Discontinuation of tyrosine kinase inhibitor(TKI)therapy after achieving a persistent deep molecular response(DMR)is an urgently needed treatment goal for chronic myeloid leukemia(CML)patients and has been included in...Discontinuation of tyrosine kinase inhibitor(TKI)therapy after achieving a persistent deep molecular response(DMR)is an urgently needed treatment goal for chronic myeloid leukemia(CML)patients and has been included in the National Comprehensive Cancer Network(NCCN)guidelines(version 2.2017)for CML.Indeed,various studies have confirmed the feasibility of discontinuing TKI therapy.In this study,we analyzed data from 45 CML patients who had discontinued TKI therapy.Univariate analysis was performed to predict factors that were potentially related to treatment-free remission(TFR)and identify the differences between early relapse and late relapse.Out of the 45 patients,20 exhibited molecular relapse after a median follow-up of 18 months(range,1-54 months),and the estimated TFR at 24 months was 40%.The univariate analysis revealed that a high Sokal score and interruptions or dose reductions during TKI treatment were the only baseline factors associated with poor outcomes.Our results indicate that TKI discontinuation could be successfully put into practice in China.展开更多
Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)rema...Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)remain major obstacles to a CML cure.In recent years,the reprogramming of mitochondrial metabolism has emerged as a hallmark of cancers,including CML,and in turn may be exploited for therapeutic purposes.Here,we investigated the effects of several drugs on the mitochondrial function of the CML cell line K562 and found that 5-aminoimidazole-4-carboxamide ribotide(AICAR)and decitabine could effectively increase the ATP content and mitochondrial biogenesis.In addition,these two drugs induced cell cycle arrest and a decrease in colony-forming capacity and promoted K562 cell differentiation.Moreover,we demonstrated that treatment with AICAR or decitabine enhanced the sensitivity o f K562 cells to imatinib,as evidenced by a combination treatment assay.Altogether,our findings indicate that TKIs combined with mitochondrial regulation may provide a therapeutic strategy for the treatment of CML.展开更多
Resistive switching memories based on ion transport and related electrochemical reactions have been extensively studied for years.To utilize the resistive switching memories for high-performance information storage ap...Resistive switching memories based on ion transport and related electrochemical reactions have been extensively studied for years.To utilize the resistive switching memories for high-performance information storage applications,a thorough understanding of the key information of ion transport process,including the mobile ion species,the ion transport paths,as well as the electrochemical reaction behaviors of these ions should be provided for material and device optimization.Moreover,ion transport is usually accompanied by processes of microstructure modification,phase transition,and energy band structure variation that lead to further modulation of other physical properties,e.g.,magnetism,optical emission/absorbance,etc.,in the resistive switching materials.Therefore,novel resistive switching memories that are controlled through additional means of magnetic or optical stimulus,or demonstrate extra functionalities beyond information storage,can be made possible via well-defined ion transportation in various switching materials and devices.In this contribution,the mechanism of ion transport and related resistive switching phenomena in thin film sandwich structures is discussed first,followed by a glanceat the recent progress in the development of high-performance and multifunctional resistive switching memories.A brief perspective of the ion transport-based resistive switching memories is addressed at the end of this review.展开更多
基金the National Natural Science Foundation of China(No.81500136 and No.81670145).
文摘Discontinuation of tyrosine kinase inhibitor(TKI)therapy after achieving a persistent deep molecular response(DMR)is an urgently needed treatment goal for chronic myeloid leukemia(CML)patients and has been included in the National Comprehensive Cancer Network(NCCN)guidelines(version 2.2017)for CML.Indeed,various studies have confirmed the feasibility of discontinuing TKI therapy.In this study,we analyzed data from 45 CML patients who had discontinued TKI therapy.Univariate analysis was performed to predict factors that were potentially related to treatment-free remission(TFR)and identify the differences between early relapse and late relapse.Out of the 45 patients,20 exhibited molecular relapse after a median follow-up of 18 months(range,1-54 months),and the estimated TFR at 24 months was 40%.The univariate analysis revealed that a high Sokal score and interruptions or dose reductions during TKI treatment were the only baseline factors associated with poor outcomes.Our results indicate that TKI discontinuation could be successfully put into practice in China.
文摘Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)remain major obstacles to a CML cure.In recent years,the reprogramming of mitochondrial metabolism has emerged as a hallmark of cancers,including CML,and in turn may be exploited for therapeutic purposes.Here,we investigated the effects of several drugs on the mitochondrial function of the CML cell line K562 and found that 5-aminoimidazole-4-carboxamide ribotide(AICAR)and decitabine could effectively increase the ATP content and mitochondrial biogenesis.In addition,these two drugs induced cell cycle arrest and a decrease in colony-forming capacity and promoted K562 cell differentiation.Moreover,we demonstrated that treatment with AICAR or decitabine enhanced the sensitivity o f K562 cells to imatinib,as evidenced by a combination treatment assay.Altogether,our findings indicate that TKIs combined with mitochondrial regulation may provide a therapeutic strategy for the treatment of CML.
基金supported by the National Basic Research Program of China(2009CB933004,2012CB933004)the National Natural Science Foundation of China(51172250,51303194,61328402,61306152)+1 种基金Zhejiang and Ningbo Natural Science Foundations(2013A610031)Science and Technology Innovative Research Team of Ningbo Municipality(2009B21005,2011B82004)
文摘Resistive switching memories based on ion transport and related electrochemical reactions have been extensively studied for years.To utilize the resistive switching memories for high-performance information storage applications,a thorough understanding of the key information of ion transport process,including the mobile ion species,the ion transport paths,as well as the electrochemical reaction behaviors of these ions should be provided for material and device optimization.Moreover,ion transport is usually accompanied by processes of microstructure modification,phase transition,and energy band structure variation that lead to further modulation of other physical properties,e.g.,magnetism,optical emission/absorbance,etc.,in the resistive switching materials.Therefore,novel resistive switching memories that are controlled through additional means of magnetic or optical stimulus,or demonstrate extra functionalities beyond information storage,can be made possible via well-defined ion transportation in various switching materials and devices.In this contribution,the mechanism of ion transport and related resistive switching phenomena in thin film sandwich structures is discussed first,followed by a glanceat the recent progress in the development of high-performance and multifunctional resistive switching memories.A brief perspective of the ion transport-based resistive switching memories is addressed at the end of this review.
