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| Reference : (E)-2'-Deoxy-2'-(Fluoromethylene)cytidine potentiates radioresponse of two human solid t... |
| Scientific congresses and symposiums : Paper published in a journal | |||
| Human health sciences : Oncology Human health sciences : Hematology | |||
| http://hdl.handle.net/2268/16997 | |||
| (E)-2'-Deoxy-2'-(Fluoromethylene)cytidine potentiates radioresponse of two human solid tumor xenografts. | |
| English | |
| Sun, L-Q [ > > ] | |
| Li, Y-X [ > > ] | |
| Guillou, L [ > > ] | |
COUCKE, Philippe  [University Hospital of Lausanne > > > >] | |
| 1998 | |
| Proceedings of the American Association for Cancer Research | |
| 5411-5417 | |
| International | |
| 0569-2261 | |
| SASRO | |
| 1998 | |
| [en] radiotherapy ; antitumor ; FMdC ; radiosensitizing effects ; cytotoxic agent | |
| [en] Antitumor and radiosensitizing effects of (E)-2'-deoxy-2'-(fluoromethylene)
cytidine (FMdC), a novel inhibitor of ribonucleotide reducÃase, were evaluated on nude mice bearing s.c. human C33-A cervix cancer and I -H7 MG glioblastoma xenografts. FMdC given once daily has a dosedependent antitumor effect. The maximum tolerated dose in the mice was reached with 10 daily i.p. administrations of 10 mg/kg over 12 days. In the case of radiotherapy (RT) alone (10 fractions over 12 days), the radiation dose required to produce local tumor control in 50% of the treated C33-A xenografts was 51.0 Gy. When combined with FMdC, the radiation dose required to produce local tumor control was reduced to 41.4 and 38.2 Gy, at respective doses of 5 and 10 mg/kg given i.p. l h before each irradiation. The corresponding enhancement ratios (ERs) were 1.2 and 1.3, respec tively. In U-87 MG xenografts, when 5-20 mg/kg FMdC combined with 30 or 40 Gy of RT, the combination treatment produced a significantly increased growth delay as compared with RT alone (P £0.002). The ERs of 5, 10, and 20 mg/kg FMdC at a dose of 30 Gy were 2.0, 1.4, and 1.8, respectively. At the 40-Gy level, ERs of 10 and 20 mg/kg FMdC were 1.4 and 1.7. When FMdC was combined with 50 Gy of RT, an increased long-term remission rate of 80-88.9% was observed, as compared with 25% for RT alone (P <0.05). FMdC produced moderate myelosuppression in the mice bearing cervix cancer, whereas leukocytosis occurred in the mice bearing glioblastoma at a low dose. Slightly increased skin toxicity (only with U-87 MG tumor) was observed, as compared with RT alone. In conclusion, FMdC is a potent cytotoxic agent and able to modify the radiation response of C33-A and U-87 MG xenografts. | |
| Researchers ; Professionals | |
| http://hdl.handle.net/2268/16997 |
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