Sea cucumber extract TBL-12 inhibits the proliferation, migration, and invasion of human prostate cancer cells through the p38 mitogen-activated protein kinase and intrinsic caspase apoptosis pathway.

BACKGROUND: Sea cucumber is a kind of nutritious echinoderm that has multiple biological activities, including antioxidant, antibacterial, and antitumor activities. However, there is no extensive study on the antitumor effect of sea cucumber extract on prostate cancer (PCa). TBL-12 is a new sea cucumber extract. In this study, we investigated the in vivo anti-PCa effect of TBL-12 and its in vitro effects on the proliferation, apoptosis, migration, and invasion of the human PCa cell lines LNCaP, 22RV1, PC-3, and DU145, and evaluated its possible mechanisms. METHODS: Cell proliferation was analyzed by cell counting kit-8 and colony formation assays. Scratch migration assay and transwell invasiveness assay were used to observe TBL-12 effect on the migration and invasion of PCa cells. Matrix metalloproteinase 2 (MMP-2) and MMP-9 expression and enzymatic activity was determined by Western blot analysis, quantitative reverse-transcription polymerase chain reaction, and gelatin zymography. Apoptosis level was detected by flow cytometry analysis. Western blot analysis was used to analyze p38 mitogen-activated protein kinase (MAPK) and apoptosis pathways. Angiogenic array analysis was used to explore autocrine and paracrine growth factors in PCa cell lines. Xenograft tumor model was built to observe the in vivo anticancer effect. RESULTS: TBL-12 could significantly inhibit tumor growth in xenograft PCa mice in vivo, and dramatically inhibit the proliferation, colony formation, migration, and invasiveness of PCa cells in vitro (P < 0.05 and P < 0.001). The expression and enzyme activity of MMP-2 and MMP-9 were significantly suppressed by TBL-12 ( P < 0.01), and decreased phosphorylation level of p38 in PCa cells was detected ( P < 0.001). Furthermore, TBL-12 could reinforce the MMP-2/MMP-9 inhibitory effect of SB203580, a specific inhibitor of the p38 MAPK pathway ( P < 0.05). Besides, TBL-12 could induce the apoptosis of PCa cells by activating caspase-9, caspase-7, and poly(ADP-ribose) polymerase and suppressing survivin, and inhibit the secretion of angiogenin, angiopoietin-2, and vascular endothelial growth factor in PCa cells. CONCLUSIONS: Sea cucumber extract TBL-12 could suppress the proliferation and metastasis of human PCa cells by inhibiting MMP-2 and MMP-9 via blocking the p38 MAPK pathway, inducing apoptosis through intrinsic caspase apoptosis pathway and inhibiting the secretion of angiogenic factors. Our findings may be of importance and significance for the research and clinical applications of sea cucumber extract in PCa treatment.

Efficacy of intra-arterial chemotherapy combined with intravesical chemotherapy in T1G3 bladder cancer when compared with intravesical chemotherapy alone after bladder-sparing surgery: a retrospective study.

PURPOSE: To assess the efficacy of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IVC) in T1G3 bladder cancer (Bca) after transurethral resection of bladder tumor (TURBT). METHODS: Our study retrospectively reviewed 200 patients with T1G3 BCa who had all undergone TURBT. The patients' medical records were divided into two groups, one group only had IVC with pirarubicin after surgery, and the other group had IAC (cisplatin and epirubicin) combined with IVC after surgery. The patients were monitored regularly by urine cytology and cystoscopy. Survival and recurrence curves were calculated using the Kaplan-Meier method. Tumor recurrence, progression and tumor-specific death rate were compared with Chi-square test. A multivariate analysis was carried out to find out potential confounders. RESULTS: A total of 200 medical record was analyzed, 131 patients received IVC, 69 IAC + IVC treatment, tumor-specific death rate between the combined IAC and IVC compared to IVC alone was 7.25 and 17.6%, respectively (p < 0.05); the tumor recurrence rate between the two groups was 31.8% (22/69) and 44.3%, respectively (58/131) (p < 0.05), and tumor recurred later in the IAC + IVC group (p < 0.05), tumor progression rate was 18.8% (13/69) and 28.2% (37/131), respectively, with p < 0.05. Overall survival was longer in IAC + IVC group (p < 0.05). Using the multivariable regression model, IAC was significantly related to disease recurrence (p < 0.05) and overall survival (p < 0.05). CONCLUSION: T1G3 BCa post-TURBT surgery patients who underwent IAC combined with IVC had a longer overall survival and increased time interval to first recurrence, lower tumor recurrence rate, progression rate and tumor-specific death rate than compared with those who only underwent IVC alone.

MTHFD2 Overexpression Predicts Poor Prognosis in Renal Cell Carcinoma and is Associated with Cell Proliferation and Vimentin-Modulated Migration and Invasion.

BACKGROUND/AIMS: To investigate the role of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) in the clinical prognosis and cell biology of renal cell carcinoma (RCC). METHODS: A total of 137 RCC tissues were evaluated by immunohistochemistry. The relationship between MTHFD2 overexpression and clinical parameters and vimentin expression was assessed. Kaplan-Meier curves and the log-rank test were applied for survival analysis according to MTHFD2 and vimentin expression in RCC tissues. The expression of MTHFD2 mRNA and protein was examined by quantitative reverse transcription PCR and western blotting, respectively. To determine further the biological activity of MTHFD2 in RCC, 786-O cells were transfected with short hairpin RNA specifically targeting MTHFD2 (shMTHFD2) with or without tumor necrosis factor (TNF)-α stimulation. Cell proliferation, cell migration and invasion and drug sensitivity were subsequently assessed using Cell Counting Kit-8, wound healing, and Transwell assays. RESULTS: Immunohistochemical analysis demonstrated that both MTHFD2 and vimentin overexpression was positively associated with clinical staging, pathological grade, and poor overall survival (all P < 0.05). MTHFD2 expression was closely correlated with vimentin overexpression in RCC (r = 0.402, P < 0.001). After knocking down MTHFD2 expression in 786-O cells, decreased cell proliferation, migration, and invasion were observed and accompanied by the reduced expression of vimentin. The effects of MTHFD2 down-regulation could be partially restrained by TNF-α treatment. Vimentin expression and cell migration and invasion, but not cell proliferation, were reversed by TNF-α stimulation. Furthermore, treatment of 786-O cells with shMTHFD2 increased their sensitivity to chemotherapy drugs. CONCLUSION: The current results demonstrated that MTHFD2 was overexpressed in RCC and associated with poor clinical characteristics, vimentin expression, and cellular features connected to malignant disease, thus, implicating MTHFD2 as a potential target for RCC therapy.

Low-dose Bacillus Calmette-Guerin versus full-dose for intermediate and high-risk of non-muscle invasive bladder cancer: a Markov model.

BACKGROUND: To compare the efficacy of low dose (27 mg) Bacillus Calmette-Guérin (BCG) and a full dose (81 mg) BCG immunotherapy for patients with intermediate and high-risk non-muscle invasive bladder cancer (NMIBC) after a typical transurethral bladder resection. METHODS: We constructed a Markov model for a 20-year simulation of the disease to compare the overall survival of patients with intermediate and high-risk of NMIBC between the full-dose therapy (FD group) and the low-dose therapy (LD group). Base case analysis, one-way and two-way sensitivity analysis and a second-order Monte Carlo analysis were performed based on data from 15 published articles. RESULTS: The expected overall survivals were 9.56 (9.55-9.57) years for FD group and 9.63 (9.61-9.64) years for LD group(P < 0.001). The estimated mortality in the FD group at 5, 10, and 20 years were 34.23%, 57.51% and 83.14%, respectively. The corresponding values in the LD group were 34.11%, 57.17%, 82.16%, respectively. Age-specific mortality and metastatic rate after undergoing radical cystectomy (RC) were the most two sensitive parameters in both groups. The rate of disease recurrence with disease worsening is the determining factor when choosing the optimal dose of BCG treatment. CONCLUSIONS: A low-dose BCG treatment may act slightly better than a full-dose BCG treatment for patients with intermediate and high-risk of NMIBC. This finding will require further high-quality studies to validate.

Vasculogenic mimicry plays an important role in adrenocortical carcinoma.

OBJECTIVES: To determine the prognostic role of vasculogenic mimicry in adrenocortical carcinoma, and to explore its relationship with vascular endothelial growth factor receptor 2 expression. METHODS: A total of 46 samples of adrenocortical carcinoma were collected and reviewed. Vasculogenic mimicry and vascular endothelial growth factor receptor 2 were detected by immunohistochemistry and double staining. Survival analysis was carried out to access pronostic significance. Three-dimensional culture method was applied to test the ability of vasculogenic mimicry formation by adrenocortical carcinoma cell lines SW-13 and H295R. Quantitative polymerase chain reaction and western blotting were used to monitor the expression of vascular endothelial growth factor receptor 2 in SW-13 and H295R. After being treated with specific inhibitor or small interfering ribonucleic acid to downregulate expression of vascular endothelial growth factor receptor 2, vasculogenic mimicry formation and cell prolifration of SW-13 cells were evaluated by 3-D culture and Cell Counting Kit-8 methods. RESULTS: Vasculogenic mimicry was observed in 19 of the 46 (41.30%) adrenocortical carcinoma samples. Both vasculogenic mimicry and vascular endothelial growth factor receptor 2 expressions showed a positive association with Weiss score and TNM stage, whereas vascular endothelial growth factor receptor 2 was also associated with tumor size (all P < 0.05). Vasculogenic mimicry was closely correlated with vascular endothelial growth factor receptor 2 expressions (r = 0.470, P < 0.01). The median overall survival of patients with vasculogenicmimicry-positive or vascular endothelial growth factor receptor 2-positive was shorter than that of patients with vasculogenic mimicry-negative or vascular endothelial growth factor receptor 2-negative (P = 0.001 and 0.028, respectively). The vasculogenic mimicry-forming SW-13 cells expressed higher levels of vascular endothelial growth factor receptor 2 than that of H295R, which was unable to form vasculogenic mimicry on Matrigel. However, downregulation of vascular endothelial growth factor receptor 2 only decreased cell proliferation, but not vasculogenic mimicry formation by SW-13 cells. CONCLUSIONS: Vasculogenic mimicry and overexpression of vascular endothelial growth factor receptor 2 seem to correlate with poor prognostic outcomes in adrenocortical carcinoma. Anti-angiogenesis treatments targeting vascular endothelial growth factor receptor 2 should be combined with therapies targeting vasculogenic mimicry in adrenocortical carcinoma.

En bloc transurethral resection with 2-micron continuous-wave laser for primary non-muscle-invasive bladder cancer: a randomized controlled trial.

PURPOSE: To evaluate the practicability of en bloc transurethral resection with 2-micron continuous-wave laser as treatment for primary non-muscle-invasive bladder cancer (NMIBC). METHODS: This was a single-center, randomized, controlled trial involving 142 patients with newly diagnosed NMIBC. All patients were randomly assigned in a 1:1 ratio to receive either laser treatment or conventional transurethral resection of bladder tumor (TURBT). All patients received intravesical chemotherapy. Follow-up was performed in 18 months. Primary outcome measure was difference of tumor recurrence rate at the end of study. RESULTS: Baseline characteristics did not differ between patients in two groups. Operation time was longer in laser group than in TURBT group (56.5 ± 37.4 vs. 41.0 ± 29.4 min, P = 0.017). Obturator nerve reflection was noted during TURBT in 18 patients, whereas none was noted during laser resection. Number of T1 tumors was higher in the laser group (25 vs. 15, P = 0.047). According to Kaplan-Meier survival curves, there was no statistical difference in the rate of recurrence in 18 months (P = 0.383). All recurrences were out of the site of first resection, and there was no progression in tumor grade. CONCLUSION: Two-micron continuous-wave laser did not diminish tumor recurrence rate in primary NMIBC for 18-months observation. However, T1 tumors were significantly higher among laser group. Clear and complete tumor bases were easily conserved by laser resection, which may enable pathologists to distinguish the T stages of bladder cancer more easily. Further studies need to be done in future.

Comparison between laparoscopic partial nephrectomy and laparoscopic ablation therapy: a meta-analysis.

OBJECTIVE: To conduct a meta-analysis of the literature evaluating comparisons on the peri-operative and oncological outcomes between laparoscopic partial nephrectomy (LPN) and laparoscopic ablation therapy (LAT) in the treatment of small renal masses (SRMs). MATERIAL AND METHODS: MEDLINE, EMBASE, Google Scholar, Cochrane Library, and CNKI were searched for clinical trials comparing LPN with LAT. Data of peri-operative and follow-up outcomes were extracted and compared. Publication bias was identified and sensitivity analysis was also performed. RESULTS: Data from 11 studies including 928 patients (525 patients in the LPN group and 403 in the LAT group) were collected. Baseline characteristics were compared and differences were found in age, preoperative renal function and proportion of solitary kidney (p < 0.05 respectively). For peri-operative outcomes, the LPN group had greater estimated blood loss, longer operative duration and length of hospital stay, and more peri-operative complications (p < 0.05, respectively). The LAT group had a significantly higher local recurrence (p < 0.05). There was no significant difference in postoperative change of renal function (p = 0.21). CONCLUSION: In comparison with LPN, LAT provides better peri-operative outcomes, but a higher local recurrence rate. LAT does not seem to provide an obvious advantage in protecting renal function. Further clinical trials with randomized design and long-term follow-up are needed.

Transurethral bipolar plasma kinetic resection of ejaculatory duct for treatment of ejaculatory duct obstruction.

To evaluate the efficacy of transurethral bipolar plasma kinetic resection of ejaculatory duct for ejaculatory duct obstruction. The clinical information of 42 cases of ejaculatory duct obstruction was analyzed between July 2008 and June 2012. The diagnostic criteria included semen analysis, fructose and neutral α-glucosidase measurement in seminal plasma, transrectal ultrasonography, magnetic resonance imaging and vasography necessarily. Endoscopic procedure with bipolar plasma kinetic resection of ejaculatory duct was performed in all patients. Among these cases followed up 6 ≈ 24 months after operation, 38 patients (90.5%) had improved semen parameters, 23 azoospermic patients (60.5%) had sperm in the semen and 13 patients' wife (31%) achieved pregnancies in 42 cases of bipolar plasma kinetic resection of ejaculatory duct. Postoperative complications ensued as epididymitis in 1 case, watery ejaculate in 1, but no serious complication was observed. Bipolar plasma kinetic resection of ejaculatory duct appears to represent a promising endoscopic treatment alternative for ejaculatory duct obstruction patients, with high efficacy, less complications, quicker recovery and satisfactory follow-up parameters.

Upregulation of BMP1 through ncRNAs correlates with adverse outcomes and immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) accounts for approximately 2-3% of all adult malignancies. Clear cell renal cell carcinoma (ccRCC), which comprises 70-80% of all RCC cases, is the most common histological subtype. METHODS: ccRCC transcriptome data and clinical information were downloaded from the TCGA database. We used the TCGA and GEPIA databases to analyze relative expression of BMP1 in various types of human cancer. GEPIA was used to perform survival analysis for BMP1 in various cancer types. Upstream binding miRNAs of BMP1 were obtained through several important target gene prediction tools. StarBase was used to predict candidate miRNAs that may bind to BMP1 and candidate lncRNAs that may bind to hsa-miR-532-3p. We analyzed the association between expression of BMP1 and immune cell infiltration levels in ccRCC using the TIMER website. The relationship between BMP1 expression levels and immune checkpoint expression levels was also investigated. RESULTS: BMP1 was upregulated in GBM, HNSC, KIRC, KIRP and STAD and downregulated in KICH and PRAD. Combined with OS and DFS, BMP1 can be used as a biomarker for poor prognosis among patients with KIRC. Through expression analysis, survival analysis and correlation analysis, LINC00685, SLC16A1-AS1, PVT1, VPS9D1-AS1, SNHG15 and the CCDC18-AS1/hsa-miR-532-3p/BMP1 axis were established as the most potential upstream ncRNA-related pathways of BMP1 in ccRCC. Furthermore, we found that BMP1 levels correlated significantly positively with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. CONCLUSION: Our results demonstrate that ncRNA-mediated high expression of BMP1 is associated with poor prognosis and tumor immune infiltration in ccRCC.

[Clinical characteristics and surgical treatment for localized Castleman's disease].

OBJECTIVE: To investigate the clinical characteristics and treatment of localized Castleman's disease (CD), and review the literatures to improve the diagnosis and management of this disease. METHODS: The clinical symptoms, histopathology, CT, MRI findings and results of surgery in 20 patients with localized CD were evaluated retrospectively. RESULTS: The average age of the patients was 37.7 years. The lesions were located in the retroperitoneal space (9 cases), mediastinum (7 cases), pelvic cavity (1 case), neck (1 case), upper arm (1 case), and axillary (1 case). All patients underwent surgical resection, including 9 cases for retroperitoneal resection (6 cases had open operation and 3 cases laparoscopic resection) and 7 cases for mediastinal resection (open operation in 5 cases and thoracoscopic resection in 2 cases). The Castleman's disease was confirmed by histopathology. There were hyaline vascular type of CD in 17 cases, plasma cell type of CD in 1 case, and mixed cellularity type of CD in 2 cases. The duration of follow-up ranged from 12 to 165 months for 16 cases. Among them 15 patients were alive without recurrence, and 1 case had recurrence in the primary site at 47 months after the operation. CONCLUSIONS: Patients with Castleman's disease have no typical clinical symptoms and have normal laboratory results. The majority of patients are of hyaline vascular type of the disease. Imaging examination is helpful to diagnosis, and the final diagnosis depends on pathologic examination. Complete surgical resection of the tumor is the best treatment for localized Castleman's disease.

Percutaneous ultrasound-guided radiofrequency ablation treatment and genetic testing for renal cell carcinoma with Von Hippel-Lindau disease.

Percutaneous ultrasound-guided radiofrequency ablation is increasingly being studied in the treatment of renal tumors. Because percutaneous ultrasound-guided radiofrequency ablation is a minimally invasive and nephron-sparing procedure, it is ideally suited for patients with a single kidney, multiple tumors, or contraindications to conventional surgery. We report on a patient with Von Hippel-Lindau (VHL) disease who had multicentric tumors in the single kidney that was successfully treated with percutaneous ultrasound-guided radiofrequncy ablation. The one-year follow-up showed that there was no local recurrence or metastasis. And genetic testing showed the patient had a T to G heterozygotic missense mutation at nucleotide 515 of VHL gene exon 1.

OIP5 Is a Novel Prognostic Biomarker in Clear Cell Renal Cell Cancer Correlating With Immune Infiltrates.

Opa interacting protein 5 (OIP5), overexpressed in some types of human cancers, has been reported to be associated with the carcinogenesis of human cancer. However, its contribution to cancer immunity remains unknown. Furthermore, the relationship between OIP5 and cancer immunity remains uncertain. In our research, we explored the different expression of OIP5 between 539 ccRCC and 72 normal renal tissues base on TCGA data set. We analyzed the associations between OIP5 expression with ccRCC progression and survival. Next, we compared immune cell profiles in cancer tissues and normal tissues in the Cancer Genome Atlas (TCGA) ccRCC cohort. We found that the level of immune cell infiltration was correlated with the copy number of OIP5 gene in ccRCC. The effect of OIP5 on immune activity was verified by Gene Set Enrichment Analysis of RNA-seq data from 32 ccRCC cell lines in the public database. Moreover, a pathway enrichment analysis of 49 OIP5-associated immunomodulators demonstrated the involvement of the T cell receptor signaling pathway, the JAK-STAT signaling pathway, the NF-kappa B signaling pathway and the primary immunodeficiency pathway. In addition, using OIP5-associated immunomodulators, we constructed multiple-gene risk prediction signatures using the Cox regression model. Our results provided insights into the role of OIP5 in tumor immunity and revealed that OIP5 may be a potential immunotherapeutic target for ccRCC. Designated immune signature is a promising prognostic biomarker in ccRCC.

[Impact of asymptomatic prostatitis on semen quality].

OBJECTIVES: To study the impact of asymptomatic prostatitis on semen parameters. METHOD: Based on the count of WBC in EPS, we assigned 152 patients with asymptomatic (type IV) prostatitis to Groups A (WBC + to + +) and B (WBC + + + to + + + +), and included 68 normal healthy men controls in Group C. All the patients were examined for the volume, pH value and liquefaction time of the semen, sperm concentration, sperm survival rate, grade a sperm percentage, morphologically normal sperm percentage, WBC count, and accompanying inflammatory cytokines. RESULTS: The semen liquefaction time, grade a sperm percentage and morphologically normal sperm percentage were (24.5 +/- 5.2) min, 20.0 +/- 4.1 and 10.5 +/- 4.8 in Group A, (30.4 +/- 5.0) min, 10.0 +/- 3.8 and 7.5 +/- 4.2 in Group B, and (18.5 +/- 5.3) min, 32.3 +/- 4.5 and 17.8 +/- 3.6 in Group C, with statistically significant differences between A and B (P < 0.01). The pH value, semen volume, sperm survival rate and sperm concentration were 7.6 +/- 0.3, (3.0 +/- 1.1) ml, 56.0 +/- 6.0 and (65.9 +/- 11.3) x 10(6)/ml in Group A, 7.7 +/- 0.3, (2.8 +/- 1.2) ml, 52.3 +/- 6.3 and (62.5 +/- 10.3) x 10(6)/ml in Group B, and 7.5 +/- 0.2, (2.9 +/- 1.2) ml, 62.1.0 +/- 5.3 and (87.7 +/- 10.1) x 10(6)/ml in Group C, with no significant differences among the three groups (P > 0.05). The contents of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) in the semen were (58.64 +/- 30.82) pg/ml and (50.57 +/- 27.48) pg/ml in Group B, significantly increased as compared with (17.68 +/- 5.65) pg/ml and (23.50 +/- 4.80) pg/ml in Group C (P < 0.01). CONCLUSION: Asymptomatic prostatitis effects significant changes in the major parameters of the patient's semen quality.

[Transrectal ultrasonography in the etiological diagnosis of male obstructive azoospermia: analysis of 695 cases].

OBJECTIVE: To assess the role of transrectal ultrasonography (TRUS) in the etiological diagnosis of male obstructive azoospermia. METHODS: We retrospectively analyzed the clinical data and TRUS findings of 695 patients with obstructive azoospermia from January 2007 to May 2009. RESULTS: Concerning the etiology of obstructive azoospermia, the main TRUS findings included ejaculatory duct abnormality (29.2%), seminal vesicle abnormality (25.4%) and prostate midline cyst (18.5%). TRUS revealed 203 cases of ejaculatory duct dilation, 177 cases of seminal vesicle abnormality (including 108 with absence or agenesis and 51 with dilation of the seminal vesicle), and 128 cases of prostate midline cyst (including 75 with ejaculatory duct cyst and 39 with Müllerian cyst). Calcification of the verumontanum or ejaculatory duct was suspected to be the causes of obstructive azoospermia in 34 cases. However, no significant etiological abnormality was found in 153 cases. Obvious etiology was shown by TRUS in 78.0% of the patients. CONCLUSION: TRUS can clearly display the structural abnormality of the ejaculatory duct and seminal vesicle, and provide important information on the etiology of male obstructive azoospermia.

[Multivariate analysis of recurrence factors for non muscle-invasive bladder urothelial carcinomas].

OBJECTIVE: To discuss the risk factors of recurrent non-muscle-invasive bladder cancer and elucidate its clinical significance. METHODS: The retrospective survival analysis of 161 patients with non-muscle-invasive bladder cancer was performed by Kaplan-Meier method, Log-rank test and COX proportional hazard model. RESULTS: On univariate analysis, the parameters of tumor stage, tumor grade, number of tumors and previous recurrence were significant for tumor recurrence (all P < 0.05). On multivariate analysis of COX proportional hazard model, all the above risk factors remained significant for tumor recurrence. The hazard ratios were as follows: tumor stage (RR = 3.810, P = 0.001), tumor grade (RR = 2.416, P = 0.009), number of tumors (RR = 1.736, P = 0.036) and previous recurrence (RR = 1.810, P = 0.010). CONCLUSION: Tumor stage and tumor grade plays the most important role in tumor recurrence.

Vimentin Overexpressions Induced by Cell Hypoxia Promote Vasculogenic Mimicry by Renal Cell Carcinoma Cells.

Vasculogenic mimicry (VM), the novel approach for tumor cells to obtain blood supply, was reported to be involved in antiangiogenic resistance and poor prognosis in renal cell carcinoma (RCC). However, the molecular mechanisms underlying VM formed by RCC cells are still not clearly depicted. In the present study, we found that OS-RC-2 acquired the VM forming ability accompanied with the increased expressions of Vimentin and AXL and decreased expression of E-Cadherin by CoCl2 treatment. Downregulation of Vimentin by siRNA severely impaired the capability of OS-RC-2 and 786-O to form VM structures induced by cell hypoxia in vitro. Moreover, knockdown of Vimentin inhibited cell migration and invasion, which could be prompted by hypoxia induction in RCC cells. In our clear cell RCC tissues, we found that VM was positively correlated with Vimentin overexpression and both predicted poor prognosis. In conclusion, Vimentin plays an important role in hypoxia induced VM formation of RCC cells and targeted Vimentin might be beneficial for RCC therapy.

Evaluation of the effects of intra-arterial chemotherapy combined with intravesical chemotherapy against intravesical chemotherapy alone after transurethral resection of bladder tumor in T1-staged Grade 3 bladder cancer.

OBJECTIVE: Comparing intra-arterial chemotherapy combined with intravesical chemotherapy against intravesical chemotherapy alone in the treatment of T1-staged Grade 3 (T1G3) bladder cancer after transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: From January 2007 to December 2012, 203 patients diagnosed with NMIBC were randomly assigned into either intra-arterial chemotherapy combined with intravesical chemotherapy group (Group A, n = 68) or intravesical chemotherapy alone group (Group B, n = 135) after TURBT. Four cycles of intra-arterial chemotherapy were administered after initial TURBT with 1-month interval between each. Intravesical chemotherapy was administered in both groups including an immediate 50 mg epirubicin instillation after TURBT and weekly maintenance for 8 weeks, and then followed by monthly maintenance for 1 year. The primary endpoint was recurrence-free survival. RESULTS: Out of 203 patients, 53 were in Group A and 98 in Group B, and they were evaluated for recurrence and progression rate where recurrence rate was 35.8% (19/53) in group A and 41.8% (41/98) in group B with a significant difference (P < 0.05) and progression rate was 20.7% (11/53) in group A and 23.5% (23/98) in group B with a significant difference (P < 0.05). Univariate and multivariate logistic regression analysis suggested that intra-arterial chemotherapy could be an independent risk factors related to both overall survival and time to first recurrence. CONCLUSIONS: Intra-arterial chemotherapy combined with intravesical chemotherapy could reduce the risk of recurrence and progression compared to intravesical chemotherapy alone in T1G3 bladder cancer.

Efficacy and Safety of Serenoa repens Extract Among Patients with Benign Prostatic Hyperplasia in China: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial.

OBJECTIVE: To evaluate the efficacy and safety of Serenoa repens among patients with benign prostatic hyperplasia (lower urinary tract symptoms/benign prostatic hyperplasia [LUTS/BPH]) in China. METHODS: We conducted a double blind, placebo-controlled study of 354 patients with LUTS/BPH from 19 institutions, to evaluate the efficacy and safety of Serenoa repens. Participants were randomly assigned (1:1) into the Serenoa repens extract (320 mg) or placebo groups for 24 weeks. Primary efficacy parameters were changes in International Prostate Symptom Score and peak urinary flow from baseline to each assessment. Secondary efficacy parameters included improvement of storage symptom and voiding symptom scores, prostate volume, urinary frequency, and total prostate-specific antigen level. Other parameters assessed were quality of life score, a four-item male sexual function questionnaire score, and International Index of Erectile Function score across the consecutive double-blind visits. RESULTS: Statistically significant improvement in the peak urinary flow, International Prostate Symptom Score, scores of storage symptoms and voiding symptoms, quality of life score, four-item male sexual function questionnaire score, and International Index of Erectile Function score were observed in the Serenoa repens extract group compared with those in the placebo group (P <.05). Two (1.18%) of 169 patients in the placebo group and 3 (1.89) of 159 patients in the Serenoa repens extract group experienced 1 or more adverse events. CONCLUSION: The Serenoa repens extract was effective, safe, well-tolerated, and clinically and statistically superior to placebo in the target LUTS/BPH population.