Development of molecular therapy targeted for tumor cell and tumor stoma of peritoneal dissemination

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1) The contraction of isolated rat aorta without endothelium induced by angiotensin II was enhanced in diabetic group compared with non-diabetic group. Sevoflurane inhibited the muscle tension in concentration-dependent manner, but isoflurane did not.Conditionally replicating (oncolytic) herpes simplex viruses (HSVs) have shown clear potential as effective agents for the treatment of solid tumors such as gastrointestinal cancer. To enhance the oncolytic capabilities of first-generation HSVs, we recently developed two new constructs. Synco-2D is derived from HSV-1 and contains two mechanisms to induce cell membrane fusion. FusOn-H2 is derived from HSV-2. It selectively targets the activated Ras signaling pathway in tumor cells and also has the ability to induce cell membrane fusion and apoptosis.METHOD.We studied the in vitro and in vivo antitumor effects of both Synco-2D and FusOn-H2 against various type of cancer.RESULTS.Both Synco-2D and FusOn-H2 lysed human gastric cancer cells in v … More itro much more readily than did Baco-1. For in vivo studies, the oncolytic viruses were administered either intratumorally or intravenously to nude mice bearing xenografted human gastric cancer, and the tumor growth rate and animal survival were monitored after treatment. In most instances, the results were compared with those for a first-generation nonfusogenic oncolytic HSV (Baco-1). A single intratumoral injection of either Synco-2D or FusOn-H2 produced a striking effect against xenografted human gastric cancer, in contrast to Baco-1, which produced only moderate antitumor activity. Two intravenous injections. of Synco-2D also inhibited the growth of human gastric cancer xenografts, while Baco-1 injections via the same route lacked any measurable antitumor effect.CONCLUSIONS.These data demonstrate that the newly constructed oncolytic HSVs have potent activity against established gastric cancer in animal models. Clinical trails to validate these results in cancer patients appear warranted. Less