Abstract
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.
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Adenoviridae / physiology*
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Adenovirus E1A Proteins / biosynthesis
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Adenovirus E1A Proteins / genetics
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Animals
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Antimetabolites, Antineoplastic / pharmacology*
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Cell Growth Processes / drug effects
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Cell Line, Tumor
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Combined Modality Therapy
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / pharmacology
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Female
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Gemcitabine
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Genetic Vectors / genetics
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Humans
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Oncolytic Virotherapy / methods*
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology
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Pancreatic Neoplasms / therapy*
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Pancreatic Neoplasms / virology
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Promoter Regions, Genetic
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Telomerase / genetics*
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Transfection
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Virus Replication
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Xenograft Model Antitumor Assays
Substances
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Adenovirus E1A Proteins
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Antimetabolites, Antineoplastic
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RNA, Messenger
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Deoxycytidine
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TERT protein, human
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Telomerase
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Gemcitabine