An Updated Meta-Analysis of the Efficacy and Safety of Prostatic Artery Embolization vs. Transurethral Resection of the Prostate in the Treatment of Benign Prostatic Hyperplasia.

Background: Prostatic artery embolization (PAE) in the treatment of benign prostatic hyperplasia (BPH) has been introduced into clinical practice, but conclusive evidence of efficacy and safety has been lacking. Objective: To compare the efficacy and safety of prostatic artery embolization (PAE) vs. transurethral resection of prostate (TURP), we performed a meta-analysis of clinical trials. Methods: We searched randomized controlled trials (RCTs) from Pubmed, Embase, Wanfang, and CNKI from January 2000 to December 2020 and used RevMan 5.0 to analyze the data after five RCTs were included. Results: The reducing of prostate volume (PV) [Median mean (MD) 14.87; 95% confidence interval (CI) 7.52-22.22; P < 0.0001] and the increasing of maximum flow rate in free uroflowmetry (Qmax) (MD 3.73; 95% CI 0.19-7.27; P = 0.004) were more obvious in TURP than in PAE; however, the rate of lower sexual dysfunction [odds ratio (OR) 0.12; 95% CI 0.05-0.30; P < 0.00001] was lower in PAE compared with TURP. Meanwhile, no conspicuous difference in International Prostate Symptoms Score (IPSS) score (MD 1.42; 95% CI -0.92 to 3.75; P = 0.23), quality of life (Qol) score (MD 0.21; 95% CI -0.31 to 0.73; P = 0.43), post void residual (PVR) (MD 21.16; 95% CI -5.58 to 47.89; P = 0.12), prostate-specific antigen (PSA) (MD 0.56; 95% CI -0.15 to 1.27; P = 0.12), and complications (OR 0.90; 95% CI 0.20-4.05; P = 0.89) between PAE and TURP group was shown. Conclusion: PAE may replace TURP as an alternative treatment for Benign prostatic hyperplasia (BPH) patients who do not want to have surgery or with operational contraindications.

Contrast-enhanced transrectal ultrasound can reduce collection of unnecessary biopsies when diagnosing prostate cancer and is predictive of biochemical recurrence following a radical prostatectomy in patients with localized prostate cancer.

BACKGROUND: To investigate the value of using contrast-enhanced transrectal ultrasound (CETRUS) to reduce unnecessary collection of biopsies during prostate cancer diagnosis and its utility in predicting biochemical recurrence in patients with localized prostate cancer. METHODS: This was a prospective study of suspected prostate cancer patients who were evaluated with CETRUS followed by a prostate biopsy. Prostate blood flow via CETRUS was graded using a 5-point scale. The relationship between CETRUS score and biopsy outcome was then analyzed for all patients; univariate and multi-variate analyses were used to determine the probable prognostic factors for biochemical recurrence in patients with localized prostate cancer that underwent a radical prostatectomy. RESULTS: A total of 347 patients were enrolled in the study. Prostate cancer was found in 164 patients. A significant positive correlation (r = 0.69, p < 0.001) was found between CETRUS scores and prostate cancer incidence. Using CETRUS scores ≥2 as the threshold for when to biopsy could have safely reduced the number of biopsies taken overall by 12.1% (42/347) and spared 23.0% (42/183) of patients from undergoing an unnecessary biopsy. 77 patients with localized prostate cancer underwent a radical prostatectomy. The median follow-up time was 30 months (range: 8-56 months) and 17 of these 77 patients exhibited biochemical recurrence during the follow-up period. 3-year biochemical recurrence-free survival rates were 86% for patients with low CETRUS scores (≤ 3) and 59% for patients with high scores (> 3; p = 0.015). Multivariate Cox regression analysis indicated that CETRUS score was an independent predictor of biochemical recurrence (HR: 7.02; 95% CI: 2.00-24.69; p = 0.002). CONCLUSIONS: CETRUS scores may be a useful tool for reducing the collection unnecessary biopsy samples during prostate cancer diagnosis and are predictive of biochemical recurrence in patients with localized prostate cancer following a radical prostatectomy.

Comparison of Serenoa repens With Tamsulosin in the Treatment of Benign Prostatic Hyperplasia: A Systematic Review and Meta-Analysis.

Studies reported that Serenoa repens was effective in relieving lower urinary tract symptoms (LUTS). This article carried out a systematic review and meta-analysis to compare Serenoa repens with tamsulosin in the treatment of benign prostatic hyperplasia (BPH) after at least 6-month treatment cycle. Four studies involving 1,080 patients (543 in the Serenoa repens group and 537 in the tamsulosin group) were included in the meta-analysis. The results were as follows: compared with tamsulosin, Serenoa repens had a same effect in treating BPH in terms of International Prostate Symptom Score (IPSS) (mean difference [MD] 0.63, 95% confidence interval [CI] [-0.33, 1.59], p = 0.20), quality of life (QoL) (MD 1.51, 95% CI [-1.51, 4.52], p = 0.33), maximum flow rate (Qmax) (MD 0.27, 95% CI [-0.15, 0.68], p = 0.21), postvoid residual volume (PVR) (MD -4.23, 95% CI [-22.97, 14.44], p = 0.65), prostate-specific antigen (PSA) (MD 0.46, 95% CI [-0.06, 0.97], p = 0.08) with the exception of prostate volume (PV) (MD -0.29, 95% CI [-0.41, -0.17], p < 0.00001). For side effects, Serenoa repens was well tolerated compared with tamsulosin especially in ejaculation disorders (odds ratio [OR] = 12.56, 95% CI [3.83, 41.18], p < 0.0001) and decreased libido (OR = 5.40; 95% CI [1.17, 24.87]; p = 0.03). This study indicated that Serenoa repens had the same effect in treating BPH compared with tamsulosin in terms of IPSS, QoL, and PVR after at least 6-month treatment cycle, however, the latter had a greater improvement in PV compared with the former. And Serenoa repens did not increase the risk of adverse events especially with respect to ejaculation disorders and libido decrease.

Meta-Analysis of Efficacy and Safety of Tadalafil Plus Tamsulosin Compared with Tadalafil Alone in Treating Men with Benign Prostatic Hyperplasia and Erectile Dysfunction.

This meta-analysis was performed to evaluate the efficacy and safety of tadalafil plus tamsulosin compared with tadalafil alone in treating men with benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) after 12 weeks' treatment. Systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched to collect randomized controlled trials. The references of related articles were also searched. Four articles including 621 patients were involved in the analysis. The study identified that combination-therapy had significant improvements in total international prostate symptom score (IPSS), quality of life (QoL) and maximum urine flow rate (Qmax) compared with monotherapy, and there were no obvious significance in respects of post-void residual volume, international index of erectile function and IPSS storage. The difference of total IPSS was mainly reflected in the change of IPSS voiding. For safety, combination-therapy had a higher incidence rate of any adverse events (AEs) and discontinuation due to AEs than monotherapy with the exception of pain. In conclusion, the combination of tadalafil and tamsulosin provided a better improvement of IPSS voiding, QoL and Qmax compared with tadalafil alone in treating men with BPH and ED, and the former therapy appeared to show a higher incidence of AEs.

miR-30c-5p Reduces Renal Ischemia-Reperfusion Involving Macrophage.

BACKGROUND Ischemia-reperfusion (I/R) leads to kidney injury. Renal I/R frequently occurs in kidney transplantations and acute kidney injuries. Recent studies reported that miR-30 stimulated immune responses and reductions in renal I/R related to anti-inflammation. Our study investigated the effects of miR-30c-5p on renal I/R and the relationship among miR-30c-5p, renal I/R, and macrophages. MATERIAL AND METHODS Sprague Dawley rats received intravenous tail injections of miR-30c-5p agomir. Then a renal I/R model were established by removing the left kidney and clamping the right renal artery. Serum creatinine (Cr) was analyzed using a serum Cr assay kit, and serum neutrophil gelatinase associated lipocalin (NGAL) was measured using a NGAL ELISA (enzyme-linked immunosorbent assay) kit. Rat kidney tissues were analyzed using hematoxylin and eosin staining. THP-1 cells treated with miR-30c-5p agomir and miR-30c-5p antagomir were measured with quantitative reverse transcription-polymerase chain reaction. Protein levels were analyzed by western blot. RESULTS MiR-30c-5p agomir reduced serum Cr, serum NGAL, and renal I/R injury. MiR-30c-5p agomir inhibited the expression of CD86 (M1 macrophage marker), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-alpha) and promoted the expression of CD206 (M2 macrophage marker), interleukin (IL)-4, and IL-10 in rat kidneys. MiR-30c-5p agomir reduced the expression of CD86 and iNOS, and increased the expression of CD206 and IL-10 in THP-1 cells. CONCLUSIONS We preliminarily demonstrated that miR-30c-5p agomir might decrease renal I/R through transformation of M1 macrophages to M2 macrophages and resulted in changes in inflammatory cytokines.

CTCF regulates the FoxO signaling pathway to affect the progression of prostate cancer.

The present research focuses on the influence of CCCTC-binding factor (CTCF) on prostate cancer (PC) via the regulation of the FoxO signalling pathway. A bioinformatics analysis was conducted to screen out target genes for CTCF in LNCaP cells and to enrich the relevant pathways in LNCaP cells. It was found that the FoxO pathway was enriched according to the ChIP-seq results of CTCF. The expression of CTCF, pFoxO1a, FoxO1a, pFoxO3a and FoxO3a was tested by RT-qPCR and Western blot. Inhibition of CTCF could lead to the up-regulation of the FoxO signalling pathway. The rates of cell proliferation, cell invasion and apoptosis were examined by MTT assay, cell invasion assay and flow cytometry under different interference conditions. Down-regulation of CTCF could suppress cell proliferation, cell invasion and facilitate cell apoptosis. Lastly, the effect of CTCF on tumour growth was determined in nude mice. Inhibition of CTCF regulated the FoxO signalling pathway, which retarded tumour growth in vivo. In conclusion, CTCF regulates the FoxO signalling pathway to affect the progress of PC.

Meta-analysis of the efficacy and safety of combination of tamsulosin plus dutasteride compared with tamsulosin monotherapy in treating benign prostatic hyperplasia.

BACKGROUND: We performed a meta-analysis to confirm the efficacy and safety of the combination of tamsulosin plus dutasteride compared with tamsulosin monotherapy in treating benign prostatic hyperplasia (BPH) during a treatment cycle of at least 1 year. METHODS: Randomized controlled trials were searched by using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. Systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The data was evaluated and statistically analyzed by using RevMan version 5.3.0. RESULTS: Five studies including 4348 patients were studied. The analysis found that the combination group was significantly greater effect in international prostate symptom score (mean difference [MD], - 1.43; 95% confidence interval [CI], - 2.20 to - 0.66; P = 0.0003), prostate volume (MD, - 10.13; 95% CI, - 12.38 to - 7.88; P < 0.00001), transitional zone volume (MD, - 3.18; 95% CI, - 3.57 to - 2.79; P<0.0001), maximum urine flow rate (MD, 1.05; 95% CI, 0.82 to 1.29; P < 0.00001), prostate specific antigen (MD, - 0.54; 95% CI, - 0.80 to - 0.29; P < 0.0001) and post-void residual volume (MD, - 3.85; 95% CI, - 4.95 to - 2.76; P < 0.00001) compared with the tamsulosin group. In terms of safety, including adverse events (odds ratio [OR], 2.06; 95% CI, 1.34 to 3.17; P = 0.001), erectile dysfunction (OR, 2.24; 95% CI, 1.73 to 2.92; P < 0.00001), ejaculation disorder (OR, 3.37; 95% CI, 1.97 to 5.79; P < 0.0001), retrograde ejaculation (OR, 2.30; 95% CI, 1.08 to 4.93; P = 0.03), decreased libido (OR, 2.25; 95% CI, 1.53 to 3.31; P < 0.0001) and loss of libido (OR, 3.38; 95% CI, 1.94 to 5.88; P<0.0001), the combination group showed poor tolerance than the tamsulosin group with the exception of dizziness (OR, 1.16; 95% CI, 0.75 to 1.80; P = 0.50). The combination group significantly reduced the risk of clinical progression than the tamsulosin group especially in incidence of BPH-related symptom progression (OR, 0.56; 95% CI, 0.46 to 0.67; P < 0.00001) and acute urinary retention (OR, 0.61; 95% CI, 0.38 to 0.98; P = 0.04). CONCLUSION: The combination of tamsulosin plus dutasteride provides a preferable therapeutic effect for BPH with a higher incidence of sexual side effects, but combination-therapy can markedly reduce risk of BPH-related symptom progression and acute urinary retention relative to tamsulosin monotherapy.

Predictive value of single-nucleotide polymorphism signature for recurrence in localised renal cell carcinoma: a retrospective analysis and multicentre validation study.

BACKGROUND: Identification of high-risk localised renal cell carcinoma is key for the selection of patients for adjuvant treatment who are at truly higher risk of reccurrence. We developed a classifier based on single-nucleotide polymorphisms (SNPs) to improve the predictive accuracy for renal cell carcinoma recurrence and investigated whether intratumour heterogeneity affected the precision of the classifier. METHODS: In this retrospective analysis and multicentre validation study, we used paraffin-embedded specimens from the training set of 227 patients from Sun Yat-sen University (Guangzhou, Guangdong, China) with localised clear cell renal cell carcinoma to examine 44 potential recurrence-associated SNPs, which were identified by exploratory bioinformatics analyses of a genome-wide association study from The Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) dataset (n=114, 906 600 SNPs). We developed a six-SNP-based classifier by use of LASSO Cox regression, based on the association between SNP status and patients' recurrence-free survival. Intratumour heterogeneity was investigated from two other regions within the same tumours in the training set. The six-SNP-based classifier was validated in the internal testing set (n=226), the independent validation set (Chinese multicentre study; 428 patients treated between Jan 1, 2004 and Dec 31, 2012, at three hospitals in China), and TCGA set (441 retrospectively identified patients who underwent resection between 1998 and 2010 for localised clear cell renal cell carcinoma in the USA). The main outcome was recurrence-free survival; the secondary outcome was overall survival. FINDINGS: Although intratumour heterogeneity was found in 48 (23%) of 206 cases in the internal testing set with complete SNP information, the predictive accuracy of the six-SNP-based classifier was similar in the three different regions of the training set (areas under the curve [AUC] at 5 years: 0·749 [95% CI 0·660-0·826] in region 1, 0·734 [0·651-0·814] in region 2, and 0·736 [0·649-0·824] in region 3). The six-SNP-based classifier precisely predicted recurrence-free survival of patients in three validation sets (hazard ratio [HR] 5·32 [95% CI 2·81-10·07] in the internal testing set, 5·39 [3·38-8·59] in the independent validation set, and 4·62 [2·48-8·61] in the TCGA set; all p<0·0001), independently of patient age or sex and tumour stage, grade, or necrosis. The classifier and the clinicopathological risk factors (tumour stage, grade, and necrosis) were combined to construct a nomogram, which had a predictive accuracy significantly higher than that of each variable alone (AUC at 5 years 0·811 [95% CI 0·756-0·861]). INTERPRETATION: Our six-SNP-based classifier could be a practical and reliable predictor that can complement the existing staging system for prediction of localised renal cell carcinoma recurrence after surgery, which might enable physicians to make more informed treatment decisions about adjuvant therapy. Intratumour heterogeneity does not seem to hamper the accuracy of the six-SNP-based classifier as a reliable predictor of recurrence. The classifier has the potential to guide treatment decisions for patients at differing risks of recurrence. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Provincial Science and Technology Foundation of China, and Guangzhou Science and Technology Foundation of China.

Meta-analysis of efficacy and safety of continuous saline bladder irrigation compared with intravesical chemotherapy after transurethral resection of bladder tumors.

PURPOSE: We performed a meta-analysis to confirm the efficacy and safety of continuous saline bladder irrigation compared with intravesical chemotherapy after transurethral resection for the treatment of non-muscle invasive bladder cancer. METHODS: Randomized controlled trials of continuous saline bladder irrigation compared with intravesical chemotherapy were searched using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The data were evaluated and statistically analyzed using RevMan version 5.3.0. RESULTS: Four studies including 861 participants which compared continuous saline bladder irrigation with intravesical chemotherapy were considered. One-year recurrence-free survival [odds ratio (OR) = 0.76, 95% CI = 0.55-1.05, p = 0.09]; 2-year recurrence-free survival (OR = 0.94, 95% CI = 0.71-1.25, p = 0.68); the median period to first recurrence (OR = - 1.01, 95% CI = - 2.96 to 0.94, p = 0.31); the number of tumor progression (OR = 0.80, 95% CI = 0.54-1.17, p = 0.25); and the number of recurrence during follow-up (OR = 1.12, 95% CI = 0.84-1.50, p = 0.43) suggested that two methods of postoperative perfusion had no significant differences. In terms of safety, including macrohematuria, frequency of urination and bladder irritation symptoms, continuous saline bladder irrigation showed better tolerance than intravesical chemotherapy. CONCLUSION: Continuous saline bladder irrigation seems to provide a better balance between prevention of recurrence and local toxicities than intravesical chemotherapy after transurethral resection of bladder tumors.

Ketamine induces reactive oxygen species and enhances autophagy in SV-HUC-1 human uroepithelial cells.

This study was aimed at exploring the underlying mechanisms of ketamine in the SV-40 immortalized human ureteral epithelial (SV-HUC-1) cells. The viability and apoptosis of SV-HUC-1 cells treated with 0.01, 0.1, and 1 mM ketamine were respectively detected via cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining. Reactive oxygen species (ROS) level was measured through ROS probe staining. Apoptosis-related proteins (B-cell lymphoma 2 [Bcl-2] and Bax) and autophagy-associated proteins (light chain 3-I [LC3-I] and LC3-II) were determined by western blot or immunofluorescent assay. Additionally, transmission electron microscopy (TEM) was used to evaluate the formation of autophagosomes. After cotreatment of 3-methyladenine (3-MA) or N-acetyl-l-cysteine (NAC), the biological functions of SV-HUC-1 cells were analyzed to determine the association of ROS with cell viability and autophagy. CCK-8 assay and TUNEL staining indicated that ketamine effectively decreased the viability of SV-HUC-1 cells and accelerated apoptosis of SV-HUC-1 cells through regulating the expression level of IKBα (phospho), nuclear factor ÐºB (P65), Bcl-2, and Bax proteins. Enhanced ROS production was also confirmed in ketamine-treated SV-HUC-1 cells treated with ketamine. Ketamine-induced autophagosomes in SV-HUC-1 cells were observed by means of TEM, and increased levels of LC3 II/I ratio and Beclin 1 were examined through western blot and immunofluorescent assay. Furthermore, ketamine exerted effects on SV-HUC-1 cells in a dose-dependent and time-dependent manner. Additionally, cotreatment of NAC with 3-MA significantly attenuated the ROS level and suppressed the cell autophagy. Ketamine promoted SV-HUC-1 cell autophagy and impaired the cell viability of SV-HUC-1 cells by inducing ROS.

Metachronous metastasis to contralateral retroperitoneal adipose tissue after radical nephrectomy: a case report and review of the literature.

Renal cell carcinoma (RCC) metastasis to the adrenal gland, perirenal adipose tissue, and ureter on the contralateral side is rare. We report a case of solitary metachronous clear cell renal cell carcinoma (ccRCC) metastasis to the contralateral retroperitoneal adipose tissue, which was identified after radical nephrectomy. A patient had undergone retroperitoneal laparoscopic radical nephrectomy for RCC in the right kidney in December 2012. Postoperative pathological analysis showed Fuhrman grade I ccRCC, T1bN0M0. Three years after surgery, a solitary tumor of 1.0 × 1.0 cm was identified by an abdominal computed tomographic scan inside the retroperitoneal fat pad in front of the left posterior abdominal wall, without adhesion to the abdominal wall. The tumor was then completely resected by retroperitoneal laparoscopic resection. Pathological analysis showed that it was a metastasized lesion from a previous tumor. Nine months after surgery, there was no sign of recurrence confirmed by radiographic follow-up. Findings from this case indicate the unpredictability of dissemination of RCC. Our findings support a follow-up regimen that includes regular postoperative computed tomographic scans to identify early metastasis. To the best of our knowledge, this is the first reported case of contralateral retroperitoneal adipose metastasis after laparoscopic tumorectomy.

Application of enhanced recovery after surgery in patients undergoing radical cystectomy.

OBJECTIVE: This study was performed to evaluate the application of enhanced recovery after surgery (ERAS) in patients undergoing radical cystectomy (RC). METHODS: The clinical data of 192 patients who underwent RC were collected in this retrospective cohort study. Among them, 91 patients who underwent ERAS were allocated to the ERAS group, and the remaining 101 patients who underwent traditional postoperative care procedures were allocated to the non-ERAS group. Perioperative indexes in the two groups were compared. The ERAS components included rehabilitation exercise, carbohydrate fluid loading, cessation of nasogastric tubes, omission of oral bowel preparation, regional local anesthesia, body-warming procedures, reduced drainage use, and early postoperative drinking and eating. RESULTS: The times from RC to first water intake, first ambulation, first anal exhaust, first defecation, and pelvic drainage tube removal were significantly shorter and the hospitalization costs were significantly lower in the ERAS than non-ERAS group. The intraoperative blood loss volume, blood transfusion rate, readmission rate, and incidence of postoperative complications were also significantly lower in the ERAS than non-ERAS group. CONCLUSION: ERAS may effectively accelerate patient rehabilitation and reduce the length of stay, incidence of postoperative complications, readmission rates, and hospitalization costs for patients undergoing RC.

Contrast-enhanced computed tomography combined with Chitosan-Fe3O4 nanoparticles targeting fibroblast growth factor receptor and vascular endothelial growth factor receptor in the screening of early esophageal cancer.

Esophageal cancer is a malignant tumor with a relatively high invasiveness, metastatic potential and worldwide incidence among human cancers. The majority of patients with esophageal cancer are diagnosed in a late tumor stage due to a lack of advanced and sensitive protocols for the diagnosis of patients with early-stage esophageal cancer. In the current study, contrast-enhanced computerized tomography (CECT) combined with Chitosan-Fe3O4 nanoparticles targeting fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR; CECT-CNFV) were used to diagnose patients with suspected esophageal cancer. A Chitosan-Fe3O4-parceled bispecific antibody targeting FGFR and VEGFR was produced and its affinity to esophageal cancer cells was determined both in vitro and in vivo. A total of 320 patients with suspected esophageal cancer were voluntarily recruited to evaluate the efficacy of CECT-CNFV in the diagnosis of early-stage esophageal cancer. All participants were subjected to CT and CECT-CNFV to detect whether tumors were present in the esophageal area. A Chitosan-Fe3O4 nanoparticles contrast agent was orally administered at 20 min prior to CT and CECT-CNFV. The results demonstrated that CECT-CNFV improved diagnostic sensitivity and provided a novel protocol for the diagnosis of tumors in patients with suspected gastric cancer at an early-stage. Furthermore, the resolution ratio of images was enhanced by CECT-CNFV, which enabled the visualization of tiny tumor nodules in esophageal tissue. Clinical data demonstrated that CECT-CNFV diagnosed 200 patients with suspected early-stage esophageal cancer and 120 patients as tumor free. In addition, CECT-CNFV exhibited higher signal enhancement of tumor nodules than CT, suggesting a higher accuracy and accumulation of nanoparticle contrast agent within the tumor nodules of esophageal tissue. Notably, the survival rate of patients with esophageal cancer diagnosed at an early-stage by CECT-CNFV was higher than the mean five-year survival rate (P<0.01). In conclusion, CECT-CNFV enhanced the sensitivity and accuracy of CT in the diagnosis of early-stage esophageal cancer. Thus, CECT-CNFV may improve the accuracy of CT in the diagnosis of mural enhancement in patients with esophageal cancer.

Clinical Significance of Peripheral Blood PCA3 Gene Expression in Early Diagnosis of Prostate Cancer.

Prostate cancer antigen 3 (PCA3) is one of the most promising genes currently investigated as a specific tumor biomarker for the diagnosis of prostate cancer. The purpose of this study was to investigate PCA3 gene expression in peripheral blood of prostate cancer (PCa) and benign prostate hyperplasia (BPH), and further to assess its clinical significance. We determined the copies of PCA3 mRNA in peripheral blood of PCa and BPH from 115 samples (PCa, n=78; BPH, n=37) using a quantitative reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) with TaqMan assay. The sensitivity and specificity of PCA3 for the diagnosis of prostate cancer was compared with that of prostate-specific antigen (PSA) by receiver operating characteristic (ROC) curve analysis. To evaluate the association between PCA mRNA and disease progression, we analyzed PCA3 levels in connection with Gleason score and TNM stage of PCa. The clinical data revealed that expression of PCA3 gene was significantly higher in PCa than in BPH. Moreover, PCA3 mRNA was significantly higher in PCa patients with a Gleason score ≥8 than in those with a Gleason score ≤7 (P<.01). The results showed that the area under the curve (AUC) was 0.790, 0.606, and 0.620 for the copy number of PCA3, PSA level, and significantly free PSA (fPSA) level, respectively. Increased PCA3 in peripheral blood is correlated with PCa, and the detection of PCA3 may significantly reduce adverse screening outcomes. PCA3 gene expression in peripheral blood had a promising clinical application in the early diagnosis of PCa.

Evaluation of Multislice Spiral Computed Tomography Perfusion Imaging for the Efficacy of Preoperative Concurrent Chemoradiotherapy in Middle-aged and Elderly Patients with Locally Advanced Gastric Cancer.

BACKGROUND This study aimed to investigate the predictive value of multislice spiral computed tomography (MSCT) perfusion imaging for the efficacy of preoperative concurrent chemoradiotherapy (CCRT) in middle-aged and elderly patients with locally advanced gastric cancer (LAGC). MATERIAL AND METHODS One-hundred twenty-six middle-aged and elderly patients with LAGC were selected. MSCT was performed before and after CCRT to obtain perfusion parameters: blood flow volume (BF), blood volume (BV), mean transit time (MTT), and permeability surface (PS). After CCRT, according to Response Evaluation Criteria in Solid Tumors (RECIST), patients were categorized into the effective group and the ineffective group. Overall survival rate was measured by Kaplan-Meier analysis. ROC curve was applied to evaluate the predictive value of perfusion parameters. Multiple logistic regression analysis was applied to analyze the association of perfusion parameters with the efficacy of preoperative treatment. RESULTS Tumor volume reduction rates of the effective and ineffective groups were 59.23±8.53% and 10.41±3.36%. BF, BV, and PS values in the effective group were significantly decreased after CCRT. ROC curves indicated high sensitivities and specificities of BF value (79.00%, 73.44%), BV value (71.00%, 75.00%), and PS value (82.30%, 90.63%). The incidence rate of weakness and anorexia in the effective group was much higher than that in the ineffective group. Patients with low BF, BV, and PS values (less their optimal cutoff values) had longer survival times than these with high BF, BV, and PS values. CONCLUSIONS MSCT might have predictive values for the efficacy of preoperative CCRT in the treatment of LAGC.

Effects of increased Kindlin-2 expression in bladder cancer stromal fibroblasts.

Kindlin-2 is a focal adhesion protein highly expressed in bladder cancer stromal fibroblasts. We investigated the prognostic significance of Kindlin-2 in bladder cancer stromal fibroblasts and evaluated the effects of Kindlin-2 on the malignant behaviors of tumor cells. Immunohistochemical staining of 203 paraffin-embedded bladder cancer tissues showed that Kindlin-2 expression correlated with advanced stage, high grade, and relapse of bladder cancer. Kaplan-Meier survival analysis demonstrated that patients exhibiting high Kindlin-2 expression had shorter survival times than those with low Kindlin-2 expression (p < 0.01). Multivariate analysis revealed that high Kindlin-2 expression leads to poor prognosis in bladder cancer. Using cancer-associated fibroblasts (CAFs) isolated from human bladder cancer tissue, we observed that Kindlin-2 knockdown decreased CAFs activation, resulting in decreased expression of α-smooth muscle actin (α-SMA) and the extracellular matrix protein fibronectin. Kindlin-2 suppression also reduced CAF-induced bladder cancer cell migration and invasion. Moreover, we found that Kindlin-2 activates CAFs and promotes the invasiveness of bladder cancer cells by stimulating TGF-ß-induced epithelial-mesenchymal transition. These results support targeting Kindlin-2 and the corresponding activated CAFs in bladder cancer therapy.

A Preclinical Study of Cell-seeded Tubularized Scaffolds Specially Secreting LL37 for Reconstruction of Long Urethral Defects.

AIM: We constructed a new artificial, long tubular acellular matrix, seeded with autologous progenitor cells transfected with the sequence to produce the antibiotic peptide LL37 and another two common seeding cells, which might be adopted for patients requiring repair of long segment of the urethra. MATERIALS AND METHODS: Autologous endothelial progenitor cells transfected by lentiviral vectors expressing antibiotic peptide LL37, as well as urothelial and smooth muscle cells from New Zealand white male rabbits, were cultured and seeded onto preconfigured acellular collagen-based tubular matrices (3 cm in length). Artificial conduits were created again in New Zealand white male rabbits and, then, evaluated by immunohistochemistry after 8 weeks. RESULTS: Cell-seeded tubularized collagen scaffolds were found to be effective in repairing long urethral defects, whereas scaffolds without cells led to poor tissue development and structures. CONCLUSION: The artificial tissue engineered tubularized scaffolds combined with genetic methods resulted in vascularized autologous grafts, which may potentially be used for urethroplasty in patients requiring repair of a long segment of the urethra.

Immortalized Cancer-associated Fibroblasts Promote Prostate Cancer Carcinogenesis, Proliferation and Invasion.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are dominant components of the prostate cancer (PCa) stroma. However, the contrasting effects of CAFs and adjacent normal prostate fibroblasts (NPFs) are still poorly defined. The senescence of non-immortalized CAFs after subculture may limit the cell number and influence experimental results of in vitro studies. In this study, we immortalized CAFs to study their role in PCa carcinogenesis, proliferation, and invasion. MATERIALS AND METHODS: We cultured and immortalized CAFs and NPFs, then compared their effect on epithelial malignant transformation by using in vitro co-culture, soft agar assay, and a mouse renal capsule xenograft model. We also compared their roles in PCa progression by using in vitro co-culture, cell viability assays, invasion assays, and a mouse xenograft model. For the mechanistic study, we screened a series of growth factors by using real-time polymerase chain reaction. RESULTS: The CAFs and NPFs were successfully cultured, immortalized, and characterized. The CAFs were able to transform prostate epithelial cells into malignant cells, but NPFs were not. The CAFs were more active in promoting proliferation of and invasion by PCa cells, and in secreting higher levels of a series of growth factors. CONCLUSION: The immortalized CAFs were more supportive of PCa carcinogenesis and progression. Targeting CAFs might be a potential option for PCa therapy. Immortalized CAFs and NPFs will also be valuable resources for future experimental exploration.