Abstract | PURPOSE: METHODS: KHT tumors were grown in C3H/HeJ mice. Combretastatin A-4 prodrug was injected intraperitoneally at doses ranging from 10 to 100 mg/kg. Tumors were irradiated in unanesthetized mice using a 137Cs source. Tumor response to combretastatin A-4 prodrug was assessed by histological evaluations as well as an in vivo to in vitro cell survival assay. RESULTS: Histological evaluation showed morphological damage of tumor cells within a few hours after drug treatment, followed by extensive central necrosis. Administering increasing doses of combretastatin A-4 prodrug to tumor-bearing mice resulted in a dose-dependent increase in cell killing irrespective of whether the tumors were irradiated or not. When combined with radiation, a 100 mg/kg dose of combretastatin A-4 prodrug reduced tumor cell survival 10-500-fold lower than that seen with radiation alone. Further, the shape of the cell survival curve observed following the combination therapy suggested that including combretastatin in the treatment had a major effect on the radiation-resistant hypoxic cell subpopulation associated with this tumor. CONCLUSION:
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Authors | L Li, A Rojiani, D W Siemann |
Journal | International journal of radiation oncology, biology, physics
(Int J Radiat Oncol Biol Phys)
Vol. 42
Issue 4
Pg. 899-903
(Nov 01 1998)
ISSN: 0360-3016 [Print] United States |
PMID | 9845118
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- Stilbenes
- fosbretabulin
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Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Blood Vessels
(drug effects)
- Combined Modality Therapy
- Dose-Response Relationship, Drug
- Drug Screening Assays, Antitumor
- Female
- Mice
- Mice, Inbred C3H
- Necrosis
- Sarcoma, Experimental
(blood supply, pathology, radiotherapy)
- Stilbenes
(pharmacology)
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