Kimberly Falana, Rob Knight, Camilia R Martin, Romina Goldszmid, K Leigh Greathouse, Joanne Gere, Howard Young, Winston Patrick Kuo
{"title":"Short Course in the Microbiome.","authors":"Kimberly Falana, Rob Knight, Camilia R Martin, Romina Goldszmid, K Leigh Greathouse, Joanne Gere, Howard Young, Winston Patrick Kuo","doi":"10.5772/61257","DOIUrl":"https://doi.org/10.5772/61257","url":null,"abstract":"<p><p>Over the past decade, it has become evident that the microbiome is an important environmental factor that affects many physiological processes, such as cell proliferation and differentiation, behaviour, immune function and metabolism. More importantly, it may contribute to a wide variety of diseases, including cancer, inflammatory diseases, metabolic diseases and responses to pathogens. We expect that international, integrative and interdisciplinary translational research teams, along with the emergence of FDA-approved platforms, will set the framework for microbiome-based therapeutics and diagnostics. We recognize that the microbiome ecosystem offers new promise for personalized/precision medicine and targeted treatment for a variety of diseases. The short course was held as a four-session webinar series in April 2015, taught by pioneers and experts in the microbiome ecosystem, covering a broad range of topics from the healthy microbiome to the effects of an altered microbiome from neonates to adults and the long term effects as it is related to disease, from asthma to cancer. We have learned to appreciate how beneficial our microbes are in breaking down our food, fighting off infections and nurturing our immune system, and this information provides us with ideas as to how we can manipulate our microbiome to prevent certain diseases. However, given the variety of applications, there are scientific challenges, though there are very promising areas in reference to the clinical benefits of understanding more about our microbiome, whether in our gut or on our skin: the outlook is bright. A summary of the short course is presented as a meeting dispatch.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/61257","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35436343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kelly J McKelvey, Katie L Powell, Anthony W Ashton, Jonathan M Morris, Sharon A McCracken
{"title":"Exosomes: Mechanisms of Uptake.","authors":"Kelly J McKelvey, Katie L Powell, Anthony W Ashton, Jonathan M Morris, Sharon A McCracken","doi":"10.5772/61186","DOIUrl":"https://doi.org/10.5772/61186","url":null,"abstract":"<p><p>Exosomes are 30-100 nm microvesicles which contain complex cellular signals of RNA, protein and lipids. Because of this, exosomes are implicated as having limitless therapeutic potential for the treatment of cancer, pregnancy complications, infections, and autoimmune diseases. To date we know a considerable amount about exosome biogenesis and secretion, but there is a paucity of data regarding the uptake of exosomes by immune and non-immune cell types (e.g., cancer cells) and the internal signalling pathways by which these exosomes elicit a cellular response. Answering these questions is of paramount importance.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/61186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35436342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Huang, Anna B Banizs, Weibin Shi, Alexander L Klibanov, Jiang He
{"title":"Size Exclusion HPLC Detection of Small-Size Impurities as a Complementary Means for Quality Analysis of Extracellular Vesicles.","authors":"Tao Huang, Anna B Banizs, Weibin Shi, Alexander L Klibanov, Jiang He","doi":"10.5772/61148","DOIUrl":"https://doi.org/10.5772/61148","url":null,"abstract":"<p><p>For extracellular vesicle research, whether for biomarker discoveries or therapeutic applications, it is critical to have high-quality samples. Both microscopy and NanoSight Tracking Analysis (NTA) for size distribution have been used to detect large vesicles. However, there is currently no well-established method that is convenient for routine quality analysis of small-size impurities in vesicle samples. In this paper we report a convenient method, called 'size-exclusion high-performance liquid chromatography' (SE-HPLC), alongside NTA and Microscopy analysis to guide and qualify the isolation and processing of vesicles. First, the SE-HPLC analysis was used to detect impurities of small-size proteins during the ultra-centrifugation process of vesicle isolation; it was then employed to test the changes of vesicles under different pH conditions or integrity after storage. As SE-HPLC is generally accessible in most institutions, it could be used as a routine means to assist researchers in examining the integrity and quality of extracellular vesicles along with other techniques either during isolation/preparation or for further engineering and storage.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/61148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35436345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anders S Frandsen, Anna Fabisiewicz, Agnieszka Jagiello-Gruszfeld, Anastasiya S Haugaard, Louise Munkhaus Petersen, Katrine Brandt Albrektsen, Sarah Nejlund, Julie Smith, Henrik Stender, Thore Hillig, György Sölétormos
{"title":"Retracing Circulating Tumour Cells for Biomarker Characterization after Enumeration.","authors":"Anders S Frandsen, Anna Fabisiewicz, Agnieszka Jagiello-Gruszfeld, Anastasiya S Haugaard, Louise Munkhaus Petersen, Katrine Brandt Albrektsen, Sarah Nejlund, Julie Smith, Henrik Stender, Thore Hillig, György Sölétormos","doi":"10.5772/60995","DOIUrl":"https://doi.org/10.5772/60995","url":null,"abstract":"<p><strong>Background: </strong>Retracing and biomarker characterization of individual circulating tumour cells (CTCs) may potentially contribute to personalized metastatic cancer therapy. This is relevant when a biopsy of the metastasis is complicated or impossible to acquire.</p><p><strong>Methods: </strong>A novel disc format was used to map and retrace individual CTCs from breast-cancer patients and nucleated cells from healthy blood donors using the CytoTrack platform. For proof of the retracing concept, CTC HER2 characterization by immunofluorescence was tested.</p><p><strong>Results: </strong>CTCs were detected and enumerated in three of four blood samples from breast-cancer patients and the locations of each individual CTCs were mapped on the discs. Nucleated cells were retraced on seven discs with 96.6%±8.5% recovery on five fields of view on each disc. Shifting of field of view for retracing was measured to 4-29 μm. In a blood sample from a HER2-positive breast-cancer patient, CTC enumeration and mapping was followed by HER2 characterization and retracing to demonstrate downstream immunofluorescence analysis of the CTC.</p><p><strong>Conclusion: </strong>Mapping and retracing of CTCs enables downstream analysis of individual CTCs for existing and future cancer genotypic and phenotypic biomarkers. Future studies will uncover this potential of the novel retracing technology.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/60995","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35430510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Lu, Ryon P Graf, Melissa Harvey, Ravi A Madan, Christopher Heery, Jennifer Marte, Sharon Beasley, Kwong Y Tsang, Rachel Krupa, Jessica Louw, Justin Wahl, Natalee Bales, Mark Landers, Dena Marrinucci, Jeffrey Schlom, James L Gulley, Ryan Dittamore
{"title":"Detection and Characterization of Circulating Tumour Cells from Frozen Peripheral Blood Mononuclear Cells.","authors":"David Lu, Ryon P Graf, Melissa Harvey, Ravi A Madan, Christopher Heery, Jennifer Marte, Sharon Beasley, Kwong Y Tsang, Rachel Krupa, Jessica Louw, Justin Wahl, Natalee Bales, Mark Landers, Dena Marrinucci, Jeffrey Schlom, James L Gulley, Ryan Dittamore","doi":"10.5772/60745","DOIUrl":"https://doi.org/10.5772/60745","url":null,"abstract":"<p><p>Retrospective analysis of patient tumour samples is a cornerstone of clinical research. CTC biomarker characterization offers a non-invasive method to analyse patient samples. However, current CTC technologies require prospective blood collection, thereby reducing the ability to utilize archived clinical cohorts with long-term outcome data. We sought to investigate CTC recovery from frozen, archived patient PBMC pellets. Matched samples from both mCRPC patients and mock samples, which were prepared by spiking healthy donor blood with cultured prostate cancer cell line cells, were processed \"fresh\" via Epic CTC Platform or from \"frozen\" PBMC pellets. Samples were analysed for CTC enumeration and biomarker characterization via immunofluorescent (IF) biomarkers, fluorescence in-situ hybridization (FISH) and CTC morphology. In the frozen patient PMBC samples, the median CTC recovery was 18%, compared to the freshly processed blood. However, abundance and localization of cytokeratin (CK) and androgen receptor (AR) protein, as measured by IF, were largely concordant between the fresh and frozen CTCs. Furthermore, a FISH analysis of PTEN loss showed high concordance in fresh vs. frozen. The observed data indicate that CTC biomarker characterization from frozen archival samples is feasible and representative of prospectively collected samples.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/60745","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35430508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shannon L Werner, Ryon P Graf, Mark Landers, David T Valenta, Matthew Schroeder, Stephanie B Greene, Natalee Bales, Ryan Dittamore, Dena Marrinucci
{"title":"Analytical Validation and Capabilities of the Epic CTC Platform: Enrichment-Free Circulating Tumour Cell Detection and Characterization.","authors":"Shannon L Werner, Ryon P Graf, Mark Landers, David T Valenta, Matthew Schroeder, Stephanie B Greene, Natalee Bales, Ryan Dittamore, Dena Marrinucci","doi":"10.5772/60725","DOIUrl":"https://doi.org/10.5772/60725","url":null,"abstract":"<p><p>The Epic Platform was developed for the unbiased detection and molecular characterization of circulating tumour cells (CTCs). Here, we report assay performance data, including accuracy, linearity, specificity and intra/inter-assay precision of CTC enumeration in healthy donor (HD) blood samples spiked with varying concentrations of cancer cell line controls (CLCs). Additionally, we demonstrate clinical feasibility for CTC detection in a small cohort of metastatic castrate-resistant prostate cancer (mCRPC) patients. The Epic Platform demonstrated accuracy, linearity and sensitivity for the enumeration of all CLC concentrations tested. Furthermore, we established the precision between multiple operators and slide staining batches and assay specificity showing zero CTCs detected in 18 healthy donor samples. In a clinical feasibility study, at least one traditional CTC/mL (CK+, CD45-, and intact nuclei) was detected in 89 % of 44 mCRPC samples, whereas 100 % of samples had CTCs enumerated if additional CTC subpopulations (CK-/CD45- and CK+ apoptotic CTCs) were included in the analysis. In addition to presenting Epic Platform's performance with respect to CTC enumeration, we provide examples of its integrated downstream capabilities, including protein biomarker expression and downstream genomic analyses at single cell resolution.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/60725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35430509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lilite Sadovska, Cristina Bajo Santos, Zane Kalniņa, Aija Linē
{"title":"Biodistribution, Uptake and Effects Caused by Cancer-Derived Extracellular Vesicles.","authors":"Lilite Sadovska, Cristina Bajo Santos, Zane Kalniņa, Aija Linē","doi":"10.5772/60522","DOIUrl":"10.5772/60522","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) have recently emerged as important mediators of intercellular communication. They are released in the extracellular space by a variety of normal and cancerous cell types and have been found in all human body fluids. Cancer-derived EVs have been shown to carry lipids, proteins, mRNAs, non-coding and structural RNAs and even extra-chromosomal DNA, which can be taken up by recipient cells and trigger diverse physiological and pathological responses. An increasing body of evidence suggests that cancer-derived EVs mediate paracrine signalling between cancer cells. This leads to the increased invasiveness, proliferation rate and chemoresistance, as well as the acquisition of the cancer stem cell phenotype. This stimulates angiogenesis and the reprogramming of normal stromal cells into cancer-promoting cell types. Furthermore, cancer-derived EVs contribute to the formation of the pre-metastatic niche and modulation of anti-tumour immune response. However, as most of these data are obtained by <i>in vitro</i> studies, it is not entirely clear which of these effects are recapitulated <i>in vivo</i>. In the current review, we summarize studies that assess the tissue distribution, trafficking, clearance and uptake of cancer-derived EVs <i>in vivo</i> and discuss the impact they have, both locally and systemically.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/60522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35430507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Year of Expanding into Circulating Biomarkers.","authors":"Shidong Jia, Winston Patrick Kuo","doi":"10.5772/60126","DOIUrl":"https://doi.org/10.5772/60126","url":null,"abstract":"<p><p>This editorial article summarizes the achievements and current challenges for the <i>Journal of Circulating Biomarkers</i> (JCB) regarding a more strategic approach to branding and attracting a high quality variety of articles. More emphasis is placed on fostering engagement with academic and industry sources operating at the cutting-edge of translational technologies applied to the field of circulating biomarkers (interface between extracellular vesicles including exosomes and microvesicles, circulating tumour cells, cell-free circulating DNA and circulating protein markers) and with those in the investment arena seeking and providing private funding for this area of research.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5772/60126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35430506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New Year, New Name and New Milestones Scope — Journal of Circulating Biomarkers","authors":"S. Jia, W. Kuo","doi":"10.5772/58638","DOIUrl":"https://doi.org/10.5772/58638","url":null,"abstract":"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).","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/10.5772/58638","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70973804","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":"Apoptotic Microparticles as Predicted Biomarkers in Patients with Chronic Heart Failure — Relevance to Inflammatory Cytokines and Outcomes","authors":"A. Berezin, A. Kremzer, Yulia V. Martovitskaya","doi":"10.5772/60062","DOIUrl":"https://doi.org/10.5772/60062","url":null,"abstract":"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.","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/10.5772/60062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70980021","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}