magnetic properties of the magnetic microspheres. Also the effects of some important parameters on the magnetic biodegradable microspheres were investigated, such as magnetite dosage in the preparation system, stirring rate of the suspension medium, and concentration of the external aqueous phase. And the antiviral activity of IFN-a-2b encapsulated in the magnetic polymeric microspheres was evaluated by the vesicular stomatitis virus (VSV) cytopathicity inhibition assay. The results showed that the properties of IFN-loaded magnetic PLGA and PLA microspheres were better than the conventional protein-loaded polymeric microspheres, such as perfect magnetic properties, higher protein encapsulation efficiency, and less effect on the antiviral activity of protein. These indicated that the magnetic PLA and PLGA microspheres containing IFN-a-2b exhibited strong potential as targeted-drug delivery vehicles, which could be rapidly localized to the immunization-related tissues easily by an external magnetic field.
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PMID:Preparation and characterization of interferon-loaded magnetic biodegradable microspheres. 1843 13