Microvesicles-delivering Smad7 have advantages over microvesicles in suppressing fibroblast differentiation in a model of Peyronie's disease.

BACKGROUND: This study compared the differences of microvesicles (MVs) and microvesicles-delivering Smad7 (Smad7-MVs) on macrophage M1 polarization and fibroblast differentiation in a model of Peyronie's disease (PD). METHODS: Overexpression of Smad7 in rat BMSCs was obtained by pCMV5-Smad7 transfection. MVs were collected from rat BMSCs using ultracentrifugation. In cells, 100 µg/mL of MVs or Smad7-MVs were used to treat the 100 ng/mL of lipopolysaccharide (LPS)-induced RAW264.7 cells or 10 ng/mL of recombinant transforming growth factor-ß1 (TGF-ß1)-induced fibroblasts. The pro-inflammatory cytokines and markers of M1 macrophages were measured in RAW264.7 cells, and the migration and markers of fibroblast differentiation were measured in fibroblasts. In rats, 50 µg of MVs or Smad7-MVs were used to treat the TGF-ß1-induced animals. The pathology of tunica albuginea (TA), the markers of M1 macrophages and fibroblast differentiation in the TA were measured. RESULTS: The MVs or Smad7-MVs treatment suppressed the LPS-induced macrophage M1 polarization and TGF-ß1-induced fibroblast differentiation. Moreover, the Smad7-MVs treatment decreased the fibroblast differentiation compared with the MVs treatment. In the TGF-ß1-induced TA of rats, MVs or Smad7-MVs treatment ameliorated the TA fibrosis by suppressing the macrophage M1 polarization and fibroblast differentiation. There was no significance on the M1-polarized macrophages between the MVs treatment and the Smad7-MVs treatment. Meanwhile, the Smad7-MVs treatment had an edge in terms of suppressing the fibroblast differentiation in the TGF-ß1-induced PD model compared with the MVs treatment. CONCLUSIONS: This study demonstrated that Smad7-MVs treatment had advantages over MVs treatment in suppressing of fibroblast differentiation in a model of PD.

Initial experience of percutaneous nephrolithotomy combined with retroperitoneal laparoendoscopic single-site partial nephrectomy in one-stage treatment of homolateral renal diseases.

This study investigated the feasibility of percutaneous nephrolithotomy (PCNL) combined with retroperitoneal laparoendoscopic single-site partial nephrectomy (LESS-PN) in one-stage treatment of homolateral renal calculi and tumors. Between October 2010 and July 2014 one-stage PCNL combined LESS-PN surgery was performed in 23 patients with homolateral renal calculi and tumors. Patients included 17 male and 8 female, ranged from 31 to 66 years old with a median age of 42.7. Operative parameters and occurrence rate of complications were recorded. In all cases renal tumors were successfully removed without converting to open surgery. One-stage clearance rate for renal calculi was 21/23 (91.3%), leaving two cases for second-stage operation of flexible ureteroscope lithotomy. The operation time was 95-186 min; average 128 min. Intraoperative blood loss was 40-200 mL; average 130 mL. Median warm ischemia time was 23.8 ± 9.5 min. There were no serious post-operative complications such as massive hemorrhage or urine leakage. Length of stay was 5-7 days, average 6 days. There was no recurrence of renal calculus, renal tumors or ureterostenosis and kidney functions were normal. In conclusion, with good practice, one-stage combined operation of PCNL and retroperitoneal LESS-PN in removing homolateral renal tumors and calculi was safe, feasible and would potentially reduce the operative trauma.

Minimally invasive surgery for patients with bulky bladder stones and large benign prostatic hyperplasia simultaneously: a novel design.

OBJECTIVE: To determine the efficacy and safety of a novel minimally invasive design for treating bulky vesical calculi and large benign prostatic hyperplasia (BPH) simultaneously. METHODS: 76 patients with large bladder stones (>4 cm) and large BPH (≥50 cm³) were treated from August 2008 to January 2011. 38 patients (group 1) underwent transurethral cystolithotripsy followed by transurethral resection of the prostate (TURP), 38 patients (group 2) received percutaneous cystolithotripsy within a laparoscopic entrapment bag and TURP by two surgeons simultaneously. 72 patients were followed up for 1 year. Patient demographics, perioperative parameters and follow-up data were compared. RESULTS: Patient baseline characteristics were comparable in the two groups. In group 1, 3 patients converted to open surgery and received blood transfusion, 4 patients had postoperative fever, 2 had residual stones and 1 developed urethral stricture postoperatively. In group 2, the mean total operative and the operative times for stone management were 71.6 and 30.1 min, respectively, the mean hemoglobin decrease was 0.80 g/dl, no patients received blood transfusion and no complications occurred, significantly superior to group 1. CONCLUSIONS: Percutaneous cystolithotripsy using a laparoscopic entrapment bag associated with TURP by two surgeons simultaneously is a highly effective, safe and minimally invasive method for managing large vesical calculi and large BPH.

LncRNA AFAP1-AS1 modulates the sensitivity of paclitaxel-resistant prostate cancer cells to paclitaxel via miR-195-5p/FKBP1A axis.

LncRNA AFAP1-AS1 has been corroborated to function in diverse cancers. Our aim was to investigate the molecular mechanism of AFAP1-AS1 in PTX resistance in PCa. The levels of AFAP1-AS1, miR-195-5p, and FKBP1A were checked by qRT-PCR. 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT) assay was employed to assess the resistance of PTX-resistant PCa cells to PTX. Flow cytometry was introduced to evaluate cell apoptosis. The protein levels of C-caspase 3 were determined by western blot. The starBase was used to predict the interaction between miR-195-5p and AFAP1-AS1. Xenograft tumor model was established to investigate the biological role of AFAP1-AS1 in PTX resistance in vivo. The levels of AFAP1-AS1 and FKBP1A were upregulated in PCa tissues and cells, as well as PTX-resistant PCa cells, while the expression of miR-195-5p was declined. Knockdown of AFAP1-AS1 promoted the sensitivity of PTX-resistant PCa cells to PTX, induced apoptosis of PTX-resistant PCa cells, whereas the impacts could be reversed by reducing the expression of miR-195-5p. FKBP1A overexpression could rescue the effects of miR-195-5p-mediated enhancement on the sensitivity of PTX-resistant PCa cells to PTX, promotion on apoptosis of PTX-resistant PCa cells. AFAP1-AS1 interacted with miR-195-5p and miR-195-5p could bind to the 3'UTR of FKBP1A. AFAP1-AS1 silencing inhibited the tumor growth in mice implanted with PC3-TXR cell. The protein level of PCNA was decreased in PC3-TXR cells transfected with sh-AFAP1-AS1, while the expression of C-caspase 3 was upregulated. AFAP1-AS1 silencing attenuated the resistance of PTX-resistant PCa cells to PTX by downregulating FKBP1A via sponging miR-195-5p.

[Laparoscopic radical cystectomy for 43 patients with invasive bladder carcinoma].

OBJECTIVE: To report initial experience with laparoscopic radical cystectomy in 43 patients with invasive bladder carcinoma. METHODS: From December 2003 to October 2006, 29 men and 14 women underwent laparoscopic radical cystectomy with extracorporeal-assisted urinary diversion for transitional cell carcinoma of the bladder (n=40), adenocarcinoma (n=2) and squamous cell arcinoma (n=1). We report the specific technical details and present initial results of our series. RESULTS: The mean operative time of laparoscopic radical cystectomy with pelvic lymph node dissection was 195.4 min, the mean blood loss 273.7 ml, and the transfusion rate 6.9%. Two procedures converted to open techniques. Lymphadenectomy detected lymph node metastasis in three patients. CONCLUSIONS: We demonstrate that the combination of laparoscopic radical cystectomy and extracorporeal urinary diversion is possible and remains a safe, feasible, and repeatable surgical technique. The laparoscopic surgery with extracorporeal urinary reconstruction is emerging as a viable alternative to open radical cystectomy while characterized by less trauma, short recovery time and low complications. Intermediate oncologic outcomes are encouraging and comparable to those of open series. To determine the oncologic outcome long-time follow-up will be necessary.

Importin-11 overexpression promotes the migration, invasion, and progression of bladder cancer associated with the deregulation of CDKN1A and THBS1.

OBJECTIVES: We recently determined that a novel oncogene, IPO11 from 5q12, participates in bladder cancer (BCa) progression. However, the biological function of IPO11 and the molecular mechanisms through which it contributes to BCa progression remain unclear. The aim of this study was to investigate the role of IPO11 in BCa aggressiveness and elucidate the molecular mechanisms underlying its effects in BCa. MATERIALS AND METHODS: The mRNA expression levels of IPO11 in BIU-87, RT4, UMUC3, EJ, 5637, T24, J82, and HT-1376 cell lines were determined using quantitative real-time polymerase chain reaction. Expression of importin-11 was detected in 134 formalin-fixed and paraffin-embedded (FFPE) BCa tissues and 10 paired nonneoplastic bladder tissue specimens by immunohistochemistry. The copy number of IPO11 was examined in 25 FFPE BCa specimens using fluorescent in situ hybridization. The effects of IPO11 on migration, invasion, and cell proliferation were investigated in EJ and 5637 cell lines using RNA interference. Potential molecular mechanisms were investigated using whole transcriptome sequencing and bioinformatic approaches in EJ cells and IPO11-silenced EJ cells and verified using quantitative real-time polymerase chain reaction. RESULTS: Endogenous IPO11 mRNA was highly expressed in 6 invasive BCa cell lines (EJ, HT-1376, UMUC3, 5637, J82, and T24) but had a low expression in the noninvasive BCa cell line BIU-87 and the papillary BCa cell line RT4. Immunohistochemical staining revealed that 87 (64.9%) of 134 FFPE BCa tissues displayed importin-11 overexpression. Moreover, importin-11 overexpression was positively associated with increased tumor stages and tumor grades, lymphatic invasion, and lymph node metastasis. Furthermore, importin-11 overexpression was detected in 100% (14/14) of BCa tissues with IPO11 amplification, and IPO11 amplification was not observed in 2 additional BCa tissues with importin-11 overexpression. Small interfering RNA-mediated knockdown of IPO11 is sufficient to inhibit the motility and invasiveness of EJ and 5637 cells. IPO11 knockdown also inhibited cell proliferation in EJ cells, whereas this was not observed in 5637 cells or the in vivo experiments. Using whole transcriptome sequencing, we found that 22 genes (including IPO11) were differentially expressed in IPO11-silenced EJ cells compared with wild-type EJ cells, 4 of which were upregulated, and 18 of which were downregulated. KEGG pathway enrichment analysis of the significantly differentially expressed genes showed that the proteoglycans in cancer pathway (pathway Id: hsa05205) was most significantly enriched among 10 genetically altered pathways and referred to 6 significantly altered genes (CDKN1A, HBEGF, PTK2, THBS1, CCNG2, and EGR1). The next 3 most significantly enriched pathways in order were the p53, ErbB, and BCa pathways. CDKN1A and THBS1 were the most 2 frequently covered genes and were involved in 9 and 6 pathways, respectively. They were also 2 key proteins in the BCa pathway (pathway Id: hsa05219) that were downregulated in IPO11-knockdown EJ cells compared with wild-type EJ cells. CONCLUSIONS: Importin-11 overexpression can promote BCa cell invasiveness, probably associated with the deregulation of CDKN1A and THBS1 primarily through the activation of the proteoglycans in cancer pathway and the classical BCa pathway. Importin-11 may be a useful target through which the progression of noninvasive BCa to invasive BCa can be blocked.

Laparoscopic radical cystectomy with extracorporeal ileal conduit urinary diversion for treatment of Chinese bladder cancer patients.

PURPOSE: To present our experience in laparoscopic radical cystectomy with extracorporeal urinary diversion for treatment of Chinese bladder cancer patients. METHODS: Between January 2003 and November 2005, 41 men and 5 women with organ-confined muscle-invasive transitional cell carcinoma of the bladder underwent laparoscopic radical cystectomy with the Bricker-type urinary diversion. The age range was 36-71 years. Laparoscopic radical cystectomy and bilateral pelvic lymphadenectomy were performed using five fan-shaped ports by a transperitoneal approach. An ileal conduit diversion was created through the site of specimen retrieval which was the second port at the region of the right pararectus. RESULTS: 46 radical cystectomies with Bricker-type ileal conduits were performed. No conversion to open surgery was necessary. Mean operating time was 220 min (range 120-249 min) for laparoscopic radical cystectomy and 75 min (range 65-120 min) for creating the ileal conduits. Mean estimated blood loss was 276 ml (range 155-567 ml). Two of the 46 patients needed blood transfusion (400 ml each). Mean days to ambulation and oral intake was 4.1 (range 3-5 days) and 3.5 (range 3-6 days), respectively. Mean hospital stay was 17.6 days (range 12-35 days). Mean follow-up was 6.1 months (range 3-19 months). Histopathological examination of the specimens revealed stage T2N0M0 in 18 cases, T3aN0M0 in 14, T3bN0M0 in 9 and T3bN1M0 in 5 (TNM staging). WHO grading: G1 in 2 cases, G2 in 26 cases and G3 in 18 cases. Pelvic metastases appeared in one case and 44 patients are alive and free of disease. Intravenous pyelogram at 3 weeks postoperatively shows no evidence of upper urinary obstruction in 45 patients. CONCLUSION: Despite technical difficulties, laparoscopic radical cystectomy with Bricker-type urinary diversion is feasible. With more experience in the surgical technique, laparoscopic radical cystectomy with extracorporeal urinary diversion can become an alternative treatment of choice in the selected patients with organ- confined bladder cancer in China.

Risk score based on three mRNA expression predicts the survival of bladder cancer.

Bladder cancer (BLCA) is one of the most malignant cancers worldwide, and its prognosis varies. 1214 BLCA samples in five different datasets and 2 platforms were enrolled in this study. By utilizing the gene expression in The Cancer Genome Atlas (TCGA) dataset, and another two datasets, in GSE13507 and GSE31684, we constructed a risk score staging system with Cox multivariate regression to evaluate predict the outcome of BLCA patients. Three genes consist of RCOR1, ST3GAL5, and COL10A1 were used to predict the survival of BLCA patients. The patients with low risk score have a better survival rate than those with high risk score, significantly. The survival profiles of another two datasets (GSE13507 and GSE31684), which were used for candidate gene selection, were similar as the training dataset (TCGA). Furthermore, survival prediction effect of risk score staging system in another 2 independent datasets, GSE40875 and E-TABM-4321, were also validated. Compared with other clinical observations, and the risk score performs better in evaluating the survival of BLCA patients. Moreover, the correlation between radiation were also evaluated, and we found that patients have a poor survival in high risk group, regardless of radiation. Gene Set Enrichment Analysis was also implemented to find the difference between high-risk and low-risk groups on biological pathways, and focal adhesion and JAK signaling pathway were significantly enriched. In summary, we developed a risk staging model for BLCA patients with three gene expression. The model is independent from and performs better than other clinical information.

PUMA decreases the growth of prostate cancer PC-3 cells independent of p53.

PUMA (p53 upregulated modulator of apoptosis), a member of the B-cell lymphoma 2 (Bcl-2) protein family, is a pro-apoptotic protein. PUMA expression is modulated by the tumor suppressor p53. PUMA has a role in rapid cell death via p53-dependent and -independent mechanisms. To evaluate whether p53 is required for PUMA-mediated apoptosis in prostate cancer cells, p53 protein was silenced in human prostate cancer PC-3 cells by using p53 small interfering RNA (siRNA). The interference efficiency of p53 on RNA and protein levels was detected by reverse transcription-quantitative polymerase chain reaction and western blotting. Cell proliferation and p21 expression were subsequently examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and western blot analysis, respectively. p53-silenced or control PC-3 cells were transfected with pCEP4-(hemagglutinin)-PUMA plasmid, or non-carrier plasmid. Enzyme-linked immunosorbent assay was used to determine cell apoptosis by measuring histone release and caspase-3 activation, and MTT assay was used to measure cell viability. In addition, the expression of pro-apoptosis protein Bax and anti-apoptosis protein Bcl-2 were evaluated. The results of the present study revealed that p53 siRNA significantly suppressed p53 RNA and protein expression in PC-3 cells. Deficiency of p53 increased the cell growth rate and decreased p21 expression. However, PUMA overexpression remained able to induce apoptosis in p53-silenced and control cells by increasing Bax expression and decreasing Bcl-2 expression, leading to the activation of caspase-3. These results suggest that PUMA may mediate apoptosis of prostate cancer PC-3 cells, potentially independently of p53. Furthermore, PUMA gene treatment to induce cancer cell apoptosis may be more efficient compared with p53-dependent apoptosis, where loss of p53 expression or function may lead to limited efficacy of PUMA expression. Therefore, the present study proposes the significant hypothesis that increasing PUMA expression may be an effective approach for the treatment of prostate cancer, regardless of p53 status.

Association between protocadherin 8 promoter hypermethylation and the pathological status of prostate cancer.

Promoter hypermethylation of tumor suppressor genes has been confirmed to serve a pivotal role in tumorigenesis. Protocadherin 8 (PCDH8), a novel tumor suppressor gene, has been reported to be inactivated by promoter hypermethylation a number of cancer types, including bladder cancer and renal cell carcinoma. The aim of the present study was to investigate the occurrence of PCDH8 hypermethylation in prostate cancer and its potential as a novel biomarker of prostate cancer. The transcriptional levels of PCDH8 were examined by quantitative polymerase chain reaction (PCR) in 82 prostate cancer tissues as well as 30 prostate hyperplasia tissues, and verified the protein level by western blot analysis of representative samples. PCDH8 expression levels were found to be reduced to 0.30±0.10 in 70.7% (58/82) of prostate cancer tissues. To identify the possible reason for mRNA downregulation, the methylation status of the PCDH8 promoter was assessed in prostate cancer tissues and prostate hyperplasia tissues by methylation-specific PCR (MSP). A total of 47 prostate cancer patients who exhibited reduced PCDH8 expression (57.3%; 47/82) also showed promoter hypermethylation (47/58). None of the samples (0/30) in the benign prostate hyperplasia group were positive on MSP. Furthermore, the associations between the methylation status of the PCDH8 promoter and various clinicopathological features of prostate cancer were analyzed, revealing that the methylation status of PCDH8 was closely associated with tumor size, tumor shape (papillary/non-papillary), tumor stage and tumor grade (all P<0.05), while there were no correlations with the age of the patients or the number of tumors (P>0.05). Additionally, patients with hypermethylation of the PCDH8 gene promoter had a relapse rate of 36.17% and a mortality rate of 29.79%, which were significantly higher than the hypermethylation-negative patients (P<0.05), indicating a poorer prognosis. Therefore, the methylation status of the PCDH8 gene in prostate cancer may be an important marker for use in the early diagnosis and prediction of prognosis in prostate cancer.

Combination of laparoscopic and open procedure in dismembered pyeloplasty: report of 51 cases.

BACKGROUND: Laparoscopic dismembered pyeloplasty with less trauma than open surgery is commonly performed for ureteropelvic junction obstruction despite a longer operating time and a long learning curve. We describe in this paper a new technique, which combines laparoscopic and open procedure in dismembered pyeloplasty, that we have developed in 51 patients and achieved excellent results. METHODS: The surgical procedure can be divided into two steps: laparoscopic dissection of the renal pelvis and proximal ureter transperitoneally; then accomplishing the pyeloplasty through the extended port incision above the ureteropelvic junction as in open surgery. RESULTS: All 51 operations were successful without conversion to open surgery. No intraoperative complications were observed. The operating time was 40 minutes to 90 minutes with an average of 57.5 minutes. The estimated blood loss was 15 ml to 30 ml with an average of 21.2 ml. Aberrant artery vessel and primary stricture as the cause of ureteropelvic junction obstruction was noted in 2 and 49 patients, respectively. Thirty-nine patients had fever to differing extents in the 4 days postoperation and no severe infection was observed. Four patients had urinary leakage with their drains being retained for 6 days, 6 days, 5 days or 8 days after the operation. The mean followup was 10.8 months (range 3 months to 36 months). The followup showed good results with symptom resolution in all the patients. Renal ultrasonography demonstrated that the average separation of the collecting systems decreased from preoperative 2.7 cm (range 2.0 cm to 4.7 cm) to postoperative 1.5 cm (range 1.0 cm to 2.3 cm). Excretory urography at 3 months postoperatively showed improved drainage. Of the 51 patients, 35 underwent two or more excretory urograms, demonstrating stable renal function, improved drainage and no evidence of recurrent obstruction. At the last followup visit, each patient was doing well. CONCLUSIONS: Combination of laparoscopic and open procedure in dismembered pyeloplasty offers a simpler, timesaving method in a minimally invasive fashion with low morbidity for patients with ureteropelvic junction obstruction. Ensuring quality of repair, the method provides a minimally invasive alternative with good results. It is worth future clinical application.

[Laparoscopic aid in upper urinary reconstructive operation].

OBJECTIVE: To evaluate the efficacy and feasibility of laparoscopic aid in upper urinary reconstructive operation. METHODS: Fifty-eight patients with ureteropelvic junction obstruction, 5 patients with upper ureter polypous, 2 patients with upper ureter stenosis, and 13 patients with upper ureter lithiasis underwent upper urinary reconstructive operation with laparoscopic aid described as follows:an incision 1 cm long was made, a 10 mm trocar and a 30 degrees laparoscope were wt in, the part with lesion was isolated and resected, and then pyeloplasty or end-to-end anastomosis of ureter was performed. RESULTS: The mean operative time was 33 minutes (25-45 minutes). The mean blood loss was 20 ml (15-25 ml). Complications such as urinary leakage and infection were observed. The double J stent was removed at 1 month after the operation. Follow-up for 3 to 15 months in 20 cases showed alleviation of hydronephrosis. CONCLUSION: An effective and safe method with less wound and operative time, combination of laparoscopic aid and open surgery in upper urinary reconstructive operation helps avoid difficult laparoscopic operation, does not increase trauma of the abdominal wall, and is worth promoting clinically.

The complete mitochondrial genome sequence of the prostate adenocarcinoma rat R3327.

The prostate adenocarcinoma of the Copenhagen rat (R3327) is recognized as a suitable model for human prostate carcinoma. In this study, we sequenced its complete mitogenome and total length of the genome was 16,310 bp (GenBank Accession Number KM820831). It contains 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. This mitochondrial genome sequence will provide new genetic resource into prostate adenocarcinoma disease.

Initial Experience of Sorafenib Neoadjuvant Therapy Combined with Retroperitoneoscopy in Treating T2 Large Renal Carcinoma.

OBJECTIVES: To investigate the safety and feasibility of sorafenib neoadjuvant therapy combined with retroperitoneoscopic radical nephrectomy (RRN) in treating T2 large renal cell carcinoma (RCC). METHODS: Retrospectively analyzed 5 cases (2 males and 3 females, aged 52-73 years) of T2 stage large RCC who receive preoperative sorafenib targeted treatment (400 mg bid for 1-3 months) and RRN between March, 2013, and July, 2014. Patient information, therapeutic regimen, drug adverse effect, tumor changes before and after surgery, and perioperative parameters were recorded. RESULTS: During the sorafenib therapy adverse effects included 2 cases of hypertension (Grade I toxicity), 1 case of hand-foot syndrome (Grade I), and 1 case of diarrhea (Grade II), which were all tolerable for patients. CT scan and histopathological tests confirmed significant reduction in the longest dimension (LD) and medium density (MD) of the tumor after therapy as well as tumor hemorrhage, necrosis, and cystic degeneration. All 5 patients received RRN surgery successfully around 2 weeks after drug discontinuation with only 1 case of perioperative complication. CONCLUSIONS: Sorafenib neoadjuvant therapy could significantly reduce the size and aggressiveness of T2 large renal tumors, thus reducing the operative challenge and enabling patients who were previously disqualified for operation to receive surgical treatment.

Application of renal-rotation techniques in retroperitoneoscopic partial nephrectomy.

Retroperitoneoscopic partial nephrectomy (RPN) is one of the standard methods for treating T1-stage renal carcinoma, which has a narrow operational space and a difficult surgical procedure. The aim of this study was to examine the safety and feasibility of renal-rotation techniques in RPN. Between April 2012 and June 2014, the renal-rotation technique in RPN was performed in 22 male and 16 female patients, aged between 31 and 75 years (mean, 52 years), with stage T1N0M0 renal-cell carcinoma. In 29 cases the tumor was located at the ventral side of the kidney, including 22 cases at the renal hilum, and in nine cases the tumor was located at the inferior pole of the kidney. The tumor size was between 1.5 and 4.6 cm (mean, 2.8 cm). The results showed that, in all 38 cases, the procedure was successfully accomplished without conversion to open surgery. There were no intraoperative complications and only three cases of postoperative complications. The surgery duration was between 45 and 116 min (mean, 59 min); blood loss was between 10 and 120 ml (mean, 40 ml) and no patients required a blood transfusion. The average kidney ischemia time was 21 min (range, 15-38 min). No patients had local recurrence or metastasis after follow-up of between one and 26 months. In conclusion, the application of the renal-rotation technique in RPN for tumors located at the ventral side, renal hilum or at the inferior pole of the kidney is safe and feasible and worth wider clinical application.

A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma.

Clear cell renal cell carcinomas (ccRCCs) display divergent clinical behaviours. Molecular markers might improve risk stratification of ccRCC. Here we use, based on genome-wide CpG methylation profiling, a LASSO model to develop a five-CpG-based assay for ccRCC prognosis that can be used with formalin-fixed paraffin-embedded specimens. The five-CpG-based classifier was validated in three independent sets from China, United States and the Cancer Genome Atlas data set. The classifier predicts the overall survival of ccRCC patients (hazard ratio=2.96-4.82; P=3.9 × 10(-6)-2.2 × 10(-9)), independent of standard clinical prognostic factors. The five-CpG-based classifier successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome in respective clinical stages and individual 'stage, size, grade and necrosis' scores. Moreover, methylation at the five CpGs correlates with expression of five genes: PITX1, FOXE3, TWF2, EHBP1L1 and RIN1. Our five-CpG-based classifier is a practical and reliable prognostic tool for ccRCC that can add prognostic value to the staging system.

The therapeutic efficacy of I131-PSCA-mAb in orthotopic mouse models of prostate cancer.

BACKGROUND: Prostate stem cell antigen (PSCA) is upregulated in prostate cancer tissues. Here we aimed to study the therapeutic efficacy of a monoclonal antibody of PSCA-labeled I131 (I131-PSCA-mAb) in orthotopic mouse models of prostate cancer. METHODS: The proliferation, apoptosis and invasion abilities of PC-3 and LNCaP cells treated with I131-PSCA-mAb were measured by methyl thiazolyl tetrazolium assay, flow cytometry and transwell culture, respectively. The human prostate cancer models were established by orthotopic implantation of PC-3 and LNCaP cells in nude mice. I131-PSCA-mAb distribution and tumor cell apoptosis in the tumor-bearing nude mice were measured. RESULTS: The inhibitory and apoptosis rates of PC-3 and LNCaP cells treated with I131-PSCA-mAb reached a maximum of 84%, 80% and 50%, 46%, respectively, which were obviously higher than in the cells treated with I131-IgG or PSCA-mAb. The invaded number of PC-3 and LNCaP cells treated with I131-PSCA-mAbe was significantly reduced (P < 0.01) compared with the control group. The ratios of I131-PSCA-mAb in tumor to intramuscular I131-PSCA-mAb (T/NT) in tumor-bearing nude mice were increased with time and reached the highest level after 8 h. T/NT stayed above 3.0 after 12 h, and the tumor could still be developed after 24 h. The number of apoptotic cells in tumor tissue of nude mice treated with I131-PSCA-mAb was larger than that in the control group. CONCLUSION: I131-PSCA-mAb has the potential to become a new targeted therapy drug for the treatment of prostate cancer.

MicroRNA expression profile analysis reveals diagnostic biomarker for human prostate cancer.

Prostate cancer is a highly prevalent disease in older men of the western world. MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via posttranscriptional inhibition of protein synthesis. To identify the diagnostic potential of miRNAs in prostate cancer, we downloaded the miRNA expression profile of prostate cancer from the GEO database and analysed the differentially expressed miRNAs (DE-miRNAs) in prostate cancerous tissue compared to non-cancerous tissue. Then, the targets of these DE-miRNAs were extracted from the database and mapped to the STRING and KEGG databases for network construction and pathway enrichment analysis. We identified a total of 16 miRNAs that showed a significant differential expression in cancer samples. A total of 9 target genes corresponding to 3 DE-miRNAs were obtained. After network and pathway enrichment analysis, we finally demonstrated that miR-20 appears to play an important role in the regulation of prostate cancer onset. MiR-20 as single biomarker or in combination could be useful in the diagnosis of prostate cancer. We anticipate our study could provide the groundwork for further experiments.