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)

Recent reports suggest that many of the biological effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate are mediated via intracellular prostaglandin biosynthesis. We have investigated whether the induction of plasminogen activator by 12-O-tetradecanoylphorbol-13-acetate in cultured HeLa cells is similarly mediated. 12-O-Tetradecanoylphorbol-13-acetate (0.5 to 50 nM) increased intra- and extracellular plasminogen activators and stimulated E- and F-type prostaglandin production. Changes in prostaglandin biosynthesis preceded those in plasminogen activator by several hr. Indomethacin (0.5 microM) abolished prostaglandin production but had no effect on either the magnitude or the time course of induction of plasminogen activator. Similar results were obtained with human skin fibroblasts and MDCK cells. Prostaglandins E1, E2, F2 alpha, and I2 had no direct effect on plasminogen activator in HeLa cells or skin fibroblasts. We conclude that in these cells, phorbol ester independently induces plasminogen activator and prostaglandin biosynthesis.
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PMID:Induction of plasminogen activator and prostaglandin biosynthesis in HeLa cells by 12-O-tetradecanoylphorbol-13-acetate. 719 16

Biochemical and clinical evidence is presented to indicate that prostaglandin (PG)E2 is the mediator of fluid and electrolyte secretion by villous adenomas of the rectum. A 64-yr-old man with a 2-mo history of mucous diarrhea had, on admission, prerenal uremia, severe hyponatremia, and hypokalemia. At sigmoidoscopy an 11 X 11-cm villous adenoma of the rectum was revealed. The rectal fluid discharge was 1800-1825 ml/day, with sodium and potassium concentrations of 150 and 12 mEq/L, respectively. Immunoreactive PGE2 levels in the rectal effluents were high (viz. 1160-1250 pg/ml vs. 200-395 pg/ml) compared with those in stool water from patients with infectious diarrhea. The concentration of vasoactive intestinal polypeptide (VIP) in the tumor was lower (viz. 10.5 pmol/g vs. 100-700 pmol/g) than in normal colonic mucosa. Indomethacin treatment (24 mg X 4 daily) reduced the rectal PGE2 excretion from 2.2 to 0.3 microgram/day and caused a decrease in the rectal fluid loss of 850 ml/day associated with a similar reduction in rectal sodium excretion. Discontinuing medication, a rise in the rectal excretions of PGE2, fluid, and sodium was observed. In conclusion, PGE2 formation in the villous adenoma appears to be the cause of fluid secretion by the abnormal tumor epithelium. The use of PG synthetase inhibitors may facilitate the preoperative correction of severe fluid-electrolyte deficits in patients with large villous adenomas of the rectum.
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PMID:Prostaglandin E2-mediated secretory diarrhea in villous adenoma of rectum: effect of treatment with indomethacin. 722 79

The in vivo administration of a prostaglandin-synthetase inhibitor inhibited or reduced tumor growth in cancer patients and experimental animals. Indomethacin, a prostaglandin-synthetase inhibitor and nonsteroidal anti-inflammatory agent commonly used in the management of arthritic patients, acted as an immune adjuvant by decreasing the production of prostaglandins. Seven cases demonstrated that indomethacin taken in the usually recommended dosages causes regression and stabilization of head and neck cancer. The following factors were also considered in this study: prostaglandin production, a survey of other reports of solid neoplasm response to prostaglandin-synthetase inhibitor administration, drug toxicity, irradiation therapy and metastases, the need for tumor biopsy, and the role that reduction in inflammation plays in tumor shrinkage.
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PMID:Regression of head and neck carcinoma with a prostaglandin-synthesis inhibitor. 729 59

Ornithine decarboxylase which forms putrescine by the decarboxyalation of ornithine, is the first and probably the rate-limiting enzyme in the biosynthesis of the other polyamines, spermidine and spermine. Epidermal ornithine decarboxylase activity is greatly elevated in response to tumor promoting agents and ultraviolet light. The purpose of this paper is to report modification of ultraviolet-induced epidermal ornithine decarboxylase activity by antiinflammatory agents. Topical triamcinolone acetonide and indomethacin were found to significantly inhibit the UV-B induction of epidermal ornithine decarboxylase in hairless mice when applied following ultraviolet light irradiation. The corticosteroid also showed inhibition of ultraviolet light increased epidermal DNA synthesis. Indomethacin failed to show any inhibition of DNA synthesis. It is suggested that these assays may be used to study drugs that may modulate some ultraviolet light effects on the epidermis.
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PMID:Antiinflammatory drug effects on ultraviolet light-induced epidermal ornithine decarboxylase and DNA synthesis. 738 Dec 32

Our previous observations on the production of prostaglandin E2 (PGE2) by bladder tumor cell lines in vitro and the enhancement of tumor cell PGE2 production upon exposure to purified peripheral blood lymphocytes from normal human donors prompted us to examine this interaction in an animal model in order to further define conditions that determine the occurrence of this phenomenon. Cell lines derived from carcinogen-induced bladder and mammary tumors and from embryo fibroblasts in Fischer rats were exposed to purified peripheral blood or splenic lymphocytes in the presence or absence of indomethacin (10(-7)M). After varying times at 37 degrees, supernatants were harvested for determination of PGE2 by radioimmunoassay. Time course studies demonstrated rapid PGE2 production with plateau levels appearing at 8 hr. Increased tumor cell PGE2 production occurred in the presence of increased numbers of lymphocytes. Indomethacin partially inhibited PGE2 production. Preincubation studies suggested that the contribution of lymphocytes to overall PGE2 production in the present system was minimal. On the basis of previous observations of PGE2-associated inhibition of lymphocyte cytotoxicity against tumor cells in vitro, the present results suggest that tumor cell PGE2 production may reflect a response of the tumor cells to challenge by effector lymphocytes and may represent a mechanism whereby tumor cells subvert an immune response mounted against them.
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PMID:Production of prostaglandin E2 by tumor cells in vitro. 742 35

GH4C1 cells are strain of rat pituitary cells which synthesize and secrete both PRL and GH. Phorbol esters, which are potent tumor promoters in mouse skin and have diverse actions in a variety of cell and tissue systems, were found to alter hormone production by GH4C1 cells. 12-O-Tetradecanoylphorbol-13-acetate (TPA), the most potent phorbol ester, stimulated both PRL synthesis and release. The synthesis of PRL was stimulated 2.3- to 6.2-fold over control values after 3 days of treatment; the ED50 for TPA was 8.9 +/- 2.1 nM (5.5 +/- 1.3 ng/ml). The release of stored PRL was stimulated within 10 min of the addition of 100 ng/ml TPA to the culture medium. Maximum stimulation of release was 1.3- to 2.3-fold over control, and the ED50 for TPA was 13.2 +/- 2.3 nM (8.1 +/- 1.4 ng/ml). Another tumor-promoting phorbol ester, phorbol 12,13-didecanoate (PDD), stimulated PRL synthesis and release to the same maximum extent at TPA, but two biologically inactive compounds, 4 alpha-PDD and phorbol, had no effect. The stimulation of PRL release by TPA was a Ca++-dependent process; Co++, a competitive antagonist of Ca++, at 2.0 mM blocked completely the stimulation of PRL release by 100 ng/ml TPA, and this block was overcome by 2.0 mM Ca++, but not by 2.0 mM Mg++. Although phorbol esters stimulate prostaglandin (PG) synthesis in certain other cells types, PGs were not required for TPA action in GH4C1 cells. Indomethacin, a PG cyclooxygenase inhibitor, at 200 ng/ml did not inhibit the stimulation of PRL synthesis and release by TPA. Furthermore, there was no detectable (less than 50 pg/ml) PGE2 or PGF2 alpha in the medium of control or TPA-treated cells. In GH3 cells, a related cell strain, TPA (100 ng/ml) decreased GH production in both control and hydrocortisone-stimulated cells to 35% of untreated control values after 3 days of incubation. TPA also altered cell morphology, but had little or no effect on cell growth. We conclude that GH cells provide a useful system to study the mechanisms of phorbol ester action on differentiated functions.
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PMID:Tumor-promoting phorbol esters affect production of prolactin and growth hormone by rat pituitary cells. 747 64

Prostaglandin E2 (PGE2) is known to downregulate the generation of lymphokine-activated killer (LAK) cell activity. Indomethacin, an inhibitor of cyclooxygenase catalyzing the biosynthesis of PGE2, has been shown to augment LAK cell activities generated from peripheral blood mononuclear cells of normal healthy individuals. This study was undertaken to examine whether or not this augmentation is also a common phenomenon in cancer patients. LAK cell activities generated in the presence and the absence of indomethacin were examined in 15 normal healthy individuals and in 83 cancer patients. Paired data analysis revealed that indomethacin exhibited a significant augmentation of LAK activity generated from healthy individuals. Indomethacin enhanced LAK activity in patients with no distant metastases (TxNxM0); but depressed LAK activity in patients with distant metastases (TxNxM1). In patients without distant metastases, indomethacin showed an upregulating effect on LAK activity in those with an early T stage (T1-2NxM0), and no such effect was detected in those with a late T stage (T3-4NxM0). Indomethacin also significantly enhanced LAK cell generation in cancer patients with an ECOG performance status of 1, but significantly inhibited LAK cell generation in patients with a performance status of 4. These results indicated that indomethacin inhibited generation of LAK cell activity in cancer patients with a poor performance status or with distant metastatic disease, who normally would be the subjects of adoptive immunotherapy. Further, PGE2 production in cultured LAK cell medium was suppressed by indomethacin in all 20 cancer patients that were examined, suggesting that other yet to be identified factors or mechanisms may be responsible for the paradoxical effects of indomethacin on LAK cell activity.
Tumour Biol 1995
PMID:Effects of indomethacin on lymphokine-activated killer cell activities in cancer patients. 760 4

The effects of indomethacin on the urinary bladder and renal pelvis in rats treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) were studied. Two hundred female Sprague-Dawley rats were divided into four groups. Group 1 received control diet without added chemicals. Group 2 was treated with indomethacin (1 mg/kg per day) in the drinking water throughout the experiment. Groups 3 and 4 received 0.2% FANFT in the diet for seven weeks followed by control diet. In addition to FANFT, Group 4 received indomethacin, 1 mg/kg per day, for the entire experiment. The rats were sacrificed after 92 weeks. There were no urothelial tumors in the control group, one renal pelvic tumor in the indomethacin group, 4 tumors in the FANFT group and 10 urothelial tumors in the FANFT + indomethacin group. The difference between Groups 3 and 4 was statistically significant (P < 0.05). Moderate and severe hyperplasia of the renal pelvic and papillary epithelium was found in 15 of 48 rats in Group 2 (indomethacin only) as compared with 6 of 49 control rats (P < 0.05). Moderate and severe hyperplasia was equally frequent in Groups 3 and 4 (14 and 17 animals in each group, respectively). Twenty-four rats in Group 2 had mammary tumors as compared to 12 animals in Group 1 (P < 0.01). Five of the tumors in Group 2 were adenocarcinomas. There was no difference between the number of mammary tumors in Groups 3 and 4 (36 and 32 animals in each group, respectively). The results suggest that indomethacin enhances FANFT-induced urinary tract carcinogenesis. Indomethacin also seems to exert some tumorigenic activity in the mammary gland.
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PMID:Effect of indomethacin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced urinary tract carcinogenesis. 761 82

The purpose of this study was to test the hypotheses that (1) surgical wounding can enhance the xenotransplantability of a human soft tissue sarcoma (HSTS26T) into subcutaneous (s.c.) tissue of nude mice, and (2) Indomethacin may reduce the xenotransplantability of this human tumor in the surgical wounding animal model by suppressing angiogenesis. The experimental method was to employ the quantitative transplantation assays (TD50, the number of tumor cells that, on average, would be expected to induce a tumor in 50% of the recipients). After an incisional wound (1.0-1.2 cm long) was made on the right leg of each experimental mouse, tumor cells were inoculated into the surgical wound, or into the contralateral leg at 24 and 72 hr postincision, and in another group tumor cells were inoculated into the wound at 72 hr postincision, plus daily s.c. injection of indomethacin, 2 mg/kg body weight for 8 consecutive days in a separate experiment. Nonincisional mice received the same inoculation as the control groups. The TD50s of surgically wounded groups were 3.5-10.7 times lower than that of the control groups. Significantly lower TD50 values were found in groups of cells inoculated into the surgical wound at 72 hr postincision (P < 0.05 or P < 0.01) and into the contralateral leg at 24 hr postincision (P = 0.05). No significant difference was found between the TD50 values in mice that received cells inoculated at 72 hr postincision plus indomethacin treatment, and those with no wound controls. Our conclusion is that the surgical wound can enhance the xenotransplantability of HSTS26T in nude mice. Indomethacin can decrease this enhancing effect level similar to that in no-wound controls and may prevent tumor recurrence in a surgical wound.
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PMID:Quantitative comparison of xenotransplantation of a human soft tissue sarcoma into the subcutaneous tissue of normal, postincision, and postincision plus indomethacin-treated nude mice. 772 70

AS101 as a new immunomodulator has been shown to induce production of a variety of cytokines such as interleukin-1, interleukin-2, colony-stimulating factor, interferon-gamma and tumor necrosis factor, and demonstrate a potential chemo-protection from chemotherapy induced immunosuppression and hematopoietic toxicity in tumor bearing mice and cancer patients on phase I and II clinical trials. This study was designed to verify whether AS101 exerts a cytoprotective effect in rats and mice with gastric lesions induced by intragastric (i.g.) instilling of 0.6N hydrochloride (HCl). AS101 given intraperitoniously (i.p) 2h before a HCl administration markedly prevented HCl-induced gastric lesions both in rats and mice. It also accelerated the ulcer repair when given i.p. 1h after a HCl treatment. Indomethacin (IND), a cyclo-oxygenase inhibitor, given i.p. at a non-ulcerogenic dose of 5mg/kg 1h before AS101 administration, abolished its protective effect. Mechanistic analysis showed that the gastric cytoprotective property of AS101 appears to be mediated through the induction of prostaglandin E2 (PGE2) and epidermal growth factor (EGF), of which, both prevent the gastric mucosa from HCl ulceration while EGF also contributes to the promotion of ulcer repair. This study adds another cytoprotective property to the known immunomodulating role of AS101.
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PMID:The cytoprotective effect of the immunomodulator AS101 against hydrochloride induced gastric lesions. 773 28


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