Browsing by Author "Polakovicova, Iva"

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    Angiotensin-(1-9) prevents cardiomyocyte hypertrophy by controlling mitochondrial dynamics via miR-129-3p/PKIA pathway
    (2020) Sotomayor-Flores, C.; Rivera-Mejias, P.; Vasquez-Trincado, C.; Lopez-Crisosto, C.; Morales, P. E.; Pennanen, C.; Polakovicova, Iva; Roa Strauch, Juan Carlos Enrique; Ocaranza, María Paz; Corvalán R., Alejandro; Aliaga-Tobar, V.; Garcia, L.; Rothermel, B. A.; Maracaja-Coutinho, V.; Ho-Xuan, H.; Meister, G.; Chiong, M.; Parra, V.; Lavandero, S.
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    Correction to : MicroRNA‑335‑5p is a potential suppressor of metastasis and invasion in gastric cancer
    (2021) Sandoval Bórquez, Alejandra; Polakovicova, Iva; Carrasco Véliz, Nicolás; Lobos González, Lorena; Riquelme, Ismael; Carrasco Avino, Gonzalo; Bizama, Carolina; Norero Muñoz, Enrique; Owen, Gareth Ivor; Roa Strauch, Juan Carlos Enrique; Corvalán R., Alejandro
    An amendment to this paper has been published and can be accessed via the original article.
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    Extracellular vesicles through the blood–brain barrier: a review
    (2022) Ramos Zaldívar, Héctor M.; Polakovicova, Iva; Salas-Huenuleo, Edison; Corvalán R., Alejandro; Kogan, Marcelo J.; Yefi Rubio, Claudia Pamela; Andía Kohnenkampf, Marcelo Edgardo
    Extracellular vesicles (EVs) are particles naturally released from cells that are delimited by a lipid bilayer and are unable to replicate. How the EVs cross the Blood–Brain barrier (BBB) in a bidirectional manner between the bloodstream and brain parenchyma remains poorly understood. Most in vitro models that have evaluated this event have relied on monolayer transwell or microfluidic organ-on-a-chip techniques that do not account for the combined effect of all cellular layers that constitute the BBB at different sites of the Central Nervous System. There has not been direct transcytosis visualization through the BBB in mammals in vivo, and evidence comes from in vivo experiments in zebrafish. Literature is scarce on this topic, and techniques describing the mechanisms of EVs motion through the BBB are inconsistent. This review will focus on in vitro and in vivo methodologies used to evaluate EVs transcytosis, how EVs overcome this fundamental structure, and discuss potential methodological approaches for future analyses to clarify these issues. Understanding how EVs cross the BBB will be essential for their future use as vehicles in pharmacology and therapeutics.
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    Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors
    (2020) Lara, Pablo.; Polakovicova, Iva; Corvalán R., Alejandro; Palma‑Florez, Sujey.; Salas-Huenuleo, Edison.; Guerrero, Simón.; Lobos González, Lorena.; Campos, América.; Muñoz Anrique, Luis.; Jorquera‑Cordero, Carla.
    Abstract Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy. Results We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules. Conclusions Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.Abstract Background Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy. Results We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules. Conclusions Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.
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    The Phylogeographic Diversity of EBV and Admixed Ancestry in the Americas-Another Model of Disrupted Human-Pathogen Co-Evolution
    (2019) Corvalán Rodríguez, Alejandro; Ruedlinger, Jenny; Mayo, Tomás de; Polakovicova, Iva; González-Hormázabal, Patricio; Aguayo, Francisco
    Epstein-Barr virus (EBV) is an etiological agent for gastric cancer with significant worldwide variations. Molecular characterizations of EBV have shown phylogeographical variations among healthy populations and in EBV-associated diseases, articularly the cosegregated BamHI-I fragment and XhoI restriction site of exon 1 of the LMP-1 gene. In the Americas, both cosegregated variants are present in EBV carriers, which aligns with the history of Asian and European human migration to this continent. Furthermore, novel recombinant variants have been found, reflecting the genetic makeup of this continent. However, in the case of EBV-associated gastric cancer (EBV-associated GC), the cosegregated European BamHI-“i” fragment and XhoI restriction site strain prevails. Thus, we propose that a disrupted coevolution between viral phylogeographical strains and mixed human ancestry in the Americas might explain the high prevalence of this particular gastric cancer subtype. This cosegregated region contains two relevant transcripts for EBV-associated GC, the BARF-1 and miR-BARTs. Thus, genome-wide association studies (GWAS) or targeted sequencing of both transcripts may be required to clarify their role as a potential source of this disrupted coevolution.