0000000000221461
AUTHOR
Ulrich Mahlknecht
Cloning, chromosomal characterization and mapping of the NAD-dependent histone deacetylases gene sirtuin 1
Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, which belongs to the silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (HDACs). The yeast Sir2 protein and its mammalian derivatives play a central role in epigenetic gene silencing, DNA repair and recombination, cell-cycle, microtubule organization, and in the regulation of aging. We have isolated and characterized the human Sirt1 genomic sequence, which spans a region of 33,660 bp and which has one single genomic locus. Determination of the exon-intron splice junctions established that SIRT1 is encoded by 9 exons ranging in size from 80 bp (exon 6) to 2,120 bp (exon 9). Charac…
Darwinism and pharmacogenomics: from 'one treatment fits all' to 'selection of the richest'?
Pharmacogenomics and pharmacogenetics are relatively new fields, and have arisen from recent advances in genetic research. They offer new perspectives on the development of pharmaceuticals, allowing drug design to be targeted specifically to the genotype of selected populations. The discussion of who will be considered for the development of these tailored drugs and who will be excluded, in a situation in which both research resources and public expenditure are limited, is provoking and has led to several, still unanswered ethical questions and concerns about fairness and the potential discrimination of fringe groups. Based on the statistical analyses of population averages, patient groups …
Characterization of the NAD-Dependent Human Histone Deacetylases Gene Sirtuin 1 and Its Implications on Aging and the Development of Malignant Disease.
Abstract A dysregulation of the tightly controlled equilibrium of acetylation and deacetylation plays a causative role in the generation as well as in the suppression of cancer. Histone acetylation modifiers are therefore gaining increasing attention as potential targets in the treatment of cancer. Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, which belongs to the silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (HDACs). The yeast Sir2 protein and its mammalian derivatives play a central role in epigenetic gene silencing, DNA repair and recombination, cell-cycle, microtubule organization, and in the regulation of aging. We…
Phase 2 Trial of the Continuous IV Administration of Interferon-? in Patients With Disseminated Malignant Melanoma
BACKGROUND Interferons have been reported to significantly contribute to tumor suppression via both induction of p53 gene expression and inhibition of angiogenesis. OBJECTIVE The assessment of treatment toxicity and antitumoral effectiveness of continuous IV administration of interferon-beta based on an overall evaluation of laboratory, radiographic, and clinical parameters observed during the trial. METHODS The authors treated patients with advanced malignant melanoma with continuous IV infusions of 1 x 10(6) IU interferon-beta daily ( approximately 0.6 x 10(6) IU interferon-beta/m2 daily). RESULTS Continuous IV administration of interferon-beta had no significant effect on overall patient…
Pharmacogenomics: questions and concerns
The progressively aging population in the western world, rising socioeconomic expenditure and increasing costs for the treatment of adverse drug reactions, lead to increasing pressure on public spending. The public acceptance of pharmacogenomics is high, therefore, because it promises individualized safe and effective treatment at lower cost. Pharmacogenomics studies the genetic polymorphisms that underlie the variability in drug response between individuals. Despite the great benefits being awaited from this new field, a number of ethical, social and legal concerns arise, which demand rapid strict international regulations in order to prevent discrimination or harm of any kind from society…