Predictive value of tissue factor bearing microparticles in cancer associated thrombosis.
ABSTRACT Venous thromboembolic events (VTE) are a common complication of cancer and its therapy. Prognostic models and biomarkers are currently under investigation as a means to identify cancer patients who are at greatest risk for developing thromboembolic complications and thus are most likely to benefit from primary thromboprophylaxis. Elevations in circulating tissue factor bearing microparticles are associated with thrombosis in cancer patients. We initiated the MicroTEC study which is a randomized, multi-center trial to evaluate the benefit of low molecular weight heparin to prevent VTE in high risk cancer patients. This review details the evidence for tissue factor bearing microparticles in the malignant state and its association with thromboembolic phenomena.
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ABSTRACT: This study aimed to explore the role of tissue factor (TF) and evaluate its antitumor effects in the biological processes of gastric cancer cells using the application of RNA interference technology to silence TF in the SGC7901 gastric cancer cell line. Specific small interfering RNA (siRNA) designed for targeting human TF was transfected into SGC7901 cells. The expression levels of TF in the cells were detected by reverse transcription-polymerase chain reaction. Cell proliferation and chemosensitivity were measured by Cell Counting Kit-8. The metastatic potential of the SGC7901 cells was determined by Transwell experiments and wound-healing assays. Cell apoptosis was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide double-staining method. The expression levels of TF mRNA were significantly reduced by the TF-siRNA in the SGC7901 cells, resulting in the suppression of cell proliferation, chemoresistance and invasion, and subsequently the induction of cell apoptosis. TF knockdown with siRNA inhibits the growth, invasion and chemoresistance and enhances the apoptosis of SGC7901 cells, providing a potential approach for gene therapy against human gastric cancer.Experimental and therapeutic medicine 05/2014; 7(5):1376-1382. DOI:10.3892/etm.2014.1591 · 0.94 Impact Factor
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ABSTRACT: The antiphospholipid syndrome is characterized by venous or arterial thrombosis and/or recurrent fetal loss in the presence of circulating antiphospholipid antibodies. These antibodies cause activation of endothelial and other cell types leading to the release of microparticles with procoagulant and pro-inflammatory properties. The aims of this study were to characterize the levels of endothelial cell, monocyte, platelet derived, and tissue factor-bearing microparticles in patients with antiphospholipid antibodies, to determine the association of circulating microparticles with anticardiolipin and anti-β2-glycoprotein antibodies, and to define the cellular origin of microparticles that express tissue factor. Microparticle content within citrated blood from 47 patients with antiphospholipid antibodies and 144 healthy controls was analyzed within 2 hours of venipuncture. Levels of Annexin-V, CD105 and CD144 (endothelial derived), CD41 (platelet derived) and tissue factor positive microparticles were significantly higher in patients than controls. Though levels of CD14 (monocyte-derived) microparticles in patient plasma were not significantly increased, increased levels of CD14 and tissue factor positive microparticles were observed in patients. Levels of microparticles that stained for CD105 and CD144 showed a positive correlation with IgG (R = 0.60, p = 0.006) and IgM anti-beta2-glycoprotein I antibodies (R = 0.58, p = 0.006). The elevation of endothelial and platelet derived microparticles in patients with APS and their correlation with anti-β2-glycoprotein I antibodies suggests a chronic state of vascular cell activation in these individuals and an important role for β2-glycoprotein I in development of the pro-thrombotic state associated with antiphospholipid antibodies.Thrombosis Research 11/2014; DOI:10.1016/j.thromres.2014.11.011 · 2.43 Impact Factor
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ABSTRACT: The proteinase-activated receptor 1 (PAR-1) plays a central role in melanoma progression and its expression level is believed to correlate with the degree of cancer invasiveness. Here, we show that PAR-1 is posttranscriptionally regulated by miR-20b microRNA in human melanoma cells. PAR-1 was found to be expressed in metastatic melanoma cells but was barely detectable in primary melanoma. By transducing primary melanoma cells with a lentivirus containing a 3′-UTR construct of PAR-1 mRNA, we could show that endogenous melanoma microRNAs interacted with PAR-1 3′-UTR and silenced a fused luciferase reporter. Transfection of an inhibitor against miR-20b into primary melanoma cells reversed this process. Finally, transfection of miR-20b mimic into metastatic melanoma cells caused downregulation of the luciferase reporter. We conclude that miR-20b regulates expression of melanoma PAR-1 receptor, which may explain the differential expression of PAR-1 observed in human melanoma.Pigment Cell & Melanoma Research 05/2014; 27(3):431–441. DOI:10.1111/pcmr.12217 · 5.64 Impact Factor