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New Year, New Name and New Milestones Scope — Journal of Circulating Biomarkers 新的一年,新的名字和新的里程碑范围-循环生物标志物杂志
Q3 Medicine Pub Date : 2014-01-01 DOI: 10.5772/58638
S. Jia, W. Kuo
This editorial article introduces a renaming of journal Exosomes and Microvesicles (EXMV) to the Journal of Circulating Biomarkers with a new editorial scope, mission and our approach for the upcoming year in relation to engaging at the international level, the translational art of the study of exosomes and microvesicles, and the interface between exosomes and microvesicles, circulating tumor cells, cell-free circulating DNA and circulating protein markers in precision medicine and drug development. There is a slight change in the members of the Editors in Chief, Editorial Board and extending collaborations to international societies, such as the American Society for Exosomes and Microvesicles (ASEMV).
这篇社论文章介绍了外泌体和微泡(EXMV)杂志更名为循环生物标志物杂志,具有新的编辑范围,任务和我们在即将到来的一年的方法,涉及到国际水平,外泌体和微泡研究的翻译艺术,外泌体和微泡之间的界面,循环肿瘤细胞,无细胞循环DNA和循环蛋白标记物在精准医学和药物开发中的应用。主编和编辑委员会的成员略有变化,并将合作扩展到国际协会,如美国外泌体和微囊泡协会(ASEMV)。
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引用次数: 1
Apoptotic Microparticles as Predicted Biomarkers in Patients with Chronic Heart Failure — Relevance to Inflammatory Cytokines and Outcomes 凋亡微粒作为慢性心力衰竭患者的预测生物标志物-与炎症细胞因子和预后相关
Q3 Medicine Pub Date : 2014-01-01 DOI: 10.5772/60062
A. Berezin, A. Kremzer, Yulia V. Martovitskaya
Aim: To evaluate the relevance of endothelial-derived apoptotic microparticles (EMPs) with inflammatory cytokine outcomes in patients with ischaemic chronic heart failure (CHF). Methods: A total of 154 patients with moderate-to-severe CHF were enrolled in the study. Flow cytometry analysis was used for quantifying the number of EMPs. All-cause mortality, CHF-related death, and CHD-readmission rates were examined. Results: During a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repetitively. Medians of circulating EMPs in survivor and non-survivor patient cohorts were 0.286 n/mL (95% CI = 0.271–0.309 n/mL) and 0.673 n/mL (95% CI = 0.65–0.74 n/mL) (P<0.001). There was a significantly lower concentration of sRANKL, OPG, TNF-alpha, sFAS, and sFAS ligand in the survivor patients when compared with those who met composed endpoints. The sFAS/sFAS ligand ratio in the non-survivor patient cohort was significantly higher than in the survivor cohort (P<0.001). In multivariate model EPMs, NYHA class, NT-pro-BNP, TNF-alpha, sFAS/sFAS ligand ratio, and OPG remained statistically significant for the cumulative endpoint: all-cause mortality, CHF-related death, and CHF-related readmission. Conclusion: Increased apoptotic circulating EMPs, OPG, and FAS-sFAS ligand ratio independently predicted cumulative survival in CHF patients.
目的:评价缺血性慢性心力衰竭(CHF)患者内皮源性凋亡微粒(EMPs)与炎症细胞因子预后的相关性。方法:共纳入154例中重度CHF患者。流式细胞术定量emp的数量。检查全因死亡率、冠心病相关死亡率和冠心病再入院率。结果:在中位随访2.18年期间,21名受试者死亡,106名受试者重复住院。幸存者和非幸存者患者队列的循环EMPs中位数分别为0.286 n/mL (95% CI = 0.271-0.309 n/mL)和0.673 n/mL (95% CI = 0.65-0.74 n/mL) (P<0.001)。与满足组成终点的患者相比,存活患者的sRANKL、OPG、tnf - α、sFAS和sFAS配体浓度显著降低。非存活患者队列中sFAS/sFAS配体比例显著高于存活患者队列(P<0.001)。在多变量模型epm中,NYHA分类、nt - probnp、tnf - α、sFAS/sFAS配体比例和OPG在累积终点:全因死亡率、chf相关死亡和chf相关再入院方面仍具有统计学意义。结论:增加的凋亡循环emp、OPG和FAS-sFAS配体比例独立预测CHF患者的累积生存。
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引用次数: 0
“I Have a Dream” 《我有一个梦想》
Q3 Medicine Pub Date : 2014-01-01 DOI: 10.5772/58709
S. Fais
“I have a dream that one day every valley shall be exalted, every hill and mountain shall be made low, the rough places will be made plains, and the crooked places will be made straight, and the glory of the Lord shall be revealed, and all the flesh shall see it together. This is our hope…” (Martin Luther King, Washington D.C., August 28, 1963)
“我有一个梦想,有一天,每一个山谷都将被填满,每一座丘陵和高山都将被削平,崎岖的地方将变成平原,弯曲的地方将变得笔直,上帝的荣耀将被揭示,所有的人都将共同看到它。”这是我们的希望……”(马丁·路德·金,1963年8月28日,华盛顿)
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引用次数: 0
Protocol Standardization Reveals MV Correlation to Healthy Donor BMI 方案标准化揭示MV与健康供体BMI的相关性
Q3 Medicine Pub Date : 2014-01-01 DOI: 10.5772/58527
P. Hexley, K. Rismiller, C. Robinson, G. Babcock
Microvesicles (MVs) are cell-derived vesicles which are of interest in a clinical setting, as they may be predictive of early signs of disease and/or of treatment progression. However, there are growing concerns about using conventional flow cytometry (cFMC) for the detection and quantification of microvesicles. These concerns range from error-sources in collection through to the physical limitations of detection. Here we present a standardized method for collection and analysis which shows that the MV numbers detected by cFCM correlate to donor Body Mass Index (BMI). Although unlikely to be comprehensive, we also demonstrate how cFCM is a useful and valid tool in the analysis of MVs.
微囊泡(mv)是细胞衍生的囊泡,在临床环境中很有意义,因为它们可以预测疾病的早期症状和/或治疗进展。然而,越来越多的人关注使用传统的流式细胞术(cFMC)来检测和定量微囊泡。这些问题的范围从收集中的错误来源到检测的物理限制。在这里,我们提出了一种标准化的收集和分析方法,表明cFCM检测到的MV数与供体体重指数(BMI)相关。虽然不太可能全面,但我们也证明了cFCM在mv分析中是一个有用和有效的工具。
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引用次数: 1
The Development of Stem Cell-Derived Exosomes as a Cell-Free Regenerative Medicine 干细胞来源外泌体作为无细胞再生医学的发展
Q3 Medicine Pub Date : 2014-01-01 DOI: 10.5772/58597
I. Vishnubhatla, R. Corteling, Lara Stevanato, C. Hicks, J. Sinden
A successful strategy in regenerative medicine over the last decade has been the translation of stem cell therapy to repair diseased or damaged tissue in a wide range of indications, despite limited evidence attributing any therapeutic benefit to cell survival or differentiation. Recent findings, however, have demonstrated that the conditioned media from stem cell cultures can produce similar efficacious effects compared to those observed for cells. This has led to the stem cell paracrine hypothesis, proposing that secreted factors released from the stem cells contribute significantly to their beneficial effects. It has been well documented that stem cells have the ability to release a range of growth factors, cytokines and chemokines relevant to their function; however, these factors are released at levels too low to account for the reported therapeutic effects. Further purification of the conditioned media has since identified that not only are small molecules released by the stem cells, but so too are a large quantity of membrane-bound vesicles, including exosomes, in a functionally relevant manner. In this review, we present our current understanding and explore the evidence supporting the development of stem cell-derived exosomes as a cell-free regenerative medicine.
在过去的十年中,再生医学的一个成功策略是将干细胞疗法转化为修复病变或受损组织的广泛适应症,尽管有限的证据归因于任何治疗益处细胞存活或分化。然而,最近的研究结果表明,干细胞培养的条件培养基可以产生与细胞培养液相似的有效效果。这导致了干细胞旁分泌假说,提出从干细胞释放的分泌因子对其有益作用起着重要作用。文献表明,干细胞具有释放一系列与其功能相关的生长因子、细胞因子和趋化因子的能力;然而,这些因素的释放水平太低,不足以解释报道的治疗效果。条件培养基的进一步纯化已经确定,不仅干细胞释放小分子,而且大量的膜结合囊泡,包括外泌体,也以功能相关的方式释放。在这篇综述中,我们介绍了我们目前的认识,并探讨了支持干细胞来源的外泌体作为无细胞再生医学发展的证据。
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引用次数: 69
Detection of Human c-Myc and EGFR Amplifications in Circulating Extracellular Vesicles in Mouse Tumour Models 小鼠肿瘤模型循环细胞外囊泡中人c-Myc和EGFR扩增的检测
Q3 Medicine Pub Date : 2014-01-01 DOI: 10.5772/59174
L. Balaj, F. Momen-Heravi, Weilin Chen, S. Sivaraman, Xuan Zhang, N. Ludwig, E. Meese, T. Wurdinger, D. Noske, A. Charest, F. Hochberg, P. Vandertop, J. Skog, W. Kuo
Essentially, all cells release extracellular vesicles (EVs) that end up in biofluids, including blood, and the contents of these EVs can provide a window into the status of the cells from which they are released. This is particularly interesting in cancer, since these EVs allow for ‘ex-vivo’ analysis of the properties of the tumours without the need for biopsy. Gene mutations, rearrangements, amplifications, and epigenetic changes in the transcriptome can be monitored in circulating EVs. In this study, we used two human tumour cell lines derived from an epidermoid carcinoma and a medulloblastoma, which had amplification for the epidermal growth factor receptor (EGFR) and c-Myc genes, respectively. Cells were implanted subcutaneously into immunocompromised mice, and levels of gene amplification in both groups of subcutaneous tumours were quantified. We then determined if elevated levels of transcripts for the human EGFR and c-Myc were represented in circulating EVs in tumour-bearing mice. The expression levels of both human EGFR (h-EGFR) and human c-Myc (h-c-Myc) mRNAs in circulating EVs correlated well with their amplified status in the tumours. This data provides further support to the idea that circulating EVs are a potential platform for tumour biomarkers.
从本质上讲,所有细胞都会释放细胞外囊泡(EVs),最终进入包括血液在内的生物体液,这些EVs的内容物可以提供一个窗口,了解细胞的状态。这在癌症中特别有趣,因为这些ev允许在不需要活检的情况下对肿瘤特性进行“离体”分析。基因突变、重排、扩增和转录组的表观遗传变化可以在循环ev中监测。在这项研究中,我们使用了来自表皮样癌和髓母细胞瘤的两种人类肿瘤细胞系,它们分别具有表皮生长因子受体(EGFR)和c-Myc基因的扩增。将细胞皮下植入免疫功能低下的小鼠,并对两组皮下肿瘤的基因扩增水平进行量化。然后,我们确定在荷瘤小鼠的循环ev中是否存在人EGFR和c-Myc转录本的升高水平。循环ev中人EGFR (h-EGFR)和人c-Myc (h-c-Myc) mrna的表达水平与其在肿瘤中的扩增状态密切相关。这一数据进一步支持了循环ev是肿瘤生物标志物潜在平台的观点。
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引用次数: 2
Short Course in Extracellular Vesicles — The Transition from Tissue to Liquid Biopsies 细胞外囊泡的短期病程-从组织活检到液体活检的转变
Q3 Medicine Pub Date : 2014-01-01 DOI: 10.5772/60053
J. Lötvall, J. Skog, A. Vlassov, A. Sacido, E. Rohde, J. Gere, W. Kuo
Extracellular vesicles (EVs), including exosomes and microvesicles, carry a variety of bio-macromolecules, including mRNA, microRNA, other non-coding RNAs, proteins and lipids. EVs have emerged as a promising, minimally invasive (liquid biopsies) and novel source of material for molecular diagnostics, and may provide a surrogate to tissue biopsy-based biomarkers for a variety of diseases. Although EVs can be easily identified and collected from biological fluids using commercial kits, further research and proper validation is needed in order for them to be useful in the clinical setting. Currently, several EV-based research and diagnostic companies have developed research-based kits and are in the process of working with clinical laboratories to develop and validate EV-based assays for a variety of diseases. The successful clinical application of EV-based diagnostic assays will require close collaboration between industry, academia, regulatory agencies and access to patient samples. We expect that international, integrative and interdisciplinary translational research teams, along with the emergence of FDA-approved platforms, will set the framework for EV-based diagnostics. We recognize that the EV field offers new promise for personalized/precision medicine and targeted treatment in a variety of diseases. A short course was held as a four-session webinar series in September and October 2014, presented by pioneers and experts in the EV domain, covering a broad range of topics from an overview of the field to its applications, and the current state and challenges of the commercialization of EVs for research and an introduction to the clinic. It was concluded with a panel discussion on the regulatory aspects and funding opportunities in this field. A summary of the short course is presented as a meeting dispatch.
细胞外囊泡(EVs),包括外泌体和微囊泡,携带多种生物大分子,包括mRNA、microRNA、其他非编码rna、蛋白质和脂质。电动汽车已经成为一种有前途的、微创的(液体活检)和分子诊断材料的新来源,并可能为各种疾病提供基于组织活检的生物标志物的替代品。虽然使用商业试剂盒可以很容易地从生物体液中识别和收集EVs,但为了使其在临床环境中有用,还需要进一步的研究和适当的验证。目前,几家基于ev的研究和诊断公司已经开发了基于研究的试剂盒,并正在与临床实验室合作,开发和验证基于ev的各种疾病检测方法。基于ev的诊断分析的成功临床应用将需要工业界、学术界、监管机构之间的密切合作,并获得患者样本。我们期待国际、综合和跨学科的转化研究团队,以及fda批准的平台的出现,将为基于ev的诊断设定框架。我们认识到,电动汽车领域为各种疾病的个性化/精准医疗和靶向治疗提供了新的希望。2014年9月和10月举办了一个短期课程,由电动汽车领域的先驱和专家介绍,包括从该领域的概述到其应用的广泛主题,以及电动汽车商业化研究和临床应用的现状和挑战。会议结束时,小组讨论了这一领域的监管方面和筹资机会。短期课程的摘要以会议简报的形式呈现。
{"title":"Short Course in Extracellular Vesicles — The Transition from Tissue to Liquid Biopsies","authors":"J. Lötvall, J. Skog, A. Vlassov, A. Sacido, E. Rohde, J. Gere, W. Kuo","doi":"10.5772/60053","DOIUrl":"https://doi.org/10.5772/60053","url":null,"abstract":"Extracellular vesicles (EVs), including exosomes and microvesicles, carry a variety of bio-macromolecules, including mRNA, microRNA, other non-coding RNAs, proteins and lipids. EVs have emerged as a promising, minimally invasive (liquid biopsies) and novel source of material for molecular diagnostics, and may provide a surrogate to tissue biopsy-based biomarkers for a variety of diseases. Although EVs can be easily identified and collected from biological fluids using commercial kits, further research and proper validation is needed in order for them to be useful in the clinical setting. Currently, several EV-based research and diagnostic companies have developed research-based kits and are in the process of working with clinical laboratories to develop and validate EV-based assays for a variety of diseases. The successful clinical application of EV-based diagnostic assays will require close collaboration between industry, academia, regulatory agencies and access to patient samples. We expect that international, integrative and interdisciplinary translational research teams, along with the emergence of FDA-approved platforms, will set the framework for EV-based diagnostics. We recognize that the EV field offers new promise for personalized/precision medicine and targeted treatment in a variety of diseases. A short course was held as a four-session webinar series in September and October 2014, presented by pioneers and experts in the EV domain, covering a broad range of topics from an overview of the field to its applications, and the current state and challenges of the commercialization of EVs for research and an introduction to the clinic. It was concluded with a panel discussion on the regulatory aspects and funding opportunities in this field. A summary of the short course is presented as a meeting dispatch.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/60053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70979762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Uncovering the Role of Erythrocyte-Derived Extracellular Vesicles in Malaria: From Immune Regulation to Cell Communication 揭示红细胞来源的细胞外囊泡在疟疾中的作用:从免疫调节到细胞通讯
Q3 Medicine Pub Date : 2014-01-01 DOI: 10.5772/58596
Johan Ankarklev, D. Hjelmqvist, Pierre-Yves Mantel
Investigation of the involvement of extracellular vesicles (EVs) in parasite biology has burgeoned in recent years. Human infecting protozoan parasites, such as Trypanosoma cruzi, Lesihmania sp. and Trichomonas vaginalis, have all demonstrated the utilization of EVs as virulence factors in order to activate or hamper host immunity. Novel findings have provided evidence that the deployment of EVs by Plasmodium sp. has a major impact in disease outcomes and serves as an integral part in controlling stage switching in its life cycle. Clinical studies have highlighted elevated levels of EVs in patients with severe malaria disease and EVs have been linked to increased sequestration of infected red blood cells to the endothelium, causing obstruction of blood flow. It has also been found that EVs produced during malaria disease activate innate immunity. Intriguingly, recent discoveries indicate that Plasmodium sp. “highjack” the erythrocyte microvesiculation system in order to cross-communicate. Both the transfer of DNA and parasite density regulation has been suggested as key mechanisms of EVs in malaria biology.
近年来,关于细胞外囊泡(EVs)在寄生虫生物学中的作用的研究迅速发展。人类感染的原生动物寄生虫,如克氏锥虫、莱希曼原虫和阴道毛滴虫,都显示出利用EVs作为毒力因子来激活或阻碍宿主免疫。新的研究结果提供了证据,证明疟原虫的ev部署对疾病结局有重大影响,并在控制其生命周期的阶段转换中起着不可或缺的作用。临床研究强调,严重疟疾患者的EVs水平升高,并且EVs与受感染的红细胞与内皮细胞的隔离增加有关,从而导致血液流动受阻。还发现疟疾期间产生的ev可激活先天免疫。有趣的是,最近的发现表明,疟原虫“劫持”红细胞微泡系统以进行交叉交流。DNA转移和寄生虫密度调节被认为是EVs在疟疾生物学中的关键机制。
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引用次数: 8
Exosomal Heat Shock Proteins as New Players in Tumour Cell-to-Cell Communication 外泌体热休克蛋白在肿瘤细胞间通讯中的新作用
Q3 Medicine Pub Date : 2014-01-01 DOI: 10.5772/58721
C. Campanella, C. C. Bavisotto, A. M. Gammazza, D. Nikolić, F. Rappa, S. David, F. Cappello, F. Bucchieri, S. Fais
Exosomes have recently been proposed as novel elements in the study of intercellular communication in normal and pathological conditions. The biomolecular composition of exosomes reflects the specialized functions of the original cells. Heat shock proteins (Hsps) are a group of chaperone proteins with diverse biological roles. In recent years, many studies have focused on the extracellular roles played by Hsps that appear to be involved in cancer development and immune system stimulation. Hsps localized on the surface of exosomes, secreted by normal and tumour cells, could be key players in intercellular cross-talk, particularly during the course of different diseases, such as cancer. Exosomal Hsps offer significant opportunities for clinical applications, including their use as potential novel biomarkers for the diagnoses or prognoses of different diseases, or for therapeutic applications and drug delivery.
外泌体最近被认为是研究正常和病理条件下细胞间通讯的新元素。外泌体的生物分子组成反映了原始细胞的特化功能。热休克蛋白(Hsps)是一类具有多种生物学作用的伴侣蛋白。近年来,许多研究都集中在热休克蛋白在癌症发展和免疫系统刺激中所起的细胞外作用上。位于正常细胞和肿瘤细胞分泌的外泌体表面的热休克蛋白可能是细胞间串扰的关键角色,特别是在不同疾病(如癌症)的过程中。外泌体热休克蛋白为临床应用提供了重要的机会,包括它们作为潜在的新型生物标志物用于不同疾病的诊断或预后,或用于治疗应用和药物输送。
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引用次数: 45
Influence of Lung Parenchyma Surgical Manipulation on Circulating Free DNA 肺实质手术操作对循环游离DNA的影响
Q3 Medicine Pub Date : 2014-01-01 DOI: 10.5772/59875
M. Anile, C. Chiappetta, D. Diso, V. Liparulo, M. Leopizzi, C. Della Rocca, F. Venuta
Objectives: Metastatic recurrence is the most frequent cause of death after surgical resection of lung cancer. Manipulation during surgery has been advocated as one of the causes contributing to promotion of spreading. Methods: We investigated if the detection of plasma circulating free DNA (cfDNA) is influenced by surgical manipulation in 25 lung cancer patients (17 males and eight females) undergoing complete resection; 20 health subjects formed the control group. Bloodstream levels of cfDNA were detected before surgery, one week and one month after surgery. Results: CfDNA levels measured preoperatively and in the control group were 23 07 ± 7 4 ng/mL and 7 5 ± 3 4 ng/mL respectively (p=0 0002); levels at one week and one month were 68 2 ± 36 2 ng/mL and 9 6 ± 3 1 ng/mL respectively. The difference between the three time points were statistically significant (preop vs. one week p=0 0006; one week vs. one month p=0 0003) with an increase in the first week and a strong decrease after one month. CfDNA levels at one month were not statistically different from those recorded in the control group. There was no correlation between preoperative cfDNA levels, tumour stage, grading and histology and patient demographics. No correlation was found between postoperative cfDNA, type of surgical procedure, histology and stage. After a median follow-up of 16 months no recurrence was detected. Conclusions: Surgical manipulation determines increased cfDNA levels in the early postoperative period; however, after one month they decrease within the normal range, at levels that are statistically comparable with healthy subjects.
目的:转移性复发是肺癌手术切除后最常见的死亡原因。术中操作被认为是促进扩散的原因之一。方法:观察25例肺癌全切除术患者(男17例,女8例)手术操作对血浆循环游离DNA (cfDNA)检测的影响;健康受试者20人作为对照组。分别于术前、术后1周和1个月检测血液中cfDNA水平。结果:术前与对照组CfDNA水平分别为23 07±7 4 ng/mL、7 5±3 4 ng/mL (p=0 0002);1周和1个月的水平分别为68 2±36 2 ng/mL和9 6±31 ng/mL。三个时间点之间的差异具有统计学意义(术前vs.一周p= 0006;一周vs一个月p=0 0003),第一周增加,一个月后大幅下降。1个月时CfDNA水平与对照组无统计学差异。术前cfDNA水平与肿瘤分期、分级、组织学和患者人口统计学无相关性。术后cfDNA与手术方式、组织学及分期无相关性。中位随访16个月后未发现复发。结论:手术操作决定术后早期cfDNA水平升高;然而,一个月后,它们在正常范围内下降,在统计上与健康受试者相当。
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引用次数: 0
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Journal of Circulating Biomarkers
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