{"title":"“I Have a Dream”","authors":"S. Fais","doi":"10.5772/58709","DOIUrl":"https://doi.org/10.5772/58709","url":null,"abstract":"“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)","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/58709","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70974930","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}
{"title":"Protocol Standardization Reveals MV Correlation to Healthy Donor BMI","authors":"P. Hexley, K. Rismiller, C. Robinson, G. Babcock","doi":"10.5772/58527","DOIUrl":"https://doi.org/10.5772/58527","url":null,"abstract":"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.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/58527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70972114","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}
I. Vishnubhatla, R. Corteling, Lara Stevanato, C. Hicks, J. Sinden
{"title":"The Development of Stem Cell-Derived Exosomes as a Cell-Free Regenerative Medicine","authors":"I. Vishnubhatla, R. Corteling, Lara Stevanato, C. Hicks, J. Sinden","doi":"10.5772/58597","DOIUrl":"https://doi.org/10.5772/58597","url":null,"abstract":"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.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/58597","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70973738","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}
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
{"title":"Detection of Human c-Myc and EGFR Amplifications in Circulating Extracellular Vesicles in Mouse Tumour Models","authors":"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","doi":"10.5772/59174","DOIUrl":"https://doi.org/10.5772/59174","url":null,"abstract":"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.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70977021","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}
J. Lötvall, J. Skog, A. Vlassov, A. Sacido, E. Rohde, J. Gere, W. Kuo
{"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":null,"pages":null},"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}
Johan Ankarklev, D. Hjelmqvist, Pierre-Yves Mantel
{"title":"Uncovering the Role of Erythrocyte-Derived Extracellular Vesicles in Malaria: From Immune Regulation to Cell Communication","authors":"Johan Ankarklev, D. Hjelmqvist, Pierre-Yves Mantel","doi":"10.5772/58596","DOIUrl":"https://doi.org/10.5772/58596","url":null,"abstract":"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.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/58596","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70973646","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}
C. Campanella, C. C. Bavisotto, A. M. Gammazza, D. Nikolić, F. Rappa, S. David, F. Cappello, F. Bucchieri, S. Fais
{"title":"Exosomal Heat Shock Proteins as New Players in Tumour Cell-to-Cell Communication","authors":"C. Campanella, C. C. Bavisotto, A. M. Gammazza, D. Nikolić, F. Rappa, S. David, F. Cappello, F. Bucchieri, S. Fais","doi":"10.5772/58721","DOIUrl":"https://doi.org/10.5772/58721","url":null,"abstract":"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.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/58721","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70974610","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}
M. Anile, C. Chiappetta, D. Diso, V. Liparulo, M. Leopizzi, C. Della Rocca, F. Venuta
{"title":"Influence of Lung Parenchyma Surgical Manipulation on Circulating Free DNA","authors":"M. Anile, C. Chiappetta, D. Diso, V. Liparulo, M. Leopizzi, C. Della Rocca, F. Venuta","doi":"10.5772/59875","DOIUrl":"https://doi.org/10.5772/59875","url":null,"abstract":"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.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/59875","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70978081","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}
Carolyn D. Roberson, Ç. Gerçel-Taylor, Ying Qi, K. Schey, D. Taylor
{"title":"Identification of Immunoreactive Tumour Antigens Using Free and Exosome-Associated Humoral Responses","authors":"Carolyn D. Roberson, Ç. Gerçel-Taylor, Ying Qi, K. Schey, D. Taylor","doi":"10.5772/57524","DOIUrl":"https://doi.org/10.5772/57524","url":null,"abstract":"Altered tumour antigens can initiate cellular and humoral immune responses; however, they often fail to eliminate tumours. In humans, the presence of cancer is generally associated with the suppression of T cell activation and effector responses, characterized as a Th1 to Th2 biased response. This Th2 response leads to the production of tumour-reactive antibodies. Further, neoplastic lesions and biological fluids of cancer patients contain an abundance of tumour-derived exosomes (TDE) expressing tumour antigens. Expression of tumour antigens on TDE may represent an antibody target and serve to block antibody binding to the tumour, implicating a role for these nanovesicles in tumour survival. In this study, ovarian tumour cell proteins were separated by two-dimensional electrophoresis (2-DE) and patient-derived antibodies were used to analyse immunoreactivity. Common immunoreactive proteins among ovarian cancer patients were identified by mass spectrometry and six proteins were selected based on recognition and correlation with cancer pathogenesis. The identity of these proteins were confirmed by immunoreactivity of patient-derived antibodies with recombinant proteins and their presence on in vivo and in vitro-derived ovarian tumour exosomes was defined. Analysis of the TDE demonstrated bound tumour-reactive immunoglobulins, exhibiting immunoreactivity with specific antigens, suggesting that patient-derived antibodies recognize tumour antigens on circulating exosomes.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/57524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70967192","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}
{"title":"Announcing Exosomes and Microvesicles, the Official Journal of the American Society for Exosomes and Microvesicles","authors":"S. Gould, D. Taylor, A. Chiesi, W. Kuo","doi":"10.5772/56520","DOIUrl":"https://doi.org/10.5772/56520","url":null,"abstract":"This editorial article introduces the new scientific journal Exosomes and Microvesicles (EXMV), the official journal of the American Society for Exosomes and Microvesicles (ASEMV), and describes its editorial line and mission in relation to the role of the Society, the state of the art of the study of exosomes and microvesicles, and the overall approach of the publication.","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70954225","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}