Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Around 80% of breast carcinomas express the tumor-associated glycoprotein-72, as demonstrated by positive immunostaining with the monoclonal antibody B72.3. We have investigated the pattern of B72.3 immunostaining in 88 breast carcinomas of different types, with the use of an immunoperoxidase technique. As tumor-associated glycoprotein-72 has mucinlike properties and is usually present in cells that show apocrine differentiation, we have also compared the results of B72.3 immunostaining in these tumors with the staining results for mucin and GCDFP-15, which is another antibody that recognizes apocrine differentiation. A variable degree of B72.3 immunostaining was seen in 60 cases (68%). The staining patterns varied with the histological type and sometimes within the same type. A significant relationship was demonstrated between B72.3 positivity and the presence of acidic mucin in the tumors, but not with their staining for GCDFP-15. The extent, distribution, and pattern of immunostaining for B72.3 varies in different types of breast carcinoma; this fact has to be taken into consideration if radiolabeled B72.3 monoclonal antibodies are going to be used for therapeutic purposes.
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PMID:Monoclonal antibody B72.3 immunostaining of breast carcinoma. Patterns of staining and relationship to mucin content and GCDFP-15 reactivity. 137 Aug 77

Two mucin-producing cell clones (16.2 and 12.2) and a mucin-deficient clone (15.2) were selected from the established human adenocarcinoma cell line HT-29 by limiting dilution and Alcian blue staining. The amounts of the mucin antigen detectable on the cell surface with the monoclonal antibody (MAb) AM-3 decreased in the order HT-29 greater than 16.2 greater than 12.2 greater than 15.2 = 0. The binding avidity of AM-3 antibody to cells as well as to mucin extracts from each cell line decreased in the same order, indicating that the epitope density on the cell-bound mucins was highest in HT-29 and lowest in 12.2 cells. The parental line and the mucin-producing cell clones 16.2 and 12.2 showed no contact inhibition and grew as aggregates, while the 15.2 cells were well spread and formed a regular monolayer. The mucin-producing cell lines injected into nude mice yielded solid tumors with different growth rates (HT-29 greater than 16.2 greater than 12.2), while the 15.2 cell clone was not tumorigenic at all. The relative amounts of total mucin-bound hexoses and of the mucin epitope AM-3 decreased in the xenografts in the order HT-29 greater than 16.2 greater than 12.2. The present system is suitable for investigating the role of mucins in growth of colon carcinoma cells and indicates that increased tumorigenicity in nude mice coincides with the increase in total mucin expression and the expression of the AM-3 mucin epitope in tumor tissue.
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PMID:Tumorigenicity, mucin production and AM-3 epitope expression in clones selected from the HT-29 colon carcinoma cell line. 137 82

Second generation antibodies to mammary mucins were produced by immunizing mice with a peptide with a sequence deduced from that of the MUC1 complementary DNA sequence (PAHGVTSAPDTRPAPGSTAP). Four monoclonal antibodies (BCP7-10) were produced which gave different reactions. BCP8 was similar in tissue reactivity (by immunoperoxidase staining) to anti-breast cancer or anti-human milk fat globule membranes (HMFG) antibodies and reacted strongly with most breast cancers and a proportion of other adenocarcinomas, whether formalin fixed or fresh, and reacted less strongly with some normal tissues. The three other antibodies (BCP7, BCP9, BCP10) reacted only with fresh tissues or a single cell line (LS174T of colon cancer origin) and gave variable weak reactions. Like many anti-mucin antibodies BCP8 reacted with HMFG, but more strongly with deglycosylated HMFG; analysis with peptides by enzyme-linked immunosorbent assay indicated reactivity with an epitope contained in the amino acid motif PDTR and using the pepscan method, the minimum epitope was DTR. MAbs BCP7, BCP9, and BCP10 did not react with HMFG; substantial reactions were obtained with deglycosylated HMFG for BCP7 and weaker reactions with BCP9 and BCP10. The finding that BCP7 reacted with breast cancer tissues and deglycosylated HMFG suggested that the epitope recognized by BCP7 was masked in native form and exposed in cancer, indicating that BCP7 could be a useful agent for analyzing differences between normal and cancer mucins. The amino acid epitopes for these antibodies were VTSA (BCP7), GSTAP (BCP9), and RPAP (BCP10). For BCP8, amino acid substitution analysis of SAPDTR indicated that substitutions were poorly tolerated (except Q for T and L/Y for R), contrasting with the substitution analysis of anti-mucin antibody reactions where virtually any amino acid can be substituted for T, indicating that in the native state T (threonine) may be O-glycosylated. The use of synthetic peptides to produce antibodies similar to those produced using crude mucins or tumor extracts represents a major advance in the production of antitumor reagents.
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PMID:Second generation anti-MUC1 peptide monoclonal antibodies. 137 8

Experiments have been performed to define conditions for the primary culture of human exocrine pancreas, as a first step towards molecular reconstruction experiments of pancreatic neoplasia. Normal human exocrine pancreas was digested using collagenase and dispase and the resulting cellular aggregates were cultured in vitro. The phenotype of the digested pancreatic cells was almost exclusively acinar (amylase-positive, keratin 19 and mucin antigens-negative), yet within 4 days of culture the cells had taken on a ductal phenotype (amylase-negative, keratin 19 and mucin antigens-positive). The kinetics of these observations exclude the possibility of overgrowth of the acinar population by a ductal sub-population, and selective adherence is excluded by examination of those cells that do not adhere, which are representative of the initiating population. We interpret these data as indicating that, under the conditions of culture, the acinar cell phenotype is not stable and can transdifferentiate to a ductal phenotype. Taken together with recent data from transgenic animals, this in vitro observation has possible implications for our view of the pathogenesis of pancreatic neoplasia.
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PMID:Rapid acinar to ductal transdifferentiation in cultured human exocrine pancreas. 137 87

A case of primary hepatic carcinoid tumor was recently encountered, which was argyrophil and showed positive reactions to serotonin, gastrin and pancreatic peptide in an immunohistochemical hormonal study. The tumor had unusual morphologic features. The neoplastic cells had a signet-ring cell appearance, similar to the signet-ring cells normally seen in mucin-producing adenocarcinoma. Ultrastructural and immunohistochemical studies revealed the formation of the signet-ring cells to have been caused by the presence of cytoplasmic inclusions consisting of cytokeratins. Further investigation, using eight monoclonal antibodies recognizing cytokeratins of different molecular weights, showed the accumulated cytokeratins to be of low and medium molecular weights. The morphologic observations in this unusual case of hepatic carcinoid tumor are described and reported cases with similar features, for which we propose the term "signet-ring cell carcinoid," are reviewed.
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PMID:Signet-ring cell carcinoid: a primary hepatic carcinoid tumor with cytoplasmic inclusions comprising of aggregates of keratin. 137 35

Nd2 was a murine monoclonal antibody produced against a mucin fraction purified from xenografts of the human pancreatic cancer cell line SW1990. The reactivity of Nd2 was reduced by trypsin, but was not influenced by neuraminidase, so the epitope recognized by Nd2 may involve peptide but not sialic acid. The antigen recognized by Nd2 was present in 83% of pancreatic cancer, whereas in tissue of normal pancreas and chronic pancreatitis no reactivity was detected. By biodistribution study, tumor/blood ratio was elevated 8.27 on the 7th day after injection of 125I-labeled Nd2, while tissue/blood ratio in liver was remained 0.53. These results indicate that Nd2 had possibilities in clinical application such as radio-immunodetection and targeting therapy of pancreatic cancer.
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PMID:[Immunohistochemical study and biodistribution of monoclonal antibody (Nd2) against human pancreatic cancer]. 138 Jun 34

Mucins are among the best described human tumor-associated antigens. At least 73 tumor-reactive anti-mucin antibodies have been described; in addition, we have previously demonstrated the existence of tumor-specific cytotoxic T-lymphocyte epitopes on the mucin produced by breast and pancreatic tumors. To determine whether the appearance of tumor-associated mucin epitopes can be explained by altered post-translational modification of mucin in tumors, or whether the generation of these epitopes requires changes in the mucin gene itself, we studied four Burkitt's lymphomas and six Epstein-Barr virus-immortalized B-cell lines transfected with an expression construct containing the mucin complementary DNA. Transfected cell lines showed stable maintenance of the mucin gene, which comprises 20 or more tandem repeats of a 60-nucleotide sequence. Transfected cells expressed many tumor-associated mucin epitopes, suggesting that the changes in mucin synthesis seen in breast and pancreatic tumors are present in other malignant cell types as well. Furthermore, even though each cell line was transfected with the identical mucin construct, each expressed a different subset of tumor-associated mucin epitopes. This suggests that the specificity of these epitopes for tumors is not due to genetic alterations of the mucin gene in tumors. Incubating transfected cells with phenyl-N-acetyl-alpha-galactosaminide, an inhibitor of O-linked glycosylation, altered cell surface carbohydrate structures and resulted in increased expression of all tumor-associated epitopes, implicating incomplete glycosylation of mucin in the generation of these epitopes. These findings suggest that alterations in the posttranslational modification of normal gene products can result in the expression of novel epitopes. Furthermore, the ability to transfect cancer patients' Epstein-Barr virus-immortalized B-cell lines with mucin will provide an unlimited supply of autologous, mucin-bearing cells with which to study these patients' T-cell response to mucin.
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PMID:Expression of tumor-associated epitopes on Epstein-Barr virus-immortalized B-cells and Burkitt's lymphomas transfected with epithelial mucin complementary DNA. 138 49

Two cases of malignant pleural tumor producing human chorionic gonadotropin, one confirmed at surgery and autopsy and the other by biopsy, are reported. Both of the patients had bilateral gynecomastia with high levels of serum human chorionic gonadotropin. The first patient underwent panpleuropneumonectomy because of diffuse malignant pleural tumor, but died five months later due to recurrent disease. The histological diagnosis was diffuse, malignant, monophasic mesothelioma of the epithelial type. Immunostaining for alpha-, beta-human chorionic gonadotropin and human placental lactogen was positive in syncytiotrophoblast-like cells. The second patient had diffuse pleural tumor with massive effusion. A pleural biopsy specimen showed diffuse proliferation of epithelioid large cells. Immunostaining for alpha, beta-human chorionic gonadotropin and human placental lactogen was positive in mono- and multinucleated bizarre giant cells mimicking trophoblasts. A diagnosis of malignant mesothelioma with trophoblastic differentiation seemed most likely in both cases in view of the clinical and pathological findings. In both cases, results of mucin histochemistry and various immunohistochemical stains for antigens or with antibodies were consistent with diagnosis of mesothelioma except in a few cells in the choriocarcinomatous portion. This may be the first report describing human chorionic gonadotropin-producing malignant mesotheliomas of the pleura.
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PMID:Malignant pleural mesothelioma producing human chorionic gonadotropin. Report of two cases. 835 15

Complementary DNA clones encoding four different mucin core peptides have been isolated. However, the expression of these mucin genes in the colon has not been systematically studied. The present investigation used Northern blot analysis to study the expression of MUC1, MUC2, MUC3, and MUC4 mRNA in paired normal and cancerous colonic tissues, and nine colon cancer cell lines. Results were correlated with the clinicopathological features of the tumors and with the immunohistochemical expression of several carbohydrate tumor-associated antigens that may reside on mucins. MUC1 mRNA was expressed in all colonic tissues, and levels in paired normal and cancer tissues were similar in most cases. MUC2 and MUC3 mRNAs were expressed in both normal and cancer tissues, but levels were often decreased in the cancers. MUC4 mRNA was present in normal mucosa with comparable or sometimes greater expression in cancers. There was no apparent correlation between the expression of any particular mucin gene or pattern of mucin genes and the site, stage, or histological type of tumor. In addition, the expression of mucin-associated carbohydrate antigens did not correlate with any individual mucin gene or group of mucin genes. In colon cancer cell lines all four MUC genes were expressed rather weakly or not at all. These results indicate that the human colon expresses a broad repertoire of mucin genes which are differentially regulated in malignancy. Whether this differential regulation of mucin genes affect the behavior of the tumor and results in the altered glycosylation commonly seen in these requires further investigation.
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PMID:Mucin gene expression in colonic tissues and cell lines. 139 23

Synthetic glycosides containing the core, -Glc-NAc beta 1,6GalNAc alpha-, acted as acceptors for beta-galactosyltransferase of human ovarian tumor. A significant amount of Gal was transferred from UDP-Gal (100 nmol) to the alpha-benzylglycoside of LacNAc beta 1,6GalNAc (LGBn) (25.1 nmol of Gal) and the alpha-ortho-nitrophenylglycosides of LacNAc beta 1,6GalNAc (22.0 nmol of Gal), GlcNAc beta 1,6GalNAc (15.5 nmol of Gal), and Fuc alpha 1,3GlcNAc beta 1,6GalNAc (25.9 nmol of Gal); LacNAc beta 1,6(Gal beta 1,3)GalNAc alpha-O-Bn (where Bn is benzyl) was almost inactive (only 1.2 nmol of Gal), indicating the Gal transfer to the alpha-GalNAc moiety. The product from LGBn was isolated in microgram quantities and identified by fast atom bombardment mass spectrometry as LacNAc beta 1,6(Gal beta 1,3)GalNAc alpha-O-Bn. The alpha GalNAc:beta 1,3Gal transferase was present in high concentration in ovarian tumor tissue (ovarian cancer serum----1.4; ascitic fluid----0.9; tumor----17.4). Asialo Cowper's gland mucin (ACGM) at 5 mg/ml reaction mixture inhibited the transfer of Gal to LGBn (25.2 and 53.4% respectively for 2 and 18 h incubation at 37 degrees C); inhibition by LGBn was 13.4 and 24.5%, respectively. In contrast to the inhibition by ACGM (25.2-31.6%), there was substantial increase (13.4-35.7%) in the inhibition by LGBn, when the incubation for 2 h at 37 degrees C was continued for 40 h at 4 degrees C, indicating the high affinity of LGBn for the enzyme at lower temp. Km for LGBn in presence of ACGM was 7.6 mM and in absence, 2.7 mM; Km for ACGM (M(r) 200,000) in presence of LGBn was 16.1 microM and Ki for ACGM (as the inhibitor) was 41.7 microM. In comparison with two normal ovarian tissues, the enzyme was found to be low (55-67%) in three ovarian tumors and high (146-260%) in two ovarian and one uterus tumors, as measured with ACGM; the synthetic acceptors showed similar activities. The enzyme had nearly the same extent of activity in the pH range 6-8. Fuc alpha 1,3GlcNAc beta 1,6GalNAc alpha-O-ONP had the highest affinity for the enzyme. The present study demonstrates the feasibility of beta 1,3Gal attachment on alpha GalNAc, which has already been substituted by beta 1,6GlcNAc, then elongated by beta 1,4Gal and also terminated by alpha 1,3Fuc.
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PMID:Mucin biosynthesis revisited. The enzymatic transfer of Gal in beta 1,3 linkage to the GalNAc moiety of the core structure R1-GlcNAc beta 1,6GalNAc alpha-O-R2. 140 Mar 9


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