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)

2-Phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) is classified as a relatively nontoxic selenium compound, probably because of its bound selenium moiety. In thiol-rich tissues, such as the kidneys, ebselen is converted into selenol intermediates. Selenols are nucleophilic agents which might be able to react with platinum compounds. The influence of ebselen on cis-diamminedichloroplatinum(II) (cisplatin)-induced nephrotoxicity in mice was assessed, using single doses of both compounds. Ebselen prevented cisplatin-induced elevations of blood urea nitrogen and serum creatinine levels and morphological kidney damage in BALB/c mice. This protective effect of ebselen was dose dependent: at a cisplatin dose of 14.5 mg/kg, maximal protection was achieved when a single dose of 10 mg of ebselen/kg was administered 1 h before cisplatin. Administration of ebselen, 10 mg/kg, 1 h after cisplatin also protected against severe nephrotoxicity. Treatment with ebselen did not reduce the antitumor activity of cisplatin against MPC 11 plasmacytoma or Prima breast tumor in BALB/c mice. However, this reduction of cisplatin-induced nephrotoxicity would be of little clinical value if it was achieved at toxic doses of ebselen. Ebselen, 10 mg/kg, did not induce blood urea nitrogen, serum creatinine, serum glutamic pyruvate transaminase, or serum glutamic oxalate elevations in the mice. These results are in agreement with the reported low toxicity of ebselen, which is now in Phase I clinical trials as an antiinflammatory drug. The present results indicate that ebselen may provide protection against cisplatin-induced nephrotoxicity, when it is given before or after cisplatin. This might open new perspectives in cancer chemotherapy.
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PMID:Selective reduction of cis-diamminedichloroplatinum(II) nephrotoxicity by ebselen. 220 70

There are excellent theoretical reasons why the mineral nutrients selenium, manganese, copper and zinc, known as the antioxidant minerals, may be involved in the prevention of cancer aetiogenesis. The biochemistry is discussed of the part played by the antioxidant minerals, in the wider context of the other dietary antioxidants vitamins A, E and C, and beta carotene, in preventing tissue damage caused by activated metabolites of oxygen. The likely part played by these oxygen metabolites is described and a detailed review given of the evidence that suggests a role for antioxidant minerals, notably selenium, in preventing carcinogenesis in a range of animal models. There follows a summary of the emerging epidemiological evidence that suggests clearly that low selenium intake is a risk factor in the aetiology of human cancer.
Med Oncol Tumor Pharmacother 1990
PMID:Mineral insufficiency and cancer. 223 36

The effects of treatment with naturally occurring antioxidants, selenium, beta-carotene, ferulic acid, esculin and eugenol during the promotional phase of tumor development were investigated in male F344 rats pre-treated with 1,2-dimethylhydrazine (DMH) and 1-methyl-1-nitrosourea (MNU). Animals were given 3 subcutaneous injections of DMH at a dose of 40 mg/kg body wt. within 1 week and then were injected with MNU i.p. at a dose of 20 mg/kg body wt. 2 times per week, for 2 weeks. Thereafter, the rats were maintained on diet containing either 0.2% beta-carotene, 2 ppm selenium, 1% ferulic acid, 1% esculin or 0.8% eugenol. At week 52, surviving rats were killed and complete histological examinations were performed. Administration of eugenol enhanced the development of both hyperplasia and papillomas in the forestomach. Although treatment with beta-carotene tended to decrease the incidence and number of large intestinal carcinomas, beta-carotene, selenium, esculin and eugenol all decreased the incidence of kidney nephroblastomas, the differences were not statistically significant. The results thus showed that eugenol exerts promoting activity for forestomach carcinogenesis while the other antioxidants might have weak organ-specific inhibitory effects under these experimental conditions.
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PMID:Effects of naturally occurring antioxidants on combined 1,2-dimethylhydrazine- and 1-methyl-1-nitrosourea-initiated carcinogenesis in F344 male rats. 224 10

Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitative are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression of transformation. Densely ionizing alpha-particles, similar to those emitted by radon daughters, are highly effective in inducing transformations and appear to interact in a supra-additive fashion with asbestos fibers. The activation of a known dominant oncogene has not yet been demonstrated in radiation-induced oncogenic transformation. The most likely mechanism for radiation activation of an oncogene would be via the production of a chromosomal translocation. Radiation also efficiently induces deletions and may thus lead to the loss of a suppressor gene.
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PMID:Modulating factors in the expression of radiation-induced oncogenic transformation. 227 10

Ozone (O3) is the major oxidant of photochemical smog. Its biological effect is attributed to its ability to cause oxidation or peroxidation of biomolecules directly and/or via free radical reactions. A sequence of events may include lipid peroxidation and loss of functional groups of enzymes, alteration of membrane permeability, and cell injury or death. An acute exposure to O3 causes lung injury involving the ciliated cell in the airways and the type 1 epithelial cell in the alveolar region. The effects are particularly localized at the junction of terminal bronchioles and alveolar ducts, as evident from a loss of cells and accumulation of inflammatory cells. In a typical short-term exposure the lung tissue response is biphasic: an initial injury-phase characterized by cell damage and loss of enzyme activities, followed by a repair-phase associated with increased metabolic activities, which coincide with a proliferation of metabolically active cells, for example, the alveolar type 2 cells and the bronchiolar Clara cells. A chronic exposure to O3 can cause or exacerbate lung diseases, including perhaps an increased lung tumor incidence in susceptible animal models. Ozone exposure also causes extrapulmonary effects involving the blood, spleen, central nervous system, and other organs. A combination of O3 and NO2, both of which occur in photochemical smog, can produce effects which may be additive or synergistic. A synergistic lung injury occurs possibly due to a formation of more powerful radicals and chemical intermediates. Dietary antioxidants, for example, vitamin E, vitamin C, and selenium, can offer a protection against O3 effects.
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PMID:Biochemical basis of ozone toxicity. 227 33

DBA/2 mice were fed for 16 weeks with Torula yeast-based synthetic diet containing various concentrations of selenium (Se). At 13th week, the mice were immunized with syngenetic L5178 Y lymphoma cells and their specific and non-specific tumor immune responses were examined 3 weeks after immunization. The results indicated that in mice fed with a diet containing 0.007 ppm Se, the serum Se level was extremely low (0.02 micrograms/ml). These Se-deficient mice were unable to elicit normal tumor-specific immune responses. Both the specific proliferation of T cells in MLTC and tumoricidal activity of CTL were very much depressed. In addition, these mice also showed impaired NK and LAK cell activity. The effects of Se supplementation varied depending on the amount of Se given. When 0.170 ppm Se was added to the low Se diet, all the immune parameters examined were restored to the normal level. When 0.567 ppm Se was added, however, the tumor immune responses remained as low as those in Se-deficient mice. This study implies that the prevalence of primary hepatocellular carcinoma in areas where Se is deficient has a profound immunological basis. Se supplementation is obviously indicated for cancer prevention in these areas but the amount of Se supplied is crucial.
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PMID:[Effects of selenium deficiency and supplementation on tumor immune response in mice]. 227 20

Both selenium and calorie restriction are anticarcinogenic in many tumor models, but the mechanisms of action are unknown. This study compared the effects of elevated selenium (Se) intake and calorie restriction on colonic cellular growth. Female weanling rats were divided into four groups: control, 40% calorie restricted, and 4 or 6 mg Se/l H2O as selenate. Control rats and rats given Se consumed the control diet ad libitum. Rats in the 40% calorie-restricted group were pair fed 40% less than the total intake of control rats with a diet designed to provide equal nutrients except calories from carbohydrate. After three weeks, rats were injected with [3H]thymidine (1 muCi/g body wt) and killed one hour later. Se at 4 and 6 mg/l H2O and 40% calorie restriction significantly decreased food intake, weight gain, colon weight, and total colon DNA compared with controls. Total number of cells per crypt was not affected by any treatment, whereas total DNA synthesis was significantly decreased, suggesting that the total number of colonic crypts are reduced by calorie restriction and Se treatment. The rate of cell division was decreased only in rats given 6 mg Se/l H2O. These results indicate that elevated Se intake and caloric restriction decrease colonic mucosal growth by decreasing growth in general, but only very high intakes of Se affect colonic cell turnover.
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PMID:The effect of elevated selenium intake on colonic cellular growth in rats. 230 Apr 97

We have developed a serum-free, hormonally defined medium for maintenance of differentiation of adult type II cells cultured on Engelbreth-Holm-Swarm (EHS) tumor basement membrane gels. This defined medium consists of 1:1 (vol/vol) mixture of Ham's F12 and Dulbecco's modified Eagle's media supplemented with insulin, dibutyryl cyclic AMP, hydrocortisone, epidermal growth factor, selenium, and albumin/linoleic acid complex. Compared to cells cultured on EHS gels in serum-supplemented medium, type II cells cultured on EHS gels in this defined medium showed increased acetate incorporation into total lipids (10-fold) and an increase in the relative percentage of acetate incorporated into phosphatidylcholine (PC) (87.8 +/- 0.4% versus 78.5 +/- 1.0% [mean +/- SE]; P less than 0.01), saturated phosphatidylcholine (SPC) (61.4 +/- 0.5% versus 55.2 +/- 0.9%; P less than 0.01), and phosphatidylglycerol (PG) (5.3 +/- 0.3% versus 0.8 +/- 0.1%; P less than 0.01) and decreased acetate incorporation into neutral lipids (9.7 +/- 0.8% versus 62.6 +/- 1.9%; P less than 0.01). No response to this defined medium was seen when type II cells were cultured on tissue culture plastic. Type II cells cultured on EHS gels in serum-supplemented medium for 4 d had numerous neutral lipid droplets in their cytoplasm. In contrast, neutral lipid droplets were not commonly observed within the cytoplasm of the cells cultured in serum-free, hormonally defined medium on EHS gels. This morphologic finding was consistent with the result that cells cultured in serum-supplemented medium significantly increased the relative percentage of acetate incorporated into neutral lipids. These data indicate that adult type II cells cultured on a reconstituted basement membrane (EHS gels) can be maintained in synthetic culture medium without serum. These culture conditions permit the expression of a pattern of differentiated phospholipid biosynthesis and cell morphology more similar to normal type II cell differentiation.
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PMID:Improved maintenance of adult rat alveolar type II cell differentiation in vitro: effect of serum-free, hormonally defined medium and a reconstituted basement membrane. 236 35

The effect of selenium intake on the development of pancreatic cancer was investigated in female Syrian golden hamsters. Four-week-old hamsters were divided into 2 groups according to the selenium level in their drinking water and were fed a purified diet containing less than 0.05 ppm selenium. Starting 4 weeks later, groups received 10 s.c. injections at weekly intervals of N'-nitrosobis(2-oxopropyl)amine (BOP) dissolved in saline, while controls received saline alone. When the animals were killed 18 weeks after the last injection, palpable tumors were less frequent in the high-selenium group than in animals receiving low-selenium supplement, the numbers of histologically diagnosed cancerous lesions also being significantly reduced by high selenium intake. The selenium level and glutathione peroxidase activity in serum and pancreas were significantly greater in the high-selenium group. Moreover, selenium levels and glutathione peroxidase activity were both significantly higher in tumor-bearing tissue. The results suggest that glutathione peroxidase is involved as an intermediate factor in prevention of carcinogenesis by selenium.
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PMID:Inhibitory effect of selenium on hamster pancreatic cancer induction by N'-nitrosobis(2-oxopropyl)amine. 236 2

The state of the thiol-dependent systems i.e. concentration of the SH-groups, activity of glutathione reductase and glutathione-S-transferase, carminomycin antitumor and toxic effects was studied under conditions of tumor growth and carminomycin therapy with the use of prophylactic rations (PR) aimed at stimulating the cell thiol-dependent and antioxidant systems for decreasing the drug toxic action. It was shown that addition of sulfur-containing amino acids, selenium and vitamin E to the ration of healthy and tumor-bearing rats (Walker carcinosarcoma 256) induced a decrease in the level of the SH-groups in the liver just likely promoting efficient extrahepatic usage of glutathione. After administration of carminomycin a long with the PR use, the liver showed the thiol-preserving capacity evidenced by a decrease or complete elimination of the above effect of the ration. The use of PR resulted in a marked increase in the glutathione-S-transferase activity in cytosol and to a lesser extent in the liver microsomes. A regulating effect of the PR on the activity of glutathione reductase was observed: its inhibition in the healthy animals and stimulation after carminomycin administration in the heart of the healthy animals and the liver of the tumor-bearing animals.
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PMID:[Thiol-dependent protective systems in alimentary prevention of the toxic effect of carminomycin]. 238 44


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