Abstract
The tumor suppressor gene FHIT spans a common fragile site and is highly susceptible to environmental carcinogens. FHIT inactivation and loss of expression is found in a large fraction of premaligant and malignant lesions. In this study, we were able to inhibit tumor development by oral gene transfer, using adenoviral or adenoassociated viral vectors expressing the human FHIT gene, in heterozygous Fhit(+/-) knockout mice, that are prone to tumor development after carcinogen exposure. We therefore suggest that FHIT gene therapy could be a novel clinical approach not only in treatment of early stages of cancer, but also in prevention of human cancer.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acid Anhydride Hydrolases*
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Adenoviridae / genetics
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Animals
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Carcinogens / adverse effects
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Dependovirus / genetics
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Dimethylnitrosamine / adverse effects
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Dimethylnitrosamine / analogs & derivatives*
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Genes, Tumor Suppressor / physiology*
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Genetic Therapy / methods*
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Genetic Vectors / genetics
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Humans
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism
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Neoplasm Proteins / physiology
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Neoplasms, Experimental / chemically induced
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Neoplasms, Experimental / pathology
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Neoplasms, Experimental / prevention & control*
Substances
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Carcinogens
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Neoplasm Proteins
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fragile histidine triad protein
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nitrosobenzylmethylamine
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Acid Anhydride Hydrolases
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Dimethylnitrosamine