Protracted temozolomide (TMZ) treatment leads to acquired TMZ resistance in glioblastoma (GBM) cells in vivo. Protracted temozolomide (TMZ) treatment leads.

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Cell Physiol Biochem 2013;32: DOI: /

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Protracted temozolomide (TMZ) treatment leads to acquired TMZ resistance in glioblastoma (GBM) cells in vivo. Protracted temozolomide (TMZ) treatment leads to acquired TMZ resistance in glioblastoma (GBM) cells in vivo. A, GBM9 cells were injected intracranially in nude mice. Brain tumors from vehicle-treated (primary) or TMZ-treated (recurrent) mice were harvested when the mice became moribund, and ex vivo cultures were generated for further characterization. B, primary (plots in black: 414, 483, and 484) and recurrent (plots in green: 419, 479, and 481) cultures were assessed for TMZ sensitivity by the colony formation assay. The fraction of surviving colonies (y-axis) is plotted against the corresponding TMZ dose (x-axis). Error bars, SD. ****, P < 0.0001 (419 vs. any primary culture); ***, P = 0.0003 (479 vs. any primary culture); **, P = 0.0017 (481 vs. any primary culture). C, primary (483 and 484) and recurrent (419 and 481) cultures were treated with 50 μmol/L TMZ for 48 hours, and cell-cycle distribution was assessed by single-parameter flow cytometry after propidium iodide staining for DNA content (x-axis). Carlos Rodrigo Gil del Alcazar et al. Mol Cancer Res 2016;14:928-940 ©2016 by American Association for Cancer Research