Long non-coding RNA SNHG8 promotes prostate cancer progression through repressing miR-384 and up-regulating HOXB7.

BACKGROUND: Multiple long non-coding RNAs (lncRNAs) have been demonstrated to function as vital regulators in the progression of prostate cancer (PCa). In the present study, we aimed to probe the function of lncRNA small nucleolar RNA host gene 8 (SNHG8) in PCa progression. METHODS: A quantitative real-time polymerase chain reaction and western blotting were utilized to measure SNHG8, microRNA-384 (miR-384) and homeobox B7 (HOXB7) expression. Call-couting kit-8 and bromodeoxyuridine experiments were employed to evaluate PCa cell proliferation. Transwell experiments were performed to detect PCa cell migration and invasion. Dual-luciferase reporter experiments and RNA immunoprecipitation experiments were conducted to determine the targeting relationships among miR-384, SNHG8 and HOXB7. RESULTS: SNHG8 was up-regulated in PCa tissues and cells. Silencing of SNHG8 suppressed the proliferation, migration and invasion of PCa cells. SNHG8 functioned as a molecular sponge to repress miR-384. The effects of SNHG8 knockdown on PCa cell proliferation, migration and invasion were counteracted by miR-384 inhibition. HOXB7 was confirmed to be a target gene of miR-384. SNHG8 knockdown repressed HOXB7 expression via targeting miR-384. CONCLUSIONS: SNHG8 promotes PCa cell proliferation, migration and invasion via decoying miR-384 and up-regulating HOXB7.

The Self-Retaining Barbed Suture for Parenchymal Repair in Laparoscopic Partial Nephrectomy: A Systematic Review and Meta-Analysis.

Objectives. The warm ischemia time (WIT) is key to successful laparoscopic partial nephrectomy (LPN). The aim of this study was to perform a meta-analysis comparing the self-retaining barbed suture (SRBS) with a non-SRBS for parenchymal repair during LPN. Methods. A systematic search of PubMed, Scopus, and the Cochrane Library was performed up to March 2018. Inclusion criteria for this study were randomized controlled trials (RCTs) and observational comparative studies assessing the SRBS and non-SRBS for parenchymal repair during LPN. Outcomes of interest included WIT, complications, overall operative time, estimated blood loss, length of hospital stay, and change of renal function. Results. One RCT and 7 retrospective studies were identified, which included a total of 461 cases. Compared with the non-SRBS, use of the SRBS for parenchymal repair during LPN was associated with shorter WIT (P < .00001), shorter overall operative time (P < .00001), lower estimated blood loss (P = .02), and better renal function preservation (P = .001). There was no significant difference between the SRBS and non-SRBS with regard to complications (P = .08) and length of hospital stay (P = .25). Conclusions. The SRBS for parenchymal repair during LPN can significantly shorten the WIT and overall operative time, decrease blood loss, and preserve renal function.

Calpain-2 triggers prostate cancer metastasis via enhancing CRMP4 promoter methylation through NF-κB/DNMT1 signaling pathway.

BACKGROUND: Metastasis is the major cause of cancer-specific death in patients with prostate cancer (PCa). We previously reported that collapsing response mediator protein-4 (CRMP4) is a PCa metastasis-suppressor gene and the hypermethylation in CRMP4 promoter is responsible for the transcription repression in metastatic PCa. However, the underlying mechanisms remain unknown. In this study, we aimed to investigate the role of calpain-2 in CRMP4 promoter hypermethylation and its functional modulation in PCa metastasis. METHODS: Calpain-2 expression in PCa tissues (n = 87) and its specific mechanisms of functional modulation in CRMP4 expression via limited enzymatic cleavage was investigated. We then focused on the cooperative crosstalk of calpain-2 and NF-κB RelA/p65 in CRMP4 promoter methylation for the initiation of PCa metastasis. Statistical differences between groups were determined using a two-tailed Student's t-test. P < 0.05 indicated statistically significant. RESULTS: Calpain-2 was differentially upregulated in metastatic PCa compared with localized PCa. Moreover, calpain-2 cleaved CRMP4 into the N-terminally fragment which promoted migration and invasion in PCa cells via nuclear translocation and activation of E2F1-mediated DNA methyltransferase 1 (DNMT1) expression. NF-κB RelA/p65 recruited DNMT1 to bind to and methylate CRMP4 promoter in which Serine276 phosphorylation of p65 was essential. Furthermore, CRMP4 exhibited anti-metastatic function via inhibiting the expression of VEGFC through Semaphorin3B-Neuropilin2 signaling. CONCLUSION: Calpain-2 may contribute to the promoter methylation of CRMP4 to repress its transcription, leading to the metastasis of PCa via enhancing VEGFC expression.

Identification of endonuclease domain-containing 1 as a novel tumor suppressor in prostate cancer.

BACKGROUND: Endonuclease domain containing 1 (ENDOD1) is implicated in tumorigenesis and aggressiveness of multiple tumors. In this study, we aimed to investigate the role of ENDOD1 in prostate cancer (PCa). METHODS: Immunohistochemistry were performed in 30 cases of benign prostatic hyperplasia (BPH) and 50 cases of PCa to identify its association with clinicopathological characteristics. Real-time PCR and western blot were used to detect ENDOD1 mRNA and protein expression in normal prostatic epithelial and PCa cell lines. MTT assays were employed to determine the effect of cell proliferation. Flow cytometry was used to explore the cell cycle distribution and apoptotic effects. Transwell migration and invasion assays were done to evaluate changes in the ability of cell migration and invasion. RESULTS: Immunoreactivity scores of ENDOD1 showed no statistical difference between BPH and low-grade PCa, whereas lower immunostaining scores were observed in high-grade compared with low-grade PCa. Real-time PCR data indicated that ENDOD1 mRNA expression was markedly increased in LNCaP and 22Rv1 cells and decreased in PC3 and DU145 cells compared to the normal epithelial cells RWPE1. Western blot showed that androgen-sensitive LNCaP cells had the highest protein expression level of ENDOD1, whereas castration-resistant PCa cell lines PC3 and DU145 had significantly lower protein levels. Meanwhile, overexpression of ENDOD1 suppressed cell proliferation, induced G0/G1 cell cycle arrest and inhibited cell migration and invasion. Conversely, siRNA-mediated silencing of ENDOD1 promoted cell proliferation, migration and invasion. No apoptotic effects occurred upon manipulation of ENDOD1 expression. CONCLUSION: Our results indicate that ENDOD1 is a novel tumor suppressor in PCa, which may be employed as a new drug target of preventing progression to metastatic castration-resistant prostate cancer.

Measurements of peri-prostatic adipose tissue by MRI predict bone metastasis in patients with newly diagnosed prostate cancer.

Objectives: To investigate the role of MRI measurements of peri-prostatic adipose tissue (PPAT) in predicting bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa). Methods: We performed a retrospective study on 156 patients newly diagnosed with PCa by prostate biopsy between October 2010 and November 2022. Clinicopathologic characteristics were collected. Measurements including PPAT volume and prostate volume were calculated by MRI, and the normalized PPAT (PPAT volume/prostate volume) was computed. Independent predictors of BM were determined by univariate and multivariate logistic regression analysis, and a new nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves were used to estimate predictive performance. Results: PPAT and normalized PPAT were associated with BM (P<0.001). Normalized PPAT positively correlated with clinical T stage(cT), clinical N stage(cN), and Grading Groups(P<0.05). The results of ROC curves indicated that PPAT and normalized PPAT had promising predictive value for BM with the AUC of 0.684 and 0.775 respectively. Univariate and multivariate analysis revealed that high normalized PPAT, cN, and alkaline phosphatase(ALP) were independently predictors of BM. The nomogram was developed and the concordance index(C-index) was 0.856. Conclusions: Normalized PPAT is an independent predictor for BM among with cN, and ALP. Normalized PPAT may help predict BM in patients with newly diagnosed prostate cancer, thus providing adjunctive information for BM risk stratification and bone scan selection.

Identification of ARHGEF38, NETO2, GOLM1, and SAPCD2 Associated With Prostate Cancer Progression by Bioinformatic Analysis and Experimental Validation.

Prostate cancer (PCa) represents one of the most prevalent types of cancers and is a large health burden for men. The pathogenic mechanisms of PCa still need further investigation. The aim of this study was to construct an effective signature to predict the prognosis of PCa patients and identify the biofunctions of signature-related genes. First, we screened differentially expressed genes (DEGs) between PCa and normal control tissues in The Cancer Genome Atlas (TCGA) and GSE46602 datasets, and we performed weighted gene co-expression network analysis (WGCNA) to determine gene modules correlated with tumors. In total, 124 differentially co-expressed genes were retained. Additionally, five genes (ARHGEF38, NETO2, PRSS21, GOLM1, and SAPCD2) were identified to develop the prognostic signature based on TCGA dataset. The five-gene risk score was verified as an independent prognostic indicator through multivariate Cox regression analyses. The expression of the five genes involved in the signature was detected in the Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), and Oncomine databases. In addition, we utilized DiseaseMeth 2.0 and MEXPRESS for further analysis and found that abnormal methylation patterns may be a potential mechanism for these five DEGs in PCa. Finally, we observed that these genes, except PRSS21, were highly expressed in tumor samples and PCa cells. Functional experiments revealed that silencing ARHGEF38, NETO2, GOLM1, and SAPCD2 suppressed the proliferation, migration, and invasiveness of PCa cells. In summary, this prognostic signature had significant clinical significance for treatment planning and prognostic evaluation of patients with PCa. Thus, ARHGEF38, NETO2, GOLM1, and SAPCD2 may serve as oncogenes in PCa.

Case selection and implementation of tubeless percutaneous nephrolithotomy.

BACKGROUND: The tubeless percutaneous nephrolithotomy (PCNL) was proposed to eliminate the side effects of the nephrostomy tube in recent years, such as pain, channel infection, postoperative bleeding, and longer hospital stay. But there is neither clinical guidelines nor consensus about tubeless PCNL in clinical practice. The study is aimed to how to implement the tubeless PCNL step by step, including case selection preoperatively, improving the technique of the surgeon, making the correct decisions at the end of the procedure, which had not been previously examined. METHODS: From January 2017 to March 2018, 364 consecutive patients requiring PCNL were comprehensively analyzed preoperatively and patients were selected for scheduled tubeless PCNL based on four aspects. The selected patients were divided into two groups according to whether the nephrostomy tube was finally placed. The mean operative time, intraoperative blood loss, stone clearance rate, visual pain score, postoperative hospitalization days and perioperative complications were all evaluated. RESULTS: Based on the preoperative evaluation, 42 patients were selected for tubeless PCNL, among which there were finally 37 cases of completed tubeless PCNL. Compared with patients undergoing conventional PCNL, there were not statistical differences in the mean operative time (P=0.207) or intraoperative blood loss (P=0.450) in the tubeless group. Stone clearance rate was 100% in both groups. The visual pain scores in the tubeless PCNL group were lower on operation day (P=0.029), first postoperative day (P<0.001) and the day of discharge (P=0.025). The postoperative hospitalization for the tubeless PCNL group was shorter than that of the control group (P<0.001). No significant difference in grade 1 complications was seen (P=0.424), and no grade 2 or higher complications were observed in either group. CONCLUSIONS: Postoperative pain was significantly relieved and postoperative hospitalization was significantly shortened in the tubeless PCNL group. Tubeless PCNL is safe if patients are carefully selected using four criteria before operation, attention is paid to four key points and five confirmations are made during operation.

A novel robust nomogram based on peripheral monocyte counts for predicting lymph node metastasis of prostate cancer.

Accurate methods for identifying pelvic lymph node metastasis (LNM) of prostate cancer (PCa) prior to surgery are still lacking. We aimed to investigate the predictive value of peripheral monocyte count (PMC) for LNM of PCa in this study. Two hundred and ninety-eight patients from three centers were divided into a training set (n = 125) and a validation set (n = 173). In the training set, the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses, and the optimal cutoff value was calculated by the receiver operating characteristic (ROC) curve. The sensitivity and specificity of the optimal cutoff were authenticated in the validation cohort. Finally, a nomogram based on the PMC was constructed for predicting LNM. Multivariate analyses of the training cohort demonstrated that clinical T stage, preoperative Gleason score, and PMC were independent risk factors for LNM. The subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405 × 109 l-1 with a sensitivity of 60.0% and a specificity of 67.8%. In the validation set, the optimal cutoff value showed significantly higher sensitivity than that of conventional magnetic resonance imaging (MRI) (0.619 vs 0.238, P < 0.001). The nomogram involving PMC, free prostate-specific antigen (fPSA), clinical T stage, preoperative Gleason score, and monocyte-to-lymphocyte ratio (MLR) was generated, which showed a robust predictive capacity for predicting LNM before the operation. Our results indicated that PMC as a single agent, or combined with other clinical parameters, showed a robust predictive capacity for LNM in PCa. It can be employed as a complementary factor for the decision of whether to conduct pelvic lymph node dissection.

Suppression of TRPM7 Inhibited Hypoxia-Induced Migration and Invasion of Androgen-Independent Prostate Cancer Cells by Enhancing RACK1-Mediated Degradation of HIF-1α.

Transient receptor potential melastatin subfamily member 7 (TRPM7) was essential in the growth and metastatic ability of prostate cancer cells. However, the effects and the relevant molecular mechanisms of TRPM7 on metastasis of prostate cancer under hypoxic atmosphere remain unclear. This study investigated the role of TRPM7 in the metastatic ability of androgen-independent prostate cancer cells under hypoxia. First, data mining was carried out to disclose the relationship between the TRPM7 gene level and the survival of prostate cancer patients. Specific siRNAs were used to knockdown target genes. Western blotting and qPCR were employed to determine protein and gene expression, respectively. The gene transcription activity was evaluated by luciferase activity assay of promoter gene. The protein interaction was determined by coimmunoprecipitation. Wound healing and transwell assays were employed to evaluated cell migration and invasion, respectively. Open access database results showed that high expression of TRPM7 was closely related to the poor survival of prostate cancer patients. Hypoxia simultaneously increased TRPM7 expression and induced HIF-1α accumulation in androgen-independent prostate cancer cells. Knockdown of TRPM7 significantly promoted HIF-1α degradation through the proteasome and inhibited EMT changes in androgen-independent prostate cancer cells under hypoxic condition. Moreover, TRPM7 knockdown increased the phosphorylation of RACK1 and strengthened the interaction between RACK1 and HIF-1α but attenuated the binding of HSP90 to HIF-1α. Whereas knockdown of RACK1 increased the binding of HSP90 to HIF-1α. Furthermore, both TRPM7 and HIF-1α knockdown significantly suppressed hypoxia-induced Annexin A1 protein expression, and suppression of HIF-1α/Annexin A1 signaling significantly inhibited hypoxia-induced cell migration and invasion of androgen-independent prostate cancer cells. Our findings demonstrate that TRPM7 knockdown promotes HIF-1α degradation via an oxygen-independent mechanism involving increased binding of RAKC1 to HIF-1α, and TRPM7-HIF-1α-Annexin A1 signaling axis plays a crucial role in the EMT, cell migration, and invasion of androgen-independent prostate cancer cells under hypoxic conditions.

MicroRNA-939 Directly Targets HDGF to Inhibit the Aggressiveness of Prostate Cancer via Deactivation of the WNT/ß-Catenin Pathway.

PURPOSE: MicroRNA-939 (miR-939) has crucial roles in several types of human cancer. However, the expression profile and precise functions of miR-939 in prostate cancer (PCa) are still unclear. This study aimed to determine miR-939 expression in PCa and explore its roles in PCa tumorigenesis. METHODS: miR-939 expression was determined in PCa tissues and cell lines using reverse transcription-quantitative polymerase chain reaction. Cell Counting Kit-8, colony formation, and flow cytometric assays were used to determine the role of miR-939 in PCa cell proliferation and apoptosis in vitro, whereas a tumor xenograft model was generated to evaluate the effect of miR-939 on tumor growth in vivo. Transwell assays were performed to investigate whether miR-939 affects the migration and invasiveness of PCa cells. RESULTS: miR-939 was found to be downregulated in PCa tissues and cell lines, and this downregulation was significantly correlated with tumor stage and lymphatic metastasis. Patients with PCa exhibiting low miR-939 expression had shorter overall survival than those exhibiting high miR-939 expression. Exogenous miR-939 expression suppressed PCa cell proliferation, colony formation, migration, and invasion in vitro; enhanced apoptosis in vitro; and decreased tumor growth in vivo. Investigation of the underlying molecular mechanisms revealed hepatoma-derived growth factor (HDGF) as a direct target gene of miR-939 in PCa. HDGF was found to be significantly upregulated in PCa tissues, and its expression was inversely correlated with miR-939 expression. HDGF silencing and miR-939 upregulation showed similar effects in PCa. Restored HDGF expression counteracted the tumor-suppressive activity of miR-939 overexpression in PCa cells. Furthermore, ectopic miR-939 expression inhibited the WNT/ß-catenin pathway activation in PCa both in vitro and in vivo by downregulating HDGF. CONCLUSION: miR-939 functions as a tumor suppressor during PCa tumorigenesis by directly targeting HDGF and deactivating the WNT/ß-catenin pathway, suggesting the miR-939/HDGF/WNT/ß-catenin pathway as an effective target for PCa therapy.

Methylcrotonoyl-CoA Carboxylase 2 Promotes Proliferation, Migration and Invasion and Inhibits Apoptosis of Prostate Cancer Cells Through Regulating GLUD1-P38 MAPK Signaling Pathway.

PURPOSE: Prostate cancer (PCa) is the most common cancer in American men, and the mechanisms of development and progression are still not completely clear. Methylcrotonoyl-CoA carboxylase 2 (MCCC2) was previously identified overexpressed in PCa with lymph node metastasis, but its specific role and mechanisms need further investigation. This study aimed to investigate the role of MCCC2 in PCa cells and its underlying mechanisms. MATERIALS AND METHODS: Quantitative RT-PCR and Western blotting were used to detect MCCC2 mRNA and protein expression in normal prostate epithelium and cancerous cells. Upon manipulation of MCCC2 expression, cell proliferation was measured by CCK-8 assays and migration and invasion were determined by transwell assays. Changes of apoptosis, cell cycle and mitochondrial membrane potential were evaluated by flow cytometry. MCCC2-mediated signaling pathways were screened by bioinformatics and verified by RT-PCR and Western blotting. Finally, immunohistochemistry was performed to detect the expression of MCCC2 and glutamate dehydrogenase 1 (GLUD1) in PCa tissues to analyze their correlation. RESULTS: We demonstrated that MCCC2 promoted cell proliferation, migration and invasion but inhibited apoptosis in PCa cells. In addition, MCCC2 in 22Rv1 cells induced mitochondrial damage. In PCa tissues, MCCC2 overexpression associated with lymph node metastasis (P=0.001) and high Gleason scores (P<0.001). MCCC2 positively correlated with GLUD1 expression in PCa tissues (r=0.435, P<0.001). Ectopic overexpression of MCCC2 up-regulated GLUD1 and p38 MAPK expression, whereas inhibition of MCCC2 decreased GLUD1 and p38 MAPK expression. CONCLUSION: MCCC2 exerts oncogenic function in PCa through regulating GLUD1-p38 MAPK signaling pathway, and it may be a potential treatment target.

RNA m6A Methyltransferase METTL3 Promotes The Growth Of Prostate Cancer By Regulating Hedgehog Pathway.

PURPOSE: N6-methyladenosine (m6A) is the most abundant internal modification on eukaryotic mRNA and gained increasing attention recently. More and more evidence suggest that m6A methylation plays crucial role in tumor genesis and development. However, its role in prostate cancer remains largely unknown. METHODS: METTL3 expression status in prostate cancer was analyzed by using TCGA database and Western blotting. m6A content was analyzed by using RNA Methylation Quantification Kit. The role of METTL3 in prostate cancer cells was determined by proliferation, survival, colony formation, and invasion assays. The m6A level of GLI1 RNA was detected by methylated RNA immunoprecipitation (MeRIP) assay. In vivo role of METTL3 was studied on xenograft models. RESULTS: We found that m6A methyltransferase METTL3 was overexpressed in prostate cancer cell lines, together with increased m6A content. Functionally, silencing of METTL3 by shRNA in prostate cancer cell lines resulted in decreased m6A content, cell proliferation, survival, colony formation, and invasion. Interestingly, overexpression of wild-type METTL3 abrogated the repression effect of METTL3 depletion on m6A content, cell proliferation, survival, colony formation, and invasion, while the overexpression of m6A catalytic site mutant METTL3 was unable to rescue the inhibitory effect caused by METTL3 depletion. Further mechanism analysis demonstrated that METTL3 silence decreased the m6A modification and expression of GLI1, an important component of hedgehog pathway, which led to cell apoptosis. Moreover, depletion of METTL3 inhibited tumor growth in vivo. CONCLUSION: Our results suggested that the m6A methyltransferase METTL3 promotes the growth and motility of prostate cancer cells by regulating hedgehog pathway.

Impact and Predictive Value of Prostate Weight on the Outcomes of Nerve Sparing Laparoscopic Radical Prostatectomy in Patients with Low Risk Prostate Cancer.

PURPOSE: To investigate the impact of prostate weight on outcomes of nerve sparing laparoscopic radical prosta-tectomy (LRP) and assess its predictive value on postoperative continence and potency recovery. MATERIALS AND METHODS: We conducted a retrospective study on the clinical data of 165 patients with low risk prostate cancer (PCa) who underwent nerve sparing LRP. All the patients included had normal preoperative uri-nary and sexual function. The association of prostate weight with perioperative data was assessed using Spearman correlation coefficient. Univariate and multivariate Cox regression analyses were employed to identify prognostic predictors for continence and potency recovery. RESULTS: Increased prostate weight was significantly associated with older age, higher prostate-specific antigen (PSA), lower biopsy and pathological T stage and Gleason score, longer operative time, and higher estimated blood loss (P < .05). The continence rates at the 3rd, 6th, and 12th month after surgery were 63.6% (105/165), 87.9% (145/165), and 95.8% (158/165); and the potency rates were 44.8% (74/165), 62.4% (103/165) and 77.6% (128/165), respectively. Furthermore, multivariate Cox analysis showed that patient age (HR = 0.52, 95% CI: 0.35- 0.76) and prostate weight (HR = 0.54, 95% CI: 0.34-0.86) were independent predictors for continence recovery, while only patient age (HR = 0.66, 95% CI: 0.45-0.96) could independently predict potency recovery. CONCLUSION: Larger prostate size was correlated with older age, higher PSA, lower tumor stage and grade, longer operative time, and more intraoperative blood loss in low risk PCa patients. Increased prostate weight may inde-pendently predict poor continence recovery after nerve sparing LRP.

A modification with threading cannula needle-assisted 4-point suspension fixation for retroperitoneal laparoscopic pyeloplasty in children with ureteropelvic junction obstruction: a cohort study in single center.

PURPOSE: To evaluate the effect and safety of modifying a threading cannula needle-assisted suspension fixation in retroperitoneal laparoscopic dismembered pyeloplasty (LDP) for children with congenital ureteropelvic junction obstruction (UPJO). METHODS: Between December 2012 and December 2017, 45 children (< 14 years of age) with congenital UPJO were divided into two groups. In Group A, children underwent conventional "no-suspension fixation" LDP; and in Group B, "4-point suspension fixation" LDP was performed to lower difficulties and shorten operative time. The perioperative clinical data were recorded and analyzed. RESULTS: No statistical difference was found between two groups in preoperative characteristics. The duration of surgery, operative time for completion of anastomosis and the length of postoperative hospital stay in Group B was remarkably shortened than that in Group A, respectively (P < 0.05 for all). There was no significant difference between two groups in terms of postoperative renal pelvic diameter (RPD) decreasing, extubation time and success rates of surgery (P > 0.05 for all). In addition, no recurrent stenosis and urine leakage in both groups, and the postoperative RPD remained at the low level in both groups during the period of follow-up. CONCLUSIONS: Our modification of the 4-point suspension fixation for retroperitoneal LDP is an effective and safe method for children with UPJO. It can simplify the surgical procedures, lower difficulties (especially in precise anastomotic suturing) and shorten the learning curve. This modification might be of particular interest to urologists for improving treatment of children with UPJO.

Statin and metformin therapy in prostate cancer patients with hyperlipidemia who underwent radiotherapy: a population-based cohort study.

PURPOSE: To evaluate the association between the use of statins and/or metformin and patient survival in prostate cancer patients in Taiwan. SUBJECTS AND METHODS: Newly diagnosed prostate cancer patients who had hyperlipidemia and received radiotherapy were identified from the National Health Insurance Research Database 2000-2010. The survival rate was estimated by the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to examine the association of mortality. Sensitivity analysis was performed to assess the risk of mortality in patients with diabetes. RESULTS: The study included 567 patients. Patients who used statins or metformin after prostate cancer diagnosis had longer average survival times (9.3 years and 8.1 years, respectively; P=0.001) compared with patients who persistently used or used the medicines prior to cancer diagnosis. Multivariate Cox regression analysis found that patients treated with statins after cancer diagnosis were significantly associated with a lower risk of mortality (aHR =0.24, 95% CI =0.09-0.66) compared to patients who did not use statins during the study period. Patients treated with metformin after cancer diagnosis were significantly associated more with an increased risk of mortality (aHR =6.78, 95% CI =2.45-18.77) compared to patients who did not use metformin during the study period. Sensitivity analysis revealed that the average survival time was similar among different medicine use groups in patients with diabetes. CONCLUSION: The finding suggests that statins and metformin use after prostate cancer diagnosis may increase survival in patients with hyperlipidemia and radiotherapy.

A Novel Modification of Transurethral Enucleation and Resection of the Prostate in Patients With Prostate Glands Larger than 80 mL: Surgical Procedures and Clinical Outcomes.

OBJECTIVE: To evaluate the efficacy and safety of the modified transurethral enucleation and resection of the prostate (M-TUERP) vs the conventional bipolar transurethral resection of the prostate (B-TURP) for the treatment of prostates larger than 80 mL. METHODS: From April 2012 to May 2014, 86 patients with a prostate volume of >80 mL were divided into 2 groups to undergo M-TUERP and B-TURP. In the M-TUERP group, we proposed combining the 12-mm trocar suprapubic cystostomy and using the techniques of "umbrella-shaped resection," "point resection," and "segmental enucleation" to modify the transurethral enucleation and resection of the prostate procedure. The perioperative clinical data were recorded and analyzed. RESULTS: There were no significant differences in preoperative characteristics between the 2 groups. Both groups were similar with the operative time. The M-TUERP group was significantly superior to the B-TURP group in terms of the weight of the resected tissue, the mean intraoperative bladder pressure, hemoglobin decrease, bladder irrigation duration, and urethral catheterization time. No transurethral resection syndrome and incontinence occurred in either group. Compared with the B-TURP group, none of the patients in the M-TUERP group suffered blood transfusion, clot retention, recatheterization, dysuria and reoperation. At the 3-year follow-up, patients who underwent M-TUERP had better international prostate symptom scores, maximum urinary flow rates, and quality of life scores. CONCLUSION: Our modification of the transurethral enucleation and resection of the prostate procedure is a safe and effective method for the surgical treatment of large-volume benign prostatic hyperplasia. It can simplify the surgical procedures, reduce complications, lower difficulties and shorten the learning curve. At 3-year follow-up, the M-TUERP shows a superior and durable clinical outcome than the B-TURP.

Association of doublecortin-like kinase 1 with tumor aggressiveness and poor biochemical recurrence-free survival in prostate cancer.

BACKGROUND: Doublecortin-like kinase 1 (DCLK1) has been proven to be involved in numerous tumors, while its role in prostate cancer (PCa) is still unclear. This study aimed at investigating the expression pattern and prognostic value of DCLK1 in PCa. PATIENTS AND METHODS: Real-time polymerase chain reaction and Western blot were employed to determine DCLK1 mRNA and protein levels in 25 paired fresh samples of PCa and benign prostatic hyperplasia (BPH) as well as in PCa cell lines. Immunohistochemistry (IHC) was also performed in 125 PCa and 65 BPH tissues to assess DCLK1 expression. Then, the association of DCLK1 expression with clinicopathological parameters and biochemical recurrence (BCR) after radical prostatectomy was statistically analyzed. In addition, the role of DCLK1 in PCa cell proliferation, migration, and invasion was evaluated by using MTT and transwell assays. RESULTS: The mRNA and protein levels of DCLK1 were markedly higher in the fresh samples of PCa than that in BPH. Consistently, IHC revealed increased expression of DCLK1 in PCa paraffin-embedded tissues compared with BPH. Moreover, increased DCLK1 expression was significantly associated with postoperative Gleason grading (P=0.012), pathological T stage (P=0.001), seminal vesicle invasion (P=0.026), and lymph node involvement (P=0.017), respectively. The Kaplan-Meier curve analysis demonstrated that high DCLK1 expression was associated with lower postoperative BCR-free survival (bRFS). Furthermore, multivariate Cox analysis showed that postoperative Gleason grading (P=0.018), pathological T stage (P<0.001), seminal vesicle invasion (P=0.012), lymph node involvement (P=0.014), and DCLK1 expression (P=0.014) were independent predictors of BCR. In vitro, the overexpression and knockdown of DCLK1 in PCa cell lines indicated that DCLK1 could promote cell proliferation, migration, and invasion. CONCLUSION: Increased DCLK1 expression is associated with PCa aggressiveness and may independently predict poor bRFS in patients with PCa.

Gold-chrysophanol nanoparticles suppress human prostate cancer progression through inactivating AKT expression and inducing apoptosis and ROS generation in vitro and in vivo.

Controlled releasing of regulations remains the most convenient method to deliver various drugs. In the present study, we precipitated gold nanoparticles with chrysophanol. The gold-chrysophanol into poly (DL-lactide-co-glycolide) nanoparticles was loaded and the biological activity of chrysophanol nanoparticles on human LNCap prostate cancer cells, was tested to acquire the sustained releasing property. The circular dichroism spectroscopy indicated that chrysophanol nanoparticles effectively resulted in conformational alterations in DNA and regulated different proteins associated with cell cycle arrest. The reactive oxygen species (ROS), apoptosis, cell cycle, DNA damage, Cyto-c and caspase-3 activity were analyzed, and the expression levels of different anti- and pro-apoptotic were studied using immunoblotting analysis. The cytotoxicity assay suggested that chrysophanol nanoparticles preferentially killed prostate cancer cells in comparison to the normal cells. Chrysophanol nanoparticles reduced histone deacetylases (HDACs) to suppress cell proliferation and induce apoptosis by arresting the cell cycle in sub-G phase. In addition, the cell cycle-related proteins, including p27, CHK1, cyclin D1, CDK1, p-AMP-activated protein kinase (AMPK) and p-protein kinase B (AKT), were regulated by chrysophanol nanoparticles to prevent human prostate cancer cell progression. Chrysophanol nanoparticles induced apoptosis in LNCap cells by promoting p53/ROS crosstalk to prevent proliferation. Pharmacokinetic study in mice indicated that chrysophanol nanoparticle injection showed high bioavailability compared to the free chrysophanol. Also, in vivo study revealed that chrysophanol nanoparticles obviously reduced tumor volume and weight. In conclusion, the data above suggested that chrysophanol nanoparticles might be effective to prevent human prostate cancer progression.

Overexpression of Cdc20 in clinically localized prostate cancer: Relation to high Gleason score and biochemical recurrence after laparoscopic radical prostatectomy.

OBJECTIVES: This study was aimed to explore Cdc20 expression and its correlation with clinicopathological characteristics and biochemical recurrence (BCR) after laparoscopic radical prostatectomy (LRP) in clinically localized prostate cancer (PCa). METHODS: Cdc20 expression was examined by immunohistochemistry in 166 cases, including 60 cases of benign hyperplasia of prostate (BPH) patients treated by transurethral resection and 106 cases of consecutive PCa patients treated by LRP without neoadjuvant therapy in a single Chinese institution. The correlation with clinicopathological features and the predictive value for BCR were statistically analyzed. RESULTS: Cdc20 expression was detected in 52 (86.7%) BPH and 97 (91.5%) PCa samples, which was statistically insignificant (P= 0.675). The rate of patients with high expression of Cdc20 was 21.7% in BPH and 37.7% in PCa (P= 0.033). A correlation was revealed between Cdc20 expression and postoperative Gleason scores (P= 0.046), positive surgical margin (P< 0.001). BCR-free survival was significantly lower in patients with high Cdc20 expression than those with low Cdc20 expression (P= 0.018). Univariate analysis indicated pTstage, post operative Gleason score, seminal vesicle invasion, lymph node invasion, surgical margin and Cdc20 expression significantly influenced BCR. Multivariate analysis revealed that postoperative Gleason score, seminal vesicle invasion, lymph node invasion, surgical margin and Cdc20 expression were independent predictors for BCR. After stratified by Gleason score and surgical margin status, Cdc20 expression and lymph node invasion remained significant in Cox regression analysis. CONCLUSIONS: Overexpression of Cdc20 may serve as an independent predictor for BCR in patients of clinically localized PCa undergoing LRP without neoadjuvant therapy.