Gene therapy and non-invasive imaging method for upper gastrointestinal cancer

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The effective treatment for the peritoneal dissemination of gastric cancer is not established. So we effort to develop Conditionally replicative adenovirus as new therapeutic strategy of these lesions.We developed new vectors which show an antitumor effect and express luciferase. Our viral vectors have luciferase expression gene in deleted E-three region which is activated when the virus replicates. E1 controlled Cox2 promoter and five-to-three chimeric fibers show good specific replicative ability in gastric cancer cells. The adenovirus death protein is retained at the deleted E-three region in order to conserve the native oncolytic capability of the virus. Our virus replicates only in tumor cells and can be detected as a luminescence in a replication-dependent manner. We visually confirmed the viral replication in subcutaneous tumors of gastric cancer cells. And it has oncolytic and lateral spread capability. Our vectors can replicate in tumor cells, so they are applicable to detection of tiny lesions by luminescent assay.In addition, we established gastric cancer cell lines which express red fluorescent protein and red fluorescent peritoneal dissemination model mice. They are treated with luciferase express adenoviral vector and we can evaluate viral replication and tumor shrinkage by using fluorescent assay and luminescent assay.In vitro examination was done and we noticed that fiber modification (5/3 chimeric fiber) was very important to achieve early viral replication. Laparotomic whole body bioluminescence imaging revealed that this virus could be used to directly visualize peritoneal dissemination lesions (189 peritoneal lesions in 12 mice) with a detection sensitivity of 78.8% and specificity of 99.3%. A combination of this imaging system and preoperative staging laparoscopy could therefore be an effective diagnostic strategy for detecting peritoneal dissemination.