Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency

[eng] The general goal of this thesis has been to progress oncolytic adenovirus therapy for PDAC, by the incorporation of novel preclinical models to test for patient-specific responses and the generation of oncolytic adenoviruses with enhanced therapeutic index. The two main objectives have been th...

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Detalles Bibliográficos
Autor: Raimondi, Giulia
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/175693
Acceso en línea:https://hdl.handle.net/2445/175693
http://hdl.handle.net/10803/671205
Access Level:acceso abierto
Palabra clave:Oncologia
Adenovirus
Micro RNAs
Cultius cel·lulars humans
Oncology
Adenoviruses
MicroRNAs
Human cell culture
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spelling Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potencyRaimondi, GiuliaOncologiaAdenovirusMicro RNAsCultius cel·lulars humansOncologyAdenovirusesMicroRNAsHuman cell culture[eng] The general goal of this thesis has been to progress oncolytic adenovirus therapy for PDAC, by the incorporation of novel preclinical models to test for patient-specific responses and the generation of oncolytic adenoviruses with enhanced therapeutic index. The two main objectives have been the following: i) Evaluate patients-derived organoids (PDOs) technology as a platform to screen for personalized virotherapy in vitro 1) Establishment of a battery of PDOs from PDAC and normal pancreatic tissues, and evaluation of their applicability in the study of adenoviral infection; 2) Screening of a battery of PDOs to identify individual sensitivities to virotherapies, and the effects derived from the combination with chemotherapy; 3) Study virotherapy-responses in metastasis originated from PDOs xenografted in mice; (ii) Improve oncolytic adenovirus potency by modulation of miRNAs deregulated in PDAC 4) Screening of aberrantly expressed miRNAs sensitizing viral oncolysis in PDAC via CRISPR/Cas9 system; 5) Generation of a miRNA sponge-adenovirus and evaluation of its oncolytic effects in vitro and in vivo; 6) Modulation of miRNA levels with the THZ1 transcriptional inhibitor, and assessment of the effects of its combination with oncolytic adenoviruses.Universitat de BarcelonaFillat i Fonts, CristinaUniversitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació2020info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/175693http://hdl.handle.net/10803/671205Tesis Doctorals - Facultat - Farmàcia i Ciències de l'Alimentacióreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaIngléscc by (c) Raimondi, Giulia, 2021http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1756932026-05-27T06:46:51Z
dc.title.none.fl_str_mv Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency
title Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency
spellingShingle Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency
Raimondi, Giulia
Oncologia
Adenovirus
Micro RNAs
Cultius cel·lulars humans
Oncology
Adenoviruses
MicroRNAs
Human cell culture
title_short Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency
title_full Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency
title_fullStr Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency
title_full_unstemmed Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency
title_sort Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency
dc.creator.none.fl_str_mv Raimondi, Giulia
author Raimondi, Giulia
author_facet Raimondi, Giulia
author_role author
dc.contributor.none.fl_str_mv Fillat i Fonts, Cristina
Universitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació
dc.subject.none.fl_str_mv Oncologia
Adenovirus
Micro RNAs
Cultius cel·lulars humans
Oncology
Adenoviruses
MicroRNAs
Human cell culture
topic Oncologia
Adenovirus
Micro RNAs
Cultius cel·lulars humans
Oncology
Adenoviruses
MicroRNAs
Human cell culture
description [eng] The general goal of this thesis has been to progress oncolytic adenovirus therapy for PDAC, by the incorporation of novel preclinical models to test for patient-specific responses and the generation of oncolytic adenoviruses with enhanced therapeutic index. The two main objectives have been the following: i) Evaluate patients-derived organoids (PDOs) technology as a platform to screen for personalized virotherapy in vitro 1) Establishment of a battery of PDOs from PDAC and normal pancreatic tissues, and evaluation of their applicability in the study of adenoviral infection; 2) Screening of a battery of PDOs to identify individual sensitivities to virotherapies, and the effects derived from the combination with chemotherapy; 3) Study virotherapy-responses in metastasis originated from PDOs xenografted in mice; (ii) Improve oncolytic adenovirus potency by modulation of miRNAs deregulated in PDAC 4) Screening of aberrantly expressed miRNAs sensitizing viral oncolysis in PDAC via CRISPR/Cas9 system; 5) Generation of a miRNA sponge-adenovirus and evaluation of its oncolytic effects in vitro and in vivo; 6) Modulation of miRNA levels with the THZ1 transcriptional inhibitor, and assessment of the effects of its combination with oncolytic adenoviruses.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/175693
http://hdl.handle.net/10803/671205
url https://hdl.handle.net/2445/175693
http://hdl.handle.net/10803/671205
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv cc by (c) Raimondi, Giulia, 2021
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Raimondi, Giulia, 2021
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Facultat - Farmàcia i Ciències de l'Alimentació
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300724

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