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 mode of action of an aromatic analogue of retinoic acid, ethyl all-trans-9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate (Ro 10-9359), a compound known to possess a considerable prophylactic and therapeutic effect on skin papillomas and carcinomas, was investigated with autoradiographic and histopathologic methods. The ip application of a single dose of 1,000 mg Ro 10-9359/kg to female Swiss mice with chemically induced skin papillomas caused a 29% regression of the mean tumor diameter after 3 days and a 51% regression after 7 days. In the tumors, the number of DNA-synthesizing cells [measured by the labeling index (LI)] and the length of the cell cycle were not affected by the retinoid; thus a mode of action at the level of cell proliferation can be excluded. In the normal skin, an increase in the LI of about 30% was observed. A small effect on the cell loss was observed; however, it was not sufficient to explain quantitatively the regression of the tumors. When measured histometrically, it appeared that the loss of the horn and the formation of necroses, 3-10 times larger than in the placebo groups, were mainly responsible for the tumor regressions caused by the retinoid. After 7 days, the proportion of stroma in the tumors was increased, and dilation of the vessels and edema in the stroma proximal to the necroses were frequent.
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PMID:Autoradiographic and histopathologic studies on the mode of action of an aromatic retinoid (Ro 10-9359) on chemically induced epithelial tumors in Swiss mice. 40 32

12-O-Tetradecanoylphorbol-13-acetate, a highly active tumor-promoting agent and lymphocyte comitogen, rapidly accelerates the transport of alpha-aminoisobutyric acid in cultured bovine lymphocytes. Structure-activity studies show that the ability of phorbol diesters to accelerate alpha-aminoisobutyric acid uptake runs parallel to their potency as lymphocyte comitogens and as tumor promoters in mouse skin. This phorbol ester-accelerated, amino acid transport is largely insensitive to the inhibition of RNA and protein synthesis by actinomycin D and cycloheximide, respectively, and is insensitive to the inhibition of membrane movement by cytochalasin B and colchicine. Retinoic acid, an antagonist of the tumor-promoting and comitogenic actions of phorbol esters also inhibits the acceleration of amino acid uptake by 12-O-tetradecanoylphorbol-13-acetate; however, the epoxy derivatives of retinoic acid and structurally related analogs, which are potent antagonists of the other aspects of phorbol ester activation of lymphocytes, are inactive in blocking amino acid uptake. Comparative studies in lymphocytes show that this phorbol ester elicits a number of metabolic responses which appear to originate at the cell membrane and that these are differentially antagonized by retinoic acid, the 5,6-epoxide of retinoic acid, and related retinoid analogs.
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PMID:Inhibition of phorbol ester-accelerated amino acid transport in bovine lymphocytes. 44 91

Topical application of retinoic acid (RA) solutions greatly enhanced the response of hairless mouse skin to a moderate dose of simulated sunlight. Tumors appeared much earlier, and in much greater numbers, in animals treated daily with 1 or 10 micrograms of RA in methanol immediately after 2 h exposure to a xenon arc filtered through 2 mm of Schott WG 320 glass (approximately equivalent in human erythema effectiveness to 5 min of mid-summer noon solar exposure in northern mid-latitudes), compared to mice treated with light and methanol only. The higher amount of RA, in combination with light, produced moderate epidermal hyperplasia and some scaling and transient erythema, but no gross ulceration or inflammation of skin. The lower amount of RA, though about equally effective in carcinogenesis, produced minimal epidermal hyperplasia compared to the ultraviolet radiation + methanol control.
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PMID:Enhancement of experimental photocarcinogenesis by topical retinoic acid. 47 13

Anti-tumour activity of an aromatic retinoic acid analog has been tested on Sarcoma J in syngeneic system. Tumour complete regression rate and median survival time of progressors mice are significantly improved. These results are at variance with previous observations suggesting the lack of activity of this compound on transplanted murine tumours. Arguments in favour of an immunological stimulation responsible for the observed anti-tumour effect are presented and discussed.
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PMID:Anti-tumour effect of an aromatic retinoic acid analog in a mouse syngeneic transplantable sarcoma. 50 92

Data are presented on the effects of retinoic acid (RA) treatment on the in vivo growth of tumors in two mouse strains. Inhibition of tumor growth as a result of systemic RA injection was observed in three out of seven tumor models. Using adult thymectomized, lethally irradiated and fetal liver (A x TFL) reconstituted mice, we found that inhibition of tumor growth is not due to direct toxic effects of RA but rather appears to be the result of stimulation of thymus-dependent immune-mediated effectors to suppress tumor growth. Results suggest that only strongly immunogenic tumors are sensitive to in vivo retinoid inhibition.
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PMID:Anti-tumor potential of retinoic acid: stimulation of immune mediated effectors. 52 77

Two intracellular proteins that bind compounds with vitamin A activity have been discovered in animal tissues. One, called cellular retinol-binding protein (CRBP), binds retinol with high specificity and affinity, but not retinal or retinoic acid. The other protein, called cellular retinoic acid-binding protein (CRABP), has high affinity for retinoic acid but does not bind retinol or retinal. CRBP is different from the well-known serum retinol binding protein. The proteins are present in many fetal tissues, whereas their tissue distribution in the adult rat differs. The levels of these proteins change differently during perinatal development, suggesting that they are regulated in a nonsynchronous manner. Some malignant tumors contain these proteins. The presence of these proteins could be an indication of whether the tumor might be inhibited by or might require vitamin A for growth. It appears that the cell nucleus is a target for retinol action, as CRBP allows specific interaction of retinol with the nucleus, showing the presence of specific binding sites for retinol. The number of these sites is dependent on the vitamin A status of the animal.
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PMID:Cellular retinol- and retinoic acid-binding proteins in vitamin A action. 57 3

12-O-Tetradecanoylphorbol-13-acetate (TPA) is an effective comitogen in phytohemagglutinin-treated bovine lymphocytes. Concurrent addition of 10(-8) M TPA gives a greater than 6-fold increase in DNA synthesis over cultures treated with the lectin alone. The delayed addition of phorbol ester, relative to the start of the lectin treatment, eliminates this synergistic action. Structure-function studies show that the comitogenic activity of different phorbol diesters runs parallel to their tumor-promoting activity. A nontoxic level (50 micronM) of retinoic acid selectively antagonizes this synergistic effect of phorbol ester. This inhibitory action requires the near-concurrent addition of retinoic acid with TPA. In contrast, the TPA-mediated induction of RNA and protein synthesis is unaffected by retinolic acid. A number of natural and synthetic retinoids were evaluated; none were as inhibitory as was retinoic acid. Lymphocyte cultures appear to provide a useful system for exploring the mechanisms of action of both TPA and retinoic acid.
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PMID:Retinoic acid inhibition of the comitogenic action of mezerein and phorbol esters in bovine lymphocytes. 62 80

Male F344 rats, 8 weeks of age, were given 16 intrarectal administrations of N-methyl-N-nitrosourea (NMU) at one of three dose levels over a period of 8 weeks. Five days after the final NMU instillation, rats were placed on one of three diets: chow with gelatin beadlets, chow with beadlets containing 0.024% 13-cis-retinoic acid, or chow and beadlets with 0.006% of the trimethylmethoxy phenyl analog of retinoic acid ethylamide. Groups of 20-40 rats were killed at 22-26 weeks after the first carcinogen treatment. The number of rats with colon carcinoma and the number of tumors per rat were dose related. In addition, "blind" histopathologic evaluation of four predesignate colon locations revealed a dose-related incidence of microscopic preinvasive and invasive colon carcinomas. The feeding of diets containing these two retinoids did not significantly alter the incidence of these parameters of carcinogenesis or the mean histopathologic score at predesignated colon locations for preinvasive or invasive neoplastic lesions. Over 90% of the colon neoplasms induced were invasive tubulopapillary adenocarcinomas. The diameters of the tumors correlated significantly with degrees of invasion of the colons. Only 1 tumor (a signet ring carcinoma) metastasized to the peritoneal cavity. Only 2 of 300 rats treated with NMU had tumors at sites other than the colon.
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PMID:Dose response to intrarectal administration of N-methyl-N-nitrosourea and histopathologic evaluation of the effect of two retinoids on colon lesions induced in rats. 65 Jul 11

A sensitive and specific high-performance liquid chromatographic assay was developed for the determination of 13-cis- and all-trans-retinoic acid in blood or urine with an overall recovery of 90 +/- 5.0% and a limit of detection of 10-20 ng/ml of sample. The method provides for rapid and simple quantitation of the compounds using 1 ml of blood. The assay was applied in the determination of blood levels of 13-cis-retinoic acid in the dog following intravenous and oral administration of 9.5 mg/kg and 2.0 mg/kg doses, and in man following a single 100-mg oral dose and following divided daily doses totalling 2 mg per kg of body weight. The assay is also applicable with minor modifications to the determination of a series of aromatic retinoic acid analogs of clinical interest as anti-tumor agents.
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PMID:Determination of retinoic acid (13-cis- and all-trans-) and aromatic retinoic acid analogs possessing anti-tumor activity, in biological fluids by high-performance liquid chromatography. 65 43

The tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA), a highly active comitogen in phytohemagglutinin-treated bovine lymphocytes, induces an 11-fold increase in ornithine decarboxylase activity over cultures treated with the lectin alone. This synergistic action of TPA could be antagonized by the simultaneous addition of the acyclic sesquiterpene, insect juvenile hormone III. Retinoic acid (vitamin A acid), an inhibitor of the tumor-promoting action of TPA in mice, was also an effective antagonist but required administration to lectin-activated lymphocytes 1 hr prior to TPA. These data suggest that metabolic activation of retinoic acid is required in order to exert its antagonistic action. Comparison of the responses in the lymphocytes and mouse skin suggests that the lymphocytes provide an excellent system for studying the molecular processes through which phorbol esters and retinoids influence the growth and differentiation of both normal and premalignant cells.
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PMID:Effects of retinoic acid and juvenile hormone on the induction of ornithine decarboxylase activity by 12-O-tetradecanoylphorbol-13-acetate. 67 97


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