目的探讨染色体区域稳定蛋白1(chromosomal region maintenance 1,CRM1)与细胞因子信号传导抑制因子1(suppressor of cytokine signaling 1,SOCS1)表达与胃癌演进、临床病理特征及预后的关系。方法采用免疫组化检测低级别上皮内瘤变胃组...目的探讨染色体区域稳定蛋白1(chromosomal region maintenance 1,CRM1)与细胞因子信号传导抑制因子1(suppressor of cytokine signaling 1,SOCS1)表达与胃癌演进、临床病理特征及预后的关系。方法采用免疫组化检测低级别上皮内瘤变胃组织27例、高级别上皮内瘤变胃组织26例,以及进展期胃癌组织67例及对应癌旁组织67例中CRM1及SOCS1蛋白表达水平,分析两者在不同病变胃黏膜中的变化以及与胃癌临床病理特征的关系,通过在线分析工具Kaplan-Meier Plotter、单因素及多因素Cox分析影响胃癌患者预后的相关因素。结果胃癌组织中CRM1表达高于癌旁组织,SOCS1表达低于癌旁组织及瘤变组织(P<0.05);CRM1在胃癌组织高表达与浸润深度及淋巴结转移有关(P<0.05);生存分析显示高表达CRM1提示预后不良(P<0.05),SOCS1表达水平与预后无关(P>0.05);在胃癌组织中,CRM1与SOCS1表达无显著相关性(R=-0.025,P=0.842)。结论CRM1和SOCS1参与胃癌发生,CRM1高表达可能参与胃癌侵袭及转移等恶性进展。展开更多
Mantle cell lymphoma （MCL） is an aggressive histotype of B-cell non-Hodgkin lymphoma. The disease has no known cure, which prompts the urgent need for novel therapeutic agents. Chromosomal region maintenance 1 （CRM...Mantle cell lymphoma （MCL） is an aggressive histotype of B-cell non-Hodgkin lymphoma. The disease has no known cure, which prompts the urgent need for novel therapeutic agents. Chromosomal region maintenance 1 （CRM1） may play a role in human neoplasia and serve as a novel target of cancer treatment. This study summarizes MCL pathogenesis and determines the involvement of CRM1 in the regulation of several vital signaling pathways contributing to MCL pathogenesis, including the pathways of cell cycle progression, DNA damage response, phosphoinositide kinase-3, nuclear factor-kB activation, and chromosomal stability. A preclinical study is also presented to compare the CRNI1 status in MCL cell lines and primary MCL cells with normal B cells, as well as the therapeutic efficiency of CRM1 inhibition in MCL in vitro and in vivo, which make these agents potential targets of novel MCL treatments.展开更多
The function of the herpes simplex virus type 1 （HSV-1） UL4 protein is still elusive. Our objective is to investigate the subcellular transport mechanism of the UL4 protein. In this study, fluorescence microscopy wa...The function of the herpes simplex virus type 1 （HSV-1） UL4 protein is still elusive. Our objective is to investigate the subcellular transport mechanism of the UL4 protein. In this study, fluorescence microscopy was employed to investigate the subcellular localization of UL4 and characterize the transport mechanism in living cells. By constructing a series of deletion mutants fused with enhanced yellow fluorescent protein （EYFP）, the nuclear export signals （NES） of UL4 were for the first time mapped to amino acid residues 178 to 186. In addition, the N-terminal 19 amino acids are identified to be required for the granule-like cytoplasmic pattem of UL4. Furthermore, the UL4 protein was demonstrated to be exported to the cytoplasm through the NES in a chromosomal region maintenance 1 （CRM1）-dependent manner involving RanGTP hydrolysis展开更多
文摘目的探讨染色体区域稳定蛋白1(chromosomal region maintenance 1,CRM1)与细胞因子信号传导抑制因子1(suppressor of cytokine signaling 1,SOCS1)表达与胃癌演进、临床病理特征及预后的关系。方法采用免疫组化检测低级别上皮内瘤变胃组织27例、高级别上皮内瘤变胃组织26例,以及进展期胃癌组织67例及对应癌旁组织67例中CRM1及SOCS1蛋白表达水平,分析两者在不同病变胃黏膜中的变化以及与胃癌临床病理特征的关系,通过在线分析工具Kaplan-Meier Plotter、单因素及多因素Cox分析影响胃癌患者预后的相关因素。结果胃癌组织中CRM1表达高于癌旁组织,SOCS1表达低于癌旁组织及瘤变组织(P<0.05);CRM1在胃癌组织高表达与浸润深度及淋巴结转移有关(P<0.05);生存分析显示高表达CRM1提示预后不良(P<0.05),SOCS1表达水平与预后无关(P>0.05);在胃癌组织中,CRM1与SOCS1表达无显著相关性(R=-0.025,P=0.842)。结论CRM1和SOCS1参与胃癌发生,CRM1高表达可能参与胃癌侵袭及转移等恶性进展。
基金supported in part by grants from Fujian Provincial Department of Science & Technology(2009-CXB-57/ 2011J01252)Bureau of Science & Technology of Xiamen,China (3502Z20094012)
文摘Mantle cell lymphoma （MCL） is an aggressive histotype of B-cell non-Hodgkin lymphoma. The disease has no known cure, which prompts the urgent need for novel therapeutic agents. Chromosomal region maintenance 1 （CRM1） may play a role in human neoplasia and serve as a novel target of cancer treatment. This study summarizes MCL pathogenesis and determines the involvement of CRM1 in the regulation of several vital signaling pathways contributing to MCL pathogenesis, including the pathways of cell cycle progression, DNA damage response, phosphoinositide kinase-3, nuclear factor-kB activation, and chromosomal stability. A preclinical study is also presented to compare the CRNI1 status in MCL cell lines and primary MCL cells with normal B cells, as well as the therapeutic efficiency of CRM1 inhibition in MCL in vitro and in vivo, which make these agents potential targets of novel MCL treatments.
基金the Major State Basic Research Development Program of China(2010CB530105 and 2011CB504802)the National Natural Science Foundation of China(30900059,30870120 and 81000736)the Start-up Fund of the Hundred Talents Program of the Chinese Academy of Sciences(20071010-141)
文摘The function of the herpes simplex virus type 1 （HSV-1） UL4 protein is still elusive. Our objective is to investigate the subcellular transport mechanism of the UL4 protein. In this study, fluorescence microscopy was employed to investigate the subcellular localization of UL4 and characterize the transport mechanism in living cells. By constructing a series of deletion mutants fused with enhanced yellow fluorescent protein （EYFP）, the nuclear export signals （NES） of UL4 were for the first time mapped to amino acid residues 178 to 186. In addition, the N-terminal 19 amino acids are identified to be required for the granule-like cytoplasmic pattem of UL4. Furthermore, the UL4 protein was demonstrated to be exported to the cytoplasm through the NES in a chromosomal region maintenance 1 （CRM1）-dependent manner involving RanGTP hydrolysis
