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• W2000652787 abstract "Management of Cushing's disease remains challenging, despite advances in its diagnosis and treatment. Here, we describe a strategy for targeting the expression of toxic genes to ACTH-producing tumor cells using adenoviral vectors. The POMC promoter was used to express either a marker gene (beta-galactosidase) or a toxic gene [herpes simplex virus thymidine kinase (TK)]. In ACTH-producing AtT20 cells, infection with recombinant adenoviruses containing the POMC promoter (AdPOMCGal; AdPOMCTK) led to high-level gene expression. Stereotactic injection of AdPOMCGal into the rat pituitary resulted in localized expression of the beta-galactosidase transgene in corticotrope cells. Cytotoxicity studies were performed using the TK-containing vectors and treatment with ganciclovir. AdPOMCTK caused greater than 95% cytotoxicity of AtT20 cells at a viral dose (multiplicity of infection, 5 plaque-forming units/cell) that induced minimal toxicity using control viruses. No cellular toxicity was seen using a nonpituitary cell line (T47D breast tumor cells). AtT20 cells transplanted into nude mice induced features of Cushing's syndrome and were used as an in vivo model of ACTH-producing tumors. Injection of the AdPOMCTK virus caused significant regression of the transplanted AtT20 tumors. These studies suggest that the POMC promoter may provide a useful gene therapy strategy for the adjunctive treatment of pituitary tumors causing ACTH-dependent Cushing's syndrome." @default.
• W2000652787 created "2016-06-24" @default.
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• W2000652787 date "2001-07-01" @default.
• W2000652787 modified "2023-09-27" @default.
• W2000652787 title "Adenovirus-Mediated Targeted Expression of Toxic Genes to Adrenocorticotropin-Producing Pituitary Tumors Using the Proopiomelanocortin Promoter1" @default.
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• W2000652787 doi "https://doi.org/10.1210/jcem.86.7.7726" @default.
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