concanavalin-a and Rectal-Neoplasms

Expression of decay-accelerating factor (DAF, CD55), a complement-regulatory glycoprotein, is enhanced in colorectal-cancer (CC) cells and colonic epithelium in ulcerative colitis (UC), and stools from these patients contain increased amounts of DAF. Carbohydrate chains of glycoproteins are often altered during malignant transformation or inflammation. In this study, we investigated whether DAF molecules in patients with CC and those with UC differ with respect to oligosaccharide side chains. We analyzed DAF in stools and homogenates of colonic-tissue specimens obtained from patients with CC or UC using solid-phase enzyme-linked assay and Western blotting for reactivity with the lectins Ulex europaeus agglutinin I (UEA-I), wheat-germ agglutinin, peanut agglutinin, and concanavalin A. UEA-I bound to DAF in stools from patients with UC but not in that from the stools of CC patients, as demonstrated on the solid-phase enzyme-linked assay (P <.05, Mann-Whitney U test) and Western blotting. Binding of UEA-I was specifically inhibited by the addition of fucose. The difference in UEA-I reactivity with DAF was observed also in colonic-tissue homogenates from patients with UC and those with CC. DAF expressed in the mucosa and excreted into the stools of UC patients is different from that expressed in CC with regard to UEA-I reactivity. Future studies should be directed toward determining whether a qualitatively unique isoform of DAF is present, of which sugar chains are specific to CC in UC patients.

Topics: Adenocarcinoma; Adult; Aged; CD55 Antigens; Colitis, Ulcerative; Colon; Colonic Neoplasms; Colorectal Neoplasms; Concanavalin A; Feces; Female; Humans; Intestinal Mucosa; Kinetics; Lectins; Male; Middle Aged; Neoplasm Staging; Plant Lectins; Rectal Neoplasms

We studied mucin histochemistry in 25 rectosigmoid adenocarcinomas and in the transitional mucosa adjacent to these tumors using standard techniques for the detection of neutral and acid sialomucins and sulfomucins and the paradoxical concanavalin A (Con A) stain. This histochemical procedure selectively detects residues of mannose in glycoproteins exposed to brief steps of oxidation and reduction. Those techniques were also used to study histologically normal mucosa of specimens with carcinoma, normal rectosigmoid mucosa of patients without inflammatory or neoplastic bowel disease, hyperplastic rectal polyps, and rectosigmoid mucosa of human fetuses. Normal mucosa and hyperplastic polyps mainly contained sulfomucins and did not display Con A binding activity with any of the variants of the stain. In contrast, fetal, transitional, and malignant mucosa predominantly showed sialomucins and although not reactive with the standard Con A sequence, displayed binding activity for the lectin after short oxidative-reductive steps. These results provide further evidence that transitional and malignant mucosa produce markedly abnormal mucins whose histochemical patterns represent a re-emergence of the fetal type found during development. The principles of the paradoxic Con A reaction may be applied to unmask lectin binding activity in apparently unreactive sites.

Topics: Adenocarcinoma; Aged; Binding Sites; Concanavalin A; Female; Fetus; Humans; Male; Middle Aged; Mucous Membrane; Pregnancy; Rectal Neoplasms; Rectum; Sigmoid Neoplasms

The expression of six lectins (Arachis hypogaea, B. simplicifolia I, concanavalin A, Dolichus biflorus, Triticum vulgaris, Lotus tetragonolobus) was studied in 24 adenocarcinomas, 24 adenomas, 20 metaplastic polyps, 17 specimens of mucosal prolapse (solitary ulcer syndrome) and 10 of normal mucosa, all taken from the rectum. Qualitative, quantitative and distributive differences in lectin expression were observed between adenocarcinoma and normal mucosa. These cancer-associated glycoprotein alterations were also observed, though to a lesser extent, in benign neoplastic and non-neoplastic lesions of the rectum. It appears therefore that the glycoprotein modifications associated with malignant transformation are not specific indicators of malignancy. It is suggested that the common denominator is a disturbance in the activities of enzymes, particularly the glycosyl-transferases and glycosidases, involved in the biosynthesis of glycoprotein. This disturbance can occur in situations where cells are less differentiated either through developmental immaturity, rapid cellular division or neoplastic de-differentiation. These changes are therefore more likely to reflect the state of differentiation rather than the malignant nature of the cells. It is shown that the greater the deviation of the lesion from normal the greater the glycoprotein alterations. The potential usefulness of lectin expressions as predictive indicators of biological behaviour of adenocarcinomas of the large bowel needs further studies.

Topics: Adenocarcinoma; Adenoma; Arachis; Concanavalin A; Histocytochemistry; Humans; Intestinal Mucosa; Lectins; Plant Lectins; Polyps; Rectal Neoplasms; Rectum; Triticum

The nature of the inhibitory activity of sera of patients with metastatic cancer on in vitro immunoassays remains unclear. Serum glycoprotein levels in cancer patients show a reasonable correlation with the clinical status, especially with progressive metastatic disease. Glycoproteins like acute phase reactants have been connected with immunosuppressive activity in cancer patients' sera. In this study, we examined the influence of glycoprotein fractions of normal and cancer sera, separated by Con A immunoadsorption, on the mixed lymphocyte culture as a reference system for suppressive activity. Glycoprotein rich fractions with the utmost recovery of the acute phase reactants inhibited the mixed lymphocyte culture in a dose-dependent manner. This effect was more pronounced in patients sera as compared to control sera. But there is evidence of additional blocking activity in the glycoprotein poor serum fraction, indicating blocking factors still to be identified.

Topics: Blood Proteins; Breast Neoplasms; Chromatography, Affinity; Colonic Neoplasms; Concanavalin A; Dose-Response Relationship, Immunologic; Electrophoresis, Polyacrylamide Gel; Glycoproteins; Humans; Immune Tolerance; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Neoplasm Proteins; Neoplasms; Rectal Neoplasms; Suppressor Factors, Immunologic

Two variants of gamma-glutamyltransferase were demonstrated in colorectal carcinomas. When compared to the enzyme in normal large bowel mucosa, one of the variants showed reduced affinity to concanavalin A and considerable charge heterogeneity largely due to variable sialic acid content. The other variant appeared to be an asialo form with no affinity to concanavalin A. The two novel forms were of identical size and antigenicity compared to the normal enzyme. They might therefore reflect different post-translational modifications of the carbohydrate moiety of the enzyme.

Topics: Aged; Chromatography, Affinity; Colonic Neoplasms; Concanavalin A; Electrophoresis; Epitopes; Female; gamma-Glutamyltransferase; Genetic Variation; Humans; Male; Middle Aged; Rectal Neoplasms

The present study confirms previous observations that in vitro T lymphocyte proliferative response to mitogens is depressed in only some untreated patients with advanced or metastatic breast and colorectal cancer. Indomethacin, a prostaglandin synthetase inhibitor, at 1.0 microgram or 0.1 microgram/ml concentration significantly enhances the PHA, Con A or PWM response in these patients with breast and colorectal cancer (P less than 0.05 - P less than 0.01). Indomethacin has no mitogenic activity. Ethyl alcohol (0.01%), in which indomethacin is dissolved, also has no mitogenic or cytotoxic activity. Although the in vitro effect of indomethacin has been well-demonstrated, the in vivo effect of this agent on cell-mediated immunity in man has not yet been thoroughly investigated and thus, further studies of the effect of indomethacin administration on in vivo and in vitro cellular immunity seem warranted.

Topics: Adult; Aged; Breast Neoplasms; Colonic Neoplasms; Concanavalin A; Ethanol; Female; Humans; Indomethacin; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; Rectal Neoplasms; Stimulation, Chemical; T-Lymphocytes

In the present study we have evaluated monocyte phagocytosis and T lymphocyte in vitro reactivity to mitogens in peripheral blood samples from 14 colorectal cancer patients, from 21 nonneoplastic control patients, and from 22 normal donors. Monocyte and lymphocyte functions were tested before and 1 and 6 months after surgery. Our results indicate the existence of increased monocyte phagocytosis and decreased mitogen reactivity in untreated patients with advanced tumors. These abnormal responses persisted and were even more pronounced after surgery and chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Colonic Neoplasms; Concanavalin A; Female; Humans; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Monocytes; Phagocytosis; Phytohemagglutinins; Rectal Neoplasms; Rosette Formation

The histochemistry of mucin in normal large intestine and in experimental colorectal cancers induced in Wistar rats with 1,2-dimethylhydrazine was analyzed by modifications of the concanavalin A-horseradish peroxidase method (paradoxical concanavalin A-staining) and high-iron diamine-Alcian blue (pH 2.5) staining (HID-AB). Quantitative analysis of each mucin reaction was done by the use of an image analyzer. Regional variations in the percentage area of "labile class III mucin" were 1 to 50% in the distal colon and 50 to 90% in the proximal colon. Regional variations in the percentage area of sulfated sialomucin were 80 approximately 100% in the distal colon and under 20% in the proximal colon. The percentage area of "labile class III mucin" in primary colorectal cancers showed region-specific variation and that in metastatic colorectal cancers also showed similar region-specific variation of colorectal mucosa where primary tumors were located. In contrast, there were no region-specific mucin reactions for sulfated sialomucin in almost all primary and metastatic colorectal cancers.

Topics: 1,2-Dimethylhydrazine; Animals; Colon; Colonic Neoplasms; Concanavalin A; Dimethylhydrazines; Epithelium; Histocytochemistry; Intestinal Mucosa; Male; Mucins; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Rectal Neoplasms

Lamina proprial lymphocytes (LPL), isolated by an EDTA-collagenase technique from patients with various colonic diseases, were investigated for LMIF release in vitro. On stimulation with the preparation of Kunin antigen, macrophage-depleted LPL from patients with severely or moderately active ulcerative colitis showed LMIF release which was significantly greater than that observed using LPL from patients with mild colitis or from those with other diseases of the large bowel, including Crohn's disease. Results similar to those obtained with LPL were found with the corresponding peripheral blood lymphocytes (PBL) stimulated by the preparation of Kunin antigen. In contrast, nonspecific stimulation in vitro with Concanavalin A showed no differences in LMIF releases by the LPL or PBL in the various disease groups. It is suggested that hypersensitivity to Kunin antigen may have pathogenic significance in ulcerative colitis.

Topics: Adolescent; Adult; Aged; Appendicitis; Colitis, Ulcerative; Colonic Diseases; Colonic Neoplasms; Concanavalin A; Crohn Disease; Edetic Acid; Female; Humans; Intestinal Mucosa; Leukocyte Migration-Inhibitory Factors; Lymphocytes; Lymphokines; Male; Microbial Collagenase; Middle Aged; Rectal Neoplasms; Rectal Prolapse

Topics: Adenocarcinoma; Aged; Cell Adhesion; Colonic Neoplasms; Concanavalin A; Cytotoxicity, Immunologic; Female; Humans; Male; Middle Aged; Phytohemagglutinins; Rectal Neoplasms; T-Lymphocytes

The use of Con A-Sepharose affinity chromatography for preparation of CEA from two metastatic liver tumors resulted in a separation of two species of CEA. One is concanavalin A-reactive CEA (CEA-M): the other is Con A-nonreactive CEA (CEA-P). Both CEA-M and CEA-P were glycoproteins and have identical antigenicity. However, 4 samples of CEA-M and CEA-P subfractions differed in their protein:carbohydrate ratios. The yield of CEA-M was greater than that of CEA-P. In electrophoresis, both CEA-M and CEA-P migrated at the region of beta-globulin of human blood serum. The isoelectric points of 4 samples of CEA-M and CEA-P subfractions from two different tumor sources differed from each other. In these preparations CEA-M usually showed a larger value of isoelectric point than CEA-P. Ultracentrifugal analysis of these four preparations revealed only a single peak, except CEA-P in case 1. Antigenic activity of CEA-M was almost completely destroyed by beta-N-acetylhexosaminidase treatment but only partly digestion with pronase. A possibility was suggested that N-acetylglucosamine at nonreducing terminal(s) is essential for the antigenic determinant groups of CEA molecule.

Topics: Binding Sites; Carbohydrates; Carcinoembryonic Antigen; Chromatography, Affinity; Concanavalin A; Hexosamines; Humans; Immunodiffusion; Immunoelectrophoresis; Liver Neoplasms; Molecular Weight; Neoplasm Metastasis; Pancreatic Neoplasms; Protein Binding; Rectal Neoplasms

Monosaccharide compositions of Con A-reactive CEA (CEA-M) and Con A-nonreactive CEA (CEA-P) separated from two different samples of CEA were analysed by gas liquid chromatography. It was revealed that all CEA subfractions possessed N-acetylglucosamine, fucose, and galactose residues. One out of 4 subfractions did not contain sialic acid and another one lacked glucose in its carbohydrate moiety. N-acetylgalactosamine was not detected in measurable amount in any of the 4 subfractions. A large amount of mannose was found in CEA-M, but only a small amount in CEA-P.

Topics: Acetylgalactosamine; Acetylglucosamine; Binding Sites; Carcinoembryonic Antigen; Chromatography, Affinity; Concanavalin A; Fucose; Galactose; Glucosamine; Humans; Liver Neoplasms; Mannose; Neoplasm Metastasis; Pancreatic Neoplasms; Protein Binding; Rectal Neoplasms; Sialic Acids