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 685,946 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.
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PMID:Vitamins and cancer prevention: issues and dilemmas. 723 79

In 34 patients with HVP-infection of the cervix and in 40 patients with CIN III standardised biopsies were taken from the involved area and normal cervical epithelium for determination of the local concentration of retinylester. In all cases diagnosis was confirmed colposcopically, cytologically and by histology. HPV infection was confirmed by in situ hybridisation. Determination of retinylester was performed by HPLC. No significant difference of local retinyl-plamitate concentration was detectable in HPV infected versus normal tissue. Retinyl-palmitate concentration was extremely lower in CIN III compared with normal cervical epithelium and HPV-infected tissue. The determination of plasma level of retinol showed no significant difference between the two groups. So it can be presumed that the reduction of retinyl-palmitat in CIN III is a local process and a local supplementation of Vitamin A might contribute to the prevention of cervical neoplasia.
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PMID:[Changes in the vitamin A status in dysplastic epithelium of the cervix]. 748 81

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.
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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

Vitamin A is metabolized to several biologically active compounds, the best known of which is retinoic acid. This compound has been shown to inhibit the growth of a variety of tumor cells and to induce a more differentiated phenotype in several tumor types. Vitamin D is metabolized to the active compound 1,25-dihydroxyvitamin D3. This vitamin is well-known for its role in maintaining calcium homeostasis in the body. Recently it has been shown that vitamin D3 can also inhibit tumor cell replication and stimulate differentiation of selected tumor types. Retinoic acid is being used clinically to treat promyelocytic leukemia, head and neck tumors as well as cervical dysplasia. Use of vitamin D3 clinically has been restricted by its affect on calcium metabolism. Recently, however, new analogs of vitamin D3 have been developed which have much less calcium mobilizing activity, yet still retain their tumor inhibitory properties. The action of both of these vitamins is mediated by nuclear receptors which have the same structure as steroid receptors. There are three nuclear retinoic acid receptors (RAR alpha, beta, and gamma), but only one vitamin D3 nuclear receptor. These receptors are expressed in very small amounts. Since the ligand should be in vast excess of receptor (ie not limiting), we explored the possibility that response to vitamin A might be mediated by control of RAR expression. Using B16 mouse melanoma cells as a model system, we found that RAR alpha and gamma mRNAs were constitutively expressed. RAR beta mRNA was induced by treatment of the cells with RA. Induction of RAR beta mRNA occurred within 1h and was not inhibited by cycloheximide. The mRNA for all three RARs was dramatically decreased with 8-bromo-cyclic AMP treatment and could not be rescued by addition of RA. Analysis of RAR gamma revealed that this decrease occurred within 1h of exposure to 8-bromo-cyclic AMP and was not blocked by simultaneous treatment with cycloheximide. Nuclear extracts from cyclic AMP-treated cells showed a large decrease in protein binding to a retinoic acid response element (RARE) oligonucleotide compared to control cells. This correlated with a marked reduction of RA-stimulated RARE-reporter gene activity in transfected cells which were treated with cyclic AMP. Pre-treatment of B16 cells with cyclic AMP prior to RA addition dramatically reduced induction of PKC alpha, an early marker of RA-induced cell differentiation. Thus, cyclic AMP can antagonize the physiological actions of RA via its ability to inhibit RAR expression.
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PMID:Use of vitamins A and D in chemoprevention and therapy of cancer: control of nuclear receptor expression and function. Vitamins, cancer and receptors. 764 20

Vitamin E was quantified in renal cell carcinomas (RCC) and in 'intact' renal cortex, obtained from 31 patients subjected either to unilateral nephrectomy or to partial resection of the only kidney. Histologically, 14 tumors consisted predominantly of clear cells (group 1) and 17 of other cell types (group 2). In both groups, a significant increase in vitamin E concentration, as compared to the 'intact' cortex, was observed: 167.8 +/- 27.9 and 68.2 +/- 15.2 micrograms/g wet tissue weight (mean +/- SEM) for groups 1 and 2, respectively, versus 10.1 +/- 0.53 micrograms/g wet tissue weight for the cortex. Although the total lipid content was also increased in tumors (especially in group 1), the vitamin E concentration in tumor tissue, calculated per milligram of total lipids, proved to be much higher in both groups than in 'intact' cortex. A significant positive correlation was observed between vitamin E and total lipid content in group 1 and 2 carcinomas. It was also found that vitamin E accumulation in RCC is unlikely to be attributed to an enhanced lipid deposit in the tumor cells. Thus, in 8 tumors of group 2 the vitamin E levels were markedly enhanced although these tumors did not differ from the cortex in total lipid concentrations. Vitamin A content determined in 17 carcinomas, when calculated per milligram of total lipids, was the same as in 'intact' cortex.
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PMID:Liposoluble vitamins E and A in human renal cortex and renal cell carcinomas. 777 11

Vitamin E was quantified in tumor tissue obtained from 17 patients with renal cell carcinoma (RCC). The tumors consisted of two groups: (I) represented primarily by clear cells (10 cases) and (II) without predominant appearance of those cells (7 cases). Vitamin E concentration in tumor tissue was compared with that in intact tissue sites of the kidney. The vitamin content in intact renal medulla was shown to be 1.5 times higher than in intact cortex. Vitamin E level in group I tumors was shown to be on average 15 and 10 times as much as in intact renal cortex and medulla, respectively. The vitamin concentration in group II tumors, as compared with the above intact renal tissues, was 7- and 5-fold higher, respectively. In spite of the high tumor total lipids levels, the vitamin E concentration, calculated per mg total lipids, was still higher in tumor tissue than in the normal renal tissues. This finding was especially demonstrable for the group I tumors. In the benign renal tumor angiomyolipoma vitamin E concentration, calculated on a wet weight basis, was higher than in intact renal tissue, but no differences were observed when a per total lipids calculation was performed. Vitamin A concentration determined in the tumor samples obtained from 6 patients was the same as in intact cortex.
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PMID:[Content of vitamins E and A in tumor tissue in kidney cancer]. 805 29

1,2-Diglycerides with long-chain fatty acid residues related to nutritional fat (LCDGs) specifically affect growth and urokinase secretion in human colonic tumor cells, but not in normal mucosa. This allows them to advance and enhance carcinogenesis in the colon and rectum. SW480 colon carcinoma cells are LCDG sensitive in the same way as primary colonic tumor cells and have therefore been used as a model system to study the mechanism of LCDG action and to search for inhibitors of tumor development in the colon. Using this model system, we have shown that the effects of LCDGs are transmitted by protein kinase C and abolished by downregulation of the enzyme. Retinol, retinoic acid, and beta-carotene in nanomolar concentrations inhibit LCDG-induced growth and urokinase secretion and block stimulation of protein kinase C. Although retinol and retinoic acid at higher concentrations also display stimulatory activity, beta-carotene does not. At 100 nM, a concentration that can easily be reached in the plasma of humans, beta-carotene reduces LCDG-induced urokinase secretion about 50%. Inasmuch as beta-carotene does not have side effects due to intrinsic activities and storage effects, beta-carotene and foods rich in carotenes could be useful in the prevention of colorectal cancer.
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PMID:Retinoids inhibit protein kinase C-dependent transduction of 1,2-diglyceride signals in human colonic tumor cells. 805 26

In synergistic combination 0.75 mmol/kg diet of N-(4-hydroxyphenyl) retinamide and 32 mmol/kg diet of glucarate inhibits the growth of primary rat mammary tumors, but are equally effective as single agents at 1.5 and 128 mmol/kg diet, respectively. Dose-response studies suggest that like retinoids, glucarate acts directly on tumor cells, rather than having an adjuvant effect. Although synergism is maintained down to at least 0.38 mmol/kg diet of the retinoid, experiments using Vitamin A-deficient diets indicates 128 mmol/kg glucarate acts independent of retinoid. Both alone and in combination, glucarate and retinoid inhibited the growth of human mammary tumor cells grown in the athymic mouse, the growth of rat mammary tumors in germfree rats and the hormone-independent MTW 9a/R rat mammary tumor. Like retinoids, glucarate suppresses protein kinase C and induces transforming growth factor-beta, in the mammary tumor cells.
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PMID:Mechanism of growth inhibition of mammary carcinomas by glucarate and the glucarate: retinoid combination. 829 19

Vitamin A and its derivatives, the retinoids, have antiproliferative effects and may induce cellular differentiation. Etretinate, a synthetic retinoid, has a more favorable therapeutic index experimentally than all-trans-retinoic acid or 13-cis-retinoic acid. Ninety patients with superficial papillary bladder tumors stages Ta and T1 entered a prospective randomized double-blind multicenter trial in Switzerland. Seventy-nine of the patients were eligible and received either 25 mg of etretinate or a placebo orally each day. The early withdrawal of a significantly greater number of patients in the placebo group for treatment failure during the first year of the study resulted in a secondary positive selection in this group. High-risk patients were removed and low-risk patients remained. In those patients who had tumor recurrences after randomization, the time to first recurrence was similar in both groups with 13.5 and 13.6 months in the placebo and etretinate groups, respectively. However, the mean interval to subsequent tumor recurrence was significantly longer in the etretinate group. The mean interval between recurrences in these subgroups was 12.7 months in the placebo arm and 20.3 months in the etretinate arm (p = 0.006). Consequently, the number of transurethral resections per patient-year was also reduced significantly in the etretinate group (p < 0.001). In patients with more than one transurethral resection of papillary tumors before randomization, the annual transurethral resection rate in the two treatment groups dropped from 1.7 to 1.3 in the 30 patients in the placebo group (NS, p = 0.1) and from 2.1 to 0.95 in the 25 patients in the etretinate group (p < 0.001). The side effects of etretinate (cheilitis, dryness of mucous membranes and skin) were acceptable to most patients. The relationship of the 3 myocardial infarcts observed in the etretinate group to the retinoid is not clear. Despite their significant effect on the recurrence rate of superficial papillary bladder tumors, retinoids should only be used in well-controlled prospective trials until more is known about their dosage-toxicity profiles.
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PMID:Adjuvant treatment with a vitamin A analogue (etretinate) after transurethral resection of superficial bladder tumors. Final analysis of a prospective, randomized multicenter trial in Switzerland. 857 94

The in vivo carcinogenic risk of hyperthermia, alone or in combination with irradiation, and the anti-carcinogenic potential of vitamin A and N-acetylcysteine (AcCys) were investigated. Starting 1 month before treatment, 160 rats were divided into four diet groups: no additives, vitamin A-enriched diet, AcCys and the combination vitamin A + AcCys. In 10 animals per diet group, the hind leg was treated with either X-irradiation alone (16 Gy), hyperthermia alone (60 min at 43 degrees C), hyperthermia 5 h prior to irradiation or hyperthermia 5 h after irradiation. Animals were observed for 2 years after treatment with regard to the development of tumours either inside or outside the treated volume. After 16 Gy alone 12 +/- 5% of the animals developed a tumour. Tumour incidence increased to 37 +/- 9% (borderline significance P = 0.07 versus treatment with X-rays alone) when hyperthermia was applied prior to X-rays, and to 24 +/- 8% (NS) with hyperthermia after irradiation. The relative risk ratio (RRR) for tumour induction was increased to 2.4 by hyperthermia if combined with X-irradiation. Pathological characterization of induced tumours showed that these were of the fibrosarcoma, osteosarcoma and carcinoma type. Vitamin A alone or in combination with AcCys slightly protected against the induction of tumours by X-rays without or with hyperthermia (RRR of 0.4). However, morphological changes such as lipid accumulation in hepatocytes and damage to the parenchyma were noticed in livers from all animals that were given a vitamin-A-enriched diet (P < 0.0001). Data from the present and past reports show that hyperthermia alone is not carcinogenic, but that it may increase radiation carcinogenesis. Treatment temperature and time of exposure to heat in addition to the radiation dose applied are important factors in the carcinogenic process. The enhancement of radiation carcinogenesis seems to occur independently of the sequence and time interval between irradiation and hyperthermia. However, not all data are consistent with this interpretation.
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PMID:Hyperthermia, radiation carcinogenesis and the protective potential of vitamin A and N-acetylcysteine. 864 44


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