Radiosensitizing effect of estramustine in malignant gliomain vitro andin vivo |
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Authors: | A. Tommy Bergenheim Björn Zackrisson Jörgen Elfverson Göran Roos Roger Henriksson |
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Affiliation: | (1) Department of Oncology, University Hospital, S-90185 Umeå, Sweden;(2) Department of Neurosurgery, University Hospital, S-90185 Umeå, Sweden;(3) Department of Pathology, University Hospital, S-90185 Umeå, Sweden |
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Abstract: | Summary Estramustine-phosphate (EMP), a combination of nornitrogen mustard and 17-estradiol, has been demonstrated to exert specific antiproliferative effects on human glioma cellsin vitro. The cytotoxic effect is, at least partially, mediated by inhibiting microtubule function. In this study the combined effect of EMP and radiation was evaluated in the human glioma cell-lines, 251-MG and 105-MG,in vitro, and in the rat glioma BT4Cin vitro andin vivo. In all cell-lines an additive effect of EMP and radiation was obtainedin vitro. Assuming equal effect of EMP is obtained in subsequent radiation fractions, the cell kill will be increased from 2–3 to 5–10 logs if delivering 30 fractions of 2 Gy combined with EMP. In the BT4C rat model the combined effect was found to be synergistic. Flow cytometry demonstrated an arrest in G2/M phase in all cell-lines after EMP treatment. This block in G2/M phase in addition to the previously demonstrated induction of free oxygen radicals, and the increase of blood flow with an assumed subsequent increase of oxygenation, might provide an explanation for the observed radiosensitizing effect of estramustine. |
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Keywords: | glioma estramustine radiotherapy chemotherapy |
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