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)

We have previously reported that both regressor (QR) and progressor (metastatic, QP) clones were obtained after the in vitro exposure of a mouse fibrosarcoma BMT-11 cl-9 to quercetin. In this study, we investigated possible mechanisms of spontaneous regression of QR clones as compared with tumorigenic QP and BMT-11 cl-9 tumor clones. We observed that BMT-11 cl-9 cells produced relatively high amounts of prostaglandin E2 (PGE2) during in vitro culture. The average production by 11 subclones of BMT-11 cl-9 cells was 9236 +/- 2829 pg/ml whereas that by 9 QR clones was 3411 +/- 2213 pg/ml (P less than 0.02). Indomethacin not only inhibited in vitro PGE2 synthesis by QP clones (high-PGE2 producers) but also the s.c. growth of QP clones in mice. Chronological changes in host immune responses to tumor-associated antigen were measured by cytotoxic T lymphocyte (CTL) activity examined after mixed lymphocyte/tumor cell culture of spleen cells obtained from tumor-bearing mice. The CTL activity disappeared abruptly in the spleen of QP-clone-bearing mice 21 days after the inoculation of tumors, whereas the spleen cells of QR-clone-inoculated mice retained their CTL activity. We determined that the mechanism responsible for the regression of these regressor clones is not due to any qualitative or quantitative increase in pre-existing membrane antigens, nor the emergence of new antigen(s) on the cell surface of the QR clones: nor was it due to enhanced susceptibility of QR clones to natural killer cells, lymphokine-activated killer cells and macrophages. These finding suggest that the regression mechanism of QR clones may be the diminished inhibition of host response to tumor-associated antigen caused by the reduced production of PGE2 by QR clones.
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PMID:Regression mechanisms of mouse fibrosarcoma cells after in vitro exposure to quercetin: diminution of tumorigenicity with a corresponding decrease in the production of prostaglandin E2. 238 81

The mode of action of rat interferon (IFN) on growth of the R3230AC mammary adenocarcinoma was studied in vivo in Fischer female rats. A dose of 1 X 10(4) units of rat IFN given thrice weekly inhibited the growth of the transplanted mammary tumors. Of the five eicosanoids measured in the tumor, the content of four arachidonate products, prostaglandin (PG) E2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane (TX) B2, was higher in mammary tumors from IFN-treated rats than the control rats. PGE2 was the major eicosanoid. In vitro PG synthesis (PGE1, PGE2, and PGF2 alpha) was lower in tumor microsomes prepared from IFN-treated tumors. These data suggest that the tumor content of four arachidonate products in the IFN-treated tumors was related to the in vivo effects of rat IFN. Indomethacin, a cyclooxygenase inhibitor, also inhibited tumor growth. Furthermore, when indomethacin was administered daily in combination with rat IFN, the tumor-inhibiting effect of rat IFN was reduced. These observations suggest that the effects of eicosanoids appear to be biphasic in this tumor model. Inhibition of arachidonic acid metabolism resulted in tumor growth inhibition, a finding consistent with the view that eicosanoid production is required for tumor enhancement. Conversely, in the experiments with rat IFN, retardation of tumor growth is associated with a greater amount of arachidonic acid metabolism, and indomethacin prevents this effect. Eicosanoids appear to be required for tumor-inhibiting effects of rat IFN, and yet inhibition in vivo of eicosanoid synthesis also resulted in retardation of tumor growth. Although the precise mechanism of action in each situation is unclear, these apparently contradicting results are consistent with the biphasic actions of eicosanoids reported in some normal tissues and transformed tumor cell lines.
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PMID:Growth inhibition and eicosanoid metabolism in the R3230AC mammary adenocarcinoma by interferon. 242 Apr 45

Okadaic acid and dinophysistoxin-1 isolated from a black sponge, Halichondria okadai are non-12-O-tetrade-canoylphorbol 13-acetate (non-TPA)-type tumor promoters of mouse skin. Okadaic acid at concentrations of 10-100 ng/ml stimulated prostaglandin E2 production in rat peritoneal macrophages. Dinophysistoxin-1 (35-methylokadaic acid) stimulated prostaglandin E2 production as strong as okadaic acid, but okadaic acid tetramethyl ether, an inactive compound as a tumor promoter, did not. Okadaic acid at 10 ng/ml (12.4 nM) stimulated prostaglandin E2 production as strongly as TPA at 10 ng/ml (16.2 nM) 20 h after incubation. Unlike TPA-type tumor promoters, okadaic acid required a lag phase before stimulation. The duration of this lag phase was dependent on the concentration of okadaic acid. Indomethacin inhibited okadaic acid-induced preostaglandin E2 production in a dose-dependent manner, and its inhibition was more strongly observed in okadaic acid-induced prostaglandin E2 production. Cycloheximide inhibited okadaic acid-induced release of radioactivity from [3H]arachidonic acid-labeled macrophages and prostaglandin E2 production dose dependently, suggesting that protein synthesis is a prerequisite for the stimulation of arachidonic acid metabolism. These results support our idea that tumor promoters, at very low concentrations, are able to stimulate arachidonic acid metabolism in rat peritoneal macrophages.
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PMID:Okadaic acid and dinophysistoxin-1, non-TPA-type tumor promoters, stimulate prostaglandin E2 production in rat peritoneal macrophages. 250 33

The effect of indomethacin on tumor-infiltrating lymphocytes (TIL) was investigated in a spontaneously developed and weakly immunogenic murine mammary adenocarcinoma (designated JC) in syngeneic immunocompetent BALB/c mice, a tumor model mimicking human disease. Unlike other chemically and virally induced tumors, the expansion of TIL was only possible with an enriched population of lymphocytes, isolated on a discontinuous density gradient then cultured in complete medium containing recombinant human interleukin-2 (rIL-2). The freshly isolated TIL exhibited no cytotoxicity against either the natural-killer-sensitive YAC-1 or the natural-killer-resistant JC cells lines. After culture in rIL-2, the TIL of the JC tumor lysed both YAC-1 and JC. The cytotoxicity of the TIL reached a maximum between the 2nd and 3rd week of culture and decreased thereafter. Antibody- and complement-depletion tests revealed that the cells bearing asialo-GM1 antigen represented the major precursor cells of the cytotoxic TIL, which may explain its nonspecific cytotoxicity. Indomethacin was shown to accelerate the cell proliferation of the rIL-2-activated TIL, but only in the initial 2 weeks of culture and not in later culture. The addition of indomethacin to the rIL-2-containing medium at the beginning of culture resulted in a fast-acting and long-lasting enhancement in cytotoxicity. These results provided a basis for the clinical use of indomethacin, i.e. acceleration in proliferation and augmentation in cytotoxicity. However, the addition of indomethacin at the end of the fourth week after rIL-2 culturing produced neither accelerated proliferation nor augmented cytotoxicity. This study also suggested that a prolonged administration of indomethacin may not be advantageous in clinical trials, since the long-term continuous presence of indomethacin in the culture has resulted in a negative effect on the growth of TIL.
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PMID:Effect of indomethacin on tumor-infiltrating lymphocytes of a spontaneously developed murine mammary adenocarcinoma. 259 84

Several studies have shown the relationship between prostaglandins (PGs) and cell proliferation. Some PGs may trigger cell division or are involved in this process. This study analyzes the effect of PG biosynthesis inhibitors on tumor growth in vivo and cachexia in Walker 256 tumor-bearing rats. Indomethacin markedly inhibited tumor growth (95.5%) while ibuprofen and aspirin reduced tumor growth by 73.9% and 59.4%, respectively. In addition, all drug-treated rats partially recovered body weight and food intake as compared to the saline-treated group. These findings suggest that PG synthesis inhibitors improve cancer cachexia.
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PMID:Effects of aspirin-like drugs on Walker 256 tumor growth and cachexia in rats. 263 46

Immunomodulation is interpreted as a temporary alert in a certain part of the immune system. The activation of immune competent cells is presented as a possible basic mechanism of this phenomenon. In the absence of a primary stimulus, immunomodulation remains physiologically silent, but it results in a modified immune response if the corresponding targets are being stimulated. For practical reasons it is suggested that distinctions be made between preventive and regulative immunomodulation. The PWM-induced IgG production of PBMCs was used as a model for the demonstration of the modulatory effect of thymopentin in vitro. Depending on the concentration of thymopentin used in the cultures, this pentapeptide can either stimulate or inhibit the induced IgG production. It also influences PGE2 production and catabolism in the cultures stimulated with PWM. Indomethacin abolishes the modulatory effect of thymopentin on IgG production in this model. It is suggested that the possibility of interactions between an immune modulator and therapeutic approaches which can influence the proportions or functions of the corresponding target cells be considered.
Med Oncol Tumor Pharmacother 1989
PMID:Immunomodulation with thymopentin: in vitro studies. 265 46

Indomethacin, a non-steroidal anti-inflammatory drug which is also a calcium antagonist and an inhibitor of prostaglandin synthesis was observed to have a chemotherapeutic effect in a mouse fibrosarcoma. More significantly, administration of the drug before exposure to either radiation or hyperthermia, enhanced their effects. Apart from tumor growth delay, tumor cures were also observed in all the three modalities tested. The data suggests a potential anti-cancer role for indomethacin in combination modalities.
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PMID:Studies on indomethacin as a potentiator for hyperthermic and radiation responses in a mouse fibrosarcoma. 273 Nov 66

Resistance of hypoxic cells to radiation and chemotherapy remains a major limitation to effective therapy of solid tumors. Misonidazole, a 2-nitroimidazole analogue, has been studied extensively as a radiosensitizer of hypoxic cells and has been shown to undergo bioreductive metabolism to exert preferential cytotoxicity against hypoxic cells. We have investigated the effects of misonidazole on the biosynthesis of prostaglandins (PGs) in a murine mammary adenocarcinoma cell line (No. 4526) under aerobic and hypoxic conditions in attempts to exploit modulation of PG levels under hypoxia as a means of improving therapeutic approaches for the treatment of solid tumors. We report a time-dependent inhibition of PG biosynthesis by the suspended cells under hypoxia induced by flushing sealed vials with N2 (1.5 liters/min). After 30 min of hypoxia, PG formation was inhibited by 50%. Indomethacin was able to further inhibit the PG formation in a concentration-dependent manner under hypoxia. Misonidazole, however, selectively increased the PGE2 biosynthesis under hypoxia by 49% at 100 microM. This increase was concentration dependent over the range of 25 to 100 microM and was blocked by indomethacin (0.1 microM). Imidazole, the heterocyclic moiety in misonidazole without the nitro function, had no effect on PG biosynthesis at these concentrations. These data suggest that arachidonic acid metabolism is sensitive to the differential oxygen levels which exist within solid tumors and that PG levels may be modulated by electron-affinic agents in hypoxic tumor cells.
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PMID:Modulation of prostaglandin biosynthesis in hypoxic murine mammary adenocarcinoma cells by misonidazole. 273 27

The effects of indomethacin and dexamethasone on carcinogenesis of the esophagus and forestomach were studied in male rats. The rats were treated by N-nitrososarcosine ethyl ester (NSEE) per os in a daily dose of 50 mg/kg body weight for 16 weeks. Indomethacin (25 mg per kg of the food) and dexamethasone (1 mg per kg of the food) were added to food on accomplishing the carcinogen treatment for another 16 weeks, thereafter the animals were sacrificed. NSEE induced the esophagus and forestomach tumors approximately in 90% of cases, mainly papillomas and rarely carcinomas, on the average more than 5 tumors per nat. Indomethacin and dexamethasone were shown to inhibit the development of the NSEE-induced tumors both in the esophagus and forestomach. The both drugs decreased tumor incidence approximately by 20% and tumor multiplicity more than twofold.
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PMID:[The inhibition of esophageal tumor development by the use of the nonsteroidal and steroidal anti-inflammatory preparations indomethacin and dexamethasone]. 274 48

The effects of adherent cell depletion, indomethacin, and prostaglandin E2 (PGE2) on murine LAK cell activity were investigated. Removal of plastic adherent cells from splenocyte suspensions either prior to 5-day culture with 1000 U/ml of recombinant human IL-2 (rIL-2) or prior to assay resulted in an enhanced LAK cell cytotoxicity compared to that of whole spleen cell suspensions. Indomethacin enhanced LAK cell cytotoxicity of whole splenocyte suspensions if present during the culture period, but had no effect on whole splenocyte or adherent cell-depleted cell suspensions if added just prior to assay. PGE2 suppressed LAK cell activity of nonadherent splenocyte but not whole splenocyte suspensions when present during the culture period. In vivo treatment of mice with indomethacin enhanced cytotoxicity directed toward both LAK sensitive, natural killer (NK) resistant (P-815) and LAK, NK sensitive (YAC-1) tumor cell targets. Splenocytes from indomethacin-treated mice cultured with additional indomethacin and rIL-2 exhibited highest LAK cell activity. The results from this study indicate that LAK cells are regulated by adherent cells which suppress LAK cell activity. This suppression can be reversed both in vitro and in vivo by indomethacin. This study has important implications for the possible clinical use of indomethacin in the potentiation of in vivo and in vitro LAK cell activity for immunotherapeutic protocols.
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PMID:Inhibition of murine lymphokine-activated killer (LAK) cell activity by adherent cells. 278 56


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