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Anticancer Res. 2015 Oct;35(10):5201-10.

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

Author information

1
Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama-city University, Kanazawa-ku, Yokohama, Japan yokotaka1026@yahoo.co.jp.
2
Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, U.S.A.
3
Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama-city University, Kanazawa-ku, Yokohama, Japan.
4
Department of Molecular Biology, Graduate School of Medicine, Yokohama-city University, Kanazawa-ku, Yokohama, Japan.
5
National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.

Abstract

BACKGROUND:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

Cox2 CRAds with 5/3 chimeric-fiber modification, therefore, appear to be a promising imaging and therapeutic tools for peritoneal dissemination of gastric cancer.

KEYWORDS:

Gastric cancer; conditionally replicative adenovirus; luminescent imaging; peritoneal dissemination

PMID:
26408678
[Indexed for MEDLINE]

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