Peripheral zone PSA density: a predominant variable to improve prostate cancer detection efficiency in men with PSA higher than 4 ng ml / 亚洲男科学杂志(英文版)

To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml

Two-micron laser resection of the prostate-tangerine technique for the treatment of large-volume prostate / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficiency and safety of two-micron laser resection of the prostate-tangerine technique (TmLRP-TT) for the treatment of large-volume ( > 70 ml) prostate in patients with benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>This retrospective analysis included 80 BPH patients with the prostatic volume larger than 70 ml, all treated by TmLRP-TT. We comparatively analyzed the levels of hemoglobin and serum sodium before and after surgery, recorded intra- and post-operative com- plications, and followed up the patients at 6 and 12 months after operation for International Prostate Symptom Score (IPSS), quality of life (QOL), maximum flow rate (Qmax), and postvoid residual urine volume (PVR).</p><p><b>RESULTS</b>All the operations were successfully completed. The mean hemoglobin decreased (0.68 +/- 0.43) g/dl intraoperatively, but no apparent reduction was observed in serum sodium. Lower urinary tract symptoms were relieved significantly in all the cases. At 12 months after surgery, IPSS was decreased by 73.89% as compared with the baseline (20.03 +/- 6.9 vs 5.23 +/- 3.59), QOL by 64.55% (4.09 +/- 1.19 vs 1.45 +/- 1.36), and PVR by 79.30% (97.31 +/- 57.90 vs 20.14 +/- 24.20 ml), while Qmax increased by 140.42% ([8.04 +/- 3.62] vs [19.33 +/- 3.28] ml/s). The incidence of complications was low either intraoperatively or during the 12 months after operation.</p><p><b>CONCLUSION</b>TmLRP-TT is a safe and effective surgical endoscopic approach to the treatment of large-volume prostate in BPH patients.</p>

Differential gene expressions in the stromal cells of the human prostate peripheral zone in males of different ages / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the gene expressions in the stromal cells of the human prostate peripheral zone (PZ) in men of different ages.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Characterization of stromal cell cultures from the prostatic peripheral zone of men at different ages / 中华男科学杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Primary stromal cells isolated from human various histological/pathological prostate have different phenotypes and tumor promotion role / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Chimeric molecules facilitate the degradation of androgen receptors and repress the growth of LNCaP cells / 亚洲男科学杂志(英文版)

Post-translational degradation of protein plays an important role in cell life. We employed chimeric molecules (dihydrotestosterone-based proteolysis-targeting chimeric molecule [DHT-PROTAC]) to facilitate androgen receptor (AR) degradation via the ubiquitin-proteasome pathway (UPP) and to investigate the role of AR in cell proliferation and viability in androgen-sensitive prostate cancer cells. Western blot analysis and immunohistochemistry were applied to analyse AR levels in LNCaP cells after DHT-PROTAC treatment. Cell counting and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell viability assay were used to evaluate cell proliferation and viability after AR elimination in both LNCaP and PC-3 cells. AR was tagged for elimination via the UPP by DHT-PROTAC, and this could be blocked by proteasome inhibitors. Degradation of AR depended on DHT-PROTAC concentration, and either DHT or an ALAPYIP-(arg)(8) peptide could compete with DHT-PROTAC. Inhibition of cell proliferation and decreased viability were observed in LNCaP cells, but not in PC-3 or 786-O cells after DHT-PROTAC treatment. These data indicate that AR elimination is facilitated via the UPP by DHT-PROTAC, and that the growth of LNCaP cells is repressed after AR degradation.

Tumor formation of prostate cancer cells influenced by stromal cells from the transitional or peripheral zones of the normal prostate / 亚洲男科学杂志(英文版)

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.

Targeted degradation of androgen receptors in androgen-independent prostate cancer cells: an experimental study / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate targeted degradation of the androgen receptor (AR) by chimeric molecules (DHT-PROTAC) via the ubiquitin-proteasome pathway in androgen-independent prostate cancer CA-2B cells, and explore the proliferation, secretion and apoptosis of the treated cells.</p><p><b>METHODS</b>C4-2B cells were treated with DHT-PROTAC, and then the expressions of the AR protein and caspase3 in the C4-2B cells were detected by immunohistochemistry and Western blot. The concentration of PSA in the supernatant was examined by ELISA. The cells were counted and their proliferation analyzed by a growth curve. The inhibitory effect on the growth of C4-2B cells was evaluated by MIT assay.</p><p><b>RESULTS</b>Compared with the control group, the DHT-PROTAC-treated group showed an obviously decreased expression of AR proteins with a significant attenuation of the band signals (P < 0.05), a 40% reduction of the AR-positive cells and a 60% decrease of the PSA concentration in the supernatant (P < 0.05). DHT-PROTAC exhibited an inhibitory effect on the C4-2B cells in a time-dependant manner (P < 0.05).</p><p><b>CONCLUSION</b>The chimeric molecule (DHT-PROTAC) can target the degradation of androgen receptors, reduce the secretion of PSA and repress the in vitro growth of C4-2B cells.</p>

Small incision combined with laparoscopy for ureteropelvic junction obstruction: comparison with retroperitoneal laparoscopic pyeloplasty / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Laparoscopic dismembered pyeloplasty is technically feasible for ureteropelvic junction (UPJ) obstruction although it is still challenged by its technical difficulty and time-consuming. In this study, we compared the initial results of retroperitoneal laparoscopic pyeloplasty versus a combined laparoscopic dissection and open reconstruction through a small incision in the treatment of UPJ obstruction.</p><p><b>METHODS</b>Sixty-four patients with primary UPJ obstruction underwent pyeloplasty: 32 patients underwent laparoscopic procedure and 32 patients underwent open assisted laparoscopic surgery including two steps, ie, laparoscopic dissection of the UPJ transperitoneally and then pyeloplasty via an extended small incision. The demographic data and intraoperative, postoperative and follow-up conditions of patients were compared between the two groups.</p><p><b>RESULTS</b>Preoperative data were comparable in the patients of the two groups. The operative time was shorter (60.9 minutes vs 157.7 minutes, P < 0.0001) and the complication rate was lower (9.4% vs 31.3%, P < 0.05) in the open assisted group than in the laparoscopic group. The estimated blood loss (42.3 ml vs 47.8 ml), time to have normal diet (37.6 hours vs 33.8 hours), and hospital stay (6.7 days vs 6.2 days) were equivalent. The operative success rate was 97% for the open assisted group and 91% for the laparoscopic group.</p><p><b>CONCLUSIONS</b>The procedure of combined small incision with laparoscopy for UPJ obstruction is technically easy, and the results are promising. It can be used as an alternative to conventional procedures.</p>

Androgen receptor functioned as a suppressor in the prostate cancer cell line PC3 in vitro and in vivo / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Prostate cancer is one of the most common urogenital tumors in the world with an increasing incidence in China. Androgen deprivation therapy is the major therapeutic option for advanced prostate cancer. However, the role of androgen receptor (AR) in hormone-refractory prostate cancer still remains unclear. This work aimed to investigate the role of AR in an androgen independent prostate cancer cell line by in vitro and in vivo studies.</p><p><b>METHODS</b>The role of AR in the proliferation and invasion/metastasis ability of PC3-AR9 (a PC3 stable clone expressing human AR driven by natural human AR promoter) were examined with MTT assay, soft agar assay, chamber invasion assay, wound healing assay, and also with orthotopic xenograft mouse model.</p><p><b>RESULTS</b>Restoring androgen receptor in PC3 cells resulted in decreased proliferation and invasion/metastasis ability in MTT, soft agar, chamber invasion and wound healing assay. In the mouse orthotopic xenograft model, PC3-AR9 resulted in smaller primary tumors and metastasis tumors, with a lower proliferation rate and higher apoptosis rate.</p><p><b>CONCLUSION</b>The AR might function as a tumor suppressor in PC3 cells both in vitro and in vivo.</p>

Expression and implication of cyclooxygenase-2 mRNA in prostate cancer / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between cyclooxygenase-2 (COX-2) mRNA expression and the biological behaviors of prostate carcinoma (PCa).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Combined treatment applied to advanced cancer of abdominal cryptorchidism (report of 12 cases) / 中华男科学杂志

<p><b>OBJECTIVE</b>To discuss the treatment of advanced cancer of abdominal cryptorchidism.</p><p><b>METHODS</b>The combined method, including preoperation chemotherapy + surgery + postoperation radiotherapy and chemotherapy, was used to treat 12 cases of the advanced cancer of abdominal cryptorchidism and the effects were evaluated.</p><p><b>RESULTS</b>The patients recovered smoothly without complications of operation. The side effect of chemotherapy and radiotherapy was very slight. Eleven out of 12 cases were followed up. All 11 cases survived and had no recurrence.</p><p><b>CONCLUSION</b>The results of combined method to treat advanced cancer of abdominal cryptorchidism is very perfect.</p>