[Dynamic change in the gene expression profile of rat benign prostate hyperplasia tissue after complete denervation].

OBJECTIVE: To investigate the dynamic change in the gene expression profile of the rat BPH tissue with progressive atrophy after complete denervation. METHODS: Twelve 29-week-old male rats with spontaneous hypertension and spontaneously developed BPH were used for this study, of which 3 were included in the control (C) group and the other 9 underwent complete denervation of the prostate. At 3, 7 and 11 days after operation (the D3, D7 and D11 groups), all the rats were sacrificed and their ventral prostatic lobes harvested for histopathological examination and RNA extraction, and the RNA samples were subjected to whole genome microarray of the expression profile, followed by real-time RT-PCR validation and bioinformatics analysis. RESULTS: Progressive atrophy of the BPH tissue was observed in the rats after complete denervation. Whole genome microarray of the expression profile was successfully performed for all the samples, and its reliability validated by real-time RT-PCR of 6 differentially expressed genes selected randomly. Hierarchical clustering analysis showed 108 up-regulated and 175 down-regulated genes in the differentially expressed ones between the D3 and C groups, 462 up-regulated and 189 down-regulated in those between the D7 and C groups, and 548 up-regulated and 256 down-regulated in those between the D11 and C groups. GO functional enrichment analysis indicated that the genes in each differentially expressed gene set participated in hundreds of molecular functions, biological processes and cellular components, while pathway enrichment analysis showed their involvement in hundreds of signaling pathways, of which many were enriched simultaneously in each differentially expressed gene set and ranked as the most enriched ones, and most of the genes involved were up-regulated and related with the activation of the complement system. CONCLUSIONS: Large numbers of abnormally expressed genes are involved in the progressive atrophy of rat BPH tissue after complete denervation, and these genes participate in hundreds of molecular functions, biological progresses, cellular components and signaling pathways. Abnormal activation of the complement system may play an important role in the progressive atrophy of the BPH tissue.

Efficacy and Safety of Medium-to-long-term Use of Tolterodine Extended Release with or without Tamsulosin in Patients with Benign Prostate Hyperplasia and Larger Prostate Size: A Double-blind, Placebo-controlled, Randomized Clinical Trial.

BACKGROUND: The medium-to-long-term use of antimuscarinics alone or in combination with an α-blocker in men with an enlarged prostate is still controversial. This double-blind, placebo-controlled, randomized clinical trial aimed to investigate the efficacy and safety of medium-to-long-term use of tolterodine extended release (ER) with or without tamsulosin in patients with benign prostate hyperplasia (BPH) and larger prostate size. METHODS: Totally, 152 patients (age ≥50 years) with BPH, International Prostate Symptom Score (IPSS) ≥12, quality-of-life (QoL) score ≥3, and total prostate volume ≥25 ml were enrolled in this study. The patients were randomized into four groups (n = 38 in each) to receive tolterodine ER placebo plus tamsulosin placebo, 0.2 mg tamsulosin plus tolterodine ER placebo, 4 mg tolterodine ER plus tamsulosin placebo, or tolterodine ER plus tamsulosin once daily for 24 weeks. IPSS (total, storage, and voiding subscales), QoL, maximum urinary flow rate (Qmax), and postvoid residual volume (PVR) were collected at baseline, and at weeks 4, 12, and 24. RESULTS: Compared with placebo, tolterodine ER plus tamsulosin significantly improved total IPSS (-7.15, -12.20, and -14.66 vs. -3.51, -5.78, and -7.23), storage IPSS (-3.56, -5.63, and -6.66 vs. -1.52, -1.21, and -2.43), voiding IPSS (-2.88, -5.10, and -6.48 vs. -1.52, -3.03, and -2.97), QoL (-1.21, -2.40, and -3.21 vs. -0.39, -1.41, and -1.60), Qmax (2.21, 7.97, and 9.72 ml/s vs. 2.15, 2.44, and 2.73 ml/s), and PVR (-17.88, -26.97, and -27.89 ml vs. -12.03, -11.16, and -16.73 ml) at weeks 4, 12, and 24, respectively; the differences were all statistically significant (P < 0.05). Adverse events (AEs) were not increased with treatment progression. Tolterodine ER alone did not improve total IPSS (-4.61, -6.79, and -5.70), voiding IPSS (-0.64, -1.83, and -1.45), QoL (-0.69, -1.21, and -1.41), or Qmax(-0.79, 2.83, and 1.11 ml/s), compared with placebo (all P > 0.05). However, a gradual increase in PVR (10.03, 10.41, and 12.89 ml) and more urinary AEs suggestive of urinary retention (11/38 vs. 4/38) were observed. CONCLUSION: Medium-to-long-term use of tolterodine ER plus tamsulosin should be recommended in patients with BPH and an enlarged prostate volume. TRIAL REGISTRATION: www.chictr.org.cn, ChiCTR-TRC-09000596; http://www.chictr.org.cn/showproj.aspx?proj=8939.