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Pagmantidis V, Méplan C, van Schothorst E, et al. Supplementation of healthy volunteers with nutritionally relevant amounts of selenium increases expression of lymphocyte protein biosynthesis genes. Am J Clin Nutr 2008; 87:181-189. This is the first study to assess the effects of modest Se supplementation (100 μ,g/ day for 6 weeks) on global gene expression in peripheral lymphocytes. Conducted with a cohort of Europeans, the supplementation increased plasma total Se and SepP levels. Consistent changes were found in the expression of 250 genes assessed in lymphocytes; these included upregulation of genes associated with protein synthesis, and may supply novel biomarkers for Se status from a readily accessible tissue pool.
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Pagmantidis V, Méplan C, van Schothorst E, et al. Supplementation of healthy volunteers with nutritionally relevant amounts of selenium increases expression of lymphocyte protein biosynthesis genes. Am J Clin Nutr 2008; 87:181-189. This is the first study to assess the effects of modest Se supplementation (100 μ,g/ day for 6 weeks) on global gene expression in peripheral lymphocytes. Conducted with a cohort of Europeans, the supplementation increased plasma total Se and SepP levels. Consistent changes were found in the expression of 250 genes assessed in lymphocytes; these included upregulation of genes associated with protein synthesis, and may supply novel biomarkers for Se status from a readily accessible tissue pool.
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14
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Ravn-Haren G, Krath B, Overad K, et al. Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolizing enzymes in healthy volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) pilot study. Br J Nutr 2008; 99:1190-1198. This study was among the first to determine the effect of long-term Se supplementation on gene expression in healthy humans. Participants (105) were randomized to 0, 100, 200 or 300 μg Se (as Se yeast) per day for 5 years. Sesupplemented individuals showed downregulation of genes for some phase 2 enzymes and upregulation of aryl hydrocarbon receptor repressor (AhRR) gene expression.
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Ravn-Haren G, Krath B, Overad K, et al. Effect of long-term selenium yeast intervention on activity and gene expression of antioxidant and xenobiotic metabolizing enzymes in healthy volunteers from the Danish Prevention of Cancer by Intervention by Selenium (PRECISE) pilot study. Br J Nutr 2008; 99:1190-1198. This study was among the first to determine the effect of long-term Se supplementation on gene expression in healthy humans. Participants (105) were randomized to 0, 100, 200 or 300 μg Se (as Se yeast) per day for 5 years. Sesupplemented individuals showed downregulation of genes for some phase 2 enzymes and upregulation of aryl hydrocarbon receptor repressor (AhRR) gene expression.
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21
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Rad52 has a role in the repair of sodium selenite-induced DNA damage in Saccharomyces cerevisiae
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This study provides the first evidence that homologous recombination is involved in the process of DNA damage from exposure to high levels of selenite
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Letavayová L, Vlasáková D, Vlčková V, et al. Rad52 has a role in the repair of sodium selenite-induced DNA damage in Saccharomyces cerevisiae. Mutat Res 2008; 652:198-203. This study provides the first evidence that homologous recombination is involved in the process of DNA damage from exposure to high levels of selenite.
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This study showed that SeMet transiently activates Akt by kinase-mediated phosphorylation and subsequently inactivates it in a PTEN-tumor suppressor-dependent fashion resulting in degradation through both caspase and proteosome pathways
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Lee J, Shin S, Kang S, et al. A novel activation-induced suicidal degradation mechanism for Akt by selenium, Int J Mol Med 2008; 21:91-97. This study showed that SeMet transiently activates Akt by kinase-mediated phosphorylation and subsequently inactivates it in a PTEN-tumor suppressor-dependent fashion resulting in degradation through both caspase and proteosome pathways.
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Wang Z, Hu H, Li G, et al. Methylseleninic acid inhibits microvascular endothelial G,cell cycle progression and decreases tumor microvessel density, Int J Cancer 2008; 122:15-24. The report extends previous work by the same group that has indicated a role of Se in impairing tumorigenesis by inhibition of neoangiogenesis. This study demonstrates that effect for a proximal metabolic precursor of the putative anticarcinogenic Se metabolite, methylselenol, showing its efficacy in promoting cell cycle arrest in telemorase-immotalized microvascular endothelial cells, and reducing microvessel density in tumors developing from prostate cancer cell xenografts.
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Wang Z, Hu H, Li G, et al. Methylseleninic acid inhibits microvascular endothelial G,cell cycle progression and decreases tumor microvessel density, Int J Cancer 2008; 122:15-24. The report extends previous work by the same group that has indicated a role of Se in impairing tumorigenesis by inhibition of neoangiogenesis. This study demonstrates that effect for a proximal metabolic precursor of the putative anticarcinogenic Se metabolite, methylselenol, showing its efficacy in promoting cell cycle arrest in telemorase-immotalized microvascular endothelial cells, and reducing microvessel density in tumors developing from prostate cancer cell xenografts.
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25
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55149108503
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Jariwalla R, Gangapurkar B, Nakamura D. Differential sensitivity of various human tumor-derived cell types to apoptosis by organic derivatives of selenium. Br J Nutr 2008 [Epub ahead of print]. This study shows that cell types differ in sensitivity to Se-induced apoptosis. They show that breast carcinoma cells to be very sensitive, showing apoptotic responses to 0.113 μmol Se. Higher levels of Se-MeSeCys and SeMet were required to produce comparable apoptotic effects in hepatoma and neuroblastoma cells, and higher levels were required for colon cancer cells and nonmalignant mammary epithelial cells.
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Jariwalla R, Gangapurkar B, Nakamura D. Differential sensitivity of various human tumor-derived cell types to apoptosis by organic derivatives of selenium. Br J Nutr 2008 [Epub ahead of print]. This study shows that cell types differ in sensitivity to Se-induced apoptosis. They show that breast carcinoma cells to be very sensitive, showing apoptotic responses to 0.113 μmol Se. Higher levels of Se-MeSeCys and SeMet were required to produce comparable apoptotic effects in hepatoma and neuroblastoma cells, and higher levels were required for colon cancer cells and nonmalignant mammary epithelial cells.
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26
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Methylseleninic acid enhances taxane drug efficacy against human prostate cancer and down-regulates antiapoptotic proteins Bcl-XL and Survivin
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This study shows that tumor accumulation of total Se is not correlated with anticarcinogenesis; SeMet supplementation caused up to eight-fold higher Se accumulation than other supplements with no appreciable effect on tumor burden
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Li G, Lee H, Wang Z, et al. Superior in vivo inhibitory efficacy of methylseleninic acid against human prostate cancer over selenomethionine or selenite. Carcinogenesis 2008; 29:1005-1012. This study shows that tumor accumulation of total Se is not correlated with anticarcinogenesis; SeMet supplementation caused up to eight-fold higher Se accumulation than other supplements with no appreciable effect on tumor burden.
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Bhattacharya A, Seshadri M, Oven S, et al. Tumor vascular maturation and improved drug delivery induced by methylselenocysteine leads to therapeutic synergy with anticancer drugs. Clin Cancer Res 2008; 14:3926-3932. The study extends the group's previous demonstration of therapeutic synergy of MeSeCys and anticancer drugs by showing that MeSeCys treatment of mice given FaDu human head and neck squamous cell carcinoma xenografts showed significant increases in tumor microvascular maturation and tumor uptake of doxorubicin.
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Bhattacharya A, Seshadri M, Oven S, et al. Tumor vascular maturation and improved drug delivery induced by methylselenocysteine leads to therapeutic synergy with anticancer drugs. Clin Cancer Res 2008; 14:3926-3932. The study extends the group's previous demonstration of therapeutic synergy of MeSeCys and anticancer drugs by showing that MeSeCys treatment of mice given FaDu human head and neck squamous cell carcinoma xenografts showed significant increases in tumor microvascular maturation and tumor uptake of doxorubicin.
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Murawaki Y, Tsuchiya H, Kanbe T, et al. Aberrant expression of selenoproteins in the progression of colorectal cancer. Cancer Lett 2008; 259:218-230. This is the first study to compare the expression of multiple selenoproteins in tumor and nontumorous tissues from human cancer patients. They found that the oxidative modifications of proteins were more in tumor tissues, but that the expression of two glutathione peroxidase isoforms (GPX1, GPX3) and SepP were decreased and GPX2 was increased.
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Murawaki Y, Tsuchiya H, Kanbe T, et al. Aberrant expression of selenoproteins in the progression of colorectal cancer. Cancer Lett 2008; 259:218-230. This is the first study to compare the expression of multiple selenoproteins in tumor and nontumorous tissues from human cancer patients. They found that the oxidative modifications of proteins were more in tumor tissues, but that the expression of two glutathione peroxidase isoforms (GPX1, GPX3) and SepP were decreased and GPX2 was increased.
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Baliga M, Wang H, Zhuo P, et al. Selenium and Gpx-1 overexpression protect mammalian cells against UV-induced DNA damage. Biol Trace Element Res 2007; 115:227-241.
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Peters U, Chatterjee N, Hayes R, et al. Variation in the selenoenzyme genes and risk of advanced distal colorectal adenoma. Cancer Epidemiol Biomarkers Prev 2008; 17:1144-1154. This study found positive associations between genetic variants at or near the SEPP1 and TXNRD1 loci and risk of advanced colorectal adenoma.
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Arsova-Sarafinovska Z, Matevska N, Eken A, et al. Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk, Int Ural Nephrol 2008 [Epub ahead of print]. This study showed that carriers of the variant Leu allele of the Pro198Leu polymorphism of cytosolic GPX1 were at decreased risk to prostate cancer in a cohort of Macedonian men.
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Arsova-Sarafinovska Z, Matevska N, Eken A, et al. Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk, Int Ural Nephrol 2008 [Epub ahead of print]. This study showed that carriers of the variant Leu allele of the Pro198Leu polymorphism of cytosolic GPX1 were at decreased risk to prostate cancer in a cohort of Macedonian men.
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Jablonska E, Gromadzinska J, Sobala W, et al. Lung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphism. Eur J Nutr 2008; 47:47-54. This study showed different risks to lung cancer for individuals of different genotype with respect to a polymorphism of the 15kDa selenoprotein (Sep15). Although plasma Se was inversely related to lung cancer risk in both genotype groups, at plasma Se levels above 80 ng/ml risk increased for individuals of the 1125 GG or GA genotypes. Individuals with the 1125 AA genotype appeared to benefit most from higher Se status.
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Jablonska E, Gromadzinska J, Sobala W, et al. Lung cancer risk associated with selenium status is modified in smoking individuals by Sep15 polymorphism. Eur J Nutr 2008; 47:47-54. This study showed different risks to lung cancer for individuals of different genotype with respect to a polymorphism of the 15kDa selenoprotein (Sep15). Although plasma Se was inversely related to lung cancer risk in both genotype groups, at plasma Se levels above 80 ng/ml risk increased for individuals of the 1125 GG or GA genotypes. Individuals with the 1125 AA genotype appeared to benefit most from higher Se status.
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Méplan C, Crosley L, Nicol F, et al. Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study). FASEB J 2007; 21:3063-3074. This study demonstrated relationships of two SNPs of SepP with plasma Se level and its response to supplementation. The SNP 24731 genotype was a determinant of presupplementation plasma Se level, whereas the SNP 25191 genotype was a determinant of the change in plasma Se level in response to supplementation.
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Méplan C, Crosley L, Nicol F, et al. Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study). FASEB J 2007; 21:3063-3074. This study demonstrated relationships of two SNPs of SepP with plasma Se level and its response to supplementation. The SNP 24731 genotype was a determinant of presupplementation plasma Se level, whereas the SNP 25191 genotype was a determinant of the change in plasma Se level in response to supplementation.
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40
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Le D, Liang X, Fomenko D, et al. Analysis of methionine/ selenomethionine oxidation and methionine sulfoxide reductase function using methionine-rich proteins and antibodies against their oxidized forms. Biochemistry 2008; 47:6685-6694. This study demonstrates that peptidyl Se(O)Met can be reduced readily to SeMet, providing a mechanism for alteration of methionine sulfoxide signaling.
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