EGFR-TKI plays an important role in the treatment of non-small-cell lung cancer. However, some researchers find that there are still some patients with primary or acquired resistance to EGFR-TKI. The present known mechanisms of acquired drug resistance finally lead to the re-activation EGFR downstream signa-ling pathways. Liver X receptor agonist has inhibition function to several critical steps of EGFR downstream sig-naling pathways PI3K-Akt-NF-κB,which makes it possible to overcome the drug resistance.

AIM:To study the relation between expression of uPAR and annexinⅡ and fibrinolytic activity in various leukemic cell lines.METHODS: The plasma activity was measured under the reaction between cells of NB4,SHI-1,K562,Jurkat,Raji and plaminogen by chromogenic assay.The protein expressions of uPAR and annexinⅡin cells of NB4,SHI-1,K562,Jurkat,Raji were detected by flow cytometry method.The mRNA expressions of uPAR and annexinⅡin cells of NB4,SHI-1,K562,Jurkat,Raji were detected by RT-PCR.RESULTS: The plasma activity in SHI-1 cells and NB4 cells were higher obviously than that in Raji,K562 and Jurkat cells.The protein expression ratio of uPAR and annexinⅡ in NB4 cells were(13.15?1.61)% and(95.97?1.19)%,respectively,they were(99.00?0.26)%,(90.35?2.15)% respectively in SHI-1 cells,and they were lower in K562,Jurkat,Raji cells.The expression of annexinⅡ mRNA in NB4 cells was higher than that in SHI-1 cells,and they were undectectable in K562 and Jurkat cells.The expression of uPAR mRNA in NB4 and SHI-1 cells were higher than that in Jurkat and K562 cells.The expression of uPAR mRNA in Raji cells was undectectable.CONCLUSION: The primary hyperfibrinolysis in leucocythemia cells was observed,and relation was closely with the expression of annexinⅡ.It might be the main reason for bleeding and disseminated intravascular coagulation in patients with acute promyelocytic leukemia and acute monocytic leukemia.

Objective To investigate the correlation between multidrug resistance gene ABCB1 C3435T polymorphism and antiplatelet drug reactivity in Chinese Han patients with ischemic stroke.Methods Consecutive inpatients with non-cardiogenic embolic ischemic stroke were enrolled.They were divided into a good response to antiplatelet drug group and poor response to antiplatelet drug group according to the results of thrombelastogram.Polymerase chain reaction-restriction fragment length polymorphism technique was use to detect the C3435T polymorphism of ABCB1 gene.Multivariate logistic regression analysis was used to determine the independent risk factors for poor response to antiplatelet drugs in patients with ischemic stroke.Results A total of 260 patients with ischemic stroke were enrolled,including 87 females (33.5％) and 173 males (66.5％).There were 193 patients (74.2％) in the good response group and 67 (25.8％)in the poor response group.The age was younger and male was more common in the good response group,and the proportions of smoking and triacylglycerol level were significantly higher (all P ＜0.05).The frequencies of TT genotype and T allele of the poor response group were significantly higher than those of the good response group (all P ＜ 0.05).Multivariable logistic regression analysis showed that triacylglycerol (odds ratio 1.045,95％ confidence interval 1.011-2.010;P =0.014) and C3435T TT genotype (odds ratio 1.512,95％ confidence interval 1.013-2.256;P=0.043) were the independent risk factors for poor response to antiplatelet drugs after adjusting confounding factors.Conclusion The C3435T TT genotype is an independent risk factor for poor response to antiplatelet drugs in Chinese Han patients with ischemic stroke.

Objective To investigate the effect of resveratrol (Res) on temozolomide (TEM) against gliomas in vivo.Methods Human glioma cell line T98G was transplanted into BALB/C-nu female nude mice to establish orthotopic human glioma cell transplanted models.Five d after modeling,the 48 successfully modeled nude mice were randomly divided into solvent control group,Res group,TEM group,combination drug group,Wnt signaling pathway agonist group,and Wnt signaling pathway inhibitor group(n=8);and dimethyl sulfoxide (10 mg/kg),Res (10 mg/kg),TEM (25 mg/kg),Res (10mg/kg+TEM (25 mg/kg),Res (10 mg/kg)+TEM (25 mg/kg)+lithium chloride (2 mg/kg),and Res (10mg/kg)+TEM (25 mg/kg)+IWR-1 (5 mg/kg) were given,respectively,once/d for 30 d.During the administration,the survival status of nude mice in each group was continuously observed,tumor volume was measured by MR imaging every 5 d.Thirty d after administration,TUNEL was used to detect the apoptosis of tumor cells,and immunofluorescence was used to detect the immunofluorescent intensity of O6-methylguanine-DNA methyltransferase (MGMT) and β-catenin in the tumor tissues.Western blotting was used to detect the protein expression levels of Wnt signaling pathway-related proteins (Wnt2,and β-catenin),MGMT,and glycogen synthase kinase 3β (GSK3β).Results As compared with the TEM group,the combination drug group and Wnt signaling pathway inhibitor group had significantly decreased tumor volumes 20,25,30,and 35 d after modeling (/P＜0.05);as compared with the combination drug group,the Wnt signaling pathway inhibitor group had significantly decreased tumor volumes while Wnt signaling pathway agonist group had significantly increased tumor volumes 20,25,30,and 35 d after modeling (P＜0.05).TUNEL showed that the apoptosis rate of tumor cells in the combination drug group and Wnt signaling pathway inhibitor group was significantly increased as compared with that in the temozolomide group (P＜0.05);as compared with that in the TEM group,the apoptosis rate of tumor cells in the Wnt signaling pathway inhibitor group was significantly increased while that in the Wnt signaling pathway agonist group was statistically decreased (P＜0.05).Western blotting results showed that as compared with those in the combination drug group,the protein expression levels ofWnt2,β-catenin,and MGMT in the Wnt signaling pathway inhibitor group were significantly reduced,and GSK-3β protein expression level was significantly increased;while the protein expression levels of Wnt2,[β-catenin,and MGMT in the Wnt signaling pathway agonist group were significantly increased,and GSK-3β protein expression level was significantly decreased (P＜0.05).Conclusion Res inhibits Wnt signaling pathway by reducing expressions of Wnt2 and β-catenin,leading to decrease in MGMT expression,thereby enhancing the anti-glioma effect of TEM.