concanavalin-a and Intestinal-Neoplasms

Topics: Adenylyl Cyclases; Biological Transport; Carbon Radioisotopes; Cell Differentiation; Cell Membrane; Concanavalin A; Dipeptidases; Disaccharidases; Glucose; Glucosyltransferases; Glycoproteins; Hexoses; Humans; Intestinal Mucosa; Intestinal Neoplasms; Mitosis; Surface Properties; Transferases; Tritium

Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme activity have shown chemopreventive activity in carcinogen-induced and transgenic rodent tumor models and clinically for colon cancer. However, the mechanism(s) by which COX-2 inhibitors reduce carcinogenesis remains controversial. We report herein that administration of the selective COX-2 inhibitor, celecoxib, significantly reduces the number of Gr1(+)CD11b(+) immature myeloid suppressor cells (IMSCs) during chemoprevention of 1,2-dimethylhydrazine diHCl-(1,2-DMH-) induction of large intestinal tumors in Swiss mice. Celecoxib administration also increased splenic lymphatic number and tumor infiltration by lymphocytes. The 1,2-DMH induction of large intestinal tumors was associated with a four-fold increase in IMSCs, and a decrease in splenic T cell number and function. Concordant with the changes in the IMSC frequency, messenger ribonucleic acid (mRNA) levels of inducible nitric oxide synthase (NOS-2) and arginase (Arg) were increased in the spleen of the tumor-bearing mice and normalized by celecoxib administration. In addition to delaying tumor induction, reducing tumor number, and increasing lymphocyte infiltration of tumors, celecoxib therapy reversed CD4(+) T cell loss, decreased IMSC numbers and increased mRNA levels of NOS-2 and Arg in the spleen. In summary, our results suggest that celecoxib chemoprevention of autochthonous intestinal tumors can regulate IMSCs and CD4(+) T cell numbers.

Topics: 1,2-Dimethylhydrazine; Adjuvants, Immunologic; Animals; Anticarcinogenic Agents; Arginase; Breast Neoplasms; Carcinogens; CD4-Positive T-Lymphocytes; Celecoxib; Cell Proliferation; Concanavalin A; Cyclooxygenase 2 Inhibitors; Female; Intestinal Neoplasms; Membrane Proteins; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Nitric Oxide Synthase Type II; Pyrazoles; RNA, Messenger; Spleen; Sulfonamides

Germ-free C57BL/6 x 129 interferon-gamma knockout (IFN-gamma(-/-)) mice and their immunocompetent (+/-, +/+) counterparts were colonized with a pure culture of Candida albicans to assess their natural susceptibility to mucosal and systemic candidiasis of endogenous origin. Colonization with a pure culture of C. albicans was not lethal for adult or neonatal IFN-gamma(-/-) gnotobiotic mice over the 15-week study. The IFN-gamma(-/-) mice were more susceptible to gastric (cardia-antrum section), anorectal, and acute systemic (intravenous challenge) candidiasis than immunocompetent controls, and some IFN-gamma(-/-) mice developed intestinal adenomas after colonization with C. albicans. The enhanced susceptibility of IFN-gamma(-/-) mice, compared with immunocompetent controls, may be associated with a poor proliferative response of spleen cells to C. albicans antigens and a T helper 2 (IgG1) serum antibody response to C. albicans antigens. Thus, IFN-gamma is important for murine resistance to gastric, anorectal, and acute systemic candidiasis.

Topics: Adenoma; Administration, Oral; Animals; Antibodies, Fungal; Candidiasis; Cell Division; Concanavalin A; Disease Models, Animal; Disease Susceptibility; Female; Genotype; Germ-Free Life; Interferon-gamma; Intestinal Neoplasms; Lipopolysaccharides; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitogens

This study analyzed the structural differences of the carbohydrate chains of circulating free alpha-submit (alpha-SU) hypersecreted in various non-tumoral (primary hypothyroids, postmenopausal women, patients with chronic uremia, normal fetuses) and tumoral (gut carcinoids, TSH-, GH- and pure alpha-secreting pituitary adenomas) clinical conditions. Carbohydrate structures of free alpha-SU were investigated by means of lectin affinity chromatography using Concanavalin A (Con-A), which allows the separation of free alpha-SU in three different fractions (unbound = UB, weakly bound = WB and firmly bound = FB) depending on the nature and maturation of glycosylated chains. The concentrations of alpha-SU in serum and in Con-A fractions were measured by a sensitive and specific IRMA. Free alpha-SU hypersecreted from postmenopausal women, primary hypothyroids, and patients with chronic uremia showed similar binding patterns to Con-A, the percentage of UB fractions (UB: 44.5 +/- 1.9%, 39.5 +/- 3.8%, 48.2 +/- 5.6% respectively) being higher than both WB and FB fractions (WB: 33.2 +/- 1.4%, 30.7 +/- 4.6%, 28.5 +/- 2.1%; FB: 22.3 +/- 0.7%, 29.8 +/- 6.6%, 23.3 +/- 4.2% respectively). In normal fetuses the amount of UB fraction was very high (UB: 70.7 +/- 5.4%). Free alpha-SU from patients with TSH- and GH-secreting adenomas showed a binding pattern to Con-A significantly different from that observed in postmenopausal women taken as controls, the WB fractions being significantly higher (WB: 56.9 +/- 16.8% and 71 +/- 12.4% respectively, P < 0.001). A typical pattern of elution on Con-A, characterized by a prevalence of immature alpha-SU molecules eluted in the FB fraction, was found in patients with pure alpha-secreting adenomas. This chromatographic behavior was significantly different from that seen in the controls, as well as in other pituitary tumors and in gut carcinoids (FB: 41.8 +/- 5.0%, 22.3 +/- 0.7%, 16.8 +/- 6.6%, 10.6 +/- 2.0% respectively). Moreover, in these latter patients the pattern of free alpha-SU binding was exactly the opposite of that observed in pure alpha-secreting adenomas, with a prevalence of mature alpha-SU molecules (UB: 59.1 +/- 4.4 vs 18.3 +/- 7.2%). In conclusion, our data on Con-A affinity chromatography clearly demonstrate that carbohydrate branching of circulating free alpha-SU varies in patients with pituitary adenomas as compared with patients with gut carcinoids or other non-tumoral conditions. Moreover, the finding of a greater prop

Topics: Adenoma; Adult; Carcinoid Tumor; Chromatography, Affinity; Concanavalin A; Fetus; Glycoconjugates; Glycoprotein Hormones, alpha Subunit; Humans; Hypothyroidism; Intestinal Neoplasms; Pituitary Neoplasms; Postmenopause; Protein Binding; Uremia

The binding of lectins to paraffin sections of nine gastric carcinomas and adjacent mucosa was examined by fluorescence microscopy. A battery of nine lectins was employed, and both intestinal and diffusely infiltrating tumors were tested. Wheat germ agglutinin and Ricinus communis agglutinin I appeared to bind to both mucus and nonmucus glycoproteins; these lectins labeled tumor cells, benign epithelial cells, and nonepithelial tissues strongly and consistently. Peanut agglutin, soybean agglutinin, Dolichos biflorus agglutinin, Bandeiraea simpifolica agglutinin, and Ulex europaeus agglutinin I bound extensively to mucosubstances in vacuoles and apices of benign epithelial cells but often bound to tumor cells focally and in some cases not at all. Neuraminidase digestion enhanced lectin staining in some tumors; but in others, especially those of the diffusely infiltrating type, neuraminidase digestion did not enhance the staining of tumor cells. The results suggest that the decrease in the proportion of tumor cells labeling with lectin relative to superficial epithelial cells can be due either to the oversialylation of mucoproteins or to the loss of glycosylating enzyme activity. Concanavalin A did not bind to mucosubstances in the vacuoles or apices of benign epithelium, but bound to mucus vacuoles of metaplastic epithelium and to coarse cytoplasmic granules in two of the tumors examined. This suggests either the abnormal addition of mannose to mucus glycoprotein or the production of a distinct glycoprotein by some gastric tumors.

Topics: Concanavalin A; Gastric Mucosa; Humans; Intestinal Neoplasms; Lectins; Ricin; Stomach Neoplasms; Wheat Germ Agglutinins

Topics: Acetamides; Adenocarcinoma; Agglutination; Animals; Carcinogens; Cell Differentiation; Cell Membrane; Colonic Neoplasms; Concanavalin A; Epithelium; Galactose; Glucosamine; Glucosyltransferases; Hydrazines; Intestinal Neoplasms; Intestines; Lectins; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Transferases