| This thesis examines the relationship between MGMT expression and treatment response in BTICs. BTICs are thought to be the barrier to tumor eradication and thus a critical target for new therapies: early data suggest that BTICs repopulate the tumor because of their increased resistance to radiation and chemotherapy. Twenty BTIC lines from resected primary GBMs were characterized for MGMT expression status using PCR and western blotting techniques. Cytotoxicity assays were used to assess BTICs for TMZ, IR, and IR+TMZ response. It was observed that BTICs exhibit varying responses to treatment (i.e. sensitivity or resistance). MGMT expression status (promoter methylation, transcript, and protein expression) is predictive of TMZ response in BTICs, but not when IR is added to treatment. Results indicate that BTICs can be sensitive to treatment, and that MGMT is predictive of response in BTICs when TMZ is used as a single agent therapy. |
