ABSTRACT
PURPOSE: The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia. METHODS: Through a procedure based on a sequence of classical statistics methods, we investigated the possible relationships between treatment efficacy/tolerability and combinations of time-independent variables as gender and genetic covariates in the form of single nucleotide polymorphisms (SNPs) or combinations thereof. Moreover, since the drug tolerability has a strong incidence on the discontinuation of the therapy, we investigated whether the time of manifestation of the most frequent toxic effects can be related to time-independent patients' characteristics or not. RESULTS: We found that a combination of two polymorphisms, namely hOCT1 c.480C>G (rs683369) and ABCB1 c.3435C>T (rs1045642), seems to play the role of predictor for imatinib in both efficacy and toxicity. Furthermore, the time of manifestation of edema toxicity is found to be associated to a combination of gender and ABCB1 c.3435C>T, whereas the time of manifestation of cramp toxicity appears related to gender. CONCLUSIONS: The novelty of this study is dual: the achievement of results that potentially have a significant clinical interest and the demonstration that the adoption of composed covariates may represent a unique tool to study different aspects of the treatment with imatinib.
Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Imatinib Mesylate/adverse effects , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Octamer Transcription Factor-1/genetics , ATP Binding Cassette Transporter, Subfamily B/genetics , Adult , Aged , Aged, 80 and over , Edema/chemically induced , Edema/genetics , Factor Analysis, Statistical , Female , Genotype , Humans , Male , Middle Aged , Muscle Cramp/chemically induced , Muscle Cramp/genetics , Pharmacogenetics , Polymorphism, Genetic , Prognosis , Sex CharacteristicsABSTRACT
The acceleration of ions in the interaction of high intensity laser pulses with overdense plasmas is investigated with particle-in-cell simulations. For circular polarization of the laser pulses, high-density ion bunches moving into the plasma are generated at the laser-plasma interaction surface. A simple analytical model accounts for the numerical observations and provides scaling laws for the ion bunch energy and generation time as a function of pulse intensity and plasma density.
