Clinically relevant doses of chemotherapy agents reversibly block formation of glioblastoma neurospheres
Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Animals; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Carmustine; Cell Adhesion; Cell Culture Techniques; Cell Death; Cell Division; Cell Line, Tumor; DNA Primers; DNA, Complementary; Dacarbazine; Exons; Glioblastoma; Humans; Mice; Mice, Nude; Neoplasm Recurrence, Local; Prognosis; Transplantation, Heterologous; Treatment Outcome
Glioblastoma patients have a poor prognosis, even after surgery, radiotherapy, and chemotherapy with temozolomide or 1,3-bis(2-chloroethy)-1-nitrosourea. We developed an in vitro recovery model using neurosphere cultures to analyze the efficacy of chemotherapy treatments, and tested whether glioblastoma neurosphere-initiating cells are resistant. Concentrations of chemotherapy drugs that inhibit neurosphere formation are similar to clinically relevant doses. Some lines underwent a transient cell cycle arrest and a robust recovery of neurosphere formation. These results indicate that glioblastoma neurospheres can regrow after treatment with chemotherapy drugs. This neurosphere recovery assay will facilitate studies of chemo-resistant subpopulations and methods to enhance glioblastoma therapy.
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Citation: Cancer Lett. 2010 Oct 28;296(2):168-77.
Mihaliak, Alicia M.; Gilbert, Candace A.; Li, Li; Daou, Marie-Claire; Moser, Richard P.; Reeves, Andrew; Cochran, Brent H.; and Ross, Alonzo H., "Clinically relevant doses of chemotherapy agents reversibly block formation of glioblastoma neurospheres" (2010). Biochemistry and Molecular Pharmacology Publications and Presentations. Paper 125.