Effects of CDK7 inhibition with THZ1 on kidney tumor development inTsc2^{+/ −} mice. (A) Experimental plan. Tsc2^+/− A/J strain mice were randomized at age 5.5 mo to vehicle (DMSO), THZ1 (10 mg/kg i.p. two times per day), or rapamycin (3 mg/kg i.p. 3 d per wk). They were treated for 1 mo, and then pathology was assessed. (B) Number of tumors per kidney observed by gross inspection for each treatment group. Each data point corresponds to one kidney. (C) Tumor volume per kidney determined by semiquantitative microscopic assessment. Each data point corresponds to one kidney. (D) Renal cystadenoma histology in the treated mice. Representative H&E tumor images are shown for each treatment cohort at 100×. Four cystadenomas are shown for vehicle (CTRL), rapamycin (RAP), and THZ1 treatment cohorts, and at least eight images per slide were analyzed for each condition (Table S7). Scale bar, 200 µm. (E) Ki-67 staining to assess cell proliferation in kidney sections from the treated mice. All images are at 100× magnification. Percentage of tumor cells with nuclear immunoreactivity of Ki-67 was scored from six random fields per section (n = 4 kidneys per group). Scale bar, 50 µm. (F) NRF2 expression by IHC in Tsc2^+/− mouse kidney tumors from control and THZ1-treated mice (n = 4 kidneys per group). Scale bar, 50 µm. (G) Relative GSH content was measured by GSH-Glo assay in kidney lysates from vehicle (CTRL) and THZ1 treatment cohorts (n = 2 kidneys per group). Each data point represents the mean ± SEM with **, P < 0.01; ***, P < 0.001.