Beier, Dagmar and Schriefer, Beate and Brawanski, Konstantin and Hau, Peter and Weis, Joachim and Schulz, Joerg B. and Beier, Christoph P. (2012) Efficacy of clinically relevant temozolomide dosing schemes in glioblastoma cancer stem cell lines. JOURNAL OF NEURO-ONCOLOGY, 109 (1). pp. 45-52. ISSN 0167-594X,
Full text not available from this repository. (Request a copy)Abstract
The effectiveness of temozolomide (TMZ) dosing schemes and the "rechallenge" of recurrent glioblastoma (GBM) with TMZ are controversial. We therefore compared the efficacy of different TMZ dosing schemes against GBM cancer stem cell (CSC) lines in vitro. In O-6-methyl-guanidine-methyl-transferase (MGMT)-negative CSC lines, all schedules (1 day on/27 days off, 5 days on/23 days off, 7 days on/7 days off, 21 days on/7 days off, continuous low-dose TMZ) depleted clonogenic cells. In TMZ-resistant CSC lines, the 7 days on/7 days off scheme showed higher toxicity as compared with the other schemes. However, clinically feasible concentrations remained ineffective in highly resistant CSC lines. In addition, none of the schedules induced long-term depletion of clonogenic cells even at the highest concentrations (up to 250 mu M). After sublethal TMZ treatment for 5 days, TMZ rechallenge of recovering CSC lines remained effective. Our data advocate CSC lines as in vitro model to address clinical questions. Using this model, our data suggest the effectiveness of TMZ in MGMT-negative CSC lines and support the concept of TMZ rechallenge. The 7 days on/7 days off scheme consistently showed the best activity of all schedules in TMZ-resistant CSC lines.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RECURRENT MALIGNANT GLIOMA; PHASE-II TRIAL; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; GENE-EXPRESSION; TUMOR; PROFILES; O-6-BENZYLGUANINE; CHEMORESISTANCE; RADIOTHERAPY; PHENOTYPE; Temozolomide; Glioblastoma cancer stem cell; MGMT; Temozolomide rechallenge |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 May 2020 05:04 |
| Last Modified: | 08 May 2020 05:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18379 |
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