Dissertation/ Thesis

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

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency
Συγγραφείς: Raimondi, Giulia
Συνεισφορές: University/Department: Universitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació
Thesis Advisors: Fillat i Fonts, Cristina, Noé Mata, Verónica
Πηγή: TDX (Tesis Doctorals en Xarxa)
Στοιχεία εκδότη: Universitat de Barcelona, 2020.
Έτος έκδοσης: 2020
Φυσική περιγραφή: 271 p.
Θεματικοί όροι: Oncologia, Oncología, Oncology, Adenovirus, Adenoviruses, Micro RNAs, MicroRNAs, Cultius cel·lulars humans, Cultivos celulares humanos, Human cell culture, Ciències de la Salut
Περιγραφή: 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.
Τύπος εγγράφου: Dissertation/Thesis
Περιγραφή αρχείου: application/pdf
Γλώσσα: English
Σύνδεσμος πρόσβασης: http://hdl.handle.net/10803/671205
Rights: L'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by/4.0/
Αριθμός Καταχώρησης: edstdx.10803.671205
Βάση Δεδομένων: TDX
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