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• W1539897412 abstract "Specificity of viral targeting into intrahepatic tumors remains critical for adenovirus gene therapy in liver cancer. We previously demonstrated that regional ionizing radiation treatment increases adenovirus uptake and transgene expression in cells and colon cancer xenografts. In this study, we tested whether radiation induces viral uptake through virus-cell membrane interaction. We found that radiation at 8 Gy induced adenoviral gene transfer in rat hepatocytes (WB) and human colon carcinoma cells (LoVo) as measured by the number of positive cells for transgene expression. This induction (24.4- and 6.5-fold, respectively) was diminished by about 50% by pre-incubation with antibody for Dynamin 2 but not for Coxackie Adenovirus receptor (CAR) or for integrin av. This inhibition appeared to result from a lesser induction of viral uptake in anti-Dynamin 2-treated cells in response to irradiation. Radiation treatment increased Dynamin 2 expression in both cells detected by immunohistochemistry staining and western blotting, and stimulated mRNA levels for Dynamin 2 in WB (1.5-fold) and LoVo (2.0-fold) cells. Inhibition of gene expression by transfecting cells using siRNA specific for Dynamin 2 significantly decreased mRNA levels in both cell types (~50%) and abolished the induction of Dynamin 2 expression mediated by irradiation. Consistently, adenoviral gene transfer in transfected cells was significantly lowered (~ 1/3). Radiation induction of viral gene transfer in WB and Lovo cells (24.4- and 6.5-fold, respectively) was significantly reduced in siRNA-transfected cells (15.5-fold and 2.7-fold, respectively). These data suggest that ionizing radiation induce adenovirus gene transfer in cells by regulating viral uptake through interaction with cellular Dynamin 2 and should provide insight into improving adenovirus targeting in tumors." @default.
• W1539897412 created "2016-06-24" @default.
• W1539897412 date "2004-05-01" @default.
• W1539897412 modified "2023-10-14" @default.
• W1539897412 title "Ionizing Radiation-Induced Adenovirus Infection Is Mediated by Dynamin 2" @default.
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• W1539897412 doi "https://doi.org/10.1016/j.ymthe.2004.06.967" @default.
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