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      Publication Trends in Exosomes Nanoparticles for Cancer Detection

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          Abstract

          Background

          Exosomes are small vesicles produced by almost all cells in the body and found in all biofluids. Cancer cell-derived exosomes are known to have distinct, measurable signatures, applicable for early cancer diagnosis. Despite the present bibliometric studies on “Cancer detection” and “Nanoparticles”, no single study exists to deal with “Exosome” bibliometric study.

          Methods

          This bibliometric work investigated the publication trends of “Exosomes” nanoparticles and its application in cancer detection, for the literature from 2008 to July 2019. The data were collected from the Web of Science Core Collection. There were variant visual maps generated to show annual publication, most- relevant authors, sources, countries, topics and keywords. The network analysis of these studies was investigated to evaluate the research trends in the field of exosomes. In addition, the data were qualitatively analyzed according to 22 top-cited articles, illustrating the frequently used subjects and methods in exosomes research area.

          Results

          The results showed that the documents in this field have improved the citation rate. The top-relevant papers are mostly published in Scientific Reports journal which has lost its popularity after 2017, while today, Analytical Chemistry is leading in publishing the most articles related to exosomes. The documents containing keywords of plasma, cells, cancer, biomarkers, and vesicles as keywords plus, are more likely to be published in PLoS One journal. The clustering of the keywords network showed that the keyword theme of “extracellular vesicles” has the highest centrality rate. In global research, USA is the most corresponding country, followed by China, Korea and Australia. Based on the qualitative analysis, the published documents with at least 50 citations have used exosome release, cargo, detection, purification and secretion, as their targets and applied cell culture or isolation as their methods.

          Conclusion

          The bibliometric study on exosomes nanoparticles for cancer detection provides a clear vision of the future research direction and identifies the potential opportunities and challenges. This may lead new researchers to select the proper subfields in exosome-related research fields.

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          Most cited references 35

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          bibliometrix : An R-tool for comprehensive science mapping analysis

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            A Comparative Study of Serum Exosome Isolation Using Differential Ultracentrifugation and Three Commercial Reagents

            Exosomes play a role in cell-to-cell signaling and serve as possible biomarkers. Isolating exosomes with reliable quality and substantial concentration is a major challenge. Our purpose is to compare the exosomes extracted by three different exosome isolation kits (miRCURY, ExoQuick, and Invitrogen Total Exosome Isolation Reagent) and differential ultracentrifugation (UC) using six different volumes of a non-cancerous human serum (5 ml, 1 ml, 500 μl, 250 μl, 100 μl, and 50 μl) and three different volumes (1 ml, 500 μl and 100 μl) of six individual commercial serum samples collected from human donors. The smaller starting volumes (100 μl and 50 μl) are used to mimic conditions of limited availability of heterogeneous biological samples. The isolated exosomes were characterized based upon size, quantity, zeta potential, CD63 and CD9 protein expression, and exosomal RNA (exRNA) quality and quantity using several complementary methods: nanoparticle tracking analysis (NTA) with ZetaView, western blot, transmission electron microscopy (TEM), the Agilent Bioanalyzer system, and droplet digital PCR (ddPCR). Our NTA results showed that all isolation techniques produced exosomes within the expected size range (40–150 nm). The three kits, though, produced a significantly higher yield (80–300 fold) of exosomes as compared to UC for all serum volumes, except 5 mL. We also found that exosomes isolated by the different techniques and serum volumes had similar zeta potentials to previous studies. Western blot analysis and TEM immunogold labelling confirmed the expression of two common exosomal protein markers, CD63 and CD9, in samples isolated by all techniques. All exosome isolations yielded high quality exRNA, containing mostly small RNA with a peak between 25 and 200 nucleotides in size. ddPCR results indicated that exosomes isolated from similar serum volumes but different isolation techniques rendered similar concentrations of two selected exRNA: hsa-miR-16 and hsa-miR-451. In summary, the three commercial exosome isolation kits are viable alternatives to UC, even when limited amounts of biological samples are available.
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              Senescence-associated exosome release from human prostate cancer cells.

              Males of advanced age represent a rapidly growing population at risk for prostate cancer. In the contemporary setting of earlier detection, a majority of prostate carcinomas are still clinically localized and often treated using radiation therapy. Our recent studies have shown that premature cellular senescence, rather than apoptosis, accounts for most of the clonogenic death induced by clinically relevant doses of irradiation in prostate cancer cells. We show here that this treatment-induced senescence was associated with a significantly increased release of exosome-like microvesicles. In premature senescence, this novel secretory phenotype was dependent on the activation of p53. In addition, the release of exosome-like microvesicles also increased during proliferative senescence in normal human diploid fibroblasts. These data support the hypothesis that senescence, initiated either by telomere attrition (e.g., aging) or DNA damage (e.g., radiotherapy), may induce a p53-dependent increase in the biogenesis of exosome-like vesicles. Ultrastructural analysis and RNA interference-mediated knockdown of Tsg101 provided significant evidence that the additional exosomes released by prematurely senescent prostate cancer cells were principally derived from multivesicular endosomes. Moreover, these exosomes were enriched in B7-H3 protein, a recently identified diagnostic marker for prostate cancer, and an abundance of what has recently been termed "exosomal shuttle RNA." Our findings are consistent with the proposal that exosomes can transfer cargos, with both immunoregulatory potential and genetic information, between cells through a novel mechanism that may be recruited to increase exosome release during accelerated and replicative cellular senescence.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                IJN
                intjnano
                International Journal of Nanomedicine
                Dove
                1176-9114
                1178-2013
                26 June 2020
                2020
                : 15
                : 4453-4470
                Affiliations
                [1 ]School of Electrical Engineering, Iran University of Science and Technology , Tehran, Iran
                [2 ]Department of Electrical Engineering, Politecnico di Milano , Milan, Italy
                [3 ]Faculty of Electrical Engineering, K. N. Toosi University of Technology , Tehran, Iran
                [4 ]Department of Mechanical and Manufacturing Engineering, University of Calgary , Calgary, Alberta T2N 1N4, Canada
                [5 ]Center for Bioengineering Research and Education, Biomedical Engineering Program, University of Calgary , Calgary, Alberta T2N 1N4, Canada
                [6 ]Research and Technology Department, Alzahra University , Vanak, Tehran, Iran
                Author notes
                Correspondence: Maysam Zamani Pedram; Amir Sanati-Nezhad Email mzpedram@kntu.ac.ir; amir.sanatinezhad@ucalgary.ca
                [*]

                These authors contributed equally to this work

                Article
                247210
                10.2147/IJN.S247210
                7326184
                32617003
                © 2020 Ale Ebrahim et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 20, Tables: 2, References: 68, Pages: 18
                Categories
                Original Research

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