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1.
Leukemia ; 30(10): 1987-1992, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27133819

RESUMO

The APL0406 study showed that arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are not inferior to standard ATRA and chemotherapy (CHT) in newly diagnosed, low-intermediaterisk acute promyelocytic leukaemia (APL). We analysed the kinetics of promyelocytic leukaemia-retinoic acid receptor-α (PML-RARα) transcripts by real-time quantitative PCR (RQ-PCR) in bone marrow samples from 184 patients and assessed the prognostic impact of fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 159 patients enrolled in this trial in Italy. After induction therapy, the reduction of PML-RARα transcripts was significantly greater in patients receiving ATRA-CHT as compared with those treated with ATRA-ATO (3.4 vs 2.9 logs; P=0.0182). Conversely, at the end of consolidation, a greater log reduction of PML-RARα transcripts was detected in the ATRA-ATO as compared with the ATRA-CHT group (6.3 vs 5.3 logs; P=0.0024). FLT3-ITD mutations had no significant impact on either event-free survival (EFS) or cumulative incidence of relapse in patients receiving ATRA-ATO, whereas a trend for inferior EFS was observed in FLT3-ITD-positive patients receiving ATRA-CHT. Our study shows at the molecular level that ATRA-ATO exerts at least equal and probably superior antileukaemic efficacy compared with ATRA-CHT in low-intermediaterisk APL. The data also suggest that ATRA-ATO may abrogate the negative prognostic impact of FLT3-ITD.


Assuntos
Arsenicais/administração & dosagem , Leucemia Promielocítica Aguda/tratamento farmacológico , Proteínas de Fusão Oncogênica/sangue , Óxidos/administração & dosagem , Tretinoína/administração & dosagem , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Idoso , Trióxido de Arsênio , Arsenicais/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Quimioterapia de Indução/métodos , Itália , Cinética , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Óxidos/uso terapêutico , Prognóstico , Tretinoína/uso terapêutico , Adulto Jovem
2.
Phys Rev E Stat Nonlin Soft Matter Phys ; 85(3 Pt 1): 031120, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22587051

RESUMO

We consider two complementary polymer strands of length L attached by a common-end monomer. The two strands bind through complementary monomers and at low temperatures form a double-stranded conformation (zipping), while at high temperature they dissociate (unzipping). This is a simple model of DNA (or RNA) hairpin formation. Here we investigate the dynamics of the strands at the equilibrium critical temperature T=T(c) using Monte Carlo Rouse dynamics. We find that the dynamics is anomalous, with a characteristic time scaling as τ∼L(2.26(2)), exceeding the Rouse time ∼L(2.18). We investigate the probability distribution function, velocity autocorrelation function, survival probability, and boundary behavior of the underlying stochastic process. These quantities scale as expected from a fractional Brownian motion with a Hurst exponent H=0.44(1). We discuss similarities to and differences from unbiased polymer translocation.


Assuntos
Modelos Químicos , Modelos Moleculares , Polímeros/química , Simulação por Computador , Conformação Molecular , Movimento (Física)
3.
Phys Rev E Stat Nonlin Soft Matter Phys ; 81(1 Pt 1): 012901, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20365418

RESUMO

Test experiments of hybridization in DNA microarrays show systematic deviations from the equilibrium isotherms. We argue that these deviations are due to the presence of a partially hybridized long-lived state, which we include in a kinetic model. Experiments confirm the model predictions for the intensity vs free-energy behavior. The existence of slow relaxation phenomena has important consequences for the specificity of microarrays as devices for the detection of a target sequence from a complex mixture of nucleic acids.


Assuntos
Modelos Genéticos , Hibridização de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Termodinâmica , Algoritmos , Cinética , Probabilidade , Temperatura
4.
Gene ; 422(1-2): 1-6, 2008 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-18621117

RESUMO

A relationship which links the fluorescence intensity histograms for perfect match (PM) and mismatch (MM) probes in Affymetrix Genechips is derived using inputs from physical-chemistry as the Langmuir and the Nearest Neighbor models. This relationship is in good agreement with experimental data from few dozens of chips belonging to about 10 different organisms. Principles of physical-chemistry impose some constant value for the average ratios of PM and MM intensities. Experimental data, however, show quite some variations in these parameters, although they follow the same inequalities as expected from hybridization free energies for oligonucleotides melting in solution. It is suggested that the anomalous experiment to experiment differences are due to 1) problems with chip design and 2) excessive fragmentation of the target in solution. The histogram analysis developed may be a useful preprocessing step to evaluate the global quality of the experimental data, prior to the calculation of the gene expression level.


Assuntos
Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Animais , Caenorhabditis elegans , Sondas de DNA , Hibridização de Ácido Nucleico , Reprodutibilidade dos Testes , Termodinâmica , Xenopus laevis
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