Diminished PI3K/mTOR pathway and increased premature mitotic entry and apoptosis in SCLC xenograft tumors. A. Immunohistochemical analysis of p-mTOR, Ki67, cleaved caspase-3, and p-histone 3 was performed in H69 and H82 xenograft tumors treated with vehicle, MLN0128, or AZD1775, or combination of both. Scale bars, 50μm (inset). Significant reduction of Ki67 positive cells (proliferation), increased cl-caspase-3 positive cells (cell death), increased p-Histone 3 (cellular stress) were observed in MLN0128, or AZD1775, or combination-treated xenograft tumors. Significant reduction of p-mTOR activity was observed in MLN0128-treated xenograft tumors. B. Quantitative cell image analysis was carried out on tissue samples viewed at 400x magnification. Percentage of positivity (brown nuclear/cytoplasmic staining) cells were scored. Vehicle-treated xenograft tumors were compared with MLN0128-, or AZD1775-, or combination-treated tumors. **p < 0.01, ***p < 0.001, ****p < 0.0001 compared with vehicle-treated xenograft tumors.