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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin E (tocopherol) enhances the growth inhibitory effects of adriamycin (ADR) on a variety of cancer cells in vitro. The role of vitamin E (d-alpha-tocopheryl) acid succinate in adjuvant chemotherapy with ADR was assessed in DU-145 human prostatic carcinoma cells in culture. Adriamycin produced a dose-dependent growth inhibition of DU-145 cells. The ID50 of DU-145 cells on the criteria: of clonal assay was 13 ng./ml. and of cell count assay was 14 ng./ml. Vitamin E succinate also inhibited the growth of DU-145 human prostatic carcinoma cells in a dose-dependent manner. 4.4 micrograms./ml. and 5.4 micrograms./ml. vitamin E succinate in the culture medium produced inhibition of growth to 50 per cent of control (ID50) in the clonal and the cell count assays respectively. When adriamycin and vitamin E succinate were used in combination, both additive and synergistic effects were observed, depending on the concentration of vitamin E succinate used. Doses of vitamin E succinate greater than its ID50 had a synergistic effect while doses smaller than its ID50 had an additive effect. In either case, the presence of vitamin E succinate caused an enhancement of tumor cell cytotoxicity of adriamycin while decreasing its ID50. Equivalent concentrations of sodium succinate and ethanol used to dissolve vitamin E succinate did not have any effect on DU-145 cells. Thus, it is concluded that the effect of vitamin E succinate is due to vitamin E and not due to succinate or ethanol. These results suggest that vitamin E may have a role in the treatment of human prostatic cancer as an adjuvant agent to adriamycin.
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PMID:Vitamin E enhances the chemotherapeutic effects of adriamycin on human prostatic carcinoma cells in vitro. 373 28

Free radicals are believed to be involved in leukocyte induced tissue injury. The present studies were performed to determine whether low density lipoprotein (LDL) might serve as a mediator of tissue injury after leukocyte induced free radical oxidation of LDL. Our results show that incubation of LDL with monocytes or polymorphonuclear leukocytes (PMN) leads to oxidation of the lipoprotein rendering it toxic to proliferating fibroblasts. Monocyte activation enhances these effects. Butylated hydroxytoluene (BHT), vitamin E (vit E) and glutathione (GSH) virtually prevent the oxidation of LDL and the formation of cytotoxic LDL, indicating that these alterations are mediated by leukocyte-derived free radicals. This is the first demonstration that short-lived free radicals emanating from phagocytic cells could mediate cell injury through the action of a stable cytotoxin formed by the oxidation of LDL. The fact that lipoproteins can transfer a cytotoxic effect from leukocytes to proliferating cells reveals a pathway for cell destruction which may have implications in atherosclerotic plaque progression, macrophage mediated toxicity to tumor cells and tissue injury by inflammatory processes.
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PMID:Monocytes and neutrophils oxidize low density lipoprotein making it cytotoxic. 386 49

Dysplasia is an alteration of organ and tissues cellular composition. It means quantitative and qualitative variations (differentiation) of the cells. More recently many Authors have investigated about epithelial neoplasia (breast, cervix, lung, respiratory tract, bladder, colon) and dysplastic epithelial processes and about their medical treatment and prevention of potentially transformative lesions. The view that certain vitamins such as vitamin A (in the form of retinol or its precursor beta-carotene) and vitamin E may protect against the risk of cancer has recently attracted much scientific attention. The potential use of retinoids (and alpha tocopherol) for chemoprevention has been demonstrated by numerous recent experiences. In gynaecology there are no evidence of therapeutical investigations about endometrial and ovarian dysplastic lesions, and then about protective role for consequent neoplasia development. Regarding cervical cancer there are only epidemiological retrospective data about dietary intake of vitamin A. The clinical trial is insufficient, perhaps for technical difficulties of administration, but we hope to obtain satisfactory results in the future. Benign breast disease, instead, so present in woman's life (in particular in fertile phase) is the most common clinical syndrome encompassing several distinct histopathological varieties. BBD is associated with an increase in breast cancer risk, particularly related to the presence of epithelial hyperplasia. In our study (collaborative study; University of L'Aquila--University of Rome) we have treated a group of women (double-blind trial) affected by breast dysplasia, with vitamin A and E association to evaluate the effectiveness of retinoids and alpha-tocopherol in reducing or resolving clinical palpable breast findings (with pain, tension, nodularity and instrumental patterns).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical use of vitamin A and E in gynecology]. 391 49

The present study showed that in the dimethylbenz[a]anthracene-induced mammary tumor model in rats, the anticarcinogenic efficacy of selenium was much attenuated when the intake of vitamin E was deficient. Selenium supplementation at 2.5 mg/kg in the diet reduced the total tumor yield by 45% and 25%, respectively, in rats with an adequate or low vitamin E intake. Measurements of selected hepatic phase I and phase II detoxifying enzymes indicated that they were not responsive to changes in dietary vitamin E or selenium levels. However, a low vitamin E intake significantly increased lipid peroxidation in the mammary fat pad regardless of selenium status, suggesting that selenium supplementation was less effective under this nutritional condition and might be associated with the higher degree of oxidant stress in the cellular environment.
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PMID:Attenuation of the anticarcinogenic action of selenium by vitamin E deficiency. 391 86

In this article I review the work of our laboratory concerning the relationship between dietary Se intake and susceptibility to mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in female rats. The effect of graded levels of Se in the diet was investigated, ranging from deficiency to excessive supplementation that produced marginal toxicity in the animals. In addition, the interdependence between Se status and fat intake was also explored. Further experiments were aimed at defining the role of Se in the initiation and promotion phases of chemical carcinogenesis. In view of the biochemical function of Se as an antioxidant, the chemopreventive efficacy of Se was compared to that of vitamin E in conjunction with their ability to inhibit lipid peroxidation. Results of this study indicated that the antitumorigenic activity of Se could not be accounted for by suppression of tissue peroxidation, although an environment with a lower oxidant stress might enhance the potency of Se in protecting against cancer. The possible mechanisms of action of Se based on the observations and characteristics of several tumor models are briefly discussed.
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PMID:Selenium inhibition of chemical carcinogenesis. 392 98

Neoplasms affecting different subsections of the large bowel appear to have different risk factors. For the major type of neoplastic disease in the large bowel, that in the descending and sigmoid colon, a good association with nutrition and specific nutritional elements has been found. The risk of this type of colon cancer is proportional to the customary dietary fat intake--high in the Western World and low in the Orient. It is inversely proportional to stool bulk, which is itself modulated by cereal fibre intake. Fat and fibre, as the two major elements implicated, are sufficiently secure with regard to underlying scientific data and understanding of mechanisms, to permit utilising them to modify risk. Thus, a dietary regimen low in total fat, 20% of calories, and higher in cereal fibre, of the order of 30 grams/day, is indicated. Such a modified nutritional intake could be expected to reduce risk, not only in the general population, but most likely also in patients who have been treated successfully by conventional means. Additional evidence suggests that regular intake of yellow and green vegetables, of foods containing calcium salts, selenium and other micro-nutrients, lower the risk even more. More research is needed to provide the data necessary for deliberate intervention with these agents. Gastric cancer, on the other hand, has a distinct set of risk factors, namely, intake of pickled and salted fish or beans. Other risk factors are associated with residence in areas where the geochemical or agricultural sources of nitrate intake are not balanced by the presence of vitamin C, vitamin E, or certain phenolic antioxidants and nitrite traps such as pyrogallol, tannins, or peptides. The possible genotoxic carcinogen is not yet known, but it could be an alkyl-nitrosamide type of aryldiazonium chemical. The formation of such compounds is inhibited by vitamin C, vitamin E, and certain antioxidants. This fact can be used to decrease deliberately the risk of gastric cancer.
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PMID:Human and laboratory studies on the causes and prevention of gastrointestinal cancer. 609 59

The effects of various forms of tocopherol (vitamin E) on the growth and differentiation of mouse melanoma (B-16) and mouse fibroblast (L-cells) cells in culture were studied. D-alpha-tocopherol acid succinate induced morphological alterations and growth inhibition in melanoma cells. When vitamin E acid succinate was removed 4 days after treatment, the above changes remained irreversible for a period of 24 hr, after which resistant cells and partially affected cells renewed cell division and eventually reached confluency. The relative efficacy of D and DL forms of vitamin E acid succinate remains to be evaluated. However, other forms of vitamin E such as DL-alpha-tocopherol free alcohol, Aquasol DL-alpha-tocopherol acetate, DL-alpha-tocopherol nicotinate, or sodium succinate with an equivalent volume of ethanol, at similar concentrations, were ineffective. Vitamin E acid succinate at similar concentrations did not induce morphological changes in fibroblasts. Melanoma cells were about 2-fold more sensitive to vitamin E acid succinate than were fibroblasts for the criterion of growth inhibition. Vitamin E acid succinate-induced morphological changes and growth inhibition in melanoma cells were expressed in hormone-supplemented serum-free medium, but the concentration requirement was about 5 times less than that needed in serum-supplemented medium. Although cyclic adenosine 3': 5'-monophosphate-stimulating agents are known to cause growth inhibition and morphological changes in melanoma cells in culture, vitamin E acid succinate-induced morphological alterations in melanoma cells are no mediated by a rise in cellular cyclic adenosine 3':5'-monophosphate. Ethanol was sufficient to increase the melanin content in melanoma cells. These data show that vitamin E acid succinate may be a potentially useful tumor therapeutic agent.
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PMID:Effects of tocopherol (vitamin E) acid succinate on morphological alterations and growth inhibition in melanoma cells in culture. 627 80

A single exposure to a low concentration (10(-10) mol/l) of tumor promoters [such as 12-O-tetradecanoylphorbol-13-acetate (TPA), phenobarbital and nafenopin] or hormones [such as epidermal growth factor (EGF), glucagon and insulin] or drugs [such as imidazole and indomethacin] stimulated the 24-h flow into DNA synthesis and mitosis of primary neonatal rat hepatocytes incubated in high-calcium (1.8 mmol/l) Eagle's FBS(10% v/v)-MEM. However, only tumor promoters acted as enhancers of hepatocytic DNA synthesis when a low-calcium (0.01 mmol/l) FBS-MEM was used. The activity of tumor promoters was totally suppressed by the simultaneous (or nearly such) addition of low doses (from 25.0 to 0.25 micrograms/ml; activity, from 100 to 0.7 U/ml) of exogenous bovine liver and ox and dog erythrocyte superoxide dismutase (SOD), independent of the calcium concentration of the medium. Even at the minimal dose administered, SOD effectively inhibited the stimulatory actions of TPA concentrations up to 10(-6) mol/l. SOD's blocking effect depended upon its enzymatic activity, as it was prevented by a specific inhibitor of SOD, sodium diethyldithiocarbamate (DDC). By contrast, SOD did not inhibit the growth stimulation elicited by hormones and drugs in hepatocytes maintained in high-calcium FBS-MEM. Moreover, several tumor promoters (namely TPA, phenobarbital, nafenopin, saccharin, teleocidin, benzoyl peroxide, BHT, DDT, lindane, clofibrate and melittin) stimulated DNA synthesis even when the hepatocytes were incubated in the serumless HiWoBa2000 medium, whatever its calcium concentration. In this synthetic medium, tumor promoters' stimulatory activity was again completely inhibited by the simultaneous administration of exogenous SOD. Known antioxidants such as retinoids, vitamin E, selenous acid, and 7,8-benzoflavone, when given simultaneously with TPA, also prevented the stimulation of hepatocytic growth. These results disclose the existence of two quite different mechanisms by which the growth of neonatal rat hepatocytes can be stimulated: (i) the physiological-pharmacological extracellular calcium-dependent SOD-insensitive system mediating the effects of EGF, glucagon, insulin, imidazole, and indomethacin; and (ii) the pathological extracellular calcium-independent SOD- and antioxidant-suppressible mechanism operated by agents belonging to the tumor promoters class and involving, as a critical step, the generation of superoxide anions on the surface of the hepatocyte plasmalemma.
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PMID:Exogenous Cu,Zn-superoxide dismutase suppresses the stimulation of neonatal rat hepatocytes' growth by tumor promoters. 633 36

Skin carcinogenesis can be operationally and mechanistically divided into at least three stages; tumor initiation, stage I and stage II of promotion. Current information suggests that reactive intermediates of skin tumor initiators are mutagenic and bind convalently to DNA of epidermal stem cells (dark basal keratinocytes) leading to some irreversible alteration in the differentiation capacity of these cells. Inhibitors of skin tumor initiation by polycyclic aromatic hydrocarbons (PAH) decrease the level of the PAH diol-epoxide bound to specific DNA adducts. The tumor promoters have been shown to have many cellular and biochemical effects in the skin. Recent data suggests that free radicals may be important in skin tumor promotion. The first stage of promotion is partially irreversible and can be accomplished by a single treatment of a tumor promoter such as TPA or by non-promoting agents such as 4-0-methyl-TPA, calcium ionophore A23187, and hydrogen peroxide, as well as wounding. These agents increase the number of dark basal keratinocytes, which suggest that these cells are important in the first stage of promotion. Prostaglandin E2 was found to specifically enhance stage I of promotion whereas the protease inhibitor tosyl phenylalanine chloromethylketone (TPCK) specially inhibited stage I of promotion and the TPA-induced dark basal keratinocytes. The second stage of promotion is initially reversible but later becomes irreversible. The weak promoting agent mezerein is an effective stage II promoter. Polyamines and epidermal cell proliferation appear to be important events in stage II of promotion. Putrescine was found to specifically enhance stage II, whereas retinoic acid (RA), diflouromethylornithine (DFMO), and butylated hydroxyanisole (BHA) specially inhibited stage II of promotion and the mezerein-induced polyamine levels. Floucinolone acetonide (FA) was found to inhibit both stages but was more effective in counteracting stage I of promotion. Although, TPA can cause a decrease in the number of glucocorticoid receptors during promotion, FA can effectively prevent this loss. Recent data suggest that skin tumor promotion can be effectively inhibited by a combination of stage I and II inhibitors. Furthermore, skin carcinogenesis can be counteracted by a combination of low and nontoxic doses of BHA, TPCK, DFMO and vitamin E.
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PMID:Multistage skin carcinogenesis: a useful model for the study of the chemoprevention of cancer. 638 17

The present study showed that vitamin E, although ineffective by itself, was able to potentiate the ability of selenium to inhibit the development of mammary tumors induced by dimethylbenz(a)anthracene (DMBA) in rats. Animals were maintained on a high-polyunsaturated fat (20% corn oil) diet in order to increase the degree of oxidant stress; additional selenium and/or vitamin E were present at a concentration of 2.5 and 1000 mg/kg of diet, respectively. It should be noted that rats tolerated these levels of supplementation very well with no obvious undesirable effect. Furthermore, our results indicated that vitamin E facilitated the anticarcinogenic action of selenium only when it was present during the proliferative phase. We then proceeded to examine whether DMBA administration would lead to any persistent damage in tissue peroxidation or changes in activities of enzymes associated with peroxide metabolism. It was found that DMBA resulted in an acute but modest increase in lipid peroxidation at 24 hr after carcinogen treatment. This perturbation was only of a transient nature. By comparing the response in a target tissue (mammary fat pad) and a non-target tissue (liver), it can be inferred that DMBA may have a differential effect on the degree of oxidant stress. The antagonistic effect of selenium and vitamin E in suppressing lipid peroxidation was then evaluated. Several conclusions can be drawn regarding the antioxidant potency of these agents in conjunction with their efficacies in cancer prevention. First, although vitamin E is a more effective antioxidant than selenium, it is apparent that systemic suppression of lipid peroxidation by vitamin E subsequent to a carcinogenic insult is not sufficient to inhibit tumor formation. Vitamin E supplementation increases significantly the microsomal hydroperoxidase activity. At the present time, it is unclear what role, if any, this enzyme plays in the synergistic effect of vitamin E and selenium in the inhibition of tumorigenesis. Secondly, the anticarcinogenic action of high levels of selenium is not related to its biochemical function in the regulation of the selenium-dependent glutathione peroxidase. The explanation for this is that the enzyme is already operating at near maximal capacity under normal physiological conditions. Additional selenium will not further increase its activity, since the enzyme protein becomes the limiting factor. Finally, vitamin E may be able to provide a more favorable climate against oxidant stress, thereby potentiating the action of selenium via some other mechanism.
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PMID:Synergistic effect of vitamin E and selenium in the chemoprevention of mammary carcinogenesis in rats. 641 56


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