PMC

AR and Ki-67 immunohistochemistry of CWR22 tumors. AR expression was similar in androgen-dependent and recurrent tumors. AR-positive cells decreased to a minimum on day 2 after castration. Nuclear localization of AR returned on day 6 after castration but its intensity was lower than in androgen-dependent tumors. Higher percentages of AR-positive cells with lower levels of AR-staining intensity were recognized on days 32, 64, 90, and 120 after castration. Left: AR immunohistochemistry (scale bar, 10 μm). A: CWR22 before castration. B: Day 2 after castration. C: Day 6 after castration. D: Day 120 after castration. E: Recurrent CWR22 ∼150 days after castration. MIB-1 detection of the Ki-67 nuclear proliferation antigen showed similar rates of cellular proliferation in T-stimulated and recurrent tumors. Proliferation decreased on day 2 after castration and reached a level that was barely detectable on days 6 and 12 after castration. Proliferation was detectable as small nests of Ki-67-positive cells on day 120 after castration. Right: Ki-67 immunohistochemistry (scale bar, 20 μm). F: CWR22 before castration. G: Day 2 after castration. H: Day 6 after castration. I: Day 120 after castration. J: Recurrent CWR22 ∼150 days after castration.

(A-J) Mean difference in heart rate, RR-Interval, SDHR, SDRR and LF/HF-ratio between baseline and during castration and between baseline and post castration in the experimental groups. Bar diagrams of (A) mean difference in heart rate [beats minute⁻¹] between baseline and during castration and (B) between baseline and post castration as well as bar diagrams of (C) mean difference in RR-Interval [ms] between baseline and during castration and (D) between baseline and post castration. The bar indicates the mean is displayed as the top of the bar and standard deviation is represented by the whiskers. Boxplots of (E) difference in standard deviation of heart rate (SDHR) [beats minute⁻¹] between baseline and during castration and (F) between baseline and post castration, (G) difference in standard deviation of RR-Interval (SDRR) [ms] between baseline and during castration and (H) between baseline and post castration and (I) difference in low frequency/high frequency (LF/HF) ratio between baseline and during castration and (J) between baseline and post castration. The boxes represent the first and third quartile and the whiskers range from minimum to maximum. The median is indicated by the band inside the box. Different letters (a, b, c, d) show significant differences between the experimental groups (p < 0.05). The superscript “^e” differentiates time periods/episodes(“^e”) from time points (MAP and respiratory rate).

Activation of β-Catenin caused continuous prostate growth after castration. PBCre4/ Catnb^Δ(ex3) and litter mate control mice were castrated at 22-23 weeks and sacrificed 5 days or 2 weeks later. a, histology of control and PBCre4/ Catnb^Δ(ex3) mouse prostates without castration. 1 and 2: BrdU staining; 3 and 4: TUNEL staining. Arrow heads indicate positive staining. b, histology of control and PBCre4/ Catnb^Δ(ex3) mouse prostates 5 days or 2 weeks post castration. 1-4, serial sections from a control mouse prostate 5 days after castration; 5-8, serial sections from a PBCre4/ Catnb^Δ(ex3) mouse prostate 5 days after castration; 9-12, serial sections from a control mouse prostate 2 weeks after castration; 13-16, serial sections from a PBCre4/ Catnb^Δ(ex3) mouse prostate 2 weeks after castration. Panel 1, 5, 9, and 13: H&E staining. Activation of β-Catenin resulted in HGPIN in PBCre4/ Catnb^Δ(ex3) mouse prostates. Panel 2, 6, 10, and 14: β-Catenin staining. While β-Catenin can only be detected on cell membranes of control prostates (panel 2 and 10), β-Catenin accumulated in cytoplasm/nucleus of PBCre4/ Catnb^Δ(ex3) mouse prostates (panel 6 and 14). Panel 3, 7, 11, and 15: BrdU staining. While control prostate stopped grow after 5 days and 2 weeks castration, activation of β-Catenin enabled PBCre4/ Catnb^Δ(ex3) mouse prostate to continuously proliferate after castration as marked by the extensive BrdU incorporation in panel 7 and 15. Panel 4, 8, 12, and 16: TUNEL assay by ApopTag staining (inset for higher magnification). Both control and PBCre4/ Catnb^Δ(ex3) mouse prostates showed apoptosis after castration. c, quantification of BrdU and TUNEL staining. column 1: prostate from control mouse without castration; 2: prostate from PBCre4/ Catnb^Δ(ex3) mouse without castration; 3: prostate from control mouse 5 days post castration; 4, prostate from PBCre4/ Catnb^Δ(ex3) mouse 5 days post castration; 5, prostate from control mouse 2 weeks post castration; 6, prostate from PBCre4/ Catnb^Δ(ex3) mouse 2 weeks post castration. * p< 0.01; ** p< 0.05, # p> 0.05. Scale bars represent 50 μm.

(A) Castration decreased the membrane time constant. (B) Castration decreased the membrane capacitance. (C) Example traces of AP in the castration and control groups, showing differences in the AHP time to peak. (D) Castration prolonged the AHP time to peak.