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【转载】癌胚抗原——carcinoembryonic antigen

热度 1已有 1845 次阅读 2011-1-12 13:28 |关键词:百度百科 blank

 
肿瘤细胞对癌胚胎抗原有强阳性细胞浆染色
癌胚抗原:正常胚胎组织所产生的成分,出生后逐渐消失,或仅存极微量。当细胞癌变时,此类抗原表达可明显增多。
     大肠癌组织可产生一种糖蛋白,作为抗原引起患者的免疫反应。此种抗原称为癌胚抗原(carcino-embryonic antigen CEA),可广泛存在于内胚叶起源的消化系统癌,也存在于正常胚胎的消化管组织中,在正常人血清中也可有微量存在。 癌胚抗原是一个广谱性肿瘤标志物,它能向人们反映出多种肿瘤的存在,对大肠癌、乳腺癌和肺癌的疗效判断、病情发展、监测和预后估计是一个较好的肿瘤标志物,但其特异性不强,灵敏度不高,对肿瘤早期诊断作用不明显。
 
基本概述
  [项目名称]癌胚抗原
  为消化道肿瘤的辅助诊断指标。
  [英文缩写]CEA
  [参考值]≤5ng/ml
编辑本段临床意义
  CEA最初发现于结肠癌和胎儿肠组织中,故名癌胚抗原。CEA升高常见于大肠癌胰腺癌胃癌、小细胞肺癌、乳腺癌、甲状腺髓样癌等。但吸烟、妊娠期和心血管疾病、糖尿病、非特异性结肠炎等疾病,15%~53%的病人血清CEA也会升高,所以CEA不是恶性肿瘤的特异性标志,在诊断上只有辅助价值。此外,血清CEA水平与大肠癌的分期有明确关系,越晚期的病变,CEA浓度越高。
  97%的健康成人血清CEA浓度在2.5ng/mI以下。
  

原发性小肠癌CEA分布

原发性结肠癌患者CEA增高占45-80%。除原发性结肠癌以外,腺胰癌、胆管癌、胃癌。食道癌、腺癌、肺癌、乳腺癌和泌尿系统的肿瘤阳性率也很高,一般在50-70%。
  良性肿瘤、炎症和退行性疾病,如结肠息肉、溃疡性结肠炎、胰腺炎和酒精性肝硬变病人CEA也有部分升高,但远远低于恶性肿瘤,一般小于20μg/L,CEA超过20 ng/ml时往往提示有消化道肿瘤。所以测定CEA可以作为良性与恶性肿瘤的鉴别诊断依据。
编辑本段要求
  空腹抽取静脉血2ml,避免溶血、污染。如不能及时送检,应分离血清后置—20℃冷冻保存。
编辑本段胃癌癌胚抗原(CEA)
  癌胚抗原(CEA)是一种酸性蛋白。癌旁正常粘膜CEA含量很少或为阴性。胃癌的CEA阳性率85.58%。其中粘液腺癌及印戒细胞癌(粘液细胞癌)为100%。电镜下见CEA同时分布于癌细胞膜,及癌细胞内胞质内的蛋白合成及转运的细胞器(如核膜、内质网、高尔基器及其分泌小泡)中,提示癌细胞合成CEA增加,因此进入腺腔的CEA也增加,由于CEA位于围绕细胞膜的糖包膜易于释入周围体液中,故体液及胃液中CEA浓度高于血清。癌细胞质内CEA含量较多的原因与癌细胞CEA合成增加及CEA排出 受阻有关。当癌细胞变性坏死时,细胞内膜结构受损破裂,CEA可出现在胞质的基质内。免疫电镜观察,见粘液细胞癌CEA分布在整个细胞膜和胞浆的膜结构中,CEA抗原决定基为糖蛋白,而肿瘤细胞的浸润和转移均与细胞膜糖蛋白的糖基化改变有关。另外粘液细胞癌还能分泌释放大量蛋白水解酶,破坏 癌细胞钙桥,溶解癌巢周围软组织。因此胃印戒细胞癌侵袭力强,转移率高。
 
Carcinoembryonic antigen
From Wikipedia, the free encyclopedia  http://en.wikipedia.org/wiki/Carcinoembryonic_antigen
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Carcinoembryonic antigen (CEA) is a glycoprotein involved in cell adhesion. It is normally produced during fetal development, but the production of CEA stops before birth. Therefore, it is not usually present in the blood of healthy adults, although levels are raised in heavy smokers. CEA is a glycosyl phosphatidyl inositol (GPI)-cell surface anchored glycoprotein whose specialized sialofucosylated glycoforms serve as functional colon carcinoma L-selectin and E-selectin ligands, which may be critical to the metastatic dissemination of colon carcinoma cells.[1][2][3]

// [edit] History

CEA was first identified in 1965 by Phil Gold and Samuel O. Freedman in human colon cancer tissue extracts.[4]

[edit] Uses

It was found that serum from individuals with colorectal carcinoma,[5] gastric carcinoma, pancreatic carcinoma, lung carcinoma and breast carcinoma, as well as individuals with medullary thyroid carcinoma, had higher levels of CEA than healthy individuals. Regions of high CEA levels in the body can be detected with the monoclonal antibody arcitumomab.

CEA measurement is mainly used as a tumor marker to identify recurrences after surgical resection, or localize cancer spread though dosage of biological fluids. The CEA blood test is not reliable for diagnosing cancer or as a screening test for early detection of cancer. Most types of cancer do not produce a high CEA. Elevated CEA levels should return to normal after successful surgical resection, or within 6 weeks of starting treatment if cancer treatment is successful.

CEA levels may also be raised in some non-neoplastic conditions like ulcerative colitis, pancreatitis, cirrhosis, COPD, Crohn's disease as well as in smokers.[6]

[edit] Genetics

CEA and related genes make up the CEA family belonging to the immunoglobulin superfamily. In humans, the carcinoembryonic antigen family consists of 29 genes, 18 of which are normally expressed.[7]

The following is a list of human genes which encode carcinoembryonic antigen-related cell adhesion proteins:

CEACAM1, CEACAM3, CEACAM4, CEACAM5, CEACAM6, CEACAM7, CEACAM8, CEACAM16, CEACAM18, CEACAM19, CEACAM20, CEACAM21

[edit] References
  1. ^ Thomas SN, Zhu F, Schnaar RL, Alves CS, Konstantopoulos K (Jun 2008). "Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E- and L-selectin in shear flow". J Biol Chem 283 (23): 15647–55. doi:10.1074/jbc.M800543200. PMID 18375392. 
  2. ^ Konstantopoulos K, Thomas SN (2009). "Cancer cells in transit: the vascular interactions of tumor cells". Annu Rev Biomed Eng 11: 177–202. doi:10.1146/annurev-bioeng-061008-124949. PMID 19413512. 
  3. ^ Thomas SN, Tong Z, Stebe KJ, Konstantopoulos K (2009). "Identification, characterization and utilization of tumor cell selectin ligands in the design of colon cancer diagnostics". Biorheology 46 (3): 207–25. doi:10.3233/BIR-2009-0534. PMID 19581728. 
  4. ^ Gold P, Freedman SO (March 1965). "DEMONSTRATION OF TUMOR-SPECIFIC ANTIGENS IN HUMAN COLONIC CARCINOMATA BY IMMUNOLOGICAL TOLERANCE AND ABSORPTION TECHNIQUES.". The Journal of experimental medicine 121: 439–62. PMID 14270243. 
  5. ^ "Cancer Diagnosis - Information About Cancer - Stanford Cancer Center". http://cancer.stanford.edu/information/cancerDiagnosis/. Retrieved 2008-10-15. 
  6. ^ Quest diagnostic
  7. ^ Hammarström S (April 1999). "The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues*1". Seminars in Cancer Biology 9 (2): 67–81. doi:10.1006/scbi.1998.0119. PMID 10202129. 
[edit] External links

扩展阅读

癌胚抗原 CEA

      癌胚抗原是 1965 年 Gold 和 Freedman 首先从胎儿及结肠癌组织中发现的。CEA 是一种分子量为 22KD 的多糖蛋白复合物,45%为蛋白质。CEA 的编码基因位于 19 号染色体。一般情况下,CEA 是由胎儿胃肠道上皮组织、胰和肝细胞所合成。通常在妊娠前 6 个月内 CEA 含量增高,出生后血清中含量已很低。96%-97%非吸烟健康成年人血清中 CEA 浓度小于 2.5μg/L,大量吸烟者有 20%-40%的人 CEA>2.5μg/L,少数 CEA>5.0μg/L。

      CEA 属于非器官特异性肿瘤相关抗原,分泌 CEA 的肿瘤大多位于空腔脏器,如胃肠道、呼吸道、泌尿道等。正常情况下 CEA 经胃肠道代谢,而肿瘤状态时的 CEA 则进入血和淋巴循环,引起血清 CEA 异常增高,使上述各种肿瘤患者的血清 CEA 均有增高。在临床上,当CEA 大于 60μg/L 时,可见于结肠癌、直肠癌、胃癌和肺癌。CEA 值升高,表明有病变残存或进展。如肺癌、乳腺癌、膀胱癌和卵巢癌患者血清 CEA 量会明显升高,大多显示为肿瘤浸润,其中约 70%为转移性癌。一般来说,手术切除后 6 周,CEA 水平恢复正常,否则提示有残存肿瘤,若 CEA 浓度持续不断升高,或其数值超过正常 5-6 倍者均提示预后不良。连续随访定量检测血清 CEA 含量,对肿瘤病情判断更具有意义。

      除血液之外,其它生物液体,如胰液和胆汁内 CEA 定量可用于诊断胰腺或胆道癌;浆液性渗出液的 CEA 定量可作为细胞学检查的辅助手段;尿液 CEA 定量可作为判断膀胱癌预后的参考。血清 CEA 定量结合甲状腺降钙素测定,有助于甲状腺髓样癌的诊断和复发的估计。

     癌胚抗原(CEA)一度被认为是消化道癌肿尤其是结肠癌的特异性免疫学表现。但以后发现某些良性疾患尤其是肝病时,循环内 CEA 也常升高,故认为其特异性不强。⑴原发性肝癌时血清 CEA 常升高;各种原发癌(特别是结肠、肺和乳房)肝转移时,CEA 水平较无肝转移者为高,近年研究发现各种来源的肝转移性癌肿组织内均有大量 CEA 存在。⑵良性肝病也常有 CEA 升高,一般为 2.5~5 毫微克/毫升,罕有超过 10 毫微克/毫升者,在各种肝病中,以酒精性肝病时升高者最多,特别是伴有活动性肝细胞损害病例;胆道疾患时血清 CEA 也可升高。

     肝病时血清 CEA 升高的原理和临床意义。目前认为,正常肠粘膜和有炎症、癌肿的肠粘膜均能产生 CEA。肝损害时,肝对血循环中 CEA 的摄取和降解能力减低,血清 CEA 即升高;如病人系肠癌伴肝转移,则一方面 CEA 产生增多,另一方面被癌肿损害的肝不能摄取、降解 CEA,则血清 CEA 更加升高。因此,在某种意义上,血清 CEA 浓度反映了肝功能状态,肝病时如血清 CEA 升高,反映肝功能不良;如癌肿病人 CEA 明显升高,应疑及肝内转移可能。  
原发性小肠癌是少见的消化道肿瘤,临床表现与发生部位、生长方式等有关。

 

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发表评论 评论 (3 个评论)

回复 sunsong7 2011-1-13 15:53
老狼说过不会有事的,更多人是自己吓自己。
回复 sunsong7 2011-1-14 18:33
Am J Physiol Lung Cell Mol Physiol. 2009 Jun;296(6):L1019-30. Epub 2009 Mar 27.  http://www.ncbi.nlm.nih.gov/pubmed/19329538

Carcinoembryonic cell adhesion molecule 6 in human lung: regulated expression of a multifunctional type II cell protein.
Kolla V, Gonzales LW, Bailey NA, Wang P, Angampalli S, Godinez MH, Madesh M, Ballard PL.

Department of Pediatrics , Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Abstract
Carcinoembryonic cell adhesion molecule 6 (CEACAM6) is a glycosylated, glycosylphosphatidylinositol (GPI)-anchored protein expressed in epithelial cells of various human tissues. It binds gram-negative bacteria and is overexpressed in cancers, where it is antiapoptotic and promotes metastases. To characterize CEACAM6 expression in developing lung, we cultured human fetal lung epithelial cells and examined responses to differentiation-promoting hormones, adenovirus expressing thyroid transcription factor-1 (TTF-1), and silencing of TTF-1 with small inhibitory RNA. Glucocorticoid and cAMP had additive stimulatory effects on CEACAM6 content, and combined treatment maximally increased transcription rate, mRNA, and protein approximately 10-fold. Knockdown of TTF-1 reduced hormone induction of CEACAM6 by 80%, and expression of recombinant TTF-1 increased CEACAM6 in a dose-dependent fashion. CEACAM6 content of lung tissue increased during the third trimester and postnatally. By immunostaining, CEACAM6 was present in fetal type II cells, but not mesenchymal cells, and localized to both the plasma membrane and within surfactant-containing lamellar bodies. CEACAM6 was secreted from cultured type II cells and was present in both surfactant and supernatant fractions of infant tracheal aspirates. In functional studies, CEACAM6 reduced inhibition of surfactant surface properties by proteins in vitro and blocked apoptosis of electroporated cultured cells. We conclude that CEACAM6 in fetal lung epithelial cells is developmentally and hormonally regulated and a target protein for TTF-1. Because CEACAM6 acts as an antiapoptotic factor and stabilizes surfactant function, in addition to a putative role in innate defense against bacteria, we propose that it is a multifunctional alveolar protein.
回复 sunsong7 2011-1-14 18:33
J Pathol. 2009 Jul;218(3):380-90. http://www.ncbi.nlm.nih.gov/pubmed/19334050

Preclinical evaluation of carcinoembryonic cell adhesion molecule (CEACAM) 6 as potential therapy target for pancreatic adenocarcinoma.
Strickland LA, Ross J, Williams S, Ross S, Romero M, Spencer S, Erickson R, Sutcliffe J, Verbeke C, Polakis P, van Bruggen N, Koeppen H.

Department of Pathology, Genentech Inc., South San Francisco, CA, USA. lauras@gene.com

Abstract
Despite the availability of new targeted therapies, ductal pancreatic adenocarcinoma continues to carry a poor prognosis. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM)6 has been reported as a potential biomarker and therapy target for this malignancy. We have evaluated CEACAM6 as a potential therapy target, using an antibody-drug conjugate (ADC). Expression of CEACAM6 in pancreatic adenocarcinomas was determined using immunohistochemistry on tissue microarrays. The expression pattern in granulocytes and granulocytic precursors was measured by flow cytometry. Murine xenograft and non-human primate models served to evaluate efficacy and safety, respectively. Robust expression of CEACAM6 was found in > 90% of invasive pancreatic adenocarcinomas as well as in intraepithelial neoplastic lesions. In the granulocytic lineage, CEACAM6 was expressed at all stages of granulocytic maturation except for the early lineage-committed precursor cell. The anti-CEACAM6 ADC showed efficacy against established CEACAM6-expressing tumours. In non-human primates, antigen-dependent toxicity of the ADC consisted of dose-dependent and reversible depletion of granulocytes and their precursors. This was associated with preferential and rapid localization of the antibody in bone marrow, as determined by sequential in vivo PET imaging of the radiolabelled anti-CEACAM6. Localization of the radiolabelled tracer could be attenuated by predosing with unlabelled antibody confirming specific accumulation in this compartment. Based on the expression pattern in normal and malignant pancreatic tissues, efficacy against established tumours and limited and reversible bone marrow toxicity, we propose that CEACAM6 should be considered for an ADC-based therapy approach against pancreatic adenocarcinomas and possibly other CEACAM6-positive neoplasms.

2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
PMID: 19334050 [PubMed - indexed for MEDLINE]

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