目的:观察真核转录起始因子4E(eIF4E)在食管癌组织中的表达并计数微淋巴管密度(MLVD),探讨eIF4E与食管癌发生和转移的关系以及在食管癌微淋巴管生成中的作用。方法:应用免疫组织化学技术检测75例食管癌石蜡标本切片中eIF4E和D2-40的表达...目的:观察真核转录起始因子4E(eIF4E)在食管癌组织中的表达并计数微淋巴管密度(MLVD),探讨eIF4E与食管癌发生和转移的关系以及在食管癌微淋巴管生成中的作用。方法:应用免疫组织化学技术检测75例食管癌石蜡标本切片中eIF4E和D2-40的表达,以26例癌旁组织、55例正常食管组织为对照;采用Image Pro Plus(IPP)6.0图像分析软件对采集的图片进行分析。结果:eIF4E在食管癌组织(0.048±0.023)中的表达较癌旁(0.028±0.023)和正常食管组织(0.013±0.016)高(P<0.05),且随着食管癌分化程度的降低,表达强度逐渐增强;eIF4E在淋巴结转移组(0.068±0.014)中的表达高于非淋巴结转移组(0.033±0.016)(P<0.05);eIF4E在中晚期食管癌组中的表达高于早期食管癌组(P<0.05);eIF4E的表达与患者的性别、年龄无关(P>0.05)。低分化食管癌组中的MLVD较中分化和高分化的MLVD高;淋巴结转移组MLVD较未转移组高(P<0.05)。eIF4E的表达与食管癌MLVD呈正相关(r=0.624,P<0.01)。结论:eIF4E在食管癌组织中有较高的表达,且与淋巴结转移、分化程度及食管癌组织的MLVD密切相关,提示食管癌的发生和淋巴转移可能与eIF4E有关,eIF4E可能作为食管癌新的标志物以及评估食管癌进展的客观指标。展开更多
Leukoencephalopathy with vanishing white matter(VWM) is one of the most prevalent inherited white matter disorders in childhood,and it′s the only known hereditary human disease due to the direct defects in protein sy...Leukoencephalopathy with vanishing white matter(VWM) is one of the most prevalent inherited white matter disorders in childhood,and it′s the only known hereditary human disease due to the direct defects in protein synthesis process,with the gene defects in EIF2B1-5,encoding the five subunits of eukaryotic translation initiation factor(eIF2B α,β,γ,δ and ε) respectively.eIF2B is essential for the protein translation initiation process,and its action is realized via eukaryotic translation initiation factor2(eIF2).Phosphorylation of eIF2α and eIF2Bε is an important way to regulate eIF2B function,and thus play a key role in control of the protein translation level under physiological condition.Mutant eIF2B results in functional defects and decrease of the overall protein translation in cells,but in increase the translation of proteins with multiple upstream open reading frames,such as activating transcription factor 4(AFT4),which leads to the susceptibility to un-folded protein response under stress,and the following apoptosis.The exact pathogenic mechanisms of VWM are far from well understood.It′s suggested that level of AFT4 in cells with eIF2B mutations is higher than in wild type cells under physiological condition,which makes the mutant cells more susceptible to endoplasmic reticulum(ER) stress and unfolded protein response(UPR).Under stress,the defect eIF2B leads to a vicious cycle of UPR activation,which may underlie the neurological aggravation in VWM patients after minor stress,a specific cli-nical feature of VWM.Elucidating the pathogenesis of VWM will be helpful to further understand the protein translation process in eukaryotic cells,and provide a clue for possible therapeutic targets and treatment strategies in the future.Abstract:SUMM ARY Leukoencephalopathy with vanishing white matter(VWM) is one of the most prevalent in-herited white matter d isorders in childhood,and i′ts the only known hered itary human d isease due to the d irect defects in protein synthesis process,with the gene defects inEIF2B1-5,encod ing the five sub-units of eukaryotic translation initiation factor(eIF2Bα,β,γ,δandε) respectively.eIF2B is essential for the protein translation initiation process,and its action is realized via eukaryotic translation initiation factor2(eIF2).Phosphorylation of eIF2αand eIF2Bεis an important way to regulate eIF2B function,and thus play a key role in control of the protein translation level under physiological cond ition.Mutant eIF2B results in functional defects and decrease of the overall protein translation in cells,but in increase the translation of proteins with multiple upstream open read ing frames,such as activating transcription factor 4(AFT4),which leads to the susceptibility to un-folded protein response under stress,and the following apoptosis.The exact pathogenic mechanisms ofVWM are far from well understood.I′ts sugges-ted that level ofAFT4 in cells with eIF2B mutations is higher than in wild type cells under physiological cond ition,which makes the mutant cellsmore susceptible to endoplasm ic reticulum(ER) stress and un-folded protein response(UPR).Under stress,the defect eIF2B leads to a vicious cycle ofUPR activa-tion,which may underlie the neurological aggravation in VWM patients afterm inor stress,a specific cli-nical feature ofVWM.E lucidating the pathogenesis ofVWM will be helpful to further understand the pro-tein translation process in eukaryotic cells,and provide a clue for possible therapeutic targets and treat-ment strategies in the future.展开更多
文摘目的:观察真核转录起始因子4E(eIF4E)在食管癌组织中的表达并计数微淋巴管密度(MLVD),探讨eIF4E与食管癌发生和转移的关系以及在食管癌微淋巴管生成中的作用。方法:应用免疫组织化学技术检测75例食管癌石蜡标本切片中eIF4E和D2-40的表达,以26例癌旁组织、55例正常食管组织为对照;采用Image Pro Plus(IPP)6.0图像分析软件对采集的图片进行分析。结果:eIF4E在食管癌组织(0.048±0.023)中的表达较癌旁(0.028±0.023)和正常食管组织(0.013±0.016)高(P<0.05),且随着食管癌分化程度的降低,表达强度逐渐增强;eIF4E在淋巴结转移组(0.068±0.014)中的表达高于非淋巴结转移组(0.033±0.016)(P<0.05);eIF4E在中晚期食管癌组中的表达高于早期食管癌组(P<0.05);eIF4E的表达与患者的性别、年龄无关(P>0.05)。低分化食管癌组中的MLVD较中分化和高分化的MLVD高;淋巴结转移组MLVD较未转移组高(P<0.05)。eIF4E的表达与食管癌MLVD呈正相关(r=0.624,P<0.01)。结论:eIF4E在食管癌组织中有较高的表达,且与淋巴结转移、分化程度及食管癌组织的MLVD密切相关,提示食管癌的发生和淋巴转移可能与eIF4E有关,eIF4E可能作为食管癌新的标志物以及评估食管癌进展的客观指标。
文摘Leukoencephalopathy with vanishing white matter(VWM) is one of the most prevalent inherited white matter disorders in childhood,and it′s the only known hereditary human disease due to the direct defects in protein synthesis process,with the gene defects in EIF2B1-5,encoding the five subunits of eukaryotic translation initiation factor(eIF2B α,β,γ,δ and ε) respectively.eIF2B is essential for the protein translation initiation process,and its action is realized via eukaryotic translation initiation factor2(eIF2).Phosphorylation of eIF2α and eIF2Bε is an important way to regulate eIF2B function,and thus play a key role in control of the protein translation level under physiological condition.Mutant eIF2B results in functional defects and decrease of the overall protein translation in cells,but in increase the translation of proteins with multiple upstream open reading frames,such as activating transcription factor 4(AFT4),which leads to the susceptibility to un-folded protein response under stress,and the following apoptosis.The exact pathogenic mechanisms of VWM are far from well understood.It′s suggested that level of AFT4 in cells with eIF2B mutations is higher than in wild type cells under physiological condition,which makes the mutant cells more susceptible to endoplasmic reticulum(ER) stress and unfolded protein response(UPR).Under stress,the defect eIF2B leads to a vicious cycle of UPR activation,which may underlie the neurological aggravation in VWM patients after minor stress,a specific cli-nical feature of VWM.Elucidating the pathogenesis of VWM will be helpful to further understand the protein translation process in eukaryotic cells,and provide a clue for possible therapeutic targets and treatment strategies in the future.Abstract:SUMM ARY Leukoencephalopathy with vanishing white matter(VWM) is one of the most prevalent in-herited white matter d isorders in childhood,and i′ts the only known hered itary human d isease due to the d irect defects in protein synthesis process,with the gene defects inEIF2B1-5,encod ing the five sub-units of eukaryotic translation initiation factor(eIF2Bα,β,γ,δandε) respectively.eIF2B is essential for the protein translation initiation process,and its action is realized via eukaryotic translation initiation factor2(eIF2).Phosphorylation of eIF2αand eIF2Bεis an important way to regulate eIF2B function,and thus play a key role in control of the protein translation level under physiological cond ition.Mutant eIF2B results in functional defects and decrease of the overall protein translation in cells,but in increase the translation of proteins with multiple upstream open read ing frames,such as activating transcription factor 4(AFT4),which leads to the susceptibility to un-folded protein response under stress,and the following apoptosis.The exact pathogenic mechanisms ofVWM are far from well understood.I′ts sugges-ted that level ofAFT4 in cells with eIF2B mutations is higher than in wild type cells under physiological cond ition,which makes the mutant cellsmore susceptible to endoplasm ic reticulum(ER) stress and un-folded protein response(UPR).Under stress,the defect eIF2B leads to a vicious cycle ofUPR activa-tion,which may underlie the neurological aggravation in VWM patients afterm inor stress,a specific cli-nical feature ofVWM.E lucidating the pathogenesis ofVWM will be helpful to further understand the pro-tein translation process in eukaryotic cells,and provide a clue for possible therapeutic targets and treat-ment strategies in the future.
