Selenium is a promising cancer chemoprevention agent. A recent randomized controlled chemoprevention trial found that selenomethionine (SeMet) supplementation for 10 months favorably effected a change in esophageal dysplasia grade among participants who started the trial with mild dysplasia. To further explore the role of SeMet in this trial, we compared gene expression profiles by treatment group using Affymetrix HU 133A chips in before/after supplementation paired normal esophageal biopsies from a subset of 29 trial participants, 16 who received SeMet, and 13 who received placebo. Using P < 0.001 as a cutoff, 11 differentially expressed genes were found in the SeMet supplementation group but these genes did not include either known selenoprotein genes or genes previously shown to be modulated by selenium treatment. Because the number of differentially expressed genes (n = 11) was less than expected by chance (n = 18), we concluded that SeMet supplementation had no measurable effect on gene expression in the normal squamous esophagus of these subjects with dysplasia.
"This work demonstrated that expression profiling in animal models may lead to the identification of novel genes involved in human prostate cancer biology. Joshi et al. (2006) compared gene expression profiles using Affymetrix HU 133A chips in before/after supplementation paired normal esophageal biopsies. They found that the number of differentially expressed genes (n=11) was less than expected by chance (n=18). "
[Show abstract][Hide abstract] ABSTRACT: Last decade has witnessed increased interest in studies dealing with molecular markers of health and disease expression of genes. Specific toxicant "signatures" have been detected using genome base technologies such as microarrays. Further toxins have been classified on the basis of these signatures. Knowledge on these signatures has helped in the identification of novel drug candidates. This review discusses the gene expression studies recently made on arsenic, cadmium, mercury, chromium, lead, copper, nickel, manganese, and other essential elements. Toxicogenomics standards and their organizations have also been briefly described. Although this information can not be considered as complete, recent reports from different laboratories on bacteria, fish, laboratory animals and humans have been summarized. It is expected that toxicogenomics data presented in this review will be helpful in planning and excretion of human health risk assessment programs.
Journal of Environmental Biology 02/2008; 29(1):1-14. · 0.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A randomized, double-blinded, placebo-controlled 2 x 2 factorial chemoprevention trial was conducted in Linxian, China to assess the effects of selenomethionine and celecoxib on the natural history of esophageal squamous dysplasia. Results from this study indicated that asymptomatic adults with mild dysplasia were more likely to show an improvement when treated with selenomethionine compared with placebo (P = 0.02). Prompted by this finding, we examined the molecular profiles associated with regression and progression of dysplastic lesions in normal mucosa from 29 individuals, a subset of the Linxian cohort, using the Affymetrix U133A chip. Twenty differentially expressed genes were associated with regression and 129 were associated with progression when we compared the change in gene expression over time. Genes associated with immune response (n = 15), cell cycle (n = 15), metabolism (n = 15), calcium transport or calcium ion activity (n = 10), regulation of transcription (n = 9), signal transduction (n = 7), cytoskeleton and microtubules (n = 5), nucleotide processing and biosynthesis (n = 4), G-coupled signaling (n = 4), and apoptosis (n = 3) were present in the list of 149 genes. Using the Expression Analysis Systematic Explorer pathway analysis program, only the immune response pathway was significantly overrepresented among these 149 genes. Individuals whose lesions regressed seemed to have higher expression of genes associated with immune stimulation, such as antigen presentation, survival of T cells, and T-cell activation (HLA-DRA, HLA-DPA1, HLA-DBQ1, CD58, and FCER1A). In contrast, individuals whose lesions progressed had higher expression of genes involved in immune suppression and inflammation (CNR2, NFATC4, NFRKB, MBP, INHBB, CMKLR1, CRP, ORMS, SERPINA7, and SERPINA1). These data suggest that local and systemic immune responses may influence the natural history of esophageal squamous dysplasia.
Cancer Research 08/2006; 66(13):6851-60. DOI:10.1158/0008-5472.CAN-06-0662 · 9.33 Impact Factor
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