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)

High levels of a novel vitamin B12-binding protein (hepatoma B12 BP) have been observed recently in plasma obtained from three adolescent patients with hepatocellular carcinoma. This protein has now been isolated in homogeneous form from the plasma and pleural fluid of two of these patients by the use of affinity chromatography with vitamin B12-Sepharose. The hepatoma B12 BP belongs to the R-type group of B12-binding proteins and is essentially indistinguishable from the recently isolated human milk and saliva R-type proteins in terms of: (a) immunologic properties based on immunodiffusion and immunoprecipitation assays; (b) amino acid composition; (c) molecular weight based on amino acid and carbohydrate content; and (d) absorption spectra. Both hepatoma B12 BPs contain more sialic acid and less fucose than the milk and saliva B12 BPs. All four proteins contain similar amounts of galactose, mannose, galactosamine, and glucosamine. Differences in sialic acid content appear to account for the differences in electrophoretic mobility that were observed among the four proteins. Differences in total carbohydrate content appear to account for the differences in apparent molecular weight that were observed with both gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tumor tissue from one of the patients contained 10 times as much R-type protein as did normal liver tissue from the same patient. This suggests, although it does not prove, that synthesis by the tumor is the cause of the high levels of R-type protein found in the plasma of certain patients with hepatocellular carcinoma. Plasma survival studies performed with rabbits indicate that the hepatoma B12 BP has a prolonged plasma survival and suggests that his parameter is also of importance.
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PMID:Isolation and characterization of a novel vitamin B12-binding protein associated with hepatocellular carcinoma. 17 Dec 83

CEA was prepared by combined isoelectric precipitation, ultrafiltration and column chromatography under controlled conditions of pH. The resulting immunologically active materials were higher in carbohydrate (85-87%), N-acetyl galactosamine (10-11.5%) and galactose (28-32%) content than that previously reported. Differences in amino acid yield were also noted; the concentrations of aspartate, serine, glycine and alanine being higher and that of lysine, histidine, arginine, proline, valine, isoleucine, leucine and tyrosine were lower than that reported for CEA prepared by previous methods. The tumor tissues for CEA extraction were obtained from two Group O Rh positive deceased. Neither preparation showed Group A or B activity as measured by hemagglutination inhibition. It is suggested that the method of purification influences the carbohydrate and amino acid yields.
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PMID:Preparation of carcinoembryonic antigen (CEA) containing significantly increased amounts of galactose and galactosamine. 17 42

The infectivity of avian RNA tumor viruses was inactivated to varying degrees by treatment with either concanavalin A (Con A) or phytohemagglutinin but not by treatment with wheat germ agglutinin. In general, leukosis viruses reacted preferentially with Con A, whereas sarcoma viruses showed more affinity for phytohemagglutinin. In a more extensive study with subgroup A of Prague Rous sarcoma virus (PR-A), the effect of inactivation by Con A could be specifically prevented by the addition of alpha-methyl-D-mannoside, alpha-methyl-D-glucoside, and N-acetyl-D-glucosamine. These sugars were also capable of eluting [3H]glucosamine-labeled material from disrupted PR-A virus, which was bound to a Con A-sepharose affinity column. A major viral glycoprotein recovered from the column had the same mobility as gp85 in polyacrylamide gel electrophoresis and could be immunoprecipitated with anti-gp85 antiserum. These results suggest that the material reacting with Con A is present on the gp85 component of the viral glycoprotein. The diversity in the reactivity of the glycoproteins of transforming and nontransforming viruses with plant lectins is discussed.
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PMID:Reactivity of avian RNA tumor viruses with lectins. 17 78

Mouse pituitary tumor cells (AtT-20/D-16v) were incubated in medium containing [3H] glucosamine or [3H] mannose. By analyzing immunoprecipitates of cell extracts and culture medium it was shown that [3H] glucosamine and [3H] mannose were incorporated into all three high molecular weight forms of ACTH; label was not incorporated into Mr=4,500 ACTH (which is thought to be similar to the 39 amino acid polypeptide form of ACTH, alpha(1-39)). Based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis the apparent molecular weights of these glycoprotein forms of ACTH were 31,000, 23,000, and 13,000. Gel filtration in 6 M guanidine HCl indicated that the molecular weights of these forms of ACTH were substantially lower; sodium dodecyl sulfate-polyacrylamide gel electrophoresis has often been found to overestimate the molecular weight of glycoproteins. A significant fraction of the high molecular weight ACTH in tumor cell extracts binds to columns of concanavalin A-agarose and can be eluted with 0.2 M alpha-methyl-D-mannopyranoside; porcine alpha(1-39) does not bind to concanavalin A-agarose. High molecular weight glycoprotein ACTH can be detected in extracts of mouse and bovine pituitary by using concavalin A affinity chromatography.
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PMID:High molecular weight forms of adrenocorticotropic hormone are glycoproteins. 18 16

Saline extraction of tumor cells from YC8 lymphoma transplanted in Balb/c Mice, of lymphocytes from animals bearing this tumor and of lymphocytes from control animals, allowed us to show important hydrolytic activities towards UDP-[(14C)]-galactose and galactose-[(14C)]-1-phosphate in normal lymphocytes. These activities disappear in lymphocytes from Mice bearing this tumor and in tumor cells themselves.
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PMID:[Demonstration of nucleotide pyrophosphatase and phosphohydrolase activities in normal lymphocyte of Balb/c mice and absence of these activities in YC8 tumor cells and in lymphocytes of animals with YC8 lymphoma]. 18 10

Plasma membranes derived from rat thyroid tumor (1-8R) which is unresponsive to thyrotropin but is responsive to dibutyryl adenosine 3':5'-cyclic monophosphate bind less than 20% of the [125I] thyrotropin which can be bound to plasma membranes from normal rat thyroids under conditions which optimize tumor membrane binding relative to normal thyroid membranes. In addition, the binding is different from thyrotropin binding to normal thyroid membranes both in its altered sensitivity to changes in hydrogen ion concentration and in a decreased sensitivity to competition by unlabeled thyrotropin. This reduced capacity to bind [125I] thyrotropin cannot be attributed to degradation of the hormone by membrane-associated proteases. Although the supernatant phase of the thyroid tumor homogenates contains a soluble component which inhibits [125I] thyrotropin binding to thyrotropin receptors on plasma membranes, its level is the same as in homogenates of normal thyroid tissue. Trypsin digestion does not expose thyrotropin receptors in a manner analogous to that seen in normal thyroid tissue. The major ganglioside in the tumor membranes is N-acetylneuraminylgalactosylglucosylceramide and the membranes lack the N-acetylgalactosaminyltransferase required for the synthesis of more complex gangliosides. In contrast, the normal rat thyroid membranes contain more complex gangliosides such as galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide and N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosyl ceramide as well as the glycosyltransferase activities required for their syntheses. Galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide can also be detected in normal membranes, but not in tumor membranes, by selective labeling with galactose oxidase (D-galactose: oxygen 6-oxidoreductase, EC 1.1.3.9) and [3H] sodium borohydride. These results support the hypothesis that gangliosides are important structural or functional components of thyrotropin receptors on thyroid plasma membranes.
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PMID:Relationship of gangliosides to the structure and function of thyrotropin receptors: their absence on plasma membranes of a thyroid tumor defective in thyrotropin receptor activity. 18 83

A selective deficiency of uridine triphosphate (UTP) was induced in AS-30D rat ascites hepatoma cells by the synergistic action of D-galactosamine and 6-azauridine. The resistance of these hepatoma cells to low concentrations of D-galactosamine (less than 2 mM) was due to their active de novo pyrimidine synthesis which compensated the trapping of uridylate in the form of uridine diphosphate-amino sugars derived from D-galactosamine. The additional blockage of de novo pyrimidine synthesis led to noncompensated uridylate trapping with a UTP content of less than 0.05 mmole/kg of cell wet weight as compared to the control level of 0.66 mmole/kg. The induction of UTP deficiency by incubating the cells with low concentrations of D-galactosamine and 6-azauridine (0.5 mM each) was not accompanied by significant changes in the content of adenine and guanine nucleotides, uridine diphosphate glucose, and uridine diphosphate galactose. The depletion of UTP pools could be reversed within 10 min by the addition of uridine; orotate or uracil were completely ineffective in these hepatoma cells. A UTP content in the range of 0.1 to 0.4 mmole/kg, induced by either 6-azauridine or D-galactosamine, was associated with a reversible depression of cell growth in suspension culture. A UTP content below 0.05 mmole/kg led to irreversible growth inhibition and to necrocytosis in culture, as well as to a loss of transplantability in vivo. Uridine reversal studies indicated that the percentage of cells able to resume growth in culture decreased with an increasing time period of UTP deficiency. The deficiency period required for irreparable or lethal damage in these hepatoma cells ranged from 3 to 20 hr. The principle of noncompensated uridylate trapping can be extended to other inhibitors of nucleotide synthesis combined with various nucleotide-trapping sugar analogs. Noncompensated nucleotide trapping may be useful for an induction of selective nucleotide deficiencies in tumor cells.
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PMID:Uridine triphosphate deficiency, growth inhibition, and death in ascites hepatoma cells induced by a combination of pyrimidine biosynthesis inhibition with uridylate trapping. 18 18

A tumorigenic anchorage-dependent cell line (H-91) was established in culture from an azo-dye-induced rat ascites hepatoma. When grown in a glucose-containing medium the cells exhibit high rates of lactic acid production characteristic of rapidly growing tumor cells. However, when glucose is replaced with galactose the cells grow equally well but exhibit only moderately elevated rates of lactic acid production. The molecular basis for this observation cannot be attributed to differences in permeability because initial rates of glucose and galactose entry into hepatoma cells are identical. Rather, the activity of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) is found to be high in hepatoma cells, about 20-fold higher than that of control and regenerating rat liver. Moreover, tumor hexokinase activity is not inhibited by low concentrations (<0.6 mM) of the reaction product glucose 6-phosphate. Additionally, 50% of the hexokinase activity of hepatoma cells is found associated with the mitochondrial fraction. This fraction is 3-fold enriched in hexokinase activity relative to the homogenate and 4-fold enriched relative to the nuclear and postmitochondrial fractions. Tumor mitochondrial hexokinase appears to be coupled directly to oxidative phosphorylation, because addition of glucose to respiring hepatoma mitochondria (after a burst of ATP synthesis) results in stimulation of respiration. In contrast, glucose has no effect on the respiration of mitochondria from control and regenerating liver. These results suggest that the high glycolytic capacity of H-91 hepatoma cells is due, at least in part, to an elevated form of hexokinase concentrated in the mitochondrial fraction of the cell.
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PMID:High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase. 19 1

To evaluate the effects of oral and intravenous nutritional repletion on tumor growth and host immunocompetence in malnourished animals, 60 adult purified protein derivative (PPD) positive Buffalo rats were inoculated with Morris hepatoma 5123 and were fed a regular diet for 14 days. All animals then were switched to a high carbohydrate, protein-free diet for the next 14 days, at which time only 30% of the animals remained PPD positive. Rats then were divided into three groups: group I underwent superior vena cava catheterization and received a constant infusion of 25% dextrose--4.25% amino acid solution; group II was switched to the regular protein diet orally ad libitum; and group III remained on the oral protein-free diet. PPD reactivities were measured prior to death 7 days later. Group I animals gained an average of 14 gm of body weight, and 91% of the animals were PPD positive. Group II animals lost an average of 17 gm of body weight, but 78% of the animals were PPD positive. Group III animals lost an average of 23 gm of body weight, and only 12% of the animals remained PPD positive. Absolute tumor weight and tumor weight: body weight ratios were not significantly different among the three groups of animals. Provision of adequate nutrition intravenously to malnourished tumor-bearing animals restores body weight and host immunocompetence without adversely stimulating tumor growth out of proportion to growth of the host.
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PMID:Effects of intravenous nutrition on tumor growth and host immunocompetence in malnourished animals. 21 54

5-thio-D-glucose (5-TDG) exerts profound effects on rapidly metabolizing tissues. We have used liquid scintillation counting to study the tissue distribution and pharmacokinetics of S-35-labeled 5-TDG in hamster models of pancreatic tumors. In the normal hamster, initial uptake of S-35 activity into kidney, liver, and blood was high, but rapidly decreased with time. The pancreatic uptake (% dose/g) never exceeded 0.75%. This level occurred only at the earliest times after administration. Uptake in all three tumor models exceeded that in pancreatic tissue within 15 min of injection. The highest tumor-to-pancreas ratio was seen in the duct-tumor model, which also exhibited the most favorable tumor-to-tissue ratio when compared with kidney, liver and muscle. Favorable ratios were most pronounced at 6 and 24 hr after injection. These studies provide impetus for the use of 5-TDG as a model compound for the synthesis of potentially useful agents for clinical detection of pancreatic tumors.
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PMID:Biodistribution and pharmacokinetics of S-35-labeled 5-thio-D-glucose in hamsters bearing pancreatic tumors. 23 49


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