1,721,035 research outputs found
Synergistic activity of gamma-linolenic acid and cytotoxic drugs against pancreatic adenocarcinoma cell lines
No full textBackground: gamma-Linolenic acid (GLA) is growth inhibitory both in vitro and in vivo, at doses non-toxic to non-cancer cells. Chemotherapeutic agents have limited activity in pancreatic cancer. Interactions between GLA and cytotoxic drugs have not previously been investigated; any synergy might improve the therapeutic effect of these agents. Aim: To investigate possible interactions between GLA and 5-fluorouracil (5-FU) or gemcitabine against pancreatic cancer cell lines in vitro. Methods: Two pancreatic cancer cell lines were exposed to GLA alone and in combination with 5-FU or gemcitabine. Residual viable biomass was measured using the MTT assay and the results analysed by the median effect method of Chou and Talalay [Adv Enzyme Regul 1984;22:27-55]. Results: GLA concentrations of 3.9- 125 µg/ml had a synergistic or additive growth inhibitory effect on all tested concentrations of gemcitabine. Synergism was demonstrated between GLA and 5-FU only at concentrations of 62.5-125 µg/ml of 5-FU. Conclusion: GLA has a synergistic effect with gemcitabine at concentrations that correspond to in vivo therapeutic doses. GLA with 5-FU is synergistic only at a tight range of high concentrations of 5-FU. GLA lacks toxic side effects and may be useful in combination with gemcitabine
Tissue factor expression and multidrug resistance in cancer: two aspects of a common cellular response to a hostile milieu
No full textTissue factor (TF) is the main physiological initiator of blood coagulation and its activation or de-encryption within plasma membranes is important for trapping, extravasation and angiogenesis in the development and spread of solid malignancies. Multidrug resistance is also an adaptive response in malignant (and normal) cells. It is often mediated by the over-expression of the P-glycoprotein (P-gP) efflux pump. Both TF and P-gP tend to be expressed together, perhaps as part of a coherent 'crisis management' response of cells to environmental change or challenge. An associated feature in such a response appears to be the reversal of normal phospholipid charge asymmetry in the plasma membrane bilayer. Responses to environmental stimuli affect function in normal and malignant tissue. Uniting the study of TF expression or de-encryption and MDR-1 phenotype would be biologically enlightening and might ultimately influence clinical cancer management and the control of thrombotic problems associated with treatment
The publication rate of abstracts presented at the British Association of Dermatologists annual meeting
No full textSeminal clotting and fibrinolytic balance: A possible physiological role in the male reproductive system
No full textSemen contains enzymes and inhibitors of the haemostatic system as well as the high molecular weight seminal vesicle (HMW-SV) proteins. The former may have roles in seminal clotting and in liquefaction through “fibrinolytic” activity, which may ultimately affect fertility. Although a limited number of studies have addressed the subject, the role of clotting and fibrinolytic factors in semen remains poorly understood. The liquefaction time and the distribution of components vary across split ejaculates. This may have an important bearing on the way clotting/fibrinolytic factors in semen are assessed. Semen contains tissue factor (TF, Thromboplastin, CD142), which originates from the prostate and is associated with prostasomes. The function of TF (and prostasomes) in semen is still a matter for speculation. Recently the presence of minute amounts of factor VII in semen has been demonstrated but its importance is uncertain. Semen also contains a thrombin-like enzyme, prothrombin fragments 1 and 2 (F1+2), D-dimer (DD) and thrombin-antithrombin (TAT) complexes. The presence of several fibrinolytic factors has been demonstrated in semen but few questions about their potential impact on semen quality have been raised. Factors found include tissue plasminogen activator (t-PA), urinary plasminogen activator (u-PA) and plasmin.There are also traces of fibrinogen, plasminogen, plasminogen activator inhibitor-1 (PAI-1), factor VIII coagulant activity (VIII:c) and fibrin monomers.The co-ordinate expression of both TF and PAI-1 by decidual cells of the endometrium is believed to be important in maintaining haemostasis during endovascular trophoblast invasion. Kallikrein-like serine protease inhibitors including prostate specific antigen (PSA) are known to be present in semen at high concentrations. In semen PSA is also found in a complex form with protein C inhibitor (PCI) with mutually inhibitory consequences. A better understanding of the spectrum of coagulating and liquefaction agents in semen to include classical haemostatic processes and the pathogenesis resulting from any imbalances between or within either system may provide the basis for the development of more selective and efficient agents affecting global fertility. Here we review aspects of male reproductive physiology in the light of recent findings concerning conventional clotting/fibrinolytic systems in human semen with a view to stimulating further research
Expression of tissue factor and tissue factor pathway inhibitor in microparticles and sub-cellular fractions of normal and malignant prostate cell lines: correlation with differentiation status
No full textMeglumine Eicosapentaenoic acid (MeEPA) a new soluble omega-3 fatty acid formulation: in vitro bladder cancer cytotoxicity tests in combination with epirubicin and mitomycin
No full textOBJECTIVE: To determine if Meglumine-Eicosapentaenoic Acid (MeEPA) acts synergistically with epirubicin and mitomycin to enhance cytotoxicity towards bladder cancer cell lines in vitro.MATERIALS AND METHODS: Bladder cancer cells were exposed to MeEPA in combination with epirubicin or mitomycin. Residual viable cell biomass was estimated with the methyl-thiazoldiphenyl tetrazolium (MTT) assay following drug exposure. Drug interaction was analysed using median effect analysis to determine levels of synergism.RESULTS: Most combinations of MeEPA with both epirubicin and mitomycin showed a high-level of synergism. At high doses, drug precipitation adversely affected MTT assay analysis suggesting antagonism of action. However, the predominant pattern was of synergism for most dose combinations tested.CONCLUSION: Bladder cancer treated by endoscopic resection alone is subject to high recurrence rates. Post-operative intravesical instillation of epirubicin and mitomycin can halve recurrence rates, but there is no evidence that disease progression to invasive bladder cancer is altered. Thus, optimisation of current treatment strategies is required. The anti-tumour activity of fatty acids is well established and MeEPA is a new, soluble formulation with the potential to enhance intravesical drug efficacy
Tissue factor: a critical role in inflammation and cancer
No full textA series of coordinated enzymatic reactions takes place in the body whenever blood clots. The major physiological initiator of these reactions is a membrane-bound glycoprotein known as tissue factor (TF), which is normally separated from the bloodstream by the vascular endothelium. Bleeding, caused by injury or tissue damage, activates a complex enzyme cascade as TF becomes exposed to the bloodstream. In disease states, leukocytes or the vascular endothelium may abnormally express TF to cause intravascular coagulation. The blood-coagulation cascade is also relevant to diseases such as hemophilia, in which patients are deficient in blood proteins necessary for clotting, and is linked to vascular diseases such as heart attack and stroke, in which clotting can lead to the occlusion of blood vessels. Coagulation is also activated in inflammation and cancer. In this article, we discuss characteristics of TF and review its role in inflammation and cancer. <br/
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