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

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

We have compared the biodistributions of [131I]B72.3 and 111In-SCN-Bz-DTPA B72.3 monoclonal antibody (MoAb) in patients with metastatic colon cancers. B72.3 is an IgG1 that recognizes a mucin-like colon cancer associated antigen. Eight patients were infused with 3-5 mCi and 0.36-20 mg of 111In-labeled B72.3 prepared with a bifunctional chelate, isothiocyanatobenzyl-DTPA (SCN-Bz-DTPA). The biodistribution was compared with that of 13 patients previously studied as part of a separate trial, with 1-10 mCi and 0.16-1.35 mg of [131I]B72.3. The Beta T1/2 in serum was 63 +/- 5 hr for 111In-SCN-Bz-DTPA B72.3 and 52 +/- 10 hr for [131I]B72.3. Whole-body retention of the 111In (T1/2 = 11.8 days) was significantly longer than for [131I]B72.3 (T1/2 = 3.3 days), p less than 0.000001. The 131I was excreted primarily through the urine. Urinary excretion of 111In was low and gamma camera images confirmed that some 111In was excreted in the bowel. Tumor localization was seen in one of seven evaluable patients receiving 111In-SCN-Bz-DTPA B72.3. Gamma camera images showed that the liver concentrates 111In but not 131I. We conclude that 111In-SCN-Bz-DTPA B72.3 is metabolized in a different manner from the iodinated B72.3. The high concentration and prolonged retention of 111In by the liver interferes with tumor imaging of metastases.
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PMID:Differences in biodistribution of indium-111-and iodine-131-labeled B72.3 monoclonal antibodies in patients with colorectal cancer. 273 61

Mucin from xenografts of LS174T human colon cancer cells was treated with anhydrous HF for 1 h at 0 degree C to give a product (HFA) with over 80% of the glucosamine and hexose removed, but retaining some galactosamine, and for 3 h at room temperature to give a product (HFB) devoid of carbohydrate. Rabbit antibodies against HFA bound to HFA much more than to HFB, and bound to native mucin to an intermediate extent. Antibodies to HFB bound to HFB more than to HFA, and did not bind to native mucin. Both HFA and native mucin bound a number of lectins, but HFB did not. By SDS/polyacrylamide-gel electrophoresis and size-exclusion h.p.l.c., native mucin and HFA are of apparent molecular mass greater than 400 kDa, whereas HFB is heterogeneous and of low molecular mass. On Western blots, antibody to HFA detected both high-molecular-mass mucin and a 90 kDa protein in homogenates of LS174T cells. Antibody to HFB detected a major 70 kDa band as well as higher-molecular-mass species. In tissue sections of normal colon and colon cancers, antibody to HFA showed both cytoplasmic and extracellular staining, whereas antibody to HFB generally stained only cytoplasmic antigens. These results indicate that anti-HFB antibody is specific for apo-mucin, whereas anti-HFA antibody is specific for GalNAc-apo-mucin.
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PMID:Deglycosylation of mucin from LS174T colon cancer cells by hydrogen fluoride treatment. 277 37

Dietary fibers may tend to enhance or inhibit chemically induced experimental colon cancer, depending on the particular fiber consumed. This study examined the relationship between colonic thymidine kinase enzyme activity and mucin histochemistry and the reported effects of various dietary fibers on chemically induced colon carcinogenesis. Fiber-supplemented diets containing fibers reported to inhibit (wheat bran) or enhance (guar gum, carrageenan) chemically induced colon carcinogenesis in the rat were selected. Four groups of male Fischer 344 rats consumed 10% wheat bran, 5% guar gum, 5% carrageenan, or fiber-free diets ad libitum for 4 weeks. At the completion of the treatment period, the distal 12 cm of colonic mucosa was scraped off and homogenized for determination of thymidine kinase activity, and a 0.5-cm section of midcolon was processed by the high-iron diamine/Alcian blue method for mucin histochemistry. Final animal weights did not differ significantly among groups. Thymidine kinase enzyme specific activity (mumole thymidine phosphate formed x 10(6)/min/mg protein, means +/- SEMs) was not significantly different in the fiber-free, wheat bran, and guar gum groups (10.98 +/- 1.50, 7.41 +/- 1.09, and 9.11 +/- 2.04, respectively) but was markedly elevated at 41.84 +/- 4.65 in the carrageenan group (alpha less than 0.001). Mucin histochemistry failed to reveal any significant differences among dietary groups.
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PMID:Alterations in colonic thymidine kinase enzyme activity induced by consumption of various dietary fibers. 284 79

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

The effects of ad libitum feeding of a chemically defined diet in liquid form on the incidence and histology of colon cancer induced by 10 weekly sc injections of 7.4 mg/kg of azoxymethane [(AOM) CAS: 25843-45-2] were investigated in W-rats. The chemically defined diet was adjusted once every 24 hours from 4 weeks before injection of the carcinogen to the end of the experiment at week 40. Oral administration of the defined diet resulted in significant increase in the incidence of colon cancer at week 40. Histologic examination showed that unlike adenocarcinomas with high mucin-producing activity, which were common in rats on pellet diet, most of the adenocarcinomas that developed in rats fed on defined diet were highly or well differentiated, with a typical glandular pattern. Administration of the chemically defined diet also resulted in marked colon mucosal hypoplasia and reduced gastrin levels in the serum at weeks 4 and 40.
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PMID:Effect of a chemically defined diet in liquid form on colon carcinogenesis in rats. 299 35

We have reported a case of microangiopathic hemolytic anemia and metastatic carcinoma of the colon in a 38-year-old woman. Despite the mucin content and the high incidence of carcinoma of the colon in western populations, there are only four cases of colon cancer among the 77 reported cases of malignancy-associated MHA.
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PMID:Microangiopathic hemolytic anemia associated with metastatic carcinoma of the colon. 305 37

Differences in colonic secretory glycoconjugates (ie, mucin) between normal and ulcerative colitis-prone patients have been noted. Similar differences may occur in a corresponding primate model, the cotton-top tamarin (CTT), Saguinus oedipus, a New World monkey which suffers from spontaneous chronic colitis and colon cancer. Lectin reagents were used to characterize and compare colonic cell surface, cytoplasmic, and secretory glycoconjugates of 9 clinically healthy cotton-top tamarins, 7 colitis-susceptible, cancer-resistant tamarins (Callithrix jacchus, Saguinus fuscicollis), and 8 colitis and cancer-resistant primates (Aotus trivirgatus, Saimiri sciureus, Macaca fascicularis, and Macaca mulatta). Paraffin-embedded colonic sections were labeled with ten different biotinylated lectins and visualized by the avidin-biotin peroxidase (ABC) method. Significant differences were demonstrated in the pattern of lectin staining between the colitis-resistant and colitis-prone groups of primates. The differences were noted with Griffonia simplicifolia-I (GS-I), Dolichos biflorus agglutinin (DBA), peanut agglutinin (PNA) before and after neuraminidase, Ricinus communis agglutinin-I (RCA-I), soybean agglutinin (SBA), Ulex europaeus agglutinin-I (UEA-I), wheat germ agglutinin (WGA), and succinylated WGA (S-WGA). Significant differences between the CTT and phylogenetically related colitis-prone but cancer-resistant tamarins were demonstrated with SBA, UEA-I, and PNA after desialylation with neuraminidase. These results suggest that differences in colonic cellular glycoconjugates between colitis- and cancer-susceptible species versus colitis-susceptible, cancer-resistant species may be associated with risk of cancer.
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PMID:Characterization of colonic cellular glycoconjugates in colitis and cancer-prone tamarins versus colitis and cancer-resistant primates. 313 57

We have developed a novel method for quantitation of lectin binding sites in mucins derived from colon tissues. Binding of peanut agglutinin and wheat germ agglutinin was measured in extracts from normal and malignant human colon epithelium. Binding of wheat germ agglutinin was used as an estimate of the total mucin present in the tissue extract. Peanut agglutinin was found to bind to mucin from normal colon, but at levels that may be difficult to appreciate by fluorescence microscopy. The yield of mucin extracted from colon cancer was more variable than that from normal colon, and the binding ratio of peanut agglutinin to wheat germ agglutinin was greater in extracts from tumors than in normal tissues. Our findings confirm the histological observation that peanut agglutinin binds more avidly to mucins from colon cancer than to those from normal colon. The finding of peanut agglutinin binding sites in mucins front normal colon was not expected. The quantitative technique may have detected small numbers of binding sites not readily appreciable by fluorescence microscopy. Alternatively, the chromatographic method for measuring lectin binding may be sufficiently sensitive to detect nonspecific binding of the lectin to terminal galactose residues other than the Thomsen-Friedenreich antigen.
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PMID:Quantitation of lectin binding sites in human colon mucins by use of peanut and wheat germ agglutinins. 313 7

The structure of colonic mucin, which is thought to be important in several diseases, including ulcerative colitis and colon cancer, is poorly understood. Mucin was isolated from nude mouse xenografts of the LS174T colonic adenocarcinoma cell line by gel filtration and CsCl density gradient centrifugation. The isolated mucin had a high content of threonine, serine, and proline, with 28% of the total amino acids O-glycosylated. The carbohydrates present were fucose, sialic acid, galactose, N-acetyl-glucosamine, and N-acetyl-galactosamine in the ratio of 0.4:1.5:1.0:0.9:1.4. Rabbit antibodies were prepared that recognized primarily protein-dependent determinants. By DEAE-cellulose chromatography, the purified mucin was found to be heterogeneous, with three major components that had small differences in carbohydrate composition. LS174T was antigenically and chromatographically similar to mucins in colon cancer tissue specimens and in nonmalignant colonic mucosae.
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PMID:Isolation and characterization of colon cancer mucin from xenografts of LS174T cells. 318 78


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