Exth-37. Targeting Glioma Stem Cells Through Combined Bmi1 and Ezh2 Inhibition

Abstract

NEURO-ONCOLOGY • NOVEMBER 2017 blood and ECF samples (using intracerebral microdialysis) were collected and letrozole was quantitated employing an HPLC method. Marked gender-dependent difference in letrozole PK were observed with both plasma and brain ECF levels being markedly higher in female rats relative to those in male rats. For instance, the steady state peak plasma and ECF letrozole levels in female rats were 4.8 µg/ml and 2.3 µg/ml, respectively. For male rats, the corresponding values were 1.0 and 0.5 µg/ml. Likewise, the steady state plasma and brain ECF area under the curve (AUC) values were 4-5 fold higher in female rats. The steady state terminal half-life (t 1/2) in female rats was markedly higher (36 ± 2 h), relative to that in male rats (13 ± 3 h). A preliminary assessment of the letrozole levels in C6 tumors excised 25 days post implantation indicated that the steady state tumor levels were in the range of 4-10 µg/g of tumor tissue. These results are facilitating dose optimization for further pre-clinical pharmacology and toxicology assessments. In addition, PK-modeling based projections will aid initial dose determination in future clinical studies.

Redox Regulator GLRX Is Associated With Tumor Immunity in Glioma

“…These results suggest that GLRX is highly expressed in mesenchymal subtype glioma and may play an oncogenic role in glioma progression. BMI1 and CD44 were reported to differentiate the mesenchymal molecular subtype from other gliomas (22,23). Thus, we took these two well-studied biomarker genes as positive controls to performed ROC curve analysis (Supplementary Figure S2C-H).…”