AIM：To investigate the altering expression profiles of efflux transporters such as breast cancer-resistance protein（BCRP）,lung resistance protein（LRP）,and multidrug resistance protein 1（MDR1） at the inner blood...AIM：To investigate the altering expression profiles of efflux transporters such as breast cancer-resistance protein（BCRP）,lung resistance protein（LRP）,and multidrug resistance protein 1（MDR1） at the inner blood-retinal barrier（BRB） during the development of early diabetic retinopathy（DR） and/or aging in mice.METHODS：Relative m RNA and protein expression profiles of these three efflux transporters in the retina during the development of early DR and/or aging in mice were examined.The differing expression profiles of Zonula occludens 1（ ZO-1） and vascular endothelial growth factor-A（ VEGFA） in the retina as well as the perfusion characterization of fluorescein isothiocyanate（FITC）-dextran and Evans blue were examined to evaluate the integrity of the inner BRB.RESULTS：There were significant alterations in these three efflux transporters＇ expression profiles in the m RNA and protein levels of the retina during the development of diabetes mellitus and/or aging.The development of early DR was confirmed by the expression profiles of ZO-1 and VEGFA in the retina as well as the compromised integrity of the inner BRB.CONCLUSION：The expression profiles of some efflux transporters such as BCRP,LRP,and MDR1 in mice retina during diabetic and/or aging conditions are tested,and the attenuated expression of BCRP,LRP,and MDR1 along with the breakdown of the inner BRB is found,which may be linked to the pathogenesis of early DR.展开更多
我们先前曾报道了舌癌耐药相关蛋白1(tongue cancer-resistant protein 1,TCRP1)的cDNA克隆,及其在平阳霉素诱导的舌癌耐药细胞系Tca8113/PYM中高表达,而该细胞同时也对顺铂耐受,提示TCRP1可能参与舌癌细胞对顺铂的耐受,但是具体机制目...我们先前曾报道了舌癌耐药相关蛋白1(tongue cancer-resistant protein 1,TCRP1)的cDNA克隆,及其在平阳霉素诱导的舌癌耐药细胞系Tca8113/PYM中高表达,而该细胞同时也对顺铂耐受,提示TCRP1可能参与舌癌细胞对顺铂的耐受,但是具体机制目前尚不清楚.本研究证明,TCRP1依赖c-myc的激活机制与舌癌细胞对顺铂耐受相关.生物信息学预测显示,TCRP1启动子存在原癌基因c-myc的结合位点;染色质免疫共沉淀(ChIP)技术证实,c-myc能通过其转录因子结合位点(transcription factor binding site,TFBS)与TCRP1启动子结合;利用半定量RT-PCR、蛋白质免疫印迹和MTS实验检测发现,将c-myc质粒导入舌癌细胞Tca8113中过表达,能显著上调TCRP1的mRNA和蛋白表达水平,且细胞对顺铂的耐受性增强;使用c-myc抑制剂或者siRNA沉默Tca8113/PYM细胞中c-myc,TCRP1的mRNA和蛋白表达水平均下降,且细胞对顺铂的敏感性增强.上述结果提示,转录因子c-myc可与TCRP1基因启动子特异性结合,上调TCRP1的表达,且该基因的表达上调与舌癌细胞对顺铂的耐受相关.展开更多
目的研究转酮醇酶样蛋白1(transketolase-like protein 1,TKTL1)在舌鳞状细胞癌中的表达,并探讨其与临床病理学参数和预后的关系。方法采用免疫组织化学方法检测45例舌鳞状细胞癌组织和对应的舌正常上皮组织中TKTL1的表达,采用log-rank...目的研究转酮醇酶样蛋白1(transketolase-like protein 1,TKTL1)在舌鳞状细胞癌中的表达,并探讨其与临床病理学参数和预后的关系。方法采用免疫组织化学方法检测45例舌鳞状细胞癌组织和对应的舌正常上皮组织中TKTL1的表达,采用log-rank检验分析TKTL1表达与患者预后之间的关系。结果舌鳞状细胞癌组织中TKTL1的阳性表达率(68.89%)高于舌正常上皮组织(15.56%),差异有统计学意义(χ2=26.235,P<0.01)。TKTL1的高表达与舌鳞状细胞癌患者的年龄、性别和组织分化程度无关(P>0.05),但与舌鳞状细胞癌患者的TNM分期和淋巴结转移密切相关(P<0.05)。通过log-rank检验发现TKTL1高表达的舌鳞状细胞癌患者的存活时间显著低于TKTL1低表达的患者,差异有统计学意义(P<0.05)。结论 TKTL1的高表达可能与舌鳞状细胞癌的发生、发展及预后关系密切。展开更多
基金Supported by the National Natural Science Foundation of China(No.81271036No.81500751)+1 种基金the Key Research Project of Shandong Province,China(No.2015GSF118121)the Natural Science Foundation of Shandong Province,China(No.ZR2015PH062)
文摘AIM：To investigate the altering expression profiles of efflux transporters such as breast cancer-resistance protein（BCRP）,lung resistance protein（LRP）,and multidrug resistance protein 1（MDR1） at the inner blood-retinal barrier（BRB） during the development of early diabetic retinopathy（DR） and/or aging in mice.METHODS：Relative m RNA and protein expression profiles of these three efflux transporters in the retina during the development of early DR and/or aging in mice were examined.The differing expression profiles of Zonula occludens 1（ ZO-1） and vascular endothelial growth factor-A（ VEGFA） in the retina as well as the perfusion characterization of fluorescein isothiocyanate（FITC）-dextran and Evans blue were examined to evaluate the integrity of the inner BRB.RESULTS：There were significant alterations in these three efflux transporters＇ expression profiles in the m RNA and protein levels of the retina during the development of diabetes mellitus and/or aging.The development of early DR was confirmed by the expression profiles of ZO-1 and VEGFA in the retina as well as the compromised integrity of the inner BRB.CONCLUSION：The expression profiles of some efflux transporters such as BCRP,LRP,and MDR1 in mice retina during diabetic and/or aging conditions are tested,and the attenuated expression of BCRP,LRP,and MDR1 along with the breakdown of the inner BRB is found,which may be linked to the pathogenesis of early DR.
文摘目的研究转酮醇酶样蛋白1(transketolase-like protein 1,TKTL1)在舌鳞状细胞癌中的表达,并探讨其与临床病理学参数和预后的关系。方法采用免疫组织化学方法检测45例舌鳞状细胞癌组织和对应的舌正常上皮组织中TKTL1的表达,采用log-rank检验分析TKTL1表达与患者预后之间的关系。结果舌鳞状细胞癌组织中TKTL1的阳性表达率(68.89%)高于舌正常上皮组织(15.56%),差异有统计学意义(χ2=26.235,P<0.01)。TKTL1的高表达与舌鳞状细胞癌患者的年龄、性别和组织分化程度无关(P>0.05),但与舌鳞状细胞癌患者的TNM分期和淋巴结转移密切相关(P<0.05)。通过log-rank检验发现TKTL1高表达的舌鳞状细胞癌患者的存活时间显著低于TKTL1低表达的患者,差异有统计学意义(P<0.05)。结论 TKTL1的高表达可能与舌鳞状细胞癌的发生、发展及预后关系密切。
