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

The content of prostaglandins in Yoshida tumor ascites fluid was evaluated by extraction of the arachidonic acid metabolites by means of octadecylsilyl-silica chromatography (ODS-extracts). The pattern of association of the icosanoids to ascites fluid colloids was determined by sequential precipitation with polyethylene glycol and extraction of the precipitates with methanol (M-extracts). Thin layer chromatographic analysis of these extracts demonstrated in the ODS-extract the presence of chromatographic fractions corresponding to prostaglandin E2 (4.6 micrograms/mL) and prostaglandin A2 (3.0 micrograms/mL), while in the M-extract only the fraction corresponding to prostaglandin A2 (9.2 micrograms/mL) was detected. This fraction was as the growth inhibitory activity reduced by approximately 60% in M-extracts from animals treated with Indomethacin. These results support previous indications that arachidonic acid metabolites are involved in the cytostatic activity of ascites fluid extracts. The preferential association of prostaglandin E2 to the ascites macroglobulin fraction could be a consequence of the presence of an unidentified tumor-dependent amphiphilic polymer in the Yoshida ascites fluid.
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PMID:Prostaglandins and the tumor-dependent growth inhibitory activity of Yoshida ascites fluid. 281 7

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

Epidermal growth factor (EGF) binds specifically (Ka = 4 X 10(9) M-1; 1.3 X 10(11) receptors/mg cellular protein) to JEG-3 cells, which respond in the succeeding 24 h by a 400% increase in hCG secretion without a significant change in cell number. Since JEG-3 cells store less than 2% of the 24-h hCG secretion, a significant increase in hCG in the culture medium reflects increased hCG biosynthesis. It is observed that a tumor promoter, phorbol myristate acetate (PMA), binds specifically to the cells (Ka = 5 X 10(8) M-1; 3.9 X 10(11) receptors/mg), reduces (33%) the affinity but not the number of EGF receptors, and stimulates hCG to the same extent as does EGF. The relative potencies of PMA (100%), phorbol dibutyrate (25%), and nonesterified phorbol (no effect) to stimulate hCG parallel their known tumor-promoting activities. Since phospholipids and fatty acids have been implicated in the mechanism of action of EGF and PMA, the effects of arachidonic acid (AA) and inhibitors of its metabolism were studied. The addition of AA had no effect on basal or PMA-stimulated hCG secretion, but it potentiated the effect of EGF by 200%. Indomethacin (a cyclooxygenase inhibitor) had an effect similar to that of AA. Nordihydroguairetic acid (a cyclooxygenase and lipoxygenase inhibitor) reduced by 90% basal and EGF- or PMA-stimulated hCG secretion. These results indicate that the AA pathway can influence the effects of EGF and PMA on hCG secretion and suggest an intermediary role for the lipoxygenase system.
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PMID:Effects of epidermal growth factor, phorbol myristate acetate, and arachidonic acid on choriogonadotropin secretion by cultured human choriocarcinoma cells. 298 49

Arachidonic acid (AA), a prostaglandin precursor, significantly potentiated sister-chromatid exchange (SCE) induction in vitro by benzo[a]pyrene (BP) and 7,12-dimethylbenz[a]anthracene (DMBA) in the aryl hydrocarbon hydroxylase (AHH)-inducible human hepatoma C-HC-4 cells, and to a lesser extent in the non-inducible rat tumor AH66-B and R1 and Chinese hamster Don-6 cells, all of which were less sensitive to these compounds than C-HC-4 cells. Indomethacin (IM), an inhibitor of prostaglandin endoperoxide synthetase (PES), moderately suppressed SCE induction by BP or DMBA in AH66-B and R1 cells, but it exerted no such effect in C-HC-4 and Don-6 cells. In C-HC-4 cells, however, IM completely eliminated the potentiating effect of AA on SCE induction by both BP and DMBA. The above findings suggest that PES in prostaglandin biosynthesis may also be involved in the metabolic activation of polycyclic aromatic hydrocarbons to genotoxic forms capable of inducing SCEs, in addition to AHH system.
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PMID:Effects of arachidonic acid and indomethacin on sister-chromatid exchange induction by polycyclic aromatic hydrocarbons in mammalian cell lines. 300 16

Rat splenic natural killer (NK) cell activity against 51Cr-labeled YAC-1 or TMT-081 tumor cells can be augmented by culturing at 37 degrees C for 18 hr. Inhibitors of the lipoxygenase pathway of arachidonic acid metabolism, NDGA, alpha-phenanthroline, quercetin, ETYA, BW755C, esculetin, and timegadine, inhibited this NK activation and also inhibited NK cytotoxicity when added directly to the NK assay. However, there was a partial loss of sensitivity of activated NK cells to suppression by NDGA, BW755C, and esculetin. Indomethacin failed to reverse the inhibition of NK activation caused by NDGA. However, LTB4 and LTC4 (0.01 microgram/ml) were able to reverse the inhibitory effect of NDGA on NK activation. Furthermore, spleen cells cultured for 18 hr synthesized detectable amount of LTC4 in their supernatants. NDGA inhibited the LTC4 synthesis in a dose-dependent manner. These data therefore suggest that leukotrienes are responsible for NK activation, and lipoxygenase activity is essential for NK cytolytic activity.
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PMID:Regulation of rat natural killing. II. Inhibition of cytolysis and activation by inhibitors of lipoxygenase: possible role of leukotrienes. 301 67

Natural killer (NK) cells and lymphokine-activated killer (LAK) cells are anomalous cytotoxic cells which are potentially important in host defense against cancer. Several studies have demonstrated that natural killer (NK) cell activity can be suppressed by chemical inhibitors of the lipoxygenase pathway through inhibition of the production of leukotriene B4 (LTB4). The present study investigated the effects of the lipoxygenase inhibitors BW755C and nordihydroguaiaretic acid (NDGA) on NK and LAK cell activity. NK cell function of fresh peripheral blood mononuclear cells (PBMC) was determined via a standard chromium release assay employing K562 as the tumor target. The LAK cell activity of PBMC which had been stimulated with 10 IU of interleukin-2 for 72 hr was determined against the NK-resistant cell line Daudi. Both BW755C and NDGA inhibited NK and LAK cell function at a variety of concentrations. Indomethacin, a prostaglandin synthesis inhibitor, did not bring about an appreciable diminution in NK or LAK cell activity. Inhibition of NK and LAK cell activities by BW755C and NDGA could be reversed by washing the effector cell suspensions prior to the cytotoxic assay or by adding LTB4 (10(-11)-10(-8) M) directly to the effector:target suspensions. These data indicate that certain arachidonic acid oxidation products of the lipoxygenase pathway are essential for the function of LAK cells.
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PMID:Reversible inhibition of lymphokine-activated killer cell activity by lipoxygenase-pathway inhibitors. 301 99

Treatment of BALB/c, C57Bl/6 or C3H/HeJ mice with non-toxic concentrations of indomethacin (75-100 micrograms/day) led to a depression of plasma neutral proteinase activity as determined with an (125I)-caseinolytic assay. Lower concentrations of indomethacin (50 micrograms/day), aspirin (1 mg/day), LiCl (3 meq/kg/day), Sulindac (100 micrograms/day), indomethacin analogs (MK-410, MK-555) or lipopolysaccharide (100 micrograms) did not induce depression in proteinase activity. Indomethacin did not directly inhibit the proteinase activity of normal plasma in vitro. The in vivo effects of indomethacin were reversible and plasma proteinase activity returned to normal values within 8 days of cessation of treatment. These results indicate that indomethacin can uniquely alter plasma proteinase homeostasis in normal mice. While effective in depressing the plasma proteinase activity of normal mice, treatment of mice bearing either the BCL1 leukemia or the B16-F10 melanoma with indomethacin did not depress the elevated plasma proteinase levels detected in tumor-bearing animals. Thus the elevation in proteinases detected in tumor-bearing animals may not be the result of increased prostaglandin synthesis and plasma proteinase activity in such disease states may be regulated differently than in normal mice. However, the ability of this potent anti-inflammatory agent to alter proteinase metabolism may contribute to its therapeutic efficacy in the management of inflammatory disease.
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PMID:Indomethacin induces the suppression of plasma neutral proteinase activity in mice: possible relationship to efficacy as an anti-inflammatory drug and induction of alterations in the immune system. 302 Feb 55

Lipoxygenase (LPO) metabolites of arachidonic acid participate in the activation and/or proliferation of a variety of cell types. In this study, we examined the role of LPO metabolites in controlling myelopoiesis and erythropoiesis in vitro. Monocyte depleted cells (MDC) prepared from human whole blood or whole mononuclear cells from human bone marrow were cultured in methylcellulose in the presence of various growth factors. Conditioned media containing human colony stimulating factors (CSF) or the tumor-promoting phorbol ester, phorbol myristate acetate (PMA), were added to induce myelopoiesis. Semipurified human erythropoietin (EPO) was added along with an endogenous source of burst-promoting activity (BPA) to induce erythropoiesis. The LPO inhibitor BW755C blocked all types of colony formation in a dose-dependent manner, with ID50 of 20 and 5 micrograms/mL for myeloid and erythroid colonies, respectively. MDC depleted of T cells were similarly inhibited by BW755C. Similar results were seen with two other LPO inhibitors, 1-phenyl-3-pyrazolidone and butylated hydroxyanisole. A fourth LPO inhibitor, nordihydroguaiaretic acid, inhibited at higher concentrations. Indomethacin, at concentrations that inhibit cyclooxygenase, had no significant effect, either alone or in combination with the LPO inhibitors. These results suggest that certain LPO products may be important mediators of both CSF- and PMA-induced myelopoiesis, and of BPA/EPO-induced erythropoiesis.
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PMID:Lipoxygenase metabolites of arachidonic acid modulate hematopoiesis. 308 46

Indomethacin was tested for its ability to augment the cytotoxic capacity of cultured bone marrow-derived macrophages (M phi) against P815 and YAC-1 tumor cells. M phi were obtained from the bone marrow of C57BL/6 mice precultured for 10-14 days and were virtually 100 percent pure. By addition of indomethacin these cells were activated to kill tumor cells in a 4-h and 18-h Cr-release assay. Since indomethacin is a potent inhibitor of the cyclooxygenase system, M phi were treated with prostaglandin E2. This treatment partially reversed indomethacin-induced cytotoxicity. Addition of other cyclooxygenase inhibitors such as acetyl-salicylic-acid, diclofenac or carprofen also induced cytotoxicity in bone marrow-derived M phi. In all experiments we failed to detect any production of interferon. Addition of anti-interferon did not alter the cytolytic capacities demonstrating that endogenously induced interferon was not relevant in this mechanism. Our data show that cyclooxygenase inhibitors induce cytolytic activity of murine M phi not only against a M phi target but also against YAC-1 cells usually considered to be targets for natural killer cells.
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PMID:Activation of cytotoxic activity in cultures of bone marrow-derived macrophages by indomethacin. 310 52

Preneoplastic and neoplastic liver and lung lesions were studied in male B6C3F1 mice given a single injection (80 mg/kg) of N-nitrosodiethylamine (DEN) intraperitoneally at 4 weeks of age, followed 1 week later by oral exposure to di(2-ethylhexyl)-phthalate (DEHP; at 6000 ppm in the diet), butylated hydroxyanisole (BHA; 7500 ppm in the diet) or indomethacin (10 ppm in the drinking water) alone or in combination (DEHP and BHA or DEHP and indomethacin), and continued for 29 weeks. DEHP or BHA alone and the combination of DEHP and BHA increased the incidence of DEN-initiated focal hepatocellular proliferative lesions (FHPL), including both microscopic hyperplastic foci and hepatocellular adenomas. Mice that received BHA alone or DEHP plus BHA had FHPL that were composed predominantly of eosinophilic hepatocytes, while FHPL in DEHP-exposed mice were basophilic. Indomethacin showed neither promotional or antipromotional effects, except for lung tumors. Mice receiving DEHP and indomethacin after DEN had significantly fewer lung lesions. A high incidence of renal papillary necrosis and nephropathy was observed in the indomethacin-DEHP exposed mice, while these lesions were not found in mice treated with indomethacin alone or DEHP alone. These findings suggest that BHA, an antioxidant, promoted pre-neoplastic liver lesions while indomethacin, a known inhibitor of prostaglandin synthesis and a chemopreventive agent for colon and mammary tumors in other studies, had no effect on liver tumor promotion by DEHP.
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PMID:Modifying effects of butylated hydroxyanisole, di(2-ethylhexyl)phthalate or indomethacin on mouse hepatocarcinogenesis initiated by N-nitrosodiethylamine. 310 26


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