About: Proteasome inhibition in cancer is associated with enhanced tumor targeting by the adeno‐associated virus/phage

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About: Proteasome inhibition in cancer is associated with enhanced tumor targeting by the adeno‐associated virus/phage Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Proteasome inhibition in cancer is associated with enhanced tumor targeting by the adeno‐associated virus/phage
Creator	Stoneham, Charlotte Hajitou, Amin Syed, Nelofer Umukoro, Eloho Yata, Teerapong Przystal, Justyna O'neill, Kevin
source	Medline; PMC
abstract	Bacteriophage (phage), which are viruses that infect bacteria only, have shown promise as vehicles for targeted cancer gene therapy, albeit with poor efficiency. Recently, we generated an improved version of phage vectors by incorporating cis genetic elements of adeno‐associated virus (AAV). This novel AAV/phage hybrid (AAVP) efficiently delivered systemically administered therapeutic genes to various tumor targets by displaying an integrin tumor‐targeting ligand on the phage capsid. However, inherent limitations in bacteriophage mean that these AAVP vectors still need to be improved. One of the limitations of AAVP in mammalian cells may be its susceptibility to proteasomal degradation. The proteasome is upregulated in cancer and it is known that it constitutes a barrier to gene delivery by certain eukaryotic viruses. We report here that inhibition of proteasome improved targeted reporter gene delivery by AAVP in cancer cells in vitro and in tumors in vivo after intravenous vector administration to tumor‐bearing mice. We also show enhanced targeted tumor cell killing by AAVP upon proteasome inhibition. The AAVP particles persisted significantly in cancer cells in vitro and in tumors in vivo after systemic administration, and accumulated polyubiquitinated coat proteins. Our results suggest that the proteasome is indeed a barrier to tumor targeting by AAVP and indicate that a combination of proteasome‐inhibiting drugs and AAVP should be considered for clinical anticancer therapy.
has issue date	2012-08-21(xsd:dateTime)
bibo:doi	10.1016/j.molonc.2012.08.001
bibo:pmid	22951279
has license	cc-by
sha1sum (hex)	d0a7af58aa5e272f1c7aef4e6908dd3059d9173e
schema:url	https://doi.org/10.1016/j.molonc.2012.08.001
resource representing a document's title	Proteasome inhibition in cancer is associated with enhanced tumor targeting by the adeno‐associated virus/phage
has PubMed Central identifier	PMC3553581
has PubMed identifier	22951279
schema:publication	Mol Oncol
resource representing a document's body	covid:d0a7af58aa5e272f1c7aef4e6908dd3059d9173e#body_text
is schema:about of	named entity 'proteasome' named entity 'targets' named entity 'efficiently' named entity 'therapeutic' named entity 'inhibition' named entity 'systemic administration' named entity 'promise' named entity 'NOVEL' named entity 'INFECT' named entity 'ONE OF' named entity 'ENHANCED' named entity 'ADMINISTRATION' named entity 'IN VIVO' named entity 'HERE' named entity 'BACTERIA ' named entity 'PROTEASOME INHIBITION' named entity 'DISPLAYING' named entity 'VERSION' named entity 'DELIVERED' named entity 'NEED' named entity 'ENHANCED' named entity 'TARGETS' named entity 'VIRUS' named entity 'REPORT' named entity 'TUMOR' named entity 'BARRIER' named entity 'TUMOR TARGETING' named entity 'OUR' named entity 'MEAN' named entity 'COAT PROTEINS' named entity 'ADENO-ASSOCIATED VIRUS' named entity 'CERTAIN' named entity 'MICE' named entity 'IMPROVED' named entity 'ACCUMULATED' named entity 'MAMMALIAN' named entity 'CLINICAL' named entity 'INHIBITING' named entity 'CANCER CELLS' named entity 'CANCER' named entity 'VECTOR' named entity 'PROMISE' named entity 'VECTORS' named entity 'CONSIDERED' named entity 'TARGETING LIGAND' named entity 'GENETIC ELEMENTS' named entity 'DRUGS' named entity 'THERAPEUTIC' named entity 'RESULTS' named entity 'CANCER' named entity 'BEARING' named entity 'RECENTLY' named entity 'PHAGE' named entity 'CELLS' named entity 'ADMINISTERED' named entity 'PROTEASOMAL DEGRADATION' named entity 'COMBINATION' named entity 'INHIBITION' named entity 'ANTICANCER THERAPY' named entity 'HAVE' named entity 'TUMOR CELL' named entity 'POOR EFFICIENCY' named entity 'PROTEASOME' named entity 'CELL KILLING' named entity 'INTRAVENOUS' named entity 'PARTICLES' named entity 'UPREGULATED' named entity 'MAY BE' named entity 'SUGGEST' named entity 'THESE' named entity 'INTEGRIN' named entity 'REPORTER GENE' named entity 'VARIOUS' named entity 'GENES' named entity 'SUSCEPTIBILITY'

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