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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In many observational studies, a higher intake of individual antioxidants is inversely associated with lung cancer risk. Data from in vitro and animal experiments suggest that there are biochemical interactions among antioxidant nutrients; therefore, consideration of multiple antioxidants simultaneously may be important in terms of risk estimation. The authors constructed a dietary antioxidant index and evaluated its ability to predict lung cancer risk within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. At baseline (1985-1988), 27,111 Finnish male smokers aged 50-69 years completed a dietary questionnaire that assessed usual frequency of consumption and portion sizes for the previous 12 months. A total of 1,787 incident cases of lung cancer were identified during a follow-up period of up to 14.4 years (1985-1999). Principal components analyses were individually applied to the carotenoid, flavonoid, and vitamin E nutrient groups, and summation of retained principal component scores, plus selenium and vitamin C, yielded the composite antioxidant index. In multivariate proportional hazards models, the relative risks for lung cancer according to increasing quintiles of the antioxidant index were 1.00 (referent), 1.00 (95% confidence interval (CI): 0.87, 1.14), 0.91 (95% CI: 0.79, 1.05), 0.79 (95% CI: 0.68, 0.92), and 0.84 (95% CI: 0.72, 0.98) (p for trend = 0.002). These findings support the hypothesis that a combination of dietary antioxidants reduces lung cancer risk in male smokers.
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PMID:Development of a comprehensive dietary antioxidant index and application to lung cancer risk in a cohort of male smokers. 1522 19

Alpha-tocopheryl succinate (TOS), a vitamin E analog, is a promising anticancer agent due to its abilities to inhibit proliferation and to induce apoptosis in a variety of human malignant cell lines, while being relatively less active toward normal cells. However, the molecular mechanisms underlying the apoptotic effects of TOS are not precisely understood. Reports that TOS can generate reactive oxygen species (ROS) prompted us to investigate the role of ROS in TOS-induced apoptosis in cancer cells. We found that the human lung cancer A549 and H460 cell lines were much more sensitive to TOS-induced apoptosis than the human glioblastoma T98G and U87MG cell lines. Our data suggested that the differential TOS sensitivity was not caused by differences in the uptake and retention of TOS between TOS-sensitive and -resistant cancer cells. The differential ability of cancer cells to generate ROS in response to TOS appears to be an important factor in determining the susceptibility of cells to TOS-induced apoptosis. Our results further suggest that TOS-induced generation of ROS is involved in caspase-independent apoptosis. Taken together, our findings suggest an important role of ROS generation in TOS-induced, caspase-independent apoptosis of cancer cells.
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PMID:Role of reactive oxygen species in the induction of apoptosis by alpha-tocopheryl succinate. 1538 62

In the present study, we examined whether the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in leukocyte DNA is higher in lung cancer patients compared to controls. Factors that may influence oxidative stress, such as antioxidant vitamins, were also determined. These parameters were analyzed in 4 groups of subjects: smokers with lung cancer, ex-smokers with lung cancer, healthy smokers with comparable smoking status and healthy nonsmokers. The 8-oxodGuo mean level in leukocytes of lung cancer patients reached values of 9.22/10(6) dGuo molecules (smokers) and 11.16/10(6) dGuo molecules (ex-smokers). These values were significantly higher than in DNA of healthy smokers and nonsmokers, where mean levels reached 6.99/10(6) dGuo molecules and 5.98/10(6) dGuo molecules, respectively. Mean levels of vitamin C in the plasma of controls and lung cancer patients were 56.17 microM (nonsmokers), 26.34 microM (healthy smokers), 23.83 microM (cancer patients, smokers) and 29.19 microM (cancer patients, ex-smokers). The difference between nonsmokers and the 3 other groups was statistically significant. Vitamin E level was significantly reduced in the plasma of cancer patients (smokers 19.94 microM, ex-smokers 19.59 microM) compared to healthy smokers (28.93 microM). No changes in vitamin A concentration were found. Our results suggest that a high level of 8-oxodGuo in leukocyte DNA and a low concentration of vitamin E in the blood may predict lung cancer risk. However, it is also possible that these phenomena may simply result from disease development.
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PMID:Oxidative DNA damage and antioxidant vitamin level: comparison among lung cancer patients, healthy smokers and nonsmokers. 1552 86

Previous evidence suggests that malignant tumours cause an decrease in the serum vitamin E level. We followed the serum alpha tocopherol in 55 lung cancer patients. The objective of the study was to evaluate the effects of treatments of lung cancer on serum vitamin E evolution. The vitamin E of patients symptomatically treated decreases from the first month and this decrease is significant (p < 0.001) in patients affected by SCLC and in those with NSCLC classified stage III and IV. The reduction of the vitamin E is also noted in the patients treated with chemotherapy (p < 0.001). Vitamin E levels improve gradually to reach standard values in the patients who followed a curative radiotherapy or benefited from the surgical ablation of the tumour. At 4 months after the surgical removal of the tumour, there was an increase in serum vitamin E concentrations and reached the normal values. This data indicates that surgical removal of lung cancer increases serum vitamin E concentrations compared to the baseline values possibly reflecting the relief of oxidative stress caused by malignant tumours.
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PMID:[Effects of treatments on serum vitamin E levels in lung cancer]. 1555 78

The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by the availability of suitable laboratory animal models. Here we report that male Hartley guinea pigs treated with cigarette smoke by inhalation twice a day for 28 days developed preneoplastic lung lesions, including bronchial hyperplasia, dysplasia and squamous metaplasia, analogous to those found in human smokers. The lesions were accompanied by increased expression of proliferating cell nuclear antigen and activation of the serine/threonine kinase Akt in the bronchial epithelium. In contrast, no lung lesions were found in guinea pigs ('sham smoked') that were submitted to identical procedures but without cigarettes. Compared with a diet low in vitamin C (50 p.p.m.) and vitamin E (15 p.p.m.), a diet high in vitamin C (4000 p.p.m.) and vitamin E (40 p.p.m.) significantly increased the incidence of these lesions. The inclusion of 1,4-phenylenebis(methylene)selenocyanate (p-XSC), a synthetic chemopreventive organoselenium compound, in the high vitamin C-high vitamin E diet at a level of 15 p.p.m. as selenium appeared to decrease the lesion incidence. Administration of (-)-epigallocatechin gallate, a powerful green tea polyphenolic antioxidant, at 560 p.p.m. in the drinking water had no effect. As in human smokers, levels of ascorbate in blood plasma, lung, liver and the adrenal glands were significantly decreased by cigarette smoke inhalation. These results identify a relevant in vivo laboratory model of cigarette smoke-induced lung cancer, suggest that p-XSC may have activity as a chemopreventive agent against cigarette smoke-induced lung lesions and provide additional evidence that very high dietary levels of certain antioxidants can have co-carcinogenic activity in cigarette smoke-induced lung cancer.
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PMID:Induction of preneoplastic lung lesions in guinea pigs by cigarette smoke inhalation and their exacerbation by high dietary levels of vitamins C and E. 1557 85

gamma-Tocopherol (gammaT), the predominant form of vitamin E in diets, but not alpha-tocopherol, the major vitamin E form in tissues and supplements, inhibits proliferation of prostate cancer cells (LNCaP and PC-3) and lung cancer cells (A549). In contrast, at similar concentrations, gammaT has no effect on normal prostate epithelial cells. Combinations of some vitamin E forms, such as gammaT and delta-tocopherol, exhibit additive or synergistic inhibitory effects. In this study, gammaT or its combination with delta-tocopherol induced apoptosis in androgen-sensitive prostate LNCaP, but not in androgen-resistant PC-3 cells, by the induction of cytochrome c release, activation of caspase 9 and caspase 3, cleavage of poly-ADP-ribose polymerase (PARP), and involvement of caspase-independent pathways. Myriocin and fumonisin B1, specific inhibitors of key enzymes (serine palmitoyltransferase and dihydroceramide synthase, respectively) in de novo synthesis of sphingolipids, significantly protected cells from gammaT-induced DNA fragmentation, cytochrome c release, PARP cleavage, and the formation of active caspase 3. Compared with vehicle-treated controls, gammaT treatment led to pronounced dihydroceramide and dihydrosphingosine accumulation, which preceded morphological and biochemical manifestations of apoptosis. In contrast, ceramide and shpingosine levels did not increase until day 3, when substantial cell death took place. Our study demonstrates that gammaT and mixed vitamin E forms induce cell death by interrupting the de novo sphingolipid pathway in a prostate cancer cell line. Thus, certain vitamin E forms may be valuable as anticancer agents.
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PMID:gamma-Tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis. 1559 15

Objective of the paper was to review the latest scientific reference data on chemoprevention possibilities of lung cancer. Lung cancer is the leading cause of cancer death in Lithuania. The current lung cancer therapy includes surgery, radiation and chemotherapy. These interventions have not produced declines in mortality rates. This overview argues strongly for new approach for controlling this disease. Chemoprevention is the use of specific natural or synthetic substances with the objective of reversing, suppressing or preventing carcinogenic progression to invasive cancer. Whether primary, secondary or tertiary prevention has the potential to improve the dismal statistics associated with this cancer? Several randomized clinical or translational chemoprevention trials have been conducted. All have so far produced either neutral (using retinal, retinyl palmitate, N-acetyl cysteine or isotretinoin) or harmful (using beta-carotene) primary endpoint results showing that lung cancer was not prevented in smokers. Secondary results supporting treatment with isotretinoin in "never" and former smokers and data from prevention trials involving selenium and vitamin E, however, are encouraging and offer a promising direction for future clinical study.
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PMID:[Chemoprevention possibilities of lung cancer]. 1563 Mar 40

The heavy burden of lung cancer, which includes the highest worldwide mortality of any cancer, and its resistance to standard approaches (smoking cessation, screening, and therapy), have motivated an intense interest in chemoprevention of this disease. Randomized controlled trials of agents (including retinoids, beta-carotene, and vitamin E) to prevent lung cancer have produced only disappointing clinical results to date. New, molecular-targeted approaches are advancing rapidly, however, with many promising targets and interactive signaling pathways for developing novel agents and combinatorial approaches in this setting. This promise is illustrated by recent studies of 15-hydroxyprostaglandin dehydrogenase, which plays a critical role in polyunsaturated fatty acid metabolism and (like another important target, prostacyclin) is downstream of cyclooxygenase-2. 15-hydroxyprostaglandin dehydrogenase degrades prostaglandin E(2), appears to have tumor suppressor activity, and can be induced both by peroxisome proliferator-activated receptor-gamma ligands and an epidermal growth factor receptor inhibitor. Other important targets/pathways include the insulin-like growth factor axis, phosphoinositide 3-kinase pathway, cyclin D and E family members, and epigenetic events. Defining highest lung cancer risk (eg, establishing molecular risk models through long-term analyses of high-risk cohorts) will facilitate the clinical development of molecular-targeted prevention that will potentially reduce the enormous burden of lung cancer.
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PMID:Advances in the biology of lung cancer chemoprevention. 1588 5

The consumption of adequate levels and proper balance of essential nutrients is critical for maintaining health. The identification, isolation, and purification of nutrients in the early 20th century raised the possibility that optimal health outcomes could be realized through nutrient supplementation. Recent attempts using this approach for cardiovascular disease and lung cancer have been disappointing, as demonstrated with vitamin E and beta carotene. Moreover, previously unrecognized risks caused by nutrient toxicity and nutrient interactions have surfaced during intervention studies. The most promising data in the area of nutrition and positive health outcomes relate to dietary patterns, not nutrient supplements. These data suggest that other factors in food or the relative presence of some foods and the absence of other foods are more important than the level of individual nutrients consumed. Finally, unknown are the implications on public health behavior of shifting the emphasis away from food toward nutrient supplements. Notwithstanding the justification for targeting recommendations for nutrient supplements to certain segments of the population (eg, the elderly), there are insufficient data to justify an alteration in public health policy from one that emphasizes food and diet to one that emphasizes nutrient supplements.
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PMID:Essential nutrients: food or supplements? Where should the emphasis be? 1603 Feb 80

Intakes of vitamins A, C and E and folate have been hypothesized to reduce lung cancer risk. We examined these associations in a pooled analysis of the primary data from 8 prospective studies from North America and Europe. Baseline vitamin intake was assessed using a validated food-frequency questionnaire, in each study. We calculated study-specific associations and pooled them using a random-effects model. During follow-up of 430,281 persons over a maximum of 6-16 years in the studies, 3,206 incident lung cancer cases were documented. Vitamin intakes were inversely associated with lung cancer risk in age-adjusted analyses; the associations were greatly attenuated after adjusting for smoking and other risk factors for lung cancer. The pooled multivariate relative risks, comparing the highest vs. lowest quintile of intake from food-only, were 0.96 (95% confidence interval (CI) 0.83-1.11) for vitamin A, 0.80 (95% CI 0.71-0.91) for vitamin C, 0.86 (95% CI 0.76-0.99) for vitamin E and 0.88 (95% CI 0.74-1.04) for folate. The association with vitamin C was not independent of our previously reported inverse association with beta-cryptoxanthin. Further, vitamin intakes from foods plus supplements were not associated with a reduced risk of lung cancer in multivariate analyses, and use of multivitamins and specific vitamin supplements was not significantly associated with lung cancer risk. The results generally did not differ across studies or by sex, smoking habits and lung cancer cell type. In conclusion, these data do not support the hypothesis that intakes of vitamins A, C and E and folate reduce lung cancer risk.
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PMID:Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: a pooled analysis of 8 prospective studies. 1615 26


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