Abagnale, Antonella
(2011)
Oncolytic adenovirus dl922-947 targets the DNA damage signaling pathway and enhances the effects of radiation therapy.
[Tesi di dottorato]
(Unpublished)
Item Type: |
Tesi di dottorato
|
Lingua: |
English |
Title: |
Oncolytic adenovirus dl922-947 targets the DNA damage signaling pathway and enhances the effects of radiation therapy |
Creators: |
Creators | Email |
---|
Abagnale, Antonella | antonellaabagnale@yahoo.it |
|
Date: |
30 November 2011 |
Number of Pages: |
172 |
Institution: |
Università degli Studi di Napoli Federico II |
Department: |
Biologia e patologia cellullare e molecolare "L. Califano" |
Scuola di dottorato: |
Medicina molecolare |
Dottorato: |
Oncologia ed endocrinologia molecolare |
Ciclo di dottorato: |
24 |
Coordinatore del Corso di dottorato: |
nome | email |
---|
Santoro, Massimo | massimo.santoro@unina.it |
|
Tutor: |
nome | email |
---|
Portella, Giuseppe | portella@unina.it |
|
Date: |
30 November 2011 |
Number of Pages: |
172 |
Uncontrolled Keywords: |
oncolytic adenovirus, DNA damage pathway |
Settori scientifico-disciplinari del MIUR: |
Area 06 - Scienze mediche > MED/05 - Patologia clinica |
[error in script]
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Date Deposited: |
09 Dec 2011 10:14 |
Last Modified: |
30 Apr 2014 19:48 |
URI: |
http://www.fedoa.unina.it/id/eprint/8817 |
DOI: |
10.6092/UNINA/FEDOA/8817 |

Abstract
Replication selective oncolytic viruses (OVs) are a rapidly expanding
therapeutic platform for cancer treatment. OVs are characterized by genetic
alterations that ablate critical viral protein functions essential for viral
replication in normal cells, but non-essential in tumor cells, thus targeting viral
replication to tumor cells.
dl1520 was the first oncolytic virus described, and we have demonstrated that
dl1520 is effective against anaplastic thyroid carcinoma (ATC) cells and tumor
xenografts; its antineoplastic effects are enhanced by paclitaxel, doxorubicin,
lovastatin and ionising radiation. We have also shown that the second
generation oncolytic adenovirus dl922-947 possesses a greater antitumor effect
than dl1520 against ATC cells, and that the anti-VEGF monoclonal antibody,
Bevacizumab, increased the effects of dl922-947 by improving viral
distribution within the tumor mass. Furthermore, we have also shown that
AZD1152, a selective Aurora B kinase inhibitor, negatively affects the growth
of anaplastic thyroid carcinoma cells and enhances the effects of oncolytic
virus dl922-947.
So far, preclinical and clinical studies have clearly shown the antineoplastic
potential of oncolytic viruses, at least for local treatment, but have also
highlighted the need to find associations that could improve their activity.
Association of viruses with specific combinations, not only able to directly kill
tumor cells but also to increase viral oncolytic activity, would represent a
powerful therapeutic tool for the treatment of human neoplasia, in particular for
diseases lacking of effective treatment.
The main treatment of ATC consists of irradiation plus chemotherapeutic
drugs. In order to identify novel treatment able to enhance the effects of OVs, I
have evaluated the effects of ionising radiation in combination with dl922-947,
focusing my attention on which type of cell death was activated in the
combined treatment. Moreover, I have studied the effects of dl922-947 on the
DNA damage response pathway and I have also evaluated the effects of an
ATM inhibitor on dl922-947’s activity.
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