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EV literature (RSS feed from PubMed)

Search terms: exosomes OR "extracellular vesicles" OR microvesicles OR microparticles. Direct link to the PubMed search here.

Particle monolayer-stabilized light-sensitive liquid marbles from polypyrrole-coated microparticles.

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Particle monolayer-stabilized light-sensitive liquid marbles from polypyrrole-coated microparticles.

Langmuir. 2020 Feb 20;:

Authors: Asaumi Y, Rey M, Vogel N, Nakamura Y, Fujii S

Abstract
Liquid marbles are water droplets coated with solid particles that prevent coalescence and allow storage, transport, and handling of liquids in the form of a powder. Here, we report on the formation of liquid marbles that are stabilized entirely by a single monolayer of solid particles and thus minimize the amount of required solid material. As stabilizing particles, we synthesize relatively-monodisperse, 80 m-sized polystyrene (PS) particles coated with heptadecafluorooctanesulfonic acid-doped polypyrrole (PPy-C8F) shell (PS/PPy-C8F particles) by aqueous chemical oxidative seeded polymerization of pyrrole using FeCl3 as an oxidant and heptadecafluorooctanesulfonic acid as a hydrophobic dopant. We characterize the physicochemical properties of the particles as a function of the PPy-C8F loading. Laser diffraction particle size analyses of dilute aqueous suspensions indicate that the polymer particles disperse stably in water medium before and after coating with the PPy-C8F shell. X-ray photoelectron spectroscopy studies indicate the formation of a PPy-C8F shell around the PS seed particles, which was further supported by a deflated morphologies observed by scanning electron microscopy after extraction of the PS component from the PS/PPy-C8F particles. We investigate the capabilities of the dried PS/PPy-C8F particles to act as a liquid marble stabilizer. Stereo- and laser microscope observations, as well as gravimetric studies, confirm that the PS/PPy-C8F particles adsorb to the water droplet surface in the form of a particle monolayer with the characteristic hexagonal close-packed structure expected for spherical (colloidal) particles. Mechanical integrity of the liquid marble increases with an increase of PPy-C8F loading of the PS/PPy-C8F particles. The water contact angle of the PS/PPy-C8F particles at air-water interface increases from 82±12º to 102±17º with an increase of PPy-C8F loading. This increase in water contact angle directly correlates with the shape of the LM, with higher contact angles giving more spherical LMs. Furthermore, the broadband light absorption properties of the PPy coating was used to control evaporation rate of the enclosed water phase on demand by irradiation with a near infrared laser. The evaporation rate could be finely controlled by the thickness of the PPy-C8F shell of the particles stabilizing the liquid marbles.

PMID: 32078776 [PubMed - as supplied by publisher]

Oral contraceptives increase platelet microparticle levels in normal-weight women with polycystic ovary syndrome.

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Oral contraceptives increase platelet microparticle levels in normal-weight women with polycystic ovary syndrome.

Hormones (Athens). 2020 Feb 20;:

Authors: Papadakis E, Sarigianni M, Tziomalos K, Mavromatidis G, Panidis D

Abstract
PURPOSE: Platelet microparticles (PMPs), which are microvesicles shed from platelets, participate in inflammation, vascular homeostasis, and thrombosis. PMPs are increased in obese women with polycystic ovary syndrome (PCOS). Agents that modulate hormonal aspects of PCOS could affect the levels of PMPs. The aim of the present study was to evaluate the effects of oral contraceptives (OCPs), antiandrogen, and metformin use for 6 and 12 months on PMPs in normal-weight women with PCOS.
METHODS: Forty-five women with PCOS and 13 healthy women were recruited. Biochemical, hormonal, and clinical parameters were recorded. Women with PCOS received treatment with OCPs, OCPs+antiandrogens, or metformin, depending on their main complaint or clinical/biochemical findings. PMPs were measured at baseline and after 6 and 12 months.
RESULTS: At baseline, patients with PCOS had higher levels of PMPs than controls (p = 0.017), which increased after 6-month treatment with OCPs (p = 0.006). Subsequently, they decreased after 12-month treatment (p = 0.046). Metformin had no effect on PMP levels.
CONCLUSION: In conclusion, PMP levels are increased in PCOS and further increase with OCP use. This effect could possibly contribute to the increased risk of venous thromboembolism associated with OCP use. However, further studies are needed to elucidate the exact role of PMPs in PCOS.

PMID: 32078734 [PubMed - as supplied by publisher]

Therapeutic potential of umbilical cord stem cells for liver regeneration.

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Therapeutic potential of umbilical cord stem cells for liver regeneration.

Curr Stem Cell Res Ther. 2020 Feb 20;:

Authors: Anwar I, Ashfaq UA, Shaukat Z

Abstract
The liver is a vital organ for life and the only internal organ that is capable of natural regeneration. Although the liver has high regeneration capacity, excessive hepatocyte death can lead to liver failure. Various factors can lead to liver damage including drug abuse, some natural products, alcohol, hepatitis and autoimmunity. Some models for studying liver injury are APAP-based model, Fas ligand (FasL), D-galactosamine/endotoxin (Gal/ET), Concanavalin A, and carbon tetrachloride, based models. The regeneration of the liver can be carried out using umbilical cord blood stem cells, which have various advantages over other stem cell types used in liver transplantation. UCB-derived stem cells lack tumorigenicity, have karyotype stability and high immunomodulatory, low risk of graft versus host disease (GVHD), low risk of transmitting somatic mutations or viral infections, low immunogenicity. They are readily available and their collection is safe and painless. This review is focussed on recent development and modern trends for the use of umbilical cord stem cells for the regeneration of liver fibrosis.

PMID: 32077830 [PubMed - as supplied by publisher]

Cholangiocarcinoma: novel therapeutic targets.

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Cholangiocarcinoma: novel therapeutic targets.

Expert Opin Ther Targets. 2020 Feb 20;:

Authors: Sato K, Glaser S, Alvaro D, Meng F, Francis H, Alpini G

Abstract
IntroductionCholangiocarcinoma (CCA) is a liver cancer derived from the biliary tree with a less than 30% five-year survival rate. Early diagnosis of CCA is challenging and treatment options are limited. Some CCA patients have genetic mutations and several therapeutic drugs or antibodies have been introduced to target abnormally expressed proteins. However, CCA is heterogeneous and patients often present with drug resistance which is attributed to multiple mutations or other factors. Novel approaches and methodologies for CCA treatments are in demand.Area coveredThis review summarizes current approaches for CCA treatments leading to the development of novel therapeutic drugs or tools for human CCA patients. A literature search was conducted in PubMed utilizing the combination of the searched term "cholangiocarcinoma" with other keywords such as "miRNA", "FGFR", "immunotherapy" or "microenvironment". Papers published within 2015-2019 were obtained for reading.Expert opinionPreclinical studies have demonstrated promising therapeutic approaches that target various cells or pathways. Recent studies have revealed that hepatic cells coordinate to promote CCA tumor progression in the tumor microenvironment, which may be a new therapeutic target. Although further studies are required, novel therapeutic tools such as extracellular vesicles could be utilized to manage CCA and its microenvironment.

PMID: 32077341 [PubMed - as supplied by publisher]

Novel Biomarkers for Evaluation of Endothelial Dysfunction.

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Novel Biomarkers for Evaluation of Endothelial Dysfunction.

Angiology. 2020 Feb 20;:3319720903586

Authors: Leite AR, Borges-Canha M, Cardoso R, Neves JS, Castro-Ferreira R, Leite-Moreira A

Abstract
Endothelial dysfunction is one of the earliest indicators of cardiovascular (CV) dysfunction, and its evaluation would be of considerable importance to stratify CV risk of many diseases and to assess the efficacy of atheroprotective treatments. Flow-mediated dilation is the most widely used method to study endothelial function. However, it is operator-dependent and can be influenced by physiological variations. Circulating biomarkers are a promising alternative. Due to the complexity of endothelial function, many of the biomarkers studied do not provide consistent information about the endothelium when measured alone. New circulating markers are being explored and some of them are thought to be suitable for the clinical setting. In this review, we focus on novel biomarkers of endothelial dysfunction, particularly endothelial microparticles, endocan, and endoglin, and discuss whether they fulfill the criteria to be applied in clinical practice.

PMID: 32077315 [PubMed - as supplied by publisher]

Targeted anti-IL-1β platelet microparticles for cardiac detoxing and repair.

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Targeted anti-IL-1β platelet microparticles for cardiac detoxing and repair.

Sci Adv. 2020 Feb;6(6):eaay0589

Authors: Li Z, Hu S, Huang K, Su T, Cores J, Cheng K

Abstract
An acute myocardial infarction (AMI) induces a sterile inflammatory response that facilitates further heart injury and promotes adverse cardiac remodeling. Interleukin-1β (IL-1β) plays a central role in the sterile inflammatory response that results from AMI. Thus, IL-1β blockage is a promising strategy for treatment of AMI. However, conventional IL-1β blockers lack targeting specificity. This increases the risk of serious side effects. To address this problem herein, we fabricated platelet microparticles (PMs) armed with anti-IL-1β antibodies to neutralize IL-1β after AMI and to prevent adverse cardiac remodeling. Our results indicate that the infarct-targeting PMs could bind to the injured heart, increasing the number of anti-IL-1β antibodies therein. The anti-IL-1β platelet PMs (IL1-PMs) protect the cardiomyocytes from apoptosis by neutralizing IL-1β and decreasing IL-1β-driven caspase-3 activity. Our findings indicate that IL1-PM is a promising cardiac detoxification agent that removes cytotoxic IL-1β during AMI and induces therapeutic cardiac repair.

PMID: 32076644 [PubMed - in process]

Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis.

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Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis.

Dis Markers. 2020;2020:2456340

Authors: Zhang L, Li H, Yuan M, Li D, Sun C, Wang G

Abstract
Background: A reliable noninvasive biomarker is not yet available for endometriosis diagnosis. Novel biomarkers for the diagnosis of endometriosis are urgently needed. The molecular constituents of exosomes, especially exosomal microRNAs (miRNAs), have considerable potential as novel biomarkers for clinical diagnosis. This study is aimed at exploring aberrant exosomal miRNA profiles by using miRNA microarray and at providing more accurate molecular biomarkers of endometriosis.
Methods: Exosomes were isolated from the serum of patients with endometriosis and negative controls and identified by electron microscopy, nanoparticle tracking analysis, and Western blot. Exosomal miRNAs were profiled by miRNA microarrays. The expression of selective serum exosomal miRNA was validated by qRT-PCR. Receiver operating characteristic (ROC) curves were established to explore the diagnostic value of selective miRNAs. Finally, GO annotation and KEGG pathway enrichment analyses were used to display possible functions associated with the two miRNAs.
Results: A total of 24 miRNAs showed differential levels of enrichment with P < 0.05 and |log2 fold change| > 1 by miRNA microarrays. Among the six selective miRNAs (i.e., miR-134-5p, miR-197-5p, miR-22-3p, miR-320a, miR-494-3p, and miR-939-5p), qRT-PCR analysis revealed that miR-22-3p and miR-320a were significantly upregulated in serum exosomes from patients with endometriosis compared with negative individuals. ROC curve revealed that the serum exosomal miR-22-3p and miR-320a yielded the area under the curve values of 0.855 and 0.827, respectively.
Conclusion: Our results demonstrated that exosomal miR-22-3p and miR-320a were significantly increased in the sera of patients with endometriosis. The two miRNAs may be useful potential biomarkers for endometriosis diagnosis.

PMID: 32076458 [PubMed - in process]

Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells.

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Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells.

Cell Rep. 2020 Feb 18;30(7):2065-2074.e4

Authors: Lucero R, Zappulli V, Sammarco A, Murillo OD, Cheah PS, Srinivasan S, Tai E, Ting DT, Wei Z, Roth ME, Laurent LC, Krichevsky AM, Breakefield XO, Milosavljevic A

Abstract
Glioblastoma (GBM) is characterized by aberrant vascularization and a complex tumor microenvironment. The failure of anti-angiogenic therapies suggests pathways of GBM neovascularization, possibly attributable to glioblastoma stem cells (GSCs) and their interplay with the tumor microenvironment. It has been established that GSC-derived extracellular vesicles (GSC-EVs) and their cargoes are proangiogenic in vitro. To further elucidate EV-mediated mechanisms of neovascularization in vitro, we perform RNA-seq and DNA methylation profiling of human brain endothelial cells exposed to GSC-EVs. To correlate these results to tumors in vivo, we perform histoepigenetic analysis of GBM molecular profiles in the TCGA collection. Remarkably, GSC-EVs and normal vascular growth factors stimulate highly distinct gene regulatory responses that converge on angiogenesis. The response to GSC-EVs shows a footprint of post-transcriptional gene silencing by EV-derived miRNAs. Our results provide insights into targetable angiogenesis pathways in GBM and miRNA candidates for liquid biopsy biomarkers.

PMID: 32075753 [PubMed - in process]

Low dose of extracellular vesicles identified that promote recovery after ischemic stroke.

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Low dose of extracellular vesicles identified that promote recovery after ischemic stroke.

Stem Cell Res Ther. 2020 Feb 19;11(1):70

Authors: Otero-Ortega L, Laso-García F, Frutos MCG, Diekhorst L, Martínez-Arroyo A, Alonso-López E, García-Bermejo ML, Rodríguez-Serrano M, Arrúe-Gonzalo M, Díez-Tejedor E, Fuentes B, Gutiérrez-Fernández M

Abstract
BACKGROUND: Mesenchymal stem cell-derived extracellular vesicles (EVs) are one of the most promising therapeutics in protective and/or regenerative therapy in animal models of stroke using a dose of 100 μg. However, whether EVs dose is related to outcomes is not known. This study aimed to identify the optimal effective dose of EVs from adipose tissue-derived mesenchymal stem cells that promote functional recovery in subcortical stroke.
MATERIALS AND METHODS: For this purpose, various doses of EVs were tested in an in vitro oxygen-glucose deprivation (OGD) model of oligodendrocytes and neuronal ischemia. At least 50 μg of EVs were necessary to induce proliferation and differentiation of oligodendrocyte and neurons in OGD conditions. For in vivo study, rats were subjected to subcortical stroke and various doses (50 μg, 100 μg, or 200 μg) of EVs were intravenously administered after 24 h.
RESULTS: All the animals in the EV groups showed significant improvement in functional tests, with an increase in tract connectivity and brain repair-associated markers, and a decrease in cell death and in astrocyte-marker expression. Cell proliferation was increased in the groups receiving 50 μg and 100 μg doses. Only the 50-μg dose was associated with significant increases in brain-derived neurotrophic factor expression.
CONCLUSION: In conclusion, 50 μg of EVs appears to be the minimal effective dose to enhance protection, brain repair, and recovery in subcortical ischemic stroke.

PMID: 32075692 [PubMed - in process]

p53's Extended Reach: The Mutant p53 Secretome.

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p53's Extended Reach: The Mutant p53 Secretome.

Biomolecules. 2020 Feb 15;10(2):

Authors: Pavlakis E, Stiewe T

Abstract
p53 suppresses tumorigenesis by activating a plethora of effector pathways. While most of these operate primarily inside of cells to limit proliferation and survival of incipient cancer cells, many extend to the extracellular space. In particular, p53 controls expression and secretion of numerous extracellular factors that are either soluble or contained within extracellular vesicles such as exosomes. As part of the cellular secretome, they execute key roles in cell-cell communication and extracellular matrix remodeling. Mutations in the p53-encoding TP53 gene are the most frequent genetic alterations in cancer cells, and therefore, have profound impact on the composition of the tumor cell secretome. In this review, we discuss how the loss or dominant-negative inhibition of wild-type p53 in concert with a gain of neomorphic properties observed for many mutant p53 proteins, shapes a tumor cell secretome that creates a supportive microenvironment at the primary tumor site and primes niches in distant organs for future metastatic colonization.

PMID: 32075247 [PubMed - in process]

Extracellular Vesicle microRNAs Contribute to the Osteogenic Inhibition of Mesenchymal Stem Cells in Multiple Myeloma.

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Extracellular Vesicle microRNAs Contribute to the Osteogenic Inhibition of Mesenchymal Stem Cells in Multiple Myeloma.

Cancers (Basel). 2020 Feb 14;12(2):

Authors: Raimondo S, Urzì O, Conigliaro A, Bosco GL, Parisi S, Carlisi M, Siragusa S, Raimondi L, Luca A, Giavaresi G, Alessandro R

Abstract
Osteolytic bone disease is the major complication associated with the progression of multiple myeloma (MM). Recently, extracellular vesicles (EVs) have emerged as mediators of MM-associated bone disease by inhibiting the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Here, we investigated a correlation between the EV-mediated osteogenic inhibition and MM vesicle content, focusing on miRNAs. By the use of a MicroRNA Card, we identified a pool of miRNAs, highly expressed in EVs, from MM cell line (MM1.S EVs), expression of which was confirmed in EVs from bone marrow (BM) plasma of patients affected by smoldering myeloma (SMM) and MM. Notably,we found that miR-129-5p, which targets different osteoblast (OBs) differentiation markers, is enriched in MM-EVs compared to SMM-EVs, thus suggesting a selective packaging correlated with pathological grade. We found that miR-129-5p can be transported to hMSCs by MM-EVs and, by the use of miRNA mimics, we investigated its role in recipient cells. Our data demonstrated that the increase of miR-129-5p levels in hMSCs under osteoblastic differentiation stimuli inhibited the expression of the transcription factor Sp1, previously described as a positive modulator of osteoblastic differentiation, and of its target the Alkaline phosphatase (ALPL), thus identifying miR-129-5p among the players of vesicle-mediated bone disease.

PMID: 32075123 [PubMed]

Transactivation of miR-202-5p by Steroidogenic Factor 1 (SF1) Induces Apoptosis in Goat Granulosa Cells by Targeting TGFβR2.

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Transactivation of miR-202-5p by Steroidogenic Factor 1 (SF1) Induces Apoptosis in Goat Granulosa Cells by Targeting TGFβR2.

Cells. 2020 Feb 14;9(2):

Authors: Ding Q, Jin M, Wang Y, Liu J, Kalds P, Wang Y, Yang Y, Wang X, Chen Y

Abstract
MicroRNAs play key roles during ovary development, with emerging evidence suggesting that miR-202-5p is specifically expressed in female animal gonads. Granulosa cells (GCs) are somatic cells that are closely related to the development of female gametes in mammalian ovaries. However, the biological roles of miR-202-5p in GCs remain unknown. Here, we show that miR-202-5p is specifically expressed in GCs and accumulates in extracellular vesicles (EVs) from large growth follicles in goat ovaries. In vitro assays showed that miR-202-5p induced apoptosis and suppressed the proliferation of goat GCs. We further revealed that miR-202-5p is a functional miRNA that targets the transforming growth factor-beta type II receptor (TGFβR2). MiR-202-5p attenuated TGF-β/SMAD signaling through the degradation of TGFβR2 at both the mRNA and protein level, decreasing p-SMAD3 levels in GCs. Moreover, we verified that steroidogenic factor 1 (SF1) is a transcriptional factor that binds to the promoters of miR-202 and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) through luciferase reporter and chromatin immunoprecipitation (ChIP) assays. That contributed to positive correlation between miR-202-5p and CYP19A1 expression and estradiol (E2) release. Furthermore, SF1 repressed TGFβR2 and p-SMAD3 levels in GCs through the transactivation of miR-202-5p. Taken together, these results suggest a mechanism by which miR-202-5p regulates canonical TGF-β/SMAD signaling through targeting TGFβR2 in GCs. This provides insight into the transcriptional regulation of miR-202 and CYP19A1 during goat ovarian follicular development.

PMID: 32075111 [PubMed - in process]

The Oviductal Extracellular Vesicles' RNA Cargo Regulates the Bovine Embryonic Transcriptome.

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The Oviductal Extracellular Vesicles' RNA Cargo Regulates the Bovine Embryonic Transcriptome.

Int J Mol Sci. 2020 Feb 14;21(4):

Authors: Bauersachs S, Mermillod P, Almiñana C

Abstract
Oviductal extracellular vesicles (oEVs) are emerging as key players in the gamete/embryo-oviduct interactions that contribute to successful pregnancy. Various positive effects of oEVs on gametes and early embryos have been found in vitro. To determine whether these effects are associated with changes of embryonic gene expression, the transcriptomes of embryos supplemented with bovine fresh (FeEVs) or frozen (FoEVs) oEVs during in vitro culture compared to controls without oEVs were analyzed by low-input RNA sequencing. Analysis of RNA-seq data revealed 221 differentially expressed genes (DEGs) between FoEV treatment and control, 67 DEGs for FeEV and FoEV treatments, and minor differences between FeEV treatment and control (28 DEGs). An integrative analysis of mRNAs and miRNAs contained in oEVs obtained in a previous study with embryonic mRNA alterations pointed to direct effects of oEV cargo on embryos (1) by increasing the concentration of delivered transcripts; (2) by translating delivered mRNAs to proteins that regulate embryonic gene expression; and (3) by oEV-derived miRNAs which downregulate embryonic mRNAs or modify gene expression in other ways. Our study provided the first high-throughput analysis of the embryonic transcriptome regulated by oEVs, increasing our knowledge on the impact of oEVs on the embryo and revealing the oEV RNA components that potentially regulate embryonic development.

PMID: 32075098 [PubMed - in process]

Extracellular Vesicle Isolation and Characterization from Periprosthetic Joint Synovial Fluid in Revision Total Joint Arthroplasty.

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Extracellular Vesicle Isolation and Characterization from Periprosthetic Joint Synovial Fluid in Revision Total Joint Arthroplasty.

J Clin Med. 2020 Feb 14;9(2):

Authors: Rüwald JM, Randau TM, Hilgers C, Masson W, Irsen S, Eymael RL, Kohlhof H, Gravius S, Burger C, Wirtz DC, Schildberg FA

Abstract
Extracellular vesicles (EVs) comprise an as yet insufficiently investigated intercellular communication pathway in the field of revision total joint arthroplasty (RTJA). This study examined whether periprosthetic joint synovial fluid contains EVs, developed a protocol for their isolation and characterized them with respect to quantity, size, surface markers as well as documented their differences between aseptic implant failure (AIF) and periprosthetic joint infection (PJI). EV isolation was accomplished using ultracentrifugation, electron microscopy (EM) and nanoparticle tracking analysis evaluated EV presence as well as particle size and quantity. EV surface markers were studied by a bead-based multiplex analysis. Using our protocol, EM confirmed the presence of EVs in periprosthetic joint synovial fluid. Higher EV particle concentrations and decreased particle sizes were apparent for PJI. Multiplex analysis confirmed EV-typical surface epitopes and revealed upregulated CD44 and HLA-DR/DP/DQ for AIF, as well as increased CD40 and CD105. Our protocol achieved isolation of EVs from periprosthetic joint synovial fluid, confirmed by EM and multiplex analysis. Characterization was documented with respect to size, concentration and epitope surface signature. Our results indicate various differences between PJI and AIF EVs. This pilot study enables new research approaches and rising diagnostic opportunities in the field of RTJA.

PMID: 32075029 [PubMed]

Somatic evolution and global expansion of an ancient transmissible cancer lineage.

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Somatic evolution and global expansion of an ancient transmissible cancer lineage.

Science. 2019 08 02;365(6452):

Authors: Baez-Ortega A, Gori K, Strakova A, Allen JL, Allum KM, Bansse-Issa L, Bhutia TN, Bisson JL, Briceño C, Castillo Domracheva A, Corrigan AM, Cran HR, Crawford JT, Davis E, de Castro KF, B de Nardi A, de Vos AP, Delgadillo Keenan L, Donelan EM, Espinoza Huerta AR, Faramade IA, Fazil M, Fotopoulou E, Fruean SN, Gallardo-Arrieta F, Glebova O, Gouletsou PG, Häfelin Manrique RF, Henriques JJGP, Horta RS, Ignatenko N, Kane Y, King C, Koenig D, Krupa A, Kruzeniski SJ, Kwon YM, Lanza-Perea M, Lazyan M, Lopez Quintana AM, Losfelt T, Marino G, Martínez Castañeda S, Martínez-López MF, Meyer M, Migneco EJ, Nakanwagi B, Neal KB, Neunzig W, Ní Leathlobhair M, Nixon SJ, Ortega-Pacheco A, Pedraza-Ordoñez F, Peleteiro MC, Polak K, Pye RJ, Reece JF, Rojas Gutierrez J, Sadia H, Schmeling SK, Shamanova O, Sherlock AG, Stammnitz M, Steenland-Smit AE, Svitich A, Tapia Martínez LJ, Thoya Ngoka I, Torres CG, Tudor EM, van der Wel MG, Viţălaru BA, Vural SA, Walkinton O, Wang J, Wehrle-Martinez AS, Widdowson SAE, Stratton MR, Alexandrov LB, Martincorena I, Murchison EP

Abstract
The canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by "metastasizing" between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage's worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer's evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.

PMID: 31371581 [PubMed - indexed for MEDLINE]

Triggering Factors in Drug Delivery Devices.

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Triggering Factors in Drug Delivery Devices.

Curr Pharm Des. 2019;25(2):107-108

Authors: Ficai A

Abstract

PMID: 31198109 [PubMed - indexed for MEDLINE]

Enhanced detection of tumour-secreted vesicles.

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Enhanced detection of tumour-secreted vesicles.

Nat Biomed Eng. 2019 06;3(6):421-422

Authors: Wan Y, Zheng SY

PMID: 31175333 [PubMed - indexed for MEDLINE]

Transcriptome maps of general eukaryotic RNA degradation factors.

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Transcriptome maps of general eukaryotic RNA degradation factors.

Elife. 2019 05 28;8:

Authors: Sohrabi-Jahromi S, Hofmann KB, Boltendahl A, Roth C, Gressel S, Baejen C, Soeding J, Cramer P

Abstract
RNA degradation pathways enable RNA processing, the regulation of RNA levels, and the surveillance of aberrant or poorly functional RNAs in cells. Here we provide transcriptome-wide RNA-binding profiles of 30 general RNA degradation factors in the yeast Saccharomyces cerevisiae. The profiles reveal the distribution of degradation factors between different RNA classes. They are consistent with the canonical degradation pathway for closed-loop forming mRNAs after deadenylation. Modeling based on mRNA half-lives suggests that most degradation factors bind intact mRNAs, whereas decapping factors are recruited only for mRNA degradation, consistent with decapping being a rate-limiting step. Decapping factors preferentially bind mRNAs with non-optimal codons, consistent with rapid degradation of inefficiently translated mRNAs. Global analysis suggests that the nuclear surveillance machinery, including the complexes Nrd1/Nab3 and TRAMP4, targets aberrant nuclear RNAs and processes snoRNAs.

PMID: 31135339 [PubMed - indexed for MEDLINE]

Hepatocellular Carcinoma: Translational Precision Medicine Approaches

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Hepatocellular Carcinoma: Translational Precision Medicine Approaches

Book. 2019

Authors: Hoshida Y

Abstract
Solid tumors release a variety of cellular components into the bloodstream that can be sampled by liquid biopsy. These blood-borne biomarkers include circulating tumor cells, exosomes, cell-free DNA, and cell-free noncoding RNA. As hepatocellular carcinoma (HCC) grows in worldwide prevalence and mortality, the application of emerging liquid biopsy technologies to HCC has been a rapidly advancing area of research. The qualitative and quantitative analysis of these biomarkers holds promise for improving the clinical care of individuals with HCC. In particular, research has focused on the role of liquid biopsy in the detection of HCC at an early and curable stage, given the major clinical need for biomarkers for this purpose. Panels of liquid biopsy biomarkers or combinations of conventional and novel assays will likely optimize sensitivity and specificity in HCC surveillance for at-risk populations. Additional applications of liquid biopsy in HCC include assessment of prognosis, monitoring treatment response and disease recurrence, and assaying underlying tumor biology. The future of liquid biopsy research will move the field from exploratory studies with heterogenous techniques to validated high-throughput molecular analyses and eventually from bench to bedside.


PMID: 32078276

 

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