Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-(all-trans-Retinoyl)amino acids were synthesized via all-trans-retinoyl chloride and an ester of the amino acid. The retinoyl derivatives of leucine, phenylalanine, alanine, tyrosine, and glutamic acid were prepared. The 13-cis-retinoyl derivatives of leucine, phenylalanine, alanine, and glycine were prepared similarly from 13-cis-retinoic acid. In assays of the retinoylamino acids for reversal of squamous metaplasia in hamster trachea organ cultures, these compounds were less active than retinoic acid, but the leucine, alanine, and phenylalanine derivatives were similar in activity to several retinamides that suppress bladder carcinogenesis in vivo. Two of the retinoylamino acids, as well as two simple retinamides, were shown to be moderately cytotoxic to murine leukemia and human epidermoid carcinoma cells in culture.
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PMID:N-(Retinoyl)amino acids. Synthesis and chemopreventive activity in vitro. 333 18

The dye-coupled intercellular communication across gap junctions in primary hamster tracheal epithelial cells has been studied in serum-free, hormone-supplemented medium. In the absence of vitamin A, non-cytotoxic concentrations of cigarette-smoke condensate (CSC) inhibited intercellular communication between tracheal epithelial cells in a concentration-dependent way. All-trans retinol and retinoic acid showed biphasic effects on intercellular communication depending on their concentration. Physiological concentrations of retinol and retinoic acid increased the dye-coupled transfer of Lucifer Yellow CH via gap junctions compared with the dimethylsulfoxide-treated tracheal epithelial cells. At pharmacological concentrations retinol slightly increased the intercellular communication in the first 2 h of the exposure period, whereas upon longer treatment times with retinol and retinoic acid, gap-junction-mediated intercellular communication was inhibited almost completely. When retinol was given to tracheal epithelial cells before exposure to CSC or simultaneously with CSC-exposure, retinol counteracted the inhibitory potential of CSC on intercellular communication. The results of the present study clearly indicate that both CSC and all-trans retinol influence the intercellular communication between primary hamster tracheal epithelial cells in serum-free, hormone-supplemented culture medium.
Carcinogenesis 1988 Feb
PMID:Effect of retinol and cigarette-smoke condensate on dye-coupled intercellular communication between hamster tracheal epithelial cells. 333 16

Nonmelanoma skin cancers, like most malignancies, increase in incidence with increasing age. However, in general they are not due to the aging process but are primarily due to solar radiation. Clinically, squamous cell carcinomas and basal cell epitheliomas are the most common cancers that occur in the Caucasian population in the United States. The role of radiation from the sun was suggested by a number of astute clinical observations reported around 1900 and subsequently has been established by epidemiologic and experimental studies. Action spectrum evaluations indicate that the ultraviolet B (UVB) rays are the most carcinogenic. However, recent studies indicate that the UVA rays can augment the cancer-producing effects of UVB rays. Other physical stimuli, including heat and wind, can also accelerate UVB carcinogenesis. Chemicals such as the polycyclic hydrocarbons, the nitrosoureas, and nitrogen mustard have an additive carcinogenic effect with UVB radiation. Also, some chemicals such as croton oil, the phorbol ester--TPA, and all-trans-retinoic (RA) acid can promote UVB-initiated carcinogenesis. RA can also inhibit UVB-induced cancer formation. The role of the immune status has received a great deal of attention. Both in experimental and clinical situations, nonspecific immune suppression results in increased cancer formation. Also, recent studies indicate that a specific T cell suppressor population can be induced in experimental animals with UVB which will inhibit rejection of tumors produced by UVB radiation. Finally, damage to DNA by UVB radiation is well established. Studies with the genetic disease xeroderma pigmentosum support the concept that such damage, if not repaired, will lead to cancer formation. It also has been suggested that unrepaired damage to deoxyribonucleic (DNA) and other macromolecules is at least in part responsible for the aging process in general.
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PMID:Photocarcinogenesis, skin cancer, and aging. 635 13

Carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol 13-acetate (TPA) in the forestomach epithelium of mice was delayed by ethyl all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate (etretinate). Beside the clear inhibitory effect during the promotion phase, however, considerable side effects occurred when administering effective doses.
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PMID:Inhibition of the promotion phase in two-step carcinogenesis in forestomach epithelium of mice by the aromatic retinoid etretinate. 641 24

Differentiation of the stem cell line rat mammary (Rama) 25 to alveolar-like cells can be monitored by the increase in production of domes (hemispheric blisters) in the cell monolayer and immunoreactive casein in the tissue culture medium. This step was accelerated not only by the synthetic inducer dimethyl sulfoxide (DMSO) but also by all-trans-retinol, all-trans-retinal, all-trans-retinoic acid (RA), and all-trans-retinyl acetate (concentration range, 0.04-4 microM) in the presence of the hormones prolactin, hydrocortisone (HC), insulin, and 17 beta-estradiol; 9-cis-all-trans-retinal was without effect. A combination of RA and HC was active in producing doming, whereas RA, all four hormones, and serum were required for maximum production of immunoreactive casein. The retinoids in the same concentration range also caused a reduction in the DNA synthetic rate in a similar time period. When Rama 25 cells were treated with RA and the four hormones yielding the droplet and doming cultures, subsequent injection of these cells into young, female inbred nu/nu (nude) mice led to a reduced incidence of tumors compared with injections of untreated cells. Tumorigenic variant cell lines were selected previously from Rama 25 that were either elongated and failed to differentiate at all to doming and casein-secreting cultures (Rama 521) or that did so spontaneously but whose rates were not accelerated by addition of DMSO (Rama 259). Both Rama 521 and Rama 259 failed to respond to the retinoids and hormones in producing domes and immunoreactive casein, in decreasing DNA synthetic rates, and in lowering the incidence of tumors induced by injection of the cell lines into nude mice. Thus the anticancer activity of the retinoids in rat mammary gland carcinogenesis may be due in part to their differentiation-inducing properties.
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PMID:Retinoid-specific induction of differentiation and reduction of the DNA synthesis rate and tumor-forming ability of a stem cell line from a rat mammary tumor. 657 40

An oral dose of all-trans-retinoic acid or 13-cis-retinoic acid in the pregnant [Lak:LVG(SYR)] hamster caused a dose-dependent increase in malformations in the offspring, but an equivalent dose of all-trans-N-ethyl retinamide or 13-cis-N-ethyl retinamide failed to result in embryotoxicity. The present results show that structural modification of the retinoid skeleton can produce compounds that retain cancer chemopreventive activity but that lack the teratogenic activity common to many synthetic and naturally occurring forms of vitamin A. The results indicate that in the case of the retinoids the two kinds of activity--interference with the process of carcinogenesis and interference with embryonic development--may be divorced.
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PMID:Amelioration of embryotoxicity by structural modification of the terminal group of cancer chemopreventive retinoids. 658 52

There is a correlation between the ability to induce the polyamine-biosynthetic enzyme ornithine decarboxylase (ODC) and the tumor-promoting ability of various carcinogens in mouse epidermis. Some agents which inhibit skin carcinogenesis also inhibit ODC induction. In this study, all-trans-retinoic acid (RA) regimens that inhibited the induction of epidermal ODC by ultraviolet-B (UVB) were tested for their ability to inhibit UVB skin carcinogenesis. Hairless mice were irradiated once daily with UVB for 20 days, receiving a total dose of UVB (17.1 kJ/sq m). Topical RA was applied immediately (RA, one dose) or applied 0, 1, 2, 3, and 4 hr (RA, five doses) after each irradiance. The mice were maintained for 52 weeks and then sacrificed. Groups treated with RA tended to have fewer mice with tumors, fewer tumors per mouse, smaller tumor diameters, and slower growing tumors than did appropriate irradiated control groups. RA given five times was more effective than was RA given one time at inhibiting UVB skin carcinogenesis. These results show that RA treatments that inhibit epidermal ODC induction may be effective in reducing the carcinogenicity of UVB.
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PMID:Inhibition of ultraviolet-B skin carcinogenesis by all-trans-retinoic acid regimens that inhibit ornithine decarboxylase induction. 684 65

The effect of 200 micrograms doses of all-trans retinoic acid, given over a long duration (daily for 8 weeks, suspended for 3 weeks, then resumed daily for 4 weeks) or short duration (daily for 30 days), on the induction of fibrosarcomas in C57BL/6J mice by MCA was evaluated. A reduced level of carcinogenesis was observed with both lengths of retinoic acid treatment, since respective incidences of MCA fibrosarcomas were 63 and 61% of those in saline-treated controls. In other studies, the effect of all-trans retinoic acid on syngeneic growth of two experimental fibrosarcomas (B6 25 and B6 27, induced previously in C57BL/6J mice by MCA) was assessed. Retinoic-acid-treated mice were more resistant to higher doses of viable B6 27 (LD50 = 2.85) and especially B6 25 (LD50 = 3.80) than were corresponding saline- or corn-oil-treated controls (LD50 less than 2.0). The strength of resistance conferred by retinoic acid treatment thus varied considerably between these tumors, despite their common strain derivation and histopathological origin. Additional studies explored the effect on B6 27 growth of giving all-trans retinoic acid during either the sensitization or challenge stage of standard syngeneic immunogenicity tests. Mice given all-trans retinoic acid during sensitization displayed a markedly increased resistance to challenge with the immunospecific B6 27 tumor (LD50 = 5.30), compared to challenged controls that received saline (LD50 = 2.60) or corn-oil (LD50 = 2.55) during preimmunization. In contrast, when B6 27-preimmunized mice were treated with all-trans retinoic acid after challenge with homologous tumor, resistance to B6 27 (assessed by tumor growth rate and LD50 dose) was not increased but remained comparable to that of saline-or corn-oil-treated controls. While the mechanism(s) by which all-trans retinoic acid inhibits syngeneic growth of MCA tumors is unknown, our results support an immunostimulatory effect, evidenced by tumor resistance in both non-immune and specifically preimmunized syngeneic hosts.
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PMID:Effect of all-trans retinoic acid on induction, lethality and immunogenicity of murine methylcholanthrene-induced fibrosarcomas. 712 73

A series of experiments was conducted to determine the efficacy of 15 synthetic retinoic acid amides (retinamides) as inhibitors of chemical carcinogenesis of the urinary bladder in C57BL/6 x DBA/2F1 mice. Eight of the retinamides tested had significant protective activity when administered at nontoxic levels in the diet. Minor structural alterations, such as the addition of a methyl or hydroxyl group to the terminal amide moiety had a major influence on the anticarcinogenic activity of the retinamides. Although 13-cis retinamides generally were less toxic on a molar basis than were their all-trans isomers, no consistent pattern of differential anticarcinogenic activity was noted among the six pairs of all-trans and 13-cis isomers tested. All-trans-4-hydroxyphenyl retinamide was among the most active and least toxic of the retinoids tested, and appears to be the compound of choice for further study.
Carcinogenesis 1982
PMID:Influence of 15 retinoic acid amides on urinary bladder carcinogenesis in the mouse. 715 Dec 60

The effects of all-trans retinoic acid (RA) in 0.05%, 0.025% and 0.005% concentrations on ultraviolet (UV) induced carcinogenesis was investigated in the skin of Uscd strain hairless mice. A carcinogenic amount of UV energy was delivered over the 12-mo period of the study. The 0.025% and 0.005% RA solutions did not alter the development of cutaneous cancers. However, the 0.05% RA concentration significantly inhibited the tumor formation in this study.
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PMID:Inhibition of ultraviolet-induced carcinogenesis by all-trans retinoic acid. 724 Jul 86


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