Enhanced antitumor effects of tumor antigen-pulsed dendritic cells by their transfection with GM-CSF gene

To investigate the biological characterization and antitumor activitites of GM-CSF gene-transfected dendritic cells, the splenic dendritic cells were infected with GM-CSF recombinant replication-deficient adenoviruses in vitro . Their enhanced expression of B7 was demonstrated by FACS analysis, and more potent stimulatory activity was confirmed by allogeneic MLR. Immunization of dendritic cells pulsed with irradiated B16 melanoma cells induced sig-nificant CTL and enabled host to resist the challenge of wild-type B16 cells. When they were transfected with GM-CSF gene subsequently, the induced CTL activity was higher, and the produced protection against B16 cell challenge and therapeutic effect on the mice with preestablished pulmonary melastases more effective. These data suggest that the dendritic cells pulsed with tumor antigen then transfected with GM-CSF gene can be used as an effective vaccine in tumor immunotherapy.     

秦岭翠雀花中生物碱成分的研究

从秦岭翠雀花(Delphinium giraldii Diels)全草中分得14个已知生物碱：tongolinine(1)、氨茴酰牛扁碱(anthranoyllycoctonine)(2)、牛扁碱(1ycoctonine)(3)、dihydrogadesine(4)、tatsiensine(5)、siwanine A(6)、delsemine A(7)、delsemine B(8)、甲基牛扁碱(methyllycaconitine)(9)、ajacine(10)、delajacine(11)、delsoline(12)、滇乌碱(yunaconitine)(13)和查斯曼宁(chasmanine)(14)。应用光谱和与已知品对照TLC法鉴定了所有化合物的结构。     

刺激蓝斑对心肌收缩力及肾交感神经放电的影响

在64只麻醉及人工呼吸的猫,观察到电刺激蓝斑(LC)能引起血压升高、心率加快,左心室收缩压升高,左心室内压最大变化率增加及肾交感神经放电(RNA)显著地增加。去缓冲神经对电刺激 LC 所引起的上述指标的增加幅度无明显影响,但可明显延长血压反应升高相以及血压恢复期的时间。LC 内微量注射谷氨酸钠可使血压下降,心率减慢,左室收缩压和左室内压最大变化率亦降低。LC 内注射海人酸,也能引起减压反应。而注射海人酸3h 后,使LC 神经元发生变性或去极化阻断时,再电刺激 LC 仍能引起明显的升压反应。以上结果表明,电刺激 LC 可使血压升高、心肌收缩力及肾交感神经放电增加,而 LC 内微量注射胞体兴奋剂则可降低血压、心率及心肌收缩力,说明电刺激 LC 引起的加压反应可能主要是兴奋了过路纤维所致,而 LC 本身神经元的兴奋引起的是减压反应。     

基因修饰的肝细胞脾内移植后体内分布和基因表达的实验研究

为探讨基因修饰的肝细胞经脾内移植途径介导肝脏基因治疗的可行性和有效性,体外用NeoR基因或IL-2基因修饰小鼠正常胚胎肝细胞BNL CL.2,经脾内移植至正常同系小鼠体内(2×10⁶/只),观察NeoR和IL-2基因在不同脏器的表达.结果发现脾内移植NeoR基因修饰的肝细胞后24h,即可通过RT-PCR在肝脏中检测出NeoR基因mRNA的表达,持续表达11周以上;此外,NeoR基因在脾脏中短暂表达(24h至1周),在肺组织中也有一过性表达(48～96h).脾内移植IL-2基因修饰的肝细胞后,肝脏中可检测到稳定表达的IL-2mRNA(24h至11周),外周血中维持一定水平(5～40pg/mL)的IL-2,能增强肝脏Kupffer细胞Ia抗原的表达及脾细胞的NK杀伤活性.提示基因修饰的肝细胞脾内移植后能定向分布至肝脏,并同化入肝组织中长期存活,有效地表达外源基因,可成为肝脏靶向性基因治疗的可行途径.     

IL-3基因转染的瘤苗与IL-2、低剂量环磷酰胺的联合抗肿瘤作用

用IL-3基因转染的瘤苗治疗实验性肺转移荷瘤小鼠,结果发现能使其肺转移性肿瘤结节比常规瘤苗治疗明显减少、存活期明显延长,而且当与IL-2或低剂量Cy合用后,可使荷瘤小鼠的肺转移结节更少,存活期更长,特别是当IL-3基因转移的瘤苗、IL-2、低剂量Cy三者合用时抗肿瘤转移作用最强,免疫学研究表明,经IL-3基因转染瘤苗治疗后,荷瘤小鼠脾脏CIL活性、NK活性、IL-2诱导的LAK活性均显著增强,脾细胞体外分泌IFN-γ和TNF水平显著升高;当与IL-2或低剂量Cy合用时,上述抗肿瘤免疫功能升高得更加明显,并且以三者联合应用后免疫功能增强最为明显,可见IL-3基因转染的瘤苗能有效地激活体内抗肿瘤免疫功能,具有显著的抗肿瘤作用.     

肿瘤相关巨噬细胞的研究进展

肿瘤相关巨噬细胞(tumor-associated macrophages, TAMs)在肿瘤微环境中扮演着重要的角色,TAMs的大量存在与不良预后密切相关。近年来,TAMs的相关问题成为研究的热点,该文就TAMs的募集、TAMs的极化状态及TAMs与肿瘤之间的相互作用问题进行了综述。该文对经典活化的M1型和替代活化的M2型巨噬细胞对肿瘤影响研究的最新进展进行了总结。此外,对TAMs的多种靶向治疗策略进行了总结和讨论。这些治疗策略中包含抑制TAMs的募集、直接清除TAMs、将M2型TAMs极化为M1型TAMs以及提高TAMs的吞噬能力等方法和手段。这些研究有助于深入理解TAMs与肿瘤相互作用的机理,并为肿瘤的联合治疗提供借鉴和参考。     

树突状细胞与肿瘤免疫系统相互作用研究进展

树突状细胞(dendritic cells, DCs)是功能最强的专职抗原呈递细胞。DCs能够摄取和呈递抗原表达共刺激分子,并迁移到淋巴器官激活T细胞,进而启动免疫反应。在肿瘤发展过程中,DCs不仅能诱导抗肿瘤免疫反应,还可以诱导免疫耐受。现对树突状细胞的生物学特性、树突状细胞与肿瘤免疫系统的相互作用等方面的最新研究进展进行综述,并介绍免疫治疗中基于树突状细胞疫苗的多种治疗方法。相关研究对于更好地理解肿瘤微环境中树突状细胞在肿瘤演化中的作用、寻找新的治疗策略以及改进治疗方法至关重要。     

微生物基因组精简优化的研究进展

微生物基因组精简优化是构建合成生物学底盘细胞的重要策略.文中从基因组精简的整体设计出发,归纳了微生物的必需基因及其确定方法,重点介绍了各种微生物基因组精简策略,分析了多种基因组精简菌株的特点,充分展示了基因组精简优化在构建合成生物学底盘细胞中的重要作用.     

In vivo distribution and gene expression of genetically modified hepatocytes after intrasplenic transplantation

To investigate the feasibility and efficacy of liver gene therapy mediated by intrasplenic transplanta-tion of genetically modified hepatocytes, the normal mouse liver cell line BNL CL. 2 cells were introduced with Neo-re-sistant (NeoR) gene or interleukin-2 (IL-2) gene in vitro, and transplanted intrasplenically into normal syngeneic mice (2 × 106 cell/mouse); subsequently, the expressions of the introduced genes in vivo were detected. The RT-PCR results showed that NeoR mRNA expressions were detectable in livers 24 h after transplantation and lasted over 11 weeks. Moreover, The NeoR mRNA was detected to be expressed temporarily in spleens (24 h- 1 week) and lungs (24-96 h) after transplantation. After intrasplenic transplantation of IL-2 gene-modified BNL CL.2 cells, the stable expressions of IL-2 mRNA in the livers of transplanted mice were detectable by RT-PCR (24 h-11 weeks), and certain levels of IL-2 (5-40 pg/mL) remained in the peripheral blood. When IL-2 gene-modified BNL CL. 2 cells were tran     

Therapeutic effects on experimental metastatic tumor-bearing mice by vaccination with GM-CSF gene-modified and tumor antigen-pulsed macrophages

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