运用HSV－tk／ACV系统进行肿瘤基因治疗研究

构建了含ｐｇｋ启动子驱动的ＨＳＶ－ｔｋ基因的反转录病毒载体ｐＬＮＴＫ，将ＨＳＶ－ｔｋ基因转移至人脑胶质瘤ＳＨＧ４４细胞（命名为ＳＨＧＬＮＴＫ）及小鼠黑色素瘤细胞Ｂ１６（命名为Ｂ１６ＬＮＴＫ）．体外实验证实核着类似物ＡＣＶ对ＳＨＧＬＮＴＫ细胞和Ｂ１６ＬＮＴＫ细胞的杀伤敏感性分别高于亲本细胞１０００和４００倍．转ＨＳＶ－ｔｋ基因细胞与亲本细胞按不同比例共培养时，亲本细胞对ＡＣＶ的敏感性明显增高，存在旁观者效应．首次应用人脑胶质瘤细胞株进行裸鼠体内实验，结果表明：ＡＣＶ能完全抑制ＳＨＧＬＮＴＫ细胞在裸小鼠体内肿瘤的形成，对裸小鼠体内已形成的ＳＨＧＬＮＴＫ肿瘤的治疗效果与对照ＳＨＧ４４肿瘤相比，肿瘤体积缩小８０％；用Ｂ１６ＬＮＴＫ细胞接种同系Ｃ５７／ＢＬ小鼠，经ＡＣＶ治疗后，Ｂ１６ＬＮＴＫ组小鼠的肿瘤较对照组Ｂ１６肿瘤小９５％．ＨＳＶ－ＴＫ／ＡＣＶ系统原位基因转移治疗ＳＨＧ荷瘤裸小鼠、Ｂ１６荷瘤小鼠，原位注射病毒悬液／ＡＣＶ治疗组的ＳＨＧ肿瘤、Ｂ１６肿瘤分别较对照组肿瘤小５０％，４３％，原位注射ＰＡ３１７／ＬＮＴＫ细胞，ＡＣＶ治疗的ＳＨＧ肿瘤较对照组肿瘤小９０％，以上实验结果，统计学上差异极显著，Ｐ＜０．０１．实验     

上消化道病内镜微波组织凝固疗法的临床应用与评价

本文报告应用内镜微波组织凝固疗法(EMCT)治疗胃息肉、胃癌、消化性溃疡三种疾病21例、39次治疗。提出了溃疡面搔刮加微波凝固治疗难治性溃疡、及EMCT联合内镜下局部注射化疗治疗进展期胃癌等方法。胃息肉13例27枚及Ⅱa型早期胃癌1例与消化性溃疡3例全部达到治愈。85.2％的胃息肉EMCT一次治疗成功,Ⅱa型早癌一次成功,消化性溃疡2例一次成功。进展期胃癌4例均达到肿块缩小、狭窄的胃腔扩大与自觉症状改善的效果。鉴于疗效显著,认为三种疾病均适用本疗法;并就EMCT的适应症、使用限度和治疗目的作了讨论;展望了以EMCT作为早期胃癌经内镜根治疗法手段之一的远景。     

Peptide aptamers: exchange of the thioredoxin-A scaffold by alternative platform proteins and its influence on target protein binding

Peptide aptamers have emerged as powerful new tools for molecular medicine. They can specifically bind to and functionally inactivate a given target molecule under intracellular conditions. Typically, peptide aptamers are generated by screening a randomized peptide expression library, displayed from the Escherichia coli thioredoxin A (TrxA) protein. Here, we transferred peptide moieties from defined TrxA-based peptide aptamers to alternative scaffold proteins, such as the green fluorescent protein and staphylococcal nuclease. Yeast and mammalian two-hybrid assays as well as in vitro binding analyses show that the TrxA scaffold can be a major determinant for the binding of peptide aptamers. In addition, we demonstrate that TrxA can correctly display peptide sequences that correspond to the binding domains of natural interaction partners. Therefore, sequence analyses of TrxA-based peptide aptamers, isolated by two-hybrid screening from randomized expression libraries, should also be useful to find cellular binding partners for a given target protein, by homology. Received 1 August 2002; received after revision 17 September 2002; accepted 19 September 2002 RID="*" ID="*"Corresponding author.     

Progress in non-viral gene delivery systems fabricated via supramolecular assembly

Gene delivery systems are one of key issues that limit the development of gene therapy. The novel non-viral gene delivery systems fabricated via supramolecular assembly have begun to show increasing promising and applications in gene therapy due to its suitable nanometric size,controllable structure and excellent biocompatibility. In this review, the fundamental and recent progress of non-viral gene supramolecular assembly is reviewed. Artificial viruses the future direction of non-viral gene delivery systems are also described.     

Investigation of hrDNA targeting vector-mediated tumor-specific suicide gene therapy for hepatocellular carcinoma

Vectors pose most pivotal problem of gene therapy[1]. Because of the high transfection efficiency both in vitro and in vivo, the viral vector has been employed in 70% clinical trials of gene therapy (http://www.wiley.co.uk/ genmed/clinical). However, thei…     

BNCT物理剂量Monte Carlo程序系统——MCDB及算法

硼中子俘获治疗(BNCT,boron neutron capture therapy)规划软件系统MCDB(Monte Carlo dosimetry inbrain),包括医学前处理、Monte Carlo物理剂量计算和后处理。采用中心点方法确定网格的材料和密度,并自动生成Monte Carlo输入文件。MCDB借鉴并发展了一套网格几何下的快速粒子径迹算法,取得了与MCNP程序一致的剂量计算结果,计算速度较MCNP程序提高2.7~3.5倍。MCDB可进行并行计算,具有线性加速比,能够满足BNCT临床对计算时间和精度的要求。     

谈《工程制图》教学中画图能力和看图能力的培养

掌握基本知识、基本方法是培养画图和看图能力的前提,组合体教学是其关键,实践是获得画图和看图能力的途径。     

Anti-amyloidogenic therapies: strategies for prevention and treatment of Alzheimer’s disease

Deposition of amyloid β-protein (Aβ) in the brain is an early and invariant neuropathological feature of Alzheimer’s disease (AD). The current search for anti-AD drugs is mainly focused on modification of the process of accumulation of Aβ in the brain. Here, we review four anti-amyloidogenic strategies: (i) reduction of Aβ production, which has mainly been approached with secretase inhibition, (ii) promotion of the Aβ degrading catabolic pathway, including an Aβ degrading enzyme, neprilysin, (iii) immunotherapy for Aβ and (iv) inhibition of Aβ aggregation. We have reported that AD patients have a favorable molecular environment for Aβ aggregation and that various compounds, such as polyphenols, interfere with Aβ aggregation and destabilize preformed Aβ fibrils. Received 21 December 2005; received after revision 14 February 2006; accepted 29 March 2006     

Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines

In the context of developing a safe genetic vaccination strategy we tested and studied globin-stabilized mRNA-based vaccination in mice. This vaccination strategy has the advantages of genetic vaccination (easy production, adaptability to any disease and inexpensive storage when lyophilized), but not the drawbacks of DNA vaccination (long-term uncontrolled expression of a transgene, possibility of integration into the host genome and possible induction of anti-DNA antibodies). We report here that injection of naked -globin untranslated region (UTR)-stabilized mRNA coding for -galactosidase is followed by detectable translation in vivo. In addition, we show that such a vaccination strategy primes a T helper 2 (Th2) type of response which can be enhanced and shifted to a Th1-type immune response by application of recombinant granulocyte/macrophage colony-stimulating factor 1 day after mRNA injection. Our data demonstrate that the administration of globin UTR-stabilized mRNA is a versatile vaccination strategy that can be manipulated to fit the requirement of antiviral, antibacterial or antitumor immunity.Received 14 June 2004; received after revision 19 July 2004; accepted 9 August 2004     

拯救灵魂:穆旦宗教选择的精神指向

作为一个现代知识分子,诗人穆旦有着"自我折磨"与"折磨人"的双重人格品质,他在对中国现实的深入思考中敏锐地洞察到:在中国人身上有着一种沉疴已久的精神疾病--"灵魂饥饿",这是传统的信仰价值体系崩溃后,新的信仰价值体系未曾建立时出现的一种病症.穆旦针对"灵魂饥饿"这一现实,通过对中外文化的对比考察,找到了一条救治这一精神疾病的药方--基督信仰,借以医治自己和别人.