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. 2021 Feb 9;113(8):1094–1104. doi: 10.1093/jnci/djab018

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Figure 4. — A combination of quetiapine and radiation with atorvastatin improves survival in mouse modelsof glioblastoma. (A) Quetiapine (QTP) and atorvastatin (ATR) synergistically decreases sphere-forming capacities (SFC) in patient-derived glioblastoma lines. All experiments in this figure have been performed with at least 3 independent biological repeats. (Two-way ANOVA; P values are indicated in the figure). (B) QTP, ATR, or a combination of both does not alter the radiation sensitivity of patient-derived glioblastoma lines. (C) Shotgun lipidomics analysis was performed with HK-374 cells treated with either control (CON), 4 Gy, 4 Gy + QTP, or 4 Gy + QTP + ATR that included at least 3 independent biological repeats. Radiation and quetiapine upregulated fatty acid, diglyceride or diacylglycerol, and cholesterol ester synthesis, and this effect was reversed by the addition of atorvastatin. (D) Treatment plan for patient-derived orthotopic xenografts using an image-guided small animal irradiator. A combination of QTP and ATR (both 30 mg/kg) with a single dose of radiation (10 Gy) statistically significantly prolongs survival in the GL261 glioma mouse model (hazard ratio [HR] of control vs 10 Gy and quetiapine and atorvastatin = 8.33, 95% confidence interval [CI] = 2.50 to 27.77) (E) and HK-374 patient-derived orthotopic xenografts (F) (log-rank HR of control vs 10 Gy and quetiapine and atorvastatin = 5.94, 95% CI = 2.21 to 15.95). All statistical tests were 2-sided.

Figure 4. — A combination of quetiapine and radiation with atorvastatin improves survival in mouse modelsof glioblastoma. (A) Quetiapine (QTP) and atorvastatin (ATR) synergistically decreases sphere-forming capacities (SFC) in patient-derived glioblastoma lines. All experiments in this figure have been performed with at least 3 independent biological repeats. (Two-way ANOVA; P values are indicated in the figure). (B) QTP, ATR, or a combination of both does not alter the radiation sensitivity of patient-derived glioblastoma lines. (C) Shotgun lipidomics analysis was performed with HK-374 cells treated with either control (CON), 4 Gy, 4 Gy + QTP, or 4 Gy + QTP + ATR that included at least 3 independent biological repeats. Radiation and quetiapine upregulated fatty acid, diglyceride or diacylglycerol, and cholesterol ester synthesis, and this effect was reversed by the addition of atorvastatin. (D) Treatment plan for patient-derived orthotopic xenografts using an image-guided small animal irradiator. A combination of QTP and ATR (both 30 mg/kg) with a single dose of radiation (10 Gy) statistically significantly prolongs survival in the GL261 glioma mouse model (hazard ratio [HR] of control vs 10 Gy and quetiapine and atorvastatin = 8.33, 95% confidence interval [CI] = 2.50 to 27.77) (E) and HK-374 patient-derived orthotopic xenografts (F) (log-rank HR of control vs 10 Gy and quetiapine and atorvastatin = 5.94, 95% CI = 2.21 to 15.95). All statistical tests were 2-sided.