Suicide gene therapy of human hepatoma and its peritonitis carcinomatosis by a vector of replicative-deficient herpes simplex virus |
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Authors: | Iwai Masaki Harada Yoshinori Ishii Michiaki Kashima Kei Mazda Osam Tamura Masakazu Wolfe Darren Goin William F Glorioso Joseph C |
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Institution: | Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. masaiwai@koto.kpu-m.ac.jp |
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Abstract: | Herpes simplex virus type 1 (HSV-1) deleted for the immediate-early gene was applied for treatment of hepatoma cells of SKHep 1 and Huh-7. Hepatoma cells were cultured in medium containing HSV1 expressing GFP gene (QOZ/HG) to determine its transfection rate, and both cell lines infected by MOI 1 of QOZ/HG were found to have high expression of GFP without cytotoxicity. Subcutaneous growth of SKHep 1 cell tumor in nude mice was significantly reduced by injection of replicative-deficient herpes virus (TOZ.1) containing Tk-gene with administration of GCV, in comparison with that of noninjected tumor. SCID mice of peritonitis carcinomatosis due to Huh-7 hepatoma cells infected with TOZ.1 could survive longer under administration of GCV than those without TOZ.1. Therefore replicative-deficient HSV1 is a useful vector for treatment of human hepatoma cells, and TOZ.1 with GCV may be applied to suicide gene therapy for hepatoma and peritonitis carcinomatosis of hepatoma cells. |
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Keywords: | replicative-deficient herpes simplex virus gene therapy hepatoma peritonitis carcinomatosis |
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