Xinghuan Wang

Capsaicin mediates cell death in bladder cancer T24 cells through reactive oxygen species production and mitochondrial depolarization.

OBJECTIVES To investigate the effects of capsaicin (CAP) on proliferation of bladder cancer T24 cells in vitro as well as on xenografts in nude mice in vivo. METHODS T24 cells were assessed for cell viability and apoptosis by 3-(4, 5-dimethylthiazol-2-yl)-3, 5-diphenyltetrazolium bromide assay and flow cytometry analysis after incubation with different concentrations of CAP. To uncover the mechanism by which CAP affected the viability of T24 cells, intracellular production of reactive oxygen species (ROS) and mitochondrial membrane potential were assessed. To study the in vivo effects of CAP, T24 cells were grown as xenografts in nude mice and CAP (5 mg/kg by wt) was subcutaneously injected into nude mice with bladder tumors. RESULTS CAP decreased the viability of T24 cells in a dose-dependent manner without marked apoptosis. CAP induced ROS production and mitochondrial membrane depolarization, thereby inducing cell death, not apoptosis, in T24 cells at a concentration of 100 microM or higher. Furthermore, these effects of CAP could be reversed by capsazepine, the antagonist of transient receptor potential vanilloid type 1 channel. In vivo experiment showed that CAP significantly slowed the growth of T24 bladder cancer xenografts as measured by size (661.80 +/- 62.03 vs 567.02 +/- 43.94 mm(3); P <.01). CONCLUSIONS CAP mediates cell death in T24 cells through calcium entry-dependent ROS production and mitochondrial depolarization, and it may have a role in the management of bladder cancer.

Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells.

We investigated the effects of transient receptor potential M8 (TRPM8) channel on the proliferation and motility of androgen-independent prostate cancer PC-3 cells. After being permanently transfected with an empty vector and cDNA encoding the TRPM8 protein, cells were analysed for cell cycle distribution and motility using flow cytometry and scratch assay. Immunocytochemistry and Ca2+ imaging analysis revealed the overexpression of functional TRPM8 channel on both endoplasmic reticulum and plasma membrane of PC-3-TRPM8 cells. Cell cycle distribution and scratch assay analysis revealed that TRPM8 induced cell cycle arrest at the G0/G1 stage (P < 0.05) and facilitated the cell apoptosis induced by starvation (P < 0.05). Furthermore, TRPM8 inhibited the migration of PC-3-TRPM8 cells (P < 0.01) through the inactivation of focal-adhesion kinase. It appears that TRPM8 was not essential for the survival of PC-3 cells; however, the overexpression of TRPM8 had negative effects on the proliferation and migration of PC-3 cells. Thus, TRPM8 and its agonists may serve as important targets for the treatment of prostate cancer.

Menthol Induces Cell Death via the TRPM8 Channel in the Human Bladder Cancer Cell Line T24

Objective: Growing evidence has shown that menthol has potent anticancer activity in various human cancers via the transient receptor potential melastatin 8 (TRPM8)-dependent pathway or in a TRPM8-independent manner. However, its effect on bladder cancer remains obscure. In the present investigation, we examined the expression of TRPM8 and the role of menthol in cells of the human bladder cancer cell line T24. Methods: RT-PCR, Western blotting and immunocytochemistry were used to confirm the expression and location of TRPM8 in T24 cells. Results: TRPM8 was highly expressed in T24 cells and located in both the cell membrane and cytoplasm. With the use of small interfering RNA to silence the expression of TRPM8, we found that menthol could increase the concentration of intracellular calcium and decrease cell viability via the TRPM8 channel in T24 cells. We also found that menthol could induce cell death through TRPM8 in T24 cells, rather than cell cycle arrest or apoptosis. Moreover, the detection of mitochondrial membrane potential showed that menthol could induce mitochondrial membrane depolarization in T24 cells. Conclusions: In the present study, we demonstrated that menthol can induce mitochondrial membrane depolarization via the TRPM8 channel in cells of the human bladder cancer cell line T24, resulting in cell death. It would be helpful to explore the precise mechanism of action of menthol in bladder cancer with a view to its possible use as intravesical chemotherapy.

The value of combined use of survivin, cytokeratin 20 and mucin 7 mRNA for bladder cancer detection in voided urine

ObjectivesTo evaluate the value of combined use of survivin, cytokeratin (CK) 20 and mucin (MUC) 7 mRNA in comparison with voided urine cytology in the detection of bladder cancer patients.MethodsOne hundred and fifty three patients and 20 healthy volunteers were evaluated by RT-PCR for detecting survivin, CK-20 and MUC7 mRNA in voided urine before cystoscopy. The three markers and cytology were evaluated independently or in combinations.ResultsThe overall sensitivity and specificity were 90.4 and 94.7% for survivin, 82.6 and 97.4% for CK-20, 62.6 and 94.7% for MUC7 and 46.0 and 100% for voided urine cytology. Combined sensitivity of voided urine cytology with the three biomarkers together was higher than either combined sensitivity of voided urine cytology with one of the biomarkers or than that of the biomarker alone.ConclusionsCombined use of the three markers can improve the sensitivity for detecting bladder cancer.

Thulium laser enucleation versus plasmakinetic resection of the prostate: a randomized prospective trial with 18-month follow-up.

OBJECTIVE To compare the clinical outcomes between thulium laser transurethral enucleation of the prostate (ThuLEP) and plasmakinetic bipolar resection of the prostate (PKRP) for treating benign prostatic hyperplasia (BPH) in a prospective randomized trial with 18 months of follow-up. METHODS The study randomized 158 consecutive patients with BPH to ThuLEP (n = 79) or PKRP (n = 79). All patients were evaluated preoperatively and at 1, 3, 6, 12, and 18 months after surgery by International Prostate Symptom Score (IPSS), quality of life score (QOLS), maximum flow rate (Qmax), and postvoid residual urine volume (PVR). RESULTS The 79 patients in each study arm each showed no significant difference in preoperative parameters. Compared with PKRP, ThuLEP required a longer operation time (65.4 vs 47.4 minutes, P = .022) but resulted in less hemoglobin decrease (0.15 vs 0.30 g/dL, P = .045). ThuLEP also needed less catheterization time (2.1 vs 3.5 days, P = .031), irrigation volume (12.4 vs 27.2 L, P = .022), and hospital stay (2.5 vs 4.6 days, P = .026). During the 1, 3, 6, 12, and 18 months of follow-up, the procedures did not demonstrate a significant difference in Qmax, IPSS, PVR, and QOLS. CONCLUSION ThuLEP and PKRP both relieve lower urinary tract symptoms equally, with high efficacy and safety. ThuLEP was statistically superior to PKRP in blood loss, catheterization time, irrigation volume, and hospital stay but inferior to PKRP in operation time. However, procedures did not differ significantly in Qmax, IPSS, PVR, and QOLS through the 18 months of follow-up.

Laparoscopic Pyelolithotomy Compared to Percutaneous Nephrolithotomy as Surgical Management for Large Renal Pelvic Calculi: A Meta-Analysis

PURPOSE We assessed the effectiveness and safety of laparoscopic pyelolithotomy and percutaneous nephrolithotomy as surgical management for solitary renal pelvic calculi larger than 2 cm. MATERIALS AND METHODS We searched PubMed®, EMBASE®, The Cochrane Library and the Web of Knowledge(SM) databases up to November 9, 2012 for relevant published studies. After data extraction and quality assessment, meta-analysis was performed using RevMan 5.1. RESULTS We identified 7 trials in a total of 176 and 187 patients treated with laparoscopic pyelolithotomy and percutaneous nephrolithotomy, respectively. Operative time and hospital stay were 50.62 minutes and 0.66 days shorter in the nephrolithotomy group (p <0.0001 and 0.04, respectively). Patients in the laparoscopic group benefited from a lesser decrease in hemoglobin (OR -1.00, 95% CI -1.77--0.23), less postoperative fever (OR 0.24, 95% CI 0.08-0.72), a lower incidence of bleeding (OR 0.29, 95% CI 0.10-0.85) and a higher stone-free rate (OR 4.85, 95% CI 1.59-14.82). Sensitivity analysis indicated that all results were stable except the stone-free rate showed no statistically significant difference between the 2 groups (OR 0.33, 95% CI 0.09-1.17). No publication bias was detected. CONCLUSIONS Current evidence suggests that laparoscopic pyelolithotomy and percutaneous nephrolithotomy are effective and safe for large renal pelvic calculi but laparoscopic pyelolithotomy seems to be more advantageous. However, given the inherent limitations of the included studies, results must be further confirmed in high quality randomized, controlled trials.

Enrichment of Prostate Cancer Stem-Like Cells from Human Prostate Cancer Cell Lines by Culture in Serum-Free Medium and Chemoradiotherapy

The discovery of rare subpopulations of cancer stem cells (CSCs) has created a new focus in cancer research. As CSCs demonstrate resistance to chemoradiation therapy relative to other cancer cells, this allows the enrichment of CSC populations by killing apoptosis-susceptible cancer cells. In this study, three commonly used human prostate cancer (PCa) cell lines (DU145, PC-3 and LNCaP) were examined for their expression of the putative stem cell markers CD133 and CD44 via flow cytometric analysis. Under normal culture conditions, CD133+/CD44+ cells were only present in the DU145 cell line, and comprised only a minor percentage (0.1% ± 0.01%) of the total population. However, the proportion of these CD133+/CD44+ prostate CSCs could be increased in these cell lines via culture in serum-free medium (SFM), or through chemotherapy or radiotherapy. Indeed, after culture in SFM, the proportion of CD133+/CD44+ cells in DU145 and PC-3 had increased to 10.3% and 3.0%, respectively. Moreover, the proportion had increased to 9.8% enriched by chemotherapy and 3.5% by radiotherapy in DU145. Colony-formation tests, cell invasion assays, and tumor xenografts in BALB/c nude mice were used to evaluate the stem cell properties of CD133+/CD44+ PCa cells that were isolated via fluorescence-activated cell sorting (FACS). CD133+/CD44+ cells had an enhanced colony-formation capability and invasive ability in vitro, and displayed greater tumorigenic properties in vivo. These results demonstrate the presence of CD133+/CD44+ prostate CSCs in established PCa cell lines and that populations of these cells can be enriched by culture in SFM or chemoradiotherapy. Finding novel therapies to override chemoradiation resistance in the prostate CSCs is the key to improve long-term results in PCa management.

Five-Year Follow-Up Results of a Randomized Controlled Trial Comparing Bipolar Plasmakinetic and Monopolar Transurethral Resection of the Prostate

Purpose To report the 5-year follow-up results of a randomized controlled trial comparing bipolar transurethral resection of the prostate (TURP) with standard monopolar TURP for the treatment of benign prostatic obstruction (BPO). Materials and Methods A total of 220 patients were randomized to bipolar plasmakinetic TURP (PK-TURP) or monopolar TURP (M-TURP). Catheterization time was the primary endpoint of this study. Secondary outcomes included operation time, hospital stay, as well as decline in postoperative serum sodium and hemoglobin levels. All patients were assessed preoperatively and followed-up at 1, 6, 12, 24, 36, 48, and 60 months postoperatively. Parameters assessed included quality of life, transrectal ultrasound, serum prostate-specific antigen level, postvoid residual urine volume, maximum urinary flow rates (Qmax), and International Prostate Symptom Score. Patient baseline characteristics, perioperative data including complications, and postoperative outcomes were compared. Complication occurrence was graded according to the modified Clavien classification system. Results PK-TURP was significantly superior to M-TURP in terms of operation time, intraoperative irrigation volume, resected tissue weight, decreases in hemoglobin and sodium, postoperative irrigation volume and time, catheterization time, and hospital stay. At 5 years postoperatively, efficacy was comparable between arms. No differences were detected in safety outcomes except that the clot retention rate was significantly greater after M-TURP. Conclusion Our results indicate that PK-TURP is equally as effective in the treatment of BPO, but has a more favorable safety profile in comparison to M-TURP. The clinical efficacy of PK-TURP is long-lasting and comparable with M-TURP.

Lycopene and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis

AbstractProstate cancer (PCa) is a common illness for aging males. Lycopene has been identified as an antioxidant agent with potential anticancer properties. Studies investigating the relation between lycopene and PCa risk have produced inconsistent results. This study aims to determine dietary lycopene consumption/circulating concentration and any potential dose–response associations with the risk of PCa. Eligible studies published in English up to April 10, 2014, were searched and identified from Pubmed, Sciencedirect Online, Wiley online library databases and hand searching. The STATA (version 12.0) was applied to process the dose–response meta-analysis. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs) and to incorporate variation between studies. The linear and nonlinear dose–response relations were evaluated with data from categories of lycopene consumption/circulating concentrations. Twenty-six studies were included with 17,517 cases of PCa reported from 563,299 participants. Although inverse association between lycopene consumption and PCa risk was not found in all studies, there was a trend that with higher lycopene intake, there was reduced incidence of PCa (P = 0.078). Removal of one Chinese study in sensitivity analysis, or recalculation using data from only high-quality studies for subgroup analysis, indicated that higher lycopene consumption significantly lowered PCa risk. Furthermore, our dose–response meta-analysis demonstrated that higher lycopene consumption was linearly associated with a reduced risk of PCa with a threshold between 9 and 21 mg/day. Consistently, higher circulating lycopene levels significantly reduced the risk of PCa. Interestingly, the concentration of circulating lycopene between 2.17 and 85 &mgr;g/dL was linearly inversed with PCa risk whereas there was no linear association >85 &mgr;g/dL. In addition, greater efficacy for the circulating lycopene concentration on preventing PCa was found for studies with high quality, follow-up >10 years and where results were adjusted by the age or the body mass index. In conclusion, our novel data demonstrates that higher lycopene consumption/circulating concentration is associated with a lower risk of PCa. However, further studies are required to determine the mechanism by which lycopene reduces the risk of PCa and if there are other factors in tomato products that might potentially decrease PCa risk and progression.

Menthol Inhibits the Proliferation and Motility of Prostate Cancer DU145 Cells

In recent years, the transient receptor potential melastatin member 8 (TRPM8) channel has emerged as a promising prognostic marker and putative therapeutic target in prostate cancer. We have found that forced overexpression of TRPM8 in PC-3 cells can inhibit the cell proliferation and motility probably through the TRPM8 activation. In this study, we aimed to investigate whether activating the TRPM8 channel by its selective agonist menthol can inhibit the proliferation and motility of androgen-independent prostate cancer (AIPC) with remarkable expression of TRPM8. Menthol is a naturally occurring compound, which has been widely used in cosmetics and pharmaceutical products, and also as flavoring in food. DU145 cells are androgen-independent but have a remarkable expression of TRPM8. The demonstration of the existence of TRPM8 and the absence of TRPA1 in DU145 cells provided the foundation for the following experiments, because both TRPM8 and TRPA1 are molecular targets of menthol. The outcome of MTT assay indicated that menthol inhibited the cell growth (p < 0.01). Cell cycle distribution and scratch assay analysis revealed that menthol induced cell cycle arrest at the G0/G1 phase (p < 0.01). Furthermore, menthol inhibited the migration of DU145 cells by downregulating the focal-adhesion kinase. So it suggests that the activation of the existing TRPM8 channels may serve as a potential and pragmatic treatment for those AIPC with remarkable expression of TRPM8, and menthol is a useful compound for future development as an anticancer agent.