1439

ALPHA ADRENERGIC STIMULATION REGULATES COX-2 EXPRESSION IN PROSTATE STROMA CELLS

Victor K Lin*, Shih-Ya Wang, Claus G Roehrborn, Dallas, TX

INTRODUCTION AND OBJECTIVE: Cyclooxygenase-2 (COX-2) has been implicated in cellular growth regulation and cancer progression. Elevated COX-2 expression has also been described in benign prostatic hyperplasia (BPH). a adrenergic stimulation regulates cellular proliferation in variety tissues including vascular smooth muscle cells. We have previously reported that a blockers may alter prostate stroma cell phenotype and a stimulation may activate MAP kinases (MAPK) in prostate cells. This study is designed to delineate a stimulated MAPK/Erk signaling mechanism in regulating COX-2 expression in prostate stroma cells.

METHODS: Human prostate stroma (HPS) cell primary cultures prepared from surgical BPH tissues, ad5-a1a adrenergic receptor (a1a-AR) viruses, immuno-blot analysis, and MAPK inhibitors were employed to assess phenylephrine (PE) stimulation on COX-2 expression and its signaling components.

RESULTS: Immuno-blot result indicated that an increase of COX-2 expression was observed within 2 hrs in 10µM PE treated HPS cells expressing viral transduced a1a-AR. Compared to non-treated cells, a 2.3 fold increase at 2 hrs and 5.4 fold increase at 30 hrs of PE treatment were detected. This PE stimulated COX-2 up-regulation is a1a-AR dependent. Signaling inhibitor analysis results indicated U0126 or PD98059, a MEK inhibitor, not only inhibited PE stimulated MAPK/Erk activation, but also strongly attenuated the PE stimulation of COX-2 up-regulation in HPS cells suggesting that COX-2 up-regulation is regulated via MAPK/Erk signaling pathways. Inhibition of PI3 kinases and PLC pathways also partially blocks the PE induced COX-2 up-regulation.

CONCLUSIONS: PE stimulation in human prostate stroma cells induces COX-2 expression, which has been shown in association with cellular growth. Furthermore, MAPK signaling in HPS cells appears to play a key role in this induction. This result suggests that, during the pathogenesis of BPH, a adrenergic stimulation may regulate cellular proliferation through MAPK activation and COX-2 up-regulation.

Session Info: Discussed Poster - Wednesday, May 25, 2005, 8:00 AM - 12:00 PM

1554

IMPACT OF PROSTATE-SPECIFIC ANTIGEN AND PROSTATE VOLUME AS PREDICTORS OF EFFICACY OUTCOMES IN PHOTOSELECTIVE VAPORIZATION PROSTATECTOMY (PVP): ANALYSIS AND RESULTS OF ONGOING PROSPECTIVE MULTICENTER STUDY AT 3 YEARS

Alexis E Te*, New York, NY; Terrence R Malloy, Philadelphia, PA; Barry S Stein, Providence, RI; James C Ulchaker, Cleveland, OH; Unyime O Nseyo, Richmond, VA; Mahmood A Hai, Wayne, MI

INTRODUCTION AND OBJECTIVE: High-power KTP laser prostatectomy or PVP with its unique 532 nm laser wavelength, pulsing regime and absorption characteristics has previously demonstrated that it can safely and efficiently vaporize prostatic adenoma with minimal bleeding and morbidity in the ongoing multicenter study. This study will report 3 year results and analyze if preoperative total prostate-specific antigen (tPSA) and prostate volume have any predictive impact on the level of clinical efficacy achieved with PVP for treatment of symptomatic benign prostatic hyperplasia (BPH).

METHODS: 139 male subjects, mean age of 67.7 ± 8.7 years, diagnosed with obstructive lower urinary tract symptoms (LUTS) secondary to BPH underwent PVP with an average 80W KTP laser at 6 sites. Each subject was divided into 4 sub groups in accordance with pre-operative tPSA levels. Group I (0 - 2 ng/mL), Group II (2.1 - 4.0 ng/mL), Group III (4.1- 6.0 ng/mL) and Group IV (6.1 - 9.8 ng/mL). Each sub-group was assessed for changes from baseline in American Urological Symptom Index (AUA SI) score, quality of life score, peak urinary flow rate, prostate volume, and post-void residual urine volume at 12, 24 and 36 months. Correlation of tPSA with all efficacy outcome parameters was performed by linear regression analysis.

RESULTS: All tPSA subgroups showed sustained improvement in all efficacy outcomes maintained through three years. Subgroups I-III showed no significant deviations in any outcome parameters at each follow-up examinations. However, there was a statistically significant deviation in level of improvement in groups I-III versus Group IV (P<.05) in symptom score and peak urinary flow rate improvement at 12 and 24 months. Combined mean prostate volumes for Groups I-III was 48.3 ± 16.7 cc (N=87) versus 83.1 ± 30.6 cc (N=52) in Group IV. Mean percent improvement in AUA SI at 1, 2 and 3 year follow-up in Groups I-III versus Group IV was 86%, 92% and 85% versus 69%, 74% and 76%, respectively. Mean percent improvement in peak urinary flow rate at 1, 2 and 3 year follow-up in Groups I-III versus Group IV was 194%, 185% and 179% versus 124%, 145% and 139%, respectively.

CONCLUSIONS: This analysis suggests there is a significant difference in efficacy outcomes in patients with tPSA < 6.0 ng/mL versus patients with tPSA > 6.0 ng/mL. However, overall results achieved with PVP have been positive and durable to three years irrespective of tPSA and prostate volume.

Session Info: Moderated Poster - Wednesday, May 25, 2005, 10:00 AM - 12:00 PM

1555

A RANDOMISED TRIAL COMPARING PHOTO-VAPORISATION AND TRANS-URETHRAL RESECTION OF THE PROSTATE IN PATIENTS

David M Bouchier-Hayes*, Paul Anderson, Scott Van Appledorn, Pat Bugeja, Anthony J Costello, Melbourne, Australia

INTRODUCTION AND OBJECTIVE: Many technologies have been mooted as equal to trans-urethral resection of the prostate without gaining widespread acceptance, often due to lack of randomised trials. The Greenlight® laser system (Laserscope, San Jose, Ca.) uses a potassium-titanyl-phosphate (KTP) crystal at 532nm to give an 80-watt laser ablation system. This study is designed to compare the outcomes of photo-vaporisation of the prostate (PVP) using this system to those from TURP in a randomised fashion.

METHODS: 120 patients with urodynamically proven obstruction and suitable for surgical intervention are randomised to undergo TURP or PVP. All patients undergo voiding flow rates, measurement of prostate volume, pressure-flow studies, International Prostate Symptom Scores (IPSS) and sexual bother scores pre-operatively and at 1,3,6,12,18 and 24 months. Irrigation use, length of catherisation time (LOC), length of hospital stay (LOS), blood loss and operative time are also assessed.

RESULTS: To date 32 patients are evaluable. Baseline flow rates and IPSSs were equivalent. The PVP group had larger prostates. Both PVP and TURP produced equivalent significant improvement in flow rates and IPSSs, and significantly shorter LOC and LOS in the PVP group. Results expressed as mean+SD (sample standard deviation) and (range). Statistical tests: student-t paired and unpaired. Adverse events were less frequent in the PVP group.

CONCLUSIONS: The early results of this trial demonstrate that PVP is an effective technique when compared to TURP, producing equivalent improvements in flow rates and IPSS scores with markedly reduced LOS, LOC and adverse events. Long-term follow-up is being undertaken to ensure durability of these initially encouraging results

Session Info: Moderated Poster - Wednesday, May 25, 2005, 10:00 AM - 12:00 PM

Read BPH Selected Abstracts - Part 4

Please log-in or register in order to submit comments.

Powered by AkoComment!