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Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice

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Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice

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dc.contributor.author Cáceres, Marta es_ES
dc.contributor.author Quesada, Rita es_ES
dc.contributor.author Iglesias, Mar es_ES
dc.contributor.author Real, Francisco X. es_ES
dc.contributor.author Villamonte, Maria es_ES
dc.contributor.author Martinez de Villarreal, Jaime es_ES
dc.contributor.author Pérez, Mónica es_ES
dc.contributor.author Andaluz, Ana es_ES
dc.contributor.author Moll, Xavier es_ES
dc.contributor.author Berjano, Enrique es_ES
dc.contributor.author Dorcaratto, Dimitri es_ES
dc.contributor.author Sánchez Velazquez, Patricia es_ES
dc.contributor.author Grande, Luis es_ES
dc.contributor.author Burdío, Fernando es_ES
dc.date.accessioned 2021-11-05T12:57:36Z
dc.date.available 2021-11-05T12:57:36Z
dc.date.issued 2020-10-27 es_ES
dc.identifier.issn 2045-2322 es_ES
dc.identifier.uri http://hdl.handle.net/10251/176168
dc.description.abstract [EN] Pancreatic duct ligation (PDL) in the murine model has been described as an exocrine pancreatic atrophy-inducing procedure. However, its influence has scarcely been described on premalignant lesions. This study describes the histological changes of premalignant lesions and the gene expression in a well-defined model of pancreatic ductal adenocarcinoma by PDL. Selective ligation of the splenic lobe of the pancreas was performed in Ptf1a-Cre((+/ki)); K-ras LSLG12Vgeo((+/ki)) mice (PDL-Kras mice). Three experimental groups were evaluated: PDL group, controls and shams. The presence and number of premalignant lesions (PanIN 1-3 and Atypical Flat Lesions-AFL) in proximal (PP) and distal (DP) pancreas were studied for each group over time. Microarray analysis was performed to find differentially expressed genes (DEG) between PP and PD. Clinical human specimens after pancreaticoduodenectomy with ductal occlusion were also evaluated. PDL-Kras mice showed an intense pattern of atrophy in DP which was shrunk to a minimal portion of tissue. Mice in control and sham groups had a 7 and 10-time increase respectively of risk of high-grade PanIN 2 and 3 and AFL in their DP than PDL-Kras mice. Furthermore, PDL-Kras mice had significantly less PanIN 1 and 2 and AFL lesions in DP compared to PP. We identified 38 DEGs comparing PP and PD. Among them, several mapped to protein secretion and digestion while others such as Nupr1 have been previously associated with PanIN and PDAC. PDL in Ptf1a-Cre((+/ki)); K-ras LSLG12Vgeo((+/ki)) mice induces a decrease in the presence of premalignant lesions in the ligated DP. This could be a potential line of research of interest in some cancerous risk patients. es_ES
dc.description.sponsorship This work was supported by the Spanish Ministerio de Economia, Industria y Competitividad under "Plan Estatal de Investigacion, Desarrollo e Innovacion Orientada a los Retos de la Sociedad", Grant No "RTI2018-094357-B-C22". es_ES
dc.language Inglés es_ES
dc.publisher Nature Publishing Group es_ES
dc.relation.ispartof Scientific Reports es_ES
dc.rights Reconocimiento (by) es_ES
dc.subject.classification TECNOLOGIA ELECTRONICA es_ES
dc.title Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1038/s41598-020-74947-4 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/AEI//RTI2018-094357-B-C22//INVESTIGACION QUIRURGICA PARA TERAPIAS ABLATIVAS INNOVADORAS/ es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica es_ES
dc.description.bibliographicCitation Cáceres, M.; Quesada, R.; Iglesias, M.; Real, FX.; Villamonte, M.; Martinez De Villarreal, J.; Pérez, M.... (2020). Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice. Scientific Reports. 10(1):1-12. https://doi.org/10.1038/s41598-020-74947-4 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.1038/s41598-020-74947-4 es_ES
dc.description.upvformatpinicio 1 es_ES
dc.description.upvformatpfin 12 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 10 es_ES
dc.description.issue 1 es_ES
dc.identifier.pmid 33110094 es_ES
dc.identifier.pmcid PMC7591874 es_ES
dc.relation.pasarela S\420466 es_ES
dc.contributor.funder Agencia Estatal de Investigación es_ES
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