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

Prostaglandins (PGs) are known to be widely distributed in the living body, and have a broad spectrum of biological effects on almost all the systems of the body. In this paper, we summarized the regulation of cell growth by PGs. Among several PGs, both PG-F2 alpha and thromboxanes stimulate the cell growth, while AGE, E2, D2 and A2 inhibit the cell growth. The role of PGF2 alpha on the cell growth may be the initiation of DNA replication. PGE1 and E2 stimulate the formation of cyclic AMP in a number of cells. Cyclic AMP plays a role in the regulation of cell growth. Therefore, the inhibitory effects of PGE on cell growth seem to be done by influencing cyclic AMP level. It is possible that PGE produced by tumor cells in vivo will suppress immune systems of the host animals. But more precise studies are required to understand exactly the self-regulation of cell growth by PGs and the mechanism of stimulatory or inhibitory effects of PGs.
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PMID:[Regulation of cell growth by prostaglandins]. 635 53

Intraperitoneal treatment with the interferon inducer, maleic anhydride-divinyl ether copolymer (MVE), has previously been demonstrated to effectively reduce metastatic growth in the lungs and prolong survival times of BALB/c mice bearing the syngeneic Madison lung (M109) carcinoma. Resistance to lung metastasis formation induced by MVE appears to result from an activation of alveolar macrophage function. Since E-type prostaglandins (PGE) suppress the cytotoxic activity of activated macrophages, we sought to determine the effect of indomethacin, a prostaglandin synthetase inhibitor, on the antimetastatic activity of MVE. An artificial metastasis model was developed in which single-cell suspensions of the M109 tumor were injected i.v. into BALB/c mice. A 52,600 molecular weight fraction of MVE (MVE-5) was administered i.p. at 20 mg/kg two days prior to tumor inoculation. MVE-5 treatment produced greater than 80 percent reduction in macroscopic lung lesion formation at Day 15 and Day 19 after tumor inoculation and a resultant 45 percent increase in lifespan. Chronic administration of indomethacin in the drinking water at 10 micrograms/ml potentiated the MVE-5 antitumor induced macrophage activation in vivo. In the absence of any evidence for an interaction between indomethacin and circulating M109 cells, it was felt that the potentiating effect could be best explained in terms of interference with PGE-mediated feedback inhibition of macrophage functional activity.
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PMID:Potentiation of nonspecific immunotherapy of experimental lung metastases by indomethacin. 642 37

The role of macrophages in tumor-mediated immunosuppression was examined, using C57B1/6 strain mice bearing four different immunosuppressive transplantable syngeneic tumors (Lewis Lung Carcinoma, B16 Melanoma, and two fibrosarcomas induced by methylcholanthrene in our laboratory). When tested for immunosuppressive activity, in inhibiting the induction of antibody formation by normal spleen cells in response to SRBC in vitro, the splenic and peritoneal macrophages from tumor-bearing mice were all significantly suppressive. The degree of suppression correlated with immunosuppression in tumor-bearing mice challenged in vivo with SRBC. Direct action of tumor cells on normal splenic macrophages in vitro caused them to become suppressive, the extent of suppression dependent on the time of interaction and on the immunosuppressive activity of the tumor cells in vivo. Pretreatment of suppressive splenic macrophages with indomethacin, a potent inhibitor of the synthesis of prostaglandins (PG), reduced significantly their immunosuppressive activity. Also, peritoneal macrophages from tumor-bearing mice produced significantly more PGE in culture than control macrophages. Thus, tumor-activated macrophages, presumably those macrophages that infiltrate the tumor in a host reaction against the tumor, serve to amplify the level of immunosuppression in the host by producing relatively large amounts of PGE that is a key physiological mediator in the activation and function of suppressor T lymphocytes. The stimulation of PGE synthesis in macrophages, as a result of their interaction with syngeneic tumors, is initiated by PGE produced in relatively large amount by the tumor cells.
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PMID:Amplification by macrophages of prostaglandin-mediated immunosuppression in mice bearing syngeneic tumors. 659 51

Plasma prostaglandins (PGs) of normal individuals and cancer patients have been examined. With the exception of a breast carcinoma patient, all patients demonstrated significant elevations in PGE levels. Lung cancer patients showed a significant decrease in PGF, while stomach cancer patients showed a marked decrease in PGB. It is suggested that the changes in PGs may play a significant role in host-tumor metabolism.
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PMID:Distribution of prostaglandins B, E and F series in plasma of cancer patients. 694 71

Prostaglandins (PGs) have been implicated as a regulator of tumor growth in mice and humans. Since natural killer cell (NK) cytotoxicity may be an important component of immune surveillance against cancer, it is appropriate to study whether the amount of PGs produced by tumors may be sufficient to suppress NK activity. Accordingly, the effect of various PGs on the NK activity of human peripheral mononuclear cells was investigated. The percentage cytotoxicity was measured by the release of Cr51 from labeled K562 and other target cells. At very high concentrations of PG (10(-6) M), suppression was seen with PGE2, PGD2, PGA2, and PGF2 alpha. However, at concentrations of PG in the physiologic range (10(-8) M), significant suppression was seen with PGE2 and PGD2 only. The percentage suppression with PGE2 ranged from 77% to 9.5% over a range of concentrations from 10(-5) to 10(-9) M (45% at 10(-8) M). Significant suppression was observed at 10(-8) M PGE2 with 4 different targets and at effector:target ratios varying from 50:1 to 12.5:1. To assess whether the suppressive effect of PGE2 was directed at the effector and/or target cell, K562 cells or effector cells were pretreated with PGE2. Significant suppression was seen with effector cell pretreatment but not with target cell pretreatment. Finally, the suppressive effects of supernatants obtained from tumor cell lines (polyoma virus-transformed murine fibroblast cell line, PY3T3) was determined. The marked suppressive effect of the supernatant could be attributed to its content of PGE. Thus, it appears that the production of PGE by tumor cells may be an important modulator of human NK activity.
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PMID:The modulation of human natural killer cell activity by prostaglandins. 695 Oct 51

Mammary tumors induced in Buffalo rats by treatment with nitrosomethyl urea will regress after oophorectomy. Their ability to synthesize and bind prostaglandins E and F2 alpha was studied in the growing and regressing states. Prostaglandins present in suspension of 100,000 xg tumor membranes after 2 hr incubation at 37 degrees C +/- 5x10(-4)M indomethacin were partially purified by silica gel column chromatography before assay by specific PG RIA. The amounts of PGE and F2 alpha synthesized rose from 0.13 and 10.5 ng/mg protein in the growing tumors to a maximum of 1.2 and 26.5 ng/mg protein 5 days after oophorectomy. Specific binding of 3H-PGE2 ad 3H-PGF2 alpha to 15,000 xg tumor membranes was achieved during a 45 min incubation at 23 degrees C +/- excess unlabelled PG. Free and bound prostaglandins were separated by filtration. Binding reached equilibrium after 30 min, was saturable and reversible. Scatchard analysis revealed high affinity binding of PGF2 alpha but only low affinity PGE2 binding in membranes obtained from growing tumors. A 2-3-fold increase in specific binding of PGE2 and PGF2 alpha was noted at 4 days after oophorectomy which represented an increase in the number of PGF2alpha receptors. PGE2 binding retained a low affinity character. The elevated PGF2 alpha synthesis rates observed in the regressing tumors coupled with a regression-associated increase in receptor number suggests that PGF2 alpha plays a significant role in hormone-dependent mammary tumor regression.
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PMID:Prostaglandin synthesis and binding is increased in regressing NMU mammary carcinoma. 695 86

This study was performed to correlate the role of exogenous and endogenous prostaglandins on humoral and cellular immune responses to and rate of growth of B-16 melanoma in vivo. B-16 melanomas synthesized 7 times as much PGE as did adjacent normal tissues, an effect that was abolished by indomethacin. In C57BL/6J mice bearing B-16 melanomas splenic plaque-forming cells, hemagglutinin titers, and delayed hypersensitivity (all to SRBC) were profoundly suppressed; these responses were significantly augmented by treating the mice with di-M-PGE2 (16, 16-dimethyl-PGE2-methyl ester), a long acting analogue of PGE2, and either further suppressed or unaffected by indomethacin, a potent inhibitor of endogenous PGE biosynthesis. Compared to control experiments, indomethacin hastened the rate of development of palpable subcutaneous B-16 tumors and facilitated the proliferation of these cells in solid tumors as well as in ascites. Pretreatment of mice with di-M-PGE2 (before inoculation with tumor cells) resulted in delay in the rate of appearance of tumors, decline in the growth rate, and increased survival. These data suggest that prostaglandins are involved in the control of in vivo tumor cell growth largely by virtue of their effects on the immune response.
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PMID:Influence of PGE on the immune response in melanoma-bearing mice. 719 Jan 76

This paper reports the results of our studies concerning the specificity and mechanism of anemia in tumor-bearing mice. Three different types of transplanted extramedullary tumors, including a carcinoma (EAC), a sarcoma (S-180), and a leukemia (L-1210) produced anemia, neutrophilia, and medullary erythroblastopenia. Because the most striking effects were observed with S-180, it was selected for detailed study. Although erythroblasts were greatly decreased in the bone marrow to about 1% in the differential count, CFU-E and BFU-E were not, suggesting inhibited maturation of erythroid progenitors. Suppression of MSC to 1/3 of normal occurred at 21 days of tumor bearing, and qualitatively abnormal MSC at 35 days failed to enhance CFU-E and BFU-E in split-phase culture. We found that these MSC from tumor-bearing mice produced suppressive levels of PGE. PGE production and erythroid colony enhancement of MSC from either normal or tumor-bearing mice was abrogated by including 5 micrograms/ml indomethacin in the split-phase culture. Medium conditioned by S-180 that was capable of suppressing the growth of MSC colonies had no direct effect on erythroid colony formation. Our results support a hypothesis that extramedullary tumors are capable of producing a lesion in the supportive tissue of the bone marrow, leading to anemia and medullary erythroblastopenia. We believe that early, the tumor suppresses the number of MSC required for maturation of erythroid precursors and later induces the normal numbers of MSC to produce suppressive levels of PGE.
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PMID:Prostaglandin E and the erythropoietic and stromal insufficiency induced by extramedullary tumor. 719 21

Enhanced synthesis of prostaglandin (PG) E by explanted fetal rat bones was initiated by lymphocyte-conditioned media but not by physiological levels of parathyroid hormone. Rapid release of PGE from bone occurred only when the lymphokine was present. Synthesis of PGE preceded and was necessary for the bone resorption caused by the lymphokine preparation. Local production of prostaglandins in response to inflammatory cell or tumor-derived factors may in part be responsible for the localized bone loss that occurs in certain pathological states.
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PMID:Lymphokine-mediated bone resorption requires endogenous prostaglandin synthesis. 726 65

Nocardia lysozyme digest (NLD), a particulate fraction from Nocardia opaca, is able to induce antitumor activity to SaL-1 tumor cells (lung sarcoma) in Balb/c mice. In mice immunized with NLD inhibition of tumor growth and prolonged survival of tumor bearing animals was observed. Macrophages isolated from peritoneal cavity and stimulated with NLD release a few arachidonic acid metabolites, mostly PGE 2. Macrophages from tumor bearing mice are more sensitive to Nocardia antigens than normal. Both in vitro and in vivo experiments have documented that Nocardia is an active immunomodulator.
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PMID:Immunomodulatory activities of Nocardia opaca. 750 60


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