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Gastric cancer (GC) is a major health concern worldwide, presenting a complex pathophysiology that has hindered many therapeutic efforts so far. In this context, purinergic signaling emerges as a promising pathway for intervention due to its known role in cancer cell proliferation and migration. In this work, we explored in more detail the role of purinergic signaling in GC with several experimental approaches. First, we measured extracellular ATP concentrations on GC-derived cell lines (AGS, MKN-45, and MKN-74), finding higher levels of extracellular ATP than those obtained for the non-tumoral gastric cell line GES-1. Next, we established the P2Y2 and P2X4 receptors (P2Y2R and P2X4R) expression profile on these cells and evaluated their role on cell proliferation and migration after applying overexpression and knockdown strategies. In general, a P2Y2R overexpression and P2X4R downregulation pattern were observed on GC cell lines, and when these patterns were modified, concomitant changes in cell viability were observed. These modifications on gene expression also modified transepithelial electrical resistance (TEER), showing that higher P2Y2R levels decreased TEER, and high P2X4R expression had the opposite effect, suggesting that P2Y2R and P2X4R activation could promote and suppress epithelial-mesenchymal transition (EMT), respectively. These effects were confirmed after treating AGS cells with UTP, a P2Y2R-agonist that modified the expression patterns towards mesenchymal markers. To further characterize the effects of P2Y2R activation on EMT, we used cDNA microarrays and observed that UTP induced important transcriptional changes on several cell processes like cell proliferation induction, apoptosis inhibition, cell differentiation induction, and cell adhesion reduction. These results suggest that purinergic signaling plays a complex role in GC pathophysiology, and changes in purinergic balance can trigger tumorigenesis in non-tumoral gastric cells.

Este trabajo fue recibido el 06 de agosto de 2018. Aceptado con modificaciones: 02 de marzo de 2019. Aceptado para ser publicado: 15 de abril de 2019. RESUMEN La obesidad es una enfermedad multifactorial definida como acumulación patológica de grasa. Su prevalencia ha aumentado enormemente en el mundo. Chile presenta una de las mayores prevalencias de obesidad de la OCDE. Su casuística simplificada comprende una diferencia sostenida entre gasto e ingesta de energía, manteniendo un delta positivo traducido en mayor acumulación de grasa. No obstante, la etiología completa de esta enfermedad comprende también factores psicológicos, genéticos, ambientales, etc. El ambiente juega un papel clave en la predisposición al consumo de alimentos, a la realización de ejercicio físico, incluso afectando la susceptibilidad genómica, exacerbando o disminuyendo la carga genética. Esta modificación de susceptibilidad genética por el ambiente se conoce como epigenética, que se refiere a una serie de modificaciones por "sobre" la genética que son altamente modificables por factores ambientales. Se ha descrito que algunas de estas modificaciones pueden heredarse de una generación a otra, lo que otorga otro nivel de complejidad al estudio de nuevas terapias complementarias para frenar la tendencia al sobrepeso. En la presente revisión se describe cuales son las modificaciones epigenéticas más frecuentes encontradas, su relación con obesidad y dieta, y finalmente como se relaciona con la transmisión transgeneracional de esta patología.

<p>The Garrotxa Volcanic Field (GVF) is one of the monogenetic Quaternary volcanic fields associated with the intraplate European Cenozoic Rift System. The GVF is located between the cities of Olot and Girona, NE Spain, and it covers an area of about 600 km<sup>2</sup>. This volcanic field ranges in age from 0.7 Ma to early Holocene and is considered active since the last eruption dated 11,000-13,000 years ago.</p> <p>The volcanic activity, mainly controlled by regional normal faults generated during the Neogene extension, was highly variable with over 50 scattered eruptive vents that were produced during short-lived monogenetic eruptions. Scoria cones represent the most common landforms of the GVF with subordinate maars and tuff rings/cones. Most of the volcanoes are located in the northern sector between the towns of Olot and Santa Pau and they stand on a folded Eocene basement. Volcanoes located in southern area of the field, close to the city of Girona, stand mainly on a fractured Paleozoic basement.</p> <p>The objective of this work is to identify eruptive processes and the geomorphic evolution of volcanic edifices and related them to environmental influencing factors. The best volcanic structures in the GVF have been selected due to their well-preserved morphologies. Cones (W<sub>co</sub>) and craters (W<sub>cr</sub>) mean diameters, as well as cones maximum height (H<sub>max</sub>), maximum crater depth (D<sub>crmax</sub>) and external slope of the cones (S<sub>median</sub>) have been measured.</p> <p>This study shows that it is possible to create a catalogue of likely eruption sequences based on field evidences and morphological/morphometric data. In this way, a more realistic eruption scenarios can be developed for different parts of the volcanic field. Morphometry can also provide rough relative age constraints on edifices. These methodologies can improve our understanding for a better evaluation of volcanic hazards in urbanized volcanic fields as the GVF.</p>

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