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)

M phi obtained directly from disaggregated murine Moloney sarcomas produced PGE2 and a hydroxy fatty acid derivative as the major products of arachidonic acid metabolism. M phi-immunoreactive PGE synthetic rates decreased substantially and cytotoxic activity was lost when freshly explanted tumor M phi were held in culture 24 hr. Such cultured M phi remained in a partially activated "primed" state, however, wherein the addition of minute (ng) amounts of bacterial lipopolysaccharide (LPS) returned cytolytic activity and PGE synthesis to original levels. Indomethacin-induced blockade of the M phi cyclooxygenase pathway inhibited PG synthesis by LPS-stimulated, primed M phi without affecting the return of cytolytic activity. We conclude, therefore, that the production of PG had no direct role in the mediation of tumor cell killing by activated M phi isolated from these neoplasms.
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PMID:Macrophage-mediated tumor cell killing: lack of dependence on the cyclooxygenase pathway of prostaglandin synthesis. 10 39

The effect of systemic administration of 16,16-dimethyl prostaglandin E2-methyl ester (di-M-PGE2) on the growth of B-16 melanoma tumors has been studied in C57BL/6J mice. Daily i.p. injection of 5 mu of di-M-PGE2 commencing on the day of tumor inoculation with 10(5) and 10(6) viable cells delayed appearance of tumors; for the smaller tumor inoculum, it also increased median survival among treated mice from 23 to 33 days. Di-M-PGE2 treatment of mice with established tumors caused significant inhibition of tumor growth, as measured by a number of parameters including tumor diameters and volumes. At the time of sacrifice, di-M-PGE2-treated mice had tumors that were an average of 32% smaller (by weight), contained 60% fewer melanoma cells, and had higher concentrations of cyclic adenosine 3':5'-monophosphate and cyclic guanosine 3':5'-monophosphate (+225% and +100%, respectively).
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PMID:Inhibition of B-16 melanoma growth in vivo by a synthetic analog of prostaglandin E2. 19 22

Vasoactive intestinal peptide (VIP) is a potent and efficient stimulator of adenosine 3':5'-cyclic monophosphate (cAMP) accumulation in a human colon carcinoma cell line, HT 29. cAMP accumulation is sensitive to a concentration of VIP as low as 3x10(-12) M. Maximum VIP-induced cAMP levels were observed with 10(-9) M VIP and are about 200 times above the basal levels. Half-maximum cAMP production was obtained at 3x10(-10) M VIP. (125)I-Labeled VIP was found to bind to HT 29 cells; this binding was competitively inhibited by concentrations of unlabeled VIP between 10(-10) and 10(-7) M. Half-maximum inhibition of binding was observed with 2x10(-9) M VIP. Secretin also stimulated cAMP accumulation in HT 29 cells, but its effectiveness was 1/1000 that of VIP. The other peptides tested at 10(-7) M, such as insulin, glucagon, bovine pancreatic polypeptide, somatostatin, octapeptide of cholecystokinin, neurotensin, and substance P, did not stimulate cAMP accumulation. Prostaglandin E(1) and catecholamines stimulated cAMP production but were 1/2.3 and 1/5.5 as efficient as VIP, respectively. Another malignant cell line from the gut, the human rectal tumor cell line HRT 18, is also sensitive to VIP. In HRT 18 cells, VIP stimulated cAMP accumulation with a maximal effect at 10(-8) M; half-maximum stimulation was observed at about 10(-9) M. These results demonstrate the presence of VIP receptors in two malignant human intestinal cell lines (HT 29 and HRT 18) in culture and provide a model for studying the action of VIP on cell proliferation.
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PMID:Vasoactive intestinal peptide: a potent stimulator of adenosine 3':5'-cyclic monophosphate accumulation in gut carcinoma cell lines in culture. 20 77

Prostaglandin E concentrations were measured in a patiet with breast carcinoma, hypercalcemia, undetectable parathyroid hormone (PTH) and no evidence of bone metastases. Catheterization of the drainage bed of her tumor documented production of E series prostaglandins. Treatment with the largest recommended doses of indomethacin for 10 days failed to lower her plasma prostaglandin E (PGE) concentrations or to correct the hypercalcemia, but it normalized urinary excretion of PGE. Subsequent chemotherapy reduced prostaglandin concentrations toward normal values concomitant with a reduction of clinically estimated tumor burden. During this period of time, serum calcium concentrations had no consistent relationship to the plasma PGE levels. We suggest that PGE merely reflected the tumor burden of this patient and did not directly contribute to the genesis of her hypercalcemia. The pertinent literature relating PGE and hypercalcemia is reviewed.
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PMID:Prostaglandin E and hypercalcemia in breast carcinoma: only a tumor marker? A need for perspective. 21 52

Mouse myeloid leukemia cells (M1) were induced to differentiate into mature macrophages and granulocytes by glucocorticoids or a protein inducer in ascitic fluid from tumor-bearing rats. Addition of nonsteroidal antiinflammatory agents to M1 cells in suspension cultures inhibited the induction of differentiation by glucocorticoid (dexamethasone) or the protein inducer. The inhibition was unrelated to cytotoxicity and was reversible. The nonsteroidal antiinflammatory agent indomethacin inhibited dexamethasone-induced differentiation only when added before the time of commitment of the cells to differentiation. The indomethacin-mediated inhibition was counteracted by prostaglandins E1 or E2 but not by prostaglandins F1alpha or F2alpha. Prostaglandin E stimulated phagocytosis induced by a suboptimal concentration of dexamethasone, but prostaglandin F did not. Moreover, lysozyme activity, which is a typical biochemical marker of macrophages, was induced in M1 cells by prostaglandin E alone, as well as by inducers of differentiation. These results suggest that prostaglandin E may be important in the induction of differentiation of myelod leukemia cells.
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PMID:Inhibition of differentiation of cultured mouse myeloid leukemia cells by nonsteroidal antiinflammatory agents and counteraction of the inhibition by prostaglandin E1. 44 17

Endogenous sources of prostaglandin production in human breast tumors were investigated by radioimmunoassay analysis of PGE2 and PGF2a productions and 3H-PGE2 conversion. PG synthetase located within the microsomal fraction mainly produced PGE2, while little PGF2a synthesis occured. In cytosol preparations. PGE2 is converted into PGF2a. In 15 tumor specimens, no relationship was observed between PGE2 production and the metabolic activity which varied widely from sample to sample. These findings demonstrate the presence of PG-9-keto-reductase in the cytosol from human breast tumors. A way of PGE2 inactivation by this enzyme is suggested since no less polar PGE2 metabolites were detected. It is concluded that PGE2 production by the microsomes will reflect the PG synthetase activity of a given human mammary carcinoma while metabolic conversion of PGE2 within the cytosol reflects the metabolic activity of the same sample. Both activities were otherwise apparently unlinked.
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PMID:Prostaglandins in human breast cancer. Identification of a cytosolic prostaglandin-9-keto-reductase activity. 52 39

The growth of the R3230AC mammary carcinoma was studied in female Fisher 344 rats that were treated with diazepam. Diazepam at 250 micrograms/animal/day (2.5 mg/kg body weight) and 500 micrograms/day was administered for 4 weeks, starting 2 days before subcutaneous transplantation of uniform pieces of the tumour. Tumour size was significantly increased in the group receiving 250 micrograms but was below the levels observed in the saline treated controls in those given 500 micrograms diazepam. Plasma PGE2 and PGF2 alpha concentrations were comparable in control and diazepam treated animals.
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PMID:The influence of diazepam administration in rats bearing the R3230AC mammary carcinoma. 55 3

The in vitro effect of exogenously added prostaglandin (PG) E1 or E2 over concentrations ranges of from 1 X 10(-4) to 1 X 10(-9) M were studied in order to determine their effect on the in vitro lymphocyte proliferation of thymic and splenic T and B cells from normal and tumor-bearing CD2F1 mice. It was found that PGE1 generally caused greater inhibition of blastogenesis than did PGE2 when reacted with splenic lymphocytes from normal mice. Indeed, PGE2 was found to be stimulatory for both Con A- and LPS-sensitive normal splenic lymphocytes. Both PGE1 and PGE2 caused potent inhibition of Con A- and PHA-sensitive splenic lymphocytes from the tumor-bearing mice. Additionally, PGE2 was found to stimulate the LPS-reactive lymphocytes from the tumored mice. PGE1 and PGE2 both inhibited the Con A- and PHA-reactive thymic lymphocytes from normal mice at the lower concentrations studied, i.e., 10(-4) to 10(-6) M. Thereafter, at concentration ranges of from 10(-7) to 10(-9) M both PGE1 and PGE2 were both found to be stimulatory. Finally, both PGE1 and PGE2 at all concentrations studied, strongly inhibited the thymic lymphocytes from tumored mice.
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PMID:The effect of prostaglandin E1 or E2 on the in vitro blastogenic response of lymphocytes from normal and tumor-bearing mice. 55 8

Alcohol appears to exert a depressive effect on host immunity. Animal models useful in studying immune responsiveness in cancer research are discussed, which could be of value in studying the effect of alcoholism. Allogeneic tumor grafts are poorly rejected in immunosuppressed mice. Of the four major cellular elements of the immune system, the macrophage appears to have a critical role in immune surveillance. Several conditions occur which abrogate or restrict the tumoricidal activity of macrophages. Stress induced by physical restraint results in depressed macrophage activation. The tumoricidal activation induced in macrophages by interferon was markedly depressed in the presence of the corticosteroids, hydrocortisone, prednisone, and dexamethasone. In addition, prostaglandins (PGE1 and PGE2) also were found to decrease interferon activation of macrophages. Since immune deficiency is a trait of alcoholism and cancer, animal models with defined, measurable, immunological parameters would be useful in studying the effect of alcohol on cellular immunity.
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PMID:Animal models in cancer research which could be useful in studies of the effect of alcohol on cellular immunity. 57 62

Daily intratumor administration of 16,16-dimethyl-PGE2-methyl ester in two different dosages inhibited tumor growth in C57Bl/6J mice bearing subcutaneous B-16 melanomas. The larger dose (20 microgram/day/mouse) produced a 68% decrease in tumor volume, a 69% decrease in tumor weight and a 60% decrease in the number of cells in mitotic phase. The smaller dose (10microgram/day/mouse) was one fifth less effective than the 20microgram dose but produced similar changes. Histological examination of tumors revealed no significant differences either in the inflammatory cell population or the amount of necrosis in the control and di-M-PGE2-treated tumors.
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PMID:Dose dependent inhibition of B-16 melanoma growth in vivo by a synthetic analogue of PGE2. 59 68


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