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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of Ehrlich ascites tumor cells in their own ascites fluid induced a reversible metabolic adaptation to these "starvation" conditions which was associated with a fragmentation of DNA. Endogenous poly(ADP-ribose) residues also increased, reaching within 1-3 h values 6-10 times higher than in cells taken directly from the mouse peritoneum. The NAD content changed only slightly while dimethyl sulfate-induced accumulation of poly(ADP-ribose) (10-fold within 30 min) was associated with a rapid depletion of NAD (85% lost at 30 min). Nevertheless, turnover of poly(ADP-ribose) as measured by the decay rate of the polymer upon addition of benzamide was dramatically stimulated in both situations, reaching apparently identical half-lives (t 1/2 approximately equal to 1 min) in "starved" and in alkylated cells. However, since penetration of benzamide into the nucleus may be the rate-limiting factor in these studies, turnover of poly(ADP-ribose) in dimethyl sulfate-treated cells may still be much higher than that in "starved" cells. In cells treated with dimethyl sulfate, suppression of poly(ADP-ribose) synthesis by benzamide did not interfere with DNA fragmentation or with DNA resealing as determined by the nucleoid procedure. By contrast, starvation induced a type of DNA incision that was prevented by benzamide. It is proposed that starvation-induced scission of DNA occurs at specific ("regulatory?") sites requiring poly(ADP-ribose) formation to take place, while fragmentation of DNA at random as seen with alkylating agents is associated with, but not dependent on, increased poly(ADP-ribosyl)ation.
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PMID:Stimulation of poly(ADP-ribosyl)ation during Ehrlich ascites tumor cell "starvation" and suppression of concomitant DNA fragmentation by benzamide. 683 44

A high molecular weight glycoconjugate has been isolated from neurite-producing neuronal tumor cells in culture and has been designated as I(0) based on its elution characteristics in gel filtration chromatography. This molecule cannot be found in a variety of nonneuronal cells. I(0) is found in the substratum-attached material or cell fraction of neurite-producing neuroblastoma cells, depending upon culture conditions. It is found in the substratum-bound fraction of B104 rat neuroblastoma cells during serum starvation and in the EGTA-detached cell fraction of B104 cells grown in chemically defined N2 medium. It occurs only in the cell fraction of the human neuroblastoma line Platt. Examination of behavioral variants of the B104 rat line further strengthens the association of I(0) with neurite production; the constitutive neurite-producing E(R)B9 variant contains I(0) while the non-neurite-producing E(R)A11 variant does not. I(0) is large, eluting in the void volume of sepharose-CL2B columns. Radioiodination of intact cells with lactoperoxidase shows I(0) to be a cell surface component. Metabolic radiolabeling studies show that it contains a high proportion of polysaccharide to protein, does not contain mannose, and is unsulfated. Alkaline borohydride reduction release two size classes of large polysaccharide chain. The alkaline reduction results, along with the mannose incorporation studies, show the presence of O-glycosidic linkages and few, if any, N-linkages. Resistance to nitrous acid deamination, insensitivity to glycosaminoglycan lyases, and the absence of sulfation, indicate that I(0) does not contain the glycosaminoglycans hyaluronic acid, chondroitin-, dermatan-, or heparin- sulfates. Affinity column chromatography reveals high binding affinity of I(0) to polyornithine and no binding to gelatin (collagen) or the glycosaminoglycans hyaluronate and heparin. These studies describe a unique high molecular weight glycoconjugate on the surface of neurite-producing neuroblastoma cell lines from two species.
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PMID:Isolation and characterization of a large, neurite-associated glycoconjugate from neuroblastoma cells. 683 76

We have established optimal conditions for the in vitro formation of peptidyl-[3H] puromycin by mammalian ribosomes. The growth conditions of cultured Ehrlich ascites tumor cells were manipulated to produce changes in the polysome profiles. The correlation between polysome content and peptidyl-[3H] puromycin formation was linear and excellent when different cell densities were compared. The percentage of ribosomes actively engaged in protein synthesis, calculated from the number of 3H-peptide bonds formed, was similar in rapidly growing Ehrlich cells (47%) and in young rat gastrocnemius muscle (44%). Starvation resulted in a 50% reduction in the number of puromycin-reactive ribosomes in rat gastrocnemius.
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PMID:Radioactive puromycin formation as an assay for the proportion of active ribosomes in mammalian cells: correlation with polysome profiles under different physiological conditions. 688 82

Glucose turnover ([3(3)H]glucose) and gluconeogenesis from alanine ([U-14C]alanine) were measured in non-tumor bearing (NTB) and tumor-bearing (TB) inbred F344 male rats during starvation and in response to graded levels of glucose infusion. All groups demonstrated a glucose turnover appropriate to the prevailing steady-state plasma glucose level. Whereas NTB animals exhibited maximal suppression of gluconeogenesis from alanine at infusion rates of 0.39 mg/100 g total body weight/minute, TB animals suppressed alanine-to-glucose conversion only at a glucose infusion rate of 0.71 mg/100 g total body weight/minute. Glucose clearance was consistently higher in TB groups but did not change in either NTB or TB groups during infusion. Blood lactate levels increased in response to glucose infusion only in TB animals. These results suggested that starved TB animals obligately utilized more glucose than did NTB controls but were able to adjust turnover appropriately to plasma glucose levels. However, gluconeogenesis was suppressed only at higher glucose infusion rates in TB rats compared to NTB animals.
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PMID:Glucose turnover and gluconeogenesis during hypocaloric glucose infusion in tumor-bearing F344 male rats. 692 21

1. The dependency of product formation on reaction time and on enzyme concentration was studied with certain purified enzymes and liver microsomal mixed-function oxidase system. 2. The product-formation-time relation was estimated with different enzyme and/or substrate concentrations for the reactions limited by diffusion. 3. The kinetic constants of the product-time relations in these diffusion systems have been verified experimentally to give a more specific and detailed characterization of an enzyme system under a variety of physiologic and reaction conditions. 4. The influence of inhibitors and activators in vitro, the effect of enzyme preparation technic, aging, starvation, pretreatment with somatotropic hormone, phenobarbital or 3-methylcholanthrene, and the effect of a tumor were studied. 5. The influence of vitamin C deficiency in guinea pig was also studied.
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PMID:The effect of chemical and physiological factors on the kinetics for product formation as it relates to enzyme activity and concentration, reaction time and to substrate adsorption and affinity. 705 28

When starved of a carbon source, early passage normal cells such as chick embryo fibroblasts, human fibroblasts, mixed culture of splenic lymphocytes as well as "normal" cell lines (Nil or CHO cells grown as monolayer cultures) maintain their ATP levels for 8 to 24 h at essentially those characteristic of cells fed glucose. Several malignant or transformed cells (Py6, PyNil, Ehrlich ascites tumor cells, CHO cells in suspension and P388 lymphoblasts) exhibit a dramatic lowering in their ATP within a few hours of the removal of glucose. Normal cells exposed to 2-deoxy-D-glucose (2-DOG) in the absence of glucose lose ATP as rapidly as starved transformed cells. The loss of ATP by transformed cells on starvation is also accelerated by 2-DOG as is cell death. 2-deoxy-D-galactose (2-DOGAL) slows the loss of ATP in glucose starved transformed cells (growing as monolayer cultures) observed when the cultures are shifted to sugar-free medium. Finally, normal cells in culture are able to maintain both their ATP levels and their viability even after prolonged cultivation in a nutrient-free medium. Cultivation of malignant cells in a nutrient-free medium causes rapid loss in their ATP, a phenomenon not preventable by the presence of ouabain.
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PMID:Starvation, deoxy-sugars, ouabain, and ATP metabolism in normal and malignant cells. 715 Oct 33

The ratio of initiation of protein synthesis in Ehrlich ascites tumor cells in culture is reduced by over 60% in the absence of a single essential amino acid. Cell-free extracts prepared from control and amino acid-starved cells retain some of the translational characteristics of these cells and are able to form [40 S.Met-tRNAfMet] initiation complexes. Studies with inhibitors show that up to 63% of the translation directed by endogenous mRNAs in vitro depends on reinitiation of polypeptide chains. Amino acid starvation inhibits this activity, as well as protein synthesis due to in vitro polysomal run-off, by up to 75%. Analysis of [40 S.Met-tRNAfMet]initiation complexes formed in vitro on native 40 S subunits shows that amino acid starvation causes up to a 77% decrease in the concentration of these complexes relative to the corresponding fed controls. This difference is eliminated by the addition of highly purified eukaryotic initiation factor eIF-2. Factor eIF-3 also stimulates [40 S.Met-tRNAfMet] formation in the cell extracts but does not abolish the difference between fed and starved preparations. Mixing experiments have not so far revealed any inhibitor of initiation complex formation in the starved cell extracts.
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PMID:The effects of amino acid starvation on regulation of polypeptide chain initiation in Ehrlich ascites tumor cells. 735 42

Adequate parenteral nutritional support improves nutritional status in cancer patients, but its effect on tumor growth remains controversial. Using a transplantable mammary adenocarcinoma in a rat-TPN model, the relative effect of different exogenous intravenous nutrients on tumor growth and host maintenance was studied. Relative to chow controls, starvation increased host depletion without reducing tumor growth. Adequate carbohydrate calories alone neither improved host maintenance nor stimulated tumor growth, yet adequate amino acids alone did improve host maintenance but also stimulated tumor growth. Adequate amino acids and carbohydrates given simultaneously maximized both host maintenance and tumor growth. In contrast, an isocaloric, isonitrogenous, intravenous diet providing non-nitrogenous calories as fat promoted host maintenance equivalent to carbohydrate-based TPN with no tumor stimulation. This apparent differential utilization of fat calories by normal and malignant cells may permit manipulation of the relative benefit of parenteral nutrition to host or to tumor, permitting host repletion without tumor stimulation or alternatively tumor stimulation at appropriate times to increase sensitivity to phase-specific antineoplastic therapy.
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PMID:Host-tumor interaction and nutrient supply. 738 37

Previously we have found that stationary Ehrlich ascites carcinoma (EAC) cells in vivo accumulated heat shock proteins (HSPs) and became resistant to necrotic death induced by prolonged energy deprivation of hyperthermia. Here we report that apoptotic death induced by nutrient starvation, transient ATP depletion, heat shock and a microtubule-disrupting drug, vinblastine, was also suppressed in stationary EAC cells comparing with exponential cells. When exponential (sensitive) cells were subjected to short-term heating with recovery to accumulate inducible form of HSP70, they also became resistant to all of the employed apoptosis-inducing exposures, and an inhibitor of cytosolic protein synthesis, cycloheximide, prevented acquisition of the resistance. It is suggested that in vivo accumulation of HSPs in stationary tumor cells can be endogenous protective device against apoptotic death induced by starvation or some anticancer treatments.
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PMID:Resistance of Ehrlich tumor cells to apoptosis can be due to accumulation of heat shock proteins. 749 72

Perfusion insufficiency, and the resultant hypoxia, often induces a compensatory neovascularization to satisfy the needs of the tissue. We have used multicellular tumor spheroids, simulating avascular microenvironments within a clonal population of glioma tumor cells, in conjunction with in situ analysis of gene expression, to study stress inducibility of candidate angiogenic factors. We show that expression of vascular endothelial growth factor (VEGF) is upregulated in chronically hypoxic niches (inner layers) of the spheroid and that expression is reversed when hypoxia is relieved by hyperoxygenation. Acute glucose deprivation--another consequence of vascular insufficiency--also activates VEGF expression. Notably, glioma cells in two distinct regions of the spheroid upregulated VEGF expression in response to hypoxia and to glucose starvation. Experiments carried out in cell monolayers established that VEGF is independently induced by these two deficiencies. Upon implantation in nude mice, spheroids were efficiently neovascularized. Concomitant with invasion of blood vessels and restoration of normoxia to the spheroid core, VEGF expression was gradually downregulated to a constitutive low level of expression, representing the output of nonstressed glioma cells. These findings show that stress-induced VEGF activity may compound angiogenic activities generated through the tumor "angiogenic switch" and suggest that stress-induced VEGF should be taken into account in any attempt to target tumor angiogenesis.
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PMID:Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis. 753 42


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