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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Anti-Tumor Activity of a miR-199-dependent Oncolytic Adenovirus
PLoS ONE, Volume 8, No. 9, Article e73964, Year 2013
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Description
The down-regulation of miR-199 occurs in nearly all primary hepatocellular carcinomas (HCCs) and HCC cell lines in comparison with normal liver. We exploited this miR-199 differential expression to develop a conditionally replication-competent oncolytic adenovirus, Ad-199T, and achieve tumor-specific viral expression and replication. To this aim, we introduced four copies of miR-199 target sites within the 3' UTR of E1A gene, essential for viral replication. As consequence, E1A expression from Ad-199T virus was tightly regulated both at RNA and protein levels in HCC derived cell lines, and replication controlled by the level of miR-199 expression. Various approaches were used to asses in vivo properties of Ad-199T. Ad-199T replication was inhibited in normal, miR-199 positive, liver parenchyma, thus resulting in reduced hepatotoxicity. Conversely, the intrahepatic delivery of Ad-199T in newborn mice led to virus replication and fast removal of implanted HepG2 liver cancer cells. The ability of Ad-199T to control tumor growth was also shown in a subcutaneous xenograft model in nude mice and in HCCs arising in immune-competent mice. In summary, we developed a novel oncolytic adenovirus, Ad-199T, which could demonstrate a therapeutic potential against liver cancer without causing significant hepatotoxicity. © 2013 Callegari et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3771938/bin/pone.0073964.s001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3771938/bin/pone.0073964.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3771938/bin/pone.0073964.s003.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3771938/bin/pone.0073964.s004.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3771938/bin/pone.0073964.s005.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3771938/bin/pone.0073964.s006.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3771938/bin/pone.0073964.s007.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3771938/bin/pone.0073964.s008.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3771938/bin/pone.0073964.s009.tif
Authors & Co-Authors
Callegari, Elisa
Italy, Ferrara
University of Ferrara
Elamin, Bahaeldin Khalid
Italy, Ferrara
University of Ferrara
Sudan, Khartoum
Khartoum University
D'Abundo, Lucilla
Italy, Ferrara
University of Ferrara
Falzoni, Simonetta
Italy, Ferrara
University of Ferrara
Donvito, Giovanna
Italy, Ferrara
University of Ferrara
Moshiri, Farzaneh
Italy, Ferrara
University of Ferrara
Iran, Tehran
Tehran University of Medical Sciences
Milazzo, Maddalena
Italy, Bologna
Irccs Azienda Ospedaliero-universitaria Di Bologna
Altavilla, Giuseppe
Italy, Padua
Università Degli Studi Di Padova
Giacomelli, Luciano
Italy, Padua
Università Degli Studi Di Padova
Fornari, F.
Italy, Bologna
Irccs Azienda Ospedaliero-universitaria Di Bologna
Hemminki, Akseli
Finland, Helsinki
Haartman Institute
Di Virgilio, Francesco
Italy, Ferrara
University of Ferrara
Gramantieri, Laura
Italy, Bologna
Irccs Azienda Ospedaliero-universitaria Di Bologna
Negrini, Massimo
Italy, Ferrara
University of Ferrara
Sabbioni, Silvia
Italy, Ferrara
University of Ferrara
Statistics
Citations: 57
Authors: 15
Affiliations: 6
Identifiers
Doi:
10.1371/journal.pone.0073964
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics