Inhibition of T24 and RT4 Human Bladder Cancer Cell Lines by Heterocyclic Molecules.

BACKGROUND Bladder cancer is a major widespread tumor of the genitourinary tract. Around 30% of patients with superficial cancers develop invasive and metastatic pathology. MATERIAL AND METHODS Some new heterocyclic 4-methyl coumarin derivatives were designed using molecular modeling studies to evaluate their potential against bladder cancer lines T24 and RT-4. The designed compounds that showed good binding affinity to T24 and RT4 were synthesized, with excellent yield. The synthesized compounds after structural evaluation were further evaluated for their antiproliferative activity by cell viability assay, cell cycle analysis, and apoptosis assay. RESULTS The compound BC-14 exhibited the best cytotoxicity against T24 cells, but were not highly active against RT4 cells. CONCLUSIONS The results of the present study may suggest the selectivity pattern of the synthesized compounds. These results should be explored further with chemical modification for other cancer types.

Long-term results of thulium laser resection of the prostate: a prospective study at multiple centers.

PURPOSE: To evaluate the long-term durability and complication rates after thulium laser resection of prostate (TmLRP) through a prospective multiple-center study. MATERIALS AND METHODS: From November 2004 to December 2011, we prospectively studied 2,216 patients with symptomatic benign prostatic hyperplasia (BPH) treated with thulium laser resection of the prostate at four medical centers. Patients were assessed on International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), and postvoid residual urine (PVR). Perioperative complications were classified according to the modified Clavien classification system. RESULTS: Of 2,216 patients treated with TmLRP, 1,353 (61.1 %), 1,129 (50.9 %), 847 (38.2 %), and 541 (24.4 %) patients were followed at 5, 6, 7, and 8 years, respectively. Postoperatively, IPSS, QoL, Qmax, and PVR showed a significant improvement from 3 month after surgery and remained significantly improved during the entire follow-up period (p < 0.01). Minor complications occurred in 526 (23.7 %) of the 2,216 patients (Clavien 1: 21.5 %; Clavien 2: 2.3 %). Major complications requiring re-interventions occurred in 48 (2.2 %) of the 2,216 patients (Clavien 3: 2.2 %). No Clavien 4 or Clavien 5 complication had occurred. Urethral stricture and bladder neck contracture occurred in 2.6 % (58) and 1.6 % (35) patients, respectively. Persistent stress incontinence was found in 0.1 % (2) of the patients. Re-operation as a result of BPH recurrence was required in 1.2 % (27) patients. CONCLUSIONS: Thulium laser resection of the prostate is a safe and effective procedure with excellent durability in the treatment of symptomatic BPH.

[Percutaneous nephroscopic 2 µm laser incision and drainage treatment of peripelvic renal cysts].

OBJECTIVE: To explore the surgical approaches, efficacy and safety of percutaneous nephroscopic 2 µm laser incision and drainage in the treatment of peripelvic renal cysts. METHODS: The peripelvic renal cysts were punctured percutaneously. A 1.5 - 4.0 cm incision was made at thin avascular area between cyst and pelvis by the 2 µm laser to connect the cyst with the renal collecting system with the help of injecting methylene blue solution into renal pelvis through ureteral catheter. The double-J tube was placed for drainage. RESULTS: The operations were successful in all cases. There were 16 males and 15 females with a mean age of 49 years old. The operative durations ranged from 25 to 120 minutes. And no severe complications occurred. The patients were followed up for an average of 12 months (range: 3 - 36). Among them, cysts disappeared in 18 cases and diminished over 1/3 in 13 cases. There was no recurrence of peripelvic renal cyst. CONCLUSION: Percutaneous nephroscopic 2 µm laser incision and drainage for peripelvic renal cyst is safe, effective and mini-invasive.

Irg1-itaconate axis protects against acute kidney injury via activation of Nrf2.

Acute kidney injury (AKI) is a common clinical implication with increased tissue damage, uncontrolled immune responses, and risk of mortality, in which ischemia-reperfusion injury (IRI) is one of the leading causes. As critical role for metabolic remodeling in inflammation, Irg1-itaconate axis has received much attention for its immunomodulation in the control of the inflammation. However, its role in the AKI and IRI remains unknown. Here, we found that Irg1 expression was negatively correlated with the expression of inflammatory cytokines during ischemia-reperfusion injury. And Irg1 deficiency promotes renal inflammation and ischemia-reperfusion injury in vivo. Itaconate treatment promoted the survival of WT mice from lethal ischemia and protected against renal IRI and systemic inflammation. Mechanistically, dimethyl itaconate protected renal cells from oxidative stress and prevented macrophage activation by enhancing the translocation of Nrf2 into the nuclei. Our study highlighted the importance of the Irg1-itaconate axis in the protecting against ischemia-reperfusion injury and acute kidney injury, providing potential therapeutic targets to control AKI.

Proliferation of Highly Cytotoxic Human Natural Killer Cells by OX40L Armed NK-92 With Secretory Neoleukin-2/15 for Cancer Immunotherapy.

Adoptive natural killer (NK) cell transfer has been demonstrated to be a promising immunotherapy approach against malignancies, but requires the administration of sufficient activated cells for treatment effectiveness. However, the paucity of clinical-grade to support the for large-scale cell expansion limits its feasibility. Here we developed a feeder-based NK cell expansion approach that utilizes OX40L armed NK-92 cell with secreting neoleukin-2/15 (Neo-2/15), a hyper-stable mimetic with a high affinity to IL-2Rßγ. The novel feeder cells (NK92-Neo2/15-OX40L) induced the expansion of NK cells with a 2180-fold expansion (median; 5 donors; range, 1767 to 2719) after 21 days of co-culture without added cytokines. These cells were highly cytotoxic against Raji cells and against several solid tumors in vivo. Mechanistically, NK92-Neo2/15-OX40L induced OX40 and OX40L expression on expanded NK cells and promoted the OX40-OX40L positive feedback loop, thus boosting NK cell function. Our data provided a novel NK cell expansion mechanism and insights into OX40-OX40L axis regulation of NK cell expansion.

The Family Attitudes of Patients With End-Stage Renal Disease Toward Living Kidney Donation in China.

BACKGROUND: Organ shortages limit the progress of organ transplantation. The family attitudes of patients with end-stage renal disease (ESRD) play an important role in advocating organ transplantation and donation. The purpose of this study was to analyze the family attitudes of patients with ESRD toward living kidney donation in China. Ethical approval was obtained from the ethics committee of Linyi People's Hospital. This study was performed in compliance with the Declaration of Helsinki. MATERIALS AND METHODS: This research was performed at 5 third-level hospitals with hemodialysis and nephrology departments, and a small section comes from urology departments. The participants were surveyed from January to November 2018. Attitudes were evaluated using a validated questionnaire concerning the psychosocial aspects of organ donation. The self-administered questionnaire was completed anonymously. Statistical analyses employed t tests and the χ2 test. RESULTS: Regarding living kidney donation, 69.1% (n = 428) of patient families favored it; however, only 30.9% (n = 192) did not support it. A favorable attitude toward living donation was mainly associated with the following variables: 1. the recipient is not more than 50 years old; 2. the recipient is a member of the immediate family; 3. the living donation is from the recipient's family member; 4. the family has previous personal experience with organ transplantation and donation; and 5. the family has a concern about the possibility of needing a transplant within the family unit (P < .05). CONCLUSIONS: Economic burden and mental stress from long-term dialysis influenced the attitudes and behavioral intentions of the families of patients with ESRD on advocating organ donation. Repeated education and constant advocacy are advised to increase the participation of families of patients with ESRD in organ donation. The results showed favorable attitudes toward living kidney donation among the families of patients with ESRD.

[Efficacy of transurethral 2 microm laser urethrotomy in the treatment of urethral stricture and atresia].

OBJECTIVE: To evaluate the curative efficacy of transurethral 2 microm thulium laser urethrotomy in the treatment of urethral stricture and atresia. METHODS: 192 patients suffering from urethral stricture (n = 179) or atresia (n = 13), all male, aged 45.4 (38-56), underwent transurethral 2 microm thulium laser urethrotomy. The maximum flow rate (MFR) was measured before operation, immediately after removing the catheter, and 3 and 6 months postoperatively. RESULTS: All the patients got fluent urination immediately after the catheter removal with the mean MFR of (16.7 +/- 3.1) ml/s, significantly higher than that before the operation [(3.2 +/- 0.3) ml/s, P < 0.01]. 157 patients got permanent fluent urination without recurrence; 35 patients got recurrence 1 to 3 weeks after the catheter removal and got final cure 3 months later after periodic urethra dilatation. Besides, 6 patients encountered incontinence and all finally got convalescence after physical therapy and exercise. The mean MFR of all the patients 3 months and 6 months postoperatively were (18.7 +/- 3.1) ml/s and (19.2 +/- 2.8) ml/s respectively, both significantly higher than that before operation (both P < 0.01). CONCLUSION: Transurethral 2 microm thulium laser urethrotomy is a safe and efficient method in the treatment of urethral stricture and atresia.

Long non-coding RNA Z38 promotes cell proliferation and metastasis in human renal cell carcinoma.

Long non-coding RNAs (LncRNAs) have been reported to serve roles in various types of malignancy, including human renal cell carcinoma (RCC), which is among the most common types of kidney cancer worldwide. The present study aimed to investigate the effects of a newly­discovered LncRNA, Z38, on cell proliferation and metastasis in RCC cells. Reverse transcription­quantitative polymerase chain reaction analysis was used to detect the transcription levels of Z38 in clinical RCC tissues and cultured RCC cells. The expression of Z38 was notably increased in patients with stage III and IVRCC compared with patients with stage I and II. Knockdown of Z38 with specific short hairpin RNAs notably decreased the proliferation rate of A498 and ACHIN cells. In addition, a colony formation assay was included to investigate the role of Z38 in cell proliferation. Transwell assays demonstrated that Z38 deprivation inhibited the migratory and invasive capability of RCC cells. The association between Z38 and the epithelial­mesenchymal transition process was investigated using western blot analysis. The results of the present study demonstrated that Z38 may serve as an important biomarker in the diagnosis and treatment of RCC in the clinic.

Association of endothelial nitric oxide synthase polymorphisms with an increased risk of erectile dysfunction.

The purpose of our meta-analysis is to examine the associations between three single nucleotide polymorphisms of endothelial nitric oxide synthase (eNOS) gene, G894T, intron 4 and T-786C, and the risk of erectile dysfunction. An electronic database search was performed to identify case-control studies reporting the association between single nucleotide polymorphisms of eNOS gene and erectile dysfunction. Stringent inclusion and exclusion criteria were employed to select high-quality studies for this meta-analysis. Comprehensive Meta-analysis 2.0 software (Biostat Inc., Englewood, New Jersey, USA) was used for statistical analysis of the data extracted from the selected studies. From the initial 203 articles retrieved from database search, this meta-analysis finally selected 12 high-quality case-control studies that conformed to our inclusion criteria. The 12 studies contained a total of 1962 patients with erectile dysfunction and 1752 healthy controls. The results of our meta-analysis showed that G894T correlated with an increased risk erectile dysfunction under both the allele and dominant models (allele: OR = 1.556, 95% CI = 1.064-2.275, P = 0.023; dominant: OR = 1.613, 95% CI = 1.050-2.476, P = 0.029). A similar association was found between T-786C and erectile dysfunction under the allele model (OR = 1.679, 95% CI = 1.341-2.102, P < 0.001), but not under the dominant model (all P > 0.05). Our meta-analysis showed that the two single nucleotide polymorphisms in eNOS gene, G894T and T-786C, are strongly associated with the risk of erectile dysfunction.

Knockdown of Long Noncoding RNA FTX Inhibits Proliferation, Migration, and Invasion in Renal Cell Carcinoma Cells.

Renal cell carcinoma (RCC) is one of the most common kidney cancers worldwide. Although great progressions have been made in the past decades, its morbidity and lethality remain increasing. Long noncoding RNAs (lncRNAs) are demonstrated to play significant roles in the tumorigenesis. This study aimed to investigate the detailed roles of lncRNA FTX in RCC cell proliferation and metastasis. Our results showed that the transcript levels of FTX in both clinical RCC tissues and the cultured RCC cells were significantly upregulated and associated with multiple clinical parameters of RCC patients, including familial status, tumor sizes, lymphatic metastasis, and TNM stages. With cell proliferation assays, colony formation assays, and cell cycle assays, we testified that knockdown of FTX in A498 and ACHIN cells with specific shRNAs inhibited cell proliferation rate, colony formation ability, and arrested cell cycle in the G0/G1 phase. FTX depletion also suppressed cell migration and invasion with Transwell assays and wound-healing assays. These data indicated the pro-oncogenic potential of FTX in RCC, which makes it a latent therapeutic target of RCC diagnosis and treatment in the clinic.

Solitary fibrous tumors of the prostate: A case report.

Increasing numbers of extrapleural solitary fibrous tumours (SFTs), including the prostate SFT, have been reported over the last 10-years. Prostate SFT is relatively uncommon, with <20 cases reported in the literature worldwide. In the present study, a prostate SFT case, which was initially misdiagnosed as benign prostatic hyperplasia, is presented. The patient was subjected to three surgeries (cystoscopy and per urethra lithocystotomy, transurethral resection of the prostate and nerve-sparing retropubic radical prostatectomy) prior to SFT diagnosis. It was demonstrated that histopathological and immunohistochemical factors (positive staining for CD34 and B cell lyphoma-2 expression) were of significant diagnostic value. Thus, nerve-sparing retropubic radical prostatectomy for total resection may be the best therapeutic strategy to treat prostate SFT, allowing the preservation of sexual function and reducing the risk of locoregional recurrence.

Golgi phosphoprotein 3 regulates metastasis of prostate cancer via matrix metalloproteinase 9.

Recent studies suggest that Golgi phosphoprotein 3 (GOLPH3) protein is a candidate metastasis gene in human cancer. The goal of this study was to determine the function of GOLPH3 in prostate cancer metastasis and to identify GOLPH3-regulated pathways and genes involved in prostate cancer metastasis. GOLPH3 expression was detected in prostate cancer. To investigate its function, PC-3 cells were stably transfected with shRNA targeting GOLPH3. Cell abilities of invasion and migration were measured in vitro. Downstream regulatory pathways of GOLPH3 were characterized using quantitative RT-PCR and Western blotting analysis. Immunohistochemical studies in prostate cancer specimens revealed a positive correlation of GOLPH3 expression with prostate cancer. GOLPH3 was expressed in prostate cancer cell lines. GOLPH3 repression resulted in the reduction of mRNA level and protein level of MMP9, accompanied with reduced phosphorylation of mTOR, EGFR and Src. Our findings suggest GOLPH3 regulate MMP9 expression which impact cell migration and invasion. This regulation is probably mediated by EGFR and Src signaling pathways.

Increased Expression of GOLPH3 is Associated with the Proliferation of Prostate Cancer.

BACKGROUND: Golgi phosphoprotein 3 (GOLPH3) is a metastasis-associated gene, however its role in cell proliferation of prostate cancer (PCa) has not yet been elucidated. METHODS: The level of expression of GOLPH3 and other genes was examined by quantitative real-time PCR (QPCR) and western blot analysis. Furthermore, we performed a comprehensive analysis of the expression of GOLPH3 in PCa using a tissue microarray (TMA) and correlated our findings with pathological parameters of PCa. RNA interference (RNAi) was used to silence the expression of GOLPH3 in PC-3 cells and to measure the effects on proliferation and cell cycle using the CCK-8 assay and flow cytometry. Western blots were also employed to assess AKT-mTOR and cell cycle-related proteins. RESULTS: We showed that the expression of GOLPH3 was located at the trans-Golgi membranes in PCa cells. We found that GOLPH3 was expressed in all PCa cells and was significantly higher in two androgen-independent cell lines, DU145 and PC-3. TMA immunohistochemistry showed that GOLPH3 was positive in 64% of cancer tissue samples compared with 20% in normal and 30% in benign samples (P<0.05). In vitro, silencing GOLPH3 expression inhibited cell proliferation and arrested the cell cycle at the G2/M phase. Silencing GOLPH3 also activated P21 expression but suppressed the expression of CDK1/2 and cyclinB1 protein together with the phosphorylation of AKT and mTOR. CONCLUSIONS: The expression of the GOLPH3 protein was significantly elevated in PCa. GOLPH3 can promote cell proliferation by enhancing the activity of AKT-mTOR signaling. Altogether, these findings suggest that GOLPH3 play important roles in proliferation and cell cycle regulation in PCa and might serve as promising biomarkers for PCa progression as well as potential therapeutic targets.

Improved nephrostomy tube can reduce percutaneous nephrolithotomy postoperative bleeding.

Renal hemorrhage is one of the most common and worrisome complications of post-percutaneous nephrolithotomy (PCNL). This study aimed at evaluating the safety, effectiveness of utilization of the absorbable hemostatic gauze cover renal tract for hemorrhage of post-PCNL. The prospective study including 188 patients with upper urinary tract calculi was carried out in the department of Urology at Linyi People's Hospital from November 2011 to September 2013. All patients underwent PCNL procedures and they were divided into two groups randomly before the procedure. Group A (n=91) was indwelled a 16F catheter as nephrostomy tube at the end of the surgery, Group B (n=97) was indwelled a 14F catheter covered with absorbable hemostatic gauze for hemostasis. Blood loss was estimated based on the mass of hemoglobin in the draining liquid and urine during postoperative duration by HiCN method. The average blood loss was 25.76±23.99 g for Group A, and 14.25±6.87 g for Group B, respectively, with statistical difference by comparison (P<0.05). The delta hemoglobin was 16.24±10.98 mmol/L for Group A, and 10.71±5.57 mmol/L for Group B, respectively, also with statistical difference by comparison (P<0.05). Nephrostomy channel applications of absorbable hemostatic gauze after PCNL can significantly reduce postoperative bleeding. Utilizing the absorbable hemostatic gauze for post-PCNL hemorrhage is safe, effective and feasible.

Impact of beta-blockers on prostate cancer mortality: a meta-analysis of 16,825 patients.

INTRODUCTION: Increasing evidence suggests that beta-blocker use might be associated with reduced mortality in prostate cancer patients. To provide a quantitative assessment of this association, we pooled data available to examine the association between beta-blocker use and mortality of prostate cancer. METHODS: We identified studies by a literature search of MEDLINE (from 1 January 1966) and EMBASE (from 1 January 1974), through 10 September 2014, and by searching the reference lists of pertinent articles. Two authors independently screened and reviewed the eligibility of each study. The primary outcomes were prostate cancer-specific mortality and all-cause mortality. RESULTS: A total of four studies including 16,825 patients were included in this meta-analysis. Analysis of all studies showed that beta-blocker use was associated with reduced prostate cancer-specific mortality (hazard ratio =0.85, 95% confidence interval =0.77-0.94), without any heterogeneity between studies (Q=3.59, I2=16.5%, P=0.309). However, we observed no association with all-cause mortality (hazard ratio =0.97, 95% confidence interval =0.90-1.04). There was also no evidence of the presence of significant heterogeneity between the four studies (Q=2.48, I2=0.0%, P=0.480). CONCLUSION: These findings indicate that beta-blocker use was associated with reduced cancer-specific mortality among prostate cancer patients taking beta-blockers.

Effectiveness of inhibitor rapamycin, saracatinib, linsitinib and JNJ-38877605 against human prostate cancer cells.

To investigate the effect of different concentrations of inhibitors rapamycin, saracatinib, linsitinib and JNJ-38877605 on PC-3 cells with CCK-8 assay, respectively. PC-3 cells were incubated with different concentrations of rapamycin, saracatinib, linsitinib and JNJ-38877605, respectively, for 48 h at 37°C, the concentrations of rapamycin were 5 nM, 10 nM, 20 nM, 50 nM, 75 nM, 100 nM; Saracatinib: 0.125 nM, 0.25 nM, 0.5 nM, 1 nM, 2.5 nM, 5 nM; Linsitinib: 2 nM, 5 nM, 10 nM, 20 nM, 40 nM, 60 nM; JNJ-38877605: 0.125 nM, 0.5 nM, 1 nM, 2.5 nM, 5 nM, 10 nM. The proliferation of PC-3 cells was examined by CCK-8. Different concentrations of inhibitor rapamycin remarkably inhibited PC-3 cell proliferation after 48 h (P<0.05), inhibitory action did not change significantly from 5 nM-100 nM; different concentrations of saracatinib, linsitinib and JNJ-38877605 did not inhibit PC-3 cell proliferation after 48 h. Rapamycin treatment at low concentration can inhibit the proliferation of PC-3 cells, while saracatinib, linsitinib and JNJ-38877605 do not inhibit PC-3 cell proliferation.

Percutaneous intrarenal marsupialization of symptomatic peripelvic renal cysts: a single-centre experience in China.

UNLABELLED: OBJECTIVE.The aim of this study was to report the authors' experience with percutaneous intrarenal marsupialization of symptomatic peripelvic renal cysts. MATERIAL AND METHODS: Thirty-one patients (16 male and 15 female, with a mean age of 49 years) with a peripelvic renal cyst associated with chronic flank or lumbar pain or urinary infection were selected for percutaneous intrarenal marsupialization with a 2 µm laser in the authors' centre from January 2005 to December 2010. Cyst size ranged from 4.5 to 10.5 (mean 6.0) cm. The cysts were punctured by a percutaneous technique guided by ultrasonography, a 20.8 F nephroscope was introduced and the whole internal surface of the cyst was inspected. Methylene blue was injected through the ureteral catheter to help identify the collecting system. A 1.5-4 cm incision was made at the avascular area of the cystic wall by the 2 µm laser to achieve intrarenal marsupialization of the cyst into the renal collecting system. One or two 6 F double-J stents were placed with the proximal end in the cyst for 2-3 months. RESULTS: The mean operation time was 50 (25-120) min. No serious complications such as massive bleeding, urine leak or infected haematoma occurred. The patients were followed up for a mean of 12 (range 3-36) months. All patients were relieved of their symptoms. Eighteen cysts disappeared after surgery, while 13 cysts reduced in size by over one-third and communicated with the renal collecting system. No enlargement of cysts was observed. CONCLUSIONS: Percutaneous intrarenal marsupialization with a 2 µm laser is an effective and safe procedure and may offer a minimally invasive alternative for the management of symptomatic peripelvic renal cysts.