Enzalutamide (Enz) is a second‐generation androgen receptor (AR) antagonist for castration‐resistant prostate cancer (CRPC) therapy, and it prolongs survival time in these patients. However, during Enz treatment, CRPC patients usually acquire resistance to Enz and often show cross‐resistance to other AR signaling inhibitors. Although glucocorticoid receptor (GR) is involved in this resistance, the role of GR has not yet been clarified. Here, we report that chronic Enz treatment induced GR‐mediated glucose transporter 4 (GLUT4) upregulation, and that upregulation was associated with resistance to Enz and other AR signaling inhibitors. Additionally, inhibition of GLUT4 suppressed cell proliferation in Enz‐resistant prostate cancer cells, which recovered from Enz resistance and cross‐resistance without changes in GR expression. Thus, a combination of Enz and a GLUT4 inhibitor could be useful in Enz‐resistant CRPC patients.

Abbreviations & Acronyms BMI = body mass index BOO = bladder outlet obstruction BPE = benign prostatic enlargement CI = confidence interval CIC = clean intermittent catheterization DO = detrusor overactivity FVC = frequency volume chart IPSS = International Prostate Symptom Score LUTD = lower urinary tract dysfunction LUTS = lower urinary tract symptoms NLUTD = neurogenic lower urinary tract dysfunction OAB = overactive bladder OABSS = overactive bladder symptom score OR = odds ratio PVR = post-void residual urine Qmax = maximum flow rate UTI = urinary tract infection VARD = vesical adaptation response to diuresis

Background and Objectives: This study was conducted to identify whether surgical stress during the peri-operative period of robot-assisted radical prostatectomy might affect biochemical recurrence in patients with positive surgical margins.Methods: Participants in the present study were 324 consecutive patients with localized prostate cancer who underwent robot-assisted radical prostatectomy between February 2013 and June 2018. Positive surgical margins were diagnosed in 61 of them. Patients with positive surgical margins were divided into those with (n = 19) and those without (n = 42) biochemical recurrence. Lymph node dissection, estimated blood loss, inhalation anesthetic volume, and surgical duration were evaluated as indicators of surgical stress. White blood cell count, C-reactive protein, body temperature, and usage of analgesics were postoperatively evaluated as surrogate markers of surgical stress. The associations between factors, including patients' characteristics and pathological features, and biochemical recurrence were investigated.Results: In univariate analyses, surgical duration (P = 0.004), D'Amico risk class (P = 0.002), Gleason score (P = 0.022) and the number of positive cores in prostate biopsy (P = 0.009) were statistically significantly associated with biochemical recurrence. In multivariate analyses, only surgical duration was significantly associated with biochemical recurrence (P = 0.042), at a cut-off value of surgical duration of 228.5 minutes.Conclusions: Prolonged surgical duration is associated with biochemical recurrence in patients with positive surgical margins. Thus, surgical duration should be limited as much as possible to reduce surgical stress, which might cause biochemical recurrence.

in the L6 spinal cord, as markers of glial activation and central sensitization, were also evaluated by RT-PCR and immunohistology.RESULTS: OAB mice showed bladder overactivity and inefficient voiding (Fig 1-a) with increased M2, M3, P2X2, P2X3, P2X4, and P2X7 levels in the bladder and increased CCL2 and CCR2 in DRG, indicating afferent hyperexcitability (Fig 1-b). CX3CR1, GFAP, and CCR2 in the L6 spinal cord were upregulated in the OAB group (Fig 1-c). However, CON mice exhibited improvements of all these parameters of afferent hyperexcitability and central sensitization. Also, CON mice showed better voiding efficiency and reduced CNS changes compared with CES mice.CONCLUSIONS: Central sensitization may be an important pathophysiological mechanism of OAB. Continuous treatment of OAB with mirabegron seems to prevent the process of central sensitization via improvement of CNS neural remodeling. Therefore, continuous OAB medication may be desirable for long-term disease control.

In order to significantly improve warpage of a PoP bottom package, Shinko developed an enhanced PoP structure. The inclusion of a support material attached to the backside of the flip chip die and over molded resin is the structure's key attribute. By adjusting the balance of each material (mold resin, substrate and support material thickness), we can better control warpage at both room temperature and reflow temperature. This enhanced thin PoP structure can be easily incorporated into a standard assembly process with existing equipment sets. This paper describes simulation results, along with measured warpage characteristics of the new package.