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)

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

Treatment of ascites tumor cells with dextran sulfate resulted in a marked inhibition of the incorporation of [14C]valine into protein in the presence of a high Na+ medium. Amino acid incorporation was restored after i.p. injection of these cells into mice or by exposure of the cells to ascites fluid in vitro. In a medium high in K+ and low in Na+, [14C]valine incorporation into protein took place in dextran treated cells. Rotenone inhibited the reaction, which could be restored by addition of both inorganic phosphate and either glucose or glucose 6-phosphate. Quercetin, an inhibitor of the Na+-K+-ATPase, markedly depressed the incorporation of [14C]valine into protein in intact sdviyrd tumor cells in a high Na+ medium. There was little or no inhibition of protein synthesis in dextran sulfate treated cells when tested in a high K+-low Na+ medium. These experiments suggest a relationship between protein synthesis and the operation of the membranous Na+-K+-ATPase.
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PMID:Protein synthesis in dextran sulfate-treated ascites tumor cells. 13 42

1-(2-Chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), a water-soluble nitrosourea, differs from 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin) by the placement of the cytotoxic group on C-1 of glucose. Its biological and biochemical properties are compared with those of chlorozotocin. At a 10% lethal dose (10 mg/kg i.p.), GANU demonstrates minimal myelosuppression. This dose failed to depress normal bone marrow DNA synthesis, in contrast to a 96% inhibition in L1210 DNA synthesis. In L1210 cell suspension, equimolar doses of GANU and chlorozotocin produced equivalent degrees of inhibition in DNA synthesis. GANU has significant L1210 activity in BALB/c X DBA/2 F1 mice treated on Day 2 of tumor growth. A 117% increased life-span and 15% 45-day survivors are atained with 15 mg/kg i.p., a 50% lethal dose. However, in concurrent studies using randomly selected littermate groups of mice, GANU proved less active than chlorozotocin which produced a 306% increased life-span (15 mg/kg i.p.). GANU and chlorozotocin have similar in vitro alkylating activity but the in vitro carbamoylating activity of GANU is sevenfold that of chlorozotocin. On a molar basis, the lethal toxicity of GANU is twice that of chlorozotocin. The significant carbamoylating activity of GANU may contribute to its greater toxicity and therefore limit the mumoles of alkylating agent that can be administered to the tumor. These structure-activity studies further confirm that the addition of a glucose carrier to a cytotoxic nitrosourea moiety can selectively reduce bone marrow toxicity while retaining antitumor activity.
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PMID:Biological and biochemical properties of 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (NSC D 254157), a nitrosourea with reduced bone marrow toxicity. 13 78

The inhibition of the proliferation of hyperdiploid Ehrlich ascites tumor cells in suspension cultures by amobarbital is coupled to an increased glycolytic activity as shown by lactic acid production and glucose consumption; higher concentrations of amobarbital than 1 mM enhance the ATP/ADP ratio of the total cell. The actual activity of pyruvate dehydrogenase of intact cells is completely inhibited in the presence of 2 mM amobarbital as was shown by the 14CO2 evolution from [114C]pyruvate or the incorporation of 14CO2 into the total lipid fraction of the cells from [U-14C]lactate. The pyruvate dehydrogenase complex from Ehrlich ascites tumor cells is completely inhibited by 1 mM amobarbital in vitro. The activity of alpha-oxoglutarate dehydrogenase is inhibited by amobarbital, too, as well as shown by measuring the 14CO2 evolution from [1-14C]glutamate with intact cells. It is suggested that the inhibition of pyruvate dehydrogenase in the presence of amobarbital is the result of a direct action on the enzyme as well as the consequence of a change in the cellular redox state or its energy charge.
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PMID:Multiple effects of amobarbital on Ehrlich ascites tumor cells. Inhibition of pyruvate dehydrogenase. 14 57

The effects of estrogens on transport and incorporation of amino acids into the R3230AC mammary adenocarcinoma were studied in vivo and in vitro. Dissociated tumor cells from ovariectomized rats, like those from diabetic rats, displayed elevated transport of proline, representing entry by the A system; transport of phenylalanine (L system) was unaltered, as was glucose transport and its utilization. Administration of estradiol valerate decreased the entry of proline into tumor cells from intact, diabetic, or ovariectomized animals; the response to the steroid hormone was greater in ovariectomized or diabetic rats compared to intact animals. The time course of the effects of estrogen treatment was examined in diabetic rats. By 72 hr, transport of both proline and leucine was significantly decreased; incorporation of leucine into proteins and uridine into RNA was significantly reduced by 24 hr after injection of estradiol valerate. The effects of estrogen in vivo to reduce transport of amino acids and their incorporation into proteins appeared to correlate with the reduced tumor growth observed. Experiments were performed to examine the effects of 17 beta-estradiol in vitro on amino acid transport into dissociated cells from ovariectomized or diabetic rats. Under these experimental conditions, 17 beta-estradiol (10(-6)M) inhibited proline transport with little or no effect on leucine transport in cells from ovariectomized rats; in cells from diabetic rats, proline transport and leucine incorporation were significantly reduced by estradiol, whereas phenylalanine transport was slightly inhibited (approximately 20%). The effect of estradiol in vitro was also manifest in tumor cells obtained from diabetic rats treated in vivo with estradiol valerate; estradiol in vitro caused a further reduction in proline transport but not in leucine transport, results that imply some specificity to the action of estrogen on the A system. Since we had earlier shown that insulin action on transport in these tumor cells were directed towards the A system, we examined the effects of insulin, estradiol, and their combination in vitro on proline and leucine transport. Insulin (10(-8) M) stimulated proline transport; 17 beta-estradiol, at a selected lower level of 10(-8) M, inhibited proline transport. When both were added in vitro, estradiol (10(-8 M) was capable of significantly reducing the insulin (10(-8) M)-induced increase in proline transport. Leucine transport was not altered in any of these experiments. Together, these data suggest that estrogens are capable of inhibiting amino acid transport into the R3230AC mammary carcinoma, an effect that is compatible with reduced tumor growth. The possible relationship of estrogen and insulin at the level of amino acid transport remains to be elucidated.
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PMID:Effects of estrogen to alter amino acid transport in R3230AC mammary carcinomas and its relationship to insulin action. 15 4

Ca2+ uptake into Ehrlich ascites tumor cells was studied at 0 degrees C in the presence of mitochondrial inhibitors, conditions that minimized complications caused by sequestration of Ca2+ into organelles or by excretion. Under these conditions Ruthenium Red inhibited Ca2+ uptake, but other previously implicated ions, such as Pi or Mg2+, had no effect. Valinomycin either inhibited or slightly stimulated Ca2+ uptake depending on the presence of excess K+ on the outside or inside of the cell, respectively. Nigericin inhibited Ca2+ transport. Based on these data we propose an electrogenic uptake of Ca2+, possibly via a Ca2+/H+ antiport mechanism. The observation that glucose inhibited Ca2+ uptake suggested that in Ehrlich ascites tumor cells an energy-driven Ca2+ expulsion mechanism is operative, similar to that in erythrocytes. Plasma membrane preparations of ascites tumor cells were found to contain a Ca2+-dependent ATPase. These preparations, when incorporated into liposomes in an inside-out orientation, catalyzed an ATP-dependent uptake of Ca2+.
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PMID:Ca2+ translocation in Ehrlich ascites tumor cells. 15 90

Several mathematical models for the development of immune reaction during cancer diseases were plotted. The models describe both stimulation of the immune system by the tumor and its suppression. Non-specific inhibition was considered which resulted from glucose deficiency accompanying the development of a malignant tumor. The inhibiting effect of antitumour antibodies on toxic influence of limphocytes-killers was taken into account. The qualitative and quantitative study of the models showed the limits for the description of real interactions between tumour and organism by the mechanisms stated.
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PMID:[Immune response dynamics during malignant tumor development]. 15 93

Cell proliferation, viability, DNA-, RNA-, protein synthesis, amino acid transport, repiration and lactate/glucose quotient of Ehrlich ascites tumor cells grown in suspension culture in serum free medium supplemented with albumin charges of different origin were studied. Optimal cell growth was obtained in nutrient medium supplemented with 1% bovine serum albumin (Cohn-fraction V, Serva). Cell proliferation under these culture conditions was delayed to 50% as compared to controls in normal medium; the rate of synthesis of macromolecules was reduced; energy metabolism was not significantly imparied. The trend of the cells in albumin medium to attach to glass was independent from the pH of the cultures between 7.2 and 8.0; it was enhanced by fatty acid deprivation of the albumin.
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PMID:Proliferation and metabolic activities of Ehrlich ascites tumor cells in chemically defined albumin media. 16 Jul 4

Mouse, hamster, and human cells were transformed at the permissive temperature by mutants from simian virus 40 (SV40) complementation group A in order to ascertain the role of the gene A function in transformation. The following parameters of transformation were monitored with the transformed cells under permissive and nonpermissive conditions: morphology; saturation density; colony formation on plastic, on cell monolayers, and in soft agar; uptake of hexose; and the expression of SV40 tumor (T) and surface (S) antigens. Cells transformed by the temperature-sensitive (ts) mutants exhibited the phenotype of transformed cells at the nonrestrictive temperature for all of the parameters studied. However, when grown at the restrictive temperature, they were phenotypically similar to normal, untransformed cells. Growth curves showed that the (ts) A mutant-transformed cells exhibited the growth characteristics of wild-type virus-transformed cells at the permissive temperature and resembled normal cells when placed under restrictive conditions. There were 3-to 51-fold reductions in the levels of saturation density, colony formation, and uptake of hexose when the mutant-transformed cells were the elevated temperature as compared to when they were grown at the permissive temperature. Mutant-transformed cells from the nonpermissive temperature were able to produce transformed foci when shifted down to permissive conditions, indicating that the phenotypically reverted cells were still viable and that the reversion was a reversible event. SV40 T antigen was present in the cells at both temperatures, but S antigen was not detected in cells maintained at the nonpremissive temperature. All of the wild-type virus-transformed cells exhbited a transformed cells exhibited a transformed phenotype when grown under either restrictive or nonrestrictive conditions. Thers results indicate that the SV40 group A mutant-transformed cells are temperature sensitive for the maintenance of growth properties characteristics of transformation. Virus rescued from the mutant-transformed cells by the transfection method was ts, suggesting that the SV40 gene A function, rather than a cellular one, is responsible for the ts behavior of the cells.
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PMID:Role of simian virus 40 gene A function in maintenance of transformation. 16 76

Mitochondria from a rat mammary tumor (R3230AC) have been compared with mitochondria from pregnant and lactating rat mammary glands, with particular attention paid to inner membrane enzymes and Transport proteins. In the tumor the mitochondrial adenosine triphosphatase was not activated by 2,4-dinitrophenol, in contrast to the mammary mitochondria from lactating or pregnant rats. Translocation of adenosine diphosphate across the inner membrane was found to be more rapid in the tumor by virtue of lovered Km adenosine diphosphate and raised Vmax. Transport of phosphate and dicarboxylic acids occurred at similar rates in all three types of mitochondria. The inner membrane proteins were also examined directly by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and some differences are noted. These results, although they indicate subtle differences between the inner mitochondrial membranes of tumor as compared with those of pregnant or lactating rat mammary glands, cannot form the basis of an explanation for enhanced glucose utilization and aerobic lactic acid production in this tumor.
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PMID:A comparative study of inner membrane enzymes and transport systems in mitochondria from R3230AC mammary tumor and normal rat mammary gland. 16 45


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