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Batch effects and pathway analysis: two potential perils in cancer studies involving DNA methylation array analysis.
Harper, KN, Peters, BA, Gamble, MV
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2013;(6):1052-60
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Abstract
BACKGROUND DNA methylation microarrays have become an increasingly popular means of studying the role of epigenetics in cancer, although the methods used to analyze these arrays are still being developed and existing methods are not always widely disseminated among microarray users. METHODS We investigated two problems likely to confront DNA methylation microarray users: (i) batch effects and (ii) the use of widely available pathway analysis software to analyze results. First, DNA taken from individuals exposed to low and high levels of drinking water arsenic were plated twice on Illumina's Infinium 450 K HumanMethylation Array, once in order of exposure and again following randomization. Second, we conducted simulations in which random CpG sites were drawn from the 450 K array and subjected to pathway analysis using Ingenuity's IPA software. RESULTS The majority of differentially methylated CpG sites identified in Run One were due to batch effects; few sites were also identified in Run Two. In addition, the pathway analysis software reported many significant associations between our data, randomly drawn from the 450 K array, and various diseases and biological functions. CONCLUSIONS These analyses illustrate the pitfalls of not properly controlling for chip-specific batch effects as well as using pathway analysis software created for gene expression arrays to analyze DNA methylation array data. IMPACT We present evidence that (i) chip-specific effects can simulate plausible differential methylation results and (ii) popular pathway analysis software developed for expression arrays can yield spurious results when used in tandem with methylation microarrays.
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Smoking and chronic rhinitis: effects of nasal irrigations with sulfurous-arsenical-ferruginous thermal water: A prospective, randomized, double-blind study.
Ottaviano, G, Marioni, G, Giacomelli, L, La Torre, FB, Staffieri, C, Marchese-Ragona, R, Staffieri, A
American journal of otolaryngology. 2012;(6):657-62
Abstract
PURPOSE Smoking is a self-destructive behavior that is known to induce remodeling of the lower airways, leading to squamous metaplasia, but little is known about its effects on the nose and paranasal sinuses. Nasal irrigations are often mentioned as measures for treating sinonasal inflammations. The purpose of our study was to compare the effects of nasal irrigations with sulfurous-arsenical-ferruginous thermal water or isotonic sodium chloride solution in smokers with nonallergic chronic rhinosinusitis, based on clinical and olfactory evidence. MATERIALS AND METHODS The present study was a prospective, randomized, double-blind study performed in a tertiary academic referral center. Seventy smokers with nonallergic chronic rhinitis were enrolled. Nasal endoscopy, rhinomanometry, nasal cytology, and odor threshold measurements were performed in subjects randomized to daily nasal irrigations with either thermal water or isotonic sodium chloride solution for 1 month. RESULTS Immediately after the treatment, the thermal water irrigations revealed a positive pharmacologic action, judging from a tendency toward lower nasal resistances (P = .07) and larger numbers of ciliated cells in the patients treated (P = .003). Endoscopic findings in the thermal water group were still better than in the control group a further 2 months later (P = .03). CONCLUSIONS Our results indicate that nasal irrigations with thermal water had a good effect on endoscopic objective signs, nasal resistances, and epithelial trophism.
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Comparison of two adsorbents for the removal of pentavalent arsenic from aqueous solutions.
Li, Q, Xu, X, Cui, H, Pang, J, Wei, Z, Sun, Z, Zhai, J
Journal of environmental management. 2012;:98-106
Abstract
Two adsorbents, magnesia-loaded fly ash cenospheres (MGLC) and manganese-loaded fly ash cenospheres (MNLC), were prepared by wet impregnation of fly ash cenospheres with MgCl(2) solution or a mixed solution of MnCl(2) and KMnO(4), respectively. Their physicochemical properties were characterized by scanning electron microscopy, X-ray diffractometry, X-ray fluorescence spectrometry, and Fourier transform infrared spectrometry. Sorption experiments were conducted to examine the effects of adsorbent dosage, pH, time, temperature, ionic strength and competing anions on As(V) removal by MGLC and MNLC. Both MGLC and MNLC had greater pH buffering capacity and were less affected by changes in ionic strength. Competing anions (carbonate and dihydric phosphate) had a larger impact on As(V) removal by MNLC than by MGLC. Adsorption on MNLC reached equilibrium at 60 min, while adsorption on MGLC reached equilibrium at 120 min. The Langmuir adsorption isotherm was a good fit for the experimental data of As(V) adsorption on MGLC and MNLC, and the adsorption kinetics for both followed the pseudo-second-order rate equation. MGLC and MNLC had a larger removal capacity for As(V) than the cenospheres. Compared with MNLC, MGLC is a better absorbent.
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Comparison of gene expression profiles in HepG2 cells exposed to arsenic, cadmium, nickel, and three model carcinogens for investigating the mechanisms of metal carcinogenesis.
Kawata, K, Shimazaki, R, Okabe, S
Environmental and molecular mutagenesis. 2009;(1):46-59
Abstract
Carcinogenesis is an important chronic toxicity of metals and metalloids, although their mechanisms of action are still unclear. Comparison of gene expression patterns induced by carcinogenic metals, metalloids, and model carcinogens would give an insight into understanding of their carcinogenic mechanisms. In this study, we examined the gene expression alteration in human hepatoma cell line, HepG2, after exposing to two metals (cadmium and nickel), a metalloid (arsenic), and three model carcinogenic chemicals N-dimethylnitrosoamine (DMN), 12-O-tetradecanoylphorbol-13-acetate (TPA), and tetrachloroethylene (TCE) using DNA microarrays with 8,795 human genes. Of the genes altered by As, Cd, and Ni exposures, 31-55% were overlapped with those altered by three model carcinogenic chemical exposures in our experiments. In particular, the metals and metalloid shared certain characteristics with TPA and TCE in remarkable upregulations of the genes associated with progression of cell cycle, which might play a central role in As, Cd, and Ni carcinogenesis. This characteristic of gene expression alteration was partially counteracted by intracellular accumulation of vitamin C in As-exposed cells, whereas the number of cell-cycle associated genes was increased in Cd- and Ni-exposed cells. In our experimental conditions, ROS might have an accelerative effect on the cell proliferation mechanisms of As, but have an inhibitory effect on those of other two heavy metals. Furthermore, based on the results of Q-PCR, the oncogene PTTG1, which was upregulated by all carcinogenic chemical exposures in the array experiments, might be a useful biomarker for evaluation of the carcinogenesis of inorganic carcinogens.