tailieunhanh - Báo cáo khoa học: " Delayed cell death associated with mitotic catastrophe in g-irradiated stem-like glioma cells"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Radiation Oncology cung cấp cho các bạn kiến thức về ngành y đề tài: Delayed cell death associated with mitotic catastrophe in g-irradiated stem-like glioma cells. | Firat et al. Radiation Oncology 2011 6 71 http content 6 1 71 RADIATION ONCOLOGY RESEARCH Open Access Delayed cell death associated with mitotic catastrophe in g-irradiated stem-like glioma cells 1112 3 1 Elke Firat Simone Gaedicke Chizuko Tsurumi Norbert Esser Astrid Weyerbrock and Gabriele Niedermann Abstract Background and Purpose Stem-like tumor cells are regarded as highly resistant to ionizing radiation IR . Previous studies have focused on apoptosis early after irradiation and the apoptosis resistance observed has been attributed to reduced DNA damage or enhanced DNA repair compared to non-stem tumor cells. Here early and late radioresponse of patient-derived stem-like glioma cells SLGCs and differentiated cells directly derived from them were examined for cell death mode and the influence of stem cell-specific growth factors. Materials and methods Primary SLGCs were propagated in serum-free medium with the stem-cell mitogens epidermal growth factor EGF and fibroblast growth factor-2 FGF-2 . Differentiation was induced by serumcontaining medium without EGF and FGF. Radiation sensitivity was evaluated by assessing proliferation clonogenic survival apoptosis and mitotic catastrophe. DNA damage-associated gH2AX as well as p53 and p21 expression were determined by Western blots. Results SLGCs failed to apoptose in the first 4 days after irradiation even at high single doses up to 10 Gy but we observed substantial cell death later than 4 days postirradiation in 3 of 6 SLGC lines treated with 5 or 10 Gy. This delayed cell death was observed in 3 of the 4 SLGC lines with nonfunctional p53 was associated with mitotic catastrophe and occurred via apoptosis. The early apoptosis resistance of the SLGCs was associated with lower gH2AX compared to differentiated cells but we found that the stem-cell culture cytokines EGF plus FGF-2 strongly reduce gH2AX levels. Nonetheless in two p53-deficient SLGC lines examined gIR-induced apoptosis even correlated .