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• W2508811074 abstract "Background: The relationship between chemotherapy and circulating microparticles in patients with cancer is complex. First, release of cancer cell-derived microparticles may contribute to resistance of cancer cells to chemotherapy. Second, chemotherapy and angiogenesis inhibiting agents promote a prothrombotic state in cancer, and microparticles have been shown to exhibit both pro- and anticoagulant features. Aim: The aim of the present exploratory study was to determine the effects of therapy on the composition and coagulant activity of circulating vesicles. Methods: Blood was collected from 11 patients with glioma and 5 patients with lung cancer, at respectively 4 and 6 different time points before and after start of two different chemotherapy regimens. Age and sex matched healthy subjects (n = 11) were included for the glioma patients. In glioma patients, temozolamide was combined with bevacizumab, an anti-angiogenic agent. Patients with stage IIIB or IV lung cancer were treated with either cisplatin and gemcitabine, or with daily radiotherapy and cetuximab. Procoagulant activity was studied in a fibrin generation test. For some experiments, the coagulant activity of exosomes and other small types of vesicles in plasma was determined by removing microparticles by centrifugation. Numbers of endothelial and tumour-derived microparticles were determined by flow cytometry. Results: Treatment did not affect the overall procoagulant activity of vesicles in cancer patients (P = 0.39). Plasma of three patients had a detectable coagulant activity in the exosome fraction before therapy, compared to plasma from six patients after chemotherapy. Levels of endothelial microparticles (CD62E+) tended to increase in the glioma (P = 0.18), but not in lung cancer patients (P = 0.41). Baseline levels of microparticles exposing vascular endothelial growth factor receptor- 1 (VEGFR-1) were increased in cancer patients compared to healthy subjects (P = 0.012), and VEGFR-1-exposing microparticles decreased by 85% after anti-angiogenic therapy in glioma patients (P = 0.021). Finally, overall, no differences could be observed in the levels of mucine-exposing microparticles, except in two lung cancer patients which showed a clear increase two days after chemotherapy. Summary/Conclusion: In this small explorative study, chemotherapy and anti-angiogenic therapy lead to specific changes in the composition of circulating vesicles, especially with regard to endothelial- and tumour-derived microparticles. These changes are markedly different between the two patients groups and even between subjects within one group, suggesting that such microparticles may be associated with prognosis or response to treatment. At baseline, the procoagulant activity was mainly associated with microparticles, whereas after chemotherapy also a part of the procoagulant activity is associated with smaller vesicles (exosomes) in some patients, suggesting a role for such vesicles in the prothrombotic state after chemotherapy." @default.
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• W2508811074 date "2013-07-01" @default.
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• W2508811074 title "Chemotherapy and anti-angiogenic drugs affect composition and coagulant phenotype of cell-derived vesicles in cancer patients" @default.
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