Journal
CANCER LETTERS
Volume 294, Issue 2, Pages 178-186Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2010.01.034
Keywords
Gemcitabine; Pancreatic cancer; CRAd; Telomerase; Virotherapy
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
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To overcome the limited clinical efficacy of conditionally replicative adenoviruses (CRAds), we investigated the effects of combination therapy with gemcitabine (GEM) and the hTERT-promoter-dependent CRAd (hTERT-CRAd), Ad5/3hTERTE1. This combination therapy exhibited enhanced cytotoxic effects on pancreatic cancer both in vitro and in vivo. Furthermore, we revealed that this enhancement effect was due to the multiple bidirectional interactions between hTERT-CRAd and GEM. The GEM-sensitizing effect of E1 expression derived from hTERT-CRAd, and the enhancement effect by GEM on hTERT promoter activity which led to the increase of adenovirus E1 and viral infectivity. This combination therapy may be a promising therapeutic approach for pancreatic cancer. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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