Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ultraviolet (UV) irradiation of C3H/HeN mice induces skin cancer and an immunosuppression that prevents the host from rejecting antigenic UV-induced tumors. The capacity of topical vitamin E (dl-alpha-tocopherol) to prevent photocarcinogenesis or the immunosuppression induced by UV irradiation were assessed. Skin cancer incidence in UV-irradiated mice was 81% at 33 weeks after the first UV exposure; application to mice of 25 mg vitamin E three times per week for three weeks before UV irradiation, and throughout the experiment, reduced this incidence to 42% (p = 0.0065, log rank test). Immunoenhancement by vitamin E was assessed by comparing levels of immunosuppression by splenocytes from normal or UV-irradiated mice, with and without topical vitamin E treatment. Transfer of splenocytes from UV-irradiated mice to naive mice prevented the recipients from rejecting a UV-induced tumor challenge, whereas splenocytes from UV-irradiated mice treated with vitamin E did not prevent recipients from rejecting a similar tumor challenge. Phenotypic analysis of splenocytes used in the passive transfer assay, conducted with a biotin-avidin-immunoperoxidase technique, revealed that vitamin E treatment of mice undergoing UV irradiation prevented the UV-induced down regulation of Ia expression in splenocytes and increased the proportion of Lyt-2+ and L3T4+ splenocytes. Therefore, chronically applied vitamin E can effectively reduce cancer formation and immunosuppression induced by UV irradiation. Prevention of UV-induced down regulation of Ia expression may have contributed to this immunomodulation.
 ...
PMID:Topical vitamin E inhibition of immunosuppression and tumorigenesis induced by ultraviolet irradiation. 203 69

Human breast carcinoma cell lines MCF-7 and MDA-MB231 were transplanted s.c. to female athymic nude mice at 3-4 weeks of age. At 7-10 days after transplantation, the mice were divided into groups and fed for 6-8 weeks one of the following semi-purified diets containing different amounts and types of fat, i.e. 5% corn oil, 20% corn oil, 20% butter, 19% beef tallow/1% corn oil and 19% fish (Menhaden) oil/1% corn oil. In addition experiments, the fish oil diets were supplemented with antioxidants (vitamin E, 8 g or 2000 IU/kg diet plus tertiary butyl hydroquinone, TBHQ, 4 g/kg diet) or ferric citrate (3 g/kg diet). Tumor peroxidation product levels were assessed by measuring 2-thiobarbituric acid reactants (TBA assay). At the termination of the studies (6-8 weeks of diet feeding) mean human breast carcinoma volume (MCF-7 and MDA-MB231) was the largest in mice fed the 20% corn oil diet, intermediate in mice fed the butter or beef tallow diets and the least in mice fed the fish oil diet. The difference in mean tumor volumes among mice fed the 20% corn oil diet and those fed the fish oil diet was significant (P less than 0.01). When comparing low (5% corn oil) and high (20% corn oil) fat diets, numerical increases in human breast carcinoma volume (MCF-7 and MDA-MB231) were consistently observed in the high-fat diet groups but these differences were not always significant. Tumor lipid peroxidation product levels were determined on the MDA-MB231 tumors; tumor lipid peroxidation levels were significantly (P less than 0.01) increased only in mice fed the fish oil diets. Supplementation of the fish oil diets with antioxidants (vitamin E + TBHQ) significantly reduced the level of tumor peroxidation products and significantly increased tumor volume (P less than 0.05). When tumor lipid peroxidation product levels in the fish oil plus antioxidant fed mice were reduced to the level of that observed in the tumors of the corn oil fed mice, no significant differences in tumor volumes were observed in these two groups. In contrast, supplementation of the fish oil diets with ferric citrate, significantly (P less than 0.05) increased tumor lipid peroxidation product levels and decreased tumor volume. Thus, the type of dietary fat can clearly affect the growth of human breast carcinomas (MCF-7 and MDA-MB231) maintained in athymic nude mice.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effect of dietary fat on growth of MCF-7 and MDA-MB231 human breast carcinomas in athymic nude mice: relationship between carcinoma growth and lipid peroxidation product levels. 207 Apr 88

alpha-Tocopherol, a superior chain-breaking, peroxyl radical-trapping antioxidant and the most active component of vitamin E, is elevated in liver tumor cells, contributing to their greater resistance towards lipid peroxidation compared to cells from normal tissues. Also, in regenerating rat liver the level of vitamin E has been found to fluctuate in phase with the rate of cell division. In order to study the biokinetics and mechanisms of the distribution of vitamin E in organs and within tissues of animals, deuterated forms of alpha-tocopherol have been synthesized and their uptake into blood and tissues has been measured by gas chromatography-mass spectrometry. Measurement of the competitive uptake from a mixture of the RRR- and SRR-alpha-tocopherol stereoisomers labelled with different amounts of deuterium shows that the liver exerts a strong preference for secretion of the natural (RRR) stereoisomer into the plasma. It is suggested that a tocopherol-binding protein plays a key role in this process.
 ...
PMID:Application of deuterated alpha-tocopherols to the biokinetics and bioavailability of vitamin E. 207 52

Thrombotic thrombocytopenic purpura (TTP) is a syndrome that occurs mainly in adults with multiorgan microvascular thrombosis consisting of thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, renal involvement, and fever. The female to male ratio is 3:2, and peak incidence occurs in the 3rd decade of life. Clinical signs are the consequence of hyaline thrombosis and occlusion of capillaries and arterioles. Renal ailment manifests itself in hematuria and proteinuria with azotemia and even overt renal failure. In severe disease, azotemia is typical of hemolytic uremic syndrome (HUS). TTP was first described in 1925 by Moschcowitz. The clinical picture of TTP consists of a prodromal phase, a viruslike disease occurring in up to 40% of patients. 60% have neurologic disturbances, 90% have purpura initially, and fever occurs in all. Anemia is often severe with hemoglobin values of 7-9 gm/dl, renal involvement in 90%, and renal failure in 40-80% of patients. Clinical variants include the acute and fulminant variety mortality, the chronic form, and the relapsing form. Predisposing factors and triggering agents are autosomal recessive inherited traits in acute idiopathic TTP, systemic diseases, tumor antigens, pregnancy and puerperium, viruses (endotoxins for HUS), and possibly oral contraceptives and hypertension. Therapy includes corticosteroids (prednisone 100-400 mg/day); heparin for postpartum HUS; and antiplatelet agents (Dextran 70, aspirin, and dipyridamole in high doses). The infusion of PGI2 is controversial; splenectomy is also questionable; and vincristine, azathioprine, and cyclophosphamide have unproven efficacy. Fresh-frozen plasma exchange is the method of choice as it produces survival in 90%. Others are iv immunoglobulins, vitamin E, and dialysis and renal transplant. Platelet transfusions are contraindicated because of sudden death and decreased survival.
 ...
PMID:Thrombotic thrombocytopenic purpura and related disorders. 210 74

Eighty young adult male Syrian hamsters were divided into four equal groups. Group 1 animals had the right buccal pouches painted with a 0.1% solution of 7,12 dimethylbenz(a)anthracene (DMBA) three times per wk for 28 wk. Group 2 animals were similarly painted with DMBA for 28 wk but were also given 140 micrograms vitamin E in 0.4 ml mineral oil three times weekly on days alternate to DMBA painting. Group 3 animals were used as DMBA-vehicle controls. Group 4 animals were vitamin E controls. Animals were killed after 28 wk, the pouches photographed and tumors counted, measured. The pouches were fixed in formalin, sectioned in paraffin and studied histologically and histochemically for tumor necrosis factors alpha and beta. All animals in Group 1 and 3 had gross tumors of the right buccal pouch. None of the animals in Group 2 had grossly visible tumors. Microscopic studies revealed that, while no gross tumors were seen in the Group 2 animals, there was histologic evidence of dysplasia and early carcinoma-in-situ undergoing degeneration. Immunohistochemical staining revealed a dense infiltrate of mononuclear cells adjacent to tumor sites with a large number of cytotoxic T lymphocytes and macrophages. Vitamin E appears to prevent tumor formation by stimulating a potent immune response to selectively destroy tumor cells as they begin to develop into recognizable microscopic foci of carcinoma.
 ...
PMID:Prevention of experimental cancer and immunostimulation by vitamin E (immunosurveillance). 211 3

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.
 ...
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.
 ...
PMID:Biochemical basis of ozone toxicity. 227 33

Vitamin E succinate inhibited proliferation of C4#1 cells, an established avian retrovirus [reticuloendotheliosis virus (REV)]-transformed immature lymphoid tumor cell line, in a dose-dependent manner. The cytostatic effects of vitamin E succinate were reversible in that treated cells regained their ability to divide after vitamin E succinate removal. Possible mechanism(s) for the antiproliferative actions of vitamin E succinate were investigated. Analyses of C4#1 cell surface membrane antigen profiles and morphology indicated that vitamin E succinate was not inducing differentiation of the tumor cells to a more mature, differentiated, nonproliferative state. Five antioxidants, including a synthetic analogue of vitamin E, Trolox, as well as the active vitamin form, DL-alpha-tocopherol, were incapable of inhibiting C4#1 tumor cell growth, indicating that a mechanism of action other than or in addition to functions as an antioxidant may be operating. Cell cycle analyses suggested that C4#1 tumor cells treated with vitamin E succinate were blocked in the G0G1/early S phases of the cell cycle. Tumor growth arrested by vitamin E succinate did not affect the expression of the REV-encoded oncogene, v-rel, at either the RNA or protein level. These studies demonstrated that vitamin E, in the form of vitamin E succinate, inhibited the growth of retrovirus-transformed tumor cells in vitro and suggested that the antiproliferative effects of vitamin E succinate did not involve antioxidant properties but rather, as yet, unidentified mechanisms leading to cell cycle blockage.
 ...
PMID:Growth-inhibitory effects of vitamin E succinate on retrovirus-transformed tumor cells in vitro. 236 34

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.
 ...
PMID:[Thiol-dependent protective systems in alimentary prevention of the toxic effect of carminomycin]. 238 44

The liver tumor promoters, phenobarbital (20-500 micrograms/ml), lindane (1,2,3,4,5,6-hexachlorocyclohexane, gamma-isomer; 0.1-5.0 micrograms/ml), and DDT (1,1-bis[4-chlorophenyl]-2,2,2-trichloroethane; 0.5-10.0 micrograms/ml), and the hydrogen peroxide-generating enzyme, glucose oxidase (0.01-0.10 units/ml) inhibited gap junctional intercellular communication between B6C3F1 mouse hepatocytes in primary culture. Addition of the antioxidants, superoxide dismutase (100 units/ml), DPPD (N,N'-diphenyl-1,4-phenylenediamine; 25 microM), and vitamin E (DL-alpha-tocopherol acetate; 100 microM), to tumor promoter-treated cultures prevented the inhibition of hepatocyte intercellular communication. DPPD and vitamin E, prevented the inhibition of hepatocyte intercellular communication by glucose oxidase. Superoxide dismutase had no effect on the inhibition of intercellular communication caused by glucose oxidase. These results suggest that activated oxygen species are produced during liver tumor promoter treatment of cultured mouse hepatocytes and are responsible for the inhibition of mouse hepatocyte intercellular communication by the promoters.
 ...
PMID:Antioxidant prevention of tumor promoter induced inhibition of mouse hepatocyte intercellular communication. 243 62


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