Biodistribution and Imaging of 131I labeled Anti- Neuropilin-1 Monoclonal Antibody in Malignant Gliomas

摘要 背景介绍 放射免疫显像（radioimmunoimagine，RII）在肿瘤早期诊断中占据重要地位，FDA已经批准了五种基于RII抗体药物用于临床肿瘤显像。但目前，现有靶点的RII分子探针面临肿瘤显像探测效能不足，并存在假阴性等诸多难题。开发针对新靶点的分子探针，是RII不断发展成熟的关键所在。神经鞭毛素受体-1（neuropilin-1，NRP-1），是Semaphorin3A和血管内皮生长因子（VEGF）的共受体，参与肿瘤血管新生，肿瘤生长和转移。它在多种肿瘤组织中高表达，并与肿瘤的恶性程度密切相关，被认为是一个很有前景的肿瘤显像与治疗靶点。但目前针对NRP-1靶点分子显像，尚缺...Abstract Background Radioimmunoimagine（RII）plays an important role in early tumor diagnosis.To date,there were only five RII drugs approved by FDA in clinical studies. However, the use of RII can be limited by the poor diagnostic efficiency and high false negative results. Therefore, it is a cornerstone for RII to futher develop a novel antibody probe targeting tumor. Neuropilin-1 (NRP-1), a co...学位：医学硕士院系专业：医学院_影像医学与核医学学号：2452011115332

Down-regulation of TSPO expression doesn't affect the productions of TNF-α,IL-1β and IL-6 in LPS-stimulated BV-2 microglia

目的研究相对分子质量(Mr)18 000转运蛋白(TSPO)基因表达下调对脂多糖(lPS)诱导bV-2小胶质细胞分泌Tnf-α,Il-1β和Il-6的影响。方法以rnA干扰技术建立TSPO基因表达下调的细胞模型,实时荧光定量PCr(QrT-PCr)和WESTErn blOT法检测转染TSPO SIrnA bV-2细胞TSPO MrnA及蛋白水平表达的效果;用QrT-PCr法检测TSPO基因下调后小胶质细胞bV-2在lPS作用下分泌Tnf-α、Il-1β和Il-6的MrnA水平表达的情况;ElISA检测TSPO基因下调小胶质细胞bV-2在lPS作用下分泌Tnf-α、Il-1β和Il-6的蛋白水平表达的变化。结果成功建立了TSPO基因下调的细胞模型,稳定表达TSPO SIrnA细胞的TSPO MrnA和蛋白水平表达均明显下降,TSPO基因下调后bV-2细胞在lPS作用下分泌Tnf-α、Il-1β和Il-6的量无变化。结论下调TSPO的表达对lPS刺激引起的小胶质细胞Tnf-α、Il-1β和Il-6的分泌无明显影响。Objective To evaluate the effect of translocator protein( TSPO,Mr18 000) on the productions of TNF-α,IL-1βand IL-6 in lipopolysaccharide( LPS)-stimulated BV-2 cells.Methods RNA interference technique was used to decrease TSPO expression in BV-2 cells.Western blotting was performed to assess the level of TSPO protein in BV-2 cells transfected with TSPO siRNA.Then the mRNA and protein levels of TNF-α,IL-1β,and IL-6 were measured in LPS-stimulated BV-2 cells by real-time quantitative PCR( qRT-PCR) and ELISA,respectively.Results The level of TSPO protein obviously decreased in BV-2 cells transfected with TSPO siRNA.However,knockdown of TSPO had no effect on the productions of TNF-α,IL-1βand IL-6 in LPS-stimulated BV-2 cells.Conclusion Down-regulated TSPO is not directly involved in regulating TNF-α,IL-1βand IL-6 productions induced by LPS in microglia.国家自然科学基金(81071182); 福建省医学创新项目(2009-CXB-46); 厦门大学生命科学学院细胞生物和肿瘤工程教育部重点实验室开发基金(2009101); 福建医科大学非直属附属医院科研发展专项基金(2008031