Abstract | BACKGROUND AND PURPOSE: Low Raf- kinase activity has been reported to be associated with radioresistance in epithelial tumor cell lines and with paclitaxel sensitivity in cervical tumor cells. Paclitaxel might thus be effective in eliminating radioresistant clones from cervical tumors, even in the absence of synergistic interaction between these therapeutic modalities. We thus established the relationship between Raf-1 kinase activity and radiosensitivity in human cervical tumor cells and determined if paclitaxel is preferentially cytotoxic to radio-resistant tumor clones. MATERIALS AND METHODS: We established and contrasted the radiation and paclitaxel sensitivity of 12 human cervical tumor clones that exhibited a wide range of Raf-1 kinase activity. RESULTS:
Raf-1 kinase activity was inversely correlated (P = 0.001) with SF2 values in the 12 cervical tumor clones studied. Paclitaxel was preferentially cytotoxic to radioresistant tumor clones, with the level of paclitaxel-induced cytotoxicity being significantly (P = 0.0016) influenced by Raf-1 kinase activity levels. CONCLUSIONS:
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Authors | R A Britten, S Perdue, J Opoku, P Craighead |
Journal | Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
(Radiother Oncol)
Vol. 48
Issue 3
Pg. 329-34
(Sep 1998)
ISSN: 0167-8140 [Print] Ireland |
PMID | 9925253
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- Radiation-Sensitizing Agents
- Proto-Oncogene Proteins c-raf
- Paclitaxel
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Topics |
- Antineoplastic Agents, Phytogenic
(toxicity)
- Cell Survival
- Combined Modality Therapy
- Female
- Humans
- Paclitaxel
(toxicity)
- Proto-Oncogene Proteins c-raf
(metabolism)
- Radiation Tolerance
- Radiation-Sensitizing Agents
(toxicity)
- Tumor Cells, Cultured
(drug effects, radiation effects)
- Uterine Cervical Neoplasms
(drug therapy, enzymology, pathology, radiotherapy)
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