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)

The tumor promoter phorbol myristate acetate (PMA) was compared to a lymphokine macrophage mitogenic factor (MMF) for its ability to induce replication of guinea pig peritoneal and alveolar macrophages. Like MMF, PMA induces DNA synthesis of both cell populations with peak thymidine incorporation at 72 hr of culture. Optimal concentrations of PMA for the peritoneal and alveolar cells were 1.6 x 10(-7) and 1.6 x 10(-9) M, respectively. The magnitude of the effect is slightly less than MMF but greater than that of phytohemagglutinin or concanavalin A. Indomethacin added to inhibit prostaglandin synthesis potentiates the effects of MMF but has little effect on the actions of PMA and the other mitogens. Potentiation by indomethacin of the effects of PMA on the peritoneal cell was observed only at the suboptimal concentration of PMA (1.6 x 10(-8) M). By adherence criteria and density gradient fractionation, the cell responding to PMA is confirmed to be the macrophage. Cell counts and nuclear radioautography confirm that replication in this system is reasonably well reflected by thymidine incorporation. The effects of PMA and its analogs as macrophage mitogens correlate with their tumor-promoting effects. Both PMA and MMF induce early increases in peritoneal macrophage levels of cyclic 3':5'-guanosine monophosphate without changes in the levels of cycles 3':5'-adenosine monophosphate. These studies indicate that PMA offers a useful probe of macrophage function.
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PMID:Effect of phorbol myristate acetate and a lymphokine on cyclic 3':5'-guanosine monophosphate levels and proliferation of macrophages. 628 56

The lymphoid cell line, Raji, was derived from a Burkitt's lymphoma and is readily inducible for Epstein-Barr virus (EBV) early antigen synthesis by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Treatment of Raji and other EBV genome-positive cells with indomethacin caused a marked inhibition of early antigen induction by 12-O-tetradecanoylphorbol-13-acetate and other chemical inducers. However, this effect did not appear to be due to inhibition of prostaglandin synthesis since the concentration of indomethacin required to inhibit EBV-early antigen induction was 50- to 100-fold higher than that normally required for the inhibition of prostaglandin synthesis. In addition, no prostaglandin synthesis was detected in 12-O-tetradecanoylphorbol-13-acetate-treated Raji cells. EBV-early antigen induction by superinfection was resistant to inhibition by indomethacin and indicates that induction by chemical inducers and by super-infection follows different pathways. Indomethacin at the concentrations required to inhibit EBV-early antigen induction also was cytostatic, which indicates that the cell cycle phase may be an important factor in viral induction.
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PMID:Effect of indomethacin on Epstein-Barr virus early antigen induction. 631 91

The correlation between prostaglandin E (PgE) and scintigrams of bone (Tc-99m MDP) and bone marrow (Tc-99m SC) was investigated in normal and VX-2-bearing rabbits. PgE in plasma of normal rabbits was 486.2 +/- 185.7 pg/ml (n = 86) and the maximum-to-minimum (max/min) ratio was 1.85 +/- 0.26 at 4 wk after tumor implantation. In rabbits with VX-2 transplanted into femoral muscles, PgE was in the normal range unless the tumor invaded bone. PgE did not increase significantly in rabbits when the tumor was transplanted into the marrow cavity. When tumor invaded bone, PgE increased markedly (to 1335 +/- 584 pg/ml). Elevation of PgE did not necessarily coincide with the appearance of positive bone scans. PgE in an indomethacin-treated group was not higher than in the untreated group. There was no significant difference between the two groups regarding the time of appearance of abnormal bone scans. However, when the number of transplanted cells in the bone marrow was reduced, the treatment with indomethacin delayed the increase in tracer uptake in the affected bone and resulted in a photon-deficient area. Indomethacin may suppress the local acceleration of calcium metabolism.
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PMID:Effects of prostaglandin on experimental bone malignancy and on scintigrams of bone and marrow. 645 15

Inhibition of the growth of a transplantable methylcholanthrene-induced tumor was achieved in mice by administering indomethacin or aspirin in the drinking water, these drugs having in common the ability to inhibit prostaglandin synthesis. Indomethacin was able to reduce the levels of prostaglandin E (PGE) in the tumor tissue. When tumors from these animals were cultured in vitro, the culture supernatant fluid from drug-treated animals showed lower levels of PGE released into the media, but after several days in culture, tumor cells from indomethacin-treated animals fully recovered their ability to produce PGE. The relative size of tumors in untreated animals was directly related to the amount of PGE activity present in these tumors.
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PMID:Inhibition of murine tumor growth and prostaglandin synthesis by indomethacin. 645 46

The intratumor and intramuscle distribution of blood flow and plasma volume was studied via isotope techniques in a transplantable rat fibrosarcoma. Administration of two prostaglandin synthesis inhibitors, indomethacin and diclofenac-sodium, had different effects. Indomethacin changed muscle plasma volume significantly towards higher values; a tendency to increased tumor plasma volume was also found. Diclofenac-sodium increased tumor blood flow, but had no significant influence on other parameters. These effects are discussed based on previous observations of reduction of tumor growth rate and tumor vascularization after administration of both drugs.
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PMID:Influence of two prostaglandin synthesis inhibitors on the intratumor distribution of blood flow and vascular volume in a transplantable rat fibrosarcoma. 646 50

The effect of the chemical carcinogen 3-methylcholanthrene (3-MCA) on mouse natural killer (NK) cells was tested in vitro applying kinetic analysis of the NK-tumor cell interaction. 3-MCA inhibited the lytic activity of spleen cells against YAC-1 target cells in a dose-dependent manner. Maximal inhibition, of Vmax was about 60% and a parallell decrease in KM values was observed. Inhibition was observed after 30 min preincubation of effector cells while pre-incubation of target cells had no effect. Inclusion of Indomethacin in the assay to exclude the possibility that prostaglandins induced by 3-MCA were the mediators of NK suppression had no effect. 3-MCA inhibited basal and interferon-activated NK lysis to about the same extent, while Vmax and KM values of effector cells pretreated with 3-MCA and assayed in the presence of interferon was close to control values. In a single cell assay for NK activity it was found that 3-MCA interfered with the lytic step of NK mediated lysis without affecting target binding. These data are in accordance with an earlier observation that a single injection of 3-MCA transiently inhibited mouse NK cells in vivo and evidence is presented that 3-MCA inhibits the lytic activity of a subpopulation of NK cells. The effects of 3-MCA were reversed by interferon.
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PMID:The effect of 3-methylcholanthrene on mouse natural killer cells in vitro. 648 Jan 95

Studies were designed to determine if treatment with indomethacin influenced the growth of a transplantable, metastatic, rat mammary tumor. Female, Wistar-Furth inbred rats were fed either a standard chow diet or a semipurified diet containing 2, 5, 10, or 20% stripped corn oil. Indomethacin was given in drinking water, and rats consumed between 2.5 and 3.0 mg indomethacin/kg body weight/day. Feeding of diets and initiation of treatment with indomethacin were started when rats were weaned (21 days old) and continued until they were killed. Approximately 5 X 10(3) mammary tumor cells (DMBA-4) were injected into the fat pad of the sixth mammary gland which is adjacent to the right inguinal lymph node. Each dietary/treatment group consisted of at least 10 rats. Since indomethacin inhibits prostaglandin synthesis, two other groups of non-tumor-bearing rats were used to determine if dietary fat and treatment with indomethacin either influenced prostaglandin E2 production (in vitro) by mononuclear cells from the spleen or altered serum levels of fatty acids. Results indicated that: (a) the rate of tumor growth in untreated rats was significantly greater when the dietary fat content was either 10 or 20% compared to diets containing either 2 or 5% fat; (b) the tumor growth-promoting effects of 10 and 20% fat diets were completely abrogated in rats treated with indomethacin; (c) treatment with indomethacin also inhibited tumor growth in rats fed diets containing either 2 or 5% fat; (d) synthesis of prostaglandin E2 by mononuclear cells from the spleens of untreated rats increased as the dietary fat content increased; (e) in indomethacin-treated rats, prostaglandin E2 synthesis was inhibited in all dietary groups and was not dependent on dietary fat; and (f) in both untreated and indomethacin-treated rats, the serum concentrations of oleic and linoleic acids were influenced to the same extent by dietary fat.
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PMID:Influence of dietary fat and indomethacin on the growth of transplantable mammary tumors in rats. 657 55

2--amino-2-thiazoline (AT) and 1-thiazolidine-4-carboxylate (TC, thioproline), which have been previously proposed as agents of reverse transformation, have been examined as antitumor agents in several rodent tumor systems. AT administration reduced tumor incidence in sym-dimethylhydrazine treated outbred ICR Swiss female mice and doubled the survival of DBA/2Ha female mice infected with polycythemic Friend leukemia virus. Indomethacin, pentoxyphylline, RA233 and diethyldithiocarbamate (DTC), with potential for altering host or tumor prostaglandin levels, platelet aggregation and host immunity, respectively, ranged from marginally effective to ineffective against Friend virus infection. AT was, however, ineffective against 4 other induced and transplanted mouse tumors and did not notably increase differentiation or decrease transformation in any of several tumor cell systems. No in vitro or in vivo tumor system was found to be more than marginally affected by TC. Thus, AT alone was of significant antitumor activity in inhibiting late stages of viral- or carcinogen induced tumor progression, but could not be demonstrated as an agent of reverse transformation.
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PMID:Antitumor studies of 2-amino-2-thiazoline and other tumor-modifying agents. 658 1

A cell culture line has been established from a colonic tumor induced in a rat by dimethylhydrazine. Indomethacin had no effect on the growth of tumors induced in syngeneic rats by s.c. injection of this cell line. Neither indomethacin, nor prostaglandin E2 modify the growth of this established cell line in vitro or alter its destruction by endotoxin-activated macrophages. Indomethacin has been reported to suppress the growth of colonic tumors induced in rats by various carcinogenic drugs. The difference between these results obtained by others on chemically-induced colon cancer and the data we have obtained with a cell line derived from a similar cancer suggests that cancer cells in established culture may loose their sensitivity to prostaglandins, prostaglandin inhibitors or prostaglandin-dependent effector host cells.
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PMID:Effect of indomethacin on the growth of colon cancer cells in syngeneic rats. 659 58

The in vivo effect of indomethacin therapy in head and neck cancer was tested using rats (Fisher 344) with implanted epithelial palatal carcinoma. Indomethacin was then given to half of the rats in their drinking water, starting two weeks after tumor implantation. The animals were then killed at four weeks and the tumor volumes were measured. It was found that four (21%) of the 19 rats were complete responders and eight (42%) of the 19 rats were partial responders. The control group showed increased tumor growth in all animals. The experimental group also demonstrated five (26%) of the 19 regional metastases. No metastases were seen in the control group. Indomethacin seems to inhibit local tumor growth, perhaps through its effects on cellular and humoral immunity and its effects on the host-tissue stroma. It also may increase tumor spread through the regional lymphatics or hematogenously. Further animal studies need to be carried out to determine the effect on cancer on a cellular and biochemical level before using it for treatment of cancer in humans.
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PMID:The effect of indomethacin on the growth of epidermoid carcinoma of the palate in rats. 663 38


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