Insulin-like growth factor-binding protein-2 promotes prostate cancer cell growth via IGF-dependent or -independent mechanisms and reduces the efficacy of docetaxel

Background: The development of androgen independence, chemo-, and radioresistance are critical markers of prostate cancer progression and the predominant reasons for its high mortality. Understanding the resistance to therapy could aid the development of more effective treatments. Aim: The aim of this study is to investigate the effects of insulin-like growth factor-binding protein-2 (IGFBP-2) on prostate cancer cell proliferation and its effects on the response to docetaxel. Methods: DU145 and PC3 cells were treated with IGFBP-2, insulin-like growth factor I (IGF-I) alone or in combination with blockade of the IGF-I receptor or integrin receptors. Cells were also treated with IGFBP-2 short interfering ribonucleic acid with or without a PTEN (phosphatase and tensin homologue deleted on chromosome 10) inhibitor or docetaxel. Tritiated thymidine incorporation was used to measure cell proliferation and Trypan blue cell counting for cell death. Levels of IGFBP-2 mRNA were measured using RT-PCR. Abundance and phosphorylation of proteins were assessed using western immunoblotting. Results: The IGFBP-2 promoted cell growth in both cell lines but with PC3 cells this was in an IGF-dependent manner, whereas with DU145 cells the effect was independent of IGF receptor activation. This IGF-independent effect of IGFBP-2 was mediated by interaction with β-1-containing integrins and a consequent increase in PTEN phosphorylation. We also determined that silencing IGFBP-2 in both cell lines increased the sensitivity of the cells to docetaxel. Conclusion: The IGFBP-2 has a key role in the growth of prostate cancer cells, and silencing IGFBP-2 expression reduced the resistance of these cells to docetaxel. Targeting IGFBP-2 may increase the efficacy of docetaxel.7 page(s

Evaluation of analgesic requirements and postoperative recovery after radical retropubic prostatectomy using long-acting spinal anesthesia

To analyze the postoperative pain, analgesic requirements, and convalescence of patients undergoing radical retropubic prostatectomy (RRP) under spinal anesthesia using long-acting morphine sulfate as preemptive analgesia. A total of 103 consecutive men underwent RRP by a single surgeon. The time to tolerate oral fluids, time to unassisted ambulation, postoperative pain levels (visual analog pain score of 0 to 10), and analgesic requirements expressed in morphine equivalents were evaluated. Baseline patient characteristics and intraoperative factors (operating room time, blood loss) were also evaluated. The mean time to tolerate oral fluids and unassisted ambulation was 11.3 +/- 7.6 hours and 20 +/- 6 hours, respectively. The mean narcotic requirements were 7.4 +/- 6.1 morphine equivalents before discharge and 28.5 +/- 25.9 morphine equivalents in the first week after discharge. The mean visual analog pain score was 4.5 +/- 2.1 at discharge and fell significantly to 1.5 +/- 1.0 by the time of Foley catheter removal on postoperative day 7 or 8. The analgesic requirements after discharge correlated with the pain score at discharge (P = 0.016). The mean time to resumption of normal preoperative activities was 19.4 +/- 9.4 days. Two patients developed postspinal anesthesia headache. No other complications attributable to the anesthetic occurred. RRP may be performed through a small modified Pfannenstiel incision under spinal anesthesia containing long-acting morphine with little postoperative pain, low narcotic requirements, and a short convalescence. A prospective, randomized study is needed to compare the early postoperative outcomes of RRP performed using general versus spinal anesthesia