Prostatic neuroendocrine cells (NE) are an integral part of prostate cancer (PCa) that are associated with PCa progression. As the current androgen-deprivation therapy (ADT) with anti-androgens may promote the neuroendocrine PCa (NEPCa) development, and few therapies can effectively suppress NEPCa, understanding the impact of NEPCa on PCa progression may help us to develop better therapies to battle PCa. Here we found NEPCa cells could increase the docetaxel-resistance of their neighboring PCa cells. Mechanism dissection revealed that through secretion of PTHrP, NEPCa cells could alter the p38/MAPK/Hsp27 signals in their neighboring PCa cells that resulted in increased androgen receptor (AR) activity via promoting AR nuclear translocation. The consequences of increased AR function might then increase docetaxel-resistance via increasing p21 expression. In vivo xenograft mice experiments also confirmed NEPCa could increase the docetaxel-resistance of neighboring PCa, and targeting this newly identified PTHrP/p38/Hsp27/AR/p21 signaling pathway with either p38 inhibitor (SB203580) or sh-PTHrP may result in improving/restoring the docetaxel sensitivity to better suppress PCa.

Erector spinae plane block and paravertebral block can provide analgesia for abdominal surgery. It is unclear whether erector spinae block is inferior to paravertebral block. We aimed to determine whether sufentanil dose and pain intensity (11-point scale) to 24 h after erector spinae block exceeded those after paravertebral block by no more than 5 lg and 1 point, respectively. We randomly allocated 166 adults to 0.4 ml.kg À1 ropivacaine 0.375% before scheduled laparoscopic nephroureterectomy, 83 each to erector spinae or paravertebral injection. We measured incision pain and intra-abdominal pain at rest and on movement 0.5 h, 2 h, 6 h, 18 h, 24 h and 48 h after surgery. Median (IQR [range]) cumulative sufentanil dose after erector spinae block was 15 (5-30 [0-105]) lg vs. 20 (10-50 [0-145]) lg after paravertebral block, median (95%CI) difference 5 lg (0-10), erector spinae non-inferiority p < 0.001. Median (IQR [range]) pain were 1.5 (1.0-2.0 [0.0-5.3]) after erector spinae block vs. 2.0 (1.0-2.5 [0.0-6.0]) after paravertebral block, median (95% CI) difference 0.3 (0.0-0.5), erector spinae non-inferiority p < 0.001. Adverse events did not differ between groups. Erector spinae block analgesia was not inferior to paravertebral block analgesia after laparoscopic nephroureterectomy.