CRISPR/Cas系统在生物核酸检测中的应用进展

传统的核酸检测技术耗时长且对操作人员的专业水平要求高,开发精准、快速、便携、低成本、高特异性和灵敏度的新核酸检测系统具有重要意义。目前,CRISPR/Cas系统不但被广泛应用于基因编辑,而且随着部分Cas蛋白“附带切割”活性的发现,灵敏度高、特异性强的CRISPR/Cas系统被逐步开发为新型生物传感工具,用于生物的核酸检测。随着各种Cas效应蛋白的发现,研究人员开发了多种基于CRISPR/Cas系统的核酸检测方法(如SHERLOCK、HOLMES、DETECTR、HUDSON和CASLFA等)可检测各种靶标(包括细菌、病毒、癌症突变等)。笔者综述了当前重要的用于不同靶标检测的CRISPR/Cas系统,包括检测核酸、其他小分子物质及病原微生物,讨论了其面临的挑战和应用潜力,最后推断,随着CRISPR/Cas系统的不断发展和完善,该系统在生物传感及临床分子检测领域的应用会越来越广泛。     

污染土壤的生物标记物研究进展

生物标记物是指示环境中污染物危害效应的生物信号。利用生物标记物进行污染土壤的检测和定量分析是最可行的方法之一。本文主要综述了近年来一些典型的、指示土壤污染的几类生物标记物 (如细胞色素P4 5 0加氧酶系统、细胞抗氧化酶及DNA指纹技术 )的最新研究进展 ,并探讨了生物标记物在污染土壤修复效果评价及其早期诊断方面的应用前景。     

抗癌药物作用预测计算方法的研究现状与展望

对精准医疗即个体化医疗理念的探讨与实践是当下医学研究的热门课题,如果精准医疗的设想实现可为患者提供更加精确有效的治疗方案,而对癌症的研究是医学界尚未攻破且意义重大的研究课题,也是和精准医疗结合最密切的课题之一。应用生物信息学的计算方法可以通过分析患者的概况来为癌症患者的药物选择提供有效方案,从而提高癌症患者的生存率。通过参考多篇使用计算方法研究抗癌药物作用的研究成果,从数据源和网络分析、机器学习和深度学习等计算方法两个方面总结了当前的研究成果,并对该课题存在的问题与未来发展趋势做出了分析与展望。     

基于电化学生物传感器的核酸肿瘤标志物检测研究进展

肿瘤生物标志物可以实现对癌症的早期诊断,监测肿瘤的发展和预后.随着高通量测序技术的发展,各种类型的核酸被发现与肿瘤的发生发展相关,可作为核酸肿瘤标志物,而且它们对癌症的早期诊断有着重要意义.由于核酸大都具有不稳定性、表达的动态性和低丰度等特点,因此快速灵敏并特异地检测该类肿瘤标志物就显得尤为重要.电化学生物传感器作为一类快速发展的检测方法能够满足这些需求.与传统的检测方法相比,电化学分析法彰显高效、灵敏、简便等优点,而且电化学检测设备装置轻便、廉价且易于微型化和集成化.近年来,用于检测核酸的电化学生物传感器取得了相当大的发展,在精准医疗中具有潜在的应用前景.本文从各种类型的核酸肿瘤标志物入手,介绍检测核酸标志物的电化学传感器在近年来的发展情况,特别是对电化学传感器体系中的探针设计和信号放大策略两个方面进行重点介绍.     

MicroRNA：从生物标志物到基因治疗

microRNA（miRNA）作为生物标志物和治疗靶点的价值已被公认。简介miRNA及其生物合成与功能,探讨 miRNA与疾病 及癌症的关系,综述miRNA在疾病治疗中及作为生物标志物的应用研究。     

在医疗保健领域开发和使用生物标记物的政策性问题

描述了发展中的生物标记物所处的科学、产业、监管和医疗保健管理系统背景,指出了可能阻碍生物标记物研究、发现、发展、商业化及最终临床应用的一些障碍,聚焦了医疗保健中基于生物标记物的诊断方法和医学检验的应用,探索了生物标记物在改良药物开发中的应用。     

蚯蚓生物标记物在土壤生态风险评价中的应用

蚯蚓在土壤中行使了很多重要的生态功能,蚯蚓生物标记物常用作土壤污染风险评价研究。这篇综述的目的是探讨当前蚯蚓生物标记物研究是否可以应用到实际的土壤污染风险评价。1)讨论了蚯蚓生物标记物在土壤污染风险评价体系中的重要性,认为它是化学分析方法的有益补充,可以提供更为全面和客观的土壤污染信息;2)综述了相关研究中所使用的蚯蚓类型,土壤类型和生物标记物类型,及其它试验设计要素和最后结果的变异,认为目前蚯蚓生物标记物研究以实验室基础研究为主,筛选出了大量的生物标记物,一定程度上揭示了生物标记物的对各类典型污染物及其组合的应答机制;同时也认为,未来的蚯蚓生物标记物研究应该重点探讨将其应用到实际的土壤污染风险评价中的可行性及如何应用;3)目前不同研究之间从试验设计到结果都具有很大的变异,难以通过综合比较获得完全可靠的具有实践意义的结论和成果,因此,有必要通过建立标准化的蚯蚓生物标记物研究方法,推动生物标记物的研究工作;4)提出了蚯蚓生物标记物研究方法标准化的具体建议,推荐了蚯蚓生物标记物走向实际应用所需要解决的问题。     

滚环扩增信号放大技术在生物检测中应用的研究进展

滚环扩增(Rolling circle amplification,RCA)是一种快速、灵敏且恒温的单链DNA(Single-stranded DNA,ssDNA)扩增技术,与染色或探针联用可实现检测信号的放大,在生物检测等方面得到广泛的应用。文中对RCA的构建方法进行了简介,综述了近几年其在致病菌、核酸肿瘤标记物、蛋白质、生物小分子和病毒等检测中的研究进展,并对其未来的发展趋势进行了展望。     

CDK4/6信号通路靶向治疗剂在癌症治疗中的研究进展

多数癌症的发生发展都具有细胞周期高度活化的特性。细胞周期蛋白依赖性激酶4/6 (CDK4/6)不仅在细胞有丝分裂中发挥了巨大作用,而且参与了衰老、凋亡和组蛋白调节等诸多生物学过程,并在多种癌症的发生发展中被异常激活。FDA批准了Palbociclib、Ribociclib和Abemaciclib等3种靶向CDK4/6的抑制剂,在临床上也取得了显著的疗效,有效地延长了内分泌治疗耐药的乳腺癌患者以及其他多种类型癌症患者的生存期。但这些抑制剂的临床应用也面临着获得性耐药等问题。文中综述了CDK4/6参与的生物调控过程,及其抑制剂在癌症治疗中的应用和面临的耐药性挑战。     

通过检测血清中hTERT的mRNA能诊断出早期癌症

日本鸟取大学医学部药物治疗学专业的三岛典正先生与研究生院医学系研究科基因医疗学专业的汐田刚史先生等人的研究小组成功开发了检测血清中hTERT的mRNA的高灵敏度定量方法[hTERT是和癌的发生、进展有关的端粒酶（telomerase）的催化单位]。并且在对多个医疗机构对临床样品的血清中hTERT的mRNA进行评估的过程中，发现在肝细胞癌的诊断上这个方法的灵敏度和特异性均优于其他肿瘤标记物．是一个能够更早期查出癌症的标记物。[第一段]     

Clinical proteomics-driven precision medicine for targeted cancer therapy: current overview and future perspectives

Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy.     

Tumour biomarkers—Tracing the molecular function and clinical implication

In recent years, with the increase in cancer mortality caused by metastasis, and with the development of individualized and precise medical treatment, early diagnosis with precision becomes the key to decrease the death rate. Since detecting tumour biomarkers in body fluids is the most non‐invasive way to identify the status of tumour development, it has been widely investigated for the usage in clinic. These biomarkers include different expression or mutation in microRNAs (miRNAs), circulating tumour DNAs (ctDNAs), proteins, exosomes and circulating tumour cells (CTCs). In the present article, we summarized and discussed some updated research on these biomarkers. We overviewed their biological functions and evaluated their multiple roles in human and small animal clinical treatment, including diagnosis of cancers, classification of cancers, prognostic and predictive values for therapy response, monitors for therapy efficacy, and anti‐cancer therapeutics. Biomarkers including different expression or mutation in miRNAs, ctDNAs, proteins, exosomes and CTCs provide more choice for early diagnosis of tumour detection at early stage before metastasis. Combination detection of these tumour biomarkers may provide higher accuracy at the lowest molecule combination number for tumour early detection. Moreover, tumour biomarkers can provide valuable suggestions for clinical anti‐cancer treatment and execute monitoring of treatment efficiency.     

HIF1A predicts the efficacy of anti-PD-1 therapy in advanced clear cell renal cell carcinoma

Immunotherapy for cancer has become a revolutionary treatment, with the progress of immunological research on cancer. Cancer patients have also become more diversified in drug selection. Individualized medical care of patients is more important in the era of precision medicine. For advanced clear cell renal cell carcinoma (ccRCC) patients, immunotherapy and targeted therapy are the two most important treatments. The development of biomarkers for predicting the efficacy of immunotherapy or targeted therapy is indispensable for individualized medicine. There is no clear biomarker that can accurately predict the efficacy of immunotherapy for advanced ccRCC patients. Our study found that HIF1A could be used as a biomarker for predicting the anti-PD-1 therapy efficacy of patients with advanced ccRCC, and its prediction accuracy was even stronger than that of PD-1/PD-L1. HIF1A is expected to help patients with advanced ccRCC choose therapeutic drugs.     

Metabolomics for mitochondrial and cancer studies

Metabolomics, a high-throughput global metabolite analysis, is a burgeoning field, and in recent times has shown substantial evidence to support its emerging role in cancer diagnosis, cancer recurrence, and prognosis, as well as its impact in identifying novel cancer biomarkers and developing cancer therapeutics. Newly evolving advances in disease diagnostics and therapy will further facilitate future growth in the field of metabolomics, especially in cancer, where there is a dire need for sensitive and more affordable diagnostic tools and an urgency to develop effective therapies and identify reliable biomarkers to predict accurately the response to a therapy. Here, we review the application of metabolomics in cancer and mitochondrial studies and its role in enabling the understanding of altered metabolism and malignant transformation during cancer growth and metastasis. The recent developments in the area of metabolic flux analysis may help to close the gap between clinical metabolomics research and the development of cancer metabolome. In the era of personalized medicine with more and more patient specific targeted therapies being used, we need reliable, dynamic, faster, and yet sensitive biomarkers both to track the disease and to develop and evolve therapies during the course of treatment. Recent advances in metabolomics along with the novel strategies to analyze, understand, and construct the metabolic pathways opens this window of opportunity in a very cost-effective manner.     

Biomarkers discovery in cancer--up-dates in methodology

Biomarkers are biomolecules that can indicate normal/pathological processes, or physiological responses to therapy. Due to the serum abundance in proteins, such as albumin and lypo/glycoproteins, biomarkers are difficult to assess. Serum biomarkers identification can contribute to personalized medicine and improve cancer diagnostic and prognostic. The paper summarizes some of the proteomics techniques and the workflow used for protein signatures identification associated to cancer development. Thus, biomarkers validated for prostatic, breast, cervical or lung cancers are presented as examples for clinical application of serum markers. In spite of the continuous research efforts, there are only few validated biomarkers that have proved a good predictive power in cancer. Modern technology and the combination of various techniques used for proteins quantification represent important means for the identification and validation of new biomarkers.     

Proteomic analysis at the bedside: early detection of cancer

Proteomic technologies promise to accelerate rapidly a new era in molecular medicine, especially in the detection and discovery of disease-related biomarkers. These technologies have no bigger impact than in the field of human cancer research. Beyond lifestyle-associated prevention strategies, early detection of cancer has the most profound impact on the ultimate course of the disease: the earlier the cancer is detected, the better the prognosis. Today, new proteomic technologies are being used to discover new diagnostic and prognostic biomarkers for the early detection and treatment of cancer that will have important implications at the bedside.     

放射性药物在肿瘤靶向治疗中的应用

放射性药物指供临床诊断或治疗用的放射性核素制剂或其标记化合物。放射性核素靶向治疗是利用对肿瘤细胞具有特异高亲和力的分子载体将核素定向导入特定的肿瘤组织,对肿瘤进行治疗。与传统的放疗和化疗相比,其具有选择性杀伤肿瘤细胞的特点。随着核医学的发展,SPECT/CT、PET/CT的普及,新靶点的发现和新型放射性药物的研发,利用放射性药物进行靶向治疗在肿瘤临床治疗中占据的地位越来越重要。本文简述了放射性药物的分类、组成及特点;综述了针对肿瘤相关抗原的放射免疫药物在非霍奇金淋巴瘤、结直肠癌和前列腺癌中的应用;受体介导的放射性核素药物在治疗神经内分泌肿瘤、前列腺癌和乳腺癌中的临床应用以及基于基因修饰的放射性药物在肿瘤靶向治疗中的实验研究进展。最后总结了放射性药物在肿瘤靶向治疗中的应用前景与面临的挑战,以期为靶向治疗肿瘤的放射性药物的开发和临床应用提供一些参考。     

Proteomic contributions to personalized cancer care

Cancer impacts each patient and family differently. Our current understanding of the disease is primarily limited to clinical hallmarks of cancer, but many specific molecular mechanisms remain elusive. Genetic markers can be used to determine predisposition to tumor development, but molecularly targeted treatment strategies that improve patient prognosis are not widely available for most cancers. Individualized care plans, also described as personalized medicine, still must be developed by understanding and implementing basic science research into clinical treatment. Proteomics holds great promise in contributing to the prevention and cure of cancer because it provides unique tools for discovery of biomarkers and therapeutic targets. As such, proteomics can help translate basic science discoveries into the clinical practice of personalized medicine. Here we describe how biological mass spectrometry and proteome analysis interact with other major patient care and research initiatives and present vignettes illustrating efforts in discovery of diagnostic biomarkers for ovarian cancer, development of treatment strategies in lung cancer, and monitoring prognosis and relapse in multiple myeloma patients.     

microRNAs: New prognostic,diagnostic, and therapeutic biomarkers in cervical cancer

Cervical cancer is as a kind of cancer beginning from the cervix. Given that cervical cancer could be observed in women who infected with papillomavirus, regular oral contraceptives, and multiple pregnancies. Early detection of cervical cancer is one of the most important aspects of the therapy of this malignancy. Despite several efforts, finding and developing new biomarkers for cervical cancer diagnosis are required. Among various prognostic, diagnostic, and therapeutic biomarkers, miRNA have been emerged as powerful biomarkers for detection, treatment, and monitoring of response to therapy in cervical cancer. Here, we summarized various miRNAs as an employable platform for prognostic, diagnostic, and therapeutic biomarkers in the treatment of cervical cancer.     

用于肿瘤治疗的免疫检查点抑制剂相关预测生物标志物的研究进展

恶性肿瘤是严重威胁人类健康和社会发展的疾病。传统的肿瘤治疗方法如手术、放疗、化疗和靶向治疗等不能完全满足临床治疗的需求,新兴的免疫治疗成为了肿瘤治疗领域的研究热点。免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)作为一种肿瘤免疫治疗方法,已获批用于治疗多种肿瘤,如肺癌、肝癌、胃癌和结直肠癌等。然而,ICIs在临床使用过程中,只有少数患者会出现持久反应,一些患者还会出现耐药和不良反应。因此,预测生物标志物的鉴定和开发对提高ICIs的治疗效果至关重要。肿瘤ICIs预测生物标志物主要包括肿瘤生物标志物、肿瘤微环境生物标志物、循环相关生物标志物、宿主环境生物标志物以及组合生物标志物等,对患者筛查、个体化治疗和预后评估具有重要意义。本文就肿瘤ICIs治疗预测生物标志物的前沿进展作一综述。