Glioma-conditioned Medium Blocks Endothelial Cells' Apoptosis Induced by Hypoxia and Promotes Its Angiogenesis via Up-regulation of u-PA/u-PAR

Objective： To investigate the role of urokinase-type plasminogen activator/urokinase-type plasminogen receptor（u-PA/u-PAR） system in glioma angiogenesis under hypoxic conditions, we studied the effect of glioma-conditioned medium on the hypoxia induced changes in human endothelial-like ECV304 cells proliferation, apoptosis, cord formation in vitro and u-PA/u-PAR expression. Methods： MTT assay was used to examine the changes in cell proliferation. Cell apoptosis was analyzed by Hoechst 33258 staining. Matrigel cord-like formation assay was used to evaluate the angiogenesis ability of ECV304 cells in vitro. Expressions of u-PA/u-PAR mRNA were detected by quantitative real-time RT-PCR. Results： Hypoxia inhibited ECV304 cells proliferation and induced cell apoptosis. Hypoxic conditioned medium（H-CM） while not normoxic conditioned medium（N-CM） of U251 glioma ceils partially blocked the effect of hypoxia on ECV304 cells proliferation and apoptosis. H-CM of U251 glioma ceils also promoted the cord formation of ECV304 cells seeded on matrigel. When u-PA or u-PAR monoclonal antibodies were added into ECV304 cells culturing medium, cord formation ability was partially inhibited. H-CM of U251 glioma cells induced uPA and uPAR expression in ECV304 cells. Conclusion： These suggest that u-PA/u-PAR system is involved in glioma angiogenesis trigged by hypoxic microenviroment.

Efficacy and safety of potent P2Y12 inhibitors vs.clopidogrel in elderly patients with acute coronary syndrome

To the Editor:Current guidelines recommended that patients with acute coronary syndrome(ACS)should receive dual anti-platelet therapy of aspirin plus P2Y12 inhibitors(clopidogrel,prasugrel,or ticagrelor)if without contraindication.Up to now,information on the clinical efficacy and safety of potent anti-platelet drugs in the elderly patients with ACS is limited,especially in very older people(age≥75 years).We searched PubMed,the Cochrane library,Web of Science,EMBASE(Excerpt Medical Database)from January 2000 to December 2019.Analysis of the data was performed using Stata software,Version 12.0(StataCorp LP,College Station,TX,USA).The overall polled results were recorded as risk ratios(RRs)and 95%confidence intervals(CIs)with two-sided P values.Finally,seven clinical studies included 8848 patients of potent oral P2Y12-inhibitors versus clopidogrel in elderly patients(age≥65 years old)with ACS were included in this meta-analysis.[1,2,3,4,5,6,7]Patients older than 65 years in the included trials were mainly treated with aspirin combined with ticagrelor,and those over 75 years were mainly treated with aspirin plus prasugrel.Five thousand six hundred and forty-eight(63.8%)received aspirin plus prasugrel,and 3839 patients(43.4%)received reduced maintenance dose prasugrel(<10 mg).The seven included studies were all high-quality studies.