Exploiting the message from cancer: the diagnostic value of extracellular vesicles for clinical applications

Kosaka, Nobuyoshi; Kogure, Akiko; Yamamoto, Tomofumi; Urabe, Fumihiko; Usuba, Wataru; Prieto‐Vila, Marta; Ochiya, Takahiro

doi:10.1038/s12276-019-0219-1

Cited by 98 publications

(83 citation statements)

References 77 publications

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“…Current advanced technologies involve using surface enhanced Raman scattering (SERS) or localized surface plasmon resonance to detect tumor-derived EVs in body fluids (Mehmet et al, 2017;Thakur et al, 2017;Zong et al, 2016). In addition, the miRNA cargo of EVs has been of interest as biomarkers for various cancers (Kosaka et al, 2019). Similarly, a microfluidic on-chip device has potential to identify parasite EVs from host biofluids.…”

Section: Discussionmentioning

confidence: 99%

Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes

Loghry

Wang

Zamanian

et al. 2020

Preprint

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Lymphatic filariasis (LF) is a disease caused by parasitic filarial nematodes that is endemic in 49 countries and affects or threatens over 890 million people. Strategies to control LF rely heavily on mass administration of anthelmintic drugs including ivermectin (IVM), a macrocyclic lactone drug considered an Essential Medicine by the WHO. However, despite its widespread use the therapeutic mode of action of IVM against filarial nematodes is not clear. We have previously reported that filarial nematodes secrete extracellular vesicles (EVs) and that their cargo has immunomodulatory properties. Here we investigate the effects of IVM and other anti-filarial drugs on parasitic nematode EV secretion, motility, and protein secretion. We show that inhibition of EV secretion was a specific property of IVM, which had consistent and significant inhibitory effects across nematode life stages and species (with the exception of male parasites). IVM inhibited EV secretion, but not parasite motility, at therapeutically relevant concentrations. Protein secretion was inhibited by IVM in the microfilariae stage, but not in any other stage tested. Our data provides evidence that inhibiting the secretion of immunomodulatory EVs by parasitic nematodes could explain, at least in part, IVM mode of action and provides a phenotype for novel drug discovery.

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Section: Discussionmentioning

confidence: 99%

Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes

Loghry

Wang

Zamanian

et al. 2020

Preprint

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“…In this study, two separate panels were used with HyperVOX implementation, each panel having a set number of flow parameters (f): a myeloid cell panel consisting of SSC-A, Lin(CD3/ CD19/CD56), CD11b, CD14, CD15, CD16, CD33, HLA-DR, and DAPI (f = 9) and a lymphoid cell panel consisting of SSC-A, CD3, CD4, CD8, CD19, CD56, and DAPI (f = 7); each panel contained a total number of hypervoxels calculated as 4 f . This resulted in a 9-dimensional array containing 4 9 , or 262 144, hypervoxel locations for the myeloid cell panel, and a 7-dimensional array containing 4 7 , or 16 384, hypervoxels locations for the lymphoid cell panel. Each location in the 9-and 7-dimensional arrays represented a position in the flow cytometry hyperspace and contained the number of events indexed to that location.…”

Section: Hypervox Implementationmentioning

confidence: 99%

“…[4][5][6][7] Several current liquid biopsy technologies have either capitalized on factors that are excreted by the tumor cells, such as circulating tumor DNA (ctDNA) and extracellular vesicles (EVs), or on circulating tumor cells (CTCs) present in the peripheral blood (PB). [8][9][10] In this study, we chose to focus not on the behavior of tumor cells themselves, but rather the response of the immune system to the presence or absence of the solid tumor as a means for detecting PCa.…”

Section: Introductionmentioning

confidence: 99%

Detecting Prostate Cancer Using Pattern Recognition Neural Networks With Flow Cytometry-Based Immunophenotyping in At-Risk Men

Dominguez¹,

Polo²,

Roop³

et al. 2020

Biomark�Insights

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Current screening methods for prostate cancer (PCa) result in a large number of false positives making it difficult for clinicians to assess disease status, thus warranting advancements in screening and early detection methods. The goal of this study was to design a liquid biopsy test that uses flow cytometry–based immunophenotyping and artificial neural network (ANN) analysis to detect PCa. Numerous myeloid and lymphoid cell populations, including myeloid-derived suppressor cells, were measured from 156 patients with PCa, 123 with benign prostatic hyperplasia (BPH), and 99 male healthy donor (HD) controls. Using pattern recognition neural network (PRNN) analysis, a type of ANN, PCa detection compared against HD resulted in 96.6% sensitivity, 87.5% specificity, and an area under the curve (AUC) value of 0.97. Detecting patients with higher risk disease (⩾Gleason 7) against lower risk disease (BPH/Gleason 6) resulted in 92.0% sensitivity, 42.7% specificity, and an AUC of 0.72. This study suggests that analyzing flow cytometry immunophenotyping data with PRNNs may prove to be a useful tool to improve PCa detection and reduce the number of unnecessary prostate biopsies performed each year.

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“…Furthermore, hepatoma cell-derived exosomes have been reported to deliver miR-103 into endothelial cells, thus inducing metastasis. It has also been documented that LncRNAs delivered by exosomes, such as Lnc-sox2ot, Lnc-h19, and LncRNA-ARSR, are closely associated with tumor progression [14,[19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Exosomes for Diagnosis and Therapy in Gastrointestinal Cancers

Scavo

Depalo

Tutino

et al. 2020

IJMS

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Exosomes are membrane-bound extracellular vesicles (EVs) released by most cells, having a size ranging from 30 to 150 nm, and are involved in mechanisms of cell-cell communication in physiological and pathological tissues. Exosomes are engaged in the transport of biomolecules, such as lipids, proteins, messenger RNAs, and microRNA, and in signal transmission through the intercellular transfer of components. In the context of proteins and nucleic acids transported from exosomes, our interest is focused on the Frizzled proteins family and related messenger RNA. Exosomes can regenerate stem cell phenotypes and convert them into cancer stem cells by regulating the Wnt pathway receptor family, namely Frizzled proteins. In particular, for gastrointestinal cancers, the Frizzled protein involved in those mechanisms is Frizzled-10 (FZD-10). Currently, increasing attention is being devoted to the protein and lipid composition of exosomes interior and membranes, representing profound knowledge of specific exosomes composition fundamental for their application as new delivering drug tools for cancer therapy. This review intends to cover the most recent literature on the use of exosome vesicles for early diagnosis, follow-up, and the use of these physiological nanovectors as drug delivery systems for gastrointestinal cancer therapy.

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Exploiting the message from cancer: the diagnostic value of extracellular vesicles for clinical applications

Cited by 98 publications

References 77 publications

Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes

Ivermectin inhibits extracellular vesicle secretion from parasitic nematodes

Detecting Prostate Cancer Using Pattern Recognition Neural Networks With Flow Cytometry-Based Immunophenotyping in At-Risk Men

Exosomes for Diagnosis and Therapy in Gastrointestinal Cancers

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