Linked Life Data

21710499

Source:http://linkedlifedata.com/resource/pubmed/id/21710499

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-6-28
pubmed:abstractText
The human Y-box binding protein 1 (YB-1) is known to be a promising target for cancer therapy. We have demonstrated that YB-1 plays an important role in the adenoviral life cycle by regulating the adenoviral E2-gene expression. Thus, we studied the oncolytic effect of the recombinant adenovirus Ad-Delo3-RGD, in which the transactivation domain CR3 of the E1A protein is ablated to enable viral replication only in YB-1 positive cancer cells. In vitro Southern Blot analysis and cytopathic effect assays demonstrate high anti-glioma potency, which was significantly increased in combination with temozolomide (TMZ), daunorubicin and cisplatin. Since vascular endothelial growth factor (VEGF) is thought to promote the hypervascular phenotype of primary, malignant brain tumors, we also tested Ad-Delo3-RGD in regard to the inhibition of VEGF expression. Indeed, we found that Ad-Delo3-RGD induced VEGF down regulation, which was even amplified under hypoxic conditions. Tumor-bearing nudemice treated with the YB-1 dependent oncolytic adenovirus showed significantly smaller tumors than untreated controls. Furthermore, combination therapy with TMZ led to a regression in all treated animals with complete tumor regression in 33 % of analyzed mice, which was verified by bioluminescence imaging and histological studies. In addition, histopathological evaluation revealed enhanced apoptosis and a reduction in tumor vessel formation, indicating that Ad-Delo3-RGD has an anti-angiogenic effect in addition to its oncolytic capacity in vivo. Hence, our results demonstrate that the combination therapy of YB-1 dependent virotherapy and TMZ is effective in a xenograft glioma mouse model and might be useful in a YB-1 based clinical setting.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1097-0215
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 UICC.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
129
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1265-76
pubmed:meshHeading
pubmed-meshheading:21710499-Adenoviridae, pubmed-meshheading:21710499-Animals, pubmed-meshheading:21710499-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:21710499-Blotting, Southern, pubmed-meshheading:21710499-Blotting, Western, pubmed-meshheading:21710499-Brain Neoplasms, pubmed-meshheading:21710499-Cisplatin, pubmed-meshheading:21710499-Combined Modality Therapy, pubmed-meshheading:21710499-Dacarbazine, pubmed-meshheading:21710499-Daunorubicin, pubmed-meshheading:21710499-Gene Therapy, pubmed-meshheading:21710499-Genetic Vectors, pubmed-meshheading:21710499-Glioma, pubmed-meshheading:21710499-Humans, pubmed-meshheading:21710499-Immunoenzyme Techniques, pubmed-meshheading:21710499-Mice, pubmed-meshheading:21710499-Mice, Nude, pubmed-meshheading:21710499-Oncolytic Virotherapy, pubmed-meshheading:21710499-RNA, Messenger, pubmed-meshheading:21710499-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21710499-Tumor Cells, Cultured, pubmed-meshheading:21710499-Virus Replication, pubmed-meshheading:21710499-Y-Box-Binding Protein 1
pubmed:year
2011
pubmed:articleTitle
YB-1 dependent virotherapy in combination with temozolomide as a multimodal therapy approach to eradicate malignant glioma.
pubmed:affiliation
Institut für Experimentelle Onkologie und Therapieforschung, Klinikum Rechts der Isar, Munich, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't