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

The cellular localization of beta-adrenergic and prostaglandin (PG) receptors and their effects on adenylate cyclase activity (AC) and testosterone production in vitro were investigated in a transplantable rat Leydig cell tumor (H-540). Separation of the tumor cells in Percoll gradients revealed that the specific binding of [3H]PGE1 and [125I]Cyanopindolol was found in the same fraction as that of [125I]LH. This fraction--judged by light microscopy of smears--consisted of tumor Leydig cells. In addition, [125I]cyanopindolol was found specifically bound in the red blood cell fraction. In the Leydig tumor cells, approx 25% of the beta-adrenergic receptors was identified as beta 1-receptors, whereas approx 75% of the receptors were of the beta 2-subtype. The AC in Percoll purified Leydig tumor cells was stimulated by hCG (6-fold), PGE1 (2-fold), PGE2 (1.5-fold), PGI1 (2-fold) and isoproterenol (2-fold). The AC in the red blood cell fraction was stimulated by isoproterenol whereas the PGs and hCG had little or no effect. hCG, isoproterenol and PGE1 were able to stimulate testosterone production in vitro. At 44 h incubation, PGE1 was the most potent stimulator of testosterone production. In conclusion, tumor Leydig cells possess hCG, PGE1, PGI2 and beta-adrenergic receptors coupled to the AC. PGE1 and beta-adrenergic agonists stimulate testosterone production after prolonged incubation in vitro.
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PMID:A transplantable rat Leydig cell tumor--5. Cellular localization of beta-adrenergic and prostaglandin receptors and their effects on testosterone production. 284 May 32

Indomethacin enhanced macrophage cytostasis against MOPC-315 tumor cells in vitro. The effect of indomethacin was inhibited by prostaglandin E2 and by the lipoxygenase inhibitor nordihydroguaiaretic acid. Prostaglandin E2 and nordihydroguaiaretic acid also inhibited indomethacin stimulation of macrophage thymidine incorporation. Indomethacin inhibited macrophage prostaglandin E2 formation and stimulated leukotriene B4 synthesis. Nordihydroguaiaretic acid inhibited leukotriene B4 production. Our data indicate that eicosanoids play a role in regulating macrophage cytostasis.
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PMID:Indomethacin stimulation of macrophage cytostasis against MOPC-315 tumor cells is inhibited by both prostaglandin E2 and nordihydroguaiaretic acid, a lipoxygenase inhibitor. 284 83

PGE2 has previously been shown to suppress various leukocyte functions. In this study, we examined whether PGE2 would affect release of TNF-alpha from rat resident peritoneal macrophages. Two different, dose-dependent effects were observed: low PGE2 concentrations (0.1 to 10 ng/ml) stimulated, whereas higher concentrations (greater than 10 ng/ml) suppressed TNF-alpha release. PGE2-stimulated TNF-alpha production was dependent on de novo protein synthesis and was associated with an intracellular rise of cGMP. The importance of cGMP as an intracellular messenger for PGE2 was confirmed by the following evidence: (1) low PGE2 concentrations preferentially increased cGMP and not cAMP and (2) cGMP, either exogenously added or endogenously generated by sodium nitroprusside, were efficient stimulators of TNF-alpha production. In contrast, agents increasing intracellular cAMP concentrations such as PGE1, higher PGE2 doses, isoproterenol, and theophylline, all suppressed TNF-alpha synthesis. Only resident, but not casein-elicited or Corynebacterium parvum-activated macrophages, were stimulated by low PGE2 concentrations to increase TNF-alpha production. In tumor cytotoxicity assays, PGE2-activated macrophages were active only against TNF-alpha-sensitive target cells. These findings demonstrate that TNF-alpha synthesis in macrophages is up-regulated by cGMP and down-regulated by cAMP, which indicates that cyclic nucleotides act as intracellular messengers for extracellular signals of macrophage activation.
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PMID:Release of tumor necrosis factor-alpha from macrophages. Enhancement and suppression are dose-dependently regulated by prostaglandin E2 and cyclic nucleotides. 284 99

Platelet activating factor (PAF) stimulated production of prostaglandin (PG) I2, PGE2, and PGF2 alpha by rat liver cells (the C-9 cell line); as little as 0.2 nM PAF was effective. Enantio-PAF was 1000-fold less effective. Lyso-PAF, at levels ranging from 0.1 to 1.0 microM, did not stimulate PGI2 production. The synthesis of PGI2 was essentially complete in 10 min. The stimulation by PAF of PGI2 production was inhibited by the PAF antagonists L-659,989, kadsurenone, L-652,731, and BN 52021; the values for 50% inhibition (IC50) were 0.02, 0.19, 0.21, and 0.73 microM, respectively. The antagonists L-659,989 and BN 52021 had no effect on the levels of 6-keto-PGF1 alpha stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), palytoxin, melittin, the Ca2+ ionophore-A-23187, colchicine, transforming growth factor alpha, or exogenous arachidonic acid. The effect of PAF on arachidonic acid metabolism was inhibited by prior exposure of the cells to PAF. Prior treatment of the rat liver cells at 37 degrees with the TPA-type tumor promoters TPA, teleocidin, and aplysiatoxin, as well as with the second stage tumor promoter mezerein, all of which activate the Ca2+/phospholipid-dependent protein kinase (protein kinase C), resulted not only in homologous desensitization to the TPA-type tumor promoters and mezerein, but also in heterologous desensitization to PAF. Stimulation of PGI2 production by palytoxin, the Ca2+ ionophore A-23187, or exogenous arachidonic acid was not inhibited by such prior treatments with the TPA-type tumor promoters. Prior treatment of the cells at 37 degrees for 30 min with the non-TPA-type tumor promoters okadaic acid or palytoxin, both of which do not activate protein kinase C, did not result in heterologous desensitization to PAF.
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PMID:Platelet-activating factor stimulates arachidonic acid metabolism in rat liver cells (C-9 cell line) by a receptor-mediated mechanism. 284 46

The regulation of prostaglandin stimulated cAMP accumulation in cells of the human T-cell leukemia line Jurkat was examined. Pretreatment with PGE2 (0.1-10 nM) for 2 hour caused a concentration dependent desensitization of the prostaglandin receptor. Tumor promoting phorbol esters (1-1000 nM) could also inhibit PGE2 stimulated cAMP production dose dependently. Inhibition of tubulin polymerization with colchicine or nocodazole (1 microM) eliminated prostaglandin but not phorbol ester induced desensitization of the receptor. It is concluded that agonist and phorbol ester induced desensitization are mediated by two distinct mechanisms and that tubulin polymerization appear to be required only for agonist induced desensitization of the prostaglandin receptor.
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PMID:Agonist but not phorbol ester induced desensitization of human lymphocyte prostaglandin receptor is dependent on tubulin polymerization. 284 28

The effects of TPA (12-O-tetradecanoylphorbol 13-acetate)-type and non-TPA-type tumor promoters on prostaglandin E2 production by peritoneal macrophages of rats were examined. Among the TPA-type tumor promoters, aplysiatoxin was most potent in stimulating prostaglandin E2 production followed by dihydroteleocidin B, teleocidin, TPA and debromoaplysiatoxin. Prostaglandin E2 production by aplysiatoxin treatment was stimulated at doses up to 0.1 ng/ml. Palytoxin, a non-TPA-type tumor promoter, also stimulated both prostaglandin E2 production and the release of radioactivity from [3H]arachidonic acid-labeled macrophages. However, the dose required for the expression of these effects by palytoxin was up to 3 pg/ml. It was suggested that the tumor promoters are associated with the activity to stimulate arachidonic acid metabolism, irrespective of their type. Cycloheximide, a protein synthesis inhibitor, inhibited both prostaglandin E2 production and the release of radioactivity from prelabeled macrophages stimulated either by the TPA-type tumor promoters or by the non-TPA-type tumor promoter. It is possible that the tumor promoters may induce the synthesis of some proteins responsible for the stimulation of arachidonate metabolism.
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PMID:Stimulation of prostaglandin E2 production by 12-O-tetradecanoylphorbol 13-acetate (TPA)-type and non-TPA-type tumor promoters in macrophages and its inhibition by cycloheximide. 285 21

Prostaglandin E (PGE) receptors and PGE-adenylate cyclase responsiveness were measured in tumor samples from a hormone-dependent subline of the transplantable MTW9 rat mammary tumor and from an autonomous subline derived from the hormone-dependent tumor. Scatchard analysis of the equilibrium binding data suggested that the hormone-dependent, slow-growing (MTW9A) tumors contain two major types of binding sites for PGE2: a high-affinity component (Kd less than 10(-9) M) and a low-affinity component [Kd greater than 10(-8) M]. The hormone-autonomous, fast-growing tumors (MTW9D), however, have lost more than 80% of the PG binding sites and exhibited mainly a predominant PGE lower affinity component (Kd greater than 10(-8) M). Loss of PGE receptors in autonomous tumors was not due to in vivo down-regulation of these receptors by excessive production of PGE, since both the hormone-dependent and autonomous tumors endogenously produce and release approximately the same amounts of PGE. Incubation of tumor tissues in vitro with PGE caused a significant stimulation of adenylate cyclase activity in the MTW9A tumors, whereas adenylate cyclase activity was not stimulated in the MTW9D tumors even in the presence of the nonhydrolyzable analogue of GTP, Gpp[NH]p. The results suggest that loss of PGE receptors and PGE-adenylate cyclase responsiveness occurs during progression of mammary tumors from hormonal dependence to autonomy and that the subsequent loss of cyclic AMP is associated with the uncontrolled growth characteristics of the autonomous tumors.
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PMID:Loss of prostaglandin E receptors during progression of rat mammary tumors from hormonal dependence to autonomy. 286 40

It has been previously reported that tumor-associated macrophages isolated after combination therapy contained an activity that inhibited thymocyte proliferation in the IL-1 comitogenic assay. The present report shows that this macrophage-derived inhibitory factor (MDIF) inhibits DNA synthesis in diverse adherent and nonadherent cells in vitro. The elution pattern seen after chromatography using Bio-Gel P10 or Sephadex G-25 columns indicated a molecular size of 3-6.5 kDa. However, full activity was retained when MDIF was passed through an Amicon filtration membrane having a cut off of 500 Da. It was also seen that other molecules less than 500 Da, such as thymidine, thimerosal, and PGE2, each of which was also shown to be growth inhibitory, eluted in a size range similar to that of MDIF after chromatographic separation. Ion exchange chromatography confirmed that MDIF was distinct from thymidine, and a radioimmunoassay indicated that PGE2 was not responsible for MDIF activity. Little or no inhibitory activity could be detected in macrophages isolated from progressing tumors or from tumors excised after cyclophosphamide treatment of tumor bearers. Given that this inhibitory activity was associated with macrophages derived from tumors induced to regress by combination therapy, the possibility is discussed that MDIF may play an important role during the regulation of immune reactions at the tumor site.
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PMID:Partial characterization of a low-molecular-weight, macrophage-derived inhibitor of DNA synthesis: a possible immunoregulatory molecule. 292 Mar 97

We have shown earlier that a decline in splenic natural killer (NK) activity during the development of transplanted or spontaneous tumors in mice results from an inactivation of NK lineage cells, mediated by prostaglandins (primarily PGE2) secreted by NK suppressor cells of the monocyte-macrophage lineage. In the present study we have used a C3H mouse mammary carcinoma model to examine whether this mechanism of NK suppression is conducive to tumor metastasis in vivo and whether a reversal of this suppression by a chronic indomethacin therapy can prevent metastatic spread from the primary tumor site. Three mammary tumor lines, all derived in our laboratory from a spontaneous C3H mammary tumor were employed: T-58 (uncloned parental line, having weak lung metastasizing ability from the subcutaneous site), C3 (a clone of T-58, showing high metastatic ability), and C10 (a nonmetastatic clone of T-58). Although the degree of NK susceptibility of these lines varied inversely with their metastatic potential, none was NK resistant. A chronic administration of indomethacin in the drinking water (14 micrograms/ml) to mice beginning on Day 4 after subcutaneous transplantation of 10(6) tumor cells resulted in a significant reduction in the growth rate of primary tumors in all hosts and led to a complete or nearly complete abrogation of lung metastasis in T-58- or C3-transplanted hosts examined at 1 month after tumor transplantation; C10-transplanted mice showed no metastasis in the control or the treated group. Concomitantly, there was a substantial restoration of splenic NK activity in all indomethacin-treated hosts. Plastic-adherent cells (greater than 95% macrophages) isolated from tumors growing in control mice, when coincubated for 20 hr with normal splenic effector cells caused a suppression of NK activity, reversible in the presence of indomethacin (10(-5) M) in vitro. Similar cells recovered from the residual primary tumors in indomethacin-treated mice had no suppressor ability. Chemically pure PGE2 (at concentrations of 0.5 to 1 X 10(-6) M, but not 0.25 X 10(-6) to 10(-8) M) also caused a suppression of NK activity of normal splenic effector cells, when added during the 4-hr 51Cr-release assay or allowed to interact with effector cells alone for a 20-hr incubation period; a removal of the cell-free PGE2 in the latter case prior to the NK assay did not relieve the suppression.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Indomethacin therapy abrogates the prostaglandin-mediated suppression of natural killer activity in tumor-bearing mice and prevents tumor metastasis. 294 21

The metabolism of arachidonic acid was investigated by radioimmunoassay and chromatographic techniques in 5 sarcomas and one embryonal carcinoma of human origin maintained as transplantable tumors in nude mice. The results obtained indicate that: the absolute quantities of arachidonic acid metabolites produced by a given tumor varied between experiments but the overall distribution pattern of these products, in general, remained constant from passage to passage; each tumor showed a different arachidonic acid metabolite profile in quality and quantity; 2 sarcomas of the same histological type could be clearly distinguished by their arachidonic acid metabolites; the predominant product in all tumors was 12-HETE or 15-HETE, whereas thromboxane A2 was synthesized in low quantities by all tumors; PGF2 alpha was synthesized at the highest rate by an alveolar rhabdomyosarcoma; PGE2 synthesis was highest in a malignant fibrous histiocytoma; and total prostaglandin synthesis was low in the chondrosarcoma and synovial-cell sarcomas. All results reported in this study are for the complete tumor which includes both neoplastic and stromal cells. The role that these products play in the biological behavior of mesenchymal tumor cells and normal tissues of the host remains to be determined.
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PMID:Prostaglandin and hydroxyeicosatetraenoic acid synthesis by human mesenchymal tumors. 299 Nov 46


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