叶酸受体介导的小分子抗肿瘤药物研究进展

靶向肿瘤细胞的药物研发近年来受到了极大的关注,除了阻断细胞信号通路的蛋白激酶抑制剂外,叶酸受体介导的药物释放也引起了研究者的广泛注意。叶酸受体在大多数人体肿瘤细胞中高度表达,而在正常细胞中很少表达或不表达。叶酸可以通过叶酸受体介导的内吞作用进入细胞,这为药物选择性释放提供了很好的途径。本文对近些年来基于叶酸受体介导的药物作用机制、设计策略,以及研发的叶酸-抗肿瘤药物缀合物进行综述,并介绍了该领域临床研究取得的最新进展。     

靶向CD155及其受体的药物研究进展

分化簇155（CD155）是一种单次跨膜的细胞表面蛋白,在正常组织中表达量很少或不表达,但在包括胰腺癌、胆管癌、结直肠癌、非小细胞肺癌、膀胱癌、乳腺癌的多种恶性肿瘤中高表达,使其能够成为抗肿瘤药物的理想靶点。CD155作为细胞黏附分子参与肿瘤细胞的黏附、迁移和极化,还作为免疫调节分子与T细胞或NK细胞上的包括TIGIT、DNAM-1、CD96的共刺激或共抑制受体相互作用,发挥免疫调节作用,影响免疫微环境。目前靶向CD155及其受体的药物研发火热,其高亲和力受体TITIG有多种药物进入III期临床,直接靶向CD155及其受体DNAM-1和CD96的肿瘤治疗也逐渐增加。通过对靶向CD155及其受体的药物研究进展进行综述,以期为后续的药物研发提供依据。     

诱导细胞凋亡的抗肿瘤抗生素

细胞凋亡是肿瘤防治的一个非常重要的机制，诱导细胞凋亡的抗肿瘤抗生素的面世开辟了肿瘤化疗药物研发的新途径。概述诱导细胞凋亡的抗肿瘤抗生素种类、来源、抗肿瘤谱及实验研究，并对其作用机制进行探讨。     

肿瘤组织中的CYP1B1及其抑制剂的抗肿瘤活性

综述细胞色素P450酶（CYP）1B1在肿瘤组织中的表达、在肿瘤的发生发展和诊断与干预中的作用以及其抑制剂的研发和抗肿瘤活性。CYP1B1在正常组织中低表达,而在许多肿瘤组织中则特异性高表达,可激活和代谢产生致癌物质,并可致多种抗癌药物代谢失活而使肿瘤耐药,因此它既可用于早期癌症的诊断,又可作为理想的抗肿瘤作用靶点而用于药物研发。     

蛋白质组学及其在肝癌诊疗中的研究进展

蛋白质组学是一门在大规模水平上研究某一类型细胞、组织或体液中的所有蛋白质组成及其功能的新兴学科。其以细胞或器官表达的所有蛋白质为研究对象,通过凝胶电泳、生物质谱及生物信息学等技术,达到分离、鉴定、分析蛋白质的目的。肝癌是世界上病死率较高的恶性肿瘤之一,运用蛋白质组学技术,可以了解肝癌的发生、发展机制,在诊断和治疗方面产生价值。本文将解释蛋白质组学的概念及主要技术,介绍蛋白质组学在肝癌研究中的意义,阐述蛋白质组学在肝癌的早期诊断,标记物的筛选以及药物靶标的选择中体现出的重要应用。随着蛋白质组学的逐步完善和现代生物技术的迅速发展,这项技术将在肝癌等生命科学领域发挥更显著的作用。     

溶质载体转运体在肿瘤中的表达及其在抗肿瘤药物研究中的现状

溶质载体(SLC)转运体负责各种内源性和外源性化合物的细胞运输，由于其生物学功能和组织特异性表达，SLC转运体不仅在药物处置扮演重要角色，而且在药物-药物相互作用中发挥着重要作用，并具有作为药物递送靶标的巨大潜力。因此，研发SLC转运体的抑制药或促进药、针对SLC转运底物的靶向前药或制剂也成为研究热点。本综述归纳了SLC转运体在肿瘤中的表达现象，首次总结了基于SLC转运体为靶点的靶向抗肿瘤药物(SLC抑制药、SLC前药和靶向SLC纳米制剂)的最新研究进展，为SLC转运体在肿瘤中的研究和应用提供参考。     

蛋白质组学与新药开发

目的将蛋白质组学应用于新药研发,为寻找到更多的新药提供依据。方法查阅文献,简述蛋白质组学在药物开发中的作用。结果与结论蛋白组学在药物开发中的作用越来越重要,通过蛋白质组学开发出的药物将得到更广泛的应用。     

蛋白质组学在药物研究中的应用

蛋白质组学作为一门新兴学科,其在药物研究中的应用,将大大加速和简化新药的研发过程。本文对蛋白质组学及其在药物研究中的应用作一综述。     

蛋白质组学及其在消化道肿瘤中的研究进展

随着人类基因组计划的完成,后基因组时代即蛋白质组学的研究已拉开了序幕。其主要任务是分析和鉴定细胞内基因所表达的全部蛋白质的结构、功能、相互作用以及它们在疾病过程中的作用。1蛋白质组学的概念广义上讲,蛋白质组是指“一个细胞或一个组织基因组所表达的全部蛋白质”。     

多靶点抗肿瘤天然产物研究进展

天然产物及其衍生物是抗肿瘤药物的重要组成部分。目前在临床上应用的天然产物来源的抗肿瘤药物以传统细胞毒类药物或靶向某一特定靶点的分子靶向药物为主,其应用受限于药物相关不良反应和肿瘤耐药。近年的研究表明,抗肿瘤活性天然产物往往能够靶向肿瘤细胞的多个靶点,影响肿瘤发生发展中的多个过程。由于肿瘤是一种多因素诱发的系统性疾病,多靶点天然产物在肿瘤治疗方面具有独特潜力。目前已发现的多靶点抗肿瘤天然产物的作用靶标和作用机制往往不够明确,限制了其进一步的开发。本文基于现代分子药理学理论,以多个典型的多靶点抗肿瘤天然产物为例进行综述,介绍了目前这些多靶点药物的作用机制、靶点确认和结构优化等研究进展,并对其作为抗肿瘤药物的研发前景进行了展望。     

Implications of salivary proteomics in drug discovery and development: a focus on cancer drug discovery

Human saliva proteomics has proven to be a novel approach in the search for protein biomarkers for non-invasive detection of human cancers. This approach may also have implications within the process of anti-cancer drug discovery. Information from saliva proteomic measurements may contribute to the target discovery and validation, assessment of efficacy and toxicity of candidate drugs, identification of disease subgroups, and prediction of responses of individual patients. In this article, we aim to give a brief overview on human saliva proteome analysis, as well as its applications to cancer biomarker discovery. Potential applications of saliva proteomics in anticancer drug discovery and development will also be discussed.     

精氨酸及其相关药物的抗肿瘤作用研究近况

已有研究发现,肿瘤细胞中的精氨酸含量与细胞的生长和凋亡有密切的关系。介绍精氨酸在机体内的代谢特征,抑制肿瘤的机制,以及目前国内外对精氨酸及精氨酸酶类抗肿瘤药物的开发和应用研究情况。     

The development of hyaluronan as a drug transporter and excipient for chemotherapeutic drugs

Despite advances in chemotherapeutic regimens, the treatment of metastatic cancer remains a challenge. A key problem with chemotherapy drugs is nonspecific drug distribution, resulting in low tumor concentrations and systemic toxicity. The holy grail of clinical cancer research has been to establish more specific ways of directing therapeutics to tumors, whether through more targeted anti-cancer agents or via the method of delivery. Many tumor cells show up-regulated expression of receptors for the polysaccharide hyaluronan (HA), resulting in HA having a high affinity for tumors. This observation has led to the preclinical development of HA-cytotoxin bioconjugates that utilize HA as the tumor recognition moiety. The primary challenges have been organ-directed toxicity and limited efficacy. An alternative, simpler strategy has been to use the large volumetric domain of HA to entrain small chemotherapeutic drugs within the HA matrix. The resultant HA/drug formulation accumulates in the microvascular of the tumor, forming a microembolism that increases drug retention at the tumor site and allows for active tumor uptake through HA receptors. Clinical trials of HA formulations of three anti-cancer drugs have been undertaken and have demonstrated that such formulations are safe and efficacious. Within these formulations we postulate that HA is acting as a novel excipient, capable of improving the therapeutic index of the active anti-cancer agent.     

Ethnobotany and ethnopharmacy--their role for anti-cancer drug development

Local and traditional knowledge has been the starting point for many successful drug development projects over the last decades. Here we discuss some examples of anti-cancer drugs which have had enormous impact as anti-cancer agents (camptothecan, taxol and derivatives) and a few examples of drugs currently under various stages of preclinical development. Ethnobotanists investigate the relationship between humans and plants in all its complexity, and such research is generally based on a detailed observation and study of the use a society makes of plants. The requirements of modern research on natural products as, for example, outlined in the Convention on Biological Diversity (Rio Convention) and the overall approach in ethnobotanical research are also discussed. Selected phytochemical-pharmacological studies based on traditional plant use are used to highlight the potential of ethnobotany driven anti-cancer research. The link between traditionally used plants and targets of the NF-kappaB pathway is discussed using on an EU-funded, multidisciplinary project as an example. Lastly the potential of chemopreventive agents derived from traditional food plants is briefly addressed.     

Combinatorial application of nucleic acid-based agents targeting protein kinases for cancer treatment

The progress made in cancer biology, genetics and biotechnology has led to a major transition in cancer drug design and development, from an emphasis on non-specific, cytotoxic agents to specific, molecular-targeted smart cancer drugs. Many of these targeted agents have shown to have improved selectivity for cancer versus normal cells and are associated with better anti-tumor efficacy and lower toxicity. The new generation of anti-cancer drugs requires low concentrations and minimizes unwanted side effects. Their use leads to enhanced anti-cancer effects and to a reduction of chemotherapy resistance. Still, resistance to common chemotherapeutic agents is a major obstacle in cancer treatment. Silencing of cancer-relevant genes is a challenging strategy to reduce resistance and to sensitize cancer cells towards anti-neoplastic agents. Resistance can be an intrinsic problem of the tumor or can be acquired during the life time of the tumor. A fascinating species of anti-cancer drugs include antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) which are able to specifically down-regulate the expression of the target genes. The combination of nucleic acid-based agents with anti-neoplastic drugs can induce synergistic induction of cell cycle arrest, apoptosis and reduced cell proliferation in vitro or tumor growth in vivo. These two strategies (ASOs and siRNAs) will help to improve current therapeutic regimens. In addition, the combination of targeted drugs with common chemotherapeutic agents might be able to make resistant cells again sensitive towards a chemotherapeutic agent.     

中枢神经系统疾病及其药物与蛋白质组学研究进展

阐述中枢神经系统疾病及其药物蛋白质组学研究的最新进展。蛋白质组学是后基因组时代的一门重要学科 ,是从整体水平对蛋白质进行综合分析 ,目前已广泛应用于临床和生物医学各个领域。蛋白质组学研究有助于阐明CNS疾病发生、发展、转归的网络机制 ,寻找疾病特异性蛋白质 ,针对疾病靶点定向合成药物 ,构建分子药理模型 ,高通量地筛选和评价药物的效应及毒副作用。可以预见 ,蛋白质组学将为CNS疾病的诊断、监测和药物研制起到不可估量的作用     

抗癌新药紫杉醇的药剂学研究概况

紫杉醇抗癌活性强，是目前抗癌药物的研究热点。本文对已经上市的紫杉醇注射液，以及目前正在开发中的紫杉醇新处方和气剂型如脂质体、静脉乳、毫微囊、植入片等的研究现状发动态进行综述。     

线粒体毒性评价及其在创新药物安全性评价中的意义

线粒体是细胞内能量和活性氧自由基(ROS)的主要来源,在病理条件下对细胞的存活与死亡具有十分重要的调控作用。线粒体是药物毒性作用的重要靶标。一些抗病毒药物、抗肿瘤药物和抗生素等可显著诱导肝脏和心脏等靶器官线粒体损伤。药物诱导的线粒体损伤可能涉及多条途径和多种机制。近年来研究表明,线粒体毒性可能是多种已上市药物被迫撤市或受到美国FDA"黑框"警告以及候选药物研发失败的重要原因。因此,在创新药物研发过程中,开展线粒体毒性评价具有十分重要的意义。     

分子生物学技术在中药领域的应用及其对中药新药研究的影响

分子生物学技术在中药领域已得到广泛应用,并对中药新药研究产生了深刻的影响.该文介绍了 PCR, RFLP, PCR- RFLP, RAPD等技术和方法在中药的分子鉴定与中药质量控制、中药进化与系统学及中药新品种选育中的应用,以及基因干预和蛋白质组学在中药作用机理研究与新药开发研究方面的应用和影响.     

抗结核病新药作用分子机制研究进展

结核菌耐药现象越来越严重,开发治疗结核病的新药非常紧迫。全球药物研发的一个明显趋势是整合分子生物学及功能基因组方法学,结核病治疗药物的研发也如此。本文综述结核病新药分子靶标的鉴定、分子作用机理与耐药机理以及几种前景较好抗结核新药的药物学特征,并重点概括其应用及研究的最新成果。这将有助于结核病新药研发。