Purpose: The purpose of this study was to present a novel therapeutic strategy combining use of intracellular magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF) and bleomycin (BLM), and to evaluat...Purpose: The purpose of this study was to present a novel therapeutic strategy combining use of intracellular magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF) and bleomycin (BLM), and to evaluate its therapeutic effect using tumor-bearing mice. Materials and Methods: MNPs (Resovist?, 1.05 mg iron) were incorporated into the hemagglutinating virus of Japan-envelope (HVJ-E) vector (~5 × 109 particles) (HVJ-E/MNPs) by centrifugation at 10,000 × g for 5 min at 4°C. Tumor-bearing mice were prepared by inoculating Colon-26 cells subcutaneously into the backs of BALB/c mice. When the tumor volume reached ~100 mm3, HVJ-E/MNPs and/or BLM were injected directly into the tumor. The AMF was applied to the mice one hour after the injection of agents (AMF treatment). The mice injected with HVJ-E/MNPs were imaged using our magnetic particle imaging (MPI) scanner immediately (13 min) before, immediately (22 min) after, and 3, 7, and 14 days after the injection of agents, and the temporal changes of the average and maximum MPI pixel values in the tumor were quantitatively evaluated. The therapeutic effect was evaluated by calculating the relative tumor volume growth (RTVG) from the tumor volumes measured each day. Transmission electron microscopic (TEM) observation of resected tumors was also performed to confirm the intracellular distribution of MNPs. Results: The AMF treatment combined with BLM significantly decreased the RTVG value compared with AMF treatment alone at 9 to 14 days, and BLM alone at 3 to 5 days after AMF treatment. The average and maximum MPI pixel values in the tumor were almost constant for 14 days. TEM observation confirmed that most of the HVJ-E/MNPs were internalized into tumor cells within one hour after injection. Conclusion: A novel therapeutic strategy with use of AMF treatment and BLM was presented, and the time-dependent change of MNPs in tumors was evaluated using MPI. The present results suggest that this novel strategy can suppress tumor volume growth over AMF treatment or BLM alone, and can be performed repeatedly with a single injection of HVJ-E/MNPs. They also suggest that HVJ-E is effective for internalizing MNPs into cancer cells and that MPI allows for longitudinal monitoring of the distribution of MNPs in tumors.展开更多
目的分析载脂蛋白E(apoE)ε4等位基因分型的健康老年人静息态全脑功能连接强度(FCS)特征,探讨apoEε4基因型调控认知正常老年人的脑功能网络拓扑组织结构的机制。方法入选的44例健康老年人的人口统计学资料、MRI数据、apoEε4信息均来...目的分析载脂蛋白E(apoE)ε4等位基因分型的健康老年人静息态全脑功能连接强度(FCS)特征,探讨apoEε4基因型调控认知正常老年人的脑功能网络拓扑组织结构的机制。方法入选的44例健康老年人的人口统计学资料、MRI数据、apoEε4信息均来自美国公开数据库。根据是否携带apoEε4将入选者分为apoEε4组14例和非apoEε4组30例。进行静息态功能MRI(rs-fMRI)扫描和神经心理学评估,采集rs-fMRI数据进行预处理,计算全脑长程和短程FCS值,比较2组差异。结果静息状态下,与非apoeEε4组比较,apoEε4组右侧岛叶长程FCS值减低(簇大小为183个体素,14656.88±3762.93 vs 20905.82±10245.85,P<0.05),左侧岛叶、右侧岛叶及右侧海马/梭状回短程FCS值减低(簇大小分别为91、232和75个体素,P<0.05)。结论携带apoEε4的健康老年人可不表现认知功能的损害,但其FCS值与非携带者存在差异,这可能是apoEε4基因潜在的神经生物学效应。展开更多
文摘Purpose: The purpose of this study was to present a novel therapeutic strategy combining use of intracellular magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF) and bleomycin (BLM), and to evaluate its therapeutic effect using tumor-bearing mice. Materials and Methods: MNPs (Resovist?, 1.05 mg iron) were incorporated into the hemagglutinating virus of Japan-envelope (HVJ-E) vector (~5 × 109 particles) (HVJ-E/MNPs) by centrifugation at 10,000 × g for 5 min at 4°C. Tumor-bearing mice were prepared by inoculating Colon-26 cells subcutaneously into the backs of BALB/c mice. When the tumor volume reached ~100 mm3, HVJ-E/MNPs and/or BLM were injected directly into the tumor. The AMF was applied to the mice one hour after the injection of agents (AMF treatment). The mice injected with HVJ-E/MNPs were imaged using our magnetic particle imaging (MPI) scanner immediately (13 min) before, immediately (22 min) after, and 3, 7, and 14 days after the injection of agents, and the temporal changes of the average and maximum MPI pixel values in the tumor were quantitatively evaluated. The therapeutic effect was evaluated by calculating the relative tumor volume growth (RTVG) from the tumor volumes measured each day. Transmission electron microscopic (TEM) observation of resected tumors was also performed to confirm the intracellular distribution of MNPs. Results: The AMF treatment combined with BLM significantly decreased the RTVG value compared with AMF treatment alone at 9 to 14 days, and BLM alone at 3 to 5 days after AMF treatment. The average and maximum MPI pixel values in the tumor were almost constant for 14 days. TEM observation confirmed that most of the HVJ-E/MNPs were internalized into tumor cells within one hour after injection. Conclusion: A novel therapeutic strategy with use of AMF treatment and BLM was presented, and the time-dependent change of MNPs in tumors was evaluated using MPI. The present results suggest that this novel strategy can suppress tumor volume growth over AMF treatment or BLM alone, and can be performed repeatedly with a single injection of HVJ-E/MNPs. They also suggest that HVJ-E is effective for internalizing MNPs into cancer cells and that MPI allows for longitudinal monitoring of the distribution of MNPs in tumors.
文摘目的分析载脂蛋白E(apoE)ε4等位基因分型的健康老年人静息态全脑功能连接强度(FCS)特征,探讨apoEε4基因型调控认知正常老年人的脑功能网络拓扑组织结构的机制。方法入选的44例健康老年人的人口统计学资料、MRI数据、apoEε4信息均来自美国公开数据库。根据是否携带apoEε4将入选者分为apoEε4组14例和非apoEε4组30例。进行静息态功能MRI(rs-fMRI)扫描和神经心理学评估,采集rs-fMRI数据进行预处理,计算全脑长程和短程FCS值,比较2组差异。结果静息状态下,与非apoeEε4组比较,apoEε4组右侧岛叶长程FCS值减低(簇大小为183个体素,14656.88±3762.93 vs 20905.82±10245.85,P<0.05),左侧岛叶、右侧岛叶及右侧海马/梭状回短程FCS值减低(簇大小分别为91、232和75个体素,P<0.05)。结论携带apoEε4的健康老年人可不表现认知功能的损害,但其FCS值与非携带者存在差异,这可能是apoEε4基因潜在的神经生物学效应。
