Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Within the hematopoietic lineage, the monoclonal antibody (MoAb) CD66 reacts with cells of the granulocyte lineage, but not with the majority of progenitor cells from human bone marrow. Our previous studies have shown that CD66 binds specifically to at least three carcinoembryonic antigen (CEA) superfamily members, ie, CEA itself, nonspecific cross-reacting antigen (NCA), and CGM1, but not to CGM6 (NCA-95). In this report, we show that CD66 will also identify the biliary glycoproteins (BGP). A full-length cDNA for the BGPc molecule (a cytoplasmic splice variant of BGPa) was isolated by expression cloning using the CD66 MoAbs. This protein has an identical extracellular and transmembrane sequence to BGPa with one N-terminal IgV like domain, three IgC-like extracellular domains (A1, B1, and A2), plus a transmembrane domain, but the cytoplasmic domain is spliced by 53 nucleotides. Reverse transcriptase-polymerase chain reaction experiments show that this splice variant can be detected in colonic carcinoma cell lines, in primary colonic adenocarcinomas, and in myeloid and B-cell lines to varying degrees. Quantitative analyses of BGPc RNA expression by RNase protection indicate that abundant levels occur only in the colonic, but not in the hematopoietic, cell lines tested. Studies presented here show that BGPc mediates homotypic adhesion and suggest that the cytoplasmic splicing does not alter the initial homotypic adhesion properties of BGPa.
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PMID:CD66 identifies the biliary glycoprotein (BGP) adhesion molecule: cloning, expression, and adhesion functions of the BGPc splice variant. 801 19

The expression of carcinoembryonic antigen (CEA)-related glycoproteins that have been associated with intercellular adhesion and that serve as receptors for mouse hepatitis virus (MHV) was analyzed in cells from the immune system of BALB/c mice using immunolabeling and RNA polymerase chain reaction amplification of receptor transcripts. These glycoproteins, which are called biliary glycoproteins, were highly expressed in B lymphocytes, including cells of the B-1a (CD5+) lineage, and in macrophages, but were not detectable in resting T lymphocytes. Similarly, murine cell lines of B cell and macrophage origin expressed messenger RNA encoding CEA-related molecules, while the corresponding mRNA was only slightly detectable in a T cell line. These CEA-related cell adhesion glycoproteins were also expressed in endothelial cells. Therefore, their specific interaction with their so far unknown ligand may be of functional importance in cellular interactions in the immune response. Monoclonal antibody directed against these glycoproteins blocked MHV-A59 infection of the B cell-derived SP20 cell line. Thus, the functional receptors for MHV on B lymphocytes, like those on murine fibroblasts, are isoforms of CEA-related glycoproteins. Treatment of B cells with anti-receptor antibody also blocked B cell-mediated cytotoxicity against MHV-A59-infected fibroblasts, indicating that this phenomenon is mediated by interaction of viral attachment protein on the infected target cells with specific CEA-related receptor glycoproteins on the effector B cells.
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PMID:B lymphocyte and macrophage expression of carcinoembryonic antigen-related adhesion molecules that serve as receptors for murine coronavirus. 820 98

This study evaluates the role of reverse-transcriptase polymerase chain reaction (RT-PCR) assay for carcinoembryonic antigen (CEA), cytokeratin 19 (CK19), and maspin transcripts to identify breast cancer cells (BCC) in leukapheresis products (LP) collected from breast cancer (BC) patients and compares these results with those obtained using immunocytochemistry (IC). Eighty-four LP obtained from 33 patients with stage II-III BC and control subjects without BC were screened for the presence of BCC by IC and CK19, CEA, and maspin expression using RT-PCR. CEA RT-PCR and IC were the only specific markers, as no false positives were detected in any patients without BC. CK19 RT-PCR gave 11% false positives, whereas maspin RT-PCR with 25% was the most unspecific marker. In LP from BC patients, positive results were observed in 70% and 63% for CK19 and CEA RT-PCR, respectively. For maspin RT-PCR, this percentage was 22%, and for IC it was 17%. There was a good correlation between the CEA and CK19 RT-PCR (p = 0.018). No correlation between CEA and CK19 RT-PCR and IC was found, and although 5 of the 6 IC+ samples were CEA+/CK19+, great discrepancies in the group of IC- samples were observed. Our data suggest that RT-PCR assays for CEA and, to a lesser extent, for CK19 have more sensitivity and specificity than IC to detect BCC in LP.
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PMID:Use of reverse-transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen, cytokeratin 19, and maspin in the detection of tumor cells in leukapheresis products from patients with breast cancer: comparison with immunocytochemistry. 1019 2

Peritoneal dissemination is the most frequent type of recurrence in patients with gastric cancer with serosal exposure, irrespective of whether they have undergone curative gastrectomy. The purpose of this study was to establish a method to detect micrometastatic cells in the abdominal cavity and predict peritoneal recurrence in patients with such gastric carcinomas. A total of 86 patients with gastric carcinoma, undergoing gastrectomy, were examined. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay was used to detect carcinoembryonic antigen (CEA) mRNA in abdominal lavage fluid. Twenty-four cases without serosal exposure were negative, while all 13 cases with macroscopic peritoneal dissemination were positive for CEA mRNA. Among the 49 cases with macroscopic serosal invasion and without peritoneal metastasis, cancer cells were detected in 27 cases with RT-PCR while in only 6 cases with conventional cytology. All cytologically-positive cases were also positive for CEA mRNA. Among the 27 CEA-positive cases, 15 patients (56%) relapsed with peritoneal metastasis within 12 months after gastrectomy. In contrast, none of the 22 CEA-negative cases had peritoneal recurrence within 16-60 months of observation, whereas in 43 cytologically-negative cases, 10 patients relapsed with peritoneal recurrence. As compared with conventional cytological examination, this method would be clinically more beneficial for detecting free cancer cells in the peritoneal cavity and for predicting peritoneal recurrence in gastric carcinoma with serosal invasion.
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PMID:Carcinoembryonic antigen mRNA in abdominal cavity as a useful predictor of peritoneal recurrence of gastric cancer with serosal exposure. 1263 1

A new tumor cell line (SUIT-4) derived from ascites of a patient with carcinoma of the pancreas has been established in tissue culture and in nude mice, and maintained for over 7 years. In tissue culture, the cells grew as a confluent monolayer with piling up of cells in some areas. The population doubling time during the exponential phase of the cell growth was 43.9 h in vitro. Chromosome count ranged from 63 to 68 with a modal number of 67. Subcutaneous injection of cultured cells into the flanks of nude mice resulted in tumor formation with a doubling time of 88.8 h. Histopathologically, xenografts in nude mice were moderately differentiated tubular adenocarcinoma, and the tumor cells showed spontaneous metastasis to the regional lymph nodes in 6 of 21 nude mice and to the lung in 4 of 21. Transmission electron microphotographs confirmed the ductal cell origin of the carcinoma and revealed that the cells had abundant mitochondria and lysosomes. SUIT-4 cells released carcinoembryonic antigen (3.08 x 10(2) ng/1 x 10(6) cells/24 h) and carbohydrate antigen 19-9 (4.75 x 10(4) U/1 x 10(6) cells/24 h) during exponential cell growth in vitro. Reverse transcriptase-polymerase chain reaction studies revealed that SUIT-4 cells expressed matrix metalloproteinases 1, 3, 7, 10 and 14.
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PMID:Establishment and characterization of a novel human pancreatic cancer cell line (SUIT-4) metastasizing to lymph nodes and lungs in nude mice. 1545 75

Free cancer cells exfoliated from the serosal surfaces of primary cancers are considered to be responsible for peritoneal dissemination, which are both the most frequent pattern of treatment failure and the most important cause of death in gastric cancer patients. Detection of free cancer cells in the peritoneal cavity at the time of surgery, therefore, is thought to be of great value in predicting peritoneal recurrence and accordingly the prognosis of gastric cancer patients. This study was designed to determine whether free cancer cells in peritoneal lavage fluid from gastric cancer patients could be identified by a reverse-transcriptase polymerase chain reaction (RT-PCR) method specific to carcinoembryonic antigen (CEA) mRNA. Simultaneously, the results from conventional cytological examination were evaluated and the levels of CEA in peritoneal lavage were determined. Of the 40 gastric cancer patients enrolling in this investigation, 11 (27.5%) were positive for CEA mRNA in their peritoneal lavage, whereas only 6 (15%) and 8 (20%) were shown to be positive by cytological examination and peritoneal CEA (pCEA) assay, respectively. Furthermore, RT-PCR positive for CEA mRNA was correlated with the depth of tumor invasion (P<0.001), lymph node metastases (P=0.004), the TNM stage (P<0.001) and peritoneal recurrence (P<0.001). The technique of RT-PCR was more sensitive than conventional cytological examination and pCEA levels in the detection of peritoneal free cancer cells as well as in the prediction of peritoneal recurrence. In addition, CEA RT-PCR had a high concordance rate (82.5%) with the combination of cytology with pCEA levels. These observations suggest that it is feasible to identify free cancer cells in peritoneal lavage by using a CEA mRNA-specific RT-PCR method, and this assay can be a promising diagnostic modality for evaluating the risk of peritoneal dissemination in gastric cancer patients following operations.
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PMID:Gastric cancer cell detection in peritoneal lavage: RT-PCR for carcinoembryonic antigen transcripts versus the combined cytology with peritoneal carcinoembryonic antigen levels. 1589 Feb 45

Persistent high mortality rates in breast cancer patients, in spite of latest advances in diagnosis and therapy, affirm the necessity of new developments in tumor biology prognostic factors. Immunocytochemical detection of disseminated breast cancer cells in bone marrow has been frequently associated with a decrease in disease-free survival as an independent prognostic factor, but methods based on molecular biology procedures must still be validated. Considering tumor heterogeneity, the multimarker approach has been suggested as a better strategy than individual marker assays. The aim of this work was evaluation of the prognostic value of a multimarker reverse-transcriptase polymerase chain reaction (RT-PCR) assay, associating four mRNA markers for the detection of disseminated breast cancer cells. We compared the prognostic significance of cytokeratin 19 (CK19), carcinoembryonic antigen (CEA), mammaglobin (MG) and the mucin MUC5B mRNA in bone marrow aspirates in the follow-up of 80 operable breast cancer patients. The best prognostic value for clinical outcome was seen for CEA mRNA, not improved for any association with other markers. Unexpectedly, some tumor mRNA in bone marrow correlates with a favorable clinical outcome, especially MUC5B. Therefore, our results suggest that not all epithelial or tumor markers have the same significance in predicting the metastatic potential of disseminated cancer cells. New parameters are needed for the identification of individual patients at high risk of tumor recurrence. Multimarker RT-PCR assays could be a good approach, but they should be performed associating mRNA markers that are able to predict tumor aggressiveness associated with poor outcome and not just epithelial markers, which only indicate the mere presence of tumor cells.
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PMID:Clinical evaluation of a panel of mRNA markers in the detection of disseminated tumor cells in patients with operable breast cancer. 1601 42

Early detection of disseminated tumor cells in the peripheral blood of patients with early stage gastric cancer could help to improve the outcome after tumor resection. The aim of this study is to evaluate the prognostic significance of tumor-related mRNA for the detection of circulating tumor cells in gastric cancer patients by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. We simultaneously analyzed human telomerase reverse transcriptase (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20) and carcinoembryonic antigen (CEA) mRNA (messenger RNA) expression in the peripheral blood of 42 gastric cancer patients and 30 healthy individuals. Additionally, analyses were carried out for the correlation of these four molecular markers with patients' clinicopathologic features, as well as the occurrence of postoperative recurrence/metastasis. Among 42 gastric cancer patients, the prevalence of mRNA for hTERT, CK-19, CK-20, and CEA was 61.9% (26/42), 69% (29/42), 61.9% (26/42), and 78.6% (33/42), respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA, while two were positive for either CK-19 mRNA or CK-20 mRNA. Positive CEA mRNA was significantly correlated with tumor size p=0.008), vessel invasion (p=0.001), depth of tumor invasion (p=0.007), lymph node metastasis (p< 0.001), and TNM stage (p<0.001). In addition, the multivariate logistic regression demonstrated that CEA mRNA expression was an independent and significant predictor for postoperative recurrence/metastasis (p=0.032). Our findings suggest that CEA mRNA may be a more reliable marker than hTERT, CK-19 and CK-20 for the detection of circulating cancer cells in gastric cancer patients' peripheral blood. Patients with positive CEA mRNA expression in peripheral blood have a significantly higher risk of postoperative recurrence/metastasis.
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PMID:Molecular detection of disseminated tumor cells in the peripheral blood of patients with gastric cancer: evaluation of their prognostic significance. 1678 43

In some patients without distant metastases according to conventional preoperative investigations, relapse occurs in distant organs within a few years after radical resection of esophageal cancer. Various attempts have been made to detect micrometastases that are not found by conventional techniques. A quantitative real-time reverse-transcriptase polymerase chain reaction was used to detect messenger RNA for carcinoembryonic antigen in 147 blood samples from 49 patients scheduled for radical resection of esophageal cancer at Juntendo University Hospital between September 2003 and June 2004. The number of circulating cancer cells was assessed and the clinical significance of detecting such micrometastases was analyzed. Multivariate analysis showed that positivity of this assay was significantly associated with pT1 or pT2 disease and stage III or stage IV disease. Patients with more than 40-50 carcinoembryonic antigen mRNA copies among 10(4) normal cells on quantitative analysis had a higher recurrence rate. The number of tumor cells circulating in the blood may have more influence on the prognosis of esophageal cancer than the presence of tumor cells.
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PMID:Circulating micrometastases of esophageal cancer detected by carcinoembryonic antigen mRNA reverse transcriptase-polymerase chain reaction: clinical implications. 1845 88

Circulating tumor cells (CTCs) have been associated with clinical outcome in various malignancies. The aim of this study was to examine CTC status in the peripheral blood of patients with esophageal squamous cell carcinoma (ESCC) before and after radiotherapy, and to evaluate its clinical significance. A total of 72 ESCC patients treated with radical radiotherapy were enrolled in this study. The nested reverse-transcriptase polymerase chain reaction was used to detect the three representative markers of CTCs, namely carcinoembryonic antigen, cytokeratin 19, and survivin. The results showed that CTC(+), a status with positive expression of at least one of these three markers, in patients with ESCC pre- and post-radiotherapy were 54.2% (39/72) and 38.9% (28/72), respectively (P= 0.059). Furthermore, CTC (+) in patients pre- or post-radiotherapy was both correlated with lymph metastasis and adverse 2-year progression-free survival. It was also found that changes in CTC status after radiotherapy could reflect patients' response to radiotherapy. The response rates in cases with CTC status pre-radiotherapy(+)/post-radiotherapy(+), pre-radiotherapy(-)/post-radiotherapy(+), pre-radiotherapy(-)/post-radiotherapy(-), pre-radiotherapy(+)/post-radiotherapy(-) were 58.3% (21/36), 0% (0/3), 73.7% (14/19), and 85.7% (12/14), respectively. In a multivariate analysis of Cox proportional hazard model, only CTC (+) post-radiotherapy was an independent unfavorable prognostic factor for ESCC apart from subsequent chemotherapy and patients' Karnofsky performance status scores. In conclusion, positive detection of CTCs in patients with ESCC after radiotherapy may be a promising biomarker for radiation efficiency and prognosis assessment in ESCC.
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PMID:Clinical significance of carcinoembryonic antigen-, cytokeratin 19-, or survivin-positive circulating tumor cells in the peripheral blood of esophageal squamous cell carcinoma patients treated with radiotherapy. 2239 49


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