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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study compares the toxic effects of the carotenoids, beta-carotene and canthaxanthin, and alpha-tocopherol (vitamin E) on human tumor cells and their normal counterparts in vitro. Seven different malignant cell lines were examined: oral carcinoma (two cell lines), breast (two cell lines), lung carcinoma (two cell lines), and malignant melanoma. The in vitro cell culture assays showed a consistent morphologic change in the affected tumor cells following treatment with carotenoid or vitamin E. A rounding of the tumor cells and eventual lifting off the tissue culture plate were observed. These changes were apparent after 1 to 5 hours of treatment depending on the tumor cell line. Associated with these observable cellular changes were quantitative reductions in proliferation (3H-thymidine proliferation) and succinic dehydrogenase activity (MTT assay). In addition, there was a noticeable change in protein expression, with an increased expression of a 70-kD protein following treatment with beta-carotene. This protein was associated with tumor cells showing a decrease in proliferation (oral carcinoma, malignant melanoma) but not with normal keratinocytes or melanocytes. These studies substantiate a selective cytotoxic effect on human tumor cell growth by carotenoids and alpha-tocopherol in vitro, and may provide an explanation of the therapeutic activity of these agents and their possible use in the treatment of premalignancy or early oral carcinoma.
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PMID:The selective cytotoxic effect of carotenoids and alpha-tocopherol on human cancer cell lines in vitro. 154 92

The authors conducted a dietary methodology study in 1984 in Finnish men aged 55-69 years in order to validate two dietary assessment instruments being used in the US-Finland Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Trial. Twelve 2-day food records collected from 162 men over a 6-month period, including every day of the week, served as the reference measure. This report focuses on three important questions for investigating diet and disease relations: 1) How many days are necessary to classify "usual" intake? 2) Is there loss as a result of using consecutive days? 3) Which days are necessary for assessment and classification of "usual" diet? A repeated-measures regression model was used to estimate the variance components and the effects of consecutive days, weekday (weekday vs. weekend), and season. Correlations between the averages of different numbers of days of food records and "true" usual intake were examined along with the resulting attenuations in relative risk. Results suggest that 7-14 days are required to adequately classify most individuals into categories of intake for most nutrients and some foods. There appears to be some loss of information from using consecutive days rather than days further apart. Weekday/weekend differences in mean intakes are slight, and the rank ordering of individuals appears to be preserved. A moderate seasonal effect is shown for classification of fruits, but only a slight one is seen for micronutrients and berries. Implications for the design of epidemiologic and validation studies are discussed.
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PMID:Variability in nutrient and food intakes among older middle-aged men. Implications for design of epidemiologic and validation studies using food recording. 223 15

Improved serum-free media were developed for the anchorage-dependent growth of A549 human lung carcinoma and B16 mouse melanoma cell lines in vitro. Type 1 transforming growth factor beta (TGF-beta 1) inhibited the growth of A549 or B16 cells under serum-free conditions or in the presence of 10% serum by 15-33%. In contrast, in the presence of micrograms/ml concentrations of polyunsaturated fatty acids (PUFAs), picomolar concentrations of TGF-beta 1 irreversibly inhibited the serum-free growth of A549 or B16 cells by 90-100%. The PUFAs alone had little effect on cell growth. Cell growth inhibition by TGF-beta 1 was not potentiated by saturated fatty acids, monounsaturated fatty acids, or prostaglandins. Inhibition of A549 or B16 cell growth by TGF-beta 1 in the presence of PUFAs was almost completely reversed by the antioxidant vitamin E, suggesting a role for lipid peroxidation in this process. Inhibition of A549 or B16 cell growth by TGF-beta 1 in the presence of 5% fetal calf serum was also potentiated by PUFAs and partially reversed by antioxidants. The presence of retinoic acid was required for maximal PUFA-dependent growth inhibition of A549 or B16 cells by TGF-beta 1 under some, but not all, conditions. These results suggest that inhibition of carcinoma and melanoma cell growth by TGF-beta 1 is mediated, in large part, by PUFAs.
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PMID:Inhibition of carcinoma and melanoma cell growth by type 1 transforming growth factor beta is dependent on the presence of polyunsaturated fatty acids. 237 Dec 87

We studied the relation of serum vitamin A (retinol), beta-carotene, vitamin E, and selenium to the risk of lung cancer, using serum that had been collected during a large blood-collection study performed in Washington County, Maryland, in 1974. Levels of the nutrients in serum samples from 99 persons who were subsequently found to have lung cancer (in 1975 to 1983) were compared with levels in 196 controls who were matched for age, sex, race, month of blood donation, and smoking history. A strong inverse association between serum beta-carotene and the risk of squamous-cell carcinoma of the lung was observed (relative odds, 4.30; 95 percent confidence limits, 1.38 and 13.41). Mean (+/- SD) levels of vitamin E were lower among the cases than the controls (10.5 +/- 3.2 vs. 11.9 +/- 4.90 mg per liter), when all histologic types of cancer were considered together. In addition, a linear trend in risk was found (P = 0.04), so that persons with serum levels of vitamin E in the lowest quintile had a 2.5 times higher risk of lung cancer than persons with levels in the highest quintile. These data support an association between low levels of serum vitamin E and the risk of any type of lung cancer and between low levels of serum beta-carotene and the risk of squamous-cell carcinoma of the lung.
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PMID:Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer. 377 37

The Alpha-Tocopherol, Beta-Carotene (ATBC) Lung Cancer Prevention Study was a randomized, double-blind, placebo-controlled, 2 x 2 factorial design, primary prevention trial testing the hypothesis that alpha-tocopherol (50 mg/day) and beta-carotene (20 mg/day) supplements reduce the incidence of lung cancer and possibly other cancers. Total and disease-specific mortality and incidence of various diseases and symptoms were monitored for safety. Between 1985 and 1993, 29,133 eligible male smokers aged 50 to 69 years at entry were randomized to receive daily active supplements or placebo capsules for 5 to 8 years (median 6.1 years), accumulating 169,751 follow-up years. This report describes the study design, methods, and protocol as well as the baseline characteristics and capsule compliance of the participants. The ATBC Study is the largest lung cancer chemoprevention trial conducted to date.
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PMID:The alpha-tocopherol, beta-carotene lung cancer prevention study: design, methods, participant characteristics, and compliance. The ATBC Cancer Prevention Study Group. 820 74

Acrolein is a highly reactive unsaturated aldehyde formed endogenously and present in the environment. Acrolein efficiently reduces glutathione-contents and is highly cytotoxic in two lung carcinoma cell lines (A-427 and SK-LU-1) and the glioblastoma cell line A-172. A-427, which has the lowest GSH content of the cell lines, is also more sensitive to growth inhibition and more depleted in GSH after acrolein exposure. A-427 is also highly sensitive to docosahexaenoic acid (22:6 n-3, DHA) and acrolein potentiates the cytotoxic effect of DHA in this cell line, but not in the DHA-resistant cell lines SK-LU-1 and A-172. Surprisingly, the cytotoxic effect of acrolein was partially reversed by vitamin E, selenite and 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen, a Se-glutathione peroxidase mimic) in A-427 cells, but not in SK-LU-1 and A-172 cells. Using the TUNEL assay a strong nuclear fluorescence was observed in DHA-treated A-427 cells, indicating death by apoptosis, whereas acrolein apparently did not induce apoptosis.
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PMID:Acrolein cytotoxicity and glutathione depletion in n-3 fatty acid sensitive- and resistant human tumor cells. 1022 83

High intakes of calcium, potassium, and fluids have been shown to be associated with lowered risk of kidney stones. The authors studied the associations between diet and risk of kidney stones in a cohort of 27,001 Finnish male smokers aged 50-69 years who were initially free of kidney stones. All men participated in the Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Study and completed a validated dietary questionnaire at baseline. After 5 years of follow-up (1985-1988), 329 men had been diagnosed with kidney stones. After data were controlled for possible confounders, the relative risk of kidney stones for men in the highest quartile of magnesium intake was 0.52 (95% confidence interval (CI) 0.32-0.85) as compared with men in the lowest quartile. Intake of fiber was directly associated with risk (relative risk (RR) = 2.06, 95% CI 1.39-3.03). Calcium intake was not associated with the risk of kidney stones. Beer consumption was inversely associated with risk of kidney stones; each bottle of beer consumed per day was estimated to reduce risk by 40% (RR = 0.60, 95% CI 0.47-0.76). In conclusion, the authors observed that magnesium intake and beer consumption were inversely associated and fiber intake was directly associated with risk of kidney stones.
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PMID:Nutrient intake and use of beverages and the risk of kidney stones among male smokers. 1041 64

Previous studies have shown that treatment of tumor cells in vitro with d-alpha-tocopheryl succinate (alpha-TS), a most effective form of vitamin E, alone or in combination with X-irradiation, reduced the growth of these cells more than that produced by individual agents. However, it is unknown whether alpha-TS, alone or in combination with gamma-irradiation, would produce similar effects on normal cells. To study this, we have compared the effects of alpha-TS on three human tumor cell lines, HeLa (cervical carcinoma), OVGI (ovarian carcinoma), and A549 (lung carcinoma), with the effects on three human normal fibroblast lines, GM2149, AG1522, and HF19. Results showed that alpha-TS treatment of HeLa cells for 20 hours caused inhibition of growth in a dose-dependent manner, but normal human fibroblasts treated similarly with alpha-TS did not show such an effect. alpha-TS treatment for 20 hours also decreased mitotic accumulation in all three tumor cell lines but did not produce such an effect in any of the normal fibroblasts. As expected, gamma-irradiation with 1 Gy decreased mitotic accumulation in human tumor cells and normal fibroblasts; however, alpha-TS treatment for 24 hours before, during, and after irradiation for the entire experimental period further decreased mitotic accumulation in human tumor cells but not in normal cells. These data suggest that effects of alpha-TS, alone or in combination with gamma-irradiation, are selective for tumor cells. Therefore, existing fear that antioxidants such as vitamin E may protect cancer cells from free radical damage during radiation therapy is not justified.
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PMID:Vitamin E (d-alpha-tocopheryl succinate) decreases mitotic accumulation in gamma-irradiated human tumor, but not in normal, cells. 1069 74

With the objective of examining the relationship between diet and adenocarcinoma of the lung, a case-control study was carried out in Uruguay. Red meat, total meat and fatty foods were associated with a significant increase in risk (odds ratios (OR) for red meat intake 1.92, 95% CI 1.27-2.90). On the other hand, fruits, tubers and all plant foods displayed significant inverse associations with adenocarcinoma of the lung (OR for total plant foods 0.39, 95% CI 0.26-0.61). Among nutrients, total fat, other fats (saturated fat) and cholesterol were associated with an increased risk of adenocarcinoma of the lung (OR for high consumption of total fat 2.28, 95% CI 1.48-3.54). The risk associated with cholesterol intake was even higher after controlling for total fat, suggesting that both nutrients (fat and cholesterol) have independent effects. Carotenoids and vitamin E displayed significantly protective effects. This effect was markedly attenuated, when these micronutrients were adjusted for total plant intake. Furthermore, red meat, fat, and cholesterol showed attenuation in its effects after adjustment for total plant foods. It could be concluded that tobacco smoking is the strongest risk factor for adenocarcinoma of the lung. Low consumption of plant foods, and in a lesser degree, high consumption of red meat, total fat and cholesterol contribute to a high risk of adenocarcinoma of the lung.
Lung Cancer 2002 Jan
PMID:Diet and adenocarcinoma of the lung: a case-control study in Uruguay. 1175 Jul 12

In this study, we investigated the role of reduced glutathione (GSH) and nuclear factor-kappaB (NFkappaB) in hypoxia-induced apoptosis. Hypoxia caused p53-dependent apoptosis in murine embryonic fibroblasts transfected with Ras and E1A. N-Acetyl-l-cysteine (NAC) but not other antioxidants, such as the vitamin E analog trolox and epigallocatechin-3-gallate, enhanced hypoxia-induced caspase-3 activation and apoptosis. NAC also enhanced hypoxia-induced apoptosis in two human cancer cell lines, MIA PaCa-2 pancreatic cancer cells and A549 lung carcinoma cells. In murine embryonic fibroblasts, all three antioxidants blocked hypoxia-induced reactive oxygen species formation. NAC did not enhance hypoxia-induced cytochrome c release but did enhance poly-(ADP ribose) polymerase cleavage, indicating that NAC acted at a post-mitochondrial level. NAC-mediated enhancement of apoptosis was mimicked by incubating cells with GSH monoester, which increased intracellular GSH similarly to NAC. Hypoxia promoted degradation of an inhibitor of kappaB(IkappaBalpha), NFkappaB-p65 translocation into the nucleus, NFkappaB binding to DNA, and subsequent transactivation of NFkappaB, which increased X chromosome-linked inhibitor of apoptosis protein levels. NAC failed to block degradation by IkappaBalpha and sequestration of the p65 subunit of NFkappaB to the nucleus. However, NAC did abrogate hypoxia-induced NFkappaB binding to DNA, NFkappaB-dependent gene expression, and induction of X chromosome-linked inhibitor of apoptosis protein. In conclusion, NAC enhanced hypoxic apoptosis by a mechanism apparently involving GSH-dependent suppression of NFkappaB transactivation.
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PMID:N-Acetyl-L-cysteine enhances apoptosis through inhibition of nuclear factor-kappaB in hypoxic murine embryonic fibroblasts. 1537 56


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