Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mucinous colorectal cancer often presents at an advanced stage. We have previously observed that mucin production by human colon-cancer cells correlates with their ability to colonize the liver in experimental animal models. The present study was undertaken in order to further elucidate the mechanisms by which production of mucin by colon-cancer cells affects metastasis. Cell lines showing high mucin production (HMP) (HM 7, HM 3 and LS LiM 6) demonstrated increased adherence to basement membrane proteins and invaded a reconstituted basement membrane to a greater extent than their counter-part cell lines showing low mucin production (LMP) (LS174T and LM 12). Adherence of the LMP parental cell line LS174T to various matrix proteins was potentiated by the addition of purified human colon-cancer mucin in a dose-dependent fashion. HMP cell lines secreted more proteolytically active type-IV collagenase than LMP lines, and collagenase activity was further stimulated by purified mucin in a dose-dependent manner. Specific inhibition of mucin O-glycosylation by benzyl-alpha-N-acetylgalactosamine significantly affected each of the metastasis-related events, with the greatest effect on the HMP cell lines. The present data further indicate that mucin may play an important role in the metastatic process.
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PMID:The role of mucin in colon-cancer metastasis. 132 40

The enzyme D-galactose oxidase (GO) oxidizes the carbon-6 position of the hydroxyl groups of galactose-N-acetyl galactosamine, which are commonly present in colon cancer cells and in rectal mucin of patients with colon cancer. We have studied the marker disaccharide galactose and N-acetylgalactosamine on tissue sections by the GO-Schiff reagent in normal, preneoplastic, and neoplastic human colorectal epithelial and compared it with peanut agglutinin reactivity. Fifty-seven (81.4%) of 70 carcinomas, 83.3% (10/12) of precancerous lesions, 50% (10/20) of the mucosa remote from cancer, and 58.1% (25/43) of the mucosa immediately adjacent to cancer showed a positive reaction with GO-Schiff, but the normal control mucosa was nonreactive. The GO-Schiff reagent showed an intense reactivity with mucinous adenocarcinomas and poorly differentiated adenocarcinomas. An intense reactivity was also seen in the intracellular mucus of abnormal dilated crypts (polyps, five of five cases; colitis, four of seven cases; and remote mucosa, 10 of 20 cases). Comparison of peanut agglutinin and GO-Schiff reactivity showed that the nonmucinous (glandular) adenocarcinomas less frequently reacted with the GO-Schiff sequence. Our results showed that the carbohydrate moiety detected by the two techniques may not necessarily be the same, warranting further biochemical analysis. Meanwhile, the data suggested that, like peanut agglutinin, the GO-Schiff sequence has the potential to identify the tumor marker either at the tissue level or by a mucin test for screening colorectal cancer or precancer.
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PMID:Detection of the tumor marker D-galactose-beta-(1-->3)-N-acetyl-D-galactosamine in colonic cancer and precancer. 133 46

In a previous work we found that human colorectal cancer tissues express increased levels of an alpha 2,6 sialyltransferase (alpha 2,6 ST) acting on N-acetyllactosaminic sequences (E.C. 2.4.99.1). In this study we have taken advantage of the known specificity of elderberry bark lectin (Sambucus nigra agglutinin, SNA) for NeuAc alpha 2, 6Gal/GalNAc structures to investigate the relationship between expression of alpha 2,6 sialyltransferase activity and occurrence of alpha 2,6-sialylated oligosaccharide sequences in human colorectal cancer cell lines. Three cell lines with opposite adhesion properties were used in this study: SW 948 cells grow adherent to the culture flask surface and express very low levels of enzyme activity; COLO 205 cells grow in non-adherent form and express the highest levels of alpha 2,6 ST activity; A non-adherent subline of SW 948 cells (SW 948 FL) was isolated and found to express high levels of alpha 2,6 ST activity. By using SNA-Sepharose chromatography we found that expression of alpha 2,6 ST activity correlates with the extent of alpha 2,6-sialylation of N-linked chains of glycoproteins but not with the presence of alpha 2,6-sialylated glycolipids.
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PMID:Alpha 2,6 sialylation of N-acetyllactosaminic sequences in human colorectal cancer cell lines. Relationship with non-adherent growth. 189 84

Biotinylated neoglycoproteins are useful to determine the expression of sugar receptors (lectins) histochemically in routinely processed tissue sections. Assessment of the presence of distinct receptor classes with specificity to beta-galactosides and to alpha- or beta-N-acetylgalactosamine, selected on the basis of their potential relevance for recognition processes within the metastatic cascade in murine model systems, was performed for a common human tumour type, colorectal cancer. The four different types of neoglycoproteins, derived from covalent attachment of commercially available derivatives of beta-N-acetylgalactosamine, differed only quantitatively in their capacity to detect specific binding on cultured cells and tissue sections, thus posing no major restriction on the choice of synthetic process for histochemical efficiency of the product. Glycocytological application revealed specific probe binding and a regulation of level of receptor expression for a human colon carcinoma cell line primarily for N-acetylgalactosamine-specific receptors upon retinoic acid-induced differentiation. Monitoring of sections of the 12 cases of primary and secondary colorectal lesions invariably disclosed the presence of the respective receptors, the extent of cell labelling in primary tumours and metastases being similar. Establishment of metastases, even in different target organs, is apparently not followed by a major phenotypic variation in this feature.
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PMID:Neoglycoprotein binding to colorectal tumour cells: comparison between primary and secondary lesions. 192 62

Galactosyltransferases (GTs) are one of the members of a family of enzymes called glycosyltransferases involved in the biosynthesis of complex carbohydrates. These enzymes catalyze the transfer of galactose from UDP-galactose to an acceptor (glycoprotein, glycolipid) containing terminal N-acetylglucosamine or N-acetylgalactosamine residue. GTs occur in soluble (milk, serum, effusions, etc.) and insoluble (membrane) forms. The GT activities on the outer surface of the cells have been correlated with a host of cellular interactions, including fertilization, cell migration, embryonic induction, chondrogenesis, contact inhibition of growth, cell adhesion, hemostasis, intestinal cell differentiation, and immune recognition. GTs have been purified to homogeneity using affinity chromatography. Most GTs are found active in the pH range 6 to 8 and at temperatures between 35 to 40 degrees C. Manganese is an essential co-factor for GT activity. Isoenzymes of GT have been recognized, especially in tumor tissues, malignant effusions, and sera of cancer patients using polyacrylamide gel electrophoresis in the presence and absence of SDS. Depending on the source of the enzyme, the molecular weights of GTs range between 40,000 to 80,000 daltons. Carcinoma-associated GT isoenzyme has been reported to have a higher molecular weight than the normal GT isoenzyme. Development of monoclonal antibody against the cancer-specific GT isoenzyme will provide help in the development of an immunoassay for the measurement of this isoenzyme in the sera and an aid in the radioimmunolocalization of the tumors in cancer patients.
CRC Crit Rev Biochem 1985
PMID:Galactosyltransferases: physical, chemical, and biological aspects. 392 3

The simple carbohydrate tumor marker D-galactose-beta-[1-->3]-N-acetyl-D-galactosamine (Gal-GalNAc) can be easily identified by a sequential galactose oxidase (GO)-Schiff reaction either on tissues or on rectal mucus samples from patients with colorectal cancer. To check the usefulness of this marker and technology in identifying cancers and precancers of other organs, we have assessed the differential expression of Gal-GalNAc in various adenocarcinomas and their corresponding normal tissues. The expression of Gal-GalNAc determined by GO-Schiff sequence was examined in a total of 133 tissue samples from 81 cases of the adenocarcinomas of the breast, ovary, pancreas, stomach, and endometrium and 52 cases of respective normal controls. None of the 52 cases of normal tissues (except 15 cases of stomach) showed expression of Gal-GalNAc. In contrast, 100% of adenocarcinomas from the breast (19 of 19), ovary (15 of 15), and pancreas (6 of 6), 94.1% of stomach (16 of 17) cancers, and 91.7% (11 of 12) of uterine adenocarcinomas expressed Gal-GalNAc. The expression of Gal-GalNAc in cancerous tissues was mostly strong and widespread and was distributed in both secreted mucin and cytoplasmic mucin droplets. The normal epithelia and their secretions in the vicinity of the carcinoma (within the "field") in the breast, bronchus, endometrium, and pancreatic duct also expressed Gal-GalNAc in contrast to normal tissues obtained from noncancerous individuals, which were totally nonreactive. It is concluded that the tumor marker Gal-GalNAc recognized by GO-Schiff sequence was highly expressed not only by a variety of adenocarcinomas but also by the apparently normal-appearing epithelia and their secretions in the vicinity of carcinomas, strongly suggesting a field effect phenomenon of carcinogenic agent(s). Identification of the marker in these secretions may have great potential in our strategies for mass screening for those cancers.
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PMID:Common expression of the tumor marker D-galactose-beta-[1-->3]-N-acetyl-D-galactosamine by different adenocarcinomas: evidence of field effect phenomenon. 780 25

Dolichos biflorus agglutinin (DBA) binds specifically to N-acetylgalactosamine (GalNAc), one of the 5 sugars contributing to the oligosaccharide component of human colorectal goblet cell mucin. DBA binds to goblet cells of the upper crypt and surface epithelium within the proximal colon and to the majority of goblet cells of the distal large bowel. DBA therefore serves as a marker of colorectal goblet cell differentiation with a distinct proximal to distal gradient effect. Previous reports indicate significant loss of DBA reactivity within morphologically normal colorectal mucosa derived from at-risk members of hereditary non-polyposis colorectal cancer (HNPCC) families. This finding could not be confirmed in the present study. Reduced binding was a relatively consistent finding in transitional mucosa, hyperplastic polyps and carcinoma, with adenomas displaying a more varied pattern of loss. Reduced binding by DBA may be explained by several mechanisms and may not necessarily reflect loss of GalNAc. The concept that lectins can be used to identify stepwise changes that occur during neoplastic evolution should not be accepted uncritically.
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PMID:Dolichos biflorus agglutinin binding in hereditary bowel cancer. 809 May 79

A synthetic peptide corresponding to the human MUC2 tandem repeat domain containing 14 Thr residues was glycosylated in vitro using UDP-GalNAc and microsomal membranes of the colorectal cancer cell line, LS180. The products were fractionated by reverse phase HPLC, which gave seven glycopeptide fractions. Their molecular weights were estimated by matrix-assisted laser desorption/ionization mass spectrometry, the values obtained corresponding to glycopeptides containing from one to ten GalNAc residues. On solid phase radioimmunoassaying involving a monoclonal anti-Tn antibody (MLS128), it was found that the glycopeptides containing nine or ten GalNAc residues were strongly immunoreactive, whereas the glycopeptides containing less than six GalNAc residues were inactive, indicating that a cluster of GalNAc-Thr is essential for the Tn antigenicity.
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PMID:Glycosylation of the tandem repeat unit of the MUC2 polypeptide leading to the synthesis of the Tn antigen. 953 76

Uridine diphosphate (UDP)-GalNAc: polypeptide N-acetylgalactosaminyltransferase (GalNAc transferase) catalyzes the initial step in mucin type O-glycosylation, and its expression has been assumed to be altered between normal epithelial cells and cancer cells. We studied the alteration of GalNAc transferase expression during the carcinogenesis of human colorectal epithelial cells. We produced polyclonal antibodies against synthetic polypeptides with specific sequence to two GalNAc transferase isozymes, T1 and T2. Surgically resected specimens from 50 patients with colorectal cancer were immunohistochemically stained, and the staining grade (percentage of positively stained cells) was compared between cancer and its normal counterpart in the same specimen. Significant signals for both T1 and T2 expression were seen in the supranuclear region of normal and cancer cells, indicating the subcellular localization of the enzymes in the Golgi apparatus. The prevalence of positive staining for T1 and T2 expression in colorectal cancer was significantly higher than that in normal epithelium (P < 0.05). However, the difference in staining grades between cancer and normal tissues varied in each patient. These results indicate that there is variability in the expression patterns of GalNAc transferase isozymes in normal and cancerous cells colorectal among individuals.
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PMID:Expression of UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase isozymes T1 and T2 in human colorectal cancer. 1108 93

We have previously shown that the normal adult colon produces a sialomucin containing the core trisaccharide 1,3 N-acetylgalactosamine. This structure was shown to be the epitope for a polyclonal antiserum that demonstrated colon "specific" activity. Antiserum binding is dependent upon the presence of O-acetylated sialic acids present at high concentrations in normal adult colon tissue. However, O-acetylation of sialic acids is decreased in colorectal cancer. Indeed, approximately 50% of colorectal carcinomas are nonreactive with this antiserum. In the current work, we used a de-O-acetylated, normal colon mucin as immunogen to generate monoclonal antibody (MAb) G47. Untreated normal colon mucins having a high O-acetylated sialic acid content were essentially nonreactive with G47. Removal of O-acetyl groups by saponification generated a reactive mucin derivative while subsequent treatment with neuraminidase abolished reactivity. By immunoperoxidase procedures MAb-G47 was reactive with approximately 85% of colorectal tumors while exhibiting relatively low reactivity with normal colon tissue. Mucins isolated from normal colon had on average less than 10% of the specific epitope as compared with mucins derived from colorectal tumors (p < 0.01). Initial immunohistochemical studies on tumors of noncolonic origin revealed few positive cases. The potential of MAb-G47 to assist in the diagnosis and/or prognosis of colorectal cancer is now being studied.
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PMID:Monoclonal antibody G47 engineered to be reactive with colorectal tumor mucin. 1183 52


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