肿瘤标志物CEA、CA199对结直肠癌TNM分期的预判价值

目的:探讨肿瘤标志物CEA、CA199浓度变化在结直肠癌TNM分期中的预判价值。方法:回顾我院2010年1月~2013年10月收治的经手术治疗的结、直肠癌患者(共96例)的有关资料,分析其术前CEA、CA199浓度水平与术后病理确定TNM分期结果的相互关系,进行相应的统计学检测。结果:结直肠癌Ⅰ~Ⅳ期CEA浓度依次为4.28±1.78、6.92±2.01、23.99±6.49和362.64±158.80 ng/mL,CA199浓度依次为12.58±2.98、13.37±2.62、36.84±10.33和238.71±103.69 U/mL,肿瘤标志物CEA、CA199的浓度随TNM分期升级而增高,通过Kruskal-Wallis秩检验分析及Spearman秩相关分析,表明CEA、CA199的血清浓度与TNM分期明显相关(P0.01)。结论:CEA、CA199血清浓度与TNM分期呈正相关,而年龄与CEA、CA199在各期中的浓度无明显相关性。因此,应用CEA、CA199的血清学测定在一定程度上具有预判结直肠癌TNM分期的价值。     

BLCA-4 在膀胱癌中作用的研究进展

摘要：近年来,膀胱癌的发病率与死亡率呈逐年上升,已成为泌尿系统最常见的肿瘤。随着分子生物技术的不断发展,核基质蛋白(NMPs)、膀胱肿瘤抗原(BTA)、透明质酸和透明质酸酶(HA-HAase)、细胞角蛋白(CK)等诸多膀胱肿瘤标志物被发现。其中,膀胱癌特异性核基质蛋白-4(BLCA-4)是一种可溶性的复合物,在正常膀胱组织中不表达而存在于膀胱癌组织中。检测尿样中BLCA-4水平有望用于膀胱癌的筛查及诊断,具有较高的敏感性和特异性,也可用于普通人群与膀胱癌高危人群(脊髓损伤患者)的筛选与检测;而术后病理组织检测BLCA-4 的表达也可为膀胱癌患者的预后预测提供参考。本文对近年来BLCA-4 在膀胱癌中的作用进行了综述。     

DCC regulates cell adhesion in human colon cancer derived HT-29 cells and associates with ezrin

The deleted in colorectal cancer (DCC) gene encodes a 170- to 190-kDa protein of the Immunoglobulin superfamily. Firstly identified as a tumor suppressor gene in human colorectal carcinomas, the main function for DCC has been described in the nervous system as part of a receptor complex for netrin-1. Moreover, roles in mucosecretory cell differentiation and as inducer of apoptosis have also been reported. DCC knockout mice supported a crucial role for this gene in axonal migration, yet questioned its implication in tumor suppression and mucosecretory differentiation. The work presented here demonstrates that a DCC-transfected HT-29 colonic human cell line (HT-29/DCC) displays an increase in cell-cell adhesion to the detriment of cell-matrix interactions: HT-29/DCC cells exhibit more and better-structured desmosomes while focal adhesions and hemidesmosomes are disrupted. HT-29/DCC cells show no changes in adherent junctions but upon treatment with TPA, HT-29/DCC cells show resistance to scattering, and maintain E-cadherin in the membrane. In addition, the actin cytoskeleton is affected in HT-29/DCC cells: stress fibers are disrupted while cortical actin remains intact. We identified a putative ERM-M (ezrin/radixin/moesin and merlin) binding domain in the juxtamembrane region of the DCC protein. In vitro pull-down assays demonstrate the interaction of the DCC cytoplasmic domain with the N-terminal region of ezrin and merlin, and co-immunoprecipitation assays in transiently DCC-transfected COS-1 cells showed that the interaction between DCC and ezrin also takes place in vivo. Altogether, our results suggest that DCC could regulate cell adhesion and migration through its association with ERM-M proteins.     

BLCA-4在膀胱癌中作用的研究进展

近年来,膀胱癌的发病率与死亡率呈逐年上升,已成为泌尿系统最常见的肿瘤。随着分子生物技术的不断发展,核基质蛋白（SMVs）、膀胱肿瘤抗原（BTA）、透明质酸和透明质酸酶（HA—Haase）、细胞角蛋O（CK）等诸多膀胱肿瘤标志物被发现。其中,膀胱癌特异性核基质蛋白-4（BLCA-4）是一种可溶性的复合物,在正常膀胱组织中不表达而存在于膀胱癌组织中。检测尿样中BLCA-4水平有望用于膀胱癌的筛查及诊断,具有较高的敏感性和特异性,也可用于普通人群与膀胱癌高危人群（脊髓损伤患者）的筛选与检测;而术后病理组织检测BLCA-4的表达也可为膀胱癌患者的预后预测提供参考。本文对近年来BLCA-4在膀胱癌中的作用进行了综述。     

MAR结合蛋白

MAR (matrix association regions)是真核基因组的DNA序列中可特异性地与核基质紧密结合的区域.MAR通过特异性地与一些MAR结合蛋白相互作用,在真核基因的复制和表达调控以及染色体的包装构建等方面发挥重要作用.MAR结合蛋白主要包括一些构成染色质或核基质的结构蛋白（如组蛋白H₁、拓扑异构酶Ⅰ和Ⅱ、HMG I/Y、Lamin B₁、Matrin等）以及一些组织特异性表达的蛋白（如SATB₁、骨钙蛋白基因启动子结合因子等）.根据它们与核基质的关系将MAR结合蛋白分为三类：核基质富含组分、核基质稀有组分以及非核基质组分,对其与MAR的相互作用进行了比较和分析.     

胃癌发生中的独特肿瘤标记物—LI-cadherin

LI-cadherin,也被称为cadherin-17,是肠上皮细胞中一种贯穿细胞膜的、钙依赖性的、介导细胞间连接的糖蛋白。与经典钙黏蛋白相比,LI-cadherin是一种具备独特结构和功能的新型钙黏蛋白。LI-cadherin由7个胞外重复序列和一个只包含20个氨基酸残基的较短的胞质尾区组成。在人体中,LI-cadherin特异性的位于肝细胞和肠细胞中的底外侧区。而LI-cadherin介导细胞连接时,既不与链蛋白结合,也不导致β-catenin的上调。一些研究发现,在胃癌中LI-cadherin的过度表达与CDX-2显著相关,而且在肠化生中CDX-2的表达总是与LI-cadherin呈现很强的成对性。最新的研究认为LI-cadherin的表达与胃癌的发生、发展、转移及预后均有关系。在针对胃癌的临床处理方面,LI-cadherin将会是有用的肿瘤标记物。     

Unraveling the organization of the internal nuclear matrix: RNA-dependent anchoring of NuMA to a lamin scaffold

Using quantitative immunoelectron microscopy we show here that when the nuclear matrix is isolated from rat hepatocytes in the presence of an inhibitor of RNase activity both lamins and the nuclear mitotic apparatus protein (NuMA) preferentially localize within the electron-dense domains of the internal nuclear matrix (INM). After RNA digestion NuMA undergoes a sharp depletion, while labeling by an antibody against lamins A and C within the electron-transparent regions increases, suggesting that a subset of lamin epitopes is masked by the interaction with RNA. We were able to explain this result by visualizing for the first time a thin web of lamin protofibrils which connects the electron-dense regions. Confirmation of these changes has been obtained by immunoblot analysis and confocal microscopy. As RNA digestion results both in the release of NuMA and in the collapse of the INM, we propose that a fraction of nuclear RNA brings about the association of NuMA islands with a lamin scaffold and that this interaction is required to maintain the latter in a state of high molecular dispersion.     

CT联合肿瘤标志物与MRI联合肿瘤标志物对于直肠癌患者术前诊断的准确率与特异性的研究

目的:探讨CT联合肿瘤标志物与MRI联合肿瘤标志物对于直肠癌患者术前诊断的准确率与特异性,为大肠癌的术前诊断提供一定的理论依据。方法:选取我院在2015年01月至2016年01月间收治的86例直肠癌患者以及64例肠道良性病变患者分别作为观察组I组和观察II组的研究对象,另外选取来我院进行健康体检的80例人员作为对照组研究,分别分析CT联合肿瘤标志物与MRI联合肿瘤标志物(CEA、CA125、CA199、CA242、CA724)对大肠癌患者诊断的准确率与特异性之间的差别。结果:观察I组肿瘤标志物水平要明显高于观察II组和对照组,差异显著,具有统计学意义;肿瘤标志物CEA、CA125、CA199、CA242、CA724对大肠癌患者检测的阳性率分别为67.44%(58/86)、26.74%(23/86)、84.88%(73/86)、72.09%(62/86)、33.72%(29/86),肿瘤标志物并联检测对大肠癌的阳性检测率为94.19%(81/86)。CT联合肿瘤标志物对大肠癌的准确率为97.67%(84/86),特异性为94.44%(136/144);MRI联合肿瘤标志物对大肠癌的阳性检测率为100.00%(86/86),特异性为98.61%(142/144)。结论:CT联合肿瘤标志物对大肠癌诊断的准确率与特异性均不如MRI联合肿瘤标志物,因此MRI联合肿瘤标志物可作为大肠癌除病理学鉴定外最佳的诊断方式。     

Nuclear matrix proteins in well and poorly differentiated human breast cancer cell lines

The nuclear matrix, besides providing the structural support of the nucleus, is involved in various cellular functions of the nucleus. Nuclear matrix proteins (NMPs), which are both tissue- and cell type–specific, are altered with transformation and state of differentiation. Furthermore, NMPs have been identified as informative markers of disease states. Here, the NMP profiles from human breast cancer cell lines and breast tumours were analyzed using two-dimension gel electrophoresis. We identified NMPs that are associated with well and poorly differentiated human breast cancer cells in vitro and in vivo. Five NMPs (NMBC 1–5) were found to be exclusive for well-differentiated human breast cancer cells, while one NMP (NMBC-6) was found to be present only in poorly differentiated human breast cancer cells. The identification of these proteins suggests the potential use of nuclear matrix proteins as prognostic indicators. J. Cell. Biochem. 66:9–15, 1997. © 1997 Wiley-Liss, Inc.     

Interaction of MAR-sequences with nuclear matrix proteins.

The recent discovery of DNA sequences responsible for the specific attachment of chromosomal DNA to the nuclear skeleton (MARs/SARs) was an important step towards our understanding of the functional and structural organization of eukaryotic chromatin [Mirkovitch et al.: Cell 44:273-282, 1984; Cockerill and Garrard: Cell 44:273-282, 1986]. A most important question, however, remains the nature of the matrix proteins involved in the specific binding of the MARs. It has been shown that topoisomerase II and histone H1 were capable of a specific interaction with SARs by the formation of precipitable complexes [Adachi et al.: EMBO J8:3997-4006, 1989; Izaurralde et al.: J Mol Biol 210:573-585, 1989]. Here, applying a different approach, we were able to "visualize" some of the skeletal proteins recognizing and specifically binding MAR-sequences. It is shown that the major matrix proteins are practically the same in both salt- and LIS-extracted matrices. However, the relative MAR-binding activity of the individual protein components may be different, depending on the method of matrix preparation. The immunological approach applied here allowed us to identify some of the individual MAR-binding matrix proteins. Histone H1 and nuclear actin are shown to be not only important components of the matrix, but to be involved in a highly efficient interaction with MAR-sequences as well. Evidence is presented that proteins recognized by the anti-HMG antibodies also participate in MAR-interactions.