start-ver=1.4
cd-journal=joma
no-vol=20
cd-vols=
no-issue=8
article-no=
start-page=437
end-page=444
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201308
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The integrin inhibitor cilengitide enhances the anti-glioma efficacy of vasculostatin-expressing oncolytic virus
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Oncolytic viral (OV) therapy has been considered as a promising treatment modality for brain tumors. Vasculostatin, the fragment of brain-specific angiogenesis inhibitor-1, shows anti-angiogenic activity against malignant gliomas. Previously, a vasculostatin-expressing oncolytic herpes simplex virus-1, Rapid Antiangiogenesis Mediated By Oncolytic virus (RAMBO), was reported to have a potent antitumor effect. Here, we investigated the therapeutic efficacy of RAMBO and cilengitide, an integrin inhibitor, combination therapy for malignant glioma. In vitro, tube formation was significantly decreased in RAMBO and cilengitide combination treatment compared with RAMBO or cilengitide monotherapy. Moreover, combination treatment induced a synergistic suppressive effect on endothelial cell migration compared with the control virus. RAMBO, combined with cilengitide, induced synergistic cytotoxicity on glioma cells. In the caspase-8 and -9 assays, the relative absorption of U87 Delta EGFR cell clusters treated with cilengitide and with RAMBO was significantly higher than that of those treated with control. In addition, the activity of caspase 3/7 was significantly increased with combination therapy. In vivo, there was a significant increase in the survival of mice treated with combination therapy compared with RAMBO or cilengitide monotherapy. These results indicate that cilengitide enhanced vasculostatin-expressing OV therapy for malignant glioma and provide a rationale for designing future clinical trials combining these two agents.
en-copyright=
kn-copyright=

en-aut-name=FujiiK
en-aut-sei=Fujii
en-aut-mei=K
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KurozumiK
en-aut-sei=Kurozumi
en-aut-mei=K
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=IchikawaT
en-aut-sei=Ichikawa
en-aut-mei=T
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=OnishiM
en-aut-sei=Onishi
en-aut-mei=M
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ShimazuY
en-aut-sei=Shimazu
en-aut-mei=Y
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=IshidaJ
en-aut-sei=Ishida
en-aut-mei=J
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=ChioccaEA
en-aut-sei=Chiocca
en-aut-mei=EA
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KaurB
en-aut-sei=Kaur
en-aut-mei=B
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=DateI
en-aut-sei=Date
en-aut-mei=I
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg

affil-num=7
en-affil=
kn-affil=Brigham & Womens Hosp, Dept Neurosurg

affil-num=8
en-affil=
kn-affil=Ohio State Univ, Dept Neurol Surg, Dardinger Lab Neurooncol & Neurosci

affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
en-keyword=cilengitide
kn-keyword=cilengitide
en-keyword=glioma
kn-keyword=glioma
en-keyword=oncolytic viral therapy
kn-keyword=oncolytic viral therapy
END