合并乙肝的实体瘤患者化疗期间预防性护肝治疗的意义研究

目的评价实体瘤患者化疗过程中预防性护肝治疗对患者肝功能损害的影响,评价预防性护肝治疗的价值。方法收集2008年2月～2012年7在我院接受化疗的实体瘤患者317例,并根据患者是否接受预防性护肝药物治疗、乙型肝炎病毒表面抗原（HBSAg）及HBV DNA状态进行分组。评价化疗后肝功能损伤的发生率及程度。结果 HBV DNA阳性乙肝患者肝功能损害发生率明显高于未合并乙肝患者（61.5%vs 34.0%,P〈0.01）;预防性使用护肝药物后,HBV DNA阳性乙肝患者肝功能损害发生率显著减少（61.5%vs 35.2%,P〈0.05）,与未合并乙肝感染的患者类似（35.2%vs 29.8%,P〉0.05）;其中轻度（Ⅰ、Ⅱ级）肝功能损害的发生率下降尤为显著（51.9%vs 28.3%,P〈0.05）。而对于未合并乙肝或HBV DNA阴性乙肝患者,预防性使用护肝药物也观察到肝功能损害发生率的下降趋势,但差异无统计学意义（P〉0.05）。结论在HBV DNA阳性的乙肝患者化疗过程中,建议在抗乙肝病毒药物基础上,预防性使用护肝药物治疗;而在HBV DNA阴性的乙肝患者以及无乙肝感染的患者中,预防性护肝治疗的作用尚有待进一步研究明确。     

MiR-21 mediates the radiation resistance of glioblastoma cells by regulating PDCD4 and hMSH2

The purpose of this study was to investigate the molecular mechanism by which miR-21 and its target genes mediate radiation resistance of glioblastoma cells.Real-time PCR was employed to detect miR-21 expression in normal brain tissues,glioblastoma tissues and glioblastoma cell lines (A172,T98G and U87MG).T98G cells were transfected with anti-miR-21 oligonucleotides,or plasmids containing PDCD4 or hMSH2 (PDCD4-pcDNA3 and hMSH2-pcDNA3).The survival curve was obtained to investigate the sensitivity of T98G cells to radiation.Cell apoptosis was measured by using the Caspase-3/7 kit and cell cycle by flow cytometry.Western blotting was performed to detect the expression of hMSH2 and PDCD4 in miR-21-inhibiting T98G cells.The results showed that miR-21 expression in glioblastoma cells and tissues was conversely associated with the radiation sensitivity.Over-expression of miR-21 resulted in radiation resistance,while knockdown of miR-21 led to higher sensitivity of glioblastma cells to radiation.After miR-21 knockdown,the apoptosis of T98G cells was significantly increased and the G2 phase arrest was more significant.In addition,miR-21 knockdown increased the expression of endogenous PDCD4 and hMSH2,which contributed to the apoptosis and G2 arrest of T98G cells.The findings suggested that miR-21 may mediate the resistance of glioblastoma cells against radiation via its target genes PDCD4 and hMSH2.MiR-21 and its target genes may be used as potential molecular targets for clinical radiotherapy sensitization in the future.