血清NSE、CYFRA21-1、CEA和CA50联检诊断肺癌及其与肺癌病理分型的关系

目的：分析肺癌及肺部良性疾病患者血清CEA、NSE、CYFRA21-1的水平变化及其与肺癌病理组织类型的关系,探讨其在肺癌诊断中的价值。方法：检测89例初治肺癌和37例良性肺病患者血清NSE、CYFRA21-1、CEA和CA50的水平。NSE采用免疫放射分析（IRMA）,CYFRA21-1和CA50采用放射免疫分析（RIA）,CEA采用化学发光免疫分析。结果：肺癌组各肿瘤标志物血清水平皆显著高于肺部良性疾病组（P〈0.05）;NSE＋CYFRA21-1＋CEA联检对肺癌诊断的灵敏度、特异性和准确性分别为87.6%、86.5%和87.3%,灵敏度和准确性明显大于各标志物单项检测（P〈0.05）;肺癌肿瘤标志物血清水平和灵敏度与病理类型有关,灵敏度：血清CEA以腺癌最高（73.9%）,血清NSE以小细胞肺癌（SCLC）最高（75.0%）,血清CYFRA21-1以鳞癌最高（80.6%）,血清CA50对各病理类型肺癌皆不高（20.5%～39.5%）。结论：NSE、CYFRA21-1、CEA肿瘤标志物检测有利于指导肺癌的病理分型,联检明显提高了对肺癌诊断的灵敏度。     

血清NSE、ProGRP、CEA、SCCA和CYFRA21-1联检在肺癌诊断中的意义

目的:探讨胃泌素释放肽前体(progastrin-releasing peptide,ProGRP)、神经特异性烯醇化酶(neuronspecific enolase,NSE)、癌胚抗原(carcino-embryonic antigen,CEA)、鳞状细胞癌抗原(squamous cell carcinomaantigen,SCCA)及细胞角蛋白19(CYFRA21-1)在肺癌诊断中的价值和临床意义。方法:分别采用化学发光法或电化学发光法检测14例肺部良性疾病、12例小细胞肺癌、29例非小细胞肺癌患者血清ProGRP、NSE、CEA、SCCA、CYFRA21-1含量。结果:NSE、ProGRP对SCLC诊断的敏感性分别为66.7%、83.3%,且NSE与ProGRP具有很好的相关性,CYFRA21-1对鳞癌诊断的敏感性为63.6%,CEA对腺癌诊断的敏感性为64.3%。SCLC组ProGRP、NSE水平均显著高于NSCLC组、肺良性疾病组,差异有统计学意义。NSCLC组,CYFRA21-1水平显著高于其余两组,差异有统计学意义。ProGRP、NSE联检对SCLC的检出率可达91.7%,CYFRA21-1、SCCA、CEA联检对腺癌、鳞癌的检出率分别为71.4%、72.7%。结论:ProGRP及ProGRP+NSE是SCLC诊断的较好指标,CYFRA21-1、CEA分别对鳞癌、腺癌具有一定的诊断价值。     

血清SCC、NSE、CYFRA21-1及CEA联合检测在肺癌诊断中的价值

目的探讨血清SCC、NSE、CYFRA21-1及CEA联合检测在肺癌的诊断价值。方法采用电化学发光免疫分析法测定血清SCC、NSE、CYFRA21-1及CEA水平及其组合,评价其在肺癌诊断中的价值。结果肺癌组四项指标显著高于对照组和肺良性疾病组,差异有统计学意义（P〈0.05）;不同病理类型的肺癌四项检测指标,差异有统计学意义（P〈0.05）;但四项指标联合检测敏感性明显高于任一个单项肿瘤标志物。结论单项肿瘤标志物对肿瘤的诊断价值有限。四项标志物联合检测有利于肺癌的早期诊断。     

胸腔积液中CYFRA21-1、NSE、CEA的水平与肺癌组织学分型及TNM分期的关系

目的：探讨胸腔积液中CYFRA21-1、NSE、CEA的水平对肺癌的诊断价值以及与肺癌组织学分型、TNM分期的关系。方法：采用电化学发光法和化学发光法分别检测253例肺癌,39例其他恶性肿瘤以及36例肺结核患者胸腔积液中CYFRA21-1、NSE和CEA的水平。结果：肺癌组胸腔积液中CYFRA21-1、NSE、CEA水平明显高于其他恶性肿瘤组和肺结核组（P〈0.01）;CYFRA21-1、NSE以及CEA分别在肺鳞癌、小细胞肺癌以及肺腺癌的胸腔积液中表达最高（P分别〈0.01、0.01和0.05）,并且随TNM分期增加而增高。结论：检测胸腔积液中CYFRA21-1、NSE、CEA水平对肺癌的鉴别诊断、组织学分型以及TNM分期有重要价值。     

血清和胸腔积液CEA、NSE、CYFRA21-1、SCC-Ag联检对肺癌诊断的临床意义

目的：探讨血清和胸腔积液中肿瘤标志物CEA、NSE、CYFRA21-1、SCC-Ag联检对肺癌诊断的临床意义。方法：采用放射免疫分析检测54例肺癌患者及35例肺良性病变（BLD）患者血清和胸腔积液中CEA、NSE、CYFRA21-1、SCC-Ag的水平。结果：肺癌组血清和胸腔积液中CEA、NSE、CYFRA21-1、SCC-Ag水平均明显高于肺良性病变组（P〈0.01）。胸腔积液中CEA、NSE、CYFRA21-1、SCC-Ag含量明显高于血清含量（P〈0.01）,血清和胸腔积液CEA、NSE、CYFRA21-1、SCC-Ag联检阳性率分别可达83.33%和92.59%。结论：血清和胸腔积液中CEA、NSE、CYFRA21-1、SCC-Ag联检可提高肺癌诊断的阳性率,在肺癌诊断中有重要价值。     

Logistic回归和ROC曲线综合评价CEA、NSE和CYFRA21-1对肺癌的诊断价值

目的应用Logistic回归和ROC曲线探讨血清癌胚抗原（carcinoembryonic antigen,CEA）、神经元特异性烯醇化酶（neuron-specificenolase,NSE）和细胞角蛋白19片段（cytokeratin 19 fragment,CYFRA21-1）在肺癌诊断中的应用。结论采用电化学发光免疫分析仪（E170）检测不同病理类型肺癌组、肺良性疾病组以及健康人血清CEA、NSE和CYFRA21-1的水平,通过Logistic回归建立回归模型,用ROC曲线分析三指标对肺癌诊断的意义。结果肺癌组CEA、NSE和CYFRA21-1的水平显著高于肺良性疾病和健康人组（P〈0.01）。腺癌组血清CEA水平最高,NSE在小细胞肺癌中灵敏度最高（81.6%）,取特异性90%时,CYFRA21-1对肺癌的诊断灵敏度最高（59.5%）。建立回归模型Y=1/[1＋EXP（5.830-0.249X1-0.198X2-0.643X3）],新变量Y的灵敏度、特异性和准确性率分别为80.9%,91.3%和84.6%。结论血清CEA、NSE和CYFRA21-1对肺癌的诊断具有较高的价值,综合运用Logistic回归和ROC曲线可以提高其肺癌诊断价值。     

三种血清标志物在肺癌中的应用价值

为分析血清CEA、CYFRA21-1及NSE在辅助鉴别诊断肺癌及肺部良性疾病临床应用价值,回顾了我院2009年1月至10月的287例肺部疾病患者以及60名健康体检者血清CEA、CYFRA21-1及NSE数据。肺癌分为三组即肺腺癌、肺鳞癌和小细胞肺癌。良性疾病组包括肺炎和肺结核等。对所测结果用统计软件SPSS16.0进行统计。结果表明：肺癌组的三项血清标志物水平明显高于良性疾病组和健康对照组（P〈0.01）。CEA在肺腺癌患者血清中浓度明显高于其它组（P〈0.01）。CYFRA21-1在肺鳞癌患者血清中浓度明显高于其它肺癌类型及良性和健康对照组（P〈0.01）,且对肺鳞癌有较高的灵敏度,而NSE在小细胞肺癌患者中的浓度及阳性率与其余组有显著性差异（P〈0.01）。CEA联合CYFRA21-1可以提高对肺腺癌和肺鳞癌的敏感度。CEA联合NSE可提高对小细胞肺癌的敏感度。三项联合检测对各型的肺癌都有较高敏感度。     

联检血清CEA、NSE、CYFRA21-1水平对晚期肺癌疗效和预后的意义

目的：探讨血清CEA、NSE和CYFRA21-1在晚期肺癌疗效评价及预后判断中的价值。方法：68例接受一线化疗的晚期肺癌患者,于化疗前及第2个周期后分别检测血清CEA、NSE、CYFRA21-1水平,同时行影像学检查评价客观疗效以及进行生存随访。选择80例肺部良性疾病患者作为对照组,并检测其血清CEA、NSE、CYFRA21-1水平。结果：肺癌组血清CEA、NSE和CYFRA21-1浓度及阳性率均显著高于对照组;化疗有效者三者水平明显下降,病情稳定和进展者三者水平无变化或升高;化疗前血清CEA、CYFRA21-1水平高、低组的预后差异有统计学意义（P〈0.05、P〈0.001）,NSE水平高、低组的患者预后差异无统计学意义（P〉0.05）。结论：血清CEA、NSE、CYFRA21-1联检在晚期肺癌病情监测、疗效评价及预后判断等方面具有重要的临床价值。     

ECLIA法测定血清细胞角蛋白19片段(CYFRA21-1)等肿瘤标志物及其临床应用

目的 探讨电化学发光免疫分析技术（ECLIA）测定血清细胞角蛋白19片段（CYFRA21—1）等肿瘤标志物及其临床应用。方法 应用ECLIA法对53例肺癌患者血清CYFRA21—1、NSE、CEA含量进行测定。并与41例肺部良性疾病患者和40例正常健康对照者进行对照分析。结果 肺癌患者血清CYFRA21-1、NSE、CEA水平明显高于肺部良性疾病组和正常对照组（P〈0．01）。CYFRA21—1在肺鳞癌中表达水平最高，NSE肺小细胞癌中表达水平最高，CEA在肺腺癌中表达水平最高。血清CYFRA21—1＋NSE＋CEA联合检测肺癌的的敏感性为88．7％，特异性为85．2％，阳性预测值为92．2％，阴性预测值为92．0％，准确性为86．6％。手术根治及放／化疗有效组患者术后CYFRA21—1、NSE、CEA水平明显下降（P〈0．01），而对放／化疗抵抗的患者三者水平在治疗前后变化不明显（P〉0．05）。结论 检测血清CYFRA21-1对肺癌诊断具有重要的临床参考价值，联合检测NSE、CEA可提高检测肺癌的敏感性和准确性．并为肺癌的病理类型评估、病情监视及疗效判断提供依据。     

血浆胃泌素释放肽前体，细胞角蛋白19和癌胚抗原对各型肺肿瘤的诊断价值

目的探讨胃泌素释放肽前体（ProGRP）,细胞角蛋白19（CYFRA21—1）,癌胚抗原（CEA）对各型肺癌的诊断价值。方法检测85例健康对照人群、49例肺良性疾病患者及143例各型肺癌患者血浆中的ProGRP,CYFRA21-1,CEA三个指标,并对小细胞肺癌（SCLC）患者进行ProGRP的跟踪监测。结果SCLC患者中ProGRP水平[中位数（M）179．1ng／m1）]明显高于肺腺癌（M35．3ng／m1）、鳞癌（肘33．3ng／m1）、健康对照（膨35．6ng／m1）和良性肺病（M33．3ng／m）,差异有统计学意义（P〈0．001）;ProGRP对SCLC的诊断灵敏度和特异性分别为60．6％和95．0％。SCLC治疗有效组,ProGRP降低了45．9％,SCLC疾病进展组,ProGRP升高了103．1％,差异均有统计学意义（P〈0．05）。CEA在肺腺癌转移组中水平（M10．22ng／ml）明显高于无转移组（M3．85ng／m1）和鳞癌组（M2．56ng／m1）,差异有统计学意义（P〈0．01）。结论血浆ProGRP是一个很好的SCLC诊断指标和疗效评价指标;CEA明显升高是腺癌肺外转移指标。     

华支睾吸虫膜抗原/排泄分泌抗原酸性磷酸酶的克隆、表达、生物学特征分析及组织定位

 目的:对华支睾吸虫(Clonorchis sinensis, Cs)成虫酸性磷酸酶 (acid phosphatase, AP)进行克隆、表达、生物学特征分析、组织定位及膜抗原/排泄分泌抗原鉴定。方法:对CsAP进行生物信息学、分子生物学、免疫组化及明胶酶谱分析。结果:从Cs cDNA文库中筛选出编码AP新基因,全长1 410 bp,重组并由大肠杆菌表达、纯化,得到分子量为55 kD的重组蛋白CsAP。Western blotting分析表明,CsAP既是膜抗原又是分泌排泄抗原;免疫组化显示,CsAP荧光显示于成虫的表皮层和肠支,在囊蚴也有显示,在雷蚴和尾蚴未显示荧光;ELISA分析表明CsAP识别华支睾吸虫病人和日本血吸虫病人存在吸虫间的交叉免疫反应,CsAP及粗抗原识别轻、中、重度感染程度华支睾吸虫病人的差别不明显。重组蛋白免疫大鼠后,总IgG抗体滴度于3周达较高峰,抗体效价大于1∶25 600。明胶降解实验表明：CsAP具降解胶原能力。结论: 上述结果表明,CsAP在大肠杆菌中高效表达,具有较好的免疫原性,但血清诊断价值不理想;CsAP可能既是膜抗原,又是排泄分泌抗原。     

Differential up-regulation of HLA-DM, invariant chain, and CD83 on myeloid and plasmacytoid dendritic cells from peripheral blood

Two main dendritic cell (DC) subsets have been described in peripheral blood, the myeloid subset or DC1 that is characterized by the presence of CD11c and the plasmacytoid subset or DC2 negative for this marker. The two subsets may perform different functions and have been defined as immunogenic (the myeloid subset) or tolerogenic (the plasmacytoid subset). The expression of human leukocyte antigen (HLA)-DM molecules, which act as peptide editors in the antigen presentation process, was studied in freshly isolated plasmacytoid and myeloid DCs from peripheral blood. The expression of the invariant chain (Ii), the major histocompatibility complex class II (MHC-II) : class II-associated Ii peptide (CLIP) complex, and CD83 was also investigated. The results showed that intracellular expression of HLA-DM and the Ii was significantly higher in the plasmacytoid than in the myeloid DC subset. In contrast, a higher fraction of cell expressing MHC-II : CLIP complex was found in the myeloid than in the plasmacytoid DC subpopulation. CD83 was not detected in any of these two subsets. Following culture of these cells with interleukin-3 (IL-3), tumor necrosis factor-alpha (TNFalpha) and/or heat shock protein-70 (HSP-70), the expression of intracellular HLA-DM was up-regulated in the myeloid DCs to levels similar to those found in the plasmacytoid DCs, whilst the Ii was down-regulated in the plasmacytoid subset to similar levels to those expressed in the myeloid DCs. In addition, CD83 was up-regulated in the myeloid (CD11c+) but not in the plasmacytoid (CD11c-) DCs. The expression pattern of these antigen-processing molecules could be related to the immaturity and function attributed to these DC subsets.     

Antigen Presentation by MHC Class II Molecules: Invariant Chain Function, Protein Trafficking, and the Molecular Basis of Diverse Determinant Capture

Major histocompatibility complex class II molecules are heterodimeric integral membrane proteins whose primary function is the presentation of antigenic peptides derived from proteins entering the endocytic pathway to CD4⁺ T lymphocytes. To accomplish this physiologic function, class II molecules must assemble in the secretory pathway without undergoing irreversible ligand association at that site, traffic efficiently to the endocytic pathway, and productively interact with protein ligands in these organelles before their ultimate expression on the plasma membrane. Here we review our work describing how invariant chain promotes the assembly and transport process, the complex itinerary of class II–invariant chain complexes through the endocytic pathway, the role of large protein fragments as substrates for class II binding, and the existence of a second pathway for antigen capture by mature class II molecules that complements that involving newly synthesized dimers. We integrate these observations into a coherent model for the operation of a class II-dependent antigen processing and presentation system able to capture diverse antigenic determinants present in proteins of varying structure.     

抗巨细胞病毒早晚期抗原单克隆抗体制备及在病毒培养物鉴定中的初步应用

目的 制备抗CMV早晚期抗原单克隆抗体并在病毒培养物鉴定中初步应用.方法 CMV感染MRC-5细胞24h、48h和72h后甲醛灭活的可溶性抗原免疫BALB/c小鼠,小鼠脾细胞与骨髓瘤细胞NS-1进行融合.酶免法筛查阳性杂交瘤并有限性稀释法进行克隆.免疫荧光及印迹对筛选后的克隆进行鉴定,最终获得的杂交瘤制备腹水并使用Protein G进行纯化.纯化后单抗应用于CAP室间质评标本以及临床标本CMV培养物的鉴定.结果 3只小鼠脾细胞与骨髓瘤细胞融合后初步筛查出约110株阳性克隆.剔除与其它抗原有交叉反应、抗体效价低、非全覆盖早晚期抗原的克隆最终获得抗CMV单抗杂交瘤1株,即23B5-1.免疫荧光显示23B5-1株单抗与CMV感染后3h-120h的MRC-5细胞均反应,即覆盖即刻、早期和晚期抗原.免疫印迹试验显示23B5-1株单抗与CMV抗原25KD-50KD之间的5个蛋白条带结合.23B5-1株单抗免疫球蛋白亚型为IgG1.Protein G纯化腹水后的单抗效价≥1∶12800.纯化单抗染色鉴定6份室间质评及10份临床标本CMV培养物全部符合.结论 初步应用显示制备的抗CMV早晚期抗原单克隆抗体性能良好.     

鼠抗丙型肝炎病毒ns－5区单克隆抗体的研究

用ＨＣＶ非结构区ｎｓ－５合成多肽抗原交联后免疫小鼠，成功地建立了３株抗ｎｓ－５单克隆抗体（ＭｃＡｂ），经检测这３株ＭｃＡｂ属于同一位点，与其它区域无明显交叉反应，具有高度特异性。ＭｃＡｂ的研制为检测ｎｓ－５抗原奠定了一定基础。     

IL-6、CEA、CA19-9和CA72-4对胃癌的诊断价值

探讨血清IL-6、CEA、CA19-9和CA72-4单独或联合检测对胃癌诊断的临床价值。采用电化学发光法分别检测73例胃癌患者（胃癌组）、50例良性胃病患者（良性胃病组）、52名健康者（对照组）血清中IL-6、CEA、CA19-9和CA72-4水平,分析4种指标对胃癌诊断的临床价值及其与临床病理因素之间的关系。在胃癌组,4种标志物血清浓度均显著高于良性胃病组和对照组,并且与肿瘤的组织学分型、浸润深度、淋巴结转移以及远端转移相关。4种标志物平行法联合检测可使诊断的灵敏度提高至86.3%,系列法联合检测可使特异性提高至98.1%。血清IL-6、CEA、CA19-9和CA72-4水平对胃癌的诊断和临床分期具有重要意义,联合检测可提高诊断灵敏度和特异性。     

Identification,isolation, and physicochemical properties of neurospecific α2-globulin

V. P. Serbskii All-Union Research Institute of General and Forensic Psychiatry, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 1, pp. 39–42, January, 1991.     

Expression of CEA, Tag-72, and Lewis-Y antigen in primary and metastatic lesions of ovarian carcinoma

Ovarian carcinoma has a high mortality rate, because most ovarian carcinomas are detected at a late stage. Traditional therapies, such as surgical debulking and chemotherapy, have not been successful in improving the long-term survival of these patients. Alternative therapies targeting various biomarkers, such as carcinoembryonic antigen (CEA), Tag-72, and Lewis-Y antigen, have been developed to treat patients with advanced ovarian cancers. To ensure that therapies targeting these biomarkers are effective, it is imperative to determine whether there is any differential expression of these targeted biomarkers between primary and metastatic ovarian carcinomas. In the present study, primary and metastatic lesions from 68 and 58 patients, respectively, including primary and matched metastatic lesions from 31 patients, were evaluated for cytoplasmic and membranous expression of CEA (clone Col-1), Tag-72 (clone CC-49), and Lewis-Y antigen (clone BR-96) by immunohistochemistry. No significant differences were observed with cytoplasmic and membranous expression of Tag-72 (CC-49) and Lewis-Y antigen (BR-96) in the primary and metastatic, matched and unmatched lesions (Wilcoxon signed-rank test). Although there was no statistically significant difference in the scores of CEA (Col-1) between primary and metastatic lesions, 5 of 11 (45%) cases with positive staining with CEA (Col-1) demonstrated discordant results between primary and metastatic lesions. There was a moderate positive correlation of the cytoplasmic and membranous expression of Tag-72 (CC-49), as well as cytoplasmic expression of BR-96 between primary and metastatic ovarian carcinomas. There was a weak negative correlation between the membranous expression of CEA (Col-1) and that of Lewis-Y antigen (BR-96); however, the difference was not statistically significant. No correlation was observed with other combinations of biomarkers. Our findings suggest that samples from either primary or metastatic ovarian carcinomas can be used for the evaluation of the expression of Tag-72 (CC-49) and Lewis-Y antigen (BR-96) to identify targets for novel therapies in patients with disseminated ovarian carcinomas. CEA (Col-1), due to its low expression and variation in phenotypic expression between primary and metastatic lesions, should be evaluated carefully in metastatic lesions before targeting the CEA antigen with CEA (Col-1)-like antibodies.     

恶性肿瘤病人血清细胞角蛋白19片段等四联检结果分析

目的 :探讨恶性肿瘤病人血清细胞角蛋白 19片段 (CYFRA2 1- 1)、恶性肿瘤特异性生长因子(TSGF)、糖链抗原 (CA5 0 )、癌胚抗原 (CEA)的含量改变在恶性肿瘤诊断中的意义。方法 :连续收集一年中各类恶性肿瘤病人共 6 89例 ,同时设立非恶性肿瘤组和健康体检组作为对照 ;采用放免或生化等方法检测血清CYFRA2 1- 1、TSGF、CA5 0、CEA的含量 ,然后分析比较。结果 :恶性肿瘤组的血清CYFRA2 1- 1、TSGF、CA5 0、CEA含量分别为 6 6 4± 14 2 5 (ng/ml)、79 73± 15 94 (U/ml)、12 37± 30 5 8(U/ml)、14 2 0± 38 76 (ng/ml) ,均明显高于非恶性肿瘤组和健康体检组 ,差异有高度显著性 (p <0 0 1)。CYFRA2 1- 1、TSGF、CA5 0、CEA测定的敏感度分别为 35 3%、6 9 1%、8 0 %、12 0 % ,测定的特异度分别为 91 7%、83 3%、98 6 %、93 1% ;四项联检的阳性率明显提高。对于各类恶性肿瘤 ,TSGF含量均高于对照组 ,差异有高度显著性 (p <0 0 1) ,检测的阳性率一般 >6 0 % ;大部分恶性肿瘤的血清CYFRA2 1- 1水平亦升高 ,与对照组相比差异有显著性 (p <0 0 5 )。结论 :通过恶性肿瘤 6 89例分析 ,联合检测血清CYFRA2 1- 1、TSGF、CA5 0、CEA含量能提高恶性肿瘤诊断的阳性率 ;CYFRA2 1- 1和TSGF测定在肿瘤临床诊断和     

血清CA19—9、CA125、CA242、CEA联检诊断胰腺癌的临床价值

目的：评价血清糖类抗原19—9（CA19—9），糖类抗原125（CA125），糖类抗原242（CA242）及癌胚抗原（CEA）四项指标联检对胰腺癌的诊断价值。方法：四项标志物均应用全自动化学免疫分析检测。结果：胰腺癌患者血清CA19—9、CA125、CA242、CEA水平明显高于胰腺良性病组，差异均有显著性（P〈0．01）。四项指标联检诊断胰腺癌的敏感性为91．7％，特异性92．1％。结论：血清CA19—9、CA125、CA242及CEA单项检测在胰腺癌诊断中特异性均偏低，且四项联检可提高胰腺癌的敏感性及特异性，临床诊断价值更大。