UMLS:C0242379 - FACTA Search

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

Worldwide, there are more than 10 million new cancer cases each year, and cancer is the cause of approximately 12% of all deaths. Given this, a large number of epidemiologic studies have been undertaken to identify potential risk factors for cancer, amongst which the association with trace elements has received considerable attention. Trace elements, such as selenium, zinc, arsenic, cadmium, and nickel, are found naturally in the environment, and human exposure derives from a variety of sources, including air, drinking water, and food. Trace elements are of particular interest given that the levels of exposure to them are potentially modifiable. In this review, we focus largely on the association between each of the trace elements noted above and risk of cancers of the lung, breast, colorectum, prostate, urinary bladder, and stomach. Overall, the evidence currently available appears to support an inverse association between selenium exposure and prostate cancer risk, and possibly also a reduction in risk with respect to lung cancer, although additional prospective studies are needed. There is also limited evidence for an inverse association between zinc and breast cancer, and again, prospective studies are needed to confirm this. Most studies have reported no association between selenium and risk of breast, colorectal, and stomach cancer, and between zinc and prostate cancer risk. There is compelling evidence in support of positive associations between arsenic and risk of both lung and bladder cancers, and between cadmium and lung cancer risk.
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PMID:Trace elements and cancer risk: a review of the epidemiologic evidence. 1718 19

Expression of cyclooxygenase-2 (COX-2) is associated with the pathogenesis of inflammation and various cancers, including lung cancer. Yin Yang 1 (YY1) is a zinc-finger transcription factor that interacts with histone acetyltransferases and deacetylases for its transcriptional activity and also is involved in inflammation and tumorigenesis. We investigated whether YY1 regulates COX-2 expression. We located a possible YY1 binding site proximal to the transcription initiation site of the COX-2 promoter. Electrophoretic mobility shift assays show that YY1 bound to the putative YY1 site in vitro. To show biological relevance, we performed chromatin immunoprecipitation assays showing that lipopolysaccharide (LPS) treatment induced YY1 binding to the cognate site in the endogenous COX-2 promoter. Overexpression of YY1 in macrophages treated with either LPS or live Pseudomonas aeruginosa increased COX-2 transcriptional activity. Furthermore, YY1 enhanced COX-2 protein expression and prostaglandin D(2) production elicited by LPS treatment. Mechanistically, we observed that LPS treatment resulted in disruption of an interaction between YY1 and p300, a histone acetyltransferase, but did not affect the interaction between YY1 and histone deacetylase 1/2. These data suggest that in response to LPS, YY1 dissociates from p300 and binds to the COX-2 promoter, contributing to COX-2 expression in an inflammatory milieu.
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PMID:Yin Yang 1 enhances cyclooxygenase-2 gene expression in macrophages. 1722 Mar 75

Previously, we reported that the paralogous zinc-finger proteins--CTCF and brother of the regulator of imprinted sites (BORIS), directly contribute to transcriptional regulation of NY-ESO-1 in lung cancer cells. To further examine mechanisms that mediate expression of this cancer-testis gene, we performed software-guided analysis of the NY-ESO-1 promoter region, which revealed several potential Sp1-binding motifs. Sequential 5-aza-2'deoxycytidine/depsipeptide FK228 treatment markedly induced BORIS expression and enhanced nuclear translocation of Sp1 in lung cancer cells. Transient transfection assays using promoter-reporter constructs, as well as gel-shift and chromatin immunoprecipitation experiments revealed that NY-ESO-1 promoter activity coincided with occupancy of the proximal Sp1-binding site in lung cancer cells. Mutations within the Sp1 recognition sequence specifically eliminated binding of Sp1 to this motif in vitro, and markedly diminished NY-ESO-1 promoter activity in vivo. siRNA-mediated inhibition of Sp1 expression decreased NY-ESO-1 promoter activity, whereas knock down of CTCF expression augmented NY-ESO-1 transcription in lung cancer cells. Co-immunoprecipitation experiments indicated that Sp1 physically interacts with BORIS but not with CTCF in vivo. Collectively, these findings suggest that BORIS recruits Sp1 to mediate de-repression of NY-ESO-1 during pulmonary carcinogenesis.
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PMID:Dynamic transcriptional regulatory complexes including BORIS, CTCF and Sp1 modulate NY-ESO-1 expression in lung cancer cells. 1726 18

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

Vitamin A deficiency has been commonly observed in patients with tuberculosis. Low serum retinol levels return to normal after antituberculosis treatment even when no supplements are provided. The deficiency of vitamin A observed in patients with tuberculosis might have contributed to the development of tuberculous disease in them. Alternatively, deficiency could be the result of loss of appetite, poor intestinal absorption, increased urinary loss of vitamin A or acute phase reaction in TB. Vitamin A deficiency lowers immunity while vitamin A supplementation reduces morbidity and mortality, particularly from measles and diarrhoea. Vitamin A supplementation also decreases the mortality rate in HIV-infected children and delays the progression of HIV disease in infected subjects. A higher incidence of lung cancer and increased mortality have been observed in smokers after beta-carotene supplementation. Zinc deficiency is also common in tuberculosis, which may impose a secondary vitamin A deficiency. Clinical trials have shown conflicting results regarding the effect of supplementation of vitamin A, alone or with other micronutrients, on time taken to sputum conversion in patients with pulmonary tuberculosis. Supplementation with multiple micronutrients (including zinc) rather than vitamin A alone may be more beneficial in patients with tuberculosis, but clinical trials on such a combination are lacking.
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PMID:Role of vitamin A supplementation in the treatment of tuberculosis. 1755 17

The binding of a series of benzoxazole analogs with different amide- and ester-linked side chains to duplex DNA in the absence and presence of divalent metal cations is examined. All ligands were found to form complexes with Ni2+, Cu2+, and Zn2+, with 2:1 ligand/metal cation binding stoichiometries dominating for ligands containing shorter side chains (2, 6, 7, and 8), while 1:1 complexes were the most abundant for ligands with long side chains (9, 10, and 11). Ligand binding with duplex DNA in the absence of metal cations was assessed, and the long side-chain ligands were found to form low abundance complexes with 1:1 ligand/DNA binding stoichiometries. The ligands with the shorter side chains only formed DNA complexes in the presence of metal cations, most notably for 7 and 8 binding to DNA in the presence of Cu2+. The binding of long side-chain ligands was enhanced by Cu2+ and to a lesser degree by Ni2+ and Zn2+. The cytotoxicities of all of the ligands against the A549 lung cancer and MCF7 breast cancer cell lines were also examined. The ligands exhibiting the most dramatic metal-enhanced DNA binding also demonstrated the greatest cytotoxic activity. Both 7 and 8 were found to be the most cytotoxic against the A549 lung cancer cell line and 8 demonstrated moderate cytotoxicity against MCF7 breast cancer cells. Metal ions also enhanced the DNA binding of the ligands with the long side chains, especially for 9, which also exhibited the highest level of cytotoxicity of the long side-chain compounds.
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PMID:Evaluation of metal-mediated DNA binding of benzoxazole ligands by electrospray ionization mass spectrometry. 1758 29

Discovered in the early 1800s, the use of cadmium and various cadmium salts started to become industrially important near the close of the 19th century, rapidly thereafter began to flourish, yet has diminished more recently. Most cadmium used in the United States is a byproduct from the smelting of zinc, lead, or copper ores, and is used to manufacture batteries. Carcinogenic activity of cadmium was discovered first in animals and only subsequently in humans. Cadmium and cadmium compounds have been classified as known human carcinogens by the International Agency for Research on Cancer and the National Toxicology Program based on epidemiologic studies showing a causal association with lung cancer, and possibly prostate cancer, and studies in experimental animals, demonstrating that cadmium causes tumors at multiple tissue sites, by various routes of exposure, and in several species and strains. Epidemiologic studies published since these evaluations suggest that cadmium is also associated with cancers of the breast, kidney, pancreas, and urinary bladder. The basic metal cationic portion of cadmium is responsible for both toxic and carcinogenic activity, and the mechanism of carcinogenicity appears to be multifactorial. Available information about the carcinogenicity of cadmium and cadmium compounds is reviewed, evaluated, and discussed.
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PMID:Cadmium-induced cancers in animals and in humans. 1771 78

UK-1 is a bis(benzoxazole) natural product displaying activity against a wide range of human cancer cell lines. A simplified analog of UK-1, 4-carbomethoxy-2-(2'-hydroxyphenyl)benzoxazole, was previously found to be almost as active as UK-1 against cancer cell lines, and similar to the natural product, formed complexes with a variety of metal ions such as Mg2+ and Zn2+. A series of 4-substituted-2-(2'-hydroxyphenyl)benzoxazole analogs of this 'minimal pharmacophore' of UK-1 were prepared. The anti-cancer activity of these analogs was examined in breast and lung cancer cell lines. Spectrophotometric titrations in methanol were carried out in order to assess the ability of UK-1 and these analogs to coordinate with Mg2+ and Cu2+ ions. Although none of the new analogs were more cytotoxic than 4-carbomethoxy-2-(2'-hydroxyphenyl)benzoxazole, some analogs were identified that display similar cytotoxicity to this simplified UK-1 analog with improved water solubility. UK-1 and all of these new analogs bind Cu2+ ions better than Mg2+ ions, and the nature of the 4-substituent is important for the Mg2+ ion binding ability of these 2-(2'-hydroxyphenyl)benzoxazoles. Previous studies of a limited number of UK-1 analogs demonstrated a correlation between Mg2+ ion binding ability and cytotoxicity; however, within this series of 4-substituted-2-(2'-hydroxyphenyl)benzoxazoles the variations in cytotoxicity do not correlate with either Mg2+ or Cu2+ ion binding ability. These results, together with recent ESI-MS studies of Cu2+-mediated DNA binding by UK-1 and analogs, indicate that UK-1 and analogs may exert their cytotoxic effects by interaction with Cu2+ or other transition metal ions, rather than Mg2+, and that metal ion-mediated DNA binding, rather than metal ion binding affinity, is important for the cytotoxic effect of these compounds. The potential role of Cu2+ ions in the cytotoxic action of UK-1 is further supported by the observation that UK-1 in the presence of Cu2+ displays enhanced cytotoxicity to MCF-7 and A549 cells when compared to UK-1 alone.
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PMID:Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2'-hydroxyphenyl)benzoxazole analogs of UK-1. 1803 1

In a large case-control study, we previously reported that dietary intakes of zinc (Zn) and copper (Cu), but not selenium (Se), were inversely associated with lung cancer risk. Because Zn, Cu, Se, iron (Fe), and calcium (Ca) are important for maintaining DNA stability, we examined their associations with DNA repair capacity (DRC) measured by the lymphocyte host-cell reactivation assay in 1,139 cases and 1,210 of the controls. Dietary intake was reported in a food frequency questionnaire. In multivariate analyses, compared to those with high dietary Cu + proficient DRC, the odds ratio (95% confidence interval) [OR (95% CI)] for lung cancer for low Cu + suboptimal DRC was 2.54 (1.97-3.27). Similar results were observed for men and women. These effects were more pronounced in older and lean subjects, those with late-stage disease, and those with a family history of cancer in first-degree relatives. Compared to subjects with high Zn + proficient DRC, the OR for lung cancer for low Zn + suboptimal DRC was 1.82 (95% CI, 1.41-2.34), with pronounced effects in men, current smokers, subjects with longer duration of smoking, those with late-stage disease, or those with a family history of cancer. An OR of 1.94 (95% CI, 1.51-2.48) was observed for low Fe + suboptimal DRC compared with high Fe + proficient DRC, and pronounced effects appeared in older, lean subjects, those with longer duration of smoking, are heavier smokers, those with a late-stage disease, and those with a family history of cancer. No significant joint associations were seen for Se or Ca and DRC. Our joint associations between Cu-DRC, Zn-DRC and Fe-DRC and lung cancer risk require confirmation in prospective studies.
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PMID:Joint effects of dietary trace metals and DNA repair capacity in lung cancer risk. 1808 84

The tobacco-specific nitrosamine, 4-(N-methyl-N-nitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), is a potent lung cancer inducer. However, how NNK induces lung cancer is still largely unknown. Haem oxygenase (HO)-1 was evaluated in 30 pairs of lung cancer tumour samples and matched nontumour tissues from patients with a history of cigarette smoking. Expression of HO-1, p21(Cip1/Waf1/Cid1) (p21), B-cell lymphoma (Bcl)-2 family members, mitogen-activated protein kinase and nuclear factor (NF)-kappaB was also studied in lung cancer cells treated with NNK. The levels of HO-1 and p21 were significantly increased in lung tumour tissues. There was a positive relationship between these two proteins in the tumour. NNK stimulated lung cell proliferation and elevated the levels of HO-1, p21, inhibitor of apoptosis protein (c-IAP)2 and Bcl-2, but downregulated Bad. These effects of NNK were blocked by zinc protoporphyrin-XII, an HO-1 inhibitor. The NNK-mediated expression of HO-1 was governed by NF-kappaB and extracellular signal-regulated kinase 1/2, since blocking either of these prevented the stimulatory effect of NNK on HO-1, as well as molecules downstream of HO-1, such as p21, c-IAP2, Bcl-2 and Bad. In conclusion, haem oxygenase-1 plays a central role in NNK-mediated cell proliferation by promoting the expression of p21(Cip1/Waf1/Cid1), inhibitor of apoptosis protein 2 and B-cell lymphoma-2 but inhibiting the activity of Bad. Nuclear factor-kappaB and extracellular signal-regulated kinase 1/2 function upstream of haem oxygenase-1. Therefore, haem oxygenase-1 is likely to be a potential target in the treatment of smoking-related lung cancer.
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PMID:Haem oxygenase-1 plays a central role in NNK-mediated lung carcinogenesis. 1850 27

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