The American journal of surgery, 2012-11, Vol.204 (5), p.741-750
2012
Details
- Autor(en) / Beteiligte
- Titel
- Generation of a novel, cyclooxygenase-2–targeted, interferon-expressing, conditionally replicative adenovirus for pancreatic cancer therapy
- Ist Teil von
- The American journal of surgery, 2012-11, Vol.204 (5), p.741-750
- Ort / Verlag
- New York, NY: Elsevier Inc
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Abstract Background Oncolytic adenoviruses provide a promising alternative for cancer treatment. Recently, adjuvant interferon (IFN)-alfa has shown significant survival benefits for pancreatic cancer, yet was impeded by systemic toxicity. To circumvent these problems adenovirus with high-level targeted IFN-alfa expression can be generated. Methods Conditionally replicative adenoviruses (CRAds) with improved virulence and selectivity for pancreatic cancer were generated. The vectors were tested in vitro, in vivo, and in human pancreatic cancer and normal tissue specimens. Results Adenoviral death protein and fiber modifications significantly improved oncolysis. CRAds selectively replicated in vitro, in vivo and showed persistent spread in cancer xenografts. They showed high-level replication in human pancreatic cancer specimens, but not in normal tissues. Improved IFN-CRAd oncolytic efficiency was shown. Conclusions Optimized cyclooxygenase-2 CRAds show highly favorable effects in vitro and in vivo. We report a pancreatic cancer–specific, highly virulent, IFN-expressing CRAd, and we believe that adenovirus-based IFN therapy offers a new treatment opportunity for pancreatic cancer patients.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0002-9610eISSN: 1879-1883DOI: 10.1016/j.amjsurg.2012.02.016Titel-ID: cdi_proquest_miscellaneous_1151705757
- Format
- –
- Schlagworte
- Adenoviral death protein (ADP), Adenoviridae - genetics, Adenoviridae - metabolism, Adenoviridae - physiology, Adenovirus, Adenovirus E3 Proteins - metabolism, Adenoviruses, Animals, Apoptosis, Biological and medical sciences, Biomarkers, Tumor - metabolism, Cancer therapies, Carcinoma, Pancreatic Ductal - metabolism, Carcinoma, Pancreatic Ductal - therapy, Carcinoma, Pancreatic Ductal - virology, Cell Line, Tumor, Conditionally replicative adenovirus (CRAd), Cox2, Cyclooxygenase 2 - metabolism, Cytokines, Design, Female, Gastroenterology. Liver. Pancreas. Abdomen, Gene therapy, Gene Transfer Techniques, General aspects, Humans, Interferon, Interferon-alfa, Interferon-alpha - metabolism, Krumdiek tissue slicer, Liver. Biliary tract. Portal circulation. Exocrine pancreas, Medical sciences, Mice, Mice, Nude, Oncolytic Virotherapy - methods, Oncolytic virus, Pancreas, Pancreatic cancer, Pancreatic Neoplasms - metabolism, Pancreatic Neoplasms - therapy, Pancreatic Neoplasms - virology, Proteins, Surgery, Tumors, Virus Replication, Xenograft Model Antitumor Assays