Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

K-m values of beta-N-acetylglucosaminidase (2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase EC 3.2.1.30), beta-N-acetylgalactosaminidase (EC 3.2.1.53), beta-galactosidase (beta-D-galactoside galactohydrolase EC 3.2.1.23) and alpha-L-fucosidase (alpha-L-fucoside fucohydrolase EC 3.2.1.51) of distal colonic tumours, induced in rats by 1,2-dimethylhydrazine, were found to be significantly different compared with the values for the enzymes of the colonic mucosa of the control and tumour-bearing animals and of the proximal colonic tumours. The inhibition kinetics data also showed a significant difference between the enzymes of the distal colon tumours and of other experimental tissues. The data on the effect of pH on enzyme kinetics (pK values) showed no significant difference in the catalytic groups of the active centres of enzymes from tumours and from the control colonic mucosa. Tumour beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase compared with the enzymes from other experimental tissues were found to be different in their thermal inactivation kinetics. K-m values of 14 days old foetal intestinal beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase were significantly different from the values obtained for the adult mucosal enzymes but were similar to those of the distal colonic tumour enzymes.
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PMID:Studies on the kinetics of glycosidases from chemically-induced rat colonic tumours and normal rat colon. 23 55

Protein synthesized in ascites cell-free extracts in response to first trimester placental mRNA was immunoprecipitated with antisera directed against the alpha subunit of human chorionic gonadotropin. The immunoprecipitable proteins were resolved on sodium dodecyl sulfate/polyacrylamide slab gels. In membrane-depleted extracts placental mRNA directed the synthesis of the "preprotein" form of the alpha subunit. However, when membranes were added to the cell-free extracts a protein migrating more slowly than pre-alpha subunit was observed. This protein was specifically adsorbed to a concanavalin A column, and its migration on sodium dodecyl sulfate gels was enhanced after treatment with alpha-mannosidase (EC 3.2.1.24) or endo-beta-N-acetylglucosaminidase C(II) or H. Similar results were obtained when mRNA was translated in lysates derived from first trimester placenta instead of in ascites cell extracts. Kinetic studies of the glycosylation reaction revealed that sugar attachment can occur just prior to release of the protein. These data show that the apoprotein of the alpha subunit can be glycosylated in vitro. The data also suggest that the glycosylated protein contains a sugar core consisting of di-N-acetylchitobiose and at least four mannose residues, some of which are alpha-linked. In addition, it appears that this carbohydrate unit is present in homologous placental membranes as well as in the ascites tumor membranes.
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PMID:mRNA-dependent synthesis of a glycosylated subunit of human chorionic gonadotropin in cell-free extracts derived from ascites tumor cells. 27 8

Placental RNA has previously been shown to direct the synthesis of an asparagine-linked mannose-rich glycosylated form of the alpha subunit of human chorionic gonadotropin (hCG-alpha) in lysates derived from mouse ascites tumor cells. Glycosylation was dependent on the presence of homologous microsomal membranes, and the glycosylated protein was sequestered into the microsomal vesicles. Here we show that when Triton X-100 is added after 60 min of translation and the incubation is continued, there is a shift of this glycosylated form to new discrete lower molecular weight proteins. The formation of these new proteins was not the apparent result of proteolysis because (i) treatment of the fully glycosylated protein or the proteins formed in the presence of Triton with endoglycosidase H resulted in the formation of a single protein migrating at the same rate on sodium dodecyl sulfate gels; (ii) the migration of nonglycosylated hCG-alpha synthesized in the presence of membranes isolated from tunicamycin-pretreated ascites tumor cells was not changed upon Triton addition; and (iii) the Triton-induced change was inhibited by mannonolactone, yeast mannan, and purified mannose oligosaccharides. It was also shown that little processing of the mannose-rich glycoprotein occurred in the presence of microsomal membranes alone. However, addition of the ribosome-free supernatant fraction to the glycoprotein resulted in processing. These data suggest that processing of the oligosaccharide core is a compartmentalized process in which removal of sugar, presumably mannose, requires a transfer of the glycoprotein from the endoplasmic reticulum to another component of the secretory cascade.
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PMID:Glycosylation of human chorionic gonadotropin in mRNA-dependent cell-free extracts: post-translational processing of an asparagine-linked mannose-rich oligosaccharide. 28 6

A secondary specific cytotoxic response is obtained when lymphocytes primed in vivo to a tumor allograft are exposed to Con A in culture. The secondary cytotoxic cells generated are specific to target cells bearing antigens of the primary sensitizing cells and are qualitatively indistinguishable from the response obtained upon secondary antigenic stimulation. The cell-mediated cytotoxicity is independent of concanavalin A (Con A) and is not affected by the Con A-specific inhibitor, alpha-methyl-D-mannose pyranoside. Furthermore, cultures containing a mixture of submitogenic concentrations of Con A and stimulating antigens showed synergy and augmentation of cytotoxic activity. It is suggested that activation of prekiller cells by Con A into CTL may be mediated via the same or similar receptors normally triggered by the stimulating antigens. Functional similarities between ConA and the lymphocyte-defined antigens of the major histocompatibility complex region are discussed.
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PMID:Concanavalin A-mediated activation of antigen-primed lymphocytes into secondary cytotoxic lymphocytes. 29 80

We have found that phagocytic leukocytes exposed to the tumor-promoting agent, 12-O-tetradecanoyl phorbol-13-acetate, efficiently release carbon-1 of 2-deoxyglucose in the form of CO2 with concurrent intracellular accumulation of a phosphorylated 5-carbon intermediate. In the absence of 12-O-tetradecanoyl phorbol-13-acetate, these cells release barely detectable amounts of CO2 from 2-deoxyglucose. 12-O-Tetradecanoyl phorbol-13-acetate, at a concentration of 1 ng/ml, has an immediate effect on CO2 release, which is temperature-dependent and linear with time and cell number. The ability of a number of phorbol ester-like compounds to enhance this catabolic pathway for 2-deoxyglucose correlates with their ability to act as tumor promotors and inflammatory agents. Although this effect of phorbol esters appears to be restricted to granulocytes, monocytes, and macrophages, the possibility arises that other mammalian cells are capable of catabolizing or can be induced to catabolize-2-deoxyglucose. Thus, 2-deoxyglucose decarboxylation should be considered whenever this analog of mannose and glucose is used as an indicator for sugar transport, especially when pharmacodynamic agents are present.
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PMID:Catabolism of 2-deoxyglucose by phagocytic leukocytes in the presence of 12-O-tetradecanoyl phorbol-13-acetate. 31 Jan 20

Methanesulfonamide, N-[4-(9-acridinylamino)-30methoxyphenyl]-(NSC-249992), an acridine derivative with significant antitumor activity in animal tumor systems, was administered to 29 patients in a phase I clinical trial. The dose ranged from 10 to 160 mg/m2 with a single dose given every 28 days. The toxic effects included moderate to severe leukopenia and mild thrombocytopenia. Myelosuppression was more severe in patients with prior whole abdominal or pelvic radiotherapy. Superficial phlebitis occurred when the drug was diluted in a volume of less than 500 ml of 5% dextrose in water. Antitumor activity was detected in one patient with ovarian carcinoma. Phase II studies are indicated with this compound since it has reproducible and reversible toxicity with some evidence of antitumor activity. The starting dose of the drug for phase II trials should be 120 mg/m2 as a single iv dose repeated at 4-week intervals.
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PMID:Phase I study of methanesulfonamide, N-[4-(9-acridinylamino)-3-methoxyphenyl]-(m-AMSA) using a single-dose schedule. 36 Dec 22

The effect of oil-attached cell-wall skeletons of BCG (BCG-CWS) and Nocardia rubra (N. rubra-CWS) on macrophage functions was examined regarding phagocytosis of zymosan particles, uptake of 2-deoxy-D-glucose (2-dG), and cytostatic activity against syngeneic tumor cells. A single intraperitoneal injection of either BCG-CWS or N. rubra-CWS in mice resulted in accumulation of a large number of macrophages in the peritoneal cavity. They demonstrated, in vitro, a significant cytostatic effect on target cells as well as increase in phagocytic activity and uptake of 2-dG. These results suggest that one of underlying mechanisms for the antitumor activity of BCG-CWS and N. rubra-CWS is possibly the activated macrophage-mediated system.
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PMID:Activation of peritoneal macrophages by oil-attached cell-wall skeleton of BCG and Nocardia rubra. 38 Oct 89

Cell surface glycoproteins of human tumor cell lines (melanomas and astrocytomas, and ovarian, bladder, stomach, cervical, laryngeal, and renal cancers) were studied by labelling with 1) neuraminidase-galactose oxidase-[3H]borohydride, 2) galactose oxidase-[3H]borohydride, and 3) dilute periodate-[3H]borohydride. The labeled components were examined by polyacrylamide gel electrophoresis and fluorography. Each tumor type had a distinctive pattern of labeled glycoproteins when the results from both procedures 1 and 2 were considered. Cell surface glycoproteins of malignant melanoma could not be labeled by procedure 2, whereas the other cell lines had at least two major glycoproteins that could be labeled by this method. Very similar profiles of melanoma glycoproteins were labeled by procedures 1 and 3. From these results the conclusion was reached that cell surface glycoproteins of melanomas are substituted with sialic acid so that their D-galactose and/or N-acetyl-D-galactosamine residues are available for oxidation by galactose oxidase only after neuraminidase treatment. An alternative explanation that these sugars are sterically accessible to galactose oxidase only after neuraminidase treatment also has to be considered. All melanoma lines studied were characterized by having two major cell surface glycoproteins with molecular weights of 110,000 and 90,000, respectively. Lines, however, varied considerably in their expression of other components. In particular, heterogeneity was shown in the expression of gp220, a component identified as fibronectin by immunoprecipitation with a specific antiserum, and in the expression of gp37/32, a pair of glycoproteins having the characteristics of la-like antigens. Of the other cell lines studied, astrocytomas most closely resembled melanoma in their glycoprotein profiles. The brain tumors, however, had two or three glycoproteins, including gp110, which could be labeled by galactose oxidase-[3H]borohydride without neuraminidase treatment.
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PMID:Cell surface glycoproteins of human tumor cell lines: unusual characteristics of malignant melanoma. 38 52

Immunochemically active fractions were obtained using Separon Hema-300-glc(R) from serum of lactic dehydrogenase virus (LDV) infected mice and from homogenates of human tumors. The mixture of proteins of tumorous origin from the cytosol giving a positive reaction in the leukocyte adherence inhibition (LAI) test was found in the same fractions showing maximum of absorbance at 340 nm in the spectrophotometer and a corresponding peak in the refractometer. Analogous peaks were not proved in material obtained from healthy controls, but they were found in some human placentas and fetal organs. The LDV fraction obtained from mouse serum served as a "control" antigen in LAI test for human tumor testing, and results corresponded with those obtained using cytosol specific for the tumor under study.
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PMID:Correlation of extracts obtained by high efficiency gel chromatography of lactic dehydrogenase virus infected mouse serum and cytosol from human tumors using leukocyte adherence inhibition assay. 39 8

The biosynthesis and secretion of a glycosylated, K-type immunoglobulin light chain (K-46) was studied in a mouse myeloma tumor, mineral oil plasmacytoma-46B. Viable single cell suspensions were prepared from excised tumors and optimal conditions were established for incorporation of amino acid and carbohydrate precursors into the protein synthesized and secreted by the cells. The glucose analog, 2-deoxy-D-glucose, was utilized as an inhibitor of glycosylation to determine the role of glycosylation in the biosynthesis, intracellular transport, and export of the protein from the cell. It was determined that 6 mM 2-deoxyglucose prevents the incorporation of glucosamine, mannose, and galactose into secreted protein, but permits the incorporation of leucine at approximately 40% of control values. The nonglycosylated protein, secreted in the presence of 2-deoxyglucose, was characterized as a nonglycosylated form of K-46 light chain by the following criteria: (a) electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate, (b) reactivity of the nonglycosylated protein with antisera prepared against native, fully glycosylated, K-46 light chain, (c) analysis of the protein by gel filtration techniques, (d) behavior of the protein on lectin-derivatized Sepharose, and (e) analysis of tryptic peptides derived from the protein. We have concluded that 2-deoxyglucose-inhibited cells synthesize and secrete the normal polypeptide chain of K-46 devoid of its carbohydrate side chain indicating that glycosylation is not an essential step in the biosynthesis, intracellular transport, or export of this protein that is normally synthesized and secreted in a glycosylated form. Under conditions of 2-deoxyglucose inhibition, the nonglycosylated form of K-46 light chain constitutes a significantly greater proportion of accumulated intracellular protein, suggesting that the biosynthesis of the polypeptide chain of K-46 light chain proceeds at a nearly normal rate, but that the absence of the carbohydrate side chain of the protein retards, but does not prevent, the intracellular transport of the protein and its export from the tumor cell.
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PMID:Glycoprotein biosynthesis in myeloma cells. Characterization on nonglycosylated immunoglobulin light chain secreted in presence of 2-deoxy-D-glucose. 40 89


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