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Surgical intervention for symptomatic benign prostatic hyperplasia is correlated with expression of the AP-1 transcription factor network.

ABSTRACT: Approximately one-third of patients fail medical treatment for benign prostatic hyperplasia and associated lower urinary tract symptoms (BPH/LUTS) requiring surgical intervention. Our purpose was to establish a molecular characterization for patients undergoing surgical intervention for LUTS to address therapeutic deficiencies.Clinical, molecular, and histopathological profiles were analyzed in 26 patients undergoing surgery for severe LUTS. Incidental transitional zone nodules were isolated from 37 patients with mild symptoms undergoing radical prostatectomy. Clinical parameters including age, prostate volume, medication, prostate specific antigen, symptom score, body mass index, and incidence of diabetes were collected. Multivariate logistic regression analysis with adjustments for potential confounding variables was used to examine associations between patient clinical characteristics and molecular targets identified through molecular profiling.Compared to incidental BPH, progressive symptomatic BPH was associated with increased expression of the activating protein-1 transcription factor/chemokine network. As expected, inverse correlations were drawn between androgen receptor levels and age, as well as between 5?-reductase inhibitor (5ARI) treatment and tissue prostate specific antigen levels; however, a novel association was also drawn between 5ARI treatment and increased c-FOS expression.This study provides molecular evidence that a network of pro-inflammatory activating protein-1 transcription factors and associated chemokines are highly enriched in symptomatic prostate disease, a profile that molecularly categorizes with many other chronic autoimmune diseases. Because 5ARI treatment was associated with increased c-FOS expression, future studies should explore whether increased activating protein-1 proteins are causal factors in the development of symptomatic prostate disease, inflammation or resistance to traditional hormonal therapy.

SUBMITTER: Lin-Tsai O

PROVIDER: S-EPMC4160824 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Surgical intervention for symptomatic benign prostatic hyperplasia is correlated with expression of the AP-1 transcription factor network.

Lin-Tsai Opal O Clark Peter E PE Miller Nicole L NL Fowke Jay H JH Hameed Omar O Hayward Simon W SW Strand Douglas W DW

The Prostate 20140205 6

<h4>Background</h4>Approximately one-third of patients fail medical treatment for benign prostatic hyperplasia and associated lower urinary tract symptoms (BPH/LUTS) requiring surgical intervention. Our purpose was to establish a molecular characterization for patients undergoing surgical intervention for LUTS to address therapeutic deficiencies.<h4>Methods</h4>Clinical, molecular, and histopathological profiles were analyzed in 26 patients undergoing surgery for severe LUTS. Incidental transiti ...[more]

PMID: 24500928

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Project description:BackgroundMale lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often uses LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a proinflammatory and profibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to proinflammatory stimuli and identified downstream targets of OPN in prostate stromal cells.MethodsImmunohistochemistry was performed on prostate sections obtained from the transition zone of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS (surgical BPH, S-BPH) or patients who underwent radical prostatectomy to remove low-grade prostate cancer (incidental BPH, I-BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging System and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot analysis. The ability of prostate cells to secrete osteopontin in response to IL-1β and TGF-β1 was determined in stromal (BHPrS-1) and epithelial (NHPrE-1 and BHPrE-1) cells by enzyme-linked immunosorbent assay. Quantitative polymerase chain reaction was used to measure gene expression changes in these cells in response to OPN.ResultsOPN immunostaining and protein levels were more abundant in S-BPH than I-BPH. Staining was distributed across all cell types with the highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF-β1 stimulated OPN secretion by NHPrE-1 cells and both IL-1β and TGF-β1 stimulated OPN secretion by BHPrS-1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2, and IL6 in BHPrS-1, but not in epithelial cell lines.ConclusionsOPN is more abundant in prostates of men with S-BPH compared to men with I-BPH. OPN secretion is stimulated by proinflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of proinflammatory mRNAs. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways.

Project description:ContextSurgical treatment is important for male lower urinary tract symptom (LUTS) management, but there are few reviews of the risks of reoperation.ObjectiveTo systematically evaluate the current evidence regarding the reoperation rates of surgical treatment for LUTS in accordance with current recommendations and guidelines.Evidence acquisitionEligible studies published up to July 2023, were searched for in the PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), and Web of Science™ (Clarivate™, Philadelphia, PA, USA) databases. STATA® (StataCorp LP, College Station, TX, USA) software was used to conduct the meta-analysis. Random-effects models were used to calculate the pooled incidences (PIs) of reoperation and the 95% confidence intervals (CIs).Evidence synthesisA total of 119 studies with 130,106 patients were included. The reoperation rate of transurethral resection of the prostate (TURP) at 1, 2, 3, and 5 years was 4.0%, 5.0%, 6.0%, and 7.7%, respectively. The reoperation rate of plasma kinetic loop resection of the prostate (PKRP) at 1, 2, 3, and 5 years was 3.5%, 3.6%, 5.7%, and 6.6%, respectively. The reoperation rate of holmium laser enucleation of the prostate (HoLEP) at 1, 2, 3, and 5 years was 2.4%, 3.3%, 5.4%, and 6.6%, respectively. The reoperation rate of photoselective vaporization of the prostate (PVP) at 1, 2, 3, and 5 years was 3.3%, 4.1%, 6.7%, and 7.1%, respectively. The reoperation rate of surgery with AquaBeam® at 1, 2, 3, and 5 years was 2.6%, 3.1%, 3.0%, and 4.1%, respectively. The reoperation rate of prostatic artery embolization (PAE) at 1, 2, 3, and 5 years was 12.2%, 20.0%, 26.4%, and 23.8%, respectively. The reoperation rate of transurethral microwave thermotherapy (TUMT) at 1, 2, 3, and 5 years was 9.9%, 19.9%, 23.3%, and 31.2%, respectively. The reoperation rate of transurethral incision of the prostate (TUIP) at 5 years was 13.4%. The reoperation rate of open prostatectomy (OP) at 1 and 5 years was 1.3% and 4.4%, respectively. The reoperation rate of thulium laser enucleation of the prostate (ThuLEP) at 1, 2, and 5 years was 3.7%, 7.7%, and 8.4%, respectively.ConclusionOur results summarized the reoperation rates of 10 surgical procedures over follow-up durations of 1, 2, 3, and 5 years, which could provide reference for urologists and LUTS patients.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023445780.

Project description:OBJECTIVE:To assess the efficacy and safety of different endoscopic surgical treatments for benign prostatic hyperplasia. DESIGN:Systematic review and network meta-analysis of randomised controlled trials. DATA SOURCES:A comprehensive search of PubMed, Embase, and Cochrane databases from inception to 31 March 2019. STUDY SELECTION:Randomised controlled trials comparing vapourisation, resection, and enucleation of the prostate using monopolar, bipolar, or various laser systems (holmium, thulium, potassium titanyl phosphate, or diode) as surgical treatments for benign prostatic hyperplasia. The primary outcomes were the maximal flow rate (Qmax) and international prostate symptoms score (IPSS) at 12 months after surgical treatment. Secondary outcomes were Qmax and IPSS values at 6, 24, and 36 months after surgical treatment; perioperative parameters; and surgical complications. DATA EXTRACTION AND SYNTHESIS:Two independent reviewers extracted the study data and performed quality assessments using the Cochrane Risk of Bias Tool. The effect sizes were summarised using weighted mean differences for continuous outcomes and odds ratios for binary outcomes. Frequentist approach to the network meta-analysis was used to estimate comparative effects and safety. Ranking probabilities of each treatment were also calculated. RESULTS:109 trials with a total of 13?676 participants were identified. Nine surgical treatments were evaluated. Enucleation achieved better Qmax and IPSS values than resection and vapourisation methods at six and 12 months after surgical treatment, and the difference maintained up to 24 and 36 months after surgical treatment. For Qmax at 12 months after surgical treatment, the best three methods compared with monopolar transurethral resection of the prostate (TURP) were bipolar enucleation (mean difference 2.42 mL/s (95% confidence interval 1.11 to 3.73)), diode laser enucleation (1.86 (-0.17 to 3.88)), and holmium laser enucleation (1.07 (0.07 to 2.08)). The worst performing method was diode laser vapourisation (-1.90 (-5.07 to 1.27)). The results of IPSS at 12 months after treatment were similar to Qmax at 12 months after treatment. The best three methods, versus monopolar TURP, were diode laser enucleation (mean difference -1.00 (-2.41 to 0.40)), bipolar enucleation (0.87 (-1.80 to 0.07)), and holmium laser enucleation (-0.84 (-1.51 to 0.58)). The worst performing method was diode laser vapourisation (1.30 (-1.16 to 3.76)). Eight new methods were better at controlling bleeding than monopolar TURP, resulting in a shorter catheterisation duration, reduced postoperative haemoglobin declination, fewer clot retention events, and lower blood transfusion rate. However, short term transient urinary incontinence might still be a concern for enucleation methods, compared with resection methods (odds ratio 1.92, 1.39 to 2.65). No substantial inconsistency between direct and indirect evidence was detected in primary or secondary outcomes. CONCLUSION:Eight new endoscopic surgical methods for benign prostatic hyperplasia appeared to be superior in safety compared with monopolar TURP. Among these new treatments, enucleation methods showed better Qmax and IPSS values than vapourisation and resection methods. STUDY REGISTRATION:CRD42018099583.

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Surgical intervention for symptomatic benign prostatic hyperplasia is correlated with expression of the AP-1 transcription factor network.

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Surgical intervention for symptomatic benign prostatic hyperplasia is correlated with expression of the AP-1 transcription factor network.

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