CD44v6及nm23-H1表达与肝细胞癌侵袭转移

目的原位检测肝细胞癌(HCC)中CD44v6 mRNA及nm23-H1 mRNA的表达,了解CD44v6 mRNA及nm23-H1 mRNA的表达与HCC侵袭转移的关系,了解HCC中CD44v6 mRNA表达与nm23-H1 mRNA表达的相关性.方法采用PCR法合成CD44v6 cDNA探针,体外转录法合成nm23-H1 cRNA探针,采用原位杂交法检测HCC 33例 CD44v6 mRNA和nm23-H1 mRNA的表达.结果侵袭转移倾向高危组的10例HCC标本中,CD44v6 mRNA和nm23-H1 mRNA的阳性率分别为80.0%(8/10)和40.0%(4/10);侵袭转移倾向低危组的23例HCC标本中,CD44v6 mRNA和nm23-H1 mRNA的阳性率分别为21.7%(5/23)和91.3%(21/23).CD44v6 mRNA的表达与HCC的侵袭转移倾向具有正相关性(P＜0.01),nm23-H1 mRNA的表达与HCC的侵袭转移倾向具有负相关性(P＜0.01),CD44v6 mRNA及nm23-H1 mRNA的表达具有负相关性(P＜0.01).结论检测CD44v6 mRNA及nm23-H1 mRNA的表达可能成为HCC转移预后判断的指标.     

原发性肝细胞癌中CD44v6和nm23H1基因的转录表达及临床意义

研究CD44v6 mRNA和nm23H1 mRNA表达与肝细胞癌（HCC）侵袭转移和预后的关系。应用原位杂交方法，检测分析HCC组织中CD44v6 mRNA和nm23H mRNA表达。99例HCC中，CD44v6 mRNA和nm23H1 mRNA表达阳性率分别为41．4％和76．8％。CD44v6mRNA表达与nm23H1mRNA表达呈负相关。CD44v6和nm23HmRNA表达均与HCC侵袭转移倾向和预后相关。检测CD44v6和nm23H1表达有可能成为HCC 侵袭转移和预后判断的病理生物学指标。     

大肠癌CD15,CD44v6和nm23H1的mRNA表达与转移及预后的相关性

目的 探讨CD15,CD44v6和nm23H1的mRNA表达与大肠癌临床病理参数和预后的关系及相关性.方法 应用原位杂交检测90例大肠癌中CD15,CD44v6和nm23H1的mRNA表达及20例原发灶和转移灶大肠癌配对标本中CD15 mRNA表达,并结合53例5 a以上随访资料分析.结果 90例大肠癌中CD15,CD44v6和nm23H1的mRNA阳性表达分别为76例(84.4%),62例(68.9%)和60例(66.7%).CD15和CD44v6的mRNA高表达及nm23H1 mRNA低表达与大肠癌Duke's分期、浆膜浸润、淋巴结转移、肝脏转移均呈正相关.大肠癌中CD15 mRNA表达与CD44v6 mRNA表达呈正相关,与nm23H1 mRNA表达呈负相关.20例原发灶和转移灶大肠癌配对标本中,CD15 mRNA表达水平一致.结论 大肠癌的侵袭转移与相关基因协同作用密切相关.在大肠癌的侵袭转移中cDl5,CD44v6和nm23H1的mRNA表达具有正、负调节的协同作用可能.CD15 mRNA可作为一个新的准确预测大肠癌侵袭转移潜能,并客观评估患者预后的生物学指标.     

大肠癌组织中CD44v6的表达及意义

目的 探讨大肠癌组织中CD44v6的表达,分析其与大肠癌临床病理指标的关系。方法采用高敏感性催化信号放大免疫组化技术,检测78例大肠癌组织、20例癌旁组织和20例正常大肠组织中CD44v6表达水平。结果大肠癌组织中CD44v6阳性表达率为83．3％,癌旁组织中为40％,正常组织中为阴性,两两比较,P〈0．01;CD44v6阳性表达与大肠癌的临床分期、分化程度、淋巴结转移及远处转移和患者预后有关（P〈0．05）。结论CD44v6的表达与大肠癌的侵袭、转移有关,并在大肠癌发生、发展中发挥重要作用。大肠癌组织中CD44v6的表达情况可作为判定其预后的新生物学指标。     

肝细胞癌CD44v6和p16基因蛋白的表达及其意义

目的探讨CD44v6和p16基因蛋白表达与肝细胞癌(HCC)转移和预后的关系。方法应用免疫组织化学方法,检测分析110例HCC组织中CD44v6及p116蛋白表达,结合随访资料分析。结果在HCC中,CD44v6和p16阳性表达率分别为42.7%和34.5%。CD44v6阳性表达的HCC转移率高(P<0.05),分化程度和患者>5年生存率低(P<0.05);p16阳性表达的HCC转移率低(P<0.05),分化程度和患者>5年生存率高(P<0.05)。CD44v6与p16表达呈负相关(r=-0.59,P<0.005)。结论CD44v6和p16表达与HCC转移和患者生存期密切相关,检测CD44v6和p16蛋白的表达可作为判断HCC预后的参考指标。     

肾癌组织中E-钙黏素和CD44v6的表达及意义

目的观察E-钙黏素和CD44v6在肾癌组织中的表达,并探讨其意义。方法采用免疫组化SP法检测45例肾癌组织和15例正常肾脏组织中的E-钙黏素和CD44 v6。结果 E-钙黏素在肾癌组织中的阳性表达率为24.4%,显著低于正常肾组织的75.0%（P〈0.05）。CD44v6在肾癌组织中的阳性表达率为48.9%,高于正常肾组织的16.7%（P〈0.05）。E-钙黏素、CD44v6与肾癌临床分期、病理分级和淋巴结转移有关（P均〈0.05）。结论肾癌组织中E-钙黏素呈低表达,CD44v6呈高表达,二者与肾癌的发生发展有关,可作为预测肾癌侵袭转移的指标。     

乳腺癌转移患者CD44v6变化及意义

采用免疫组化法检测乳腺癌患者原发灶及转移灶中黏附分子CD44v6、增殖细胞核抗原（PCNA）及雌激素受体（ER）的表达情况。结果显示，原发灶CD44v6及PCNA表达阳性细胞数及平均灰度均高于转移灶（P〈0．05）；转移灶中，CD44v6与PCNA表达呈正相关（r=0．54，P〈0．05）。提示CD44v6表达与乳腺癌转移有关，是判定其预后的有价值指标。     

黏附分子CD44的表达及其糖基化与肝癌转移的相关性

目的 探讨CD44S及其变异体CD44v分子的表达和其糖基化与肝癌细胞侵袭转移的关系. 方法 用免疫组织化学法、量子点、RT-PCR、Western blot、细胞免疫荧光染色、甲基化特异性聚合酶链反应等技术检测转移与非转移性肝癌组织、不同转移潜能人肝癌细胞株中CD44S及其变异体CD44v的定位与表达;并应用多重凝集素印迹法检测这些细胞株中CD44v6的糖基化差异.组间均数比较应用方差分析及t检验,多组间等级资料的比较采用Wilcoxon秩和检验,各组间率的比较采用x2检验.结果 免疫组织化学结果显示,CD44S蛋白定位以细胞质为主; CD44v3、CD44v4/5蛋白定位于细胞膜与细胞质;而CD44v6主要定位于细胞膜.组织芯片结果显示,相对于CD44S及其他CD44v,CD44v6在转移组的表达水平高于非转移组(阳性率为75％与46％),差异具有统计学意义(x2=8.828,P＜0.05);量子点检测(t=2.392,P＜0.05)与血清学检测(t=2.56,P＜0.05)也证实这一结果.Western blot结果显示,CD44v6的表达与肝癌细胞转移潜能呈正相关.此外,在MHCC97L、MHCC97H肝癌细胞中CD44v6基因启动子发生不完全甲基化,而在Hep3B细胞中则发生完全甲基化.而且,相对于Hep3B细胞,MHCC97L及MHCC97H细胞中CD44v6蛋白对朝鲜槐凝集素、黑接骨木凝集素及麦胚凝激素的亲和力较高. 结论 在CD44S及其变异体CD44v中,CD44v6蛋白的高表达与肝癌转移潜能的增强呈正相关;其高表达可能与基因启动子低甲基化有关.此外,CD44v6蛋白唾液酸寡糖链的增加可能与肝癌细胞转移潜能增高有关.     

变异型CD44分子和癌细胞的侵袭及转移

变异型CD44（CD44v）对癌细胞侵袭及转移有着密切的关系,本文拟从侵袭、转移癌组织中CD44v的表达情况和CD44v在癌细胞侵袭、转移中的机理两个方面,结合国内外有关研究的结果对CD44v和癌细胞侵袭、转移的关系作进一步综述。     

CD44s和CD44v6在肺癌组织中的表达及意义

采用免疫组化法检测107例肺癌组织中标准型CD44（CD44s）和变异型CD44（CD44v）6的表达,结果，17例小细胞肺癌（SCLC）中，CD44v6和CD44s均无表达;非小细胞肺癌（NSCLC）中，CD44v6和CD44s在鳞癌中的阳性表达率（81．0％和83．3％）均高于腺癌（39．6％和54．2％），P均〈0．05;无淋巴结转移的NSCLC中，CD44v6阳性表达率（34．0％）低于CD44s（78．0％）。P〈0．05；有淋巴结转移的NSCLC中．CD44v6阳性表达率（90．0％）高于CD44s（55．0％），P〈0．05。NSCLC的CD44v6和CD44s表达与其病理类型、临床分期、肿瘤分级及淋巴结转移均有关（P均〈0．05）。认为CD44v6和CD44s可以作为鉴别SCLC与NSCLC及判断肺癌病理类型、临床分期、肿瘤分级及淋巴结转移的参考指标。     

Immunohistological patterns of myeloid antigens: tissue distribution of CD13, CD14, CD16, CD31, CD36, CD65, CD66 and CD67

Summary. A number of differentiation antigens on myeloid cells have been defined on the CD classification system by the four International Workshops on Human Leucocyte Differentiation Antigens. The distribution of eight of these antigens (CD13, CD14, CD16, CD31, CD36, CD65, CD66, CD67) have been studied in human tissues, with the aim of documenting their immunohistological patterns and their degree of myeloid restriction. CD13, the most widely distributed antigen, was found in skin, bile canaliculi, kidney and pancreas. CD14 was not restricted to monocytes and tissue macrophages, being also strongly expressed on dendritic reticulum cells. CD 16 was expressed on granulocytes and tissue macrophages (alveolar and Kupffer cells) and in the red pulp of the spleen. CD31 and CD36 gave a characteristic staining of vascular endothelium, corresponding to their identification as the platelet glycoproteins gp IIa and gp IV. Antibodies against the most recently defined myeloid antigens (CD65, CD66 and CD67) appeared to be more specific for myeloid differentiation than previously described 'myeloid antigens'.     

CD4+, CD33-, CD13-, CD14- acute monoblastic leukaemia.

We report a case of acute monoblastic leukaemia in which the expression of the CD4 antigen occurred in the absence of myeloid and monocytic lineage specific markers. Unexpected marker profiles have biological and diagnostic implications and we also suggest that the inappropriate expression of the CD4 antigen may be implicated in the poor prognosis of this case.     

肝硬变和肝细胞癌组织中CD54,CD80,CD86和HLA-ABC的表达

目的探讨CD54,CD80,CD86和HLA-ABC在肝硬变的免疫损伤和抗肝癌免疫中的意义.方法用免疫组化方法检测CD54,CD80,CD86和HLA-ABC在肝硬变(n=30)和肝癌(n=48)中的表达、定位和分布.结果在LC中,CD54阳性率为40%(12/30),CD80为50%(15/30),CD86为37%(11/30),HLA-ABC为63%(19/30);在HCC中,CD54阳性率为77%(37/48),CD80为19%(9/47),CD86为13%(6/47),HLA-ABC为30%(12/40);在癌周围组织(PCT)中,CD54为阴性,CD80阳性率为44%(14/32),CD86为47%(15/32),HLA-ABC为53%(17/32).统计学处理显示,在LC中,CD54阳性率显著低于HCC(P＜0.01);CD80(P＜0.01),CD86(P＜0.05)和HLA-ABC(P＜0.01)均显著高于HCC;而与PCT无显著差别.在HCC中,CD80(P＜0.05),CD86(P＜0.01),HLA-ABC(P＜0.05),均显著低于PCT.结论 CD54,CD80,CD86和HLA-ABC在LC和HCC中的同时足量表达有可能引起肝细胞损伤和有效抗肿瘤免疫应答,而CD80,CD86表达的缺失或不足可能是HCC产生免疫逃避的主要原因.     

Expression of cytoadhesion molecules (CD56, CD54, CD18 and CD29) by myeloma plasma cells

Recently we reported the expression of the human natural killer cell associated antigen CD56 (Leu 19/NKH1) in plasma cells of a majority of multiple myeloma (MM) patients. CD56 is known to be an isoform of the human neural adhesion molecule N-CAM which is involved in homotypic adhesive interactions. By immunophenotyping using four CD56 specific monoclonal antibodies and immunoprecipitation analysis we here confirm that the Leu 19 antigen expressed by myeloma plasma cells is identical to N-CAM and corresponds to the 145 kDa isoform. Because of the possible biological role of adhesion molecules on myeloma cells, we compared the expression of N-CAM with the intercellular adhesion molecule 1 (ICAM-1) and the beta 1 and beta 2 integrins. By immunogold-silver staining of cytospin preparations of mononuclear cell suspensions, bone marrow plasma cells of 17 MM patients were analysed. Plasma cells expressed N-CAM (CD56) in 14 patients. ICAM-1 (CD54) in 16 patients, and beta 2 integrins (CD18) in eight patients. beta 1 integrins (CD29) were expressed in all patients. The expression of beta 2 integrins was always very weak while N-CAM, ICAM-1 and the beta 1 integrins showed a moderate to strong positivity. The plasma cells of five haematological normal individuals lacked significant N-CAM expression but were positive for ICAM-1 and both integrin subgroups. One plasma cell leukaemia patient and two out of four end-stage MM patients showed no expression of N-CAM or beta 2 integrins on their circulating plasma cells. Among 11 previously established myeloma cell lines, surface expression of ICAM-1 and the integrins was detected in most cases, while N-CAM was present in only four lines. Most cell lines showed coexpression of the fibronectin receptors (VLA-4 and VLA-5) and the laminin receptor (VLA-6). The collagen receptor (VLA-2) was not expressed. The N-CAM negative cell lines included four cell lines that were derived from plasma cell leukaemia patients. These results indicate that the expression of adhesion molecules is an intrinsic part of the biology of multiple myeloma.     

The "ex vivo" patterns of CD2/CD7, CD57/CD11c,CD38/CD11b,CD45RA/CD45RO,and CD11a/HLA-DR expression identify acute/early and chronic/late NK-cell activation states

To define a dynamic sequence of phenotypic changes related to early and late phases of NK-cell activation, we have analyzed by four-color flow cytometry the immunophenotype of normal blood NK-cells from 12 healthy individuals and compared it with those from 15 patients with acute viral infections and 15 patients with either chronic infections or tumors. Although a great interindividual variability was found, nonstimulated CD56(+) NK-cells, present in normal blood samples, usually were CD2(-/+lo), CD7(+hi), HLA-DR(-), CD11b(+), CD38(+), CD11a(+hi), CD45RA(+hi), and CD45RO(-), the expression of CD11c and CD57 being heterogeneous and variable. Recently activated NK-cells, herein corresponding to NK-cells from patients with acute viral infections, displayed a pattern of expression of CD2/CD7 similar to that referred to above, but they typically showed higher levels of CD11a, CD38, and HLA-DR, as well as downregulation of CD11b and CD45RA, accompanied in some cases by coexpression of CD45RO; in addition, these NK-cells were CD11c(+) and CD57(-/+lo). Late-activated NK-cells, represented by NK-cells present in patients with chronic infections and tumors, converted into a CD2(+hi)/CD7(-/+lo) immunophenotype and expressed heterogeneously low levels of CD38 and CD11b; moreover, they were CD57(+) and CD11c(-/+). At this stage, most NK-cells had already reverted into their original CD45RA(+)/CD45RO(-)/HLA-DR(-) phenotype. In summary, we show that the patterns of expression of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR may help us to define the immunophenotypic profiles associated with early and late NK-cell activation phases in 'in vivo' models.     

非小细胞肺癌患者CD3+、CD4+、CD8+、CD44+表达的临床研究

目的研究非小细胞肺癌患者外周血淋巴细胞中CD3+、CD4+、CD8+、CD4+4的表达水平。方法取65例非小细胞肺癌患者及22例健康正常人外周静脉血,应用流式细胞仪检验非小细胞肺癌患者(实验组)与健康人外周血淋巴细胞中(对照组)CD3+、CD4+、CD8+、CD4+4的表达水平。结果实验组与对照组CD3+、CD3+CD4+、CD3+CD8+、CD4+4在淋巴细胞中的比例存在显著性差异(P<0.05),其中,实验组占总淋巴细胞的比例分别为48.07±10.33%、30.93±6.68%、17.13±3.37%、55.45±4.35%;对照组CD3+、CD3+CD4+、CD3+CD8+、CD4+4占总淋巴细胞的比例分别为58.83±10.88%、34.89±6.45%、23.91±4.42%、62.85±7.56%;但鳞癌与腺癌组CD4+4的表达无显著性差异(P>0.05),其中,鳞癌组CD4+4所占比例为61.32±8.06%,腺癌组为64.43±6.76%。结论非小细胞肺癌患者外周血T细胞亚群及CD4+4的表达水平较正常组均低,其表达水平与组织类型无关。     

高脂血症患者血清补体C3、C4、备解素和白细胞补体调节蛋白CD35、CD55、CD59的表达

目的:探讨高脂血症患者血清补体和外周血白细胞补体调节蛋白的表达及其在动脉粥样硬化中的意义。方法:选高脂血症患者46例(高脂血症组),年龄、性别、体重指数匹配的正常人20例作为正常对照组,用免疫散射比浊法测血清补体C3、C4、备解素(Pf);用流式细胞术测定外周血中性粒细胞、淋巴细胞和单核细胞CD35、CD55、CD59的表达,观察上述指标在高脂血症组中的变化,分析影响因素。结果:高脂血症组血清C3、C4、Pf水平较正常对照组明显升高(P<0.01);补体C3、C4水平与血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)明显正相关(P<0.01),Pf与TC、LDLC正相关(P<0.01)。CD35阳性淋巴细胞、单核细胞、粒细胞百分率较正常对照组升高(P<0.05),CD35阳性淋巴细胞、粒细胞百分率与TG呈正相关(P<0.05～0.01);CD55阳性淋巴细胞平均荧光强度较正常对照组下降(P<0.05);CD59阳性淋巴细胞、单核细胞百分率较正常对照组下降(P<0.05)。结论:高脂血症患者血清补体C3、C4、Pf升高,白细胞补体调节蛋白表达改变,补体及补体调节蛋白的改变与血脂水平相关,表明脂代谢紊乱可影响补体及补体调节蛋白的表达,提示补体及补体调节蛋白可能参与动脉粥样硬化的病理生理过程。     

Molecular associations between the T-lymphocyte antigen receptor complex and the surface antigens CD2, CD4, or CD8 and CD5.

The T-cell antigen receptor (TCR) complex is the key structure involved in signal transduction in T cells. To analyze associations between the TCR complex and other molecules, immunoprecipitations were carried out, followed by phosphorylation of molecules in vitro by tyrosine kinases associated with the precipitated molecules. This provided a sensitive assay for molecular complexes, and associations were demonstrated between the TCR complex and the surface antigens CD2, CD4, or CD8 and CD5 in normal rat T cells. The complexes were readily seen in immunoprecipitates from Brij 96 but not Nonidet P-40 detergent extracts. The multimolecular complexes are associated with the internal tyrosine kinases p56lck and p59fyn. The presence of p56lck associated with CD4 or CD8 was also examined in early thymocytes, natural killer cells, and macrophages. The kinase was present in all cases except that of normal macrophages.     

Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA-associated vasculitides

OBJECTIVE: To assess circulating immunoregulatory cytokines and soluble surface markers of T and B cell activation in the plasma of patients with Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangiitis (MPA) during active and inactive disease, in order to establish their value in discriminating between disease entities and as markers of disease activity. METHODS: Plasma levels of IL-4, IL-5, IL-10, IL-12, IL-13, IFN-gamma and soluble CD23, CD26 and CD30 were determined by enzyme-linked immunosorbent assay in patients with WG (n = 21), CSS (n = 19) and MPA (n = 14) during active disease and remission. RESULTS: Concerning cytokines, no differences were observed for IFN-gamma, IL-4, IL-5 and IL-13. Plasma levels of IL-12 were decreased in all subgroups of patients. On the contrary, IL-10 levels were significantly elevated only in patients with CSS. Levels of sCD30 were significantly increased in patients with active generalized WG and CSS, but not in those with MPA and localized WG, correlating with the disease extent and activity. sCD26 levels were markedly decreased in patients with generalized WG, CSS and MPA and increased towards remission. sCD23 levels were slightly, but not significantly increased in CSS and generalized WG. CONCLUSION: Regarding the investigated immunoregulatory cytokines (Th1/Th2 type), only the measurement of plasma levels of IL-10 discriminated CSS from WG and MPA. The reported data could indicate a similar status of T cell activation in generalized WG and CSS, and possibly a shift in peripheral immunity towards a more humoral dominated immune response. The differences observed between patients with the localized and generalized forms of WG seem to reflect the clinically known biphasic course of this disease.     

Structure and expression of the human thymocyte antigens CD1a, CD1b, and CD1c

The CD1 human antigens are a family of at least three components, CD1a, CD1b, and CD1c, that are characteristic of the cortical stage of thymocyte maturation. CD1a was originally named HTA1 or T6 and thought to be the human equivalent of mouse Tla. The genes coding for all three have now been identified by transfection into mouse cells. The transfectants express the surface antigens that can then be recognized by the corresponding cluster of monoclonal antibodies used to define the three members of CD1. The full sequence of the genomic DNA is described for all three. The intron-exon structure of CD1a is deduced by comparison with a near-full-length cDNA clone. Similar structures are proposed for the other two, largely based on sequence homology. An unusually long 5'-untranslated exon (280 bases long) is highly conserved between the three genes, suggesting an important but unknown function. CD1c has a duplicated form of this exon that is thought to be spliced out. The major homology between the three antigens is in the beta 2-microglobulin-binding domain. The general relatedness to major histocompatibility complex class I and class II molecules is significant but low, with no section of higher homology to mouse Tla.