Affinito, Alessandra (2017) Identification of selective aptamer ligands for Glioblastoma Stem Cells as new therapeutic tools for Glioblastoma. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: Identification of selective aptamer ligands for Glioblastoma Stem Cells as new therapeutic tools for Glioblastoma
Creators:
CreatorsEmail
Affinito, Alessandraaleaffi4@gmail.com
Date: 11 December 2017
Number of Pages: 80
Institution: Università degli Studi di Napoli Federico II
Department: dep14
Dottorato: phd054
Ciclo di dottorato: 30
Coordinatore del Corso di dottorato:
nomeemail
Avvedimento, Vittorio Enricovittorioenrico.avvedimento@unina.it
Tutor:
nomeemail
Condorelli, GerolamaUNSPECIFIED
Date: 11 December 2017
Number of Pages: 80
Uncontrolled Keywords: Glioblastoma, Aptamers, Cancer stem cells
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/04 - Patologia generale
Date Deposited: 27 Dec 2017 23:56
Last Modified: 19 Mar 2019 09:41
URI: http://www.fedoa.unina.it/id/eprint/12251

Abstract

Glioblastoma (GBM) is the most frequent and aggressive primary brain tumour in adults. Standard treatments for GBM patients consist of tumour resection, radiotherapy (RT) and chemotherapy with alkylating agent Temozolomide (TMZ). However, despite advances in surgical and medical treatment, prognosis for GBM patients remains dismal, with a median survival of 14–15 months. A small population of cancer stem cells (glioblastoma stem cells, GSCs), that retains stem cell properties including self-renewal and multipotency, has been implicated as responsible for the frequent relapse of glioblastoma and its resistance to conventional therapeutic. Thus, the identification of new molecules that can specifically target these GSCs is a fundamental challenge for the development of effective glioma therapies. In this study, we developed a differential whole cell-SELEX, an  in vitro  evolution-based approach, which allowed us to generate RNA-ligands with high affinity and specificity for GSCs, named aptamers. These nucleic acids were obtained by iterative evolution of a random pool of sequences using human primary GSCs as target. The obtained aptamer, 40L had been proved to be selective for GSCs, distinguishing them from tumor differentiated cells. Moreover, 40L revealed to be functionally active on target cells and able to inhibit stemness, cell growth and migration in vitro as well as in vivo. In conclusion, our results indicate that 40L and its short form A40s can selectively target GSCs and, given the crucial role of these cells in GBM recurrence and multi-drug resistance, 40L and A40s represent innovative drug candidates with a great potential in the GBM treatment.

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