Search results for "pharmacogenetics"
showing 10 items of 90 documents
Increased Hospital Stay and Allograft Disfunction in Renal Transplant Recipients with Cyp2c19 AA Variant in SNP rs4244285
2012
Pharmacogenetics correlates certain genetic variants, such as single nucleotide polymorphisms (SNPs), with blood drug levels, efficacy, and adverse effects of the treatment. Tacrolimus is mainly metabolized via CYP3A4/5, whereas CYP2C19 and CYP3A4/5 are responsible for omeprazole metabolism. Omeprazole inhibits tacrolimus metabolism via CYP3A5 in patients carrying variant alleles of CYP2C19, increasing tacrolimus blood concentrations. Seventy-five renal transplant recipients treated with tacrolimus and concomitant omeprazole were genotyped in a panel of 37 SNPs with use of Sequenom MassArray. The patients with CYP2C19*2/*2 genotype (n = 4) showed a median posttransplantation hospital stay o…
Pharmacogenomics: questions and concerns
2005
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…
Darwinism and pharmacogenomics: from 'one treatment fits all' to 'selection of the richest'?
2004
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 …
Bioassays to monitor taspase1 function for the identification of pharmacogenetic inhibitors
2011
Background Threonine Aspartase 1 (Taspase1) mediates cleavage of the mixed lineage leukemia (MLL) protein and leukemia provoking MLL-fusions. In contrast to other proteases, the understanding of Taspase1's (patho)biological relevance and function is limited, since neither small molecule inhibitors nor cell based functional assays for Taspase1 are currently available. Methodology/Findings Efficient cell-based assays to probe Taspase1 function in vivo are presented here. These are composed of glutathione S-transferase, autofluorescent protein variants, Taspase1 cleavage sites and rational combinations of nuclear import and export signals. The biosensors localize predominantly to the cytoplasm…
Polymorphisms of pro-inflammatory genes and Alzheimer's disease risk: A pharmacogenomic approach.
2006
Clinically and pathologically Alzheimer's disease (AD) represents a sequential progressive neurodegenerative disorder. AD is etiologically heterogeneous and accounts for a majority of dementia in western societies. Inflammation clearly occurs in pathologically vulnerable regions of the AD brain and the search for genetic factors influencing the pathogenesis of AD has lead to the identification of numerous gene polymorphisms that might act as susceptibility modifiers. Accordingly, several reports have indicated that the risk of AD is substantially influenced by several genetic polymorphisms in the promoter region, or other untranslated regions, of genes encoding inflammatory mediators, altho…
Genetics and genomics of BNCT among basics and perspectives
2017
The Boron neutron capture therapy (BNCT) bases its therapeutic action on the selective ability to induce DNA damage of tumor cells with the aim to cause their death by apoptosis or necrosis, preserving as much as possible the normal cells. The genetic variability is an evolutionary mechanism of species survival and improvement according to which diversity in genetic configurations exists among individuals of a population, revealed also in different tolerance to insults and reparative ability of DNA damage induced by physical and chemical agents. A tumor, due to its intrinsic genomic instability, acquires the mutator phenotype and may, during the cell duplications, generate in the same indiv…
Machine Learning: An Overview and Applications in Pharmacogenetics.
2021
This narrative review aims to provide an overview of the main Machine Learning (ML) techniques and their applications in pharmacogenetics (such as antidepressant, anti-cancer and warfarin drugs) over the past 10 years. ML deals with the study, the design and the development of algorithms that give computers capability to learn without being explicitly programmed. ML is a sub-field of artificial intelligence, and to date, it has demonstrated satisfactory performance on a wide range of tasks in biomedicine. According to the final goal, ML can be defined as Supervised (SML) or as Unsupervised (UML). SML techniques are applied when prediction is the focus of the research. On the other hand, UML…
The role of polymorphisms of thiopurine methyltransferase in therapy with Azathioprine: preliminary study
2018
Azathioprine is an immunosuppressant drug belonging to the class of thiopurines widely used in clinical therapy. Its immunosuppressive action is linked to the substantial action mechanism in the inhibition of the synthesis of nitrogenous bases purine carried out in T-lymphocyte. The level of such medication limit resides in side effects such as myelosuppression and the development of tumours. The occurrence of side effects is linked to the presence of genetic polymorphisms of Thiopurine methyltransferase (TPMT). To date, 40 allelic variants for TPMT have been detected. However, those responsible for the reduction of enzyme activity are three: *2, *3A, *3C. The presence of one of the three p…
Molecular docking and pharmacogenomics of vinca alkaloids and their monomeric precursors, vindoline and catharanthine.
2011
International audience; Vinblastine and vincristine are dimeric indole alkaloids derived from (formerly: ). Their monomeric precursor molecules are vindoline and catharanthine. While vinblastine and vincristine are well-known mitotic spindle poisons, not much is known about vindoline and catharanthine. Vindoline and catharanthine showed weak cytotoxicity, while vinblastine, vincristine, and the semisynthetic vindesine and vinorelbine revealed high cytotoxicity towards cancer cells. This may reflect a general biological principle of poisonous plants. Highly toxic compounds are not only active towards predators, but also towards plant tissues. Hence, plants need mechanisms to protect themselv…
The Relevance of Genetic Factors in Tumor Therapy and the Underlying Pharmacogenetic Principles
2017
In the following chapter it is shown that only by the combination of pharmacological and genetic research programs new relevant findings of tumor formation and progression can be gained. This then lead to an improved and individualized therapy of the patients in the area of application.