RESUMO
AIM: To evaluate the efficacy and safety of the BR regimen containing bendamustine in patients with chronic lymphocytic leukemia (CLL) who have not previously received specific therapy. SUBJECTS AND METHODS: The results of the Russian prospective observational multicenter study BEN-001 (2012-2015) covering 196 CLL patients from 34 centers of the Russian Federation were analyzed. The diagnosis was confirmed by the results of peripheral blood lymphocyte immunophenotyping. A centralized approach was employed to make IGHV gene mutational status analysis, FISH examination, and minimal residual disease according to standardized methods. Quality-of-life (QOL) indicators were estimated using the EQ-5D and FACT-Leu questionnaires. Survival rates were calculated applying by the Kaplan-Meier method. RESULTS: The patients' median age was 61 years. 41% of patients had a decline in estimated creatinine clearance less than 70 ml/min/1.73 m2. The combination of bendamustine and rituximab could achieve a common response in 83.2% of the patients, including complete remission in 59.7%. Eradication of minimal residual disease was achieved in 23 (27.4%) of 84 patients. Two-year progression-free survival rates were 85.9%. The QOL indicators were noted to be improved during the treatment. CONCLUSION: The investigation shows the good tolerability of bendamustine when it is used in clinical practice. Due to the high cost of new drugs (ibrutinib, obinutuzumab, ofatumumab, etc.) and toxicity of the FCR regimen, the combination including bendamustine can be the best first-line therapy option for all CLL patients, regardless of their age and comorbidity.
Assuntos
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Neoplasia Residual , Qualidade de Vida , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/psicologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/diagnóstico , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/etiologia , Indução de Remissão/métodos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Federação Russa/epidemiologia , Resultado do TratamentoRESUMO
The stability of mRNA and its translation efficacy in higher eukaryotes are influenced by the interaction of 3'-untranscribed regions (3'-UTRs) with microRNAs and RNA-binding proteins. Since Saccharomyces cerevisiae lack microRNAs, it is possible to evaluate the contribution of only 3'-UTRs' and RNA-binding proteins' interaction in post-transcriptional regulation. For this, the post-transcriptional regulation of Drosophila limk1 gene encoding for the key enzyme of actin remodeling was studied in yeast. Analysis of limkl mRNA 3'-UTRs revealed the potential sites of yeast transcriptional termination. Computer remodeling demonstrated the possibility of secondary structure formation in limkl mRNA 3'-UTRs. For an evaluation of the functional activity of Drosophila 3'-UTRs in yeast, the reporter gene PHO5 encoding for yeast acid phosphatase (AP) fused to different variants of Drosophila limk1 mRNA 3'-UTRs (513, 1075, 1554 bp) was used. Assessments of AP activity and RT-PCR demonstrated that Drosophila limkl gene 3'-UTRs were functionally active and recognized in yeast. Therefore, yeast might be used as an appropriate model system for studies of 3'-UTR's role in post-transcriptional regulation.
Assuntos
Regiões 3' não Traduzidas , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Quinases Lim/metabolismo , RNA Mensageiro/metabolismo , Saccharomyces cerevisiae/genética , Fosfatase Ácida/genética , Fosfatase Ácida/metabolismo , Animais , Proteínas de Drosophila/genética , Genes Reporter , Quinases Lim/genética , RNA Mensageiro/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
We report a theoretical study of micelles from diblock copolymers with an insoluble core-forming block and an amphiphilic ionic corona-forming block. We calculate the micelle structural parameters depending on the composition of the coronal block (ratio between the non-polar and ion-containing groups) as well as solvent quality and polarity for the coronal block. We focus on the effect of ion pair formation in a low polar corona medium and predict the existence of novel micelles with ionomer-type coronae. In these micelles most part of counterions is bound with ions in polymer chains. Two consecutive jump-like first-order phase transitions between different-type micelles can take place in the solution upon change of hydrophobic/polyelectrolyte balance within the micelle corona: large micelles with polyelectrolyte collapsed coronae â large micelles with ionomer-type coronae â small micelles with polyelectrolyte swollen coronae. These transitions are accompanied by non-monotonous change in the micelle aggregation number. New insight into the role of counterions is important for design of stimuli responsive systems.
