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- Hoshino, Ayuko, et al.
(author)
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Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers
- 2020
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In: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 182:4, s. 1044-
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Journal article (peer-reviewed)abstract
- There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n =151) and plasma-derived (n =120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.
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- Mateescu, B., et al.
(author)
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Obstacles and opportunities in the functional analysis of extracellular vesicle RNA - An ISEV position paper
- 2017
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In: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 6:1
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Journal article (peer-reviewed)abstract
- The release of RNA-containing extracellular vesicles (EV) into the extracellular milieu has been demonstrated in a multitude of different in vitro cell systems and in a variety of body fluids. RNA-containing EV are in the limelight for their capacity to communicate genetically encoded messages to other cells, their suitability as candidate biomarkers for diseases, and their use as therapeutic agents. Although EV-RNA has attracted enormous interest from basic researchers, clinicians, and industry, we currently have limited knowledge on which mechanisms drive and regulate RNA incorporation into EV and on how RNAencoded messages affect signalling processes in EV-targeted cells. Moreover, EV-RNA research faces various technical challenges, such as standardisation of EV isolationmethods, optimisation of methodologies to isolate and characteriseminute quantities of RNA found in EV, and development of approaches to demonstrate functional transfer of EV-RNA in vivo. These topics were discussed at the 2015 EV-RNA workshop of the International Society for Extracellular Vesicles. This position paper was written by the participants of the workshop not only to give an overview of the current state of knowledge in the field, but also to clarify that our incomplete knowledge - of the nature of EV(-RNA)s and of how to effectively and reliably study them - currently prohibits the implementation of gold standards in EV-RNA research. In addition, this paper creates awareness of possibilities and limitations of currently used strategies to investigate EV-RNA and calls for caution in interpretation of the obtained data. © 2017 The Author(s).
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- Herrera, A, et al.
(author)
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Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
- 2018
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In: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 7:9, s. 76-
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Journal article (peer-reviewed)abstract
- Carcinomas, such as colon cancer, initiate their invasion by rescuing the innate plasticity of both epithelial cells and stromal cells. Although Snail is a transcriptional factor involved in the Epithelial-Mesenchymal Transition, in recent years, many studies have also identified the major role of Snail in the activation of Cancer-Associated Fibroblast (CAF) cells and the remodeling of the extracellular matrix. In CAFs, Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant. High expression of both SNAI1 and PDGF receptors is associated with poor prognosis in cancer patients, but the mechanism(s) that underlie these connections are not understood. In this study, we demonstrate that PDGF-activated fibroblasts stimulate extracellular matrix (ECM) fiber remodeling and deposition. Furthermore, we describe how SNAI1, through the FAK pathway, is a necessary factor for ECM fiber organization. The parallel-oriented fibers are used by endothelial cells as “tracks”, facilitating their activation and the creation of tubular structures mimicking in vivo capillary formation. Accordingly, Snail1 expression in fibroblasts was required for the co-adjuvant effect of these cells on matrix remodeling and neoangiogenesis when co-xenografted in nude mice. Finally, in tumor samples from colorectal cancer patients a direct association between stromal SNAI1 expression and the endothelial marker CD34 was observed. In summary, our results advance the understanding of PDGF/SNAI1-activated CAFs in matrix remodeling and angiogenesis stimulation.
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- Massarotti, D., et al.
(author)
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Incipient Berezinskii-Kosterlitz-Thouless transition in two-dimensional coplanar Josephson junctions
- 2016
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In: Physical Review B. - 2469-9969 .- 2469-9950. ; 94:5
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Journal article (peer-reviewed)abstract
- Superconducting hybrid junctions are revealing a variety of effects. Some of them are due to the special layout of these devices, which often use a coplanar configuration with relatively large barrier channels and the possibility of hosting Pearl vortices. A Josephson junction with a quasi-ideal two-dimensional barrier has been realized by growing graphene on SiC with Al electrodes. Chemical vapor deposition offers centimeter size monolayer areas where it is possible to realize a comparative analysis of different devices with nominally the same barrier. In samples with a graphene gap below 400 nm, we have found evidence of Josephson coherence in the presence of an incipient Berezinskii-Kosterlitz-Thouless transition. When the magnetic field is cycled, a remarkable hysteretic collapse and revival of the Josephson supercurrent occurs. Similar hysteresis are found in granular systems and are usually justified within the Bean critical state model (CSM). We show that the CSM, with appropriate account for the low-dimensional geometry, can partly explain the odd features measured in these junctions.
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