Frequency and clinical implications of monoclonal antibody detection of tumor-associated antigens in serum of patients with lung cancer

We previously showed that a panel of monoclonal antibodies (MAb) (5E8, 5C7, and 1F10) that detect serum tumor-associated antigens (TAA) could distinguish patients with lung cancer from those without to a highly significant degree. However, among patients with lung cancer, the frequency and clinical importance of serum TAA expression were not established. Therefore, we analyzed the serum and initial clinical characteristics of 52 Philadelphia VA patients with newly diagnosed lung cancer seen over a 13-month period. A modified semiquantitative ELISA was employed to determine MAb reactivity. Our cohort was characterized by a mean age of 65 +/- 9 year (SD) and mean Karnovsky score of 74 +/- 10; marked weight loss was present in 28 subjects, and 39 presented with either Stage III or IV disease. The panel detected TAAs in 38 of 52 cases (sensitivity 73%; 95% Cl, 60-83%), including 13 of 22 squamous cell, 9 of 12 adenocarcinoma, 10 of 11 undifferentiated, and 6 of 7 small cell carcinomas. No significant differences were found between the reactive and nonreactive patients in terms of age, stage at presentation, histologic subtype, performance status, or weight loss. However, 1F10 and 5C7 were each associated with a greater risk of early death by Cox proportional hazard analysis (p = 0.017 and 0.006, respectively) even when other prognostic variables are accounted for. We conclude that specific serum TAA can be detected in the majority of lung cancer patients with all major histologic subtypes in a cohort with advanced tumors and poor prognostic indices.(ABSTRACT TRUNCATED AT 250 WORDS)     

单克隆抗体介导的肝癌靶向治疗

单克隆抗体（单抗）介导的肝细胞癌（HCC）靶向治疗近来发展迅速。多种单抗如抗HCC、抗血管内皮生长因子（VEGF）、抗表皮生长因子受体（EGFR）和抗肿瘤坏死因子α（TNF-α）等抗体所介导的HCC放射免疫治疗,抗体介导酶前体药物治疗,免疫脂质体治疗,HCC发生相关信号途径干预等,已在HCC治疗研究中取得了明显进展,部分已经进入临床研究。本文就近年来单抗介导的HCC靶向治疗进行综述。     

The detection of quantitative serum p53 protein in lung cancer

p53 protein, which accumulates intracellularly in over half of all human tumors, has been reported to be variably present in the sera of patients with various malignancies. In this study, it was aimed to detect p53 protein in the sera of lung cancer patients, and to verify its value as a marker of p53 alterations in lung cancer. A pantropic quantitative ELISA technique was used to detect serum p53 protein of 94 newly diagnosed patients with lung cancer. Serum samples were collected on admission before any treatment. There was no detectable serum p53 protein in the control group including 34 healthy volunteers. Serum p53 protein was present in only 3 (3.2%) of 94 patients. In nonsmall cell lung cancer (NSCLC) group, serum p53 protein had been detected in 2 (2.8%) of 72 patients, and it was detectable in 1 (4.5%) of 22 patients in SCLC group. Serum levels of p53 protein ranged from 1 U/mL to 31.25 U/mL in positive samples. Patients who had p53 protein in their serum samples, were at late stage and had poor prognosis. In conclusion; prognostic value of detectable serum p53 protein levels could not be define, because of the small number of p53 positive patients. The use of quantitative serum p53 protein analysis with ELISA is of very limited value as a marker in evaluating p53 changes in lung cancer patients, despite the fact that is an easy technique to perform.     

Monoclonal antibody-mediated enhancement of growth hormone activity in vivo

This work demonstrates that complexing hGH with monoclonal antibody EBl (MAB-EBl) can produce a striking potentiation of the somatogenic actions of hGH in vivo in Snell dwarf mice. In short-term experiments significant increases in cartilage metabolism and body weight were noted; these responses were dose-dependent for both MAB-EBl and hGH concentration. Increased growth was also observed in long-term experiments. In marmosets where MAB-EBl cross-reacts with endogenous GH, MAB-EBl alone enhanced the actions of endogenous GH. A new perspective may be necessary to incorporate these results into the current concept of antibody action.     

血清肿瘤标记物检测在肺癌诊断中的应用价值

目的探讨血清肿瘤标记物癌胚抗原（CEA）、神经元特异烯醇化酶（NSE）、细胞角蛋白19片段（CYFRA21-1）、组织多肽抗原（TPA）、癌抗原153（CA153）以及癌抗原242（CA242）在肺癌临床诊断中的应用价值。方法采用电化学发光法（ECLIA）分别对肺癌组、肺部良性疾病组患者及健康人的血清肿瘤标记物浓度进行检测分析。结果肺癌组患者6种血清肿瘤标记物浓度均显著高于肺部良性疾病组和健康对照组患者（P〈0．05）;其中在不同病理类型肺癌患者血清中的CEA、NSE及CYFRA21-1水平总体比较,差异有统计学意义（P〈0．05）,各血清肿瘤标记物单独检测灵敏度较低,进行联合检测灵敏度则可大大提高。结论血清肿瘤标记物的联合检测可显著提高肺癌检测的特异性、敏感性。同时可为肺癌临床分期及病理类型的鉴别提供重要参考。     

肿瘤标志物联合检测在肺癌早期诊断中的应用

目的：探讨外周血肿瘤标志物癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）、细胞角质蛋白19片段（CYFRA21-1）、糖链抗原125（CA125）、糖链抗原19-9（CA19-9）、糖链抗原15-3（CA15-3）联合检测在肺癌早期诊断中的应用价值。方法：采用Elecsys2010电化学发光仪检测80例肺癌患者,55例肺部良性疾病患者,40例健康人血清中CEA、NSE、CYFRA21-1、CA125、CA19-9、CA153等肿瘤标志物的水平。结果：肺癌患者中CEA、NSE、CYFRA21-1、CA125、CA19-9、CA153等6种标志物显著高于正常对照组及肺部良性疾病组,差异有统计学意义（P〈0.01）。6项标志物不同组合对不同分期肺癌检出的敏感性均高于单项标志物。其中第6种CY-FRA21-1＋CA125＋NSE和第7种CYFRA21-1＋CA125＋NSE＋CEA组合的敏感性较其他组合均高,特别是对早期患者检出率明显提高,但第7种方式成本较高且6、7两种方式检出率差异无统计学意义。结论：CYFRA21-1＋CA125＋NSE联合检测能提高肺癌的早期诊断率。     

血清Pro-GRP和NSE检测在小细胞肺癌中的意义

目的探讨血清胃泌素释放肽前体（Pro-GRP）检测在小细胞肺癌诊断中的价值,并与神经元特异性烯醇酶（NSE）进行比较。方法采用电化学发光法检测68例小细胞肺癌,120例非小细胞肺癌,30例肺部良性疾病和150例健康人血清Pro-GRP和NSE的含量。结果小细胞肺癌患者血清Pro-GRP和NSE水平显著高于非小细胞肺癌、良性疾病组和健康人（P〈0.05）。Pro-GRP和NSE对在小细胞肺癌诊断的敏感性分别为80.9%和83.8%,特异性分别为90.2%和58.2%;Pro-GRP和NSE浓度在化疗后均下降;在复发/进展的患者中,Pro-GRP的阳性率显著高于NSE（85%vs50%,P〈0.05）。结论血清Pro-GRP检测对小细胞肺癌诊断敏感性和特异性强;还可以反映疗效,监测复发。     

Monoclonal antibodies against EGFR in non-small cell lung cancer

Blockade of the epidermal growth factor receptor (EGFR) by monoclonal antibodies is a strategy to improve outcome in patients with non-small cell lung cancer. Cetuximab, a chimeric anti-EGFR monoclonal antibody, has been studied in combination with different chemotherapy protocols in both phase II and phase III trials in patients with advanced NSCLC. In the phase III FLEX trial, cetuximab added to cisplatin/vinorelbine resulted in an absolute overall survival benefit of 1.2 months compared to the same chemotherapy alone in patients with advanced EGFR-expressing NSCLC. In the second phase III trial, cetuximab added to carboplatin plus paclitaxed failed to improve progression-free survival but suggested a survival benefit similar to that seen in the FLEX trial. However, the benefit in survival reached statistical significance only in the FLEX trial. A meta-analysis that included patients from four randomized trials confirmed the efficacy of cetuximab when added to chemotherapy. Thus addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced NSCLC. Matuzumab and panitumumab have also been evaluated in phase II trials. Necitumumab is currently evaluated in combination with chemotherapy in two randomized phase III trials.     

神经元特异性烯醇化酶检测在小细胞肺癌预后中的价值

目的 评价化疗前后血清神经元特异性烯醇化酶（NSE）检测在非手术治疗小细胞肺癌（SCLC）患者中的预后价值。方法 收集1997年6月－2000年12月上海市肺科医院内科收治144例SCLC患者,均于化疗前（D1）和化疗后21d(D21)检测NSE水平,进行预后单因素和多因素分析。结果 144例患者中D1－NSE阳性98例,占68.1%;阴性46例,占31.9%。D210－NSE阳性57例,占39.6%;阴性87例,占60.4%;单因素分析D1－NSE和D21－NSE均是提示预后有价值的指标;但COX多因素分析时,只有D21－NSE是提示预后的独立指标。结论 D21－NSE是提示小细胞肺癌预后的独立指标,在临床上有较重要的应用价值。     

Early detection of lung cancer

The overall 5-year survival of lung cancer is only 10% in Europe and 15% in the United States, and progress in curative treatments during the last 20 years has been modest. Late diagnosis of extensive disease is the main reason of failure. Early detection with low-dose spiral computed tomography (CT) is one of the most promising development of clinical research, and continuous improvements in technology can make this instrument more effective than mammography in breast cancer detection. In order to prove the benefit of early detection by reduction of lung cancer mortality, we need to enroll large numbers of high-risk individuals in multicentric prospective randomized trials combining primary prevention by smoking cessation with diagnostic intervention with low-dose spiral CT, optimal management of cancer and minimum damage for healthy individuals. Molecular biology research within early detection trials, combining genomic and proteomic analysis of blood and sputum, may improve the differential diagnosis, define the individual risk of cancer incidence and failure, and help target therapies on the basis of biologic profile.     

联合检测血清肿瘤标志物对肺癌的诊断价值

目的探讨肿瘤标志物神经特异性烯醇化酶(NSE)、细胞角蛋白(CYFRA21-1)、癌胚抗原(CEA)、糖类抗原125(CA125)对肺癌的诊断价值。方法用电化学发光法分别检测70例肺癌、50例肺良性疾病患者及50名正常人的血清NSE、CYFRA21-1、CEA、CA125的含量并进行分析。结果三组4种肿瘤标志物检测比较差异有统计学意义(P均<0.01);肺癌组患者NSE、CYFRA21-1、CEA、CA125水平高于良性肺疾病患者和健康人(P均<0.01)。血清中NSE在小细胞肺癌中水平高于其他类型肺癌(P均<0.01),CY-FRA21-1在鳞癌中水平高于其他类型肺癌(P均<0.05);单项NSE灵敏度最高为87.14%,联合检测以任一阳性时,灵敏度最高达98.57%,优于单项检测;NSE、CYFRA21-1、CEA灵敏度分别在小细胞肺癌、鳞癌、腺癌中最高。结论肿瘤标志物NSE、CYFRA21-1、CEA、CA125对肺癌的辅助诊断、鉴别诊断和分型有非常重要的临床意义。     

血清肿瘤分子标记物联合动态检测对肺癌诊疗的临床应用

目的探讨血清肿瘤分子标记物癌胚抗原(CEA)、鳞状上皮癌抗原(Scc-Ag)、胃泌素释放肽前体31-98(Pro-GRP31-98)联合动态监测在肺癌早期诊断和监控治疗中的临床应用价值。 方法选取156例肺癌患者(肺癌组)、50例肺部良性病变患者(良性对照组)及50例健康体检者(正常对照组)为研究对象,采用电化学发光法及酶联免疫法检测三组人群血清CEA、Scc-Ag、Pro-GRP31-98水平,分析血清肿瘤分子标记物CEA、Scc-Ag、Pro-GRP31-98在肺癌早期诊断、临床分期、病理组织学分型、监控复发转移及判断预后的相关性。 结果(1)肺癌组患者血清CEA、Scc-Ag、Pro-GRP31-98水平明显高于良性病变组及正常对照组,差异有统计学意义(P<0.01)。良性病变组与正常对照组血清CEA、Scc-Ag、Pro-GRP31-98水平比较无统计学差异(P>0.05);(2)肺癌患者血清CEA、Scc-Ag、Pro-GRP31-98水平与性别、年龄、肿瘤发生部位无明显相关性(均P>0.05);与肿瘤大小、临床分期、组织学类型、复发转移及治疗后明显相关,肺癌高分期(Ⅲ、Ⅳ期)组、转移组、复发组、治疗前与低分期(Ⅰ、Ⅱ期)组、无转移组、无复发组、治疗后血清CEA、Scc-Ag、Pro-GRP31-98水平相比较有明显增高(均P<0.01);(3)CEA、Scc-Ag、Pro-GRP31-98分别在肺腺癌、鳞癌、小细胞癌血清阳性检出率较高,与其它两种病理组织学类型比较差异有统计学意义(P<0.01);(4)CEA、Scc-Ag、Pro-GRP31-98诊断肺癌的敏感性分别为51.28%、48.72%、50.50%,特异性分别为96.00%、98.00%、94.00%,准确性分别为62.14%、60.68%、62.62%;两两组合CEA＋ Scc-Ag、CEA＋Pro-GRP31-98、Scc-Ag＋Pro-GRP31-98诊断肺癌的敏感性分别为61.54%、64.74%、62.18%,特异性分别为92.00%、90.00%、92.00%,准确性分别为69.27%、71.22%、69.76%;三项肿瘤分子标记物联合检测虽特异性有所降低(86.00%),但敏感性、准确性明显提高,分别为96.46%、93.17%,与各单项及部分组合检测比较差异有统计学意义(均P<0.01)。 结论肿瘤分子标记物CEA、Scc-Ag、Pro-GRP31-98与肺癌的发生发展密切相关,联合检测可以做到相互补充、相互印证,有利于早期诊断、临床早期干预;动态检测可以监控肿瘤复发、转移,指导治疗及评估预后。     

非小细胞肺癌患者血清中miR-22检测的临床意义

目的探讨非小细胞肺癌(NSCLC)患者血清中miR-22的表达水平及其临床意义。方法采用实时荧光定量PCR法检测健康人对照和NSCLC患者血清中miR-22的表达量,并构建受试者操作特征(ROC)曲线计算miR-22的敏感性和特异性。结果 NSCLC患者化疗前血清中miR-22的表达水平显著高于正常人组(P0.05);miR-22在Ⅲ期+Ⅳ期中的表达水平显著高于Ⅰ期+Ⅱ期(P0.05);miR-22对Ⅲ期+Ⅳ期NSCLC检测的敏感性明显高于Ⅰ期+Ⅱ期(P0.01);miR-22在鳞癌和腺癌中的表达量无统计学差异(P0.05);与化疗前比较,晚期NSCLC患者miR-22的表达量明显降低(P0.05)。结论血清miR-22可能与NSCLC的形成和发展有关,NSCLC患者miR-22的检测对于NSCLC的辅助诊断和化疗疗效评价有一定的临床应用价值。     

肺癌患者肺功能检测

目的探讨肺癌患者的肺功能改变。方法通过对126例肺癌患者的肺功能进行检测,并与84例健康人进行对照。结果肺癌患者的肺通气及弥散功能指标明显低于正常,与对照组相比有显著性差异。结论肺癌患者存在肺功能的减退,肺癌患者手术前或化疗前应常规检测肺功能,以便确定最佳治疗方案。     

Carbohydrate antigens in pleural effusion from patients with lung cancer

Sialosylated Lewisa (S-Lea) is an active antigen determinant of CA19-9 which is well known as a tumor maker. Sialosylated Lewisx (S-Lex) is a positional isomer of S-Lea. The positive percent of S-Lex and CA19-9 in pleural effusion from the patients with primary lung cancer was 49.1% and 40.0%, respectively. However, most S-Lea positive effusions showed a positive level of S-Lex. Therefore, S-Lex is considered to be more useful as a tumor marker than CA19-9. The studies on gel chromatography of the effusion obtained from a patients showed high levels of both antigens using sephacryl S-1000 revealed that the molecular weights of S-Lex and CA19-9 were more than 2 X 10(6) and the elution profile of S-Lex coincided with that of CA19-9 fractionated effusions using the monoclonal antibodies to the antigens showed the same pattern of elution profiles of these carbohydrates. From these results, we concluded that the carriers of S-Lex and CA19-9 in pleural effusion from lung cancer might be the same molecules with a high molecular weight more than 2 X 10(6).     

Monoclonal antibodies against Opisthorchis viverrini antigens

Summary Monoclonal antibodies (MoAb) were produced against somatic antigens of adult human liver fluke Opisthorchis viverrini. Earlier studies attached diagnostic potential to an 89–90 kD antigen present in both somatic extracts and in vitro culture supernatants as well as to the abundant 16–17 kD tegumental protein doublet. Mice made excellent immune responses to low dose somatic extract adsorbed onto nitrocellulose or to the 80–95 kD region of SDS gel Western blots. The antigen specificities of hybridomas reactive with somatic antigen by ELISA were determined by radioimmunoprecipitation or immunoblotting. Six MoAb reacted with the desired 16 kD tegumental protein. A 90 kD somatic protein was identified by 9 clones. By indirect immunofluorescence, monoclonals reactive with the 16 kD polypeptide identified the outermost surface of the tegument. The 90 kD antigen was associated with all major muscle systems, most strikingly the crossed subtegumental layers, oral and ventral suckers, pharynx and a thin layer surrounding caeca. The biochemical identity of this muscle-associated antigen is unknown, but it is clearly distinct from the previously identified species-specific 89 kD exoantigen. The 16 kD tegumental protein shares epitopes with a number of related flukes. However, 2 MoAb which react with this protein show no crossreaction.     

肿瘤标志物在肺癌诊断、病理分型和临床分期中的价值

目的研究血清肿瘤相关抗原125（CA125）、199（CA199）、癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）、细胞角蛋白19片段（CYFRA21—1）在肺癌诊断、病理分型和临床分期中的价值。方法选取郑州大学第一附属医院2011年6月至2012年9月入院患者309例血清标本,采用电化学免疫荧光发光法检测血清肿瘤标志物的浓度。结果肺癌患者5种血清肿瘤标志物水平均高于肺部良性病变组。单项检测,腺癌、鳞癌、小细胞肺癌（SCCL）敏感度最高者分别为CYFRA21—1和CEA、CYFRA21—1、NSE。联合检测CA125＋CEA＋NSE＋CYFRA21—1敏感度达87．26％。CA125、CEA、CYFRA21—1在肺癌不同TNM分期的表达阳性率及表达高度不同。结论血清5种肿瘤标志物诊断肺癌价值较高,其中CYFRA21—1诊断价值最大,联合检测可以提高肺癌诊断敏感度。CA125、CEA、CYFRA21—1在肺癌临床分期中价值较大。     

Monoclonal immunoscintigraphy for detection of metastasis and recurrence of colorectal cancer

AIM:To assess the clinical role of monoclonal immunoscintigraphy for the detection of metastasis and recurrence of colorectal cancer.METHODS:Monoclonal immunoscintigraphy was performed in patients operated on for colorectal adenocar-cinoma suspected of local recurrence and metastatic disease.The results were compared with conventional diagnostics.RESULTS:Immunoscintigraphic investigation was done in 53 patients.Tumor recurrence occurred in 38 patients,and was confirmed by other diagnostic modalities in 35.I...