Imaging and antitumoral effect of a cyclo-oxygenase 2-specific replicative adenovirus for small metastatic gastric cancer lesions

Takashi Kosaka, Julia Davydova, Hidetaka A. Ono, Hirotoshi Akiyama, Shu Ichi Hirai, Shigeo Ohno, Fumitaka Takeshita, Kazunori Aoki, Takahiro Ochiya, Masato Yamamoto, Chikara Kunisaki, Itaru Endo

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5201-5210
Number of pages10
JournalAnticancer Research
Volume35
Issue number10
StatePublished - Oct 1 2015

Keywords

  • Conditionally replicative adenovirus
  • Gastric cancer
  • Luminescent imaging
  • Peritoneal dissemination

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