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

Quercetin is a naturally occurring flavonoid, chemically related to cromolyn. Quercetin has been shown to inhibit antigen- and mitogen-induced histamine release from rat mast cells and basophils of subjects with hay fever, to increase cyclic adenosine monophosphate (AMP) in Ehrlich ascites tumor cells and to inhibit phosphodiesterase and certain adenosine triphosphatase (ATPase) systems. We have studied the effect of quercetin on mouse T cell responses. When 5 x 10(-6) to 5 x 10(-5) M quercetin is present throughout either allogeneic mixed leukocyte culture (MLC) or cytotoxic T lymphocyte (CTL) assay culture, inhibition of in vitro CTL generation or effector function results, respectively (inhibition is 75-100% at 2 x 10(-5) M and 100% at 5 x 10(-5) M). Quercetin also inhibits concanavalin A-induced DNA synthesis. Addition of Cu2+ strongly blocks the effects of quercetin in all systems tested, in a concentration dependent fashion, while Mg2+ and Ca2+ have little or no effect and Mn2+ and Co2+ have a significant but slight blocking effect on quercetin-mediated inhibition of both CTL generation and function. In kinetic studies, evidence was obtained for the existence of a major quercetin-sensitive step in CTL induction, between 3 and 24 hr of the MLC.
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PMID:Quercetin inhibition of the induction and function of cytotoxic T lymphocytes. 621 17

Freshly isolated human T lymphocytes were separated into two subpopulations on the basis of their ability to form E rosettes after treatment with the phosphodiesterase inhibitor, theophylline. T cells that retained the ability to form E rosettes (T-res cells) and those that failed to form E rosettes (T-sens cells) were assayed for natural killer (NK) cell activity against 51Cr-labeled K562 tumor cells and for the ability to proliferate and kill allogeneic cells in mixed-lymphocyte culture (MLC). T-sens cells were highly enriched for NK activity. In contrast, T-res cells exhibited much less activity than either T-sens or unseparated T cells (T-sens greater than unseparated T cells approximately equal to unseparated PBL approximately equal to non-T cells greater than T-res cells). T-sens cells were poorly responsive to allogeneic cells in proliferation assays and demonstrated greater levels of cytotoxicity against allogeneic cells than T-res cells. T cells stimulated with allogeneic lymphocytes for 7 days were cytotoxic for K562 targets while comparably stimulated non-T cells and T cells cultured with medium were not cytotoxic. Cold target inhibition experiments suggested that within the T-sens subset there are overlapping populations which mediate cytotoxicity against K562 and allogeneic cells. These studies demonstrate that freshly isolated human T cells are composed of heterogeneous populations which differ in their ability to mediate NK and to generate cytotoxic T lymphocytes in culture.
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PMID:Spontaneous and alloantigen-induced cytotoxicity by human T-lymphocyte subpopulations. 622 61

The interaction between metastasizing tumor cells and the hemostatic system of the host has been implicated in successful tumor cell dissemination. Prostacyclin (PGI2) decreases metastasis from tail vein injected B16 amelanotic melanoma (B16a) cells when administered 15 min prior to tumor cells. This effect is potentiated by a phosphodiesterase inhibitor. Initial trapping of 125I Udr labelled tumor cells in pulmonary vascular beds is unaltered by PGI2 but retention time is decreased. PGI2 decreases retention time even when administered 60 min post tumor cells. Structurally unrelated thromboxane (TX) synthetase inhibitors and a TXA2 receptor antagonist also reduce metastasis from tail vein injected B16a cells. Furthermore, one inhibitor, 1-(7-carboxyheptyl)imidazole, when injected intraperitoneally reduced spontaneous metastasis from subcutaneous B16a and Lewis lung carcinoma tumors. These results suggest that selective manipulation of PGI2 and TXA2 can reduce the hematogenous spread of tumor cells.
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PMID:Inhibition of tumor cell metastasis by modulation of the vascular prostacyclin/thromboxane A2 system. 624 6

The phenotype of three ectoenzymes was determined for murine resident peritoneal macrophages, macrophages elicited in vivo by treatment of mice with thioglycollate, Corynebacterium parvum or pyran, and for resident macrophages activated in vitro by treatment with lymphokine. The relationship of these biochemical markers to macrophage antiviral and anti-tumor activity was established. Thioglycollate-elicited macrophages showed a unique ectoenzyme phenotype, with increased leucine aminopeptidase and alkaline phosphodiesterase I activity and markedly reduced 5'-nucleotidase activity as compared with resident macrophages. Thioglycollate-elicited macrophages exhibited extrinsic antiviral activity against herpes simplex virus but did not show anti-tumor activity. Another ectoenzyme phenotype was shared by macrophages elicited in vivo by treatment of mice with the immunomodulators or in vitro by treatment with antigen-specific lymphokine. These macrophage populations showed increased levels of leucine aminopeptidase but reduced levels of both 5'-nucleotidase and alkaline phosphodiesterase. This ectoenzyme phenotype was associated with the acquisition by the macrophages of selective anti-tumor activity. There appear to be clear distinctions in biochemical markers and functional properties among macrophages activated by different mechanisms.
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PMID:Changes in macrophage ectoenzymes associated with anti-tumor activity. 625 Nov 33

The effect of the alkylating agent 2,3,5-tris(ethyleneimino)benzoquinone (Trenimon) on the uptake of 2-aminoisobutyric acid, 1-aminocyclopentane-1-carboxylic acid (cycloleucine), 3-O-methyl-D-glucose, and 86Rb was studied. All transport studies were performed at nonsaturating conditions where the specific transport system was rate limiting for the uptake. The activities of all systems are reduced after treatment with the alkylating agent. The impairment of the plasma membrane is expressed 30 sec after exposure to the drug, as measured by the 86Rb uptake, and lasts for at least 12 hr according to the reduced 3-O-methyl-D-glucose uptake. Inhibition of protein synthesis by cycloheximide for 2 hr does not affect the uptake of 86Rb. The short interval which is necessary before an inhibition of 86Rb uptake can be registered and the resistance of the 86Rb transport system to an inhibition of protein synthesis are considered as indicative for a direct alkylation of a membrane constituent. Treatment with the alkylating agent increases the cyclic adenosine 3':5'-monophosphate of the cells. This effect is not due to an effect on adenylate cyclase or the membrane-bound cyclic adenosine 3':5'-monophosphate phosphodiesterase. In view of the known correlations between plasma membrane functions and the regulation of cell division, it is proposed that the growth inhibition by Trenimon of Ehrlich ascites tumor cells may be caused by its interaction with the plasma membrane.
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PMID:Interaction of the alkylating antitumor agent 2,3,5-tris(ethyleneimino)benzoquinone with the plasma membrane of Ehrlich ascites tumor cells. 625 62

When applied to mouse skin in vivo, both the strong tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) (2 nmol) and the divalent cation ionophore A 23187 (200 nmol) caused the same responses, i.e., skin inflammation and prostaglandin E2-mediated epidermal hyperplasia. In both cases, these events were accompanied by certain biochemical reactions in the epidermis such as an increase in the biosynthesis of and sensitivity to prostaglandin E2, increase in ornithine decarboxylase and phosphodiesterase activities, and refractoriness of cyclic adenosine 3':5'-monophosphate production to beta-adrenergic stimulation. In contrast to A 23187, TPA did not induce degranulation of mast cells; whereas, in contrast with TPA, A 23187 did not show tumor-promoting activity. These results indicate that the observed biological effects of TPA are no indication of tumor-promoting ability and that, on the other hand, the mitogenic effects of A 23187 are possibly not due to its properties as a calcium ionophore.
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PMID:Prostaglandin E-mediated mitogenic stimulation of mouse epidermis in vivo by divalent cation ionophore A 23187 and by tumor promoter 12-O-tetradecanoylphorbol-13-acetate. 625 72

In this study, adenylate cyclase, phosphodiesterase and cyclic adenosine 3',5'-monophosphate (cAMP) levels were measured in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors with different growth characteristics in both intact and ovariectomized rats. Tumors were classified as growing, stable, or regressing over a 10-14-day period before excision. Regressing or static tumors had a higher cAMP concentration relative to tumors that were growing actively. This was due to high adenylate cyclase activity and low phosphodiesterase (both high and low Km) activities. Although estrogen deprivation resulted in a much greater rate of tumor regression than would occur spontaneously under normal conditions, the levels of adenylate cyclase, phosphodiesterases and cAMP were the same in tumors obtained from either intact or ovariectomized rats, when comparisons were made within the same category of tumor. These observations suggest that cAMP metabolism is independent of estrogen, since it is related to enhancement or retardation of growth rather than to the presence of absence of estrogen.
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PMID:Regulation of cyclic adenosine 3',5'-monophosphate in relation to growth of dimethylbenz[a]anthracene-induced mammary tumors in rats. 626 41

Biopsy samples were obtained from tumor tissue and surrounding normal tissue from the same organs of the same patients in 25 patients. Adequate studies could be performed on all parameters in 18 tissue pairs: 12 malignant melanomas, 4 sarcomas, and 2 others. Significantly higher levels of cAMP low affinity phosphodiesterases were found in the tumors as compared to the controls. Similar differences were seen in the high affinity cAMP phosphodiesterases, but these were of borderline significance. High affinity cGMP phosphodiesterase levels did not differ significantly between normal and neoplastic tissue samples. Low affinity cGMP phosphodiesterases were not detectable in either tissues. These studies together with earlier experimental findings suggest possible auxiliary therapeutic trials with phosphodiesterase inhibitors.
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PMID:Cyclic nucleotide phosphodiesterases in normal and malignant human tissues. 627 86

LLC-PK1 cells in culture do not concentrate alpha-methylglucoside (alpha-meG) during their early growth phase but develop the capacity to concentrate this hexose as the growth rate decreases in confluent cultures. The concentrating ability is dependent on the Na+ electrochemical gradient and is inhibited by phlorizin with KI,0.5 approximately 0.2 microM. The development of the concentrative capacity can be accelerated by the Friend cell inducer hexamethylene bisacetamide (HMBA) and by the phosphodiesterase inhibitors dibutyryl cAMP, theophylline, and 1-methyl-3-isobutylxanthine (MIX). In cultures treated with any of these differentiation-accelerating chemicals, the development of alpha-meG concentrating capacity is severely inhibited by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) but not by inactive (in tumor promotion) analogs of TPA. In all cases, an early event in the development of alpha-meG accumulating capacity is an elevated intracellular cAMP concentration; however the results suggest that this increase in cAMP may be necessary but not sufficient to induce the differentiated hexose-accumulating capacity.
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PMID:Development of Na+-dependent hexose transport in a cultured line of porcine kidney cells. 627

Plasma membrane extracts from Herpes simplex virus type 1 transformed hamster embryo fibroblasts were chromatographed on Lens culinaris lectin coupled to Sepharose (LcH-Sepharose) and analysed by dodecyl sulphate polyacrylamide gel electrophoresis. Coomassie blue-staining revealed two major protein bands with apparent molecular weights of 125 000 and of about 75 000-90 000. In plasma membranes isolated from these tumor cells prior labeled with [3H]fucose or [3H]glucosamine these bands contained the highest amounts of incorporated radioactivity. Separation by LcH-Sepharose-affinity chromatography as well as metabolic labeling clearly demonstrates their glycoprotein character. The 125 000 protein coincides with alkaline phosphodiesterase I activity with a Km of 6 . 10(-4) M for TMP p-nitrophenyl ester and is competitively inhibited by UDP-N-acetylglucosamine. This enzymatic activity is also present in normal hamster embryo fibroblasts. Gel electrophoresis of the Lens culinaris lectin-binding glycoproteins from plasma membranes of normal hamster embryo fibroblasts additionally revealed a strong alkaline phosphatase activity represented by an apparent molecular weight of 150 000, while HSV1 hamster tumor cells contain only a very weak activity of this enzyme activity. HSV-lytically infected cells, however, have unchanged levels of alkaline phosphatase activity, whereas alkaline phosphodiesterase activity increases slightly.
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PMID:Alkaline phosphodiesterase I and alkaline phosphatase I in plasma membranes of herpes simplex virus type 1 transformed hamster cells. 627 77


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