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Contains fulltext : 71286.pdf (publisher's version ) (Open Access), PURPOSE: There are no accurate prognostic biomarkers specific for rectal cancer. Epigenetic aberrations, in the form of DNA methylation, accumulate early during rectal tumor formation. In a preliminary study, we investigated absolute quantitative methylation changes associated with tumor progression of rectal tissue at multiple genomic methylated-in-tumor (MINT) loci sequences. We then explored in a different clinical patient group whether these epigenetic changes could be correlated with clinical outcome. PATIENTS AND METHODS: Absolute quantitative assessment of methylated alleles was used to assay methylation changes at MINT 1, 2, 3, 12, 17, 25, and 31 in sets of normal, adenomatous, and malignant tissues from 46 patients with rectal cancer. Methylation levels of these biomarkers were then assessed in operative specimens of 251 patients who underwent total mesorectal excision (TME) without neoadjuvant radiotherapy in a multicenter clinical trial. RESULTS: Methylation at MINT 2, 3, and 31 increased 11-fold (P = .005), 15-fold (P < .001), and two-fold (P = .02), respectively, during adenomatous transformation in normal rectal epithelium. Unsupervised grouping analyses of quantitative MINT methylation data of TME trial patients demonstrated two prognostic subclasses. In multivariate analysis of node-negative patients, this subclassification was the only predictor for distant recurrence (hazard ratio [HR], 4.17; 95% CI, 1.72 to 10.10; P = .002), cancer-specific survival (HR, 3.74; 95% CI, 1.4 to 9.43; P = .003), and overall survival (HR, 2.68; 95% CI, 1.41 to 5.11; P = .005). CONCLUSION: Methylation levels of specific MINT loci can be used as prognostic variables in patients with American Joint Committee on Cancer stage I and II rectal cancer. Quantitative epigenetic classification of rectal cancer merits evaluation as a stratification factor for adjuvant treatment in early disease.

Reviews are presented of natural and anthropogenic Hg sources, emissions from European Hg mines, contamination from gold and silver mine tailings in the Americas, industrial contamination in North America, remediation techniques, abatement of metallurgical pollution, the contamination of Minamata Bay and chemical interactions with surface biomolecules. Case studies follow of industrial and mining sites, emissions and atmospheric dispersion, remediation and contamination of aquatic systems. The mining papers include one on atmospheric Hg at Mount Amiata, Italy, three on Hg in plants, human blood and food webs in Idrija, Slovenia, one on vegetation at Rudnany, Slovakia, one on modern contamination from historical Ag-Au amalgamation at Carson River, Nevada, and Jordan Creek, Idaho, and one on gold mining in Siberia as a source of contamination. Treatments discussed include the use of modified zeolites, sulphur-impregnated activated carbon, low-temperature heat treatment and electrochemical leaching. The book concludes with a subject index., Reviews are presented of natural and anthropogenic Hg sources, emissions from European Hg mines, contamination from gold and silver mine tailings in the Americas, industrial contamination in North America, remediation techniques, abatement of metallurgical pollution, the contamination of Minamata Bay and chemical interactions with surface biomolecules. Case studies follow of industrial and mining sites, emissions and atmospheric dispersion, remediation and contamination of aquatic systems. The mining papers include one on atmospheric Hg at Mount Amiata, Italy, three on Hg in plants, human blood and food webs in Idrija, Slovenia, one on vegetation at Rudnany, Slovakia, one on modern contamination from historical Ag-Au amalgamation at Carson River, Nevada, and Jordan Creek, Idaho, and one on gold mining in Siberia as a source of contamination. Treatments discussed include the use of modified zeolites, sulphur-impregnated activated carbon, low-temperature heat treatment and electrochemical leaching. The book concludes with a subject index.

Mikrobiologi, Kviksølv, Biotilgængelighed