Abstract
The effect of the antiviral agent (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (cidofovir) on the EBV-associated tumor nasopharyngeal carcinoma (NPC) was evaluated in NPC xenografts in athymic mice. Intratumoral injection arrested tumor growth within 1 week, and by 4 weeks, tumors regressed to 8-75% (39 +/- 33%) of the original size, whereas control tumors injected with PBS grew to 282 +/- 25% of the original size. Ganciclovir slowed but did not arrest or cause regression of tumor growth. A striking antitumor effect was also produced by systemic administration; at 4 weeks, tumors were 79 +/- 49% of the original size, compared with 635 +/- 91% for the controls. Widespread apoptosis was detected after treatment for 2-6 days in C15 as well as two other NPC xenografts, C17 and C18; the latter NPCs have mutations in the p53 gene. These data indicate that cidofovir induces rapid cell death through apoptosis in EBV-transformed epithelial cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adolescent
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Animals
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Antiviral Agents / therapeutic use*
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Apoptosis / drug effects
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Carcinoma / drug therapy*
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Carcinoma / genetics
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Carcinoma / pathology
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Carcinoma / virology
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Cidofovir
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Cytosine / analogs & derivatives*
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Cytosine / therapeutic use
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Drug Screening Assays, Antitumor
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Female
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Ganciclovir / pharmacology
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Ganciclovir / therapeutic use
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Genes, p53
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Herpesviridae Infections / drug therapy*
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Herpesviridae Infections / pathology
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Herpesviridae Infections / virology
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Herpesvirus 4, Human / drug effects*
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Herpesvirus 4, Human / pathogenicity
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Humans
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Injections, Intralesional
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Mice
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Mice, Nude
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Nasopharyngeal Neoplasms / drug therapy*
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Nasopharyngeal Neoplasms / genetics
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Nasopharyngeal Neoplasms / pathology
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Nasopharyngeal Neoplasms / virology
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Neoplasm Transplantation
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Organophosphonates*
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Organophosphorus Compounds / therapeutic use*
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Tumor Virus Infections / drug therapy*
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Tumor Virus Infections / pathology
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Tumor Virus Infections / virology
Substances
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Antiviral Agents
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Organophosphonates
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Organophosphorus Compounds
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Cytosine
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Cidofovir
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Ganciclovir