Imaging and Antitumoral Effect of a Cyclo-oxygenase 2-specific Replicative Adenovirus for Small Metastatic Gastric Cancer Lesions

Long-term outcomes of patients with peritoneal dissemination of gastric cancer remain unsatisfactory despite advances in treatment modalities. Internal luminescence conditionally replicative adenovirus (CRAd) presents a novel approach for cancer treatment and imaging. 3CL is a modified cyclooxygenas...

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Bibliographic Details
Published in:Anticancer research 2015-10, Vol.35 (10), p.5201-5210
Main Authors: Kosaka, Takashi, Davydova, Julia, Ono, Hidetaka A, Akiyama, Hirotoshi, Hirai, Shu-Ichi, Ohno, Shigeo, Takeshita, Fumitaka, Aoki, Kazunori, Ochiya, Takahiro, Yamamoto, Masato, Kunisaki, Chikara, Endo, Itaru
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Cyclooxygenase 2 - genetics
Cyclooxygenase 2 - metabolism
Dependovirus - genetics
Dependovirus - physiology
Diagnostic Imaging - methods
Female
Genetic Vectors - administration & dosage
Humans
Luciferases - genetics
Luciferases - metabolism
Mice
Neoplasm Transplantation
Peritoneal Neoplasms - secondary
Peritoneal Neoplasms - therapy
Peritoneal Neoplasms - virology
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Sensitivity and Specificity
Stomach Neoplasms - therapy
Stomach Neoplasms - virology
Survival Analysis
Treatment Outcome
Xenograft Model Antitumor Assays
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Summary:Long-term outcomes of patients with peritoneal dissemination of gastric cancer remain unsatisfactory despite advances in treatment modalities. Internal luminescence conditionally replicative adenovirus (CRAd) presents a novel approach for cancer treatment and imaging. 3CL is a modified cyclooxygenase-2 (COX2) promoter-driven CRAd which contains the luciferase expression gene for bioluminescence imaging. The visualizing and therapeutic effect of 3CL was evaluated in a mouse model of peritoneal dissemination. Intraperitoneal injection of 3CL achieved the shrinkage and reduction of lesions of peritoneal dissemination. Six model mice treated with 3CL had a significantly longer mean survival time than 6 mock-treated mice (85.7 versus 34.3 days, p=0.0005). By whole-body bioluminescent imaging, the sensitivity and specificity of peritoneal dissemination detection through macroscopic inspection were 58.1% and 83.2%, respectively, whereas 3CL viral imaging modality yielded corresponding values of 78.8% and 99.3%. Peritoneal lesions detected by imaging histologically contained cancer cells and necrotic tissue, which originated from viral oncolytic effects. Cox2 CRAds with 5/3 chimeric-fiber modification, therefore, appear to be a promising imaging and therapeutic tools for peritoneal dissemination of gastric cancer.
ISSN:1791-7530