Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Patch clamp studies on colonic tumor cell line T84 show the presence of chloride channels. 2. The channels are activated by forskolin, PGE2, or 8-Br-cAMP. 3. Single channel conductance was ca 40 pS at the reversal potential, increasing to 70 pS at +80 mV and decreasing to 25 pS at -80 mV. 4. Relative permeabilities were I greater than Br greater than Cl greater than F.
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PMID:Biophysical properties of a chloride channel in the apical membrane of a secretory epithelial cell. 246 Feb 84

The macrophage-activating properties of murine recombinant granulocyte-macrophage (GM)-CSF were studied in murine peritoneal macrophages with respect to metabolism, endocytosis, PGE2 and TNF-alpha release, and tumor cytotoxicity. GM-CSF was found to be a potent stimulus for RNA and protein synthesis, glucose consumption, pinocytosis, and FcR-independent phagocytosis. Macrophages were activated by GM-CSF to kill TNF-alpha-insensitive Eb lymphoma cells but failed to generate cytotoxicity against TNF-alpha-sensitive L929 cells. Although GM-CSF alone was incapable of stimulating TNF-alpha release, it primed macrophages for elevated TNF-alpha production in response to IFN-gamma plus LPS. The priming effect of GM-CSF disappeared upon longer incubation (greater than 12 h) and was followed by a strongly reduced responsiveness to stimuli that release TNF-alpha. Late-stage suppression could be reverted by treatment with the cyclooxygenase blocker indomethacin, and GM-CSF-induced priming for enhanced TNF-alpha release was entirely restored. The responsible arachidonic acid product mediating suppression was found to be PGE2, because 1) GM-CSF-primed macrophages released enhanced amounts of PGE2 and 2) indomethacin-restored macrophages were again suppressed when exogenous PGE2 was added back in amounts produced by GM-CSF-primed macrophages. Although GM-CSF potently induced TNF-alpha gene transcription by 20 h of treatment, PGE2 interfered with translation into the secreted TNF-alpha protein. These data show that GM-CSF is capable of priming for the enhanced release of two factors, initially for TNF-alpha and subsequently for PGE2. The temporally delayed generation of these two mediators suggests an autoregulatory circuit in which the later produced PGE2 limits GM-CSF-induced macrophage activation.
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PMID:Macrophage activation by granulocyte/macrophage colony-stimulating factor. Priming for enhanced release of tumor necrosis factor-alpha and prostaglandin E2. 247 21

Prostaglandin (PG) and thromboxane (TX) production by homogenates of human intracranial tumors (33 gliomas, 32 meningiomas, six brain metastases) and "normal" brain (n = 26) from tumor-bearing patients was studied. PGF2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha (the hydrolysis product of PGI2) and TXB2 (the hydrolysis product of TXA2) were determined by high-resolution gas chromatography-mass spectrometry after ex vivo metabolism of endogenous arachidonic acid. Prostanoid profiles (relative abundance of each metabolite) were different for gliomas and meningiomas, but similar for gliomas and their nontumoral counterpart, i.e., "normal" brain. Mean overall prostanoid production was significantly higher in gliomas (539 +/- 95) and meningiomas (523 +/- 69) than in "normal" brain (198 +/- 23). Prostanoid synthesis significantly increased with anaplastic grade (glioblastomas greater than anaplastic astrocytomas greater than slow-growing astrocytomas greater than "normal" brain), while profiles did not substantially change (TXB2 was the most and 6-keto-PGF1 alpha the least abundant product). Meningioma profiles showed no marked prevalence of any particular metabolite and no major differences between histological subgroups. All brain metastases from different carcinomas (n = 5) showed a prevalence of TXB2 and PGE2 and very low PGD2 synthesis.
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PMID:Prostaglandin and thromboxane synthesis by human intracranial tumors. 249 82

We attempted to analyse the mode of action of Hochu-ekkito on host defense mechanism, especially the effect of the drug on macrophage activation. Peptone-induced murine peritoneal exudate macrophages were incubated with/without Hochu-ekkito and interferon-gamma (IFN-gamma) for 16 hours at 37 degrees C, and then the supernatants harvested were assayed for the activities of TNF, IL-1 and prostaglandin E2. Cytotoxic activity of the macrophages against 51Cr-labeled EL-4 tumor cells was also assayed. It was found that Hochu-ekkito rendered macrophages cytotoxic against EL-4 cells. Hochu-ekkito also augmented the production of TNF, IL-1 or Prostaglandin E2 from macrophages. Synergistic effect of IFN-gamma for augmenting production of TNF or cytotoxic activity was noted. These results suggested that Hochu-ekkito activated macrophages directly in vitro.
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PMID:[Activation of macrophages with Hochu-ekkito]. 249 65

The mechanism(s) by which dietary linoleic acid (18:2n-6) enhances mammary tumor growth and metastasis is not known. Since arachidonic acid (20:4n-6)-derived prostaglandins (PG) may play a role in the metastatic dissemination of tumor cells, the ability of two murine mammary tumor cell lines, 4526 (metastasis positive) and line 168 (spontaneous metastasis negative), to convert 18:2n-6 into prostaglandins was examined. Cells were initially incubated with [14C]18:2n-6 and after 8-24 h the [14C]fatty acids were quantitated by high-performance liquid chromatography following transesterification. [14C]18:2n-6 was metabolized primarily to [14C]dihomogammalinolenic acid (20:3n-6) in line 4526 cells and [14C]20:4n-6 in line 168 cells. Examination of cellular fatty acid levels revealed a 20:3n-6/20:4n-6 ratio of 1.79 +/- 0.36 and 0.20 +/- 0.02 in line 4526 and 168 cells, respectively. These data are consistent with an inherently lower delta 5 desaturase activity in line 4526 relative to 168. To assess the metabolism of 18:2n-6 into eicosanoid products, the cell lines were prelabeled with [14C]18:2n-6 or 0-40 microM nonradiolabeled 18:2n-6 overnight and subsequently stimulated with calcium ionophore A23187 for 1 h. Total PGE production, as determined by radioimmunoassay, was greater in 168 relative to 4526 cells at all 18:2n-6 concentrations. 14C-prostaglandins detected by high-performance liquid chromatography and argentation thin-layer chromatography were: PGF1 alpha and PGE1 (derived from 20:3n-6) and PGF2 alpha and PGE 2 (derived from 20:4n-6) from line 4526; PGE1 and PGE2 from line 168. PGE1/PGE2 ratios were 1.43 +/- 0.07 and 0.23 +/- 0.03 for 4526 and 168 lines, respectively. Neither cell line synthesized lipoxygenase products following [14C]18:2n-6 or [3H]-20:4n-6 incubations under the conditions employed. Additional studies are warranted in order to define the biological properties of 1- and 2-series cyclooxygenase products as they relate to tumor cell metastasis.
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PMID:Linoleic acid metabolism in metastatic and nonmetastatic murine mammary tumor cells. 250 44

Detectable levels (greater than or equal to 0.2 pmol/10(6) cells) of one or more prostanoid species resultant to calcium ionophore A23187-induced biosynthesis from endogenous arachidonic acid were distributed in 28 cell lines derived from different histological classes of lung tumors as follows: large cell undifferentiated carcinoma (3 of 3 cell lines); adenosquamous carcinoma (1 of 2 cell lines); squamous cell carcinoma (0 of 2 cell lines); adenocarcinoma (9 of 10 cell lines); bronchioloalveolar cell carcinoma (2 of 2 cell lines); and small cell carcinoma (1 of 9 cell lines). Using the mean levels of 9 alpha,11 beta-prostaglandin F2, prostaglandin F2 alpha, prostaglandin D2, prostaglandin E2, thromboxane B2 and 6-keto-prostaglandin F1 alpha as an index of prostaglandin H (PGH) synthase activity, the distribution in cell lines representative of the different histological classes of human lung tumors exhibiting PGH synthase activity exceeding mean values greater than or equal to 2 pmol/10(6) cells was as follows: large cell undifferentiated carcinoma (3 of 3 cell lines), adenosquamous carcinoma (1 of 2 cell lines), adenocarcinoma (8 of 10) cell lines), bronchioloalveolar cell carcinoma (2 of 2 cell lines) and small cell carcinoma (0 of 9 cell lines). Three different prostanoid species accumulated to mean levels greater than or equal to 2 pmol/10(6) cells. Prostaglandin E2 levels exceeded 2 pmol/10(6) cells in 14 of the 16 cell lines in which this prostanoid accumulated to detectable levels. Cumulative levels of prostaglandin F2 alpha exceeded 2 pmol/10(6) cells in 9 of the 15 cell lines in which prostaglandin F2 alpha reached detectable levels. Detectable levels of thromboxane B2 were observed in five cell lines with thromboxane B2 accumulation exceeding 2 pmol/10(6) cells in two of the five cell lines. 9 alpha,11 beta-prostaglandin F2 and 6-keto-prostaglandin F1 alpha accumulated to detectable levels in the culture medium of one cell line, while prostaglandin D2 accumulation to detectable levels was observed in two cell lines. Stimulation of cultured human lung tumor cells exhibiting PGH synthase activity greater than or equal to 2 pmol/10(6) cells in the presence of 10(-5) M exogenous arachidonic acid resulted in a 2- to 4-fold increase in the accumulation of individual prostanoids, while the inclusion of a 10(-5) M exogenous concentration of arachidonic acid failed to stimulate detectable prostanoid production in human lung tumor cells in which PGH synthase activity was not previously expressed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evidence for prostanoid biosynthesis as a biochemical feature of certain subclasses of non-small cell carcinomas of the lung as determined in established cell lines derived from human lung tumors. 253 93

Virgin female Sprague-Dawley rats (50 days of age) were administered a single intragastric 10-mg dose of 7,12-dimethylbenz(a)anthracene (DMBA). Twenty-one days later they were placed on diets containing either 20% corn oil (CO), 15% menhaden oil plus 5% corn oil (MO + CO), 20% CO plus 0.5% w/w of the irreversible ornithine decarboxylase inhibitor, D,L-2-difluoromethylornithine (CO + DFMO), 20% CO plus 0.004% w/w of the cyclooxygenase inhibitor indomethacin (CO + INDO), 20% CO + 0.004% INDO + 0.5% DFMO (CO + INDO + DFMO), or 15% MO + 5% CO + 0.5% DFMO (MO + CO + DFMO). The incidence of DMBA-induced mammary tumors was significantly reduced in rats fed diets containing DFMO but not in rats fed the diet containing indomethacin. Incidences of mammary tumors at 16 weeks post-DMBA were 86% in rats fed the CO diet, 83% in rats ingesting the diet containing CO + INDO, 28% in rats fed CO + DFMO, 32% in rats fed diet containing CO + INDO + DFMO, 59% in rats fed the MO + CO diet, and 24% in rats fed the MO + CO + DFMO diet. The average number of tumors and tumor burden per tumor-bearing rat were reduced and tumor latency was increased in all rats fed diets containing DFMO. Body weight gain, but not food intake, of rats fed the 20% fat + 0.5% DFMO diets was significantly less than in rats fed the 20% fat diets. Prostaglandin E and leukotriene (LTB4) syntheses, ODC activity and mammary tumorigenesis were significantly inhibited by feeding the diet containing menhaden oil or by adding 0.5% DFMO to any of the high fat diets. Feeding a 20% CO diet containing 0.004% INDO significantly reduced prostaglandin synthesis and ODC activity and increased LTB4 synthesis of mammary tumors but did not inhibit mammary tumorigenesis. This study suggests that the 5-lipoxygenase product LTB4 may be involved in mammary tumor production. Whereas a decrease in LTB4 appears to be associated with a decrease in tumorigenesis, an increase (as seen in the indomethacin group) was not associated with any change in the tumorigenic response.
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PMID:Effects of D,L-2-difluoromethylornithine and indomethacin on mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets. 253 26

The biochemical mechanisms involved in the activation and killing of tumor targets by large granular lymphocytes (LGL) have not yet been clearly defined. This laboratory has investigated these processes by analyzing the effects of protein kinase C (PKC) inhibitors (1-(5-isoquinolinesulfonyl)2-methyl-piperazine-dihydrochloride and retinol) on LGL cytotoxicity and IFN-gamma production. We now report that PKC inhibitors block the LGL functions of 1) NK activity, 2) IFN-gamma production, and 3) LAK activity induced by IL-2. Complete inhibition of cytotoxic activity occurs rapidly because only 2.5 h treatment of the LGL with the inhibitors was required. However, the inhibition of NK activity by the PKC inhibitors could be reversed by IL-2 or the synthetic diacylglycerol, L-gamma-1-oleyl-2-acetol-sn-3-glycerol (OAG), but not by IFN-alpha. The reversal of inhibition observed with OAG indicates that, in these studies, (1-(5-isoquinolinesulfonyl)2-methyl-piperazine-dihydrochloride is inhibiting PKC activity and not the activity of other cellular kinases. Furthermore, inhibition of LGL functional activity with PGE2 could not be reversed with OAG, supporting the contention that PG inhibition of NK activity is mediated by a pathway that does not directly involve PKC. These results indicate, in addition to IL-2-mediated events, that basal NK activity is under PKC regulatory control.
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PMID:Modulation of CD3- large granular lymphocyte functions by agonist and antagonists of protein kinase C: effects on NK and lymphokine-activated killer activity and production of IFN-gamma. 254 2

In order to investigate the production of PGE2 and its' function in human hepatocellular carcinoma, the effects of indomethacin and PGE2 on tumor growth were examined using in vivo and in vitro techniques. HH2-6 cells produced PGE2 in the culture media, and the inverse relationship was observed in between the cell proliferation and the culture supernatant PGE2 levels. While in vivo, plasma and tumor tissue PGE2 levels of tumor bearing nude mice were significantly increased for 1 or 2 weeks after tumor inoculation. In the case of which indomethacin was injected daily into the abdominal cavity (4 mg/kg body weight), the elevation of plasma and tissue PGE2 levels was remarkably suppressed, and the latent time of tumor growth was also prolonged. On the other hand, another case of which PGE2 was injected (10 micrograms or 0.1 microgram i.p.) at first 10 days revealed shortened latent time. These results indicate the intimate relation between PGE2 and latent time on tumor growth. Furthermore, histological findings suggest that tumor derived PGE2 might play an important role in tumor angiogenesis.
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PMID:[In vivo and in vitro studies on PGE2 production and function in human hepatocellular carcinoma]. 254 95

The biological activity, including metabolism and modulation of ornithine decarboxylase activity and DNA synthesis, of arachidonic acid (AA) and eicosapentaenoic acid (EPA) were compared in epidermal cells from SENCAR mice. Radiolabelled AA and EPA were found to be similarly incorporated into and released from membrane phospholipids of unstimulated cultures. However, when cells were stimulated with the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA), the release of AA was significantly higher than the release of EPA. The extent of metabolism of AA and EPA to prostaglandins was determined in both freeze-thawed cell preparations and in viable cultured cells. In the freeze-thawed preparations, use of AA as a substrate resulted in significantly more PGF than when EPA was used as the substrate. However, more PGE3 was formed than PGE2. PGD levels were the same for either fatty acid precursor. Prostaglandin production was also determined in viable cultured cells since other influences such as phospholipase A2 activity can modify prostaglandin production. Control cultures prelabelled with either AA or EPA produced similar amounts of the respective PGF, PGE, and PGD. However, TPA-stimulated cultures produced significantly higher amounts of each prostaglandin in cultures prelabelled with AA compared to cells prelabelled with EPA. HETE or HEPE production was the same both for cultured cells prelabelled with AA or EPA and for homogenates from uncultured cells incubated directly with the radiolabelled fatty acids. TPA-induced ornithine decarboxylase (ODC) was significantly higher in AA-treated cultures compared to EPA-treated cultures. AA supports DNA synthesis to a greater extent than EPA, either alone or in the presence of TPA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Eicosapentaenoic and arachidonic acid: comparison of metabolism and activity in murine epidermal cells. 254 33


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