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@ARTICLE{Schipper:128262,
author = {H. Schipper and V. Alla and C. Meier and D. Nettelbeck$^*$
and O. Herchenröder and B. M. Pützer},
title = {{E}radication of metastatic melanoma through cooperative
expression of {RNA}-based {HDAC}1 inhibitor and p73 by
oncolytic adenovirus.},
journal = {OncoTarget},
volume = {5},
number = {15},
issn = {1949-2553},
address = {[S.l.]},
publisher = {Impact Journals LLC},
reportid = {DKFZ-2017-04279},
pages = {5893 - 5907},
year = {2014},
abstract = {Malignant melanoma is a highly aggressive cancer that
retains functional p53 and p73, and drug unresponsiveness
largely depends on defects in death pathways after
epigenetic gene silencing in conjunction with an imbalanced
p73/DNp73 ratio. We constructed oncolytic viruses armed with
an inhibitor of deacetylation and/or p73 to specifically
target metastatic cancer. Arming of the viruses is aimed at
lifting epigenetic blockage and re-opening apoptotic
programs in a staggered manner enabling both, efficient
virus replication and balanced destruction of target cells
through apoptosis. Our results showed that cooperative
expression of shHDAC1 and p73 efficiently enhances apoptosis
induction and autophagy of infected cells which reinforces
progeny production. In vitro analyses revealed $100\%$
cytotoxicity after infecting cells with OV.shHDAC1.p73 at a
lower virus dose compared to control viruses. Intriguingly,
OV.shHDAC1.p73 acts as a potent inhibitor of highly
metastatic xenograft tumors in vivo. Tumor expansion was
significantly reduced after intratumoral injection of 3 x
10⁸ PFU of either OV.shHDAC1 or OV.p73 and, most
important, complete regression could be achieved in 100 $\%$
of tumors treated with OV.shHDAC1.p73. Our results point out
that the combination of high replication capacity and
simultaneous restoration of cell death routes significantly
enhance antitumor activity.},
keywords = {DNA-Binding Proteins (NLM Chemicals) / Nuclear Proteins
(NLM Chemicals) / RNA, Small Interfering (NLM Chemicals) /
Tumor Protein p73 (NLM Chemicals) / Tumor Suppressor
Proteins (NLM Chemicals) / p73 protein, human (NLM
Chemicals) / HDAC1 protein, human (NLM Chemicals) / Histone
Deacetylase 1 (NLM Chemicals)},
cin = {F110},
ddc = {610},
cid = {I:(DE-He78)F110-20160331},
pnm = {316 - Infections and cancer (POF3-316)},
pid = {G:(DE-HGF)POF3-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25071017},
pmc = {pmc:PMC4171600},
doi = {10.18632/oncotarget.1839},
url = {https://inrepo02.dkfz.de/record/128262},
}