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

Cancer-associated mucins in the colon are antigenically distinct and glycosylated differently from their normal counterparts. Mucin-rich glycoconjugate preparations were made from nine non-neoplastic colons, seven colon cancers, and two different xenografts from mucin-producing human colon cancer cell lines, and radiolabeled with 3H. The preparation was applied to a DEAE-cellulose ion-exchange column, and eluted with a discontinuous ascending NaCl gradient resulting in seven discrete fractions or 'species'. Over half of the 3H-labeled glycoconjugates from specimens of non-neoplastic colonic epithelium eluted in fraction V (eluted with 0.25 NaCl). Significantly less of the 3H-labeled glycoconjugates from specimens of colon cancer eluted in fraction V (34%, P less than 0.0005), and there were significant increases in glycoconjugates eluted in fractions IV (P less than 0.008), III (P less than 0.0005), and II (P less than 0.028). Additional samples were prepared without the radiolabeling procedures, chromatographed on a DEAE-cellulose ion-exchange column, and analyzed for monosaccharide content. Each of the fractions contained the monosaccharides expected in mucin-type glycoproteins, but only sialic acid was differentially expressed in the seven fractions or 'species', occurring principally in the more charged species. However, differences in sialic acid content were not sufficient to explain the differences in retention on the ion-exchange column, nor were differences in O-acetylation of the mucins. Mucin-type glycoconjugates from colon cancers are relatively less charged than those from the normal colon, and elute at lower ionic strengths. Of interest, cancer-associated mucins appear to be of lower molecular weight than their normal counterparts. Additional studies of oligosaccharide and apomucin structure will be required to explain the molecular basis of these differences in charge.
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PMID:Analysis of cancer-associated colonic mucin by ion-exchange chromatography: evidence for a mucin species of lower molecular charge and weight in cancer. 265 12

Colon cancer cells in culture synthesize and secrete mucin glycoproteins, which carry a number of cancer-associated antigens. However, the structures and mechanisms of biosynthetic processing are not well understood. Mucins synthesized and secreted by LS174T human colon cancer cells were compared to those in LS174T xenografts in athymic mice. Mucins radiolabeled with glucosamine or sulfate were purified by gel filtration and cesium chloride density gradient centrifugation. The mucins were of high molecular weight and were resistant to chondroitinase ABC, hyaluronidase and HNO2 treatment. They were, however, susceptible to pronase digestion and mild alkaline treatment. Using radiochemical precursors, the cellular mucin was shown to contain fucose, galactose, N-acetylgalactosamine, N-acetylglucosamine, N-acetylneuraminic acid, and sulfate. Oligosaccharides released by beta-elimination had N-acetylgalactosaminitol as the reduced amino sugar and also unreduced galactosamine, indicating that there is N-acetyl-galactosamine O-glycosidically attached to protein core and also peripheral N-acetyl-galactosamine not directly linked to protein. DEAE-cellulose chromatography of mucins showed two major peaks with both intracellular and secreted mucins, but xenograft mucins also had more acidic components. Sulfate-labeled mucins were shifted to less acidic peaks by neuraminidase digestion, which indicates that the same mucin molecules are both sialylated and sulfated. We conclude that the intracellular mucins of cultured colon cancer cells, those secreted into the medium, and those in nude mouse xenografts are chemically similar, but differ in sialic acid and sulfate content. This experimental model system, LS174T cells maintained in culture and as nude mouse xenografts, may be useful for further biosynthetic and structural studies of colon cancer mucin.
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PMID:Comparison of metabolically labeled mucins of LS174T human colon cancer cells in tissue culture and xenograft. 273 49

Mucin glycoproteins are major secretory products of the colon and contain O-linked oligosaccharides synthesized on a polypeptide backbone. The initial step in the synthesis of O-linked oligosaccharides is the addition of N-acetylgalactosamine to serine or threonine residues forming the Tn antigen. This substance can then receive additional carbohydrate residues such as sialic acid to form sialosyl-Tn antigen, or galactose to form T antigen. In the colon, the T antigen is an oncodevelopmental cancer-associated antigen but little is known about Tn and sialosyl-Tn expression. The present comparative immunohistochemical study was performed to analyze the expression of these antigens in fetal, normal adult, and malignant colorectal tissues with an aim toward elucidating whether Tn and sialosyl-Tn are also oncodevelopmental colon cancer-associated antigens and to gain insight into the earliest steps of mucin glycosylation in colonocytes. We used three reagents to detect Tn antigen (two monoclonal antibodies ETn1.01 and CU-1, and one lectin Vicia villosa), two reagents to detect sialosyl-Tn (monoclonal antibodies TKH2 and B72.3) and one to detect T antigen (monoclonal antibody AH9-16). Except for occasional reactivity with VVA and CU-1, cells of normal colonic mucosa did not express Tn, sialosyl-Tn, or T antigens. However, in the transitional mucosa immediately adjacent to cancer, all three antigens were expressed (ranging from 35 to 67% of cases depending upon the reagent). In colon cancers, the percentage of cases expressing each antigen were as follows: Tn 72-81%, sialosyl-Tn 93-96%, and T 71%. Unlike T antigen, which was preferentially expressed by moderately well- and well-differentiated adenocarcinomas, both Tn and sialosyl-Tn antigens were expressed by most histological subsets of colon cancers, including poorly differentiated adenocarcinomas and mucinous (colloid and signet ring cell type) carcinomas. The majority of cancers expressed both Tn and sialosyl-Tn, usually in association with T antigen. Only one cancer lacked all three antigens. Fetal colonic mucosal cells expressed all three antigens, particularly in goblet cell mucin. These results indicate that like T antigen, Tn and sialosyl-Tn are oncodevelopmental cancer-associated antigens in the colon. Moreover, Tn and sialosyl-Tn antigens appear to be useful markers of poorly differentiated adenocarcinomas and mucinous carcinomas: two histological subsets that often fail to express other cancer-associated antigens and that are often associated with a poor clinical outcome.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Expression of Tn, sialosyl-Tn, and T antigens in human colon cancer. 290 46

Several alterations in carbohydrate antigen expression can occur in colon cancers. Modified structures such as extended LeX and LeY antigens could serve as cancer-associated antigens in the human colon, although none is specific only for colon cancer. Since LeX and LeY antigens are present in fetal tissues, but not in adult normal tissues, these antigens appear to be oncodevelopmental in nature. The expression in colon cancers of extended LeX and LeY antigens with internal fucosylation or terminal sialylation is considered rather cancer-specific since normal colonic mucosa does not express these antigens. Furthermore, these molecules may also be "markers" for premalignancy, since adenomatous polyps, but not hyperplastic polyps are capable of exhibiting these changes and antigenic expression often correlates with malignant potential in adenomatous polyps. The precise biochemical and molecular mechanisms for these alterations in LeX and LeY expression and their biological significance are not well understood at the present time. However, it is likely that the regulation of the glycosyltransferase enzymes responsible for the processes of polylactosamine elongation, fucosylation, and sialylation may be aberrant. Obviously further studies are needed to elucidate these mechanisms. However, it appears that the monoclonal antibodies directed against extended LeX and LeY antigens are a useful adjunct in the diagnosis of colonic neoplasia, and may also be helpful in elucidating the molecular and biochemical mechanisms involved in the adenoma-carcinoma sequence.
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PMID:Carbohydrate antigen expression in the adenoma-carcinoma sequence. 305 24

Advances in the understanding of biochemical and molecular processes associated with cellular growth and differentiation, as well as colonic carcinogenesis hold promise for the development of new diagnostic and therapeutic modalities for this disease. Altered glycosylation of cell surface and secreted glycoconjugates appear to be useful markers in differentiating normal from malignant colonic tissue. New information regarding deletion and inappropriate expression of several blood group-related carbohydrate antigens as well as the synthesis of unique cancer-related carbohydrate structures has been derived from the use of monoclonal antibody technology, and may lead to more sensitive and specific screening tests and targeted therapies. Several glycoprotein markers for colon cancer have been studied whose diagnostic accuracy may surpass the limited sensitivity and specificity of traditional markers such as CEA. Colorectal cancers contain numerous quantitative and qualitative differences in metabolic and synthetic enzyme activities compared with normal colonic mucosa, which may be of potential importance in designing chemotherapeutic regimens or for following disease activity. Other cancer-associated markers, such as increases in orthinine decarboxylase activity and crypt cell labeling reflect abnormal proliferative activity and may be correlated with premalignant states. Studies of protooncogene expression and certain chromosomal deletions will provide insight into mechanisms of carcinogenesis and may also serve to define high-risk individuals. It is likely that as the biochemical and molecular mechanisms underlying malignancy are further delineated, cancer-associated markers will be defined that will improve diagnostic and more importantly, therapeutic efficacy.
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PMID:Biochemical and other markers of colon cancer. 306 43

Mucin has been purified from nude mouse xenografts of SW1990 human pancreatic cancer cells. The mucin was eluted at the void volume of Sepharose CL-4B and was of density greater than 1.3 in CsCl gradients. The isolated mucin had a high content of threonine, serine, and proline, with 31% of the amino acid residues O-glycosylated. The average oligosaccharide composition was NeuAc1.8Fuc0.7Gal2.0GlcNAc1.7GalNAc1.4. Polyclonal rabbit antibodies prepared against the purified mucin recognized primarily mucin polypeptide, and there was extensive immunological cross-reaction between SW1990 pancreatic cancer mucin and LS174T colon cancer mucin. However, using carbohydrate-specific monoclonal antibodies, the two mucins were found to differ. SW1990 mucin had more Lewis, sialyl Lewis, and sialyl Lewis activity, while the colon cancer mucin had more sialyl T antigen. Since pancreatic mucins, whether from normal pancreas or pancreatic cancer, have not previously been well characterized, the availability of SW1990 pancreatic cancer mucin may be useful as a model for studying the expressing of organ-specific or cancer-associated antigens.
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PMID:Pancreatic cancer mucin from xenografts of SW1990 cells: isolation, characterization, and comparison to colon cancer mucin. 322 46

The LewisX (LeX) antigen [characterized by trisaccharide Gal beta 1----4 (Fuc alpha 1----3)N-acetylglucosamine] is an oncodevelopmental antigen in the human colon. Monoclonal antibodies (MoAbs), anti-SSEA-1 and AH8-183, which recognize LeX antigen either on short oligosaccharide side chains or as a terminal immunodeterminant on longer carbohydrate side chains of glycoconjugates, bind to most colon cancer tissues but also to some normal colon mucosae. However, the monoclonal antibodies FH1, FH4, FH6, and IB9, which recognize extended difucosylated and trifucosylated LeX structures or their sialylated derivatives, are more cancer-associated because they rarely bind to normal colon mucosa. In the present study, these MoAbs were used to compare the expression of various LeX-related antigens in premalignant (adenomatous) and nonpremalignant (hyperplastic) colorectal polyps. Antigen expression in polyps was also compared to antigen expressions of normal colon mucosa and colon cancer tissues. The four MoAbs recognizing extended LeX antigens bound to adenomatous polyps (APs) significantly more than to hyperplastic polyps (HPs). In contrast, anti-SSEA-1 and AH8-183 recognizing monofucosyl LeX were less able to distinguish between APs and HPs. In APs, staining with the four MoAbs recognizing extended LeX antigens correlated with the premalignant parameters of larger polyp size, more severe dysplasia, and increased villose component. However, staining with AH8-183 correlated only with polyp size, and anti-SSEA-1 correlated only with polyp size and degree of dysplasia. In general, the staining frequency of HPs was similar to that of normal colon mucosa, although FH6, which did not stain any specimens of normal mucosa, stained a few HPs. The staining frequency of APs was less than that of colon cancer tissues, but these differences were generally not statistically significant. In conclusion, extended LeX antigens and their sialylated derivatives are cancer-associated antigens that are expressed preferentially in premalignant colon polyps, that tend to correlate with malignant potential in these polyps, and that may eventually help to define mechanisms involved in the polyp-to-cancer sequence.
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PMID:Expression of LewisX and sialylated LewisX antigens in human colorectal polyps. 346 62

A detailed retrospective analysis was undertaken of the effect of perioperative blood transfusion on long-term survival of 113 patients with Dukes' Stages A, B and C1 cancer of the colon and 383 patients with invasive cancer of the breast who were treated in our institution between 1973 and 1978 and followed for 5 to 10 years. In the patients with colon cancer, a significant adverse effect of transfusion on long-term survival was seen. In this group there was a cumulative 5-year overall survival of 48% for the transfused and 74% for the nontransfused patients (P = 0.007, log-rank test). Perioperative blood transfusion was associated with a relative risk of 3.42 for all deaths (P = 0.005) and 4.25 for death due to cancer (P = 0.03), after adjustment for other important variables such as age, sex, stage, location of tumor, surgical procedure, and preoperative hemoglobin level. In contrast, in our study group of patients with breast cancers, who all underwent a modified radical mastectomy, no effect of blood transfusion on long-term survival was seen. Multivariate analysis adjusting for size of tumor, number of positive regional lymph nodes, menopausal status, estrogen receptor status and the addition or absence of chemotherapy, did not show any increased risk in all deaths or death due to cancer associated with blood transfusion. Although no definite explanation is available, our data show that there seems to be a difference in the relationship between perioperative blood transfusion and survival for colon and breast cancer patients.
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PMID:Perioperative blood transfusion and cancer prognosis. Different effects of blood transfusion on prognosis of colon and breast cancer patients. 380 42

The binding of fluorescein isothiocyanate (FITC)-conjugated lectins to mucin in the human colon was studied by using fluorescence microscopy. In normal mucosa, lectins that preferentially bind to exposed N-acetyl-galactosamine residues (Dolichos biflorus agglutinin and soybean agglutinin) bound selectively to the goblet cell mucin of well-differentiated cells in the upper colonic crypt. By contrast, lectins that require exposed non-reducing galactose residues for binding (Ricinus communis agglutinin1 and Bauhinia purpurea agglutinin) preferentially labeled the mucin of less-differentiated goblet cells located in the lower portion of the colonic crypt. The lectin derived from Arachis hypogaea (peanut agglutinin) has a high affinity for a carbohydrate structure not normally exposed in human tissues. This lectin did not label the goblet cell mucin in the normal colon. However, the mucin was labeled in all 21 colon cancer specimens examined. Additionally, the nonmalignant epithelium immediately adjacent to colon cancer (termed "transitional mucosa") also contained goblet cell mucin that was labeled by FITC-peanut agglutinin. Three conclusions may be drawn from the selective binding characteristics of FITC-lectins to colonic mucins. First, an alteration in the exposed, nonreducing carbohydrate residues occurs in human colonic mucin during the process of goblet cell differentiation. Second, an exposed carbohydrate structure that is not normally present in human tissues is expressed in the mucin produced by malignant colonic epithelium. Third, the presence of the cancer-associated carbohydrate structure in the mucin of transitional mucosa suggests that this tissue may be in the process of early malignant transformation.
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PMID:Alterations in human colonic mucin occurring with cellular differentiation and malignant transformation. 695 52

By means of the macrophage electrophoretic mobility technique we could show lymphocytes of patients suffering from cancers of the digestive system to be sensitized to carcinoembryonic antigen (CEA). These findings conflict with the common view that CEA is not immunogenic in humans. The aim of the present study was to look as to whether conventional anti-CEA sera can neutralize the activity of a CEA preparation which is responsible for the human lymphocyte response. When 60 ng CEA were preincubated with highly diluted anti-CEA serum and the resulting immune complexes were thereafter co-precipitated by protein A-sepharose, positive lymphocyte responses could no longer be obtained. This effect was observed with 3 anti-CEA sera in 3 cancer patients (colon cancer, stomach cancer, teratocarcinoma), who's lymphocytes responded to CEA by lymphokine release. Normal serum had no neutralizing effect. The anti-CEA sera did not influence the activity of another tumour-relevant extract (teratocarcinoma-derived), to which cancer patients' lymphocytes reacted regardless of the tumour site. The lymphocytes from an oesophagus carcinoma patient, though reacting to the teratocarcinoma preparation, did not respond to CEA, thus, logically, all other tests with normal serum and anti-CEA sera were negative, too. The results show that the digest system cancer-associated lymphocyte reactivity to CEA can be abrogated by conventional anti-CEA sera, which finding indicates that there exist closely CEA-associated "tumour-specific" antigenicities.
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PMID:Sensitization of human lymphocytes to carcinoembryonic antigen (CEA): neutralization experiments with anti-CEA sera. 707 17


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