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The sterile inflammation (SI) of the urinary tract is a common problem requiring serious consideration after prostatectomy. This study mainly focuses on the role of the reactive oxygen species-NLR family, pyrin domain-containing 3 (ROS-NLRP3) signaling pathway in SI after thulium laser resection of the prostate (TmLRP). Urinary cytokines were determined in patients who received TmLRP, and heat shock protein 70 (HSP70) was detected in the resected tissues. The involvement of ROS signaling in HSP70-induced inflammation was explored in THP-1 cells with or without N-acetyl- l-cysteine (NAC) pretreatment. The function of NLRP3 and Caspase-1 was determined by Western blot analysis, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction. These phenomena and mechanisms were verified by the beagle models that received TmLRP. Clinical urine samples after TmLRP showed high expression of inflammatory factors and peaked 3-5 days after surgery. The high expression of HSP70 in the resected tissues was observed. After HSP70 stimulation, the expression of ROS, NLRP3, Caspase-1, and interleukin-18 (IL-18) increased significantly and could be reduced by ROS inhibitor NAC. The expression of IL-1β and IL-18 could be inhibited by NLRP3 or Caspase-1 inhibitors. In beagle models that received TmLRP, HSP70, NLRP3, Caspase-1, IL-1β, and IL-18 were highly expressed in the wound tissue or urine, and could also be reduced by NAC pretreatment. Activation of the ROS-NLRP3 signaling pathway induces SI in the wound after prostatectomy. Inhibition of this pathway may be effective for clinical prevention and treatment of SI and related complications after prostatectomy., (© 2022 Wiley Periodicals LLC.)

Objective: The present study aimed to investigate the effects of an imbalance in the estrogen/androgen ratio on prostate fibrosis., Methods: Different concentrations of dihydrotestosterone (DHT) or estradiol (E 2 ) dissolved in corn oil were injected subcutaneously into the nape of the castrated Sprague-Dawley (SD) rats over 28 consecutive days. Masson's trichrome staining and immunohistochemical staining were performed to detect the content of collagen fibers and the expression of collagen I, fibronectin, and elastin in the rat prostate of each group, respectively. DHT + E 2 at different concentrations was administered to human normal prostate stromal immortalized cells (WPMY-1 cells) for 1 week. The expression of collagen I, fibronectin, elastin, transforming growth factor-β 1 (TGF-β 1 ), Smad3, and Smad7 was detected by Western blotting (WB). Then, WPMY-1 cells treated with 10 nM DHT + 5 pM E 2 were incubated with the TGF-β/Smad pathway inhibitor SD208 for 1 week, after which collagen I, fibronectin, and elastin expression was detected by WB., Results: Compared with the uncastrated control and corn oil injection groups, the collagen fiber content and collagen I and fibronectin expression were increased and elastin expression was decreased in the castrated rat prostate with corn oil injection group (p < 0.01). Compared to castrated corn oil injection group, collagen fiber content, collagen I, and fibronectin expression were significantly decreased, and elastin expression was significantly increased in the castrated rat prostate 0.15 mg/kg DHT treatment group (p < 0.01). Following treatment with 0.15 mg/kg DHT, the content of collagen fibers, and the expression of collagen I and fibronectin were increased, and the expression of elastin was decreased in the rat prostate with increasing concentrations of E 2 treatment group compared to the 0.15 mg/kg DHT group (p < 0.05, p < 0.01). Following treatment with 0.05 mg/kg E 2 , the collagen fiber content and the expression of collagen I and fibronectin were decreased, and the expression of elastin was increased in the rat prostate with increasing DHT concentration treatment group compared to the 0.05 mg/kg E 2 group (p < 0.05, p < 0.01). Compared with the Control group, the expression of collagen I, fibronectin, TGF-β 1 and Smad3 was decreased, and the expression of elastin and Smad7 was increased in WPMY-1 cells after treatment with 10 nM DHT (p < 0.01). Following treatment with 10 nM DHT, the expression of collagen I, fibronectin, TGF-β 1 , and Smad3 was increased, and the expression of elastin and Smad7 was decreased in WPMY-1 cells with increasing E 2 concentration treatment compared to the 10 nM DHT group (p < 0.05, p < 0.01). Following treatment with 5 pM E 2 , the expression of collagen I, fibronectin, TGF-β 1 , and Smad3 was decreased, and elastin and Smad7 expression was increased with increasing DHT concentration compared to the 5 pM E 2 group (p < 0.05, p < 0.01). Compared to the 10 nM DHT + 5 pM E 2 group, the expressions of collagen I and fibronectin were decreased; the expression of elastin was increased in WPMY-1 cells after the supplement of TGF-β/Smad pathway inhibitor SD208 group (p < 0.05, p < 0.01)., Conclusions: An imbalance in the estrogen/androgen ratio may affect prostate fibrosis. E 2 may activate the degree of prostate fibrosis. In contrast to the effect of E 2 , DHT may inhibit the degree of prostate fibrosis, which might involve the TGF-β/Smad signaling pathway., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

We conducted the present study to assess the correlation of the prostatic anatomical parameters, especially the ratio of peripheral zone thickness and transitional zone thickness, with clinical and uroflowmetry characteristics suggestive of benign prostate hyperplasia (BPH). A total of 468 consecutive patients with a detailed medical history were identified. All patients were evaluated by scoring subjective symptoms with the International Prostate Symptom Score (IPSS) and quality of life (QoL). The prostatic anatomical parameters were measured using transrectal ultrasonography, and postvoid residual urine and maximum flow rate (Q max ) values were also determined. Pearson's correlation analysis revealed that both total prostate volume (TPV; r = 0.160, P < 0.001) and transitional zone volume (TZV; r = 0.104, P = 0.016) increased with patients' age; however, no correlations were observed of TPV, TZV, transitional zone index (TZI), and transitional zone thickness (TZT) with IPSS or QoL (all P >0.05). Peripheral to transitional zone index (PTI) was found negatively correlated with total IPSS (r = -0.113, P = 0.024), storage IPSS (r = -0.103, P = 0.041), and voiding IPSS (r = -0.123, P = 0.014). As regards the uroflowmetry characteristics, PTI (r = 0.157, P = 0.007) was indicated to be positively correlated with Q max and negatively correlated with TZI (r = -0.119, P = 0.042) and TZT (r = -0.118, P = 0.045), but not correlated with TPV, TZV, or peripheral zone thickness (PZT) (all P > 0.05). Postvoid residual urine (PVR) had not correlated with all the prostatic anatomical variables (all P > 0.05). This is the first study that formally proposed the concept of PTI, which is an easy-to-measure prostate anatomical parameter which significantly correlates with total IPSS, storage IPSS, voiding IPSS, and Q max , suggesting that PTI would be useful in evaluating and managing men with lower urinary tract symptoms (LUTS)/BPH. However, well-designed studies are mandatory to verify the clinical utility of PTI., Competing Interests: None

This study compared the diagnostic efficacy of transrectal ultrasound (TRUS)-guided prostate biopsy (TRBx) and transperineal prostate biopsy (TPBx) in patients with suspected prostate cancer (PCa). We enrolled 2962 men who underwent transrectal (n = 1216) or transperineal (n = 1746) systematic 12-core prostate biopsy. Clinical data including age, prostate-specific antigen (PSA) level, and prostate volume (PV) were recorded. To minimize confounding, we performed propensity score-matching analysis. We measured and compared PCa detection rates between TRBx and TPBx, which were stratified by clinical characteristics and Gleason scores. The effects of clinical characteristics on PCa detection rate were assessed by logistic regression. For all patients, TPBx detected a higher proportion of clinically significant PCa (P < 0.001). Logistic regression analyses illustrated that PV had a smaller impact on PCa detection rate of TPBx compared with TRBx. Propensity score-matching analysis showed that the detection rates in TRBx were higher than those in TPBx for patients aged >- 80 years (80.4% vs 56.5%, P = 0.004) and with PSA level 20.1-100.0 ng ml -1 (80.8% vs 69.1%, P = 0.040). In conclusion, TPBx was associated with a higher detection rate of clinically significant PCa than TRBx was; however, because of the high detection rate at certain ages and PSA levels, biopsy approaches should be optimized according to patents' clinical characteristics., Competing Interests: None

Background: This study investigated shallow heat injury to prostate stromal fibroblasts and epithelial cells and their interaction to regulate the wound healing and the underlying molecular events., Methods: Prostate stromal fibroblasts and epithelial cells were cultured individually or cocultured and subjected to shallow heat injury for assessments of cell proliferation, migration, apoptosis, cell cycle distribution, and gene expression. The supernatant of heat-injured WPMY-1 cells was collected for exosome extraction and assessments. Furthermore, beagle dogs received thulium laser resection of the prostate (TmLRP) and randomly divided into Gefitinib, GW4869, and control treatment for the histological analysis, tissue re-epithelialization, and epidermal growth factor receptor (EGFR) expression on the prostatic wound surface. Immunofluorescence was to evaluate p63-positive basal progenitor cell trans-differentiation and macrophage polarization and ELISA was to detect cytokine levels in beagles' urine., Results: Shallow heat injury caused these cells to enter a stressed state and enhanced their crosstalk. The prostate stromal fibroblasts produced and secreted more exosomal-EGFR and other cytokines and chemokines after shallow heat injury, resulting in increased proliferation and migration of prostate epithelial cells during wound healing. The wound healing of the canine prostatic urethra following the TmLRP procedure was slower in the Gefitinib and GW4869 treatment group than in the control group of animals. Immunofluorescence and ELISA showed that reduced EGFR expression interrupted macrophage polarization but increased the inflammatory response., Conclusions: Shallow heat injury was able to promote the interaction of prostate stromal cells with prostate epithelial cells to enhance wound healing. Stromal-derived exosomal-EGFR plays a crucial role in the balance of the macrophage polarization and prostatic wound healing., (© 2019 Wiley Periodicals, Inc.)

Objectives: 5α-reductase inhibitor (5-ARI) is a commonly used medicine in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Our study mainly focuses on the mechanism of BPH development after 5ARI treatment., Materials and Methods: Prostate specimens from patients were collected. Insulin-like growth factor 1 (IGF-1), Beclin-1, LC3 levels, was analysed by immunohistochemistry. The role IGF-1 on autophagic flux in prostate epithelial cells was studied. Additionally, effect of autophagy on recombinant grafts consisting of prostate stromal and epithelial cells in nude mice was investigated., Results: We demonstrated that IGF-1 expression is down-regulated in prostate fibroblasts after long-term 5-ARI application. A decrease in IGF-1 levels was found to activate autophagic flux through the mTOR pathway in prostate epithelial cells, while the inhibition of IGF-1 receptor function induced autophagy in prostate epithelial cells. In addition, we revealed that blocking autophagic flux initiation can reduce the volume of recombinant grafts in vivo. Finally, our findings suggest that long-term 5-ARI application reduces IGF-1 secretion by prostatic stromal cells, thereby inducing autophagy of prostatic epithelial cells, which is one of the mechanisms underlying BPH pathogenesis and progression., Conclusions: Focusing on the autophagy induced by low levels of IGF-1 in prostatic epithelial cells, after elucidating AR signalling impairment of prostate stromal cells, might provide a novel strategy for the treatment and prevention of BPH development., (© 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

Thulium laser resection of the prostate (TmLRP), a major treatment for benign prostatic hyperplasia (BPH), has several postoperative complications that affect the patients' quality of life. The aim of this study was to investigate the effect of the M1 macrophage-secreted reactive oxygen species (ROS) on prostatic wound healing, and the role of MAPK signaling in this process. A co-culture model in vitro was established using macrophages and prostate epithelial or stromal cells. Cell proliferation, migration, apoptosis, MAPK pathway-related gene expression levels were evaluated by standard assays. In addition, an in vivo model of prostatectomy was established in beagles by subjecting them to TmLRP, and were either treated with N-acetyl-L-cysteine (NAC) and or placebo. Wound healing and re-epithelialization were analyzed histopathologically in both groups, in addition to macrophage polarization, oxidative stress levels and MAPK pathway-related proteins expressions. Intracellular ROS levels were significantly increased in the prostate epithelial and stromal cells following co-culture with M1-like macrophages and H 2 O 2 exposure via MAPK activation, which affected their proliferation, migration and apoptosis, and delayed the wound healing process. The cellular functions and wound healing capacity of the prostate cells were restored by blocking or clearing the macrophage-secreted ROS. In the beagle model, increased ROS levels impaired cellular functions, and appropriate removing ROS accelerated the wound healing process., (Copyright © 2019. Published by Elsevier Inc.)

Background: Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra., Methods: Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated., Results: The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened., Conclusion: Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate 77:708-717, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Often, pathological Gleason Score (GS) and stage of prostate cancer (PCa) were inconsistent with biopsy GS and clinical stage. However, there were no widely accepted methods predicting upgrading and upstaging PCa. In our study, we investigated the association between serum testosterone and upgrading or upstaging of PCa after radical prostatectomy (RP). We enrolled 167 patients with PCa with biopsy GS ≤6, clinical stage ≤T2c, and prostate-specific antigen (PSA) <10 ng ml-1 from April 2009 to April 2015. Data including age, body mass index, preoperative PSA level, comorbidity, clinical presentation, and preoperative serum total testosterone level were collected. Upgrading occurred in 62 (37.1%) patients, and upstaging occurred in 73 (43.7%) patients. Preoperative testosterone was lower in the upgrading than nonupgrading group (3.72 vs 4.56, P< 0.01). Patients in the upstaging group had lower preoperative testosterone than those in the nonupstaging group (3.84 vs 4.57, P= 0.01). In multivariate logistic regression analysis, as both continuous and categorical variables, low serum testosterone was confirmed to be an independent predictor of pathological upgrading (P = 0.01 and P= 0.01) and upstaging (P = 0.01 and P = 0.02) after RP. We suggest that low serum testosterone (<3 ng ml-1 ) is associated with a high rate of upgrading and upstaging after RP. It is better for surgeons to ensure close monitoring of PSA levels and imaging examination when selecting non-RP treatment, to be cautious in proceeding with nerve-sparing surgery, and to be enthusiastic in performing extended lymph node dissection when selecting RP treatment for patients with low serum testosterone.

The purpose of this study is to characterize the re-epithelialization of wound healing in canine prostatic urethra and to evaluate the effect of this re-epithelialization way after two-micron laser resection of the prostate (TmLRP). TmLRP and partial bladder neck mucosa were performed in 15 healthy adult male crossbred canines. Wound specimens were harvested at 3 days, and 1, 2, 3, and 4 weeks after operation, respectively. The histopathologic characteristics were observed by hematoxylin and eosin staining. The expression of cytokeratin 14 (CK14), CK5, CK18, synaptophysin (Syn), chromogranin A (CgA), uroplakin, transforming growth factor-β1 (TGF-β1 ), and TGF-β type II receptor in prostatic urethra wound were examined by immunohistochemistry and real-time polymerase chain reaction, respectively. Van Gieson staining was performed to determine the expression of collagen fibers in prostatic urethra and bladder neck would. The results showed that the re-epithelialization of the prostatic urethra resulted from the mobilization of proliferating epithelial cells from residual prostate tissue under the wound. The proliferating cells expressed CK14, CK5, but not CK18, Syn, and CgA and re-epithelialize expressed uroplakin since 3 weeks. There were enhanced TGF-β1 and TGF-β type II receptor expression in proliferating cells and regenerated cells, which correlated with specific phases of re-epithelialization. Compared with the re-epithelialization of the bladder neck, re-epithelialization of canine prostatic urethra was faster, and the expression of collagen fibers was relatively low. In conclusion, re-epithelialization in canine prostatic urethra resulted from prostate basal cells after TmLRP and this re-epithelialization way may represent the ideal healing method from anatomic repair to functional recovery after injury.

Thulium laser resection of the prostate-tangerine technique (TmLRP-TT) dissects whole prostatic lobes off the surgical capsule, similar to peeling a tangerine. The present study aimed to evaluate the safety and efficacy of TmLRP-TT for older symptomatic benign prostatic hyperplasia patients with large prostates during 18 months of follow-up. A prospective analysis of 95 consecutive patients with large prostates (>80 ml) who underwent surgical treatment using TmLRP-TT was carried out. All patients were evaluated preoperatively and at 1, 6, 12, and 18 months postoperatively by the International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Q max), postvoid residual urine volume (PVR), International Index of Erectile Function 5 (IIEF-5), urine analysis, and urine culture. Perioperative complications were recorded and graded by the modified Clavien classification system (CCS). Mean preoperative prostate volume was 106.81 ± 24.79 ml. TmLRP-TT was successfully completed in all patients. The mean operative duration, catheterization time, and hospital stay were 95.36 ± 27.06 min, 2.25 ± 0.9 days, and 5.39 ± 1.18 days, respectively. The decrease in mean hemoglobin level was 1.23 ± 0.72 g/dl, and that in mean serum sodium level was 0.71 ± 2.56 mmol/l. Within the observation period of 18 months, the patients showed an improvement in IPSS (20.01 ± 7.08 vs. 4.96 ± 3.68), QoL (4.10 ± 1.16 vs. 1.23 ± 1.30), Q max (8.14 ± 3.81 ml/s vs. 18.33 ± 2.56 ml/s) and PVR (102.70 ± 70.64 ml vs. 20.28 ± 30.02 ml), compared with baseline values (P < 0.001). IIEF-5 remained stable. Minor complications occurred in 10 (10.52 %) of 95 patients (Clavien grade 1, 9.47 % and grade 2, 1.05 %). There were no severe complications requiring reintervention (Clavien grade 3, 0 % and grade 4, 0 %). TmLRP-TT is a safe and effective surgical endoscopic technique associated with a low complication rate in large prostates as assessed during an 18-month follow-up period. It is a promising technology, which may be considered as one of the alternatives to open simple prostatectomy (OP) for large prostates in the future.

Aging is a major risk factor for prostate cancer (PCa), and prostatic stromal cells may also promote PCa progression. Accordingly, stromal cells do not equally promote PCa in older males and younger males. Therefore, it is also possible that the expression of androgen receptors (ARs) by prostatic stromal cells in older versus younger males plays different roles in PCa progression. Using a gene knockdown technique and coculture system, we found that the knockdown of the AR in prostatic stromal cells obtained from younger males could promote the invasiveness and metastasis of cocultured PC3/LNCaP cells in vitro. By contrast, the invasiveness and metastasis of LNCaP cells was inhibited when cocultured with prostatic stromal cells from older males that when AR expression was knocked down. Moreover, after targeting AR expression with small hairpin RNA (shRNA), matrix metalloproteinase (MMP) expression in stromal cells was observed to increase in the younger group, but decreased or remained unchanged in the older group. One exception, however, was observed with MMP9. In vivo, after knocking down AR expression in prostatic stromal cells, the incidence of metastatic lymph nodes was observed to increase in the younger age group, but decreased in the older age group. Together, these data suggest that the AR in prostatic stromal cells played opposite roles in PCa metastasis for older versus younger males. Therefore, collectively, the function of the AR in prostatic stromal cells appears to change with age, and this may account for the increased incidence of PCa in older males.

Objective: To study the gene expressions in the stromal cells of the human prostate peripheral zone (PZ) in men of different ages., Methods: We primarily cultured stromal cells from the normal prostate PZ of men aged 23 -32 (young group) and 56 -75 years (old group), profiled the gene signature of the PZ cells by cDNA microarray, and defined the differential gene expression patterns by hierarchical cluster analysis. Among the differential genes, we selected and confirmed up-regulated genes by quantitative real time PCR (Q-PCR), and identified their protein coding by Western blotting., Results: There were significant differences in the gene expressions of the PZ cells between the old and young groups. Based on the fold change ratio of > or = 2 or < or = 0.5, 509 up-regulated and 188 down-regulated genes were selected in the PZ cells. A subset of significantly differential genes influencing the growth of adjacent epithelial cells were identified, including HGF, IGF2, IGFBP5 and MMP1 in the old males., Conclusion: Stromal cells in the prostate PZ were more active in older males in promoting the malignant progression of adjacent prostate epithelial cells, which might be due to the increased expression of extracellular paracrining mediators.

This study was designed to investigate the association between immune inflammation and androgen receptor (AR) expression in benign prostatic hyperplasia (BPH). We retrospectively analyzed 105 prostatectomy specimens. An immune inflammation score for each specimen was defined by combining three immunohistochemical markers (CD4, CD8 and CD20). The immunohistochemical markers were CD4 and CD8 for T lymphocytes, CD20 for B lymphocytes and AR antibody for the AR in BPH samples. Rates of CD4, CD8, CD20 and AR expression in BPH were 20 (19.0%), 21 (20.0%), 101 (96.2%) and 48 (45.7%), respectively. Total prostate volume (TPV) was higher in the immune inflammation group than in the non-immune inflammation group (62.7 ml vs. 49.2 ml, t=2.482, P<0.05). Patients in the immune inflammation group had a higher serum prostate-specific antigen (PSA) than those in the non-inflammation group (7.5 ng ml(-1 )vs. 5.4 ng ml(-1), t=2.771, P<0.05). Specifically, the immune inflammation group showed a higher rate of AR expression than the non-inflammation group (56.1% vs. 28.2%, χ(2)=7.665, P<0.05). Our study revealed a strong association between immune inflammation and TPV, serum PSA and AR expression in BPH tissue. Prostate hyperplasia caused by an immune inflammatory process may contribute to BPH progression over time. Therefore, the inflammatory response involved in BPH may be a prime therapeutic target.

It is well known that prostate cancer (PCa) occurs predominantly in the peripheral zone (PZ), whereas benign prostatic hyperplasia (BPH) typically develops in the transition zone. To identify possible mechanisms underlying zonal differences, we compared the effects of prostate stromal cells derived from the peripheral zone (PZsc) and the transition zone (TZsc) on a PCa epithelial cell line (PC3) in the presence of sex hormones. First, we observed that androgen receptor (AR) mRNA was more highly expressed in PZsc than TZsc when the cells were treated with dihydrotestosterone (DHT) and β-oestradiol (E2) (P<0.05). By ELISA, we looked for differences in the secretion of peptide growth factors from PZsc and TZsc. We found that keratinocyte growth factor (KGF) secretion increased with increasing concentrations of DHT (P<0.01) and was higher in PZsc than TZsc. Under treatment with DHT plus E2, PZsc secreted more transforming growth factor-β1 (TGF-β1) than TZsc, but this pattern was reversed when the cells were treated with E2 only. With increasing concentrations of DHT, insulin-like growth factor-1 (IGF-1) secretion increased in PZsc but decreased in TZsc. To further characterize the effects of PZsc and TZsc on PC3 cells, we developed a coculture model and performed MTT assays, Western blot analysis and real-time RT-PCR. We found that PZsc promoted PC3 cell proliferation and progression better than TZsc, particularly when treated with 10 nmol l(-1) DHT plus 10 nmol l(-1) E2. In conclusion, our data suggest that PZsc may have a greater capacity to induce PCa development and progression than TZsc via growth factors regulated by sex hormones. These findings provide possible mechanisms underlying zonal differences in prostate diseases, which may aid the search for novel therapeutic targets for PCa.

Prostate cancer (PCa) is an age-related disease, and the stromal microenvironment plays an important role in prostatic malignant progression. However, the differences in prostate stromal cells present in young and old tissue are still obscure. We established primary cultured stromal cells from normal prostatic peripheral zone (PZ) of donors of varying ages and found that cultured stromal cells from old donors (PZ-old) were more enlarged and polygonal than those from young donors (PZ-young). Furthermore, based on immunocytochemical and ultrastructural analysis, the components of stromal cells changed from a majority of fibroblasts to a mixture of fibroblasts and myofibroblasts with increasing donor age. Using a three-dimensional in vitro culture system, we found that PZ-old stromal cells could enhance the proliferation, migration and invasion of cocultured benign BPH-1 and PC-3 cells. Using an in vivo tissue recombination system, we also found that PZ-old stromal cells are more effective than PZ-young cells in promoting tumour formation by BPH-1 cells of high passage (>100) and PC-3 cells. To probe the possible mechanism of these effects, we performed cDNA microarray analysis and profiled 509 upregulated genes and 188 downregulated genes in PZ-old cells. Among the changed genes, we found genes coding for a subset of paracrine factors that are capable of influencing adjacent epithelial cells; these include hepatocyte growth factor (HGF), fibroblast growth factor 5 (FGF5), insulin-like growth factor 2 (IGF2), insulin-like growth factor-binding protein 4 (IGFBP4), IGFBP5 and matrix metallopeptidase 1 (MMP1). Changes in the expression of these genes were further confirmed by quantitative real-time polymerase chain reaction (PCR), Western blotting and enzyme-linked immunosorbent assays. Overall, our findings indicate that stromal cells from prostate PZ of old donors are more active than similar cells from young donors in promoting the malignant process of adjacent epithelial cells. This finding hints at a new potential strategy for the prevention of PCa.

The purpose of the current ex vivo study was to compare the speed of vaporesection of human prostatic tissue with benign prostatic hyperplasia (BPH) and the depth of tissue damage using 70- and 120-W 2-µm laser devices. Fresh prostatic tissue specimens were obtained from five patients by open prostatectomy, and were divided into separate groups (70 and 120 W) based on the energy of the laser output (70 and 120 W, respectively). The vaporesection speed, coagulation zone depth and the necrotic tissue layer in the prostatic tissue were evaluated. The current result showed that the speeds (mean±s.d.) of vaporesection were 5.21 ± 0.66 and 10.39 ± 1.15 g/5 min for the 70 and 120 W groups, respectively (P=0.000). There was no difference in the depth of necrosis/coagulation (0.98 ± 0.13/0.30 ± 0.09 and 0.99 ± 0.12/0.31 ± 0.08 mm) for the 70 and 120 W groups, respectively. In conclusion, both 70- and 120-W 2-µm laser devices had superficial tissue damage during the vaporesection of human prostate tissue; moreover, the 120-W laser offers a higher vaporesection speed than the 70-W laser.

Background: Prostate stromal cells are known to regulate epithelial growth as well as support and maintain epithelial function. However, how stromal cells regulate epithelial cells and what differences among various histological/pathological prostate stromal cells in prostate cancer progression still remain unclear. This study aimed to investigate the different phenotypes of human various histological/pathological prostate stromal cells, and their role in tumor promotion., Methods: The different phenotypes of the human normal prostatic peripheral zonal primary stromal cells (NPPF), transitional zonal primary stromal cells (NPTF), and prostate cancer associated primary stromal cells (CAF) were examined with growth curves and Annexin V-fluorescein isothiocyanate (FITC) assay. The different effects on prostate cancer cell line C4-2B by NPPF, NPTF, and CAF were examined with MTT assay and Annexin V-FITC assay. The gene expression of different histological/pathological prostate stromal cells was profiled by microarray and hierarchical cluster analysis., Results: The growth rate of NPPF, NPTF and CAF gradually increased, followed by decreasing apoptosis. In vitro stromal-C4-2B cell line co-culture models, the proliferation and apoptosis of C4-2B cell line were differently affected by human various histological/pathological prostate stromal cells. CAF showed the most powerful effect to C4-2B cell line, as opposed to a weakest effect of NPTF. Microarray and hierarchical cluster analysis showed that the differentially expressed genes of CAF and NPPF were less than NPPF and NPTF, or CAF and NPTF. This was consistent with clinical observations that prostate cancer mostly derived from the peripheral zone and does not usually occur in the transitional zone., Conclusion: NPPF, NPTF and CAF possess extremely different biological characteristics and gene expression, which may play an important role in genesis and development of prostate cancer.

Objective: To characterize age-related cellular phenotype alterations and growth rates of human prostatic stromal cell cultures from the normal prostatic peripheral zone of young donors (PZ-young) and old donors (PZ-old)., Methods: We isolated stromal cells from 10 donors of different ages, assessed the cellular phenotypes by immunocytostaining for prolyl-4-hydroxylase, alpha-smooth muscle actin (alpha-SMA) and desmin, and analysed the ultrastructure by transmission electron microscopy (TEM). The proliferation and apoptosis of the cells were determined by Cell Counting Kit-8 assay and flow cytometry, respectively., Results: All the stromal cells were positive for prolyl-4-hydroxylase regardless of the donors' age, while alpha-SMA and desmin positive cells increased with their age. The positive expressions of alpha-SMA and desmin were (2.56 +/- 1.81)% and (0.89 +/- 0.93)% in PZ-young, and (38.89 +/- 11.22)% and (14.89 +/- 5.97)% in PZ-old (P < 0.01). The alpha-SMA- and/or desmin-positive stromal cells were morphologically large, flat and polygonal. Ultrastructural analysis showed that the cell cultures from PZ-old were richer in rough endoplasmic reticulum and golgi complexes. The stromal cells of PZ-old had a lower growth rate than that of PZ-young (P < 0.01), but there was no significant difference in the apoptosis rate between the two groups., Conclusion: Cellular phenotypes of human prostate stromal cell cultures change with the increase of age from predominantly typical fibroblasts to a mixture of fibroblasts and myofibroblasts, which might responsible for the high incidence of prostate cancer in elderly men.

Objective: To study the different proportions of intermediate epithelial cells in human prostate cancer tissue and their clinical significance., Methods: We performed immunohistochemical staining for Cytokeratin 5 (CK5) and Cytokeratin 8 (CK8) on 60 samples of human prostate cancer, determined the proportions of intermediate epithelial cells in the cancer tissue, and classified the samples into 2 types, one with a majority of intermediate epithelial cells (CaP-INT, n = 32), and the other composed mostly of luminal epithelial cells (CaP-LUM, n = 28). Then we compared the 2 types of prostate cancer in the expression of the androgen receptor (AR), age of the patient, serum t-PSA, prostate volume, Gleason score, clinical stage, androgen resistance, and incidence of distant metastasis., Results: CaP-INT showed a significantly lower expression of AR ([24.42 +/- 11.41] %) and a higher incidence of distant metastasis (n = 14) than CaP-LUM ([77.21 +/- 10.22] % and n = 4) (P < 0.05). In the CaP-INT group, 6 of the 26 endocrinologically treated cases developed into androgen-independent prostate cancer (AIPC), while in the CaP-LUM group, only 1 out of 23 (P < 0.05). The former also showed remarkably higher clinical stages than the latter (P < 0.05), but no significant differences were found in age, serum t-PSA, prostate volume and Gleason score between the two groups (P > 0.05)., Conclusion: A higher proportion of intermediate epithelial cells may lead to increased invasiveness and metastasis of human prostate cancer.

This study was designed to investigate the different involvements of prostatic stromal cells from the normal transitional zone (TZ) or peripheral zone (PZ) in the carcinogenesis of prostate cancer (PCa) epithelial cells (PC-3) in vitro and in vivo co-culture models. Ultra-structures and gene expression profiles of primary cultures of human prostatic stromal cells from the normal TZ or PZ were analyzed by electron microscopy and microarray analysis. In vitro and in vivo co-culture models composed of normal TZ or PZ stromal cells and human PCa PC-3 cells were established. We assessed tumor growth and weight in the in vivo nude mice model. There are morphological and ultra-structural differences in stromal cells from TZ and PZ of the normal prostate. In all, 514 differentially expressed genes were selected by microarray analysis; 483 genes were more highly expressed in stromal cells from TZ and 31 were more highly expressed in those from PZ. Co-culture with PZ stromal cells and transforming growth factor-beta1 (TGF-beta1) increased the tumor growth of PC-3 cells in vitro and in vivo, as well as Bcl-2 expression. On the other hand, stromal cells of TZ suppressed PC-3 cell tumor growth in the mouse model. We conclude that ultra-structures and gene expression differ between the stromal cells from TZ or PZ of the normal prostate, and stroma-epithelium interactions from TZ or PZ might be responsible for the distinct zonal localization of prostate tumor formation.

Objective: To determine and compare the difference of cell apoptosis and proliferation in the transition and peripheral zones in the human prostate., Methods: Seventeen normal prostate glands from organ donors were sampled from normal men according to McNeal/s zonal anatomy, and 20 hyperplastic transition zones obtained from prostatectomy specimens of BPH patients. Cell proliferation and Bcl-2 expression were assessed by immunostaining using PCNA and anti-Bcl-2 antibodies, while apoptotic bodies were specifically stained using TUNEL. Bcl-2 mRNA expression was detected by RT-PCR., Results: In the normal epithelium, the rates of cell proliferation and apoptosis were markedly decreased in the transition zone as compared with the peripheral zone. The proliferation index was significantly increased in the hyperplastic transition zone in BPH, while the apoptosis index significantly decreased in comparison with the normal prostate. Bcl-2 was significantly greater in the normal transition epithelium than in the peripheral zone, and over-expressed in the hyperplastic transition zone. There was a significant negative correlation between the Bcl-2 expression and the apoptosis of the epithelial cells in the hyperplastic transition zone (r(s) = -0.867, P < 0.01)., Conclusion: The hyperplastic transition zone may result from both an increase of cell proliferation and a failure of cell apoptosis. Increased expression of Bcl-2 may participate in the BPH process by blocking cell apoptosis.

Objective: To investigate the relationship between cyclooxygenase-2 (COX-2) mRNA expression and the biological behaviors of prostate carcinoma (PCa)., Methods: The expression of COX-2 mRNA was detected by RT-PCR method in 32 samples of PCa and the COX-2/GAPDH value was determined. Seven normal prostate tissues were served as control., Results: The expression of COX-2 mRNA in normal tissue of 7 control cases was all negative. There was statistical correlation between the COX-2/GAPDH and the Gleason scores of PCa. There also showed statistical correlation between the COX-2/GAPDH and the stages of PCa., Conclusion: COX-2 mRNA play an important role in occurrence and progression of the PCa. COX-2 is a tumor marker which may be the possible prognostic factor of PCa.

Objective: To detect the expression of different genes in the transitional zone and peripheral zone of human normal prostate., Methods: Seventeen specimens of normal prostate gland were obtained from dead kidney donors and patients undergoing total cystectomy. The transitional zone and peripheral zone were isolated. Twenty specimens of benign prostate hypertrophy (BPH) were obtained from patients undergoing prostatic enucleation. The periurethral significantly hypertrophic nodules were isolated. BioDoor Chip-40S containing 6700 clones of targeting gene cDNA was used to detect the gene expression. The peripheral zone RNA samples were labeled with cy3, and the transitional zone RNA samples labeled with Cy5. The genes with the ratio average (RA) < 0.5 or > 2 were identified as differentially expressed genes, and those with a RA < 0.2 or > 4 were identified as the most significantly differentially expressed genes. RT-PCR was used to investigate semi-quantitatively the expression of epidermal growth factor (EGF) mRNA in the 17 specimens of transitional zone and peripheral zone from the 17 normal prostate glands and the 20 specimens of periurethral zone from BPH., Results: A total of 640 genes differentially expressed in transitional zone and peripheral zone were screened out (comprising 269 unknown genes and 371 known genes), of which 294 genes were expressed in the transitional zone and 346 in the peripheral zone. Fourteen genes were identified as markedly differentially expressed, among which the EGF gene was highly expressed in the central zone, and the OSF-1 (osteoblast stimulating factor-1) gene was highly expressed in the peripheral zone. RT-PCR proved that in comparison with the expression of the internal marker beta-actin gene, the expression levels of EGF in the normal transitional zone and in the periurethral zone from BPH were markedly higher than that in the peripheral zone., Conclusion: There are differently expressed genes between the peripheral zone and central zone of normal human prostate, which may be the background of different biological behavior between these zones. EGF may markedly contribute to the growth of central zone of normal prostate.

Objective: To investigate the expression of androgen receptor (AR) isoforms in normal human prostate., Methods: Fourteen normal prostatic specimens from donors, aged 25 on average (21-28 yr), were analyzed by high resolution isoelectric focusing (IEF). The expression of AR isoforms was demonstrated in all 14 normal human prostatic tissues., Results: Four types of AR isoforms were detected with isoelectric point value at 6.5, 6.0, 5.8 and 5.3 in 14 prostatic specimens. Binding of 3H-dihydrotestosterone (DHT) to these four AR isoforms was inhibited by the addition of 100-fold excess of DHT and testosterone. No effect of progesterone, estradiol and diethylstilbestrol on tritiated hormone binding was observed., Conclusions: There are four AR isoforms in normal human prostate. The expression of AR isoforms is different from one another.

Aim: To study the characteristic pattern of the age-related growth of the human prostate gland., Methods: The volume (weight) of the prostate in 1,601 males, aged from newborn to 92 years, was determined by B-ultrasonography., Results: Prostatic volume determination by B-ultrasonography in 1601 males (1301 normal subjects and 300 BPH patients) pointed out that the age-stratified growth of human prostate could be categorized into 4 life stages: (1) the first slow growing phase (from newborn to 9 years): the prostate grows slowly at a rate of 0.14 g per year; (2) the first rapid growing phase (from 10 to 30 years): the prostate grows at a rate of 0.84 g per year; (3) the second slow growing phase (from 30 to 50 years), the prostate grows at a rate of 0.21 g per year; (4) the second rapid growing phase (from 50 to 90 years): the prostate grows at one of the following rates: in one group the growth rate is of 0.50 g per year and in the other 1.20 g per year, leading to benign prostatic hyperplasia (BPH)., Conclusion: The volumes of the prostate are different in different age groups and it grows with age at different rates in four life phases. The prostate growth in phases can be expressed by the following equation: Y=19.36+1.36X'-0.58X'(2+0.33X'3), where Y = prostate volume, X = age (up to 70 years), X'=(X-35.5)/10.

Objectives: To investigate the androgen receptor (AR) isoforms expression in human benign and malignant prostatic tissues and LNCaP cells., Methods: Using high resolution isoelectric focusing (IEF), the different expression of AR isoforms were demosntrated in human benign and malignant prostatic tissues and LNCaP cells., Results: Data were obtained from 41 AR-positive BPH, three prostatic cancer specimens, and LNCaP cells. From these materials, three types of AR isoforms were detected with pI values at 6.5, 6.0 and 5.3. In the case of BPH tissues, 15 (36.5%) specimens expressed all the three types of isoforms at pI 6.5, 6.0 and 5.3, and 10 (24.4%) samples contained isoforms at pI 6.5 and 5.3, five (12.2%) samples indicated isoforms at pI 6.5 and 6.0, four (9.8%) showed the isoforms at pI 6.0 and 5.3. Of all the 41 specimens, two (4.9%) and two (4.9%) as well as three (7.3%) denoted the isoforme at pI 6.5, 6.0 and 5.3 respectively. As for three prostatic cancer specimens, one sample showed all the three types of AR isoforms at pI 6.5, 6.0, 5.3, but another specimen expressed at pI 6.5 and 6.0, and only one failed to indicate any types of isoforms. LNCaP cells expressed all three types of AR isoforms at pI 6.5, 6.0 and 5.3. Binding of 3H-dihydrotestosterone to these three types of isoforms was inhibited by the addition of 100-fold excess of DHT and testosterone. No effect of progesterone, oestradiol and diethylstilboestrol on tritiated hormone binding was observed., Conclusions: The expression of AR isoforms is different among various patients and different between BPH and LNCaP cells, though no clear explanation could be induced for this. These results suggest the possibility of explaining effective hormonal therapy to prostatic disease in the future.

Objective: The aim of the present study was to observe the effect of the stroma proportion in hyperplasia nodules on the clinical symptoms of benign prostatic hyperplasia (BPH) patients and to identify the different genes and pathways in prostatic hyperplasia nodules between patients with epithelial-dominated hyperplasia (EDH) and stromal-dominated hyperplasia (SDH) nodules. Methods: Sixty-seven BPH patient samples underwent transurethral resection of the prostate (TURP) were collected and retrospectively analyzed. The differences in clinical parameters between the EDH and SDH groups were investigated. Collagen fiber percentage was assessed, and the correlation with clinical parameters was evaluated. mRNA sequencing in hyperplasia nodules of 8 BPH patients was performed, and differentially expressed genes (DEGs) between the EDH and SDH groups were screened. These DEGs were analyzed using GO, KEGG and PPI analysis. Results: The results showed the IPSS was significantly higher in the SDH group than in the EDH group (p < 0.01). The collagen fiber percentage of BPH nodules was higher in the SDH group than in the EDH group (p < 0.05), and the collagen fiber percentage was positively correlated with the IPSS (r = 0.4058, p = 0.0007). A total of 172 DEGs were obtained, including 63 up-regulated genes and 109 down-regulated genes. GO and KEGG pathway enrichment analyses showed DEGs were mainly enriched in extracellular matrix structural constituents. The top 10 hub genes were associated to the components of extracellular matrix and fibrosis. Conclusion: These results suggested that the symptoms of BPH patients with SDH nodules may be associated with prostate fibrosis and fibrosis may be a significant contributing factor in BPH/LUTS patients with SDH nodules. [ABSTRACT FROM AUTHOR]