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

Several responses suggested to be critical components of phorbol ester tumor promotion were compared in 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion-sensitive SSIN and TPA promotion-resistant C57BL/6J mice. SSIN mice treated topically with 2 micrograms of TPA showed extensive hyperplasia accompanied by edema, measured as a 26% increase in water content of the skin. Only a very slight hyperplasia and 7% increased water content occurred after TPA treatment of C57BL/6J mice. The induction of ornithine decarboxylase was determined to be the same both in vivo and in vitro for SSIN and C57BL/6J mice, which does not correlate with the histological observations. Because hyperplasia and inflammation can be mediated by arachidonic acid metabolites, it was hypothesized that differences in this metabolic pathway would correlate with the histological responses. No significant qualitative or quantitative differences, however, were observed in the profiles of the major cyclooxygenase products between the strains of mice. Prostaglandin E2, the principal prostaglandin, was synthesized at a 3-fold greater level than prostaglandins D2 or F2 alpha in response to TPA. The most abundant lipoxygenase product was 12-hydroxyeicosatetraenoic acid followed by 8-, 15-, and 5-hydroxyeicosatetraenoic acid. 8-Lipoxygenase activity is elevated 24 h after TPA treatment in the SSIN mice by approximately 4-fold; no elevation is seen in C57BL/6J mice. A comparison of the oxidant response to TPA as well as to phospholipase C showed that SSIN epidermal cells generated a higher level, measured by chemiluminescence, than C57BL/6J cells. This suggests that oxidant generation or possibly 8-lipoxygenase activity may be the basis for the sensitivity or resistance to TPA as a hyperplasiogen and as a tumor promoter.
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PMID:Phorbol ester induction of 8-lipoxygenase in inbred SENCAR (SSIN) but not C57BL/6J mice correlated with hyperplasia, edema, and oxidant generation but not ornithine decarboxylase induction. 333 28

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

Some studies report that endothelial cells preferentially take up the lipoxygenase-derived arachidonic acid metabolite, 5-hydroxyeicosatetraenoic acid (5-HETE), released from stimulated leukocytes (polymorphonuclear leukocytes, PMNs), whereas others report that endothelial cells preferentially take up 12-HETE released from platelets. The biological relevance of these observations, however, is unknown. Recently, we and others have found that, under basal conditions, endothelial cells, PMNs and tumor cells metabolize linoleic acid via the lipoxygenase enzyme to 13-hydroxyoctadecadienoic acid (13-HODE). We propose that endogenous levels of these metabolites regulate blood-vessel wall cell adhesion. In this study, we have measured (1) the relative binding of 5-, 12- and 15-HETE, and 13-HODE to endothelial cell monolayers, and (2) their effects on endothelial cell adhesivity with platelets, PMNs and tumor cells. There was a dose-related and specific binding of 5-[3H]HETE to endothelial cells but no binding of 12- or 15-HETE or 13-HODE. Platelet or PMN adhesion to endothelial cells was unaffected by the 5-HETE binding, but tumor cell adhesion was blocked by 40% (P less than 0.01). Interestingly, preincubation of endothelial cells with 13-HODE, 12-HETE or 15-HETE decreased platelet adhesion to endothelial cells (P less than 0.05), even though these metabolites did not bind to the endothelial cells. We conclude that 5-HETE preferentially binds to endothelial cells and interferes with a specific receptor for tumor cells, whereas the other metabolites neither bind to cells nor affect cell adhesion.
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PMID:Binding of 13-HODE and 5-, 12- and 15-HETE to endothelial cells and subsequent platelet, neutrophil and tumor cell adhesion. 339 Apr 52

There is evidence suggesting a role of eicosanoids in the growth of certain tumors. In this study, tissue samples were collected from basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin. Both BCCs and SCCs contained more prostaglandin E2 and F2 alpha (PGE2 and PGF2 alpha) than normal epidermis. In vitro incubation of tumor samples with arachidonic acid also resulted in PGE2 and PGF2 alpha formation. Basal cell carcinomas exhibiting a histologically aggressive growth pattern contained higher levels of prostaglandins than those with a nonaggressive growth pattern, both in vivo and after in vitro incubation. Lipoxygenase products (12- and 15-hydroxyeicosatetraenoic acid) were present in smaller amounts than cyclo-oxygenase products (PGE2 and PGF2 alpha) in vivo. Compared with normal epidermis, SCCs and, particularly, BCCs produced smaller amounts of 12-hydroxyeicosatetraenoic acid during in vitro incubation with arachidonic acid. The levels of lipoxygenase products were not related to the tumor growth pattern. These results indicate that excessive prostaglandin levels in BCCs may be associated with an aggressive growth pattern.
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PMID:Arachidonic acid metabolites in cutaneous carcinomas. Evidence suggesting that elevated levels of prostaglandins in basal cell carcinomas are associated with an aggressive growth pattern. 345 41

15-Methyl-prostaglandin E1 (15-M-PGE1), a synthetic stable, prostaglandin E1 analogue was examined for ability to inhibit motility in a line of murine tumor cells. Inhibition of random motility and motility stimulated by 12-O-tetradecanoyl phorbol acetate was seen at concentrations of 15-M-PGE1 as low as 1 microM. Inhibition of laminin-stimulated motility was observed with 10 microM 15-M-PGE1. The murine tumor cells used in this study produced high levels of prostaglandins. When the cells were treated with either indomethacin or ibuprofen, prostaglandin levels (measured as prostaglandin E2 by radioimmunoassay) were reduced by greater than 95% without a corresponding increase in lipoxygenase products. When indomethacin or ibuprofen-treated cells were compared to control cells in regards to motility, they were more active. These studies show that E-series prostaglandins can modulate motility in the murine fibrosarcoma cells and suggest that the production of endogenous cyclooxygenase metabolites by the murine tumor cells may regulate, at least in part, the responsiveness of the cells to stimulation.
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PMID:Modulation of tumor cell motility by prostaglandins and inhibitors of prostaglandin synthesis. 346 58

Eicosanoids are unsaturated fatty acid compounds derived from 20-carbon 'essential' fatty acids, the most important being arachidonate. Both cyclooxygenase and lipoxygenase products of arachidonate are abundant in the human gut and their biological effects include modulation of fluid and electrolyte secretion, motor activity, mucosal blood flow, and cytoprotection, in addition to chemotaxis and immune response in inflammation. In health, these lipid mediators reinforce or synergize normal homeostatic mechanisms that could proceed in their absence. Receptors for control of intestinal secretion can be divided into two major classes, one of which triggers the production of cyclic AMP and another, which initiates phospholipid breakdown and arachidonate release. An intimate connection appears to exist between phospholipid metabolism, cytosolic Ca2+ levels, electrogenic anion secretion, Na+ pump rate, electroneutral Na+/H+ exchange activity, and intracellular pH. Ca2+-dependent secretagogues affect fluid and electrolyte transport in the small and the large bowel by increasing Ca2+ entry and Ca2+ mobilization through stimulation of eicosanoid formation, prostaglandins of the E type being the most important. Secretory diarrhoea may be thought of, therefore, as cellular Ca2+ intoxication. Uncontrolled formation of eicosanoids, perhaps with a changed spectrum of arachidonate metabolites, may not only be the source of diarrhoea associated with mucosal inflammation, but may also be critical for cell proliferation resulting in abnormal cell differentiation, which seems to be the link between long-standing inflammatory bowel disease and the increased risk of colonic neoplasia. A better understanding of the pathophysiological role of eicosanoids in diarrhoeal disease has allowed reinterpretation of the rationale behind current therapy.
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PMID:Eicosanoids and their role in the pathogenesis of diarrhoeal diseases. 352 95

The antitumor action of inhibitors of cyclooxygenase (indomethacin) and lipoxygenase activity (nordihydroguaiaretic acid) of arachidonic acid cascade was investigated in the chemically induced large bowel tumors in Sprague-Dawley rats. Indomethacin treatment completely prevented the carcinogenic effect of methylazoxymethanol. Thus, no tumors were found in the 14 rat test group, compared with 13 of 14 tumor-bearing rats in the untreated control group. Although nordihydroguaiaretic acid treatment does not abolish prostaglandin synthesis, it does reduce the effect of the carcinogen and tumors were found in only five of 14 treated rats. From this study it can be postulated that not only is reduction in prostaglandin formation responsible for the inhibition of tumor growth, but also leukotrienes may play some role.
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PMID:Antitumor effects of inhibitors of arachidonic acid cascade on experimentally induced intestinal tumors. 380 7

In vivo studies have shown that inhibitors of cyclooxygenase metabolism of arachidonic acid may diminish growth and metastasis of certain tumors. Because cyclooxygenase inhibition may increase the production of lipoxygenase products of arachidonic acid metabolism, we have investigated the effect of two such products, 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-hydroxyeicosatetraenoic acid (15-HETE) on tumor cell proliferation in vitro. When neuroblastoma cells (SK-N-SH) in culture were treated with 12-HETE for 18 hr, incorporation of [3H]thymidine was inhibited up to 64% at concentrations from 20 to 50 microM. Under the same conditions, 15-HETE resulted in inhibition of up to 46%, while arachidonic acid had no apparent effect. When evaluated in the presence of serum, 12-HETE at a concentration of 120 microM produced a 20.6 +/- 2.8% (S.E.) inhibition of the increase in total DNA content over 48 hr, while 15-HETE at this concentration produced a 16.5 +/- 5.3% inhibition. We conclude that 12-HETE, the product of platelet lipoxygenase, and 15-HETE, a product of neutrophil and lymphocyte lipoxygenases, can inhibit human neuroblastoma cell growth in vitro and may play a role in the effect of cyclooxygenase inhibitors on tumor growth in vivo.
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PMID:Inhibition of human malignant neuroblastoma cell DNA synthesis by lipoxygenase metabolites of arachidonic acid. 391 50

The antilymphocytic and antiphlogistic agent cyclosporin A (CsA) inhibits in vivo various effects induced by the tumor promoting phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA). These include the edema of the mouse ear, the alkaline phosphatase (AP) activity and the ornithine decarboxylase (ODC) activity in mouse epidermis as well as the generation of a specific arachidonic acid (AA) metabolite in mouse epidermis. AA metabolism in an epidermal cell-free system of mouse epidermis was not suppressed by CsA. According to thin layer chromatography the TPA-induced and as yet unidentified AA metabolite exhibits a polarity between that of 5-HETE and 12-/15-HETE. Studies with inhibitors indicate it to be a lipoxygenase product.
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PMID:Cyclosporin A inhibits biological effects of tumor promoting phorbol esters. 391 31

Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity.
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PMID:Human platelets exert cytotoxic effects on tumor cells. 392 50


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