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Benign Prostate Hyperplasia (benign + prostate_hyperplasia)
Selected AbstractsApoptosis regulators Fau and Bcl-G are down-regulated in prostate cancerTHE PROSTATE, Issue 14 2010Mark R. Pickard Abstract BACKGROUND The molecular control of cell death through apoptosis is compromised in prostate cancer cells, resulting in inappropriate cell survival and resistance to cytotoxic therapy. Reduced expression of the functionally connected apoptosis-regulators and candidate tumor suppressors Fau and Bcl-G has recently been implicated in oncogenesis in other tissues. The present study examines the hypothesis that reduced expression of these genes may be involved in prostate cancer. METHODS Fau and Bcl-G mRNA levels were determined by real time RT-PCR in two independent prostate tissue collections. In experiments in vitro, Fau and Bcl-G levels in prostate cancer cell lines were reduced using RNA interference and the effects on sensitivity to UVC irradiation were determined. RESULTS Fau and Bcl-G mRNA levels were both lower in prostate cancer tissue than in normal prostate and Benign Prostate Hyperplasia. Active down-regulation of Fau and Bcl-G expression in vitro resulted in decreased sensitivity to UVC-induced cytotoxicity. Simultaneous down-regulation of Fau and Bcl-G produced a decrease in sensitivity which was similar to either gene alone. CONCLUSIONS Fau and Bcl-G mRNA levels are both decreased in prostate cancer. In prostate cancer cell lines in vitro such down-regulation results in reduced sensitivity to UVC-induced cytotoxicity, consistent with the putative roles of these genes as candidate prostate tumor suppressors. The absence of an additive effect when Fau and Bcl-G were down-regulated simultaneously is consistent with the two genes acting in the same apoptosis pathway, for example, with the pro-apoptotic effects of Fau being mediated through modulation of Bcl-G. Prostate 70: 1513,1523, 2010. © 2010 Wiley-Liss, Inc. [source] Reversal of benign prostate hyperplasia by selective occlusion of impaired venous drainage in the male reproductive system: novel mechanism, new treatmentANDROLOGIA, Issue 5 2008Y. Gat Summary The prostate is an androgen-regulated exocrine gland producing over 30% of the noncellular components of the semen and promoting optimal conditions for survival and motility of sperm in the vagina. Benign prostate hyperplasia (BPH) is the most common benign neoplasm in men. Its aetiology is not clear, and therefore, current medical treatments are directed towards the symptoms. Though testosterone is known to be the promoter of prostate cell proliferation, no causal relation between serum testosterone levels and BPH has been found. In this study, we propose a novel and tested pathophysiological mechanism for the evolution of BPH and suggest a tested and effective treatment. We found that in all BPH patients, the one-way valves in the vertically oriented internal spermatic veins are destroyed (clinically manifested as varicocele), causing elevated hydrostatic pressure, some 6-fold greater than normal, in the venous drainage of the male reproductive system. The elevated pressure propagates to all interconnected vessels leading to a unique biological phenomenon: venous blood flows retrograde from the higher pressure in the testicular venous drainage system to the low pressure in the prostatic drainage system directly to the prostate (law of communicating vessels). We have found that free testosterone levels in this blood are markedly elevated, with a concentration of some 130-fold above serum level. Consequently, the prostate is exposed to: (i) increased venous pressure that causes hypertrophy; (ii) elevated concentration of free testosterone causing hyperplasia. We have treated 28 BPH patients using a technique that restores normal pressure in the venous drainage in the male reproductive system. The back-pressure and the back-flow of blood from the testicular to the prostate drainage system were eliminated and, consequently, a rapid reduction in prostate volume and a regression of prostate symptoms took place. [source] Comparison of microvessel densities in rat prostate tissues treated with finasteride, bicalutamide and surgical castration: A preliminary studyINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2005CEVDET KAYA Abstract Background: A group of anti-androgens with different mechanisms of action and adverse effects have been investigated in patients with gross hematuria related to benign prostate hyperplasia; however, there is not yet any consensus about the standard management of these patients. The present study aims to identify if any one type of the hormonal intervention is superior in terms of the suppression of microvessel formation in the prostate. Materials and methods: A total of 28 mature, healthy male Sprague,Dawley rats (300 ± 50 g) were used in this study. The rats were randomly assigned to one of four groups (n = 7 per group). The effects of three different hormonal therapies on angiogenesis and microvascularity in rat ventral prostate were compared. Groups 1 and 2 were treated for 28 days with finasteride and bicalutamide, respectively, and rats from Group 3 underwent surgical castration. Following treatment, all rats included in the study underwent dissection of the ventral prostate and immunohistochemical analysis of microvessel density by factor VIII-related antigen. Results: The mean number of microvessels in the finasteride and bicalutamide groups was 24.5 (±8.44 SE) and 27 (±9.89 SE) respectively. In contrast, the castration and control groups had microvessel numbers of 12.9 (±5.35 SE) and 40.3 (±5.03 SE) respectively. Differences were statistically significant between all three treatment groups and the controls (P < 0.005); the number of microvessels in rat prostate tissues of the control group was significantly higher than the treatment groups. Mean microvessel densities in the bicalutamide and finasteride groups were significantly higher than microvessel densities in the castration group (P < 0.005). There was no statistically significant difference between mean microvessel number in rat prostate tissue treated with finasteride or bicalutamide (P > 0.05). Conclusions: Even though finasteride was not as effective as castration in reducing microvessel number, its effect was equal to that of bicalutamide in terms of suppressing the angiogenesis in prostatic tissue. Based on the findings of the present study, finasteride might offer a viable option in the management of macroscopic hematuria by inhibition of microvessel formation within the prostatic tissue. Further clinical studies are warranted. [source] Classification of fixed urological cells using Raman tweezersJOURNAL OF BIOPHOTONICS, Issue 1-2 2009Tim J. Harvey Abstract In this paper we report on preliminary investigations into using Raman tweezers to classify urological cell lines. This builds on earlier work within the group, whereby Raman tweezer methodologies were developed, and the application of this technique to differentiate between live prostate cancer (CaP) and bladder cells lines (PC-3 and MGH-U1 respectively) was demonstrated. In this present study we analysed chemically fixed cells using two different fixative methods; SurePathTM (a commercial available liquid based cytology media) and 4% v/v formalin/PBS fixatives. The study has been expanded from our previous live cell study to include the androgen sensitive CaP cell line LNCaP, primary benign prostate hyperplasia (BPH) cells as well as primary urethral cells. Raman light from the cells was collected using a 514.5 nm Ar-ion laser excitation source in back-scattering configuration mode. Principal component-linear discriminate analysis (PC-LDA) models of resulting cell spectra were generated and these were validated using a blind comparison. Sensitivities and specificities of > 72% and 90% respectively, for SurePath fixed cells, and > 93% and 98% respectively for 4% v/v formalin/PBS fixed cells was achieved. The higher prediction results for the formalin fixed cells can be attributed to a better signal-to-noise ratio for spectra obtained from these cells. Following on from this work, urological cell lines were exposed to urine for up to 12 hours to determine the effect of urine on the ability to classify these cells. Results indicate that urine has no detrimental effect on prediction results. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Early Results of Photoselective Vaporization of the Prostate in Medical Control-failed PatientsLUTS, Issue 2 2009Shen Kuang CHANG Objectives: We present here our early results and learning curve for photoselective vaporization of the prostate (PVP) performed by an experienced urologist and we provide an analysis of the morbidity and early functional outcomes. Methods: Forty-four patients were selected, from May 2006 to January 2009, who had benign prostate hyperplasia (BPH) accompanied by lower urinary tract symptoms (LUTS). After undergoing PVP for BPH at our hospital, the patients were followed up for approximately 2 years. PVP was performed by the same experienced urologist using potassium-titanyl-phosphate (KTP) laser. Baseline characteristics, preoperative and perioperative data, and postoperative complications were evaluated. Regular outpatient department follow-up was conducted after patients were discharged from the hospital at 1, 4 and 12 weeks. Results: The mean age of the 44 patients was 71.6 years. The mean prostate volume was 47.52 mL. The mean PVP surgery time was 79.11 min. The mean urinary catheterization time was 23.41 h. Few complications arose after PVP, except that 47.7% of the patients developed pyuria after being discharged from hospital. The average hospital stay was 2.45 days. There were no significant differences in the efficiency of tissue vaporization among the patients. Conclusion: PVP for BPH has various advantages, including reducing postoperative complications. An experienced urologist can easily perform PVP. However, early results show no significant differences in the efficiency for the PVP technique. [source] A critical review of the pharmacology of the plant extract of Pygeum africanum in the treatment of LUTS,NEUROUROLOGY AND URODYNAMICS, Issue 4 2007Alan D. Edgar Abstract Despite an unremitting increase in the number of patients presenting symptoms of benign prostate hyperplasia (BPH), the viable treatment options remain relatively limited when compared to other disorders of aging. This has spurred an interest in so-called alternative medicines, many of which continue to be used in spite of the more recent emergence of rationally targeted therapies. Nonetheless, in the case of plant extracts, the vast majority of these have not been subjected to the same rigorous pre-clinical pharmacological testing and large-scale clinical trials now required by health authorities. Furthermore, demonstration of their clinical efficacy in BPH has been hindered by trials of limited duration with a high placebo response. Beginning with a preliminary demonstration of in vitro inhibition of growth factor-mediated fibroblast proliferation with Pygeum africanum extract, a detailed series of in vitro and in vivo studies on prostate growth and bladder function were undertaken. These studies, reviewed herein, have permitted the identification of putative molecular targets of Pygeum africanum extract affecting both growth factor-mediated prostate growth as well as specific parameters of bladder function. These results, corroborated in part by short-term clinical efficacy, set the stage for a large-scale clinical trial to investigate the efficacy of Pygeum africanum extract in the treatment of lower urinary tract symptoms. Neurourol. Urodynam. 26:458,463, 2007. © 2007 Wiley-Liss, Inc. [source] Comparison of the Effect of the Aromatase Inhibitor, Anastrazole, to the Antioestrogen, Tamoxifen Citrate, on Canine Prostate and SemenREPRODUCTION IN DOMESTIC ANIMALS, Issue 2009G Gonzalez Contents This study compared the efficiency of the aromatase inhibitor, anastrazole, with the antioestrogenic receptor blocker, tamoxifen, on normal (NRL) and hyperplastic prostate glands. Forty healthy dogs were classified as NRL (n = 18) or abnormal (ABN) with benign prostate hyperplasia (n = 22). The dogs were randomly assigned to one of the following six groups, treated for 60 days; oral placebo for normal (NRL-PLC; n = 6) and abnormal (ABN-PLC; n = 6), oral anastrazole 0.25,1 mg/day, for normal (NRL-ANZ, n = 6) and abnormal (ABN-ANZ, n = 8) and oral tamoxifen citrate 2.5,10 mg/day for normal (NRL-TMX; n = 6) and abnormal (ABN-TMX; n = 8) dogs. The dogs were evaluated before treatment and then monthly for 4 months. At the end of the treatment, the prostatic volume decreased by 28.5 ± 4.3%, 21.6 ± 6.3% and 0.7 ± 1.0% in the ABN-TMX, ABN-ANZ and ABN-PLC (p < 0.01), respectively. From then on, prostatic volume began to increase without reaching pre-treatment values at the end of the study. In the ABN animals, there were no differences for this parameter between ANZ and TMX treatment (p > 0.1), whereas in the NRL animals ANZ produced a less pronounced decrease (p < 0.05), libido, testicular consistency and scrotal diameter decreased during treatment in the TMX group (p > 0.05). These parameters and sperm volume, count, motility and morphological abnormalities remained unaltered throughout the study in the ANZ and PLC groups (p > 0.05). There were no haematological nor biochemical side effects. Anastrazole might offer a safe and effective alternative for the medical management of dogs with benign prostatic hyperplasia. [source] Monocyte chemotactic protein-1 (MCP-1/CCL2) is associated with prostatic growth dysregulation and benign prostatic hyperplasiaTHE PROSTATE, Issue 5 2010Kazutoshi Fujita Abstract BACKGROUND Chronic inflammation is commonly observed in benign prostate hyperplasia (BPH), and prostate tissue often contains increased inflammatory infiltrates, including T cells and macrophages. Cytokines are not only key mediators of inflammation but may also play important roles in the initiation and progression of BPH. METHODS In order to determine what cytokines might be involved in prostatic enlargement, expressed prostatic secretions (EPS) from ex vivo prostates were analyzed by human cytokine antibody microarray and ELISA. Prostate epithelial cells (PrEC) and prostate stromal cells (PrSC) were used for ELISA, proliferation, and Western blot assays. RESULTS Monocyte chemotactic protein-1 (MCP-1/CCL2) was one of the most elevated proteins in secretions from large prostate glands. PrSC were found to secrete MCP-1; Western blotting showed that both PrSC and PrEC express the MCP-1 receptor CCR2 which by RT-PCR was the CCR2b isoform. Proliferation assays showed that MCP-1 stimulates the proliferation of PrEC, but not PrSC, and that a specific MCP-1 antagonist (RS102895) suppressed this effect. Conditioned medium from PrSC stimulated the proliferation of PrEC as well, an effect completely inhibited by both RS102895 and a neutralizing anti-MCP-1 monoclonal antibody. The inflammatory cytokines interleukin (IL)-1,, interferon-,, and IL-2 enhanced the secretion of MCP-1 from PrEC and PrSC. In addition, MCP-1 levels in EPS correlated with mRNA levels of the macrophage marker CD68 in the same secretions. CONCLUSIONS The cytokine MCP-1, of apparent prostatic stromal cell origin, may play an important role in prostatic enlargement and BPH, and is a candidate biomarker for these pathologic processes. Prostate 70: 473,481, 2010. © 2009 Wiley-Liss, Inc. [source] Quantitative RT-PCR analysis of estrogen receptor gene expression in laser microdissected prostate cancer tissueTHE PROSTATE, Issue 8 2009Thomas J. Walton Abstract BACKGROUND Real-time quantitative RT-PCR analysis of laser microdissected tissue is considered the most accurate technique for determining tissue gene expression. The discovery of estrogen receptor beta (ER,) has focussed renewed interest on the role of estrogen receptors in prostate cancer, yet few studies have utilized the technique to analyze estrogen receptor gene expression in prostate cancer. METHODS Fresh tissue was obtained from 11 radical prostatectomy specimens and from 6 patients with benign prostate hyperplasia. Pure populations of benign and malignant prostate epithelium were laser microdissected, followed by RNA isolation and electrophoresis. Quantitative RT-PCR was performed using primers for androgen receptor (AR), estrogen receptor beta (ER,), estrogen receptor alpha (ER,), progesterone receptor (PGR) and prostate specific antigen (PSA), with normalization to two housekeeping genes. Differences in gene expression were analyzed using the Mann,Whitney U -test. Correlation coefficients were analyzed using Spearman's test. RESULTS Significant positive correlations were seen when AR and AR-dependent PSA, and ER, and ER,-dependent PGR were compared, indicating a representative population of RNA transcripts. ER, gene expression was significantly over-expressed in the cancer group compared with benign controls (P,<,0.01). In contrast, PGR expression was significantly down-regulated in the cancer group (P,<,0.05). There were no significant differences in AR, ER, or PSA expression between the groups. This study represents the first to show an upregulation of ER, gene expression in laser microdissected prostate cancer specimens. CONCLUSIONS In concert with recent studies the findings suggest differential production of ER, splice variants, which may play important roles in the genesis of prostate cancer. Prostate 69: 810,819, 2009. © 2009 Wiley-Liss, Inc. [source] cGMP-enhancing- and ,1A/,1D -adrenoceptor blockade-derived inhibition of Rho-kinase by KMUP-1 provides optimal prostate relaxation and epithelial cell anti-proliferation efficacyTHE PROSTATE, Issue 13 2007Chi-Ming Liu Abstract Background Soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) and Rho kinase (ROCK2) pathways are important in the regulation of prostate smooth muscle tone. This study is aimed to examine the relaxation activities of a sGC activator and PDE5A/ROCK2 inhibitor KMUP-1 in rat prostate and associated anti-proliferation activity in human prostatic epithelial cells. Methods The action characteristics of KMUP-1 were identified by isometric tension measurement, receptor binding assay, Western blotting and radioimmunoassay in rat prostate. Anti-proliferation activity of KMUP-1 in human prostatic epithelial PZ-HPV-7 cells was identified using flow cytometry and real time QRT-PCR. Results KMUP-1 inhibited phenylephrine-induced contractility in a concentration-dependent manner. KMUP-1 possessed potent ,1A/,1D -adrenoceptor binding inhibition activity, increased cAMP/cGMP levels and increased the expression of sGC, PKG, and PKA protein in rat prostate. Moreover, KMUP-1 inhibited phenylephrine-induced ROCK2 expression. KMUP-1 inhibited cell growth, arrested the cell cycle at G0/G1 phase and increased the expression of p21 in PZ-HPV-7 cells. Conclusions These results broaden our knowledge of sGC/cGMP/PKG and ROCK2 regulation on the relaxation and proliferation of prostate, which may help in the design of benign prostate hyperplasia (BPH) therapies that target these signaling pathways. KMUP-1 possesses the potential benefit in the treatment of BPH by its ,1A/,1D -adrenoceptor blockade, sGC activation, inhibition of PDE5A and ROCK2 and p21 protein enhancement, leading to attenuation of the smooth muscle tone and the proliferation of epithelial PZ-HPV-7 cells. The synergistic contribution of these pathways by KMUP-1 may benefit BPH patients with lower urinary tract symptoms. Prostate 67: 1397,1410, 2007. © 2007 Wiley-Liss, Inc. [source] Reversal of benign prostate hyperplasia by selective occlusion of impaired venous drainage in the male reproductive system: novel mechanism, new treatmentANDROLOGIA, Issue 5 2008Y. Gat Summary The prostate is an androgen-regulated exocrine gland producing over 30% of the noncellular components of the semen and promoting optimal conditions for survival and motility of sperm in the vagina. Benign prostate hyperplasia (BPH) is the most common benign neoplasm in men. Its aetiology is not clear, and therefore, current medical treatments are directed towards the symptoms. Though testosterone is known to be the promoter of prostate cell proliferation, no causal relation between serum testosterone levels and BPH has been found. In this study, we propose a novel and tested pathophysiological mechanism for the evolution of BPH and suggest a tested and effective treatment. We found that in all BPH patients, the one-way valves in the vertically oriented internal spermatic veins are destroyed (clinically manifested as varicocele), causing elevated hydrostatic pressure, some 6-fold greater than normal, in the venous drainage of the male reproductive system. The elevated pressure propagates to all interconnected vessels leading to a unique biological phenomenon: venous blood flows retrograde from the higher pressure in the testicular venous drainage system to the low pressure in the prostatic drainage system directly to the prostate (law of communicating vessels). We have found that free testosterone levels in this blood are markedly elevated, with a concentration of some 130-fold above serum level. Consequently, the prostate is exposed to: (i) increased venous pressure that causes hypertrophy; (ii) elevated concentration of free testosterone causing hyperplasia. We have treated 28 BPH patients using a technique that restores normal pressure in the venous drainage in the male reproductive system. The back-pressure and the back-flow of blood from the testicular to the prostate drainage system were eliminated and, consequently, a rapid reduction in prostate volume and a regression of prostate symptoms took place. [source] Safety aspects of androgen treatment with 5,-dihydrotestosteroneANDROLOGIA, Issue 6 2007S. Sakhri Summary 5,-Dihydrotestosterone (DHT), the most powerful naturally occurring androgen, is commercially available since 1982 as a gel. In view of its considerably higher biopotency (three to six times) than of testosterone, side effects, particularly on the main target organ of androgens, the prostate, are anticipated. In fact, DHT appears to be a prostate-sparing androgen for two reasons. Unlike testosterone, it does not undergo any further amplification in biopotency through 5, reduction in the prostate. Secondly, it is likely to lead to less aromatisation of testosterone to oestradiol in the prostate, thus reducing local oestradiol concentrations. Oestrogens have been implicated in the aetiology of benign prostate hyperplasia and prostate cancer. However, aromatisation of testosterone has appeared to be essential for the maintenance of bone mineral density. Administration of DHT reduces circulating oestradiol levels, but the levels remain above the levels critical for the antiresorptive effect of oestrogens on bone. Effects of DHT on erythropoiesis and on lipids are very similar to those of testosterone. Safety concerns regarding androgen treatment with DHT are similar to those of treatment with testosterone, while the effects of DHT on the prostate are likely to be less biopotent. [source] | ||||||||||||||||||||||