单克隆抗体老年人大肠癌初筛效果观察

老年人大肠癌,5年生存率低,早期诊断大肠癌,是降低死亡率的关键。国外将年龄大于50岁人群作为重点普查对象[1]。虽然结肠镜普查是最特异的方法,因工作量大,技术要求高而少用[2]。以隐血试验初筛确定高危人群,然后纤维结肠镜确诊,但隐血法受多种因素影响敏感性不高[3]。为探索单克隆抗体在老年人大肠癌普查效果我们,应用以新型抗人胃肠癌单抗CMU15系列[4]制备的大便金标免疫试剂对2,356例年龄≥50岁的邮电职工进行大便初筛,同时与大便隐血试验作对照,现总结如下。材料与方法受检人群:2,356例均为广东地区邮电职工,年龄≥50,男女比2.8∶1。…     

外周血基因表达谱检测在大肠癌筛查中的应用研究进展

对大肠癌的筛查有助于早期诊断及早期治疗,提高生存率.目前临床常规诊断方法包括粪便隐血检测、粪便DNA突变检测、结肠镜检查和乙状结肠镜检查.其中,粪便隐血检测联合结肠镜检查方案被广泛应用于自然人群的筛查,尽管经济有效,但这一联合方案存在一定的局限性,难以满足大规模人群筛查的要求.外周血基因表达谱检测是近年来迅速发展起来的大肠癌检测技术,具有微创、灵敏度高、人群依从性好等优点.文章介绍了外周血mRNA作为大肠癌生物标志物的研究进展,并对该技术在大肠癌筛查中的进一步应用进行了展望.     

上海市宝山地区社区居民大肠癌筛查结果分析

目的:分析上海市宝山地区社区居民大肠癌筛查结果,探究国内大肠癌筛查模式在大肠癌诊断中的临床意义.方法:选取2017年06月至2019年06月上海市宝山地区按照社区大肠癌筛查流程完成筛查且评定为初筛阳性,并至我院完成全结肠镜诊断性检查且获取检查结果的人群作为研究对象,共769例.根据肠镜结果,分成病变组和正常组,分析两组...     

大肠癌无创早期诊断的核酸检测技术研究进展

摘 要：大肠癌无创早期诊断有利于提高患者的生存率和顺应性,对粪便和血液中人源核酸进行检测是大肠癌无创早期诊断的重要途径,具有高特异性、高灵敏度和适用于大规模人群筛查等优点。核酸检测技术包括DNA检测技术和RNA检测技术,全文就这两类核酸检测技术应用于大肠癌早期无创诊断的研究进展进行概述。     

上海市社区居民大肠癌筛查便隐血检测效果分析

背景与目的：上海市为符合条件的居民提供免费的大肠癌筛查服务,通过对上海市居民大肠癌筛查中两次便隐血检测和后续诊断检查结果的分析,评价筛查中两次便隐血检测的效果,为基于人群的疾病筛查项目提供科学依据。方法：筛查的目标人群为50~74岁的上海居民,使用两次免疫法便隐血检测和危险度评估为初筛,初筛阳性者进行肠镜检查。结果：筛查期间,共有809 528人完成了两次便隐血检测,便隐血检测阳性者共有104 953人,其中第一次阳性的人数为47 421人,阳性率为5.9%,第二次阳性的人数为36 462人,阳性率为4.5%,两次阳性的人数为21 070人,阳性率为2.6%。便隐血检测阳性的筛查对象中,有49 339人接受了肠镜检查,肠镜检查顺应性为47.0%。两次阳性的筛查对象的肠镜参与率明显高于单次阳性的筛查对象（P<0.001）。在所有筛查出的大肠癌和癌前期病变中,仅进行一次便隐血检测可以诊断出大肠癌1 200例,占79.5%;发现癌前期病变3 777例,占68.1%。进行第二次便隐血检测可以多诊断出大肠癌310例,占20.5%;发现癌前期病变1 767例,占31.9%。结论：相比于单次便隐血检测, 进行两次便隐血检测的初筛可以更有效地检测出阳性对象,两次便隐血检测可提高后续肠镜检查的参与率,所检出的大肠癌和癌前期病变数量也均有所提高且增量成本较低。因此建议在以人群为基础的大肠癌筛查中采用两次或更多次数的便隐血检测,以提高筛查效率。     

浙江省永康市大肠癌机会性筛查结果分析

[目的]了解机会性筛查在永康市大肠癌防治中的可行性.[方法]采用问卷调查及粪便隐血试验(FOBT)对40～74岁人群进行初筛,确定高危人群后,进行结直肠镜精筛,分析筛查对象的依从性、大肠的病变情况和大肠癌的早诊早治情况.[结果] 36 679人完成了初筛,其中FOBT的依从率为51.10％;评估高危人群5941人,进行肠镜检查5431人,检出各种大肠病变患者1006例,其中大肠癌患者163例,早期大肠癌患者54例,大肠癌的早诊率为59.48％,各种大肠病变的治疗率为98.51％.[结论]机会性筛查适合于永康市大肠癌的筛查,可检出更多大肠癌,特别是早期大肠癌及癌前病变.     

MC5抗原和CEA在大肠良,恶性病变表达的对比研究

为了探讨大肠息肉与大肠癌之间的病因学关系,研究抗人大肠癌单克隆抗体MC_5对大肠癌早期诊断的价值,我们应用MC_5抗大肠癌及抗CEA两种单克隆抗体,通过抗生物素—生物素—酶复合物法(ABC法),对147例大肠良、恶性病变及大肠正常粘膜进行MC_5抗原和CEA表达对比研究,现报告如下:     

中国人遗传性大肠癌综合征的特征及诊疗规范

大肠癌在我国的发病率和死亡率均呈逐年上升趋势,其中5%~6%为遗传性大肠癌。遗传性大肠癌综合征是指一系列可引起遗传性大肠癌的疾病,患者患大肠癌的风险显著高于普通人群,早期筛查及干预可降低患者患癌风险。总结了中国人遗传性大肠癌综合征(如Lynch综合征、家族性腺瘤性息肉病和Peutz-Jeghers综合征等)的临床及遗传学特征,并概述了国内外遗传性大肠癌综合征的诊疗、监测规范,以期加深人们对这些疾病的认识,帮助医务人员早期、准确诊断,及时采取干预及筛查措施。     

大肠癌患者手术前后血清TNFα及SIL—2R的动态观察

目的：探索大肠癌患者手术前后血清ＴＮＦα及ＳＩＬ－２Ｒ的变化规律。方法：采用ＥＬＩＳＡ双抗夹心法，检测１９例大肠癌患者在手术前后血清中ＴＮＦα及ＳＩＬ－２Ｒ的变化。结果：大肠癌患者血清中ＴＮＦα及ＳＬ－２Ｒ水平显著高于正常值，大肠癌患者术皇７天ＴＮＦα及ＳＩＬ－２Ｒ水平明显低于术前。结论：大肠癌患者术后２１天或更长时间测定ＴＮＦα及ＳＩＬ－２Ｒ水平，对该病的诊断及治疗效果判断有重要临床价值。     

沈阳市苏家屯地区大肠癌筛查结果分析

[目的]通过大肠癌早诊早治项目,分析沈阳市苏家屯地区居民大肠癌发病情况。[方法]对苏家屯地区40~74岁人群采用问卷调查和粪便潜血实验免疫金标法（FIT）相结合筛出高危人群,对高危人群进行全大肠镜检查。[结果]目标人群40 157人中接受初筛人数为16 893人,顺应率为42.07%。初筛出高危人群3139人,占筛查人数18.58%。进行肠镜检查1655人,顺应率为52.72%。检出进展期腺瘤、大肠癌及类癌共83例。早诊率为95.18%,治疗率为100%。苏家屯地区居民大肠癌检出率为37.35/10万。[结论]苏家屯地区大肠癌检出率略高于我国农村地区平均水平。大肠癌筛查方案适用于城郊地区开展,可提高大肠癌的早诊率,对提高治愈率及延长生存期有重要意义。     

Decay accelerating factor and colorectal cancer

Objective: To review the significance of decay accelerating factor (DAF) in the colorectal cancer, we searched the data from PubMed and selected the related articles for review. It was found that DAF were expressed in the adenomas and adenocarcinoma of colorcctal tissues. The release of DAF in the stool of the patients was also detectable. It increased more significantly in the stool of patients with colorectal cancer than other gastrointestinal cancer. Its detection by ELISA method may render a good test for the noninvasive diagnosis of colorectal cancer. It can be concluded that DAF is expressed extensively in colorectal cancer. And the detection of DAF released in the stool of colorectal cancer patients may be a good noninvasive method for the diagnosis of colorectal cancer.     

Detection of patients with cancer by monoclonal antibody directed to lactoneotetraosylceramide (paragloboside)

A hybridoma producing monoclonal antibody (H11) directed to lactoneotetraosylceramide (paragloboside) has been established from spleen cells of a mouse immunized with paragloboside. The monoclonal antibody H11 (immunoglobulin M type) was selected from five clones showing different reactivities with paragloboside. The monoclonal antibody was highly specific to paragloboside and lacked reactivity with other glycolipids including glucosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, gangliotriaosylceramide, gangliotetraosylceramide, and GalNAc beta 1-4[NeuAc alpha 2-3]Gal beta 1-4Glc beta 1-1Cer. However, the monoclonal antibody (H11) was found to bind to lactosamine-containing glycolipids at their terminals, such as i- and I-type glycolipids as well as paragloboside. A two-step sandwich radioimmunoassay method for paragloboside antigen in serum was established by using the monoclonal antibody. The mean paragloboside antigen concentration in the sera from 20 normal individuals was 25.3 ng/ml. If the cutoff value was set at 80.9 ng/ml [25.3 + 2 x 27.8 (SD)], only 1 of 20 healthy controls had an elevated paragloboside value in the serum, whereas sera from 9 of 12 (75.0%) hepatoma, 4 of 10 (40%) pancreatic cancer, 16 of 40 (40.0%) stomach cancer, and 6 of 10 (60%) lung cancer patients had elevated paragloboside values. Sera from 3 of 8 hepatitis patients and 7 of 10 liver cirrhosis patients were estimated to be positive but sera from 16 patients with benign disease had paragloboside levels lower than the cutoff value. A larger amount of the antigen was found in liver metastases from colorectal carcinoma compared to the normal counterpart. The antigen was also detected in the medium of various human cancer cells and meconium. However, the antigen in the sera, medium, meconium, and cancer tissue seemed to be associated with glycoprotein or lipoprotein, because most of the antigen activity was eluted in the void volume fraction on high-performance liquid chromatography with a gel filtration column.     

Detection of serum anti-P53 antibodies from patients with colorectal cancer in China using a combination of P53- and phage-ELISA: correlation to clinical parameters

Background: Colorectal cancer is one of the most common malignant tumors in China. The aims of this research were to increase the sensitivity of anti-p53 antibody detection in the sera of patients with colorectal cancer and to assist in their diagnosis. Methods: Sixty-seven non-selected Chinese with colorectal cancer were involved in this study. Anti-p53 antibodies in serum were detected by ELISA using recombinant human wild-type p53 protein and hybrid phage as the coating antigen. Correlations between the anti-p53 antibodies and clinicopathological parameters were also analyzed. Results: The detection efficiency of anti-p53 antibodies in the patients with colorectal cancer was increased (46.3%, 31/67) through the combination of the two ELISA methods compared with each method alone. The titer of serum anti-p53 antibodies was not associated with clinicopathological parameters, but there was a significant correlation between their presence, the CEA level, and the stage of the patient’s colorectal cancer. Conclusions: These results demonstrate that combination of the two ELISA methods increased the detection rate of anti-p53 antibodies in patients with colorectal cancer. This research may provide a useful method to complement conventional clinical diagnosis.     

Adenoma-derived antibody, Adnab-9 recognizes a membrane-bound glycoprotein in colonic tissue and effluent material from patients with colorectal neoplasia.

The binding in pre-colonoscopic effluent of Adnab-9, a monoclonal antibody raised against colonic adenomas, was evaluated for specificity in the diagnosis of colorectal cancer. A heterogeneous group of 58 patients was evaluated by ELISA. Effluent samples and tissue extracts were subjected to Western blotting or ELISA to confirm specificity. Immunohistochemistry was performed on the cancer tissue sections. The proportion of positive effluent binding was higher in the cancer when compared to the normal group (P = 0.036). A dominant 87 M(r) band was found in adenoma extracts and some effluent samples. Adnab-9 binding in effluent samples predominated in membrane-bound fractions. Immunohistochemistry showed no specific staining in the cancer cells. The antigen recognised is a glycoprotein shown by effects of N-glycanase digestion and not cross-reactive with carcinoembryonic antigen. Non-gastro-intestinal tissue extracts did not bind Adnab-9. The major 87 M(r) adenoma-derived antigen may be found in effluent material, particularly in the membrane-bound fraction.     

Immunoscintigraphy of colorectal cancer using a monoclonal antibody 77-1

The monoclonal antibody (mAb) 77-1 recognizes epithelial membrane antigen (EMA) expressed by the majority of colorectal cancers. Following administration of indium-111 labelled 77-1, gamma camera imaging was carried out on 16 patients with known or suspected colorectal cancer prior to surgery or endoscopic laser therapy. Fourteen of the patients were found to have cancer, with one patient having two primary lesions. Two patients suspected of tumour recurrence were not found to have a lesion at laparotomy. Imaging before operation or laser therapy detected 10 out of 15 lesions (67%). Tumours which produced positive images were found to express the target antigen on immunocytochemical staining of the excised tumours. A mean tumour to normal colon ratio of 1.63 +/- S.D. 0.46 and a mean tumour to blood ratio of 3.60 +/- 1.48 were found at day 6 after antibody administration. A high uptake of radiolabel by the liver prevented the detection of hepatic metastases, present in three patients. Of the two patients with suspected recurrence a false positive scan was found in one owing to the presence of inflammatory tissue. Indium-111 labelled 77-1 may have a role in the imaging or targeting of colorectal cancer.     

抗人肝癌血管内皮功能性单抗的筛选与鉴定

目的:筛选、鉴定抗人肝癌血管内皮功能性单抗,为治疗肝癌提供靶向治疗剂,并为分离获得肝癌相关的分子靶标打下基础。方法:采用活细胞荧光、MTT细胞增殖实验、成管实验和动物体内治疗实验,筛选鉴定抑制肝癌内皮细胞的功能性单抗。结果:从能与肝癌内皮细胞膜反应的119株克隆中,筛选出16株单抗显著地抑制肝癌内皮增殖其抑制率达21%~46%,46株能显著抑制肝癌内皮细胞的成管,3株单抗1F9、12B5和1B11能显著抑制肝癌移植瘤的生长抑制率分别为50.8%、48.7%和47.0%。选择1株体内抑瘤效果最好的1B11单抗,通过抗体抗原亲和层析法进行纯化,并对纯化的单抗的相关抗原蛋白进行免疫组织化学实验鉴定,结果显示1B11抗原在肝癌血管组织较高的表达而在正常肝血管组织极少表达。蛋白质印迹法显示其抗原相对分子质量约46×103。结论:采用大容量功能性抗体库技术成功获得了多株具有抑制肝癌内皮恶性生物学行为的功能性单抗,体内外抑制肺癌的生长,具有成为肺癌靶向治疗剂的潜力。其中1株可能是一个靶向治疗肝癌的新靶位。     

Applications of novel monoclonal antibodies specific for synuclein-gamma in evaluating its levels in sera and cancer tissues from colorectal cancer patients

Overexpressions of synuclein-gamma (SNCG) in different cancers display stage-specific patterns. At present, appropriate anti-SNCG monoclonal antibodies (mAbs) with high specificity and affinity are unavailable for different immunoassays in clinical applications. In this study, we generated 10 mAbs against endogenous SNCG and evaluated SNCG levels in several colorectal cancer cell lines, serum samples and tumor tissues from colorectal cancer (CRC) patients. Elevated SNCG levels in cancer cell lines evaluated by a novel sandwich ELISA were consistent with data obtained from Western blot. Secreted SNCG protein levels in sera from CRC patients could be detected by the sandwich ELISA and were further confirmed by Western blot analysis following SNCG enrichment. Immunohistochemical results showed that SNCG was highly expressed in tumor cells of CRC patients, but was undetectable in the adjacent normal epithelium. Taken together, these novel anti-SNCG mAbs specifically recognized endogenous SNCG and were suitable for measuring SNCG levels in cell lysates, human serum samples, and tumor tissues. Elevated serum SNCG and overexpressed SNCG in tumor tissue from CRC patients suggest SNCG is a potential biomarker for CRC.     

Microsatellite analysis of fecal DNA for colorectal cancer detection

BACKGROUND AND OBJECTIVES: The advent of noninvasive methods of testing for colorectal cancer that have a high level of specificity and sensitivity is eagerly awaited. METHODS: Thirty patients with sporadic colorectal cancer and 11 patients with hereditary nonpolyposis colon cancer (HNPCC) enrolled in this study. We analyzed the loss of heterozygosity (LOH) in matched genomic DNA extracted from blood and surgical specimens (tumor and tumor-free colonic mucosa), and the corresponding oral rinse and stool specimens using seven microsatellite loci (APC, p53, DCC, hMLH1, D9S162, D9S171, and IFNA). To reduce the normal colonocyte DNA contamination of the stool samples, we compared three different methods for fecal genomic DNA extraction. As normal controls, we analyzed the LOH using the oral rinse and stool samples from 15 individuals without cancer. RESULTS: The LOH determined from the oral rinse and the stool samples matched those determined from the blood and the neoplastic tissue. All patients with HNPCC had microsatellite alterations at hMLH-1 in tumor DNA and corresponding fecal DNA. There were significant differences in the frequency of p53-LOH and D9S171-LOH between the group with sporadic disease and those with HNSCC (P = 0.0031 and 0.0294, respectively). Two cases with D9S162-LOH were detected in individuals without cancer. For the patients with sporadic disease, using p53 and adenomatous polyposis coli (APC), the sensitivity of the fecal DNA analysis was 96.7% (95% CI, 83-100) with a specificity of 100%. CONCLUSION: We demonstrate that LOH analysis using oral rinse and stool samples may be a suitable screening tool for colorectal cancer.     

Antitumor immune response and interleukin 2 production induced in colorectal cancer patients by immunization with human monoclonal anti-idiotypic antibody

The immunogenicity of human anti-idiotypic antibody has been investigated using a human monoclonal anti-idiotypic antibody (105AD7) which interacts with the binding site of 791T/36, a mouse monoclonal antibody against gp72 antigen. This antigen is frequently expressed in gastrointestinal cancer, therefore, six patients with advanced colorectal cancer have been immunized with 105AD7 as an aluminum hydroxide gel precipitate in a phase I clinical study. Cryopreserved blood mononuclear cells were tested for in vitro proliferative responses by [3H]thymidine incorporation; plasma samples were tested by enzyme-linked immunosorbent assay for anti-anti-idiotypic and antitumor antibodies, and for interleukin 2. Proliferative responses to gp72 positive tumor cells were seen in four of five patients tested; parallel in vitro responses to 105AD7 anti-idiotypic antibody were seen in most of these patients. Interleukin 2 was detected in the plasma of four of six patients after 105AD7 immunization, with peak levels up to 7 units/ml. No toxicity related to anti-idiotype immunization and no antitumor or anti-anti-idiotype antibodies were seen. This study shows that human monoclonal anti-idiotype 105AD7 is immunogenic in cancer patients, inducing cellular antitumor responses and interleukin 2 production. This suggests that human monoclonal anti-idiotype antibodies may have considerable potential for immunotherapy of human cancer.     

Localisation of gastrointestinal cancer with a 131 I labelled monoclonal antibody to CEA

The localisation of tumour deposits by a 131 I labelled monoclonal antibody to carcinoembryonic antigen (CEA) has been evaluated in 24 patients with primary gastric, oesophageal and colorectal cancer and in 26 patients with clinically suspected recurrent gastric and colorectal cancer. Seventeen of 20 primary sites and 6/15 associated secondary sites were correctly identified by external scanning. Measurement of radiolabelled antibody in the resected specimens demonstrated a 2.6-3.3 fold increase in comparison with the surrounding normal tissue (P less than 0.01). The antibody scans were compared with computerised tomography (CT) in the detection of recurrent disease. The respective sensitivities and specificities for the two investigations were 61% and 33% for antibody scanning and 64% and 100% for CT. Assessment of the distribution of labelled antibody demonstrated rapid clearance with less than 2% detectable in serum samples at 24 h. The implications of these findings together with the mechanisms of excretion are discussed.