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)

Retinoic acid is a weak promotor of skin tumorigenesis in Charles River CD-1 mice. Multiple papillomas were seen in 17% of the mice treated 3 times weekly with 5.1 micrograms retinoic acid for 20 weeks after initiation by a single treatment with 50 micrograms 7,12-dimethylbenz[alpha]anthracene (DMBA). These results suggest the necessity of a more thorough evaluation of retinoids as tumor promoters before their serious consideration as anti-cancer agents in man.
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PMID:Retinoic acid promotion of papilloma formation in mouse skin. 681 Nov 29

Papillomas and carcinomas were induced on the skin of mice by initiation with dimethylbenzanthracene, followed by promotion with 12-O-tetradecanoylphorbol-13-acetate. Retinoic acid was applied topically, either chronically, throughout the promotion period, or acutely, to the papillomas or carcinomas. All tumor types were verified histologically. Tumor tissue was incubated with labeled glucosamine and labeled glycoproteins released into media were fractionated on DEAE-Sephadex. For papillomas, one peak (eluted with 0.17 M NaCl) appeared and another (0.40 M) all but disappeared as a result of retinoic acid treatment. Carcinomas also showed the 0.40 M peak released by papillomas, which was also suppressed by retinoic acid. Carcinomas released a 0.26 M peak instead of the 0.17 M peak in response to the retinoid. All three peaks yielded single, symmetrical peaks on gel filtration columns. They were all resistant to mild alkaline hydrolysis. Labeling experiments revealed the presence also of mannose, galactose, and traces of fucose in all three glycoproteins. The 0.17 and 0.26 M peaks were bound by concanavalin A-Sepharose columns, the 0.40 M peak was not. Molecular weights, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were approximately 80,000 and 105,000 (0.17 M peak), 67,000 (0.26 M peak), 70,000 and 80,000 (0.4 M peak).
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PMID:Effect of retinoic acid on the synthesis of glycoproteins of mouse skin tumors during progression from promoted skin through papillomas to carcinomas. 683 17

Imbalance in the Kb and Db region encoded molecules is observed in Lewis lung carcinoma clones. The uncloned metastatic population and the D122 high-metastatic clone show no expression of H-2Kb products, while the nonmetastatic A9 clone expresses Kb products. Twenty-nine new subclones of 3LL and A9 were analyzed for D-end and K-end membrane expression, primary growth rate and metastatic spread. We show that the imbalance in H-2Kb to H-2Db is correlated with metastatic properties of a given clone, but local tumor growth is not. A "low Kb/low Db" phenotype is nonmetastatic as is a "high Kb/high Db" phenotype; a "low Kb/high Db" is highly metastatic and a "medium Kb/high Db" is moderately metastatic. We find support for this notion of imbalance in experiments on MHC modulation by interferon and retinoic acid. Interferon increases both Kb and Db expression of A9 and D122 clones yet the net increase of Db was greater than Kb. This was associated with an increase in metastasis formation. Retinoic acid increases the expression of the Db gene product on the nonmetastatic A9, clone, without apparent changes in Kb expression. This treatment shifts the A9 to a high-metastatic phenotype. The significance of this imbalance to the tumor--host relationship is discussed.
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PMID:MHC imbalance and metastatic spread in Lewis lung carcinoma clones. 686 90

Retinoic acid induced lysozyme activity in mouse myeloid leukemia M1 cells. It also stimulated the synthesis and release of prostaglandins such as prostaglandin F2alpha, E2, and D2 by the cells. The particulate fraction of retinoic acid-treated M1 cells converted arachidonate to prostaglandins, and this conversion was almost completely inhibited by indomethacin. Retinol, retinal and retinyl acetate, but not the pyridyl analog of retinoic acid, also induced lysozyme activity and stimulated synthesis and release of prostaglandins. Indomethacin inhibited the induction of lysozyme activity by retinoic acid. The induction of lysozyme activity and the stimulation of prostaglandin E2 production were dependent on the concentration of retinoic acid. Kinetic studies showed that stimulation of prostaglandin E2 production by retinoic acid was followed by induction of lysozyme activity. The tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and phorbol 12,13-didecanoate inhibited the induction of lysozyme activity by retinoic acid, but 4 alpha-phorbol didecanoate and phorbol did not. TPA and phorbol 12, 13-didecanoate, but not 4 alpha -phorbol didecanoate, also inhibited the stimulation of prostaglandin E2 production by retinoic acid. These results suggest that stimulation by retinoic acid of prostaglandin E2 production in M1 cells is a prerequisite for the induction of lysozyme activity. On the other hand, both retinoic acid and TPA inhibited the induction by dexamethasone of phagocytic activity, which is a typical functional marker of differentiation of M1 cells, without causing significant growth inhibition. Suboptimal concentrations of retinoic acid and TPA had synergistic inhibitory effects on the induction of phagocytic activity of M1 cells by dexamethasone.
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PMID:Stimulation by retinoic acid of prostaglandin production and its inhibition by tumor promoters in mouse myeloid leukemia cells. 694 53

Addition of 12-tetradecanoylphorbol 13-acetate (TPA) to cultures of intact Swiss mouse 3T3 fibroblasts induced a dose-dependent increase in ornithine decarboxylase (OrnDCase) activity. Over the same concentration range, 10(-9) to 10(-6) M, TPA induced the release of radioactively labeled fibronectin (FN) from the cells into the culture medium. Retinoic acid, a derivative of vitamin A, inhibited in a dose-dependent manner both the increase in OrnDCase activity and the release of FN induced by TPA. To examine the effects of TPA and retinoic acid in enucleated cells, the cells were treated with 7.5 micrograms of cytochalasin B per ml of medium during centrifugation at 10,000 X g for 35 min at 37 degrees C. In a series of five experiments, the treated cells were 94.7 +/- 4.8% (+/- SEM) enucleated as measured by [3H]thymidine incorporation and verified by Giesma staining for nuclei. In the enucleated cells, TPA did not induce increased OrnDCase activity but did induce FN release in a dose-dependent fashion over the same concentration range effective for FN release from intact cells. Moreover, addition of retinoic acid to the enucleated cells inhibited the phorbol ester-induced release of FN in a dose-dependent manner. A series of phorbol ester derivatives showed the same order of activity in causing FN release from the enucleated cells as reported for inducing OrnDcase activity in intact cells or in promoting mouse skin tumors in vivo. Similarly, several retinoids were tested for their ability to inhibit the phorbol ester-induced release of FN from enucleated cells. The efficacy of the retinoids in preventing FN release paralleled their activity in inhibiting phorbol ester-induced OrnDCase activity and skin tumor promotion, as reported in the literature. We conclude that at least one aspect of tumor promotion induced by phorbol esters--the loss of FN--does not require the cell nucleus, and further, that retinoids can inhibit this aspect of tumor promotion without nuclear involvement.
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PMID:Retinoids and phorbol esters alter release of fibronectin from enucleated cells. 695 35

Effects produced by long-term application of three immune modifiers (azimexon, retinoic acid, and tuftsin) on the depressed immune systems of 18-month-old inbred C57BL/6 female mice were investigated. The effect of each agent was examined on four cell types (cytotoxic T-cells, K-cells, NK cells, and macrophages) possibly involved in antitumor defenses and on the spontaneous tumor development that accompanied advancing age. Three substances chosen for this study appeared able to alter immune parameters, and each one displayed its own pattern of activity. Common to all three agents were an increase of age-depressed tumoricidal activity of peritoneal macrophages and no effect on the depressed NK activity of spleen cells. Retinoic acid increased splenic K-cell activity, already elevated in aged mice and unaffected by the other two agents. Cytotoxic T-cell activity, diminished by age, was stimulated considerably by retinoic acid and by tuftsin but only slightly by azimexon. Histopathologic studies revealed a decrease in the incidence of spontaneous tumors in the 3 treated groups. This decrease was statistically significant in the retinoic acid- and tuftsin-treated groups when compared with the incidence in untreated mice of the same age. Correlation of drug-induced modifications of the immune system with tumor incidence in aged mice was attempted.
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PMID:Prevention of spontaneous tumors of aged mice by immunopharmacologic manipulation: study of immune antitumor mechanisms. 697 61

A single topical application of 17 nmol 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to the skin of hairless mice induces characteristic transient alterations in the epidermal cells turnover and maturation (0.96 h), associated in time with characteristic changes in the activities of L-ornithine carboxy-lyase (E.C. 4.1.1.17) (ODC) and S-adenosyl-L-methionine carboxy-lyase (E.C.4.1.1.50) (SAM-D) and in the accumulation of polyamines. The effects on these responses of local pretreatment of the skin with retinoic acid 1 h prior to TPA were investigated at selected time points. Retinoic acid inhibited the TPA-induced ODC activity and the ensuing accumulation of putrescine, but did not alter the TPA-induced SAM-D activity or the molar ratio of spermidine/spermine. This pretreatment also decreased in number of dividing basal cells in the first TPA-induced synchronized wave of proliferating cells. However, during the subsequent period of proliferation, the number of dividing cells in the retinoic acid pretreated group was comparatively increased. Hence, at four levels of retinoic acid (0.17, 1.70, 17.0 and 170 nmol), which all inhibited the TPA-induced ODC effectively, there was no change in the total number of basal cells that divided during 16-48 h after TPA-application. Theory is put forward the retinoic acid might exert its antitumorigenic effect during tumor promotion with TPA by interfering with the rate and/or quality of epidermal cell maturation, rather than by inhibiting cell proliferation.
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PMID:Effect of retinoic acid pretreatment on 12-O-tetradecanoylphorbol-13-acetate-induced cell population kinetics and polyamine biosynthesis in hairless mouse epidermis. 708 72

Retinoic acid-binding protein is present in metastatic murine colon tumors as well as in Lewis lung tumors and in lungs and brains of mice bearing these tumors; however, this protein is below the limits of detection in weakly-metastatic carcinomas and in normal lung, colon, or brains. These observations are interesting since they concern the possibility of measuring the binding protein levels of colon tumors in clinical specimens as biochemical markers in human malignancy. A total of thirty-three human colon tumors and related materials were analyzed for the presence of the binding protein. The interfering serum albumin, which nonspecifically binds retinoic acid, was eliminated by affinity chromatography. Of the twenty colon, cecum, and rectum tumors analyzed, 80% contained the binding protein in detectable amounts, and 20% showed nondetectable or marginally detectable amounts. Twenty-two percent of the human colon segments isolated from patients suspected for colon tumors contained the binding protein in readily detectable amounts, whereas 78% revealed nondetectable to marginally detectable amounts. The retinoic acid-binding protein of human colon tumor shared the same ligand specificity, thiol functions in ligand-binding, and sedimentation coefficient as the binding protein isolated from chick embryo skin. However, the human protein exhibited altered isoelectric pH.
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PMID:Retinoic acid-binding protein in experimental and human colon tumors. 718 79

The ability of the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), to induce chemotaxis in three different populations of mouse peritoneal macrophages was studied. TPA in the range of 10(-9) to 10(-7) M produced a dose- and time-related increase in chemotaxis in resident, thioglycollate-elicited, and divinyl ether maleic anhydride copolymer-activated macrophages. A maximal response was obtained after 4 hr incubation with 10(-7) M TPA, and this concentration of TPA was as effective as inducing chemotaxis as was endotoxin-activated mouse serum. Orientation of macrophages towards TPA was also observed by microscopy. Within 2 hr, cells exposed to TPA sent out cytoplasmic processes along the TPA gradient. Parallel arrays of cells oriented towards the TPA were observed after 4 hr incubation. Two other diterpene tumor promoters, phorbol-12,13-didecanoate and mezerein, were also chemotactic for the macrophages, as was the peptide epidermal growth factor, which shares a number of effects with TPA on cells in culture. On the other hand, two phorbol esters inactive as tumor promoters, 4-alpha-phorbol-12,13-didecanoate and phorbol, were not chemotactic for macrophages. Retinoic acid, which inhibits tumor promotion, inhibited TPA-induced, but not endotoxin-activated mouse serum-induced chemotaxis. These findings, taken together with previous studies, indicate that phorbol ester tumor promoters are potent modulators of macrophage function.
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PMID:Induction of chemotaxis in mouse peritoneal macrophages by phorbol ester tumor promoters. 721 60

Retinoic acid-binding protein (RABP), which is distinctly present in embryonic colon and lung, is below the limits of detection in adult mouse colon and lung. The binding protein is present in malignant murine colon tumors as well as in lungs of animals bearing subcutaneously implanted tumors. Primary cell cultures from 1 g of colon tumor 26 gave rise to about 10(7) tumor cells and yielded 30 mg of extractable protein. The lower limit for detection of RABP, based on the appearance of its specific 2S peak after sucrose density gradient sedimentation, was 0.1 mg of protein, which corresponds to 3.3 x 10(4) tumor cells. After subcutaneous implantation of colon tumor 26 in mice, no RABP peak was evident in the lung extracts up to the fourth day. From the fifth day onwards, RABP appeared in lung extracts, possibly as a consequence of pulmonary metastasis. Fragments of mouse lungs containing the metastatic tumor foci were reimplanted subcutaneously and produced tumors that contained RABP at levels comparable to those in colon tumor 26. The primary subcutaneous tumors and pulmonary metastatic tumors showed the same histologic appearance--an undifferentiated carcinoma. On the 15th day of subcutaneous implantation of colon tumor 26 in mice, RABP was detected in lung and brain but in none of the other tissues where the protein is normally undetectable. After intraperitoneal implantation of colon tumor 26 in mice, no well-defined RABP peaks were detected from their liver extracts. None of the three normal human colon extracts analyzed for RABP or a dihydrotestosterone-binding protein (DHTBP) contained any detectable amounts of either of the binding proteins. However, 70% of the human colon tumors contained RABP and 90% contained DHTBP. Both of these binding proteins were evident in the two human colon tissues adjoining colon tumors.
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PMID:The presence of binding proteins for retinoic acid and dihydrotestosterone in murine and human colon tumors. 743 18


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