Treatment of pancreatic cancer using an oncolytic virus harboring the lipocalin-2 gene.
Cancer
; 118(21): 5217-26, 2012 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-22517373
ABSTRACT
BACKGROUND:
The 5-year survival rate for patients with pancreatic cancer is <5%, and it is always resistant to the current chemoradiotherapy. Therefore, new, effective agents for the treatment of pancreatic cancer are urgently needed. The promising strategy of cancer-targeting gene virotherapy (CTGVT) has demonstrated great anticancer potential. The objective of the current study was to determine whether 1 CTGVT approach, oncolytic virus (OV)-harboring lipocalin-2, is capable of treating pancreatic cancer.METHODS:
Tissue microarrays were constructed to detect the expression of lipocalin-2 in 60 specimens of pancreatic adenocarcinoma. The clinical significance of lipocalin-2 was investigated in an analysis of correlations between lipocalin-2 expression and matched clinical characteristics. A lipocalin-2-expressing OV, ZD55-lipocalin-2, was constructed by deleting the adenoviral protein E1B55kD. The antitumor efficacy and mechanisms of the OV were investigated in pancreatic cancer cells with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in vitro and in vivo.RESULTS:
Lipocalin-2 expression was correlated with a good prognosis in patients with pancreatic adenocarcinoma. ZD55-lipocalin-2 dramatically inhibited the growth of pancreatic cancer in vitro and in vivo by inducing cytolysis and caspase-dependent apoptosis.CONCLUSIONS:
Higher lipocalin-2 expression predicted a better prognosis in patients with pancreatic cancer. The results indicated that ZD55-lipocalin-2, which specifically expressed higher levels of lipocalin-2 in tumor cells, may serve as a potent anticancer drug for pancreatic cancer therapy, especially for patients who have pancreatic adenocarcinoma with KRAS mutations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Proteínas de Fase Aguda
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Terapia Genética
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Proteínas Proto-Oncogênicas
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Terapia Viral Oncolítica
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Lipocalinas
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article