Specific anti-tumor effect induced by attenuated Salmonella typhimurium vaccine expressing extracellular region of vascular endothelial growth factor receptor 2

The purposes of this research were to study the stable expression of exogenous gene encoding therapeutic protein in attenuated Salmonella typhimurium, observe the metabolism of oral gene vaccine carried by attenuated Salmonella typhimurium in BALB/c mouse, and investigate the feasibility of prevention and treatment of tumors by the recombinant bacteria. Recombinant plasmid pcDNA3.1 VEGFR2(n1-7) was transformed into competent attenuated Salmonella typhimurium SL3261 to develop oral DNA vaccine SL3261-pcDNA3.1 VEGFR2(n1-7). To observe whether the exogenous gene can be expressed in the recombinant bacteria, PCR was performed to amplify the CMV promoter of the eukaryotic expression vector as the proof of stable expression of exogenous protein; transmission elec- tron microscopy (TEM) was applied to observe the morphology of the recombinant bacteria to confirm that the exogenous gene has no impact on the growth of the bacteria, and then BALB/c mice were immunized with the gene vaccine. After inoculation of the gene vaccine, the recombinant bacteria SL3261 could be detected in the tissues such as small intestine, colon, liver and spleen. And then, mice in each group were challenged with tumor cells. The results of animal experiment showed that tumor growth of the mice in experimental group was inhibited and survival time of immunized mice was prolonged compared with control groups. A higher lymphocyte infiltration in tumors from animals treated with DNA vaccine was observed. Immunohistochemical analysis of tumor samples revealed an en- hanced accumulation of CD8 cytotoxic T lymphocytes, as well as an increase in CD4 cells in the tumors of animals treated with the oral gene vaccine compared to tumors from control group mice. Ultrastructure of the tumor tissue showed that tumor cells in the samples of the immunized mice were well-differentiated. Our research confirmed that the exogenous gene can be stably expressed in the attenuated Salmonella typhimurium and has no impact on the growth of the recombinant bacteria; the exogenous gene can de delivered to the host by attenuated Salmonella typhimurium to produce anti-tumor effect with no obvious cytotoxity to the host. In this study, it is established that attenuated Salmonella typhimurium could be used as a vector for oral gene vaccine, and our study provided a theoretical basis for the body distribution and the metabolism of the recombinant bacteria. This strategy may provide a simple, safe and effective way for the prevention and treatment of tumors.     

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核磁共振跟踪反应法研究5—O—乙酰基—2.3-双脱氧-D.L-呋喃戊糖基氯的合成

以乙酸四氢呋喃甲酯为原料,通过自由基氯化反应,合成双脱氧核苷类抗艾滋病药物的重要中间体化合物5—0—乙酰基—2.3—双脱氧—D.L—吹喃戊糖基氯.对于此种不稳定的中间体化合物,用~1HNMR跟踪监测反应物的方法,研究了改变反应时间、反应温度和反应物摩尔比对反应产物的影响,获得了最佳的反应条件,使其收率从10％提高到50％左右.     

C~3I系统理论评述

本文综述了C~3I系统研究中的主要问题与现状,讨论了该系统的建模、效能分析以及影响理论研究的几个因素,并对未来C~3I系统理论的主要问题、难点以及解决手段等进行了探讨。     

处理优化约束条件的微分方程法

在文[1]中,作者曾提出求解一般约束优化问题的一种新方法。本文利用微分方程对约束条件做进一步的讨论,证明了从一可行点的某邻域出发的该微分方程组的解关于部分变元总收敛到问题(1.1)的可行点。     

Lipschitz条件题设的完善

本文给出了函数单侧极值点的定义,并证明了连续函数的单侧极值点所成之集与实数集等势,且利用此完善了函数满足Lipschitz 条件的题设。