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

We have examined the interaction of dexamethasone with the ZR75-1 human breast cancer cell line to determine if glucocorticoids might directly inhibit growth of breast cancer cells. Growth of these cells in serum-free medium was stimulated significantly by physiological concentrations of insulin (0.1 to 1.0 nM). Pharmacological concentrations of dexamethasone (10 nM) reduced cell number below that found in controls and nearly abolished the effect of insulin after several days in culture. Thymidine and uridine, but not leucine, incorporation into macromolecules or acetate incorporation into fatty acids were similarly inhibited by dexamethasone in the presence of absence of insulin. Dexamethasone did not inhibit insulin effects by altering insulin receptor affinity or concentration, as determined by Scatchard analyses of insulin binding. Net thymidine uptake into the trichloroacetic acid-soluble fraction of the cell was stimulated by insulin and inhibited by dexamethasone also inhibited thymidine kinase activity multiple potential sites of glucocorticoid action that directly oppose the effects of insulin. They also suggest that glucocorticoids have a direct inhibitory effect on proliferation of human breast cancer cells, which may help explain breast tumor regression following pharmacological glucocorticoid therapy.
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PMID:Direct inhibition of growth and antagonism of insulin action by glucocorticoids in human breast cancer cells in culture. 44 41

The possibility of differentiating estrogen-sensitive human breast cancer using incorporation studies with labeled uridine as a precursor of RNA metabolism is described. The purpose of this study was to explore inadequate function of the estrogen receptor as an alternative or supplementary aid in selecting patients for hormonal manipulation. The disadvantage of the test is that only hormone dependence of a proliferating tumor cell population can be evaluated. Highly differentiated breast cancer cells exhibit the greatest estrogen sensitivity. The hormone-dependent tumors of premenopausal women show an increase in RNA synthesis, whereas uridine incorporation appeared to be inhibited in postmenopausal women.
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PMID:[Effect of estradiol on RNA biosynthesis of human breast carcinoma cells in vitro]. 45 27

Several biochemical parameters were examined relative to the sensitivity or resistance of representative rodent tumors to N-(phosphonacetyl)-L-aspartate (PALA). The activity of the target enzyme, L-aspartate transcarbamylase (ATCase), was evaluated in homogenates of a spectrum of murine neoplasms. ATCase activity was significantly lower in PALA-sensitive as opposed to PALA-refractory tumors. However, among tumors sensitive to PALA, there was no clearcut relationship between ATCase activity and degree of sensitivity to PALA. Thus, a number of hypotheses were proposed to explain differential sensitivity to PALA in vivo. Enzyme activities in the salvage pathway which phosphorylate pyrimidine nucleosides and deoxynucleosides were found to be greater in refractory tumors. The uptake of PALA, in vitro, though quite slow, was found to be two to eight times greater in two sensitive tumors as compared to the refractory L1210 leukemia. However, in vivo, 24 hours following graduated doses of PALA, nearly identical intratumoral drug concentrations were observed in representative sensitive and refractory tumors. Thus, ultimately, PALA transport would not appear to correlate with differences in drug sensitivity. A number of other biochemical parameters were also found to have no association with sensitivity to PALA in vivo. These included: kinetics of inhibition of ATCase, capacity for restitution of ATCase activity after a dose of PALA, degree of inhibition of ATCase at various doses of PALA, detoxification of PALA by tumor cells, kinetics of uptake of uridine, or catabolism of pyrimidines or pyrimidine nucleosides.
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PMID:Mechanisms of sensitivity or resistance of murine tumors to N-(phosphonacetyl)-L-aspartate (PALA). 47 6

Concentrations of intracellular orthophosphate were determined in Ehrlich ascites tumor cells incubated with glucose, inosine, or uridine in media of different orthophosphate concentration. The effects of orthophosphate concentration on the accumulation of lactate and of phosphoribosyl pyrophosphate and on concentrations of ribose 1-phosphate and ribose 5-phosphate in tumor cells incubated with glucose were also determined. Both the phosphorolysis of inosine and the rate of catabolism of ATP in cells incubated with 2-deoxyglucose were also influenced by the orthophosphate concentration of the medium.
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PMID:Role of orthophosphate concentration in the regulation of ribose phosphate synthesis and purine metabolism in Ehrlich ascites tumor cells. 56 Sep 2

Treatment of the solid Walker carcinosarcoma of the rat for a period of one year with cyclophosphamide (40 mg/kg at each passage; tumours were transplanted weekly) resulted in the formation of a cyclophosphamide-resistant tumour cell line. Without further treatment, animals injected with non-treated or cyclophosphamide pre-treated cells survived for 10 days on an average. After therapy with cyclophosphamide (2 x 38 mg/kg), rats with non-treated tumour cells survived 22 days whereas those with pre-treated tumours survived only for 17 days. Tumour cells which were shown to be sensitive in vivo also exhibited a larger reduction in 3H-thymidine and 3H-uridine incorporation in the in vitro short term test after incubation with urine from cyclophosphamide-treated rats or with 4-hydroperoxy-cyclophosphamide. The resistance to cyclophosphamide which was detected in animal experiments with Walker carcinosarcoma can therefore also be observed using the in vitro short term test.
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PMID:Detection of induced tumour-resistance to cyclophosphamide by the in vitro short term test. 57 79

The inhibition of uridine and thymidine in Ehrlich ascites cells is a basic property of the methylhydrazone structure and is reinforced by introducing a beta-chloroethyl group. This was shown by variation of the substituents at the N'-nitrogen atom of N'-methyl-N'-beta-chloroethyl-benzaldehyde hydrazone. Probably this action is due to an ethylenimmonium intermediate. This is derived from the observation that substituents which increase the nucleophilic property of the N'-nitrogen atom show a greater inhibitory effect in vitro. The therapeutic effect, however, is not enhanced when tested on the solid Ehrlich ascites tumor of mice. A better therapeutic effect resulted from introduction of chlorine atoms in positions 3 and 4 of the ring which inhbiits as well a probable metabolic hydroxylation of the ring.
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PMID:[On structure-activity relationships of N'methyl-N'-beta-chloroethyl-benzaldehyde hydrazones (author's transl)]. 58 10

Tumor cells in a cytostatic state caused by macrophages and antibody were isolated. Such suppressed cells excluded vital dye, incorporated uridine and leucine, and metabolized glucose. They did not, however incorporate thymidine, nor did they resume cell division in culture. During prolonged culture, these cells eventually died. In this system, cytostasis was an all-or-nothing phenomenon at the level of the individual cell. Once in the cytostatic state tumor cells did not resume proliferation.
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PMID:Tumor cell cytostasis by macrophages and antibody in vitro. II. Isolation and characterization of suppressed cells. 65 62

In a pilot study of 40 patients with inoperable bronchiogenic carcinomas the results of clinical therapy were compared with those of in vitro tests by measuring the effects of cytostatic agents on the incorporation of precursors into DNA and RNA in tumour cells incubated in vitro for short periods. Tumour cells that showed little inhibition by the cytostatic agents in vitro (less than 30% inhibition at a concentration of 10(-2) mg/ml adriamycin) came from patients who responded poorly to cytostatic therapy. On the other hand, tumour cells that were strongly inhibited in vitro (greater than 30% inhibition) came from tumours which proved to be sensitive to the chemotherapy given to the patient. A strong correlation existed between the inhibition of uridine incorporation by the tumour cells in vitro by adriamycin and the responses of the tumour to clinical therapy even when combination-therapy was given without adriamycin. There was also a significant correlation between the inhibiting effect of adriamycin in vitro and the survival time of the tumour patients.
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PMID:[Resistance testing and chemotherapy results of bronchial tumours (author's transl)]. 66 81

Incorporation of uracil and orotic acid into the ribonucleic acid (RNA) fraction of rat liver during carcinogenesis induced with 3'-methyl-4-(dimethylamino)azobenzene was investigated. Uracil incorporation was found to be gradually elevated during the early stage (about 2 weeks) of the carcinogenesis, although not in the normal rat liver homogenates contacted with the carcinogen for a short hours, and the elevated uptake was maintained until tumor induction. On the other hand, orotic acid incorporation reverted to the original level after a temporary increase during the early stage. In a good agreement with the increased uracil incorporation, activities of both uridine phosphorylase and uridine kinase involved in the salvage pathway of RNA synthesis also increased during the early stage, and their activities in the liver were maintained at elevated levels after discontinuance of the carcinogen feeding. The activity of uridine monophosphate (UMP) pyrophosphorylase, converting uracil to UMP, was not detected during the early stage. Significance of the activation of the salvage pathway of RNA synthesis during the early stage of an axo dye-induced carcinogenesis were discussed.
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PMID:Elevation of the salvage synthesis of ribonucleic acid in the rat liver during the induction of hepatoma with 3'-methyl-4-(dimethylamino)azobenzene. 72 24

The therapeutic activity of ftorafur was compared to that of 5-fluorouracil (5-FU) in a number of tumor systems. The drugs were active against ip L1210 leukemia when administered ip, sc, or orally. Administration every fourth day x 3 proved to be the most effective treatment schedule for both drugs, although significant activity was seen on all treatment schedules tested. Both congeners had activity against sc implanted L1210 leukemia as well as a limited effect on the ic implanted tumor. 5-FU produced greater increases in lifespan of mice bearing L1210 leukemia than did ftorafur. 5-FU was also more effective against ip B16 melanoma and ip Gardner 6C3HED lymphosarcoma. Ftorafur was ineffective in the treatment of mice bearing ip P388 leukemia, a tumor which is quite sensitive to 5-FU. At approximately equimolar doses both drugs produced a persistent inhibition of 2'-deoxyuridine incorporation into DNA of L1210 cells in vivo. Ftorafur produced a greater inhibition of uridine incorporation into RNA than did 5-FU, which may account for the lower therapeutic activity of ftorafur. In combination chemotherapy of L1210 leukemia 5-FU plus ftorafur was no more effective than 5-FU alone, neither of the congeners was synergistic with either adriamycin or actinomycin D, and in combination with methotrexate therapeutic synergism was observed with 5-FU but not with ftorafur. After eight transplant generations of exposure to ftorafur, a subline of L1210 leukemia became totally resistant to ftorafur and simultaneously cross-resistant to 5-FU. Doses of ftorafur and 5-FU which were optimally effective in mice bearing the parental L1210 line were lethal to mice implanted with the ftorafur-resistant subline. When treatment of the resistant subline was discontinued after nine transplant generations of exposure to ftorafur, sensitivity to 5-FU returned after three transplant generations without ftorafur. The subline retained its resistance to ftorafur until eight transplant generations after cessation of ftorafur treatment. Another subline of L1210 leukemia exposed to 5-fU for 20 transplant generations proved to be completely resistant to 5-fu and cross-resistant to ftorafur. The mutual cross-resistance between ftorafur and 5-FU supports the contention that ftorafur acts primarily as a depot form of 5-FU.
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PMID:Comparison of 5-fluorouracil and ftorafur. II. Therapeutic response and development of resistance in murine tumors. 79 50


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