RNA-dependent RNA polymerase encoded by hepatitis C virus: biomedical applications

The hepatitis C viruses (HCVs) are a group of small enveloped RNA viruses that have been viewed as a leading cause of chronic hepatitis in humans. Infections by HCV represent a serious global health problem, because millions of people worldwide are infected and no efficient treatment is available at the present time. Since HCV was identified in 1989, considerable effort has been devoted to the discovery and development of novel molecules to treat HCV-related diseases. One of the approaches is the development of novel inhibitors that interrupt the normal functions of HCV NS5B, an RNA-dependent RNA polymerase essential to HCV replication. This review summarizes recent advances in the biochemical and structural understanding of HCV NS5B polymerase as well as in the development of antiviral agents targeting this important enzyme. Received 19 March 2002; received after revision 23 April 2002; accepted 23 April 2002     

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.     

慢病毒载体研究进展

慢病毒作为一种特殊的逆转录病毒,与通常使用的逆转录病毒载体和腺病毒载体比较,具有可感染分裂细胞及非分裂细胞、转移基因片段容量较大、目的基因表达时间长、不易诱发宿主免疫反应等优点,已成为当前基因治疗和转基因动物中载体研究的热点。近年来对其基础生物学特性、载体改造及其应用等研究均取得了较大进展。本文就慢病毒载体及应用方面的研究进展作一综述。     

姜黄素对鼻咽癌细胞株CNE-2Z—H5裸鼠移植瘤增殖的影响

目的：研究姜黄素对人低分化鼻咽癌细胞系亚克隆株CNE-2Z—HS裸鼠移植瘤生长和增殖的影响。方法：复制人低分化鼻咽癌细胞系亚克隆株CNE-2Z-H5裸鼠移植瘤模型，观察姜黄素对移植瘤生长的影响。结果裸鼠体内实验显示姜黄素可以抑制移植瘤的生长。不同浓度姜黄素组移植瘤瘤重与溶剂对照组比较有降低趋势，高剂量组降低更明显，差异有极显著性（P〈O．001），抑瘤率达59．75％。结论姜黄素可以抑制CNE-2Z—H5细胞裸鼠移植瘤的生长，其可能在鼻咽癌的治疗中具有一定的价值，值得进一步深入研究。     

端粒酶与妇科肿瘤诊治的研究进展

端粒酶是一种RNA依赖的逆转录酶,其激活是细胞永生化和肿瘤形成的关键步骤。在妇科肿瘤的发生过程中,端粒酶活性和hTERT的表达与肿瘤的进展具有相关性。端粒酶及其催化亚单位成为妇科肿瘤早期诊断和预后判断的生物学指标。因此,抑制端粒酶活性有望成为妇科肿瘤治疗的新策略。     

孤独症儿童治疗方法概况

自1943年以来,经过半个多世纪的时间,关于孤独症的理论与治疗技术日趋成熟。本文对一些主要治疗方法与技术进行了简要回顾,着重介绍了近年来在美国有广泛应用的RDI疗法。针对我国孤独症教育治疗不足的现状对治疗过程中的问题进行了一定归纳。     

原发性肝癌介入治疗的护理

目的:明确原发性肝癌介入治疗护理经验及注意事项.方法:回顾性分析2004年~2005年我院所收治的42例原发性肝癌患者的临床资料.结果:经皮经导管肝动脉栓塞术前后,由于精神因素、体质差异、化疗药物等的作用,患者都有不同程度紧张、恶心、呕吐、腹痛、发热等症状.结论:通过正确的术前、术中及术后的护理,可以使肝癌介入治疗顺利进行,减少副作用,提高疗效.     

激光治疗肿瘤的计算研究

根据激光治疗肿瘤的机理建立了激光治疗肿瘤的理论计算模型,并应用有限元计算方法对双光纤照射椭球形肿瘤组织的模型进行了定量计算研究;研究结果表明,对于长轴为2.0 cm、短轴为1.2 cm的实心椭球形肿瘤体,将2个直径为0.4 mm的球状光纤对称放置在主轴上相距0.8~1.0 cm的范围内,可以使光动力学的效果和热疗的效果同时达到最佳值。     

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。     

姜黄素对鼻咽癌细胞株CNE-2Z-H5裸鼠移植瘤增殖的影响

目的研究姜黄素对人低分化鼻咽癌细胞系亚克隆株CNE-2Z-H5裸鼠移植瘤生长和增殖的影响。方法复制人低分化鼻咽癌细胞系亚克隆株CNE-2Z-H5裸鼠移植瘤模型,观察姜黄素对移植瘤生长的影响。结果裸鼠体内实验显示姜黄素可以抑制移植瘤的生长。不同浓度姜黄素组移植瘤瘤重与溶剂对照组比较有降低趋势,高剂量组降低更明显,差异有极显著性(P<0.001),抑瘤率达59.75%。结论姜黄素可以抑制CNE-2Z-H5细胞裸鼠移植瘤的生长,其可能在鼻咽癌的治疗中具有一定的价值,值得进一步深入研究。