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

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

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

Se is an unusual trace element in having its own codon in mRNA that specifies its insertion into selenoproteins as selenocysteine (SeCys), by means of a mechanism requiring a large SeCys-insertion complex. This exacting insertion machinery for selenoprotein production has implications for the Se requirements for cancer prevention. If Se may protect against cancer, an adequate intake of Se is desirable. However, the level of intake in Europe and some parts of the world is not adequate for full expression of protective selenoproteins. The evidence for Se as a cancer preventive agent includes that from geographic, animal, prospective and intervention studies. Newly-published prospective studies on oesophageal, gastric-cardia and lung cancer have reinforced previous evidence, which is particularly strong for prostate cancer. Interventions with Se have shown benefit in reducing the risk of cancer incidence and mortality in all cancers combined, and specifically in liver, prostate, colo-rectal and lung cancers. The effect seems to be strongest in those individuals with the lowest Se status. As the level of Se that appears to be required for optimal effect is higher than that previously understood to be required to maximise the activity of selenoenzymes, the question has been raised as to whether selenoproteins are involved in the anti-cancer process. However, recent evidence showing an association between Se, reduction of DNA damage and oxidative stress together with data showing an effect of selenoprotein genotype on cancer risk implies that selenoproteins are indeed implicated. The likelihood of simultaneous and consecutive effects at different cancer stages still allows an important role for anti-cancer Se metabolites such as methyl selenol formed from gamma-glutamyl-selenomethyl-SeCys and selenomethyl-SeCys, components identified in certain plants and Se-enriched yeast that have anti-cancer effects. There is some evidence that Se may affect not only cancer risk but also progression and metastasis. Current primary and secondary prevention trials of Se are underway in the USA, including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) relating to prostate cancer, although a large European trial is still desirable given the likelihood of a stronger effect in populations of lower Se status.
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PMID:Selenium in cancer prevention: a review of the evidence and mechanism of action. 1631 96

Clinical chemoprevention trials of lung cancer have been somewhat disappointing and the development of highly effective chemopreventive agents is urgently needed. We previously showed that the organoselenium 1,4-phenylenebis(methylene)selenocyanate (p-XSC) is a potent chemopreventive agent in numerous preclinical animal models including a lung tumor model that employs carcinogens found in tobacco smoke. The goal of this study is to define molecular targets that will be highly promising in the design of future chemoprevention trials of non-small cell lung cancer (NSCLC), which is by far the most common type of lung cancer cases. In the present investigation, we showed that p-XSC at several doses (2.5, 5, 10 and 20 microM) including physiological levels (2.5-5.0 microM) of selenium is capable of inhibiting cell growth in a dose-dependent manner and inducing apoptosis in three NSCLC cells (NCI-H460, NCI-1299 and A549). To clarify the mechanism involved at the molecular level, we focused only on NCI-460 cells and examined the effects of p-XSC on markers that are known to be critical in the development of NSCLC. Using western blot analysis, we showed that p-XSC reduced the expression of cyclooxygenase-2 (COX-2) and phospholipase A2 (PLA2); although p-XSC inhibited both Akt and p-Akt but its effect was not significant. Using cDNA microarray approach (3800 genes per array) we found that p-XSC upregulates 22 genes by > or = 2-fold while downregulates 13 genes by < or = 0.5-fold; these altered genes include transcriptional factors, growth factors and those involved in xenobiotic metabolism as well as pro- and anti-apoptotic genes. Expression of selected genes was confirmed by RT-PCR; p-XSC reduced the levels of COX-2, PLA2, NF-kappaB and Cyclin D1 but enhanced the levels of glutathione peroxidase-5. Collectively, the results of this study showed that p-XSC alters several molecular markers in a manner that can account for its inhibitory effect of cell growth and induction of apoptosis; therefore, p-XSC may be considered a promising candidate for clinical chemoprevention of NSCLC.
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PMID:Molecular targets of the chemopreventive agent 1,4-phenylenebis (methylene)-selenocyanate in human non-small cell lung cancer. 1639 72

The relationship between allergies and cancer incidence and the role played by histamine on the immune system and on inhibiting tumor growth have been the subject of study in our group. The influence of histamine dosage on free radicals was investigated in both lung cancer and healthy subjects. Plasmatic selenium levels in the same patients were assayed in order to highlight the role played by free radicals in lung cancer. The role of selenium on the genesis of lung cancer is well known. Thirty-seven male patients with lung adenocarcinoma or squamous carcinoma were tested. The control group included thirty-nine healthy male subjects. The results indicated a significant decrease in histamine plasma levels in subjects with cancer (p=0.0038) compared to the healthy subjects. Smoking significantly reduced the histamine plasma levels in cancer patients (p=0.0044). Such a decrease was not significant in the controls (p=0.063). A significant decrease in selenium plasma levels in the cancer patients (p=0.005) was also observed. The data suggest that histamine and selenium are two factors involved in the pathogenesis of lung cancer, which could be used in protective and therapeutic strategies.
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PMID:Histamine and selenium in lung cancer. 1688 17

We examined the effect of supplementation with four different combinations of vitamins and minerals in the prevention of lung cancer mortality among 29,584 healthy adults from Linxian, China. In accord with a partial factorial design, the participants were randomly assigned to take either a vitamin/mineral combination or a placebo for 5.25 years. The combinations tested in this trial were as follows: factor A, retinol and zinc; factor B, riboflavin and niacin; factor C, ascorbic acid and molybdenum; factor D, beta-carotene, alpha-tocopherol, and selenium. Lung cancer deaths (n = 147) identified during the trial period (1986-1991) and 10 years after the trial ended (1991-2001) were the study outcome. No significant differences in lung cancer death rates were found for any of the four combinations of supplements tested in this study, using log-rank tests (all P values are >0.20) or Cox proportional hazards models adjusted for age, sex, commune, and other treatments. No significant interactions were seen for age, sex, or smoking status. Supplementation with combinations of vitamins and minerals at nutrient-repletion levels for 5.25 years did not reduce lung cancer mortality in this nutrient-inadequate population in Linxian, China.
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PMID:Lung cancer chemoprevention: a randomized, double-blind trial in Linxian, China. 1689 51

Selenium is an essential nutrient, a component of several anti-oxidant enzymes, and a possible factor in cancer risk, including lung cancer. We determined the subtoxic range of selenium concentration (as sodium selenite) required to increase and maintain the expression of anti-oxidant selenoproteins gluthathione peroxidases GPX1 and GPX4 at a constant level in cultures of human lung adenocarcinoma cell lines (H460, H1703 and H1944) and in HPL1D, a non-transformed lung epithelial cell line. Selenium dose-dependently increased GPX1 protein expression 1.8-fold in HPL1D cells and approximately 40-fold in H460 and H1944 cancer cells, with maximum effects at 20-40 nM. GPX4 protein was also increased, but more so in HPL1D (five-fold) than in H460 or H1944 cells (two- to three-fold). GPX1 mRNA showed similar patterns but differences of lesser magnitude. GPX1 protein and activity level was not consistently detectable in H1703 cells, with or without Se supplementation; its mRNA was present but very low. GPX4 protein level was also low in H1703 cells, but was markedly increased by selenium supplementation (48-fold). These results confirm a role for selenium in risk of lung cancer and the independent regulation of GPX1 and GPX4. Characterization of individual tumors with regard to GPX1 and GPX4 levels and regulation might be useful for interpretation of clinical studies on effects of selenium in lung cancer risk.
Lung Cancer 2007 Jan
PMID:Effects of selenium supplementation on expression of glutathione peroxidase isoforms in cultured human lung adenocarcinoma cell lines. 1705 96

Zinc, copper and selenium are important cofactors for several enzymes that play a role in maintaining DNA integrity. However, limited epidemiologic research on these dietary trace metals and lung cancer risk is available. In an ongoing study of 1,676 incident lung cancer cases and 1,676 matched healthy controls, we studied the associations between dietary zinc, copper and selenium and lung cancer risk. Using multiple logistic regression analysis, the odds ratios (OR) and 95% confidence intervals (CI) of lung cancer for all subjects by increasing quartiles of dietary zinc intake were 1.0, 0.80 (0.65-0.99), 0.64 (0.51-0.81), 0.57 (0.42-0.75), respectively (p trend = 0.0004); similar results were found for men. For dietary copper, the ORs and 95% CI for all subjects were 1.0, 0.59 (0.49-0.73), 0.51 (0.41-0.64), 0.34 (0.26-0.45), respectively (p trend < 0.0001); similar reductions in risk and trend were observed by gender. Dietary selenium intake was not associated with risk, except for a significant inverse trend (p = 0.04) in men. Protective trends (p < 0.05) against lung cancer with increased dietary zinc intake were also found for all ages, BMI > 25, current smokers, pack-years < or =30, light drinkers and participants without emphysema. Increased dietary copper intake was associated with protective trends (p < 0.05) across all ages, BMI, smoking and vitamin/mineral supplement categories, pack-years < or =30 and 30.1-51.75 and participants without emphysema. Our results suggest that dietary zinc and copper intakes are associated with reduced risk of lung cancer. Given the known limitations of case-control studies, these findings must be interpreted with caution and warrant further investigation.
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PMID:Dietary zinc, copper and selenium, and risk of lung cancer. 1713 34

Selenium has been associated with anticancer activity by affecting multiple cellular processes. We reasoned that the simultaneous modulation of multiple radioresponse regulators by selenium should increase radiosensitivity if selenium is combined with radiation in cancer therapy. Therefore, we explored the possibility of whether we could obtain an enhancement of radiosensitivity by the combination of selenium and ionizing radiation. We used two human lung cancer cell lines, NCI-H460 and H1299, as well as a human diploid lung fibroblast, WI-38, as the normal cell counterpart. The combined treatment of the cancer cell lines with Seleno-methionine and ionizing radiation resulted in increased cell killing as assessed by clonogenic survival assay whereas it had little effect on the normal diploid WI-38 cells. The increased radiosensitivity in the cancer cells was correlated with the attenuation of the key proteins involved in either cell survival signaling [Akt, EGFR (epidermal growth factor receptor), ErbB2 and Raf1] or DNA damage response (Mre11, Rad50, Nbs1, Ku80, 53BP1 and DNAPK). The attenuation of the proteins by the selenium compound was possibly caused by the effect on transcription and on protein stability since selenium treatment decreased both the RNA transcript and the protein stability of EGFR and DNAPK. By contrast, Seleno-L-methionine had no effect on the protein profile of a normal diploid fibroblast which is consistent with an intact radiosensitivity. These data provide possible clinical applications, as selenium selectively enhanced the radiosensitivity of the tumor cells whereas that of the normal cells was unaffected. Moreover, the selective decrease of cell proliferation signaling in tumor cells but not in normal cells should facilitate the repopulation of normal cells required for healing during radiation therapy. On the whole, the results suggest that the cancer preventive activity of selenium can be combined with ionizing radiation to improve the control of lung cancer.
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PMID:Enhanced lung cancer cell killing by the combination of selenium and ionizing radiation. 1714

Transcriptomics provides the tool for deciphering gene expression networks, and proteomics links these networks to protein products. The third crucial partner is metabolomics, which defines the metabolic network(s) linked to gene expression. NMR and mass spectrometry enable the broad screen analysis of the metabolome and its transformation pathways, transcending classical targeted metabolic studies. These tools were combined to investigate the anticancer mechanisms of different selenium forms in human lung cancer cells. Using 2-D NMR and tandem-MS, we mapped perturbations of 13C labeling patterns in numerous metabolites induced by selenite and selenomethionine. This information was used to interpret selenite-induced changes in gene expression networks. Linking metabolic dysfunctions to altered gene expression profiles provided new insights into the regulatory network underlying the metabolic dysfunctions, enabled the assembly of discrete gene expression events into functional pathways, and revealed protein targets for proteomic analysis.
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PMID:Integrating metabolomics and transcriptomics for probing SE anticancer mechanisms. 1714 97


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