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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many cancer-associated antigens are present on mucin glycoproteins. These include peripheral antigens such as sialyl Lea and sialyl Lex and core region carbohydrate antigens such as T, Tn, and Sialyl Tn. We have recently described an inhibitor of mucin glycosylation, benzyl-alpha-GalNAc. The purpose of this study was to determine its effect on expression of mucin carbohydrate antigens. HM7 colon cancer cells were treated for 2 days in culture with 2 mM benzyl-alpha-GalNAc. This treatment did not affect viability or doubling time, but inhibited synthesis of [3H]glucosamine-labeled mucins. There was also secretion of benzyl-oligosaccharides and a decrease in the proportion of long oligosaccharides on 3H-labeled mucins. Mucins were purified from spent media by gel filtration and assayed for binding of monoclonal antibodies and lectins. Mucins from benzyl-alpha-GalNAc-treated cells had increased binding of peanut agglutinin (specific for T antigen, Gal beta 3GalNAc) and Vicia villosa agglutinin B4 (specific for Tn antigen, GalNAc alpha-Thr/Ser), but decreased binding of monoclonal antibodies 19-9, SNH3, and 91.9H (specific for sialyl Lea, sialyl Lex, and sulfomucin, respectively). Treatment of the cells with benzyl-alpha-GalNAc also decreased their binding to E-selectin (ELAM-1), which recognizes sialyl Lea and sialyl Lex. Thus, benzyl-alpha-GalNAc treatment, which decreases the level of peripheral carbohydrate carbohydrate antigens on mucins with accumulation of core region antigens, may be useful in modifying the immunological and biological properties of colon cancer cells.
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PMID:Effect of benzyl-alpha-GalNAc, an inhibitor of mucin glycosylation, on cancer-associated antigens in human colon cancer cells. 128 81

Molecular size of SPan-1 antigen and co-expression between SPan-1 epitope and Lewis phenotype determinants (LPD) on the same molecule in sera from patients with pancreatic, gastric and colon cancer and in culture medium from cancer cell line were studied. Column chromatography study on culture medium and sera showed that SPan-1 immunoreactivity was found in the void volume region as single major peak, or followed by one or two minor peak in the included volume. All of 4 pancreatic cancer cell lines showed molecular size heterogeneity. Co-expression between SPan-1 epitope and LPD on the same molecule was recognized in sera from cancer patients with Lewis a or Lewis b positive, but not in patients with Lewis a-, b-. Molecular carrying SPan-1 epitope had more frequently SPan-1 epitope than LPD in sera from cancer patients. These findings suggest that molecular size heterogeneity of SPan-1 antigen was more often in pancreatic cancer cells and overexpression of SPan-1 epitope on the same molecule seems to be specific for cancer.
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PMID:[Molecular size heterogeneity of SPan-1 antigen and co-expression with Lewis phenotype determinants in sera from gastrointestinal malignant diseases]. 138 Sep 97

Eight red blood cell (RBC) Le(a-b-) individuals were selected from a series of patients with bladder or colon cancer. Defined by the presence or absence of alpha 1-4-L-fucosyltransferase activity in saliva, four of these patients were characterized as non-genuine Lewis negative [RBC Le(a-b-) with alpha 1-4-L-fucosyltransferase activity in saliva], and four as genuine Lewis negative [RBC Le(a-b-) with no alpha 1-4-L-fucosyltransferase activity in saliva]. Stainings of paraffin embedded formalin fixed tissue sections for Lea and Leb antigens were performed by means of an indirect immunohistochemical method on all malignant and benign tissue previously removed from these eight patients. Leb antigens were always expressed independently of both the Lewis and the secretor status of the individual. Lea antigens, on the other hand, showed a different staining pattern. Although primarily expressed in non-genuine Le(a-b-) individuals, Lea antigens were expressed in genuine Le(a-b-) individuals as well--to a limited extent, but still detectable. Thus, these findings seem to show that the Lewis antigen expression is tissue dependent, and it is not possible to predict tissue Lewis antigen expression by merely examining erythrocytes or saliva.
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PMID:Lewis antigen expression in benign and malignant tissues from RBC Le(a-b-) cancer patients. 175 78

Molecules bearing the carbohydrate antigen 19-9 (CA19-9) epitope were prepared from serum and ascites of a patient with colon cancer or from the SW 1116 cell culture supernatant. Their plasma clearance mechanism was investigated in rats. The clearance curves of the molecules from three different sources showed a biphasic decrease. The coexistence of epitopes of CA19-9 and desialylated CA19-9 (Lea) in the same molecule was demonstrated by double-determinant enzyme immunoassays. CA19-9-bearing molecules with a low expression of Lea epitope, which were derived from the serum of a patient with colon cancer, showed mainly a slow disappearance, while the molecules with a high expression of Lea epitope from SW 1116 cells showed mainly a rapid disappearance. Thus, the clearance rate of the CA19-9-bearing molecules might be determined by their degrees of sialylation. This observation will be helpful for understanding the in vivo metabolism of CA19-9-bearing molecules.
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PMID:Mechanism of clearance of circulating CA19-9 in rats. 230 66

The monoclonal antibody NCC-CO-450 (IgM kappa) was selected by screening of reactivity with high-molecular-weight antigens (Mr greater than 10(6] isolated from ascitic fluid of a colon cancer patient. This antibody detected heterogeneous but predominantly high-molecular-weight antigens in 4 of 6 ascitic fluid samples from gastrointestinal cancer patients by immunoblotting analysis. A sandwich radioimmunoassay was developed in order to examine the serum level of this antigen, and the cutoff value was defined as the mean plus 2 SD of values obtained with sera from normal donors. While 97% (93 of 96) of sera had a negative antigen value in normal donors, 56% (14 of 25) of patients with colorectal carcinoma and 40% (8 of 20) of patients with gastric carcinoma showed a positive antigen value. The distribution of the antigen in sera of patients with various cancers did not show any correlation with the distribution of carcinoembryonic antigen or CA 19-9. From immunohistochemical and biochemical analyses, NCC-CO-450 antigen was characterized as a mucin-like glycoprotein abundant in normal colonic epithelium as well as in carcinomas of the colon, stomach, and pancreas. The immunohistochemical reactivity of NCC-CO-450 was distinct from that of other monoclonal antibodies reported to be useful for serological diagnosis. The epitope recognized by NCC-CO-450 is considered to be an O-linked carbohydrate chain without terminal sialic acid but is different from the known carbohydrate chains, i.e., Lea, Lex, LeY, Tn, sialyl-Lea, and sialyl sugar chain defined by NCC-ST-439 in a competitive binding inhibition assay of monoclonal antibodies. This newly defined antigen is a good example of a normal antigen shed from cancer cells that can be used successfully as a serum tumor marker.
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PMID:Selection of a monoclonal antibody reactive with a high-molecular-weight glycoprotein circulating in the body fluid of gastrointestinal cancer patients. 245 34

Two mouse monoclonal antibodies (MoAbs), KM-93 raised against human lung adenocarcinoma and KM-231 raised against human gastric cancer, were useful in serum diagnosis of several human cancer. KM-93 and KM-231 recognize sialyl Lex epitope and sialyl Lea epitope, respectively, expressed on glycoprotein and glycolipid. We established a new "cocktail" sandwich enzyme-linked immunosorbent assay system using the two MoAbs and the advantage of this assay system, which can simultaneously detect sialyl Lex and sialyl Lea antigens, is assessed in the present study. The new assay system is composed of a mixture of KM-93 and KM-231 as 1st antibodies and a mixture of biotinylated two MoAbs as 2nd antibodies. We evaluated the concentration of MoAbs and optimized it to gain high cancer-positivity. This assay system covered sialyl Lex positive and/or sialyl Lea-positive sera and gave a high rate of positive results in lung adenocarcinoma (62.3%), gastric cancer (32.5%), colon cancer (37.5%), pancreatic cancer (83.3%), bile duct and gall bladder cancer (66.7%) and hepatoma (76.9%), whereas positive results in healthy adults remained low. Positive results in benign diseases of lung (12.5%), pancreas (10.8%), gall bladder and bile duct (9.1%) were very low, but were higher in liver cirrhosis (33.3%), hepatitis and liver injury (34.8%). Simultaneous detection of two carbohydrate antigens, sialyl Lex and sialyl Lea was clearly superior to single detection.
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PMID:Advantage of cocktail-use of two anti-tumor monoclonal antibodies, KM-93 and KM-231, in serum diagnosis of cancer. 247 31

The CA 19-9 antigen is a monosialosyl Lea blood group antigen which has been shown to be a useful tumor-associated antigen for the diagnosis of gastrointestinal cancers. Recently, a sialylated derivative of this antigen, disialosyl Lea, was isolated from a colon cancer liver metastasis and a monoclonal antibody (FH7) recognizing this novel determinant was developed. The present study simultaneously compared the expression of Lea, monosialosyl Lea, and disialosyl Lea antigens in a variety of nonmalignant, premalignant, and malignant tissues of the colorectum and pancreas with an aim toward elucidating whether disialosyl Lea is expressed as a tumor-associated antigen. In normal colonic mucosa, disialosyl Lea expression closely resembled Lea expression in overall frequency, segmental distribution, and cellular localization whereas monosialosyl Lea (CA 19-9) was essentially absent. Along the crypt axis, Lea was more often expressed in goblet cells of the upper crypt whereas disialosyl Lea was found in goblet cells along the entire crypt. Fetal colonic mucosa expressed all three antigens, as did most colorectal cancers regardless of location within the colon or degree of differentiation. The majority of hyperplastic polyps and practically all adenomatous polyps also expressed these three antigens, and in adenomas, antigen expression was independent of polyp size, villous morphology, or degree of dysplasia. In the normal pancreas, the three antigens were expressed on ductal, ductular and centroacinar cells of all specimens. The majority of pancreatic cancers expressed all three antigens. Thus, in the normal colon, the absence of monosialosyl Lea (CA 19-9) in the presence of disialosyl Lea suggests that an alpha 2,6 sialyltransferase is active, which results in the masking of CA 19-9 antigen expression. These results further support the concept that specific sialyltransferases play a role in regulating the expression of tumor-associated antigens.
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PMID:Immunohistochemical comparison of Lea, monosialosyl Lea (CA 19-9), and disialosyl Lea antigens in human colorectal and pancreatic tissues. 328 36

Serological and immunopathological analysis of the expression of Lea, Leb, X, and Y blood group antigens on cell lines and tissues was performed using a panel of mouse monoclonal antibodies. The distribution of the antigens was determined on 155 malignant tumor cell lines of various types and 10 short term cultures of normal fibroblasts and kidney cells. Among colon cancers, all four blood group antigens were expressed on the majority of cell lines. On lung, breast, bladder, and ovarian cancer cell lines, X and Y antigens were the main specificities found, whereas few of the renal and hematopoietic tumor cell lines demonstrated any of the four blood group antigens. No blood group antigens could be detected on astrocytoma or melanoma cell lines. The expression of the antigens was also analyzed on frozen sections of colon carcinoma and adjacent normal colon tissue from 42 patients using the immunoperoxidase method. Lea and X were detected throughout the normal colon and on most colonic tumors. In poorly differentiated colon cancer and in metastatic cancer, decrease of Lea antigen was observed. Leb and Y expression was observed in only 20-45% of normal tissue samples but in almost all colonic carcinoma tissues. A selected number of tumor and normal specimens from patients whose secretor status was known were examined in more detail. Both the staining of the tissues and the reactivity of blood group glycolipids from the same specimens were determined. These studies confirmed the above findings and demonstrated the unexpected ability of tumors of nonsecretors to express Leb and/or Y antigens. In such individuals, in whom the expression of Leb and Y antigens in normal tissues is absent or minimal, these antigens provide possible targets for immunodiagnosis and therapy.
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PMID:Expression of Lewisa, Lewisb, X, and Y blood group antigens in human colonic tumors and normal tissue and in human tumor-derived cell lines. 351 Jul 28

Three samples of carcinoembryonic antigens were purified from liver metastases of primary colon cancer. The asparagine-linked sugar chains of carcinoembryonic antigens (CEA) were released as oligosaccharides by hydrazinolysis and the structures of oligosaccharides, thus obtained, was studied in combination with methylation analysis and several limited exoglycosidase digestions. All three CEAs contain approximately 25 asparagine-linked sugar chains in one molecule and about 10% of them was high mannose type. However, structural features of the outer chain moieties of the remaining complex-type sugar chains were different by CEA samples. The complex-type sugar chains were mono-, bi-, tri-, and tetraantennary with Man alpha 1----6(+/- GlcNAc beta 1----4)(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(+/- Fuc alpha 1----6)GlcNAc as their cores, half of which were bisected; 86% of their proximal N-acetylglucosamine was fucosylated. The major outer chains in two samples were N-acetyllactosamine and Gal beta 1----4(Fuc alpha 1----3)GlcNAc (X-antigenic determinant) and the remaining one sample contained Fuc alpha 1----2Gal beta 1----4(Fuc alpha 1----3)GlcNAc (Y-antigenic determinant) as an additional major outer chain. Furthermore, small amounts of type 1 chain and Lea antigenic determinant were found in some samples. Acidic oligosaccharides consisted of sialic acid containing fractions and sialidase-resistant fractions, and their contents seemed to be in a reciprocal relationship. Sialic acid was linked at the C-3 and C-6 positions of the nonreducing terminal galactose residues of the outer chains.
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PMID:Structural studies of the carbohydrate moieties of carcinoembryonic antigens. 358 Oct 81

Sialyl Lewis a/sialyl Lewis x antigens, which panels of monoclonal antibodies can recognize, are synthesized by a series of glycosyltransferases. Especially, alpha (1,3)/(1,4) fucosyltransferases and/or alpha(2,3)sialyltransferases regulate expression patterns temporally and spatially, such as in epithelium of digestive systems or in leukocytes. The carbohydrate ligands of P-selectin and E-selectin have been identified as sialyl Lewis x expressed on granulocytes, monocytes, and natural killer cells. Expression of sialyl Lewis x on these cells is mainly determined by Fuc-TVII, but as for the counterparts of sialyl-transferases, there remains much uncertainty. P-selectin-dependent adhesion of tumor cells and E-selectin-dependent adhesion of tumor cells to endothelial cells play some role for tumor cell aggregation leading to microembolism and hematogenous metastasis of cancers. We have found expression of some fucosyltransferases (Fuc-TIII, VI, VII) and a sialyltransferase (ST3O) are increased in colon cancer tissues coincidentally with sialyl Lewis a antigens, with which E-selectin can interact. As already started in many laboratories, genetic manipulation of glycosylation pathways in gene-targeted animals has an outstanding potential to yield clues to oligosaccharide function.
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PMID:[Structures, synthesis and functions of sialyl Le(a)/sialyl Le(x) antigens]. 763 14


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