Clinical Medicine: Oncology
Synopsis: An open access, peer reviewed electronic journal that covers cancer research and treatment.
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Aims and scope:
Clinical Medicine: Oncology is an international peer reviewed open access journal which publishes articles on all aspects of cancer research and treatment. Of particular interest are the following topics:
- Molecular biology
- Genetics
- Pathophysiology
- Epidemiology
- Clinical interventions
- Controlled trials
- The diagnosis and treatment of patients with cancer
- Therapeutics, pharmacology and drug delivery
- Techniques of cancer surgery
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The Effect of Docetaxel (Taxotere®) on Human Gastric Cancer Cells Exhibiting Low-Dose Radiation Hypersensitivity
Elizabeth K. Balcer-Kubiczek1,2, Mona Attarpour1, Jian Z. Wang3 and William F. Regine1,2
1University of Maryland School of Medicine, Department of Radiation Oncology, Baltimore, MD 21201, U.S.A. 2University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, U.S.A. 3The Ohio State University College of Medicine, Department of Radiation Medicine, Columbus, OH 43210, U.S.A.
Abstract
Low-dose radiation hypersensitivity (HRS) describes a phenomenon of excessive sensitivity to X ray doses <0.5 Gy. Docetaxel is a taxane shown to arrest cells in the G2/M phase of the cell cycle. Some previous studies suggested that HRS might result from the abrogation of the early G2 checkpoint arrest. First we tested whether HRS occurs in gastric cancer—derived cells, and whether pre-treatment of cells with low docetaxel concentrations can enhance the magnitude of HRS in gastric cancer cells. The results demonstrated HRS at ∼0.3 Gy and the synergy between 0.3 Gy and docetaxel (3 nM for 24 h), and the additivity of other drug/dose combinations. The synergistic effect was associated with a significant docetaxel-induced G2 accumulation. Next, we evaluated in time-course experiments ATM kinase activity and proteins associated with the induction and maintenance of the early G2 checkpoint. The results of multi-immunoblot analysis demonstrate that HRS does not correlate with the ATM-dependent early G2 checkpoint arrest. We speculate that G2 checkpoint adaptation, a phenomenon associated with a prolonged cell cycle arrest, might be involved in HRS. Our results also suggest a new approach for the improvement the effectiveness of docetaxel-based radiotherapy using low doses per fraction.
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