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Objective To explore the expression of cullin 4A (CUL4A) in cholangiocarcinoma tissues and its clinical significance.Methods Primary fresh cholangiocarcinoma tissues (n =35) and normal bile duct tissues (n =15) from patients who underwent curative surgery in Binzhou People's Hospital of Shandong Province from February 2011 to December 2013 were collected.The expressions of CUL4A mRNA were detected by quantitative real-time PCR (qRT-PCR).Then,cholangiocarcinoma tissues (n =72) and normal bile duct tissues (n =36) from patients who underwent curative surgery in Binzhou People's Hospital of Shandong Province from January 2008 to January 2014 were collected.The expressions of CUL4A protein were tested by immunohistochemistry.The relationships between the expression of CUL4A and the patients' clinicopathologic features and prognosis were analyzed.Results The expression of CUL4A mRNA in cholangiocarcinoma tissues was obviously higher than that in normal bile duct tissues (3.876 ±0.975 vs.1.216 ±0.265),and the difference was statistically significant (t =12.23,P ＜ 0.001).The positive rates of CUL4A protein in cholangiocarcinoma and normal bile duct tissues were 70.8％ (51/72) and 2.8％ (1/36) respectively,and the difference was statistically significant (x2 =44.524,P ＜ 0.001).The expression of CUL4A protein in cholangiocarcinoma was related to the differentiated degree (x2 =4.341,P =0.037),neural invasion (x2 =8.326,P =0.004),TNM stage (x2 =7.745,P =0.005),lymph node metastasis (x2 =3.869,P =0.049) and vascular invasion (x2 =5.555,P =0.018).Survival analysis results showed that the median survival time of CUL4A positive patients was significantly shorter than that of CUL4A negative patients (32.40 months vs.51.30 months),and the difference was statistically significant (x2 =6.561,P =0.011).Conclusion The expression of CUL4A in cholangiocarcinoma tissues is higher than that in normal bile tissues.CUL4A plays an important role in the process of tumor invasion and metastasis and indicates poor prognosis,which may become a potential target for the diagnosis and therapy of the cholangiocarcinoma.
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Objective To investigate the effects of MMI-166 on apoptosis and apoptosis-related protein expression of human pancreatic cancer SW1990 cells and its transplanted tumor,and explore possible mechanism.Methods The human pancreatic cancer xenograft model was constructed by using human pancreatic cancer SW1990 cells.Tumor-bearing nude mice were randomly divided into control and MMI-166 groups,and they were treated with normal saline or MMI-166 (200 mg · kg-1 · d-1) for 28 days.Apoptosis index (AI),p53,c-Myc,Bax,Bcl-2,Survivin,Caspase-1,Fas proteins were detected by deoxynucl-eotidyl transferase-mediated nick end labeling (TUNEL method) and Western blot.MMI-166 of different concentrations (0,50,100 μg/ml) were used to treat human pancreatic cancer SW1990 cell for 24 h.The c-Myc,Survivin proteins expressions were measured by Western blotting.Results Apoptosis index in MMI-166 group was 81.1 ±7.9,which was significantly higher than that in control group (21.3 ±2.2,P =0.000) ; the expressions of c-Myc,Survivin were 7715 ± 2229,4594 ± 1240,which were significantly higher than those in control group (16870 ± 2446,15208 ± 1903,P =0.000) ; the expressions of p53,Bax,Bcl-2,Caspase-1,Fas were not significantly different from those in control group.After 50,100 μg/ml MMI-166 treatment,the expression of c-Myc was significantly down-regulated (0.098 ± 0.003,0.073 ± 0.008 vs.0.169 ± 0.007,F =189.361,P ＜ 0.05) ; and the expression of Survivin was not significantly changed.Conclusions MMI-166 may induce cell apoptosis of SW1990 by down-regulating the expression of c-Myc.
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The effect of free radicals induced by electrolysis on endothelium derived relaxing factor (EDRF) was studied in the isolated rabbit basilar artery using bioassaytechnique. It was found that after the injury was made by the free radicals, the relaxa-tion of the artery rings induced by Ach was decreased markedly while the contractioninduced by NE was very much augmented. Meanwhile, in the basilar arteries MDA con-tent was increased and SOD activity was decreased. Pretreated the basilar artery with SOD,led to the recovery of decreased relaxation and attenuation of changes in MDA and SOD.These results suggested that during subarachnoid hemorrhage, the release of EDRF wasdecreased which was closely related to the free radicals injury of the basilar arteries.
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Three lines of studies (lung in sito, isolated perfused lung and cultured pulmonary artery endothelial cell, PAEC) were undertaken in our laboratory in recent years which demonstrated that oxygen free radicals (OFRs) participates in the pathogenesis of rat lung edema induced by oleic acid (OA). The OFRs derived from xanthine/xanthine oxidase in PAEC might play a primary and initial role, whereas that derived from PMNs might act as an important but secondary and amplifying role in the pathogenesis of lung edema induced by OA.