257,397 research outputs found
Long-Range Chromosomal Mapping of the Carcinoembryonic Antigen (CEA) Gene Family Cluster
No full textA long-range physical map of the carcinoembryonic antigen (CEA) gene family cluster, which is located on the long arm of chromosome 19, has been constructed. This was achieved by hybridization analysis of large DNA fragments separated by pulse-field gel electrophoresis and of DNA from human/rodent somatic cell hybrids, as well as the assembly of ordered sets of cosmids for this gene region into contigs. The different approaches yielded very similar results and indicate that the entire gene family is contained within a region located at position 19q13.1–q13.2 between the CYP2A and the D19S15/D19S8 markers. The physical linkage of nine genes belonging to the CEA subgroup and their location with respect to the pregnancy-specific glycoprotein (PSG) subgroup genes have been determined, and the latter are located closer to the telomere. From large groups of ordered cosmid clones, the identity of all known CEA subgroup genes has been confirmed either by hybridization using gene-specific probes or by DNA sequencing. These studies have identified a new member of the CEA subgroup (CGM8), which probably represents a pseudogene due to the existence of two stop codons, one in the leader and one in the N-terminal domain exons. The gene order and orientation, which were determined by hybridization with probes from the 5′ and 3′ regions of the genes, are as follows: cen/3′-CGM7-5′/3′-CGM2-5′/5′-CEA-3′/5′-NCA-3′/5′- CGM1-3′/3′-BGP-5′/3′-CGM9-5′/3′-CGM6-5′/5′-CGM8-3′/PSGcluster/qter
A Polymerase-chain-reaction Assay for the Specific Identification of Transcripts Encoded by Individual Carcinoembryonic Antigen (CEA)-gene-family Members
No full textCarcinoembryonic antigen (CEA) is a tumor marker that belongs to a family of closely related molecules with variable expression patterns. We have developed sets of oligonucleotide primers for the specific amplification of transcripts from individual CEA-family members using the reverse transcriptase/ polymerase chain reaction (RT/PCR). Specific primer sets were designed for CEA, non-specific cross-reacting antigen (NCA), biliary glycoprotein (BGP), carcinoembryonic antigen gene-family members 1, 6 and 7 (CGMI, CGM6 and CGM7), and one set for all pregnancy-specific glycoprotein (PSG) transcripts. Primers were first tested for their specificity against individual cDNA clones and product-hybridization with internal, transcript-specific oligonucleotides. Total RNA from 12 brain and 63 gynecological tumors were then tested for expression of CEA-related transcripts. None were found in tumors located in the brain, including various mesenchymal and neuro-epithelial tumors. CEA and NCA transcripts were, however, present in an adenocarcinoma located in the nasal sinuses. In ovarian mucinous adenocarcinomas, we always found co-expression of CEA and NCA transcripts, and occasionally BGP mRNA. CEA-related transcripts were also found in some serous, endometrioid and clear-cell ovarian carcinomas. CEA, NCA and BGP transcripts were present in endometrial carcinomas of the uterus and cervical carcinomas, whereas uterine leiomyomas were completely negative. No transcripts were found from CGM 1, CGM6, CGM7 or from PSG genes in any of the tumors tested. The PCR data were compared with immunohistochemical investigations of ovarian tumors at the protein level using CEA (26/3/13)-, NCA-50/90 (9A6FR) and NCA-95 (80H3)-specific monoclonal antibodies
Preoperative CYFRA 21-1 and CEA as Prognostic Factors in Patients with Stage I Non-Small Cell Lung Cancer
No full textObjective: To validate the prognostic value of preoperative levels of CYFRA 21-1, CEA and the corresponding tumor marker index (TMI) in patients with stage I non-small cell lung cancer (NSCLC). Methods: Two hundred forty stage I NSCLC patients (80 in pT1 and 160 in pT2; 100 squamous cell carcinomas, 91 adenocarcinomas, 32 large-cell carcinomas, 17 with other histologies; 171 males and 69 females) who had complete resection (R0) between 1986 and 2004 were included in the analysis. CYFRA 21-1 and CEA were measured using the Elecsys system (Roche) and AxSym-System (Abbott), respectively. Univariate analysis was performed using the Kaplan-Meier method to identify potential associations between survival and age, gender, CYFRA 21-1, CEA and TMI. Results: Overall 3- and 5-year survival rates were 74 and 64%, respectively. Male gender (p = 0.0009) and age 1 70 years (p = 0.0041) were associated with a worse prognosis; there were no differences between pT1 and pT2 nor between histological subtypes. Three- year survival was 72% for CYFRA 21-1 levels > 3.3 ng/ml versus 75% for levels 6.7 ng/ ml versus 75% for CEA 70 years were associated with a worse outcome, but elevated levels of CEA and CYFRA 21-1, and TMI risk were not. Copyright (C) 2008 S. Karger AG, Basel
Carcinoembryonic Antigen Gene Family
No full textThe carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin supergene family and can be divided into two main subgroups based on sequence comparisons. In humans it is clustered on the long arm of chromosome 19 and consists of approximately 20 genes. The CEA subgroup genes code for CEA and its classical crossreacting antigens, which are mainly membrane-bound, whereas the other subgroup genes encode the pregnancy-specific glycoproteins (PSG), which are secreted. Splice variants of individual genes and differential post-translational modifications of the resulting proteins, e.g., by glycosylation, indicate a high complexity in the number of putative CEA-related molecules. So far, only a limited number of CEA-related antigens in humans have been unequivocally assigned to a specific gene. Rodent CEA-related genes reveal a high sequence divergence and, in part, a completely different domain organization than the human CEA gene family, making it difficult to determine individual gene counterparts. However, rodent CEA-related genes can be assigned to human subgroups based on similarity of expression patterns, which is characteristic for the subgroups. Various functions have been determined for members of the CEA subgroup in vitro, including cell adhesion, bacterial binding, an accessory role for collagen binding or ecto-ATPases activity. Based on all that is known so far on its biology, the clinical outlook for the CEA family has been reassessed
CEA, CYFRA 21-1, NSE, and ProGRP in the diagnosis of lung cancer: a multivariate approach
No full textWe retrospectively studied the single and combined diagnostic value of carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA 21-1), neuron specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP), which were routinely analysed in patients with lung tumours of unknown origin at the time of admission to hospital. Inclusion criteria were the determination of CEA (AxSYM/Abbott), CYFRA 21-1 (ElecSys/Roche) and NSE (Kryptor/Brahms). We examined 1747 patients, where 1325 suffered from lung cancer (LC; small cell lung cancer, SCLC: n=194; non-small cell lung cancer, NSCLC: n = 1015; others: n = 116), 318 from benign lung diseases and 104 from lung metastases due to another primary malignancy. As ProGRP (ELISA ALSI/IBL) became available only recently, there are less data points of this marker. In total, 99.8% of LC patients released at least one of the four biomarkers (defined as values exceeding the median of healthy controls), and for the discrimination between benign disease (BID) and malignant lung disease each marker reached 100% tumour specificity at high levels (CEA: 20 ng/mL; CYFRA 21-1: 40 ng/mL; NSE: 45 ng/mL; ProGRP: 250 pg/mL). At a specificity of > 99%, ProGRP reached the highest diagnostic efficacy for SCLC with 57% true positive results, CEA had the highest capacity (17%) to detect malignant lung tumours in general and adenocarcinomas of the lung with 29%. CYFRA 21-1 was dominant for squamous cell carcinomas (12%). Combining the four markers leads with the prerequisite of high specificity (> 99%) to 50% true positives for malignant lung tumours, 44% for NSCLC, 36% for squamous cell carcinomas, 53% for adenocarcinomas, and 78% for SCLC, respectively. In cases of lung tumours of unknown origin, the combined use of CEA, CYFRA 21-1, NSE and ProGRP is useful for the differentiation between benign and primary or secondary malignant disease and suggests the assignment to histological subtypes
The Carcinoembryonic Antigen Gene Family
No full textThe molecular cloning of carcinoembryonic antigen (CEA) and several cross-reacting antigens reveals a basic domain structure for the whole family, which shows structural similarities to the immunoglobulin superfamily. The CEA family consists of approximately 10 genes which are localized in two clusters on chromosome 19. So far, mRNA species for five of these genes have been identified which show tissue variability in their transcriptional activity. Expression of some of these genes in heterologous systems has been achieved, allowing the localization of some epitopes. The characterization of a CEA gene family in the rat and a comparison with its human counterpart has been utilized in the development of an evolutionary model
Characterization of Murine Carcinoembryonic Antigen Gene Family Members
No full textThe carcinoembryonic antigen (CEA) is a human tumor marker whose gene belongs to a family with more than 20 members. This gene family codes for a group of proteins with in vitro cell adhesion properties and for a group of abundantly expressed pregnancy-specific glycoproteins (PSG) with unknown functions. As a basis for in vivo functional studies, we have started to analyze the murine CEA gene family and have identified five new members (Cea-2 to Cea-6). cDNA clones were isolated for Cea-2, Cea-3, and Cea-6. The deduced amino acid sequences of Cea-2 and Cea-6 indicate three IgV-like (N), followed by one IgC-like (A) domain (N1-N2-N3-A). We have also partially characterized the Cea-2 gene and two additional ones, Cea-4 and Cea-5. Cea-2 and Cea-4 are separated by only 16 kb, suggesting a close linkage of murine CEA-related genes, as found for the human CEA gene family. Cea-5 was located to the proximal region of mouse Chromosome (Chr) 7, which is syntenic to part of human Chr 19, containing the human CEA gene family cluster. Cea-2, Cea-3, and a Cea-4-like gene are differentially transcribed in the placenta during pregnancy, but not in other organs tested. This expression pattern strongly suggests that they represent counterparts of the human PSG subgroup members, despite the presence of multiple IgV-like domains, a feature not found for human PSGs. The more distantly related Cea-5 seems to be ubiquitously expressed. The putative promoter region of Cea-2 lacks typical TATA-or CAAT-boxes, but contains other conserved motifs that could play a role in the initiation of transcription
Mice Transgenic for the Human Carcinoembryonic Antigen Gene Maintain Its Spatiotemporal Expression Pattern
No full textThe tumor marker carcinoembryonic antigen (CEA) is predominantly expressed in epithelial cells along the gastrointestinal tract and in a variety of adenocarcinomas. As a basis for investigating its in vivo regulation and for establishing an animal model for tumor immunotherapy, transgenic mice were generated with a 33-kilobase cosmid clone insert containing the complete human CEA gene and flanking sequences. CEA was found in the tongue, esophagus, stomach, small intestine, cecum, colon, and trachea and at low levels in the lung, testis, and uterus of adult mice of independent transgenic strains. CEA was first detected at day 10.5 of embryonic development (embryonic day 10.5) in primary trophoblast giant cells and was found in the developing gut, urethra, trachea, lung, and nucleus pulposus of the vertebral column from embryonic day 14.5 onwards. From embryonic day 16.5 CEA was also visible in the nasal mucosa and tongue. Because this spatiotemporal expression pattern correlates well with that known for humans, it follows that the transferred genomic region contains all of the regulatory elements required for the correct expression of CEA. Furthermore, although mice apparently lack an endogenous CEA gene, the entire repertoire of transcription factors necessary for correct expression of the CEA transgene is conserved between mice and humans. After tumor induction, these immunocompetent mice will serve as a model for optimizing various forms of immunotherapy, using CEA as a target antigen
New CEA handbooks for criticality safety assessment demonstrations
No full textInternational audienceCriticality safety assessment demonstrations may be supported by basic 1D calculations performed by neutron transport deterministic codes (standard calculations). In the case of the French CRISTAL V2.0 package, critical and permissible values for simple geometries like spheres, infinite height cylinders or infinite section slabs are determined with the APOLLO2 cell code and its discrete ordinates SN module (standard route). The most pertinent values (e.g. values at optimal moderation) are aggregated in documents called handbooks.45 years after the first and up to now unique French handbook, nicknamed “Maubert” from his author, this paper presents new handbooks, prepared by CEA. They compile latest CRISTAL V2.0 standard route results from more than 250 standard calculation reports. Two handbooks have currently been produced: one with critical values, the other with permissible values with a neutron effective multiplication factor, keff, criterion equal to 0.95. They both present results for uranium, plutonium, mixed media, and pure actinides fissile material with various physico-chemical, densities and isotopic compositions. The influence of various reflecting and moderating materials has been investigated. Moreover, criticality parameters for several fissile media containing homogeneous neutron absorbers (boron, gadolinium, cadmium) have been determined.These handbooks are available to everyone on request.Additionally, this paper discusses some singular and unexpected results observed while producing those handbooks
Cloning of a Carcinoembryonic Antigen Gene Family Member Expressed in Leukocytes of Chronic Myeloid Leukemia Patients and Bone Marrow
No full textThe carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin superfamily and can be subdivided into the CEA and pregnancy-specific glycoprotein subgroups. The basic structure of the encoded proteins consists of, in addition to a leader, one IgV-like and 2, 3, or 6 IgC-like domains. These domains are followed by varying COOH-terminal regions responsible for secretion, transmembrane anchoring, or insertion into the membrane by a glycosyl phosphatidylinositol tail. Here we report on the characterization of CGM6, a new member of the CEA gene subgroup, by complementary DNA cloning. The deduced coding region comprises 349 amino acids and consists of a leader, one IgV-like, two IgC-like domains, and a hydrophobic region, which is replaced by a glycosyl phosphatidylinositol moiety in the mature protein. CGM6 transcripts were only found thus far in leukocytes of chronic myeloid leukemia patients, in normal bone marrow, and in marginal amounts in normal granulocytes. The CGM6 gene product might, therefore, represent a myeloid marker. Analyses of CGM6 protein-expressing HeLa transfectants with monoclonal antibodies strongly indicate that the CGM6 gene codes for the CEA family member NCA-95
- …
