title: Imaging and Antitumoral Effect of a Cyclo-oxygenase 2-specific Replicative Adenovirus for Small Metastatic Gastric Cancer Lesions.
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.
  
  
  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.
  
  
  CONCLUSIONS
  Cox2 CRAds with 5/3 chimeric-fiber modification, therefore, appear to be a promising imaging and therapeutic tools for peritoneal dissemination of gastric cancer.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama-city University, Kanazawa-ku, Yokohama, Japan yokotaka1026@yahoo.co.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kosaka
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, U.S.A.
authors.forename: Julia
authors.initials: J
authors.lastname: Davydova
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama-city University, Kanazawa-ku, Yokohama, Japan.
authors.forename: Hidetaka A
authors.initials: HA
authors.lastname: Ono
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama-city University, Kanazawa-ku, Yokohama, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Department of Molecular Biology, Graduate School of Medicine, Yokohama-city University, Kanazawa-ku, Yokohama, Japan.
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Hirai
authors.affiliation: Department of Molecular Biology, Graduate School of Medicine, Yokohama-city University, Kanazawa-ku, Yokohama, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
authors.affiliation: National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Takeshita
authors.affiliation: National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Aoki
authors.affiliation: National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
authors.affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, U.S.A.
authors.forename: Masato
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama-city University, Kanazawa-ku, Yokohama, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Kunisaki
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama-city University, Kanazawa-ku, Yokohama, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics / Q000502:physiology*; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000628:therapy* / Q000821:virology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000628:therapy* / Q000821:virology*; D016019:Survival Analysis; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D011994:Recombinant Proteins; D008156:Luciferases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Gastric cancer; conditionally replicative adenovirus; luminescent imaging; peritoneal dissemination