Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Redox-active iron present at physiological levels in the pulmonary epithelial lining fluid may lead to damage of lung tissue under some circumstances. For example, factors that increase potential for oxidative stress, such as higher intake of heme iron or higher intake of vitamin C in the presence of high intake of iron, might increase the risk of lung cancer, whereas higher intake of the antioxidant zinc might decrease that risk. During 16 yr of follow-up, 34,708 postmenopausal women, aged 55-69 yr at baseline who completed a food-frequency questionnaire for the Iowa Women's Health Study, were followed for 700 incident lung cancers. When subjects were stratified by intake of vitamin C supplements, among women who took vitamin C supplements of >500 mg/day, after adjusting for age, total energy intake, cigarette smoking, alcohol consumption, and dietary zinc or dietary heme iron intake, relative risks across categories of dietary heme iron intake were 1.0, 0.85, 0.93, 1.32, 1.70, and 3.77 (P for trend = 0.05; P for interaction = 0.08), whereas corresponding figures for dietary zinc intake were 1.0, 1.15, 0.71, 0.84, 0.61, and 0.11 (P for trend = 0.12; P for interaction = 0.04). The strength of the associations of heme iron and zinc intake with lung cancer appeared to be stronger with increasing levels of vitamin C supplement intake. Our results suggest that high dietary heme iron intake may increase the risk of lung cancer, whereas high dietary zinc may decrease the risk of lung cancer among postmenopausal women who consume high-dose vitamin C supplements. This finding may be of particular importance to smokers, for whom vitamin C supplementation is a common recommendation.
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PMID:Interaction among heme iron, zinc, and supplemental vitamin C intake on the risk of lung cancer: Iowa Women's Health Study. 1620 44

Ornithine decarboxylase (ODC) is a marker of lung cancer and is a key enzyme in the synthesis of polyamines, which are necessary for the promotion of the growth of malignant cells. This study assesses the dose-dependent effect of N-acetylcysteine (NAC), a chemopreventive agent, in combination with vitamin C (VC) on the activity of ODC in lung carcinoma cell line, NCI-H82. The cells were subjected to supplementation of NAC and VC both individually and in combination at different dosages for 24 h as well as 48 h. The cells were incubated with radiolabeled L-ornithine (14C) after the supplementation of NAC and VC individually as well as in combination. A microprocedure was carried out to estimate the activity of ODC in cells after 24 and 48 h of incubation. The activity which was found to be elevated in control cells was decreased significantly on drug supplementation in dose-dependent fashion. The content of nucleic acids also exhibited similar result and [3H]-thymidine incorporation was also affected by the supplementation.
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PMID:The effect of N-acetylcysteine in combination with vitamin C on the activity of ornithine decarboxylase of lung carcinoma cells--In vitro. 1657 59

Recent epidemiological and risk assessment studies have found a very high risk of lung cancer among chromium(VI)-exposed workers even at permissible levels of exposure. However, mechanistic views on the key genotoxic role of transient Cr(V) intermediates were more consistent with the threshold or highly non-linear (heavy dose) models of genetic damage by intracellular Cr(VI). In this work, we examined the production of mutagenic DNA lesions during metabolism of Cr(VI) by its dominant reducer ascorbate (vitamin C) under conditions promoting increased yield of transient Cr forms. We found that slow reductive activation of Cr(VI) by limited concentrations of ascorbate resulted in a greater yield of DCFH-oxidizing Cr intermediates but these species were unable to cause DNA strand breaks. Cr(VI)-ascorbate reactions generated a high number of Cr-DNA adducts that were responsible for all mutagenic responses detected in Cr(VI)-treated pSP189 shuttle plasmids following their replication in human cells. Mutagenicity of DNA damage resulting from the reactions with increased stability of Cr intermediates was approximately four times lower relative to the conditions lacking detectable Cr(V) formation. Unlike other reactions, slow reduction of Cr(VI) with ascorbate produced Cr-DNA adducts that were more resistant to dissociation by chelators, suggesting multicoordinate binding of Cr(III) to DNA. Overall, our findings do not support the possibility that increased Cr(V) formation at depleted ascorbate levels modeling heavy dose exposures causes higher levels of mutagenic DNA damage.
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PMID:Lower mutagenicity but higher stability of Cr-DNA adducts formed during gradual chromate activation with ascorbate. 1671 65

Tumor growth and abnormal cell survival were shown to be associated with a number of cellular metabolic abnormalities revealed by impaired oral glucose tolerance, depressed lipoprotein lipase activity leading to hypertriglyceridemia, and changes in amino acid profile as evidenced by increased plasma free tryptophan levels in patients with breast, lung, colon, stomach, and other cancers from various origins. The above findings seem to relate to or indicate a shift to non-oxidative metabolic pathways in cancer. In contrast to normal cells, cancer cells may lose the ability to utilize aerobic respiration due to either defective mitochondria or hypoxia within the tumor microenvironments. Glucose was shown to be the major energy source in cancer cells where it utilizes aerobic /anaerobic glycolysis with the resultant lactic acid formation. The role of energetic modulations and use of glycolytic inhibitors on cancer / normal cell survival is not clearly established in the literature. Therefore, the purpose of this study was to evaluate six glycolytic inhibitors namely, sodium ascorbate, oxalic acid, oxaloacetic acid, sodium citrate, fructose diphosphate (FDP) and sodium bicarbonate at microM concentrations on growing A549 (lung cancer) and MRC-5 (normal; human lung fibroblast) cell lines with the objective of determining their influence on cell survival. Exposed and non-exposed cells were tested with phase contrast micro scanning, survival / death and metabolic activity trends through MTT-assays, as well as death end-point determinations by testing re-growth on complete media. Results showed that oxalic acid and oxaloacetic acid both influenced the pH of the medium and resulted in differential massive cell debris within the exposure period. Sodium ascorbate, sodium citrate, sodium bicarbonate and FDP did not cause pH changes; however, they caused detectable cell disfigurement and loss of metabolic activity and survival/ death end points with the resultant death of the A549 cell line. MRC-5 cells were differentially unaffected by exposure to sodium ascorbate, sodium citrate, sodium bicarbonate, and oxaloacxetic acid, underwent complete recovery and remained both attached and healthy for 6 weeks upon subculture when transferred to a new complete medium. Oxalic acid did not show differential modulation with the consequent loss of survival and death of the MRC-5 cell line. These studies show the potential for exploiting cellular metabolic differences in cancer control.
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PMID:Differential modulation of intracellular energetics in A549 and MRC-5 cells. 1748 66

Nutritional theories have been greatly strengthened by the results of the AREDS study, showing efficiency of high doses of beta-carotene, vitamin C and E, and Zinc to prevent severe forms of age-related macular degeneration (AMD). Despite an excellent tolerance of these high doses, some concerns have been expressed about potential side-effects of non nutritional doses. For example, high doses of beta carotene should not be given to smokers because they could activate the occurrence of a lung cancer. Many ophthalmologists replace beta carotene by lutein and zeaxanthin, while efficiency of this association has not been proven. The AREDS study raises many questions but stimulates the research into the prevention of AMD. Future studies should include polyunsaturated fatty acids and lutein and zeaxanthin supplementations as they seem to be among the most promising preventive therapies in AMD.
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PMID:[Vitamins for prevention of age related macular degeneration: efficacy and risk]. 1755 30

101F6 is a candidate tumor suppressor gene harbored on chromosome 3p21.3, a region with frequent and early allele loss and genetic alterations in many human cancers. We previously showed that enforced expression of wild-type 101F6 by adenoviral vector-mediated gene transfer significantly inhibited tumor cell growth in 3p21.3-deficient non-small cell lung cancer (NSCLC) cells in vitro and in vivo. The molecular mechanism of 101F6-mediated tumor suppression is largely unknown. A computer-aided structural and functional model predicts the 101F6 protein to be a member of the cytochrome b561 protein family that is involved in the regeneration of the antioxidant ascorbate. 101F6 protein is expressed in normal lung bronchial epithelial cells and fibroblasts but is lost in most lung cancers. Treatment with 101F6 nanoparticle-mediated gene transfer in combination with a subpharmacologic dose (200-500 micromol/L) of ascorbate synergistically and selectively inhibited lung cancer cell growth in vitro. Systemic injection of 101F6 nanoparticles plus the i.p. injection of ascorbate synergistically inhibited both tumor formation and growth in human NSCLC H322 orthotopic lung cancer mouse models (P<0.001). Furthermore, exogenous expression of 101F6 enhanced intracellular uptake of ascorbate, leading to an accumulation of cytotoxic H(2)O(2) and a synergistic killing of tumor cells through caspase-independent apoptotic and autophagic pathways. The antitumor synergism showed by the combination treatment with systemic administration of 101F6 nanoparticles and ascorbate on lung cancer offers an attractive therapeutic strategy for future clinical trials in cancer prevention and treatment.
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PMID:Tumor suppressor 101F6 and ascorbate synergistically and selectively inhibit non-small cell lung cancer growth by caspase-independent apoptosis and autophagy. 1761 88

The modulatory efficacy of capsaicin on lung mitochondrial enzyme system with reference to mitochondrial lipid peroxidation (LPO), antioxidants, key citric acid cycle enzymes and respiratory chain enzymes during benzo(a)pyrene (B(a)P) induced lung cancer in Swiss albino mice was studied. Elevations in mitochondrial LPO along with decrements in enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), non-enzymic antioxidants (reduced glutathione (GSH), vitamin C, vitamin E and vitamin A), citric acid cycle enzymes (isocitrate dehydrogenase (ICDH), alpha-ketoglutarate dehydrogenase (alpha-KDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH)), and respiratory chain enzymes (NADH dehydrogenase and Cytochrome c oxidase) were observed in B(a)P (50mg/kg body weight) administered animals. CAP (10mg/kg body weight) pretreatment decreased lung mitochondrial LPO and augmented the activities of enzymic, non-enzymic antioxidants, citric acid cycle enzymes and respiratory chain enzymes to near normalcy revealing its chemoprotective function during B(a)P induced lung cancer.
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PMID:Stabilization of pulmonary mitochondrial enzyme system by capsaicin during benzo(a)pyrene induced experimental lung cancer. 1802 35

Chemoprevention has emerged as a very effective preventive measure against carcinogenesis. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on benzo(a)pyrene (B(a)P) induced carcinogenesis. In the present study, the efficacy of quercetin on the level of lipid peroxides, activities of antioxidant enzymes and tumor marker enzymes in B(a)P induced experimental lung carcinogenesis in Swiss albino mice was assessed. In lung cancer bearing animals there was an increase in lung weight, lipid peroxidation and marker enzymes such as aryl hydrocarbon hydroxylase, gamma glutamyl transpeptidase, 5'-nucleotidase, lactate dehydrogenase and adenosine deaminase with subsequent decrease in body weight and antioxidant enzymes-superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, reduced glutathione, vitamin E and vitamin C. Quercetin supplementation (25 mg/kg body weight) attenuated all these alterations, which indicates the anticancer effect that was further confirmed by histopathological analysis. Overall, the above data shows that the anticancer effect of quercetin is more pronounced when used as an chemopreventive agent rather than as a chemotherapeutic agent against B(a)P induced lung carcinogenesis.
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PMID:The effects of quercetin on antioxidant status and tumor markers in the lung and serum of mice treated with benzo(a)pyrene. 1805 10

Lung cancer is the leading cause of cancer deaths worldwide. Epidemiological studies have shown that exposure to cooking oil fumes (COF) is a risk factor for lung cancer. Trans, trans-2,4-decadienal (tt-DDE), a dienaldehyde, is abundant in heated oils and COF. Previously, we found that long-term exposure (45 days) to a sub-lethal dose (1 microM) of tt-DDE significantly increased growth of human bronchial epithelial cells (BEAS-2B). Aims of this study are to understand the mechanism of tt-DDE-induced cell proliferation and possible protective effects of antioxidant, vitamin C and N-acetylcysteine (NAC) in BEAS-2B cells. Utilizing the real-time RT-PCR and Western immunoblotting, we found that p27 mRNA and protein levels were significantly increased by 1 microM tt-DDE treatment. Co-treatment with vitamin C or NAC partially prevented tt-DDE-induced cell proliferation. In addition, the downstream targets of p27, including CDK4, cyclin D1 and phosphorylated-Rb proteins, increased in 1 microM tt-DDE-treated cells and these changes were prevented by NAC co-treatment. Therefore, these results suggest that tt-DDE increased cell proliferation via inhibition of p27 expression, increase in CDK4/cyclin D1 protein accumulation and enhancement of Rb phosphorylation. Increased cell proliferation is considered as the early stages of lung carcinogenesis. Administration of antioxidants may prevent COF-associated lung carcinogenesis.
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PMID:Trans, trans-2,4-decadienal induced cell proliferation via p27 pathway in human bronchial epithelial cells. 1818 74

Vitamin E and beta-carotene affect the immune function and might influence the predisposition of man to infections. To examine whether vitamin E or beta-carotene supplementation affects tuberculosis risk, we analysed data of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC)Study, a randomised controlled trial which examined the effects of vitamin E (50 mg/d) and beta-carotene (20 mg/d) on lung cancer. The trial was conducted in the general community in Finland in 1985-93; the intervention lasted for 6.1 years (median). The ATBC Study cohort consists of 29,023 males aged 50-69 years, smoking at baseline, with no tuberculosis diagnosis prior to randomisation. Vitamin E supplementation had no overall effect on the incidence of tuberculosis (risk ratio (RR) = 1.18; 95% CI 0.87, 1.59) nor had beta-carotene (RR = 1.07; 95% CI 0.80, 1.45). Nevertheless, dietary vitamin C intake significantly modified the vitamin E effect. Among participants who obtained 90 mg/d or more of vitamin Cin foods (n 13,502), vitamin E supplementation increased tuberculosis risk by 72 (95% CI 4, 185)%. This effect was restricted to participants who smoked heavily. Finally, in participants not supplemented with vitamin E, dietary vitamin C had a negative association with tuberculosis risk so that the adjusted risk was 60 (95% CI 16, 81)% lower in the highest intake quartile compared with the lowest. Our finding that vitamin E seemed to transiently increase the risk of tuberculosis in those who smoked heavily and had high dietary vitamin C intake should increase caution towards vitamin E supplementation for improving the immune system.
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PMID:Vitamin E supplementation may transiently increase tuberculosis risk in males who smoke heavily and have high dietary vitamin C intake. 1857 Jun 87


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