Irradiation enhances the therapeutic effect of the oncolytic adenovirus XVir-N-31 in brain tumor initiating cells.
Int J Mol Med
; 44(4): 1484-1494, 2019 Oct.
Article
em En
| MEDLINE
| ID: mdl-31432139
ABSTRACT
Virotherapy using oncolytic viruses is an upcoming therapy strategy for cancer treatment. A variety of preclinical and clinical trials have indicated that adenoviruses may be used as potent agents in the treatment of a variety of cancers, and also for the treatment of brain tumors. In these studies, it has also been shown that oncovirotherapy is safe in terms of toxicity and side effects. In addition, previous studies have presented evidence for a significant role of oncovirotherapy in the activation of antitumor immune responses. With regard to oncolytic adenoviruses, we have demonstrated previously that the multifunctional protein Ybox binding protein1 (YB1) is a potent factor that was used to develop an YB1dependent oncolytic adenovirus (XVirN31). XVirN31 provides the opportunity for tumorselective replication and exhibited marked oncolytic properties in a mouse glioma tumor model using therapyresistant brain tumor initiating cells (BTICs). In a number of, but not all, patients with glioma, YB1 is primarily located in the nucleus; this promotes XVirN31replication and subsequently tumor cell lysis. However, in certain BTICs, only a small amount of YB1 has been identified to be nuclear, and therefore virus replication is suboptimal. YB1 in BTICs was demonstrated to be translocated into the nucleus following irradiation, which was accompanied by an enhancement in XVirN31 production. R28 glioma spheres implanted in living organotypic human brain slices exhibited a significantly delayed growth rate when preirradiated prior to XVirN31infection as compared with single treatment methods. Consistent with the in vitro data, R28 gliomabearing mice exhibited a prolonged mean and median survival following single tumor irradiation prior to intratumoral XVirN31 injection, compared with the single treatment methods. In conclusion, the present study demonstrated that in an experimental glioma model, tumor irradiation strengthened the effect of an XVirN31based oncovirotherapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Radiação Ionizante
/
Células-Tronco Neoplásicas
/
Neoplasias Encefálicas
/
Adenoviridae
/
Vírus Oncolíticos
/
Terapia Viral Oncolítica
/
Vetores Genéticos
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Int J Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Alemanha