Estudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástrico

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dc.contributor.advisorGuerrero Fonseca, Carlos Arturo
dc.contributor.authorSossa Rojas, Henry
dc.contributor.orcid0000-0001-7854-0689spa
dc.contributor.researchgroupBiología Celularspa
dc.contributor.researchgroupBiología Molecular de Virusspa
dc.contributor.researchgroupBiotecnología Microbianaspa
dc.date.accessioned2023-04-24T13:40:56Z
dc.date.available2023-04-24T13:40:56Z
dc.date.issued2022-07-01
dc.descriptionilustraciones, fotografías a colorspa
dc.description.abstractA pesar de los avances en la investigación en ciencias biomédicas, el cáncer gástrico sigue siendo una de las principales causas de morbilidad y mortalidad en el mundo debido a la limitada eficacia de las terapias convencionales. El objetivo de este estudio fue examinar el potencial oncolítico del aislamiento rotaviral Wt1-5 en muestras de adenocarcinomas gástricos obtenidas de seis pacientes sometidos a gastrectomías radicales en el Hospital Universitario de la Samaritana. Para lograrlo, se evaluó la capacidad del rotavirus para propagarse en el tumor y la importancia de la expresión de las proteínas correceptoras de membrana citoplasmática αVβ3, PDI, Hsc70, Hsp90, Hsp70, Hsp60 y Hsp40 durante la infección de las células tumorales. Se encontró que estas proteínas se expresan de forma diferencial en las células tumorales en comparación con el tejido no tumoral adyacente y que las células neoplásicas se infectaron significativamente en comparación con el tejido no tumoral adyacente, lo que inicio un efecto oncolítico. A las 12 h.p.i, se observó que la apoptosis era uno de los tipos de muerte que se evidenciaba al evaluar la expresión de caspasa 3, caspasa 9, PARP, citocromo C, BAX, BID, p53 y Bcl-2, así como al observar cambios morfológicos, como la marginación de la cromatina, condensación y fragmentación nuclear. Finalmente, en las horas posteriores a la infección (60 h.p.i), se observó una oncólisis que comprometió todo el espesor del tumor. En consecuencia, los resultados de este trabajo sugieren que el RV Wt1-5 puede ser una terapia coadyuvante a las terapias convencionales y/o terapias dirigidas en el manejo del cáncer gástrico. Además, la infección ex vivo del modelo de tejido tumoral también mostró características de respuesta inmune que pueden explorarse en estudios futuros. (Texto tomado de la fuente)spa
dc.description.abstractDespite advances in biomedical science research, gastric cancer remains one of the leading causes of morbidity and mortality worldwide due to the limited efficacy of conventional therapies. The aim of this study was to examine the oncolytic potential of the rotaviral Wt1-5 isolate in gastric adenocarcinoma simples obtained from six patients undergoing radical gastrectomies at the Hospital Universitario de la Samaritana. To achieve this, the ability of the rotavirus to propagate in the tumor and the importance of the expression of the cytoplasmic membrane coreceptor proteins αVβ3, PDI, Hsc70, Hsp90, Hsp70, Hsp60, and Hsp40 during tumor cell infection were evaluated. It was found that these proteins were differentially expressed in tumor cells compared to adjacent non-tumor tissue, and neoplastic cells were significantly infected compared to adjacent non-tumor tissue, initiating an oncolytic effect. At 12 h.p.i, apoptosis was observed as one of the types of cell death, evidenced by the expression of caspase 3, caspase 9, PARP, cytochrome C, BAX, BID, p53, and Bcl-2, as well as morphological changes such as chromatin margination, condensation, and nuclear fragmentation. Finally, in the hours following infection (60 h.p.i), complete oncotic destruction of the tumor thickness was observed. Consequently, the results of this work suggest that RV Wt1-5 may be an adjuvant therapy to conventional and/or targeted therapies in the management of gastric cancer. In addition, ex vivo infection of the tumor tissue model also showed characteristics of immune response that can be explored in future studies.eng
dc.description.degreelevelDoctoradospa
dc.description.researchareaVirus Oncolíticosspa
dc.format.extent162 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.cospa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/83759
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeBogotá,Colombiaspa
dc.publisher.programBogotá - Ciencias - Doctorado en Biotecnologíaspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseReconocimiento 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/spa
dc.subject.ddc610 - Medicina y salud::615 - Farmacología y terapéuticaspa
dc.subject.ddc610 - Medicina y salud::611 - Anatomía humana, citología, histologíaspa
dc.subject.ddc610 - Medicina y salud::616 - Enfermedadesspa
dc.subject.decsNeoplasias gástricasspa
dc.subject.decsStomach Neoplasmseng
dc.subject.decsGastrectomíaspa
dc.subject.decsGastrectomyeng
dc.subject.proposalRotavirusspa
dc.subject.proposalTerapia viral oncolíticaspa
dc.subject.proposalCáncer gástricospa
dc.subject.proposalApoptosisspa
dc.subject.proposalLisis tumoralspa
dc.subject.proposalRotaviruseng
dc.subject.proposalOncolytic viral therapyeng
dc.subject.proposalGastric cancereng
dc.subject.proposalApoptosiseng
dc.subject.proposalTumor lysiseng
dc.titleEstudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástricospa
dc.title.translatedOncolytic potential of human rotaviral isolation Wt 1-5 in gastric adenocarcinomaeng
dc.typeTrabajo de grado - Doctoradospa
dc.type.coarhttp://purl.org/coar/resource_type/c_db06spa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/doctoralThesisspa
dc.type.redcolhttp://purl.org/redcol/resource_type/TDspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
dcterms.audience.professionaldevelopmentAdministradoresspa
dcterms.audience.professionaldevelopmentBibliotecariosspa
dcterms.audience.professionaldevelopmentConsejerosspa
dcterms.audience.professionaldevelopmentEstudiantesspa
dcterms.audience.professionaldevelopmentGrupos comunitariosspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
dcterms.audience.professionaldevelopmentMaestrosspa
dcterms.audience.professionaldevelopmentMedios de comunicaciónspa
dcterms.audience.professionaldevelopmentPadres y familiasspa
dcterms.audience.professionaldevelopmentPersonal de apoyo escolarspa
dcterms.audience.professionaldevelopmentProveedores de ayuda financiera para estudiantesspa
dcterms.audience.professionaldevelopmentPúblico generalspa
dcterms.audience.professionaldevelopmentReceptores de fondos federales y solicitantesspa
dcterms.audience.professionaldevelopmentResponsables políticosspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa
oaire.awardtitleEstudio del potencial oncolítico del aislamiento rotaviral humano Wt1-5 en adenocarcinoma gástricospa

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