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)

(1) The mitochondrial ATPase (EC 3.6.1.3) Ehrlich ascites cell mitochondria, was inhibited by D-glucose under physiological concentrations of ATP. The generation of ADP by the mitochondrial bound hexokinase, seems to be the reason for the D-glucose inhibitory effect. Reversal of the inhibitory effect of ADP on Ehrlich ascites cell mitochondria ATPase by an ATP-regenerating system was achieved. (2) Dissociation of mitochondrial bound hexokinase from the mitochondria eliminated the inhibitory effect of D-glucose. Rebinding of the hexokinase to the mitochondria regenerated the D-glucose inhibitory effect on Ehrlich ascites cell mitochondria ATPase. (3) Bioflavonoids such as quercetin inhibit the mitochondrial hexokinase activity, but do not change the mitochondrial ATPase activity of isolated Ehrlich ascites tumor cell mitochondria. (4) The inhibitory effect of bioflavonoids on mitochondrial bound hexokinase activity is shown to be dissociable from the ascites tumor cell mitochondria and seems to be associated with regulatory rather than catalitic sites of the enzyme.
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PMID:Bioflavonoid regulation of ATPase and hexokinase activity in Ehrlich ascites cell mitochondria. 1 95

The carbohydrate moiety of carcinoembryonic antigen could be sequentially degraded by repeated cycles of periodate oxidation, reduction, and mild acid hydrolysis (Smith degradation). After three complete degradations, all fucose and sialic acid, 80% of the galactose, 65% of the mannose, and about 40% of the N-acetylglucosamine were eliminated without impairing the ability of degraded carcinoembryonic antigen to react with specific antisera against the antigen. Inhibition studies in a carcinoembryonic antigen/rabbit anti-carcinoembryonic antigen precipitating system with oligosaccharides covering previously known internal structures of glycoproteins and presumably corresponding to the internal carbohydrate region of the antigen, demonstrated that none of the compounds tested was inhibitory. Nor could any inhibitory effect on the binding of carcinoembryonic antigen to antibody against the antigen in a radioimmunoassay system be domonstrated for the carbohydrate moiety prepared by hydrazinolysis or the glyco peptide fraction isolated after papain degradation of the antigen. However, if carcinoembryonic antigen is completely reduced and alkylated, with three intrachain disulfide bonds cleaved per 10-5 g, the immunological activity is reduced to 3-5% of untreated antigen. Furthermore, treatment of the antigen with 0.5 NaOH at 20 degrees for 2 hr completely abolished its ability to react with antiserum, whereas its ability to precipitate with a series of lectins was unchanged. No release of low-molecular-weight carbohydrate orchange in sugar composition of alkali-treated antigen was observed. Our tentative conclusion is that the carbohydrate moiety of carcinoembryonic antigen does not contain the tumor-associated determinant(s).
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PMID:Nature of the tumor-associated determinant(s) of carcinoembryonic antigen. 4 56

Plasma and prostatic fluid from man, dog, and baboon were measured for carcinoembryonic antigen (CEA) by a radioimmunoassay technique. No CEA was detected in plasma, prostatic fluid, or seminal fluid in 12 dogs and three baboons. Elevated CEA (less than 2.5 ng/ml) was found in 13 of 20 human prostatic fluids. It was inferred that there was no immunologic cross-reactivity of CEA among man, dog, and baboon. CEA has been isolated and purified from liver tumors. Biochemical studies reveal that CEA consists of 60 percent carbohydrate and 40 percent protein. It contains the following carbohydrates: fucose, mannose, galactose, sialic acid, N-acetylglucosamine, and a small amount of N-acetylgalactosamine. The following amino acids were found in CEA: lysine, histidine, arginine, aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, emthionine, isoleucine, leucine, tyrosine, phenylalanine, and cysteine. The amino acid sequence (first 30 amino acids) of the N-terminal has been determined. The N-terminal amino acid was lysine. Using this study as a model, other tumor antigens from prostatic tumor tissues are being investigated. The acid phosphatase isoenzyme from prostatic tissue was also studied. After a series of purifications, two chromatographic fractions were obtained. Treatment with neuraminidase removed the sialic acid content of the molecule, changed the isoelectric focusing patterns, and abolished the chromatographic heterogeneity. Sedimentation studies indicated a molecular weight of about 100,000. Biochemical studies showed that prostatic acid phosphatase isoenzyme is a glycoprotein which consists of 7 percent carbohydrate and 93 percent protein. It contains fucose, galactose, mannose, sialic acid, N-acetylglucosamine, and the following amino acids: aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, tryptophan, and cysteine. An antiserum to this purified prostatic acid phosphatase isoenzyme is being prepared in animals.
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PMID:Tumor antigen and acid phosphatase isoenzyme in prostatic cancer. 4 19

Uridine 5'-diphosphate-galactose:glycoprotein galactosyltransferase activity was demonstrated in homogenates of normal ovary and ovarian epithelial adenocarcinomas. The specific activity of the enzyme in ovarian tumors was 3 to 5 times higher than in normal ovaries when the enzyme was assayed under identical conditions. The glycoprotein fetuin, from which terminal sialic acid and penultimate galactose were removed (fetuin minus N-acetylneuraminis acid and galactose), acted as an excellent exogenous acceptor. Galactosyltransferase from normal ovary and ovarian tumor cells had similar properties. Both required Mn2+ and Triton X-100 and had broad pH optima between 5.5 and 7. Galactosyltransferase activity was also measured in serum samples from ovarian cancer patients and normal healthy individuals in the presence of fetuin minus N-acetylneuraminic acid and galactose as exogenous acceptor. The enzyme levels were significantly elevated in the sera of ovarian cancer patients as compared to normal controls. The differences in the levels of this enzyme in the tissues and sera of normal individuals and ovarian cancer patients were not due to differential levels of the degrading enzymes such as uridine 5'-diphosphate-galactose pyrophosphatase or beta-D-galactosidase. Serial determinations were carried out on the sera of 5 ovarian cancer patients over a long period of time. The serum level of galactosyltransferase activity appeared to correlate with tumor volume as well as with the clinical status of the patient, which suggests possible leakage of the tumor enzyme into the host sera. Serial determination of this enzyme level in ovarian cancer patients seems promising in measuring tumor progression or success of therapeutic approaches.
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PMID:Uridine 5'-diphosphate-galactose:glycoprotein galactosyltransferase activity in the ovarian cancer patient. 5 28

Fucosyltransferase levels in 6 established strains of spontaneously metastasizing rat mammary tumors (STMT-058, MT-449, DMBA-4, SMT-077, TMT-081, and SMT-2A) were compared with 4 nonmetastasizing strains (MT-W9B, MT-W9A, MT-100, and MT-66) as controls. Two acceptors were prepared from fetuin for the assay, one by acid hydrolysis of N-acetylneuraminic acid and the other by the stepwise removal of N-acetylneuraminic acid and penultimate galactose by Smith degradation. The enzyme that transfers fucose to the first acceptor was designated fucosyltransferase A, whereas the one that uses the second acceptor was designated fucosyltransferase B. Both types of fucosyltransferases were found in this rat mammary tumor system. Whereas the levels of fucosyltransferase A in the 2 tumor groups were comparable, those of fucosyltransferase B were sixfold to sevenfold higher in the metastasizing tumors. This difference in the level of fucosyltransferase B was not caused either by differential hydrolysis of GDP-fucose by pyrophosphatase in the 2 groups or by hydrolysis of the product by fucosidases. Presence of any other inhibitor(s) or activator(s) of fucosyltransferase was excluded by mixing experiments. Optimal conditions for the assay of this enzyme were determined in a representative strain from each group. Under all circumstances, the activity of fucosyltransferase B was higher in the metastasizing tumors. The enzyme was inhibited by nucleoside diphosphates and triphosphates, and guanosine nucleotides were the most efficient inhibitors. Subcellular distributions of the two fucosyltransferases were similar, 35-50% of the enzyme activity being present in the crude microsomes. When plasma membrane factions were prepared from the microsomes, the major part (50-70%) of the enzyme was associated with the light and heavy plasma membrane fractions. Increased activity of fucosyltransferase B in the group of metastasizing tumors may have reflected faster synthesis and shedding of fucose-containing glycoprotein antigens. Similar molecules possibly were also synthesized in the nonmetastasizing cells but at a much slower rate, because the antigen is not easily lost from the cell surface. Any alteration of the specificity of this focosyltransferase in the metastasizing tumors, in addition, may have caused antigen modulation.
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PMID:Fucosyltransferase activity in metastasizing and nonmetastasizing rat mammary carcinomas. 7 84

The present experiments demonstrate that animals carrying large peripheral intramuscular tumours were free of spontaneous pulmonary metastases. Secondaries in the lung emerged, however, after administration of agents such as trypsin, 10% dextrose or antiserum to alpha-2-macroglobulin (AMG). Such metastases also appeared in animals treated with trypsin after amputation of the tumour-bearing limb. It is believed that the pulmonary vessels of tumour-bearing animals are lined with a layer of tumour-associated AMG. The presence of this peptide on vascular endothelium blocks the transmigration of tumour cells. Tumour emboli may remain dormant, i.e. unattached, in the vascular lumen. Agents inactivating AMG or enhancing vascular permeability (proteases, antisera to AMG or vasodilators) may promote the emergence of a latent tumour cell into an overt state. This is confirmed by the above experiments and by the microscopic appearance of the pulmonary vessels of test animals (shift of tumour cells from the intravascular to the perivascular space). It is suggested that latency is determined by the state of permeability of the vessels harbouring tumour emboli.
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PMID:On the latency of tumour cells. 8 78

Urine samples of normal male Fischer rats or rats fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide for 6,8 or 30 weeks were collected and centrifuged 50 weeks after beginning treatment. After being sonicated and assayed (with purified desialylated ovine submaxillary mucin as acceptor glycoprotein), the exfoliated bladder cells obtained from the urines of treated rats showed uridine 5'-diphosphate galactose:glycoprotein transferase activity. The specific enzymatic activity of the enzyme from cells of 30-week-treated rats was about 10 times higher than from normal rats. The enzyme from cells of hyperplastic rats (treated 6 or 8 weeks) was only slightly higher in specific activity than that of normal rats. A similar was obtained at a later stage of bladder tumor induction, when the urines from 30-week-treated rats contained blood. A correction was made for protein contributed by the blood clot. The possibility that the blood clot contributed galactosyl transferase activity was excluded. Activity of the enzyme was detected in normal rat bladder tissue and in normal human urine.
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PMID:Uridine 5'-diphosphate galactose: glycoprotein galactosyl transferase activity in exfoliated bladder epithelial cells in rats fed N-(4-(5-nitro-2-furyl)-2-thiazolyl) formamide. 9 27

In an attempt to modulate the recognition processes that occur on lymphocyte membranes in mixed lymphocyte culture, responding cortisone resistant thymocytes or stimulating spleen cells (treated with mitomycin C) were pretreated with native concanavalin A (N-Con A) or succinyl-Con A (S-Con A). Highly significant cell proliferation was observed in syngeneic combinations when either the responding cells or the stimulating cells were so treated with Con A, although Con A pretreatment alone was never mitogenic. In allogeneic combinations the proliferative response with Con A pretreatment of either partner on day 3 was five to seven times higher than in the normal mixed lymphocyte reactions. The triggering of proliferation was dependent on two factors: (a) The presence of spleen cells as the stimulating cells (thymocytes were much less effective). (b) The binding of Con A molecules to either one of the partners, the effect being abrogated by the specific inhibitor of Con A, alpha-mannopyranoside. The optimal concentration of S-Con A was about twice that of N-Con A. Even more striking was the observation that cultures in which either one of the partners was pretreated with Con A in allogeneic combinations showed a strong suppression (60-80% inhibition) in the subsequent generation of the cytotoxic lymphocytes (CL). The Con A concentration required to trigger a proliferative response corresponded to that for suppressing the generation of CL. Con A pretreatment did not result in a cytotoxic activity toward syngeneic tumor cells.
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PMID:Concanavalin A potentiates syngeneic response in murine lymphocytes. 12 28

Dissociated cells of the R3230AC mammary tumor were found to take up glucose by diffusion and by a passive carrier system. Using labeled 3-O-methylglucose as the probe, the following properties of the passive carrier were identified: (1) specificity for glucose, (2) competition by galactose and mannose but not by mannitol and fructose, (3) inhibition by phloretin but not by phloridzin, (4) temperature sensitivity, and (5) a Km for transport of 3-4 mM. The effects of insulin in vitro on carrier-mediated glucose transport were investigated in tumor cells from diabetic rats. At 10-9 M insulin, a time-related decrease in v for transport was observed resulting in an increased calculated Km (2- to 3-fold increase after 60-90 min incubation with insulin); only slight effects on V were obtained. This unusual response in v to insulin was observed when glucose was present in the medium at 2 mM and 5 mM, but not at 20 mM glucose. The effect of insulin to decrease the v was dose-related, with the major effects seen between 10-10M and 10-8M. The apparent decrease in glucose entry in vitro may in part explain the ability of insulin to inhibit growth of this tumor in vivo.
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PMID:Effect of insulin to decrease glucose transport in dissociated cells from the R3230AC mammary adenocarcinoma of diabetic rats. 13 24

By light microscopy the subdermal nodule of a patient with fibrodysplasia ossificans progressiva (FOP) had a fibromatoid histologic appearance. The cytoplasm of the cells stained strongly for mannose-rich glycoprotein with the concanavalin A-horseradish peroxidase (con A-HRP) method. The tumors also exhibited abundant hyaluronidase-digestible mucopolysaccharide in the interstitium with various basic staining reagents. This material appeared to consist principally of hyaluronic acid or chondroitin sulfate with few or mainly masked sulfate esters. At the ultrastructural level, cells interpreted as the tumor cells in the subdermal nodule from the patient displayed extremely hyperplastic granular reticulum and well-developed Golgi elements and appeared very active in synthesis and secretion of protein. The material in the dilated cisternae of the granular reticulum stained for glycoprotein with the con-A-HRP method. Macrophages which comprised the other main cell type in the nodules commonly contacted the tumor cells and occasionally evidenced engulfment of these cells. The intercellular matrix of the nonossified subdermal nodule exhibited greatly increased mucosubstance and, by electron microscopy, showed an unusual network of dialyzed iron-reactive acid muco-substance in the interstitium.
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PMID:Histochemical and ultrastructural studies in fibrodysplasia ossificans progressiva (myositis ossificans progressiva). 14 Dec 14


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