Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and immunotherapy.Normalization of tumor vasculature as well as depletion of...Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and immunotherapy.Normalization of tumor vasculature as well as depletion of glutathione(GSH)can improve the TME.Here,we developed a novel therapeutic nanoparticle functional enzyme ultra QDAU5 nanoparticles(FEUQ Nps)based on a fluorescence-on and releasable strategy by combining a vascular normalization inducer,a GSH depleting agent,and an activated fluorophore.In which the cleavage of disulfide bonds releases active molecules that induce vascular normalization and improve the hypoxic microenvironment.In addition,it may deplete GSH in cancer cells,thus inducing the production of reactive oxygen species(ROS)and lipid peroxide(LPO)and promoting iron toxicity.It may also lead to endoplasmic stress and release of calmodulin,which activates the immune system.Meanwhile,quenched fluorophores are turned on in the presence of galactosidase(GLU)for tumor-specific labeling.In summary,we developed novel therapeutic agent nanoparticles with the function of vascular normalization inducers to achieve specific labeling of hepatocellular carcinoma while exerting efficient antitumor effects in vivo.展开更多
目的:分析来那度胺、硼替佐米及地塞米松(lenalidomide,bortezomib and dexamethasone,RVD)方案治疗新诊断多发性骨髓瘤(newly diagnosed multiple myeloma,NDMM)患者的疗效和安全性.方法:回顾性分析2015年1月至2019年5月首都医科大学...目的:分析来那度胺、硼替佐米及地塞米松(lenalidomide,bortezomib and dexamethasone,RVD)方案治疗新诊断多发性骨髓瘤(newly diagnosed multiple myeloma,NDMM)患者的疗效和安全性.方法:回顾性分析2015年1月至2019年5月首都医科大学附属北京朝阳医院收治的48例NDMM患者,统计其临床特征及治疗疗效.结果:48例患者的中位年龄为59(34~79)岁,Durie-Salmon分期Ⅲ期患者44例;ISS分期Ⅱ期患者15例,Ⅲ期患者19例,12例伴浆细胞瘤,细胞遗传学高危患者占32.5%.全部患者接受RVD方案化疗,中位4(1~9)个周期,总有效率97.9%,完全缓解(complete response,CR)率为35.4%,4个周期较2个周期化疗后非常好的部分缓解(very good partial response,VGPR)以上疗效提高为(84.6% vs. 64.1%);平均采集CD34+细胞数4.2(±2.6)×106/kg;诱导治疗后下一代流式微小残留病变(minimal residual disease,MRD)阴性率为20.6%,其中2例移植前MRD阳性者在移植后MRD转阴.治疗过程中2例发生3~4级血液学毒性,未发生3级以上非血液学不良事件.结论:采用RVD方案治疗NDMM患者4个疗程,缓解率高,不良反应可耐受,且不影响干细胞采集.RVD诱导联合自体造血干细胞移植可进一步提高MRD阴性率.展开更多
基金supported by the National Natural Science Foundation of China(NSFC,No.82173742)the Science Fund for Distinguished Young Scholars of Shaanxi Province(No.2022JC-54)the Key Research and Development Program of Shaanxi Province(No.2023-YBSF-131).
文摘Remodeling tumor microenvironment(TME)is a very promising and effective strategy to enhance the effects of chemotherapy,photodynamic therapy,and immunotherapy.Normalization of tumor vasculature as well as depletion of glutathione(GSH)can improve the TME.Here,we developed a novel therapeutic nanoparticle functional enzyme ultra QDAU5 nanoparticles(FEUQ Nps)based on a fluorescence-on and releasable strategy by combining a vascular normalization inducer,a GSH depleting agent,and an activated fluorophore.In which the cleavage of disulfide bonds releases active molecules that induce vascular normalization and improve the hypoxic microenvironment.In addition,it may deplete GSH in cancer cells,thus inducing the production of reactive oxygen species(ROS)and lipid peroxide(LPO)and promoting iron toxicity.It may also lead to endoplasmic stress and release of calmodulin,which activates the immune system.Meanwhile,quenched fluorophores are turned on in the presence of galactosidase(GLU)for tumor-specific labeling.In summary,we developed novel therapeutic agent nanoparticles with the function of vascular normalization inducers to achieve specific labeling of hepatocellular carcinoma while exerting efficient antitumor effects in vivo.
文摘目的:分析来那度胺、硼替佐米及地塞米松(lenalidomide,bortezomib and dexamethasone,RVD)方案治疗新诊断多发性骨髓瘤(newly diagnosed multiple myeloma,NDMM)患者的疗效和安全性.方法:回顾性分析2015年1月至2019年5月首都医科大学附属北京朝阳医院收治的48例NDMM患者,统计其临床特征及治疗疗效.结果:48例患者的中位年龄为59(34~79)岁,Durie-Salmon分期Ⅲ期患者44例;ISS分期Ⅱ期患者15例,Ⅲ期患者19例,12例伴浆细胞瘤,细胞遗传学高危患者占32.5%.全部患者接受RVD方案化疗,中位4(1~9)个周期,总有效率97.9%,完全缓解(complete response,CR)率为35.4%,4个周期较2个周期化疗后非常好的部分缓解(very good partial response,VGPR)以上疗效提高为(84.6% vs. 64.1%);平均采集CD34+细胞数4.2(±2.6)×106/kg;诱导治疗后下一代流式微小残留病变(minimal residual disease,MRD)阴性率为20.6%,其中2例移植前MRD阳性者在移植后MRD转阴.治疗过程中2例发生3~4级血液学毒性,未发生3级以上非血液学不良事件.结论:采用RVD方案治疗NDMM患者4个疗程,缓解率高,不良反应可耐受,且不影响干细胞采集.RVD诱导联合自体造血干细胞移植可进一步提高MRD阴性率.
