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

Activation of cell phospholipase, release of arachidonic acid and stimulation of prostaglandin synthesis were studied in a newly described human tumor cell line (Lu-65). In the Lu-65 tumor cell line, the calcium ionophore A23187 (2 microM) caused a 100% increase in the release of 3H-arachidonic acid and a 7-fold increase in the synthesis of prostaglandin E2. 1-oleoyl, -2-acetyl-glycerol (100 microM) increased arachidonate release and prostaglandin E2 synthesis by 100%. A23187 and the protein kinase C activators, 1,2-dioctanoyl-glycerol and 1-oleoyl, -2-acetyl-glycerol, decreased the specific radioactivity of 3H-arachidonate in phosphatidylinositol by 37% and 57%, respectively. The effects of A23187 were blocked in Ca2+-free media or in the presence of the phospholipase A2 inhibitor, p-bromophenacyl bromide, while those of 1-oleoyl, -2-acetyl-glycerol were not. The data provide evidence in a human tumor cell line for calcium/phospholipase A2-dependent and independent pathways for arachidonic acid release, both of which preferentially hydrolyze phosphatidylinositol.
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PMID:A23187 and protein kinase C activators stimulate phosphatidylinositol metabolism and prostaglandin synthesis in a human lung cancer cell line. 314 61

Toxicity has been observed in mice receiving recombinant human tumor necrosis factor (rhTNF). In the present experiments, several chemicals were used to determine whether they could prevent the lethality of rhTNF without impairing its antitumor activity. Injection of phospholipase A2, cyclooxygenase, and lipoxygenase inhibitors at the same time as rhTNF administration could prevent the lethality of rhTNF, but the antitumor activity was also reduced. Urinastatin and reduced glutathione could prevent the lethality while reducing the activity. In contrast, by pretreatment with O2 scavengers, the lethality of rhTNF was markedly reduced without impairment of the antitumor activity of rhTNF. Antihistamines exerted no influence on the lethality of rhTNF. Histopathologic examinations have demonstrated that the capillaries of the tumor tissue show aggregation of platelets and formation of fibrin adherent to the vascular surface after TNF administration. Heparin or protamine revealed no effects against the lethality of rhTNF. These results strongly suggest that the arachidonic cascade is deeply related to the antitumor activity of TNF and its side effects. Pretreatment with O2 scavengers, especially bismuth subnitrate, could prevent the lethality of rhTNF without impairing its antitumor activity.
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PMID:Preventive effects of several chemicals against lethality of recombinant human tumor necrosis factor. 337 34

I examined whether the phorbol ester-mediated inhibition of glycerol 3-phosphate dehydrogenase (GPDH) induction could be mimicked by raising the cellular diacylglycerol levels. Phorbol ester tumor promoters and diacylglycerols activate protein kinase C. An increase in radiolabeled diacylglycerol levels in C6 rat glioma cells was observed when cells were prelabeled overnight with [3H]arachidonic acid and treated with either phospholipase C (Clostridium perfringens) or 2-bromooctanoate. The increase was dose dependent. The diacylglycerols competed with [20-3H]phorbol 12,13-dibutyrate in binding to the phorbol ester receptor. A Scatchard analysis of the binding of cells treated with 0.1 unit/ml of phospholipase C demonstrated that the inhibition was mainly due to a decrease in binding affinity and not in the total number of binding sites. 2-Bromooctanoate and phospholipase C, but not the synthetic diacylglycerol 1-oleoyl 2-acetyl glycerol, inhibited the glucocorticoid induction of GPDH levels. Boiled phospholipase C, phospholipase A2, or phospholipase D was ineffective in inhibiting induction, a result suggesting that the inhibition was not due to nonspecific membrane perturbation. Thus, inhibition of the glucocorticoid-mediated increase in GPDH induction is most likely mediated by protein kinase C, and not by an alternate phorbol ester receptor.
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PMID:Increased diacylglycerol levels inhibit [20-3H]phorbol 12,13-dibutyrate binding and the glucocorticoid-mediated increase in glycerol phosphate phosphate dehydrogenase levels in C6 rat glioma cells. 346 28

This study examined the platelet-aggregating and procoagulant activities of two hematogenously disseminating tumors, a mouse lymphoblastic leukemia (L5178Y) and a mouse renal adenocarcinoma (RAG). Tumor-induced human platelet aggregation was inhibited by addition of the following agents to platelet-rich plasma (PRP): a calcium channel blocker (verapamil), a chelator of divalent cations (EDTA), stimulators of adenylate cyclase (2-fluoroadenosine and forskolin), and inhibitors of cAMP phosphodiesterase (oxagrelate and papaverine). The platelet-aggregating activities of both cell lines were completely blocked by treatment of the cells with heat, sonication, phospholipase A2, and Triton X-100. These data suggest that L5178Y and RAG cell-induced human platelet aggregation are dependent on a heat-labile phospholipid component of the tumor cell membrane. L5178Y cells had greater platelet-aggregating activity in human plasma than in rat or mouse plasma, whereas RAG cells had greater procoagulant activity in rat or mouse plasma than in human plasma. The procoagulant activity of RAG cells in rat and mouse plasma was demonstrated by three lines of evidence: RAG cells induced heparinized PRP to clot; the thrombin inhibitor DAPA lengthened of the clotting time and the lag time before aggregation; and RAG cells shortened of the recalcification time of the plasma. The above data indicate that RAG cell-induced murine platelet aggregation and coagulation is dependent on thrombin generation.
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PMID:Murine tumor-induced platelet aggregation and coagulation: mechanisms, inhibitors, and species differences. 359 Jan 14

Teleocidin (5 micrograms/mouse), a potent tumor promoting indole alkaloid from Streptomyces, induced epidermal ornithine decarboxylase (ODC) in CD-1 mice. Teleocidin-caused ODC induction was inhibited by the treatment of indomethacin (2 mumol/mouse), a selective cyclooxygenase inhibitor, and p-bromophenacyl bromide (BPB) (30 mumol/mouse), a phospholipase A2 inhibitor. Teleocidin-caused ODC induction inhibited by indomethacin was completely restored by concurrent application of prostaglandin E2 (PGE2) (140 nmol/mouse). On the other hand, teleocidin-caused ODC induction inhibited by BPB was not restored by the treatment of mice with PGE2, but partially restored by the treatment with arachidonic acid (1 mumol/mouse). Treatment of mice with lipoxygenase inhibitors such as BW755C (30 mumol/mouse), nordihydroguaiaretic acid (NDGA) (30 mumol/mouse), quercetin (10 mumol/mouse), and 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861) (10 mumol/mouse) clearly suppressed ODC induction by teleocidin. Moreover, both NDGA (30 mumol/mouse) and quercetin (10 mumol/mouse) inhibited the restoring effect of PGE2. Therefore, our present results suggest that arachidonate metabolites, i.e., not only cyclooxygenase product(s) but also lipoxygenase product(s), are involved in the mechanism of ODC induction by teleocidin.
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PMID:Inhibition of teleocidin-caused epidermal ornithine decarboxylase induction by phospholipase A2-, cyclooxygenase- and lipoxygenase-inhibitors. 392 44

The chromosome-damaging effect of PMA in blood cultures is mediated by secondary products which are formed by the cells in response to the interaction with this tumor promoter. Since this effect could be influenced by antioxidant enzymes and by inhibitors of arachidonic acid metabolism, the present study was undertaken in order to determine whether the formation of these clastogenic substances is concomitant with the formation of AA metabolites and other lipid peroxidation products. Besides the clastogenic effect of ethyl-acetate extracts, the similarities of cytogenetic and biochemical results (conjugated dienes and TBA-reactive material) obtained for the influence of other blood cells than lymphocytes in the culture system, the importance of PHA stimulation and the protective effect of antioxidant enzymes were arguments in favour of a causal relationship between chromosome damage and lipid peroxidation (enzymatic or nonenzymatic). If AA release from membrane phospholipids was prevented by inhibition of phospholipase A2, neither conjugated dienes nor TBA-reactive material were found, and chromosome damage was reduced considerably. However, the results obtained with inhibitors of the cyclo- and lipoxygenase pathway were not conclusive, and discrepancies were also observed in the time course of appearance of clastogenic material and lipid peroxidation products.
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PMID:Lipid peroxidation products and clastogenic material in culture media of human leukocytes exposed to the tumor promoter phorbol-myristate-acetate. 393 6

Platelet-aggregating and thrombin-generating activities of B16 and 3LL cells were inhibited by trypsin, phospholipase A2 and by heating, but not by neuraminidase. It was confirmed that the platelet aggregation effect of these cells is due to thrombin generation. The lung-colonizing ability of treated cells injected intravenously was directly proportional to the ability to generate thrombin and to aggregate platelets. These results suggest that B16 and 3LL cells aggregate platelets through thrombin generation probably via their heat-labile surface lipoprotein, and that emboli composed of platelets, fibrin, and tumor cells may aid further the metastatic process.
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PMID:Platelet-aggregating activities of metastasizing tumor cells. IV. Effects of cell surface modification on thrombin generation, platelet aggregation and subsequent lung colonization. 394 Oct 29

Treatment of newborn murine epidermal cells with phospholipase C results in the generation of a chemiluminescence response similar to that previously described for phorbol ester tumor promoters. Based on inhibitor studies, the oxidant, believed to be superoxide anion, is most likely generated from lipoxygenase metabolism of arachidonic acid. The specificity of the response to phospholipase C from C. perfringens and not from B. cereus or phospholipase A2 suggests specific phospholipids are involved. The response observed appears to arise from the phospholipid-protein kinase c model for phorbol ester binding and activity.
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PMID:Phospholipase C mimics tumor promoter-induced chemiluminescence in murine epidermal cells. 405 80

We studied the in vitro responsiveness of prolactin-secreting MtTW15 and 7315a pituitary tumor cells to stimulation by selected secretagogues using a perifusion technique. Prolactin release by these cells was refractory to thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP). In contrast, 50 mM K+, dibutyryl cAMP, theophylline, phospholipase A2 and phorbol myristate acetate all increased prolactin release from both tumor cell types. Phospholipase C increased prolactin release from 7315a but not from MtTW15 cells. TRH increased 32P incorporation into phosphatidylinositol in the 7315a but not in the MtTW15 tumor cells. Therefore, the refractoriness of these tumors to TRH and VIP may be at least partially due to a defect in the receptor or in the process that couples receptor binding and intracellular biochemical processes. In the MtTW15 tumor at least part of the defect may be related to phospholipid hydrolysis.
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PMID:Prolactin release from MtTW15 and 7315a pituitary tumors is refractory to TRH and VIP stimulation. 608 25

The effects of the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) and the plant lectin concanavalin A (Con A) on glucose uptake in murine thymocytes were studied. TPA induces a rapid dose-dependent increase in the uptake of 2-deoxyglucose and in the transport of 3-0-methylglucose. Con A also elicits a time- and dose-dependent enhancement of 2-deoxyglucose uptake. The effect of Con A, however, is less pronounced. The effect of combined treatment of thymocytes with Con A and TPA is not additive. Cytochalasin B completely inhibits the basal, as well as TPA- and Con A-enhanced, 2-deoxyglucose uptake. Dexamethasone markedly inhibits basal 2-deoxyglucose uptake, but is less inhibitory to enhanced 2-deoxyglucose uptake induced by TPA and Con A. The effect of TPA on 2-deoxyglucose uptake and 3-0-methylglucose transport is refractory to inhibition by isobutyl methyl xanthine, dibutyryl cyclic AMP, and ethyleneglycol tetraacetic acid. These agents markedly inhibit the enhancement of 2-deoxyglucose (2-DOG) uptake by Con A. p-Bromophenacyl bromide, an inhibitor of phospholipase A2, also selectively inhibits Con A enhancement of 2-DOG uptake. Taken together, the results suggest that Con A and TPA exert their stimulatory effect on glucose uptake by different activating mechanisms, but they may share a final common transport pathway.
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PMID:12-0-tetradecanoylphorbol-13-acetate and concanavalin A enhance glucose uptake in thymocytes by different mechanisms. 619 67


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