ICOS Costimulation at the Tumor Site in Combination with CTLA-4 Blockade Therapy Elicits Strong Tumor Immunity

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新型肿瘤标志物:Mu-GlcNAc

作者发现了一个新的肿瘤标志物MA153,其化学结构为Mu-GlcNAc（粘蛋白1-N-乙酰氨基葡萄糖）,它可与单克隆抗体Ma695和相关Aptamer（适配体MA153-A）形成Ma695-Mu-GlcNAc-MA153-A式的夹心反应。临床血清学检测表明,Mu-GlcNAc存在于癌症患者血中,以1U/mL为正常界值,Mu-GlcNAc的肿瘤特异度达95%,癌症检出的灵敏度对乳腺癌、胰腺癌、肝癌、肺癌、食管癌、口腔癌、结肠癌、胆管癌、卵巢癌、宫颈癌、子宫癌,分别为80%、74%、68%、70%、75%、50%、60%、55%、70%、64%、60%。本研究资料显示,Mu-GlcNAc是一个新的良好广谱肿瘤标志物。     

Rational design and performance testing of aptamer-based electrochemical biosensors for adenosine

This work emphasizes on the design criteria of aptamer-based biosensors for adenosine and the comparison of their performances by using both electrochemical and biochemical methods. The adenosine biosensors have been typically prepared by hybridizing a short bridging DNA (modified with a thiol for the attachment to gold electrode) to the aptamer strand that releases upon adenosine binding. We have carefully compared the two “isomeric” designs, one with the thiol-linker tethered to the 3′-hydroxyl and the other to the 5′-phosphate end of the bridging DNA. It has been demonstrated through electrochemical and gel electrophoresis experiments that the 3′-thiol bridged sensor shows much better performance than its 5′-counterpart on surface, whereas in solution phase the two sensor systems are equally sensitive. We believe that the “transient” secondary structure of the aptamer sequence restricts the freedom of the strand displacement upon analyte binding, leading to a sluggish release of the aptamer strand from the 5′-thiol-bridging DNA.     

核酸适体在儿童恶性肿瘤诊断与靶向治疗中的研究进展

核酸适体（aptamer）是运用指数富集的配体系统进化技术（SELEX）从体外人工合成的随机寡核苷酸序列库中经过多轮筛选后得到的单链DNA或RNA,它可以高亲和力与金属离子、小分子、糖类、脂质以及蛋白质等靶标特异性结合,具有制备方便、热稳定性好、低免疫原性等优点。核酸适体在分子成像、生物传感、疾病早期诊断及药物靶向治疗等生物医学领域中有很大的应用潜能。在儿童恶性肿瘤中,核酸适体技术具有实现肿瘤的早期诊断以及靶向治疗的应用前景,可避免传统化疗带来的儿童生长发育障碍以及远期的脏器功能不良等副作用。本文总结了与儿童恶性肿瘤相关的核酸适体筛选与应用的研究进展。     

SELEX技术筛选特异性结合高转移性肺癌细胞Anip973的单链DNA适配子

目的:筛选获得一种高亲和力的能特异性结合高转移性肺癌细胞Anip973的单链DNA适配子.方法:体外合成全长88 nt的单链DNA文库,通过反复的SELEX筛选获得特异性结合Anip973细胞的单链DNA适配子,并通过生物素-辣根过氧化物酶-链霉亲和素系统初步测定筛选的适配子与细胞的亲和力,将结合力最高的适配子库进一步...     

利用SELEX技术构建靶向光敏药物

肿瘤是目前威胁人类健康最凶险的疾病之一.寻找选择性好、副作用小的防治恶性肿瘤的新方法仍然是当今医学研究的热点.光动力学疗法是近年来兴起的极具应用前景的肿瘤治疗新方法.开发新型靶向光敏剂和开展靶向光动力治疗是进一步发展光动力治疗肿瘤的重要方向.本文简述了目前光动力治疗及常用光敏剂的研究现状,并提出通过指数式富集法配体进化技术即SELEX技术构建靶向光敏药物的新设想.     

Targeted cancer drug delivery with aptamer-functionalized polymeric nanoparticles

Abstract

Based on exceptional advantages of aptamers, increasing attention has been presented in the utilise of them as targeted ligands for cancer drug delivery. Recently, the progress of aptamer-targeted nanoparticles has presented new therapeutic systems for several types of cancer with decreased toxicity and improved efficacy. We highlight some of the promising formulations of aptamer-conjugated polymeric nanoparticles for specific targeted drug delivery to cancer cells. This review paper focuses on the current progresses in the use of the novel strategies to aptamer-targeted drug delivery for chemotherapy. An extensive literature review was performed using internet database, mainly PubMed based on MeSH keywords. The searches included full-text publications written in English without any limitation in date. The abstracts, reviews, books as well as studies without obvious relating of aptamers as targeted ligands for cancer drug delivery were excluded from the study. The reviewed literature revealed that aptamers with ability to modify and conjugate to various molecules can be used as targeted cancer therapy agents. However, development of aptamers unique to each individual’s tumour to the development of personalised medicine seems to be needed.     

适配子型压电石英晶体传感器检测人免疫球蛋白E的实验研究

目的研制适配子型压电子石英晶体传感器阵列与常用的免疫分析方法进行比较,以评价压电石英晶体传感器阵列检测灵敏度、特异性与临床检测的可行性。方法以AT切型、基频10MHz的镀金石英晶体作为换能器,将抗人免疫球蛋白E适配子固定在石英晶体电极表面,用2×5检测池阵列构建新型适配子型压电石英晶体传感器;分别进行标准品及人血清免疫球蛋白E的检测,研究了检测灵敏度、特异性等检测指标。结果该传感器可快速完成检测且无非特异性反应,在检测范围内传感器的响应特性良好,压电晶体频率偏移值与免疫球蛋白浓度呈良好的线性关系;将此免疫传感器用于人血清标本的测定,结果与化学发光法符合(r值=0.9924)。结论研制的传感器阵列具有灵敏度高、特异性好,检测通量高,无需标记,操作简便,能实时在线检测等优点,可用于临床实验诊断,具有较高的临床推广应用价值。