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Anticancer Res ; 35(10): 5201-10, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26408678

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.


Subject(s)
Cyclooxygenase 2/metabolism , Dependovirus/physiology , Diagnostic Imaging/methods , Luciferases/metabolism , Peritoneal Neoplasms/therapy , Peritoneal Neoplasms/virology , Stomach Neoplasms/therapy , Stomach Neoplasms/virology , Animals , Cell Line, Tumor , Cyclooxygenase 2/genetics , Dependovirus/genetics , Female , Genetic Vectors/administration & dosage , Humans , Luciferases/genetics , Mice , Neoplasm Transplantation , Peritoneal Neoplasms/secondary , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sensitivity and Specificity , Survival Analysis , Treatment Outcome , Xenograft Model Antitumor Assays
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