Abstract |
In an effort to improve the therapeutic outcome for squamous cell cancer of the head and neck, we have used the enzyme cytosine deaminase (CD) and the prodrug 5-fluorocytosine (5-FC) as a means to deliver the chemotherapeutic agent 5-fluorouracil (5-FU) in a tumor-specific manner and have evaluated the use of this treatment in combination with external-beam radiation. Infection of SCCVII cells in culture with a CD-expressing retrovirus and treatment with 5-FC was cytotoxic depending on the time of treatment and dose of 5-FC. An orthotopic model of squamous cell cancer of the head and neck was used in vivo to study the CD/5-FC system both alone and with concurrent radiation due to the radiosensitizing properties that 5-FU generates in situ. Treated mice were imaged using magnetic resonance imaging (MRI), and their survival was evaluated. Neither 5-FU nor radiation either alone or combined provided a survival advantage. In contrast, 5-FC treatment prolonged survival and decreased tumor burden compared to control animals, but the tumors recurred after the treatment ceased. Finally, combined treatment with concurrent administration of 5-FC and radiation resulted in a synergistic decrease in tumor growth and enhanced survival over treatment with 5-FC or radiation alone.
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Authors | D A Hamstra, D J Rice, A Pu, D Oyedijo, B D Ross, A Rehemtulla |
Journal | Radiation research
(Radiat Res)
Vol. 152
Issue 5
Pg. 499-507
(Nov 1999)
ISSN: 0033-7587 [Print] United States |
PMID | 10521927
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antimetabolites, Antineoplastic
- Prodrugs
- Flucytosine
- Nucleoside Deaminases
- Cytosine Deaminase
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Topics |
- Animals
- Antimetabolites, Antineoplastic
(therapeutic use)
- Carcinoma, Squamous Cell
(drug therapy, radiotherapy, therapy)
- Cell Division
- Combined Modality Therapy
- Cytosine Deaminase
- Disease Models, Animal
- Flucytosine
(therapeutic use)
- Head and Neck Neoplasms
(drug therapy, radiotherapy, therapy)
- Mice
- Nucleoside Deaminases
(therapeutic use)
- Prodrugs
(therapeutic use)
- Retroviridae
(genetics)
- Transduction, Genetic
- Tumor Cells, Cultured
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