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

Vitamins are a class of organic compounds that are components of an adequate diet. They or their derivatives function as coenzymes, cellular antioxidants, and/or regulators of gene expression. Fourteen vitamins are recognized in human nutrition (Vitamins A, D, E, K, B1, B2, B6, B12, C, niacin, folacin, pantothenic acid, biotin, choline), with deficiencies or excesses in intake leading to changes in protein, nucleic acid, carbohydrates, fat and/or mineral metabolism. Thus, the integrity of physiological systems, including those associated with detoxification, cellular repair, immune processes, and neural and endocrine function, depends upon the nutritional and vitamin status of the host. For these reasons, it may be anticipated that the adequacy of the vitamin supply to cells and tissues would affect the development, progress, and outcome of cancers. In this review, the definition and functions of and requirements and recommended allowance for vitamins are discussed briefly before exploring the evidence, largely from studies in experimental animals, that indicates the nature of the link between vitamins and cancer. Although evidence based on studies in animal systems reveals that vitamin intake and status can modulate the outcome of experimental carcinogenesis, the findings are often conflicting and difficult to interpret. Furthermore, it is not yet possible to develop a suitable prediction of the role of the individual vitamins in tumor development. The significance of these observations for human nutrition and cancer prevention, particularly in reference to ascorbic acid (vitamin C), vitamin E, and B-complex vitamins is considered. Vitamin A and retinoid compounds are discussed elsewhere in the symposium. The many popular misconceptions and unsound advice concerning vitamins and health, including "fake" vitamins-pangamic acid ("vitamin B15") and laetrile ("vitamin B17")-are also discussed. On the basis of current evidence, it would be inappropriate to recommend either substantial changes in habitual vitamin intakes, as provided by an adequate, well-balanced diet, or promotion of megavitamin intakes, as a means of reducing risk from cancers in the human population. However, a prudent approach toward diet and food habits, as a means of better optimizing the health consequences of our complex lifestyle is to be recommended.
 ...
PMID:Vitamins and cancer prevention: issues and dilemmas. 723 79

Dietary data relating in 406 patients with gastrointestinal cancers (cases) and 812 controls have been analysed to test the hypotheses that dietary vitamin A (retinol) and its precursor, carotene, may be protective agents in human carcinogenesis. There was no deficit among cases in the intake of retinol-containing food items whereas several of the main carotene-containing fruits and vegetables were eaten less often among cases than among controls. However, when total daily intake was estimated, there was no protective effect of carotene, perhaps implying that some other constituent of the fruits and vegetables is protective.
 ...
PMID:A note on the role of dietary retinol and carotene in human gastro-intestinal cancer. 730 88

Liarozole has been reported to inhibit P450 enzymes responsible for the catabolism of retinoic acid. This suggests that it may increase the effectiveness of cancer chemopreventive agents, such as retinoic acid, and pro-vitamin A carotenoids, such as beta-carotene, which may yield retinoids. To test this we have utilized the 10T1/2 cell assay system of neoplastic transformation. Simultaneous treatment with Liarozole (10(-5) M) potentiated by a factor of 1000 the ability of low concentrations of retinoic acid (10(-10) M) to inhibit carcinogen-induced neoplastic transformation, to up-regulate gap junctional communication and to increase connexin43 expression. When tested under conventional culture conditions, Liarozole itself partially suppressed neoplastic transformation and up-regulated gap junctional communication; this ability appears due to the presence of retinol in the serum component of cell culture medium. When assays for junctional communication and of connexin43 expression were performed under defined conditions, in the absence of serum, Liarozole was ineffective alone, yet still augmented the effects of retinoic acid. HPLC analysis of cell culture medium demonstrated that Liarozole (10(-5) M) completely protected retinoic acid (10(-6) M) from catabolism over a 48 h period. Potential effects of Liarozole on the activities of carotenoids were also examined. Inhibition of neoplastic transformation by the pro-vitamin A carotenoid beta-carotene, but not by the non-pro-vitamin A carotenoid canthaxanthin, was moderately potentiated by Liarozole. The augmentation of response to beta-carotene was more apparent when tested under defined conditions; here Liarozole strongly increased junctional communication and Cx43 expression. In contrast, Liarozole did not potentiate the activity of canthaxanthin under defined conditions, while increasing the activity of 4-keto retinoic acid, a likely metabolite. Liarozole also elevated connexin43 expression in early passage human fibroblasts. These data indicate that rapid catabolism of retinoic acid limits its in vitro activities, that a portion of the action of beta-carotene as a cancer preventive agent is due to its conversion to retinoic acid and that canthaxathin exerts its chemopreventive action largely independent of conversion to 4-keto retinoic acid.
Carcinogenesis 1995 Sep
PMID:Liarozole potentiates the cancer chemopreventive activity of and the up-regulation of gap junctional communication and connexin43 expression by retinoic acid and beta-carotene in 10T1/2 cells. 755 78

The anticarcinogenic effects of beta-carotene (BC) have been extensively investigated, but only in vitro assays have examined the ability of BC to modulate gene mutation. In view of the current interest in the provitamin as a cancer chemopreventive agent, and the association between mutagenesis and carcinogenesis, we have dosed Fischer 344 rats with model carcinogen N-ethyl-N-nitrosourea (ENU) and investigated the relationships among BC intake, its tissue accumulation, and antimutagen activity. Animals received drinking water supplemented with BC at doses of 0-0.25% ad libitum, using three dosing schedules. In one group BC dosing commenced before, and continued for three alternating weeks after i.p. injection of 100 mg ENU/kg; another group was given BC only after mutagen treatment. Animals from the first two groups were sacrificed 5 weeks post-mutagen treatment, and cells were isolated from the spleen to determine the frequency of 6-thioguanine- resistant (6-TGr) T-lymphocytes. The presence of BC caused a reduction in the frequency of 6-TGr T-cells produced by ENU, but the inhibition was non-linear within the range of BC doses used. BC intake only after mutagen treatment was more effective than the combination of pre- and post-mutagen intake. In the third group, rats were treated with 100 mg ENU/kg, and BC administration was continued at a fixed dose of 0.15% in the drinking water for 2, 4, 6, or 8 weeks. Measurement of the frequency of 6-TGr T-cells at the end of the specified times showed > 50% reduction in ENU-mediated mutagenicity throughout the experiment. Analysis of BC levels in the liver and in the spleen following BC intake before and during mutagen exposure revealed higher levels than when BC was given only after mutagen treatment. Continuous intake of BC also showed increased tissue levels. There were some correlations observed between BC tissue levels and the antimutagenic effects for the first two groups, but these correlations were not statistically significant, possibly due to the small numbers of animals used. Taken together, the results demonstrate that intact BC is absorbed, stored, and exerted antimutagenic effects against a chemical carcinogen in rats without first being transformed to retinol in the gastrointestinal tract.
Carcinogenesis 1995 Sep
PMID:In vivo antimutagenic activity of beta-carotene in rat spleen lymphocytes. 755 82

The cellular transport, metabolism and biological activity of retinoids are mediated by their specific binding proteins and nuclear receptors. For an understanding of the mode of action of retinoids with potential cancer chemopreventive or other biological activity, it is important to study their interactions with these binding proteins and receptors. In our attempts to understand the action of N-(4-hydroxyphenyl)retinamide (4HPR) and other retinamides in the prevention of cancer, we observed that 4HPR binds to a serum protein with a molecular size of approximately 20,000. The retinoid, however, did not show any binding affinity for cellular retinol-binding protein (CRABP) or for cellular retinoic acid-binding protein (CRABP). However, it showed binding affinity for the nuclear receptors of retinoic acid (RARs) equivalent to 15% of that of retinoic acid. The physicochemical properties of the 4HPR binding protein in the serum were identical to those of serum retinol binding protein (RBP). Antibodies against RBP quantitatively immunoprecipitated the protein-4HPR complex, confirming that the retinoid specifically binds to RBP. Although retinol and 4HPR cross-competed for RBP binding, N-phenylretinamide, in which the 4-hydroxyl group is absent, and N-(4-methoxyphenyl)retinamide, a major cellular metabolite of 4HPR, in which the hydroxyl group is blocked, did not show affinity for the binding protein. The results indicate that the hydroxyl group of 4HPR is essential for binding of this type of retinoid to RBP. Thus, our studies suggest that serum transport of 4HPR may be facilitated by RBP. To bind more efficiently to CRBP, CRABP, or RARs/RXRs, the retinoid may require further metabolic change.
Carcinogenesis 1995 Oct
PMID:N-(4-hydroxyphenyl)retinamide: interactions with retinoid-binding proteins/receptors. 758 62

Solar radiations (UV A and B) can cause epidermis photoaging and skin cancers. These frequently irreversible effects result from the in situ generation of free radicals. However, it has been noted that nutritional factors can modulate photochemical damage, in particular the common carotenoids present in food, which can be considered as potential prophylactic agents against carcinogenesis. We investigated the effect of UV A and B radiations on the skin of the SKH1 hairless mouse fed a diet either lacking in vitamin A or supplemented with retinol, beta-carotene or astaxanthin. The latter is an oxygenated carotenoid (like canthaxanthin) without provitamin A activity and with strong singlet oxygen quenching ability. After analysing of vitamin status of each group (plasma retinol concentrations and hepatic reserves), we searched for UV-induced modifications of polyamine metabolism by measuring epidermal ornithine decarboxylase (ODC) activity and free polyamines concentration (putrescine, spermidine and spermine). In the basal state without irradiation, differences in ODC activity between groups were nonsignificant; but after UV stimulation, ODC increased markedly in the skin of vitamin A-deficient animals, much more than in other groups. Curiously, the addition of astaxanthin or beta-carotene to the regimen containing retinol reduced the protective effect of retinol alone. Regarding polyamines after irradiation, putrescine was significantly increased in the skin of deficient animals, in parallel with ODC activity. However, astaxanthin had a stronger inhibitory effect on putrescine accumulation than retinol, and decreased spermidine and spermine concentrations: this suggests a specific action on transglutaminases.
 ...
PMID:Vitamin A status and metabolism of cutaneous polyamines in the hairless mouse after UV irradiation: action of beta-carotene and astaxanthin. 759 36

Vitamin A and beta-carotene protect against respiratory tract cancer by inhibiting the formation of DNA damage and controlling cellular proliferation and differentiation. Recently, it has been shown that the p53 tumor-suppressor gene plays a crucial role in the etiology of respiratory tract cancer. In the present study, we investigated the relationship between benzo[a]pyrene (B[a]P)-DNA adducts, cell proliferation and p53 expression and the possible effect of beta-carotene on such a relationship in tracheal epithelium of hamsters given intratracheal instillations of B[a]P-Fe2O3 particles suspended in saline. DNA-adducts were quantified by the 32P-postlabeling assay, cell proliferation was quantified by immunocytochemical detection of incorporated BrdU during S-phase, and p53 protein was detected by immunohistochemistry with an antibody that recognized both the wild-type and the mutated protein (BioGenex, Clone BP53-12-1). A clear relationship appeared to exist between the extent of B[a]P-DNA adduct formation, the induction of cell proliferation and the expression of p53 protein in hamster tracheal epithelium. These results suggest that B[a]P induces cell proliferation in hamster tracheal epithelial cells most likely by the induction of mutations in the p53 gene. Furthermore, beta-carotene was not found to influence the formation of B[a]P-DNA adducts, which is probably due to the high B[a]P dose. Moreover, beta-carotene did not statistically significantly affect cell proliferation and p53-protein expression in hamster tracheal epithelial cells.
Carcinogenesis 1995 Jul
PMID:Relation between benzo[a]pyrene-DNA adducts, cell proliferation and p53 expression in tracheal epithelium of hamsters fed a high beta-carotene diet. 761 97

Concentrations of carotenoids, retinoids and tocopherols were determined in the homogenate of macroscopically normal appearing oropharyngeal mucosa from 10 chronic alcoholics and from 11 control patients. All the alcoholics except one had oropharyngeal cancer. No significant difference was found in tissue levels of carotenoids and tocopherols between alcoholics and controls. Furthermore, in seven of 11 controls, retinol was undetectable in the oropharyngeal mucosa, while in the alcoholics only two out of 10 had unmeasurable retinol levels. These results do not support the concept that ethanol-associated oropharyngeal carcinogenesis is due, at least in part, to local deficiencies in retinoids, carotenoids or alpha-tocopherols.
 ...
PMID:Carotenoid, retinoid and vitamin E status of the oropharyngeal mucosa in the alcoholic. 766 34

Preclinical studies make fenretinide attractive for prevention and treatment of breast cancer. It inhibits mammary gland end bud formation in developing animals. Carcinogen-induced mammary cancer is suppressed by fenretinide, both at early and late stages of carcinogenesis, in young and mature rats. Fenretinide causes regression of invasive rat mammary cancer. Cytostatic activity has been demonstrated against human breast cancer cell lines. Autocrine stimulation of human breast cancer cell lines by tgf-alpha, insulin-like growth factors I and II is significantly abrogated by fenretinide. The human half-life is 24 hours. Absorption is markedly affected by meal content. Serum levels of 1 mM are achieved at doses of 200 mg/day. This dose significantly suppresses serum IGF-I levels in women. This concentration is capable of suppressing human breast cancer growth in vitro. A 3-day drug holiday is given each month in order to restore serum retinol levels. Under these circumstances, fenretinide is well tolerated. A phase III trial evaluating the efficacy of fenretinide for breast cancer prevention in high-risk women has been completed. Tamoxifen enhances the effectiveness of fenretinide in carcinogenesis models. The combination can be safely administered to women. A phase III adjuvant trial of tamoxifen, with or without fenretinide will be conducted in the United States.
 ...
PMID:Breast cancer and fenretinide, an analogue of vitamin A. 780 27

Retinoids, which are derivatives of vitamin A, have a variety of effects on normal cellular differentiation and on the process of carcinogenesis. A number of novel endogenous retinol metabolites have been identified recently. The response of many cell types to retinoid treatment is mediated by retinoid receptors, and involves changes in gene expression, cell growth and cell differentiation. The gene encoding one of the retinoic acid receptors is disrupted by the chromosome translocations associated with acute promyelocytic leukemia, and the expression of another is altered in epithelial tumors; both of these findings have important implications for the use of retinoids as anti-carcinogenic agents. It has been demonstrated recently that certain homeobox genes are regulated by retinoids; these genes may also prove to be useful agents for anti-carcinogenic therapies.
 ...
PMID:Vitamin A, differentiation and cancer. 788 May 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>