Inhibition of integrin receptors reduces extracellular matrix levels, ameliorating benign prostate hyperplasia.

Although a high prevalence of benign prostate hyperplasia (BPH) has been documented, the risk factors are poorly understood. Metabolic syndrome increases the risk of BPH. Succinylation, a type of posttranslational modification, mostly targets metabolic processes. The level of succinylation was investigated in 4 BPH patients and 4 healthy controls. Additionally, 176 patients with BPH were analyzed by using pan-antisuccinyllysine antibody blotting. TMT-labeling proteomic and sc-RNAseq Cellchat analyses were employed to identify key signaling factors involved in the development of BPH. In vivo and in vitro experiments were used to confirm the role of integrin receptors. The global succinylation level in BPH was higher than that in the healthy prostate. Positive correlations of prostate volume with IHC score sand urodynamics testing were found in large clinical cohorts. The extracellular matrix (ECM), metabolic processes and immune signaling were involved in succinylation in BPH, as indicated by using TMT-labeling proteomic analysis, and this finding was also confirmed by sc-RNAseq CellChat analysis. The proteins upregulated in SIRT5 knockout WPMY-1 cells were also enriched in the extracellular matrix and metabolic processes. More importantly, integrin receptor inhibition in a mouse model of BPH significantly ameliorated prostate hyperplasia. High levels of succinylation modifications were found in BPH, and succinylated proteins influenced the activation of the ECM. Inhibition of ECM signaling further ameliorated prostate hyperplasia in mice.

Morusin exerts anti-cancer activity in renal cell carcinoma by disturbing MAPK signaling pathways.

BACKGROUND: Renal cell carcinoma (RCC) has gradually become a severe type of kidney malignant tumor, which warrants an urgent need for highly efficacious therapeutic agents. Morusin, a typical prenylated flavonoid, has been revealed to possess anticarcinogenic effects against several cancers by inhibiting cell proliferation and tumorigenesis. METHODS: Cells proliferation was examined by CCK-8. Migration assays were performed using a 24-well transwell chamber. Apoptotic cells were detected using the Annexin V PE/7-AAD apoptosis detection kit. Cell cycle analysis was carried out by flow cytometry. Western blotting and quantitative real time (qRT) PCR were used to exam the change of target gene in mRNA and protein level. Nude mouse xenograft experiments were performed to identify vivo function of morusin. RESULTS: Here, we evaluated the effect of morusin against RCC. We treated three RCC cell lines, 769-P, 786-O, and OSRC-2, with morusin to study its effects on cell growth, migration, apoptosis, cell cycle and cancer-related pathways. Additionally, we assessed the effects of morusin on tumor growth using a nude mouse model. Morusin could inhibit cell growth and migration, induce cell apoptosis and downregulate apoptosis-related proteins, and disturb the cell cycle arrest in the G1 phase. Additionally, morusin could suppress RCC tumorigenesis in vivo. Moreover, mitogen-activated protein kinase (MAPK) signal pathways were found to be involved in morusin-induced anti-cancer activity. P-p38 and P-JNK levels were up-regulated by morusin, while the ERK phosphorylation level was down-regulated. CONCLUSIONS: Our results show that morusin could inhibit the growth of RCC cells in vitro and in vivo through MAPK signal pathways. Thus, morusin could be a potential anti-cancer agent for RCC.

DUSP9 Suppresses Proliferation and Migration of Clear Cell Renal Cell Carcinoma via the mTOR Pathway.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most common urologic tumors. However, the carcinogenic mechanism of ccRCC remains unclear. This study aimed to investigate the effects of dual specificity phosphatase 9 (DUSP9) in ccRCC. METHODS: Cell proliferation and migration abilities were detected by Cell Counting kit-8, wound-healing (scratch) assay and transwell assay. The expression of mRNA in ccRCC was measured by qPCR. Western blot and immunohistochemical staining were used for protein expression. In addition, nude mouse xenograft experiment establishes an in vivo model to detect the inhibitory effect of DUSP9 on tumor proliferation. RESULTS: DUSP9 was significantly down-regulated in both ccRCC cell lines and ccRCC tissues compared to that in non-cancer cell lines and normal tissues. Besides, DUSP9 suppressed proliferation and migration of ccRCC cell lines in vitro. Importantly, the inhibition of tumor growth by DUSP9 was confirmed by xenograft tumor studies. And DUSP9 could inhibit both phosphorylation of mTOR and expression of its pathway-associated proteins Sox2, c-Myc, and HIF-1α, which are involved in cell proliferation and migration. CONCLUSION: Taken together, our results uncovered DUSP9 as a tumor suppressor in ccRCC, acting by regulating cell proliferation and migration via the mTOR pathway.

RRM1 predicts clinical outcome of high-and intermediate-risk non-muscle-invasive bladder cancer patients treated with intravesical gemcitabine monotherapy.

BACKGROUND: The expression level of ribonucleotide reductase subunit M1 (RRM1) is closely related to the effect of gemcitabine-based therapy in advanced bladder cancer. However, the value of RRM1 expression in predicting progression-free survival in non-muscle-invasive bladder cancer (NMIBC) patients treated with intravesical gemcitabine chemotherapy has not been elucidated. METHODS: This study randomly assigned 162 patients to either the RRM1-known group or the unknown group. We collected cancer tissues from 81 patients to evaluate the mRNA expression of RRM1 by using liquid chip technology. All patients were diagnosed and then treated with intravesical gemcitabine monotherapy immediately after transurethral resection of the bladder tumour (TURBT). RESULTS: RRM1 expression was high in 21% (17/81) of patients. The RRM1 mRNA level was not correlated with sex, age, weight, performance status, or CUA/EAU risk (p > 0.05). Progression-free survival (PFS) was significantly longer for patients with low RRM1 expression than for patients with high and unknown RRM1 expression (p = 0.009). Additionally, the 1- and 2-year relapse rates also differed according to RRM1 expression level. The 1-year relapse rates for RRM1-low, RRM1-high and RRM1-unknown patients were 0, 17.7 and 6.2% (p = 0.009), while the 2-year relapse rates for these groups were 3.1, 29.4, and 11.1% (p = 0.005), respectively. CONCLUSIONS: This preliminary study showed that low RRM1 expression was associated with longer progression-free survival and lower 1-year/2-year relapse rates in NMIBC patients treated with intravesical gemcitabine monotherapy, despite the need for further verification with large sample sizes and considering more mixed factors and biases.

Calcium-activated nucleotidase 1 silencing inhibits proliferation, migration, and invasion in human clear cell renal cell carcinoma.

Calcium-activated nucleotidase 1 (CANT1, belongs to the apyrase family, is widely expressed in various organs. However, the biological function of CANT1 remains poorly explored. In this study, we aimed to investigate the expression profile and functions of CANT1 in clear cell renal cell carcinoma (ccRCC). Our data show that the protein level of CANT1 was significantly higher in tumor tissues than in adjacent normal tissues. CANT1 silencing suppressed cell proliferation, migration, and invasion obviously in 769-P and 786-O cells, arrested cell cycle in S phase and promoted apoptosis in 769-P cells. In conclusion, the present study shows the different expression mode of CANT1 in human ccRCC tumor tissue and adjacent normal tissue, denotes the function of CANT1 in ccRCC cells and provides potential molecular mechanisms and pathways of CANT1 antitumor function in ccRCC.

MicroRNA-34a Attenuates Paclitaxel Resistance in Prostate Cancer Cells via Direct Suppression of JAG1/Notch1 Axis.

BACKGROUND/AIMS: Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically centered on paclitaxel-based chemotherapy. In this study, we aimed to evaluate whether miR-34a attenuates chemoresistance to paclitaxel by regulating target genes associated with drug resistance. METHODS: We used data from The Cancer Genome Atlas to compare miR-34a expression levels in prostate cancer (PC) tissues with normal prostate tissues. The effects of miR-34a inhibition and overexpression on PC proliferation were evaluated in vitro via Cell Counting Kit-8 (CCK-8) proliferation, colony formation, apoptosis, and cell-cycle assays. A luciferase reporter assay was employed to identify the interactions between miR-34a and specific target genes. To determine the effects of up-regulation of miR-34a on tumor growth and chemo-resistance in vivo, we injected PC cells overexpressing miR-34a into nude mice subcutaneously and evaluated the rate of tumor growth during paclitaxel treatment. We examined changes in the expression levels of miR-34a target genes JAG1 and Notch1 and their downstream genes via miR-34a transfection by quantitative reverse transcription PCR (qRT-PCR) and western blot assay. RESULTS: miR-34a served as an independent predictor of reduced patient survival. MiR-34a was down-regulated in PC-3PR cells compared with PC-3 cells. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to paclitaxel while miR-34a down-regulation resulted in chemoresistance to paclitaxel in vitro. A study of gain and loss in a series of functional assays revealed that PC cells expressing miR-34a were chemosensitive. Furthermore, the overexpression of miR-34a increased the sensitivity of PC-3PR cells to chemotherapy in vivo. The luciferase reporter assay confirmed that JAG1 and Notch1 were directly targeted by miR-34a. Interestingly, western blot analysis and qRT-PCR confirmed that miR-34a inhibited the Notch1 signaling pathway. We found that miR-34a increased the chemosensitivity of PC-3PR cells by directly repressing the TCF1/ LEF1 axis. CONCLUSION: Our results showed that miR-34a is involved in the development of chemosensitivity to paclitaxel. By regulating the JAG1/Notch1 axis, miR-34a or its target genes JAG1 or Notch1 might serve as potential predictive biomarkers of response to paclitaxel-based chemotherapy and/or therapeutic targets that will help to overcome chemoresistance at the mCRPC stage.

MicroRNA-34a Attenuates Metastasis and Chemoresistance of Bladder Cancer Cells by Targeting the TCF1/LEF1 Axis.

BACKGROUND/AIMS: Chemoresistance is largely responsible for relapses of bladder cancer during clinical therapy. However, the molecular mechanisms involved in the chemoresistance of bladder cancer are unclear. Growing evidence supports the theory that microRNAs (miRNAs) play an important role in chemotherapeutic drug resistance because they are downregulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. More specifically, the extent and precise mechanism of the involvement of miR-34as in chemoresistance to epirubicin (EPI) in the treatment of bladder cancer remains unclear. METHODS: In this study, real-time quantitative polymerase chain reaction (PCR) was used to analyze the expression of miR-34a in bladder cancer cell line BIU87 and its EPI chemoresistant cell line BIU87/ADR. The miR-34a profiles in bladder cancer tissues were obtained from The Cancer Genome Atlas database. The effect of miR-34a on chemosensitivity was evaluated by cell viability assays, colony formation assays, and in vivo experimentation. Apoptosis and the cell cycle were examined by flow cytometry. A luciferase reporter assay was used to assess the target genes of miR-34a. Western blot and qPCR were used to analyze the expression of target proteins and downstream molecules. RESULTS: The downregulation of miR-34a in bladder cancer serves as an independent predictor of reduced patient survival. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to EPI, while miR-34a downregulation resulted in chemoresistance to EPI in vitro. Moreover, it was found that miR-34a increased the sensitivity of BIU87/ADR cells to chemotherapy in vivo. The luciferase reporter assay ascertained that TCF1 and LEF1 are direct target genes of miR-34a. It was found that miR-34a increased chemosensitivity in BIU87/ADR cells by inhibiting the TCF1/LEF1 axis. CONCLUSIONS: The results of this study indicate that miR-34a contributes to the chemosensitivity of BIU87/ADR by inhibiting the TCF1/LEF1 axis. Consequently, miR-34a is a determinant of BIU87 chemosensitivity and may therefore serve as a potential therapeutic target in bladder cancer treatment.

The role of HCN channels in peristaltic dysfunction in human ureteral tuberculosis.

OBJECTIVE: To explore the role of HCN channels in ureteral peristaltic dysfunction by comparing the changes in HCN channel levels between normal and tuberculous ureters. METHODS: A total of 32 specimens of human upper ureters were collected by nephrectomy from patients with renal tumor (control group, n = 16) or from patients with renal tuberculosis (experimental group, n = 16); the two groups did not receive radiotherapy, chemotherapy, immunotherapy, or any other special treatment before the surgical procedure. An experimental study on smooth muscle strips of human upper ureters showed variation in contraction amplitude and frequency after adding ZD7288, a specific blocker of HCN channels. The expression of HCN channels in the ureter was confirmed by Western blot (WB) and by confocal analysis of double immunostaining for c-kit and HCN channel proteins. RESULTS: Before the addition of ZD7288, the experimental and control groups showed significant differences in the frequency and amplitude of the spontaneous contraction of isolated ureteral smooth muscle strips. After ZD7288 was added, the frequency and amplitude of the contractions of the ureteral smooth muscle strips were significantly lower in both groups. The differences observed before and after ZD7288 treatment in each group were significant (P < 0.001), and the difference in contraction amplitude observed between the two groups before ZD7288 was also significantly different (P < 0.001). By using WB technology, we showed that the expression of HCN channels was present in normal human ureters, with the expression of HCN4 and HCN1 being the highest; the expression of HCN4 and HCN1 in the control and experimental groups were both statistically significant (P < 0.001). HCN4 and HCN1 were expressed in the mucosal and smooth muscle layers of human control ureters and tuberculous ureters, as revealed by a confocal analysis of double immunostaining for c-kit and HCNs proteins; there were significant differences between the two groups (P < 0.001). CONCLUSION: Four HCN channels are expressed in the ureter, mainly HCN4 and HCN1, suggesting that HCN channels are involved in the peristaltic contraction of ureteral ICCs, which may be an important reason for peristaltic dysfunction in ureteric tuberculosis.

Long noncoding RNA PVT1 inhibits renal cancer cell apoptosis by up-regulating Mcl-1.

Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) is up-regulated in various human cancers, and our results indicated that PVT1 was up-regulated in clear cell renal cell carcinoma tissues. The Cancer Genome Atlas cohort analysis revealed that in clear cell renal cell carcinoma, higher PVT1 expression correlated with advanced TNM stage, histological grade, and poor survival. PVT1 knockdown promoted apoptosis, inhibited renal cancer cell proliferation, decreased Mcl-1, and increased cleaved caspase-3 and cleaved PARP. PVT1 increased Mcl-1 mRNA levels in renal cancer cells by promoting mRNA stability without influencing its transcription. in vitro, the enhanced apoptosis arising from PVT1 suppression was attenuated by overexpressing Mcl-1. In addition, in vivo experiments showed that PVT1 knockdown repressed xenograft tumor growth, while Mcl-1 overexpression partially rescued xenograft tumor growth. These results indicate the PVT1/Mcl-1 pathway inhibits renal cancer cell apoptosis in vitro and in vivo. PVT1 may thus serve as a novel biomarker, and the PVT1/Mcl-1 pathway may be a useful therapeutic target for clear cell renal cell carcinoma.

Corticomedullary mixed tumour resembling a small adrenal gland-involvement of cancer stem cells: case report.

BACKGROUND: Adrenal corticomedullary mixed tumours are very rare. Its mechanism is rarely reported. Here we report the first case of a corticomedullary mixed tumour resembling a "small adrenal gland" with distinct arrangement of the cortical and medullary layers. We further hypothesize regarding the tumorigenic mechanism of this tumour. CASE PRESENTATION: A 58-year man had been diagnosed with diabetes and hypertension for 3 years. His 24-h urine vanillylmandelic acid (VMA) levels were slightly elevated. An abnormal circadian cortisol rhythm was noted, and his cortisol levels were not suppressed by dexamethasone. Abdominal computed tomography (CT) revealed a right adrenal gland lesion (diameter, 30 × 38 mm), while an enhanced CT showed enhancement and hypervascularization. The tumour was positive for adrenocorticotropic hormone, chromogranin A (CGA), and steroidogenic factor-1 (SF-1) on the tumour surface. Acetaldehyde dehydrogenase 1(ALDH1), CD44, CD133, Nestin, Nerve growth factor receptor (NGFR), and Sex determining region y-box 9(SOX9) staining were positive. Although administration of medications for diabetes and hypertension was stopped until surgery was performed, the blood sugar level and blood pressure were maintained after surgery. CONCLUSIONS: This is the first report about a possible mechanism by which cancer stem cells induce adrenal corticomedullary tumours.

Circulating miR-205: a promising biomarker for the detection and prognosis evaluation of bladder cancer.

MicroRNA (miRNA) expression profile analysis indicated that miR-205 was upregulated in bladder cancer tissue compared to healthy tissue. The aim of this study is to analyze value of circulating miR-205 for the detection and prognosis evaluation of bladder cancer (BC). Eighty-nine patients with BC and 56 healthy controls (HC) were enrolled in the study. miR-205 expression was determined using TaqMan quantitative real-time polymerase chain reaction assay and further correlated with patients' clinicopathological parameters and follow-up data. The results indicated that plasma miR-205 was upregulated in BC compared with HC (P < 0.001) and in muscle invasive BC (MIBC) compared to nonmuscle invasive BC (NMIBC) (P = 0.016). miR-205 yielded an area under the receiver-operating characteristic curve of 0.950 with 76.4 % sensitivity and 96.4 % specificity in discriminating BC from HC, and 0.668 with 57.1 % sensitivity and 77.0 % specificity in distinguishing MIBC from NMIBC. Plasma miR-205 expression was significantly associated with tumor stage (P < 0.001) and pathological grade (P = 0.048). The results indicated that BC patients with high miR-205 expression experienced shorter disease-free survival and disease-specific survival (P = 0.022 and P = 0.026; P = 0.027 and P = 0.034; respectively), which was not proven by multivariate Cox regression analysis (multi-Cox) (P = 0.0765 and P = 0.279, respectively). Log-rank test showed that NMIBC patients with high miR-205 expression experienced shorter cancer-free survival (P = 0.044). Log-rank test and univariate and multivariate Cox regression analyses did not indicate that high miR-205 expression in NMIBC patients was associated with cancer-specific survival (P = 0.079, P = 0.089, and P = 0.201, respectively). In conclusion, miR-205 may be a promising biomarker for the detection and prognosis evaluation of BC.

Association of Vitamin E Intake with Reduced Risk of Kidney Cancer: A Meta-Analysis of Observational Studies.

BACKGROUND: Several observational studies suggested that vitamin E intake is related to the risk of kidney cancer; however, the results of published studies are inconsistent. MATERIAL AND METHODS: A meta-analysis was performed to assess the relationship between vitamin E intake and the risk of kidney cancer by searching PubMed and Medline through August 2015. We computed pooled relative risks (RR) and 95%CI of kidney cancer for the highest versus lowest level of vitamin E intake. RESULTS: A total of 13 observational studies (7 case-control and 6 cohort) were included. The pooled RR (95%CI) of kidney cancer for the highest vs. the lowest level of vitamin E intake was 0.81 (0.69-0.94). In subgroup-analysis, this study found an inverse relationship between vitamin E intake and kidney cancer risk, which was not significantly modified by study design, study population, or sex distribution except in the cohort studies. CONCLUSIONS: Results of the present study suggest an inverse relationship between vitamin E intake and kidney cancer risk. However, additional well designed cohort studies and randomized controlled trials that focus on the relationship between vitamin E intake and kidney cancer risk are needed.

Meta-analysis of the effect of postoperative radiotherapy on prognosis of prostatic cancer following radical prostatectomy.

OBJECTIVE: A systematic evaluation was carried out over the effectiveness and safety of postoperative radiotherapy following radical prostatectomy. METHOD: The randomized controlled trials that were concerned with postoperative radiotherapy for prostatic cancer and published before June 2014 were searched in PubMed, EMBASE, Cochrane Library, CBM, CNKI and VIP databases. Two researchers conducted quality evaluation and data extraction independently for all included literature. Rev Man 5.2 software was used for statistical analysis. RESULTS: Finally 5 randomized control trials involving 2290 cases were included. Meta-analysis showed that the approaches of radical prostatectomy with or without postoperative radiotherapy did not differ significantly in terms of overall survival (HR=1.09, 95% C1: 0.75-1.60, P=0.65). However, significant difference was found in biochemical progression-free survival (HR=0.54, 95% CI: 0.42-0.69, P < 0.001). CONCLUSION: Evidences show that postoperative radiotherapy following radical prostatectomy can increase biochemical progression-free survival but not overall survival.

Bladder extragastrointestinal stromal tumor in an adolescent patient: A case-based review.

Extragastrointestinal stromal tumors (EGISTs) are mesenchymal tumors occurring outside the gastrointestinal tract, with histological, immunohistochemical and molecular genetic characteristics similar to those of gastrointestinal stromal tumors (GISTs). The immunohistochemical examination usually demonstrates a positive expression for CD117. GISTs are rare neoplasms and EGISTs are even less common. This is the report of a case of EGIST in the urinary bladder of a 15-year-old adolescent female patient who presented with painless gross hematuria. Pelvic computed tomography revealed an irregular soft tissue density mass, sized 5.7×4.8 cm, in the bladder. Partial cystectomy was performed in April, 2011. There was no recurrence during follow-up over the next 35 months, as determined by transabdoninal ultrasonography and cystoscopic examination. The patient in this study did not receive any molecular-targeted drugs. To the best of our knowledge, this is the first reported case of an EGIST of the urinary bladder in an adolescent patient.

Total retroperitoneal laparoscopic nephroureterectomy with bladder-cuff resection for upper urinary tract transitional cell carcinoma.

BACKGROUND: Open nephroureterectomy (ONU) and bladder cuff resection (ONU-BCR) has been the gold standard of surgical treatment for upper urinary tract transitional cell carcinoma (UUT-TCC). The aim of this study is to introduce a modified total retroperitoneal laparoscopic nephroureterectomy (LNU) with bladder-cuff resection (LNU-BCR) method for treating UUT-TCC and compare its clinical efficacy with ONU-BCR. METHODS: Sixty-five patients with UUT-TCC, who underwent ONU-BCR (n = 36) or LNU-BCR (n = 29) between January 2008 and June 2012, were analyzed in this retrospective study. Perioperative data as well as incidence of disease recurrence at the primary site or distant metastasis was compared in patients with at least 6 months follow-up. RESULTS: As compared with patients with ONU-BCR, the patients with LNU-BCR had significantly shorter operative time, lower estimated blood loss, shorter time to oral intake, lower analgesic dose, shorter duration of analgesic use, shorter duration of incision drainage tube, shorter time to ambulation out of bed and reduced postoperative hospital stay (all, p < .05). No significant difference in postoperative complications or incidence of bladder carcinoma recurrence and distant metastasis during the follow-up period was observed. CONCLUSIONS: The modified LNU-BCR represents an effective and safe alternative technique to ONU-BCR with the advantages of reduced invasiveness, bleeding and hospitalization.

XRCC1 Arg194Trp and Arg280His polymorphisms increase bladder cancer risk in Asian population: evidence from a meta-analysis.

BACKGROUND: A lot of studies have investigated the correlation between x-ray cross complementing group 1 (XRCC1) polymorphisms and bladder cancer risk, but the results in Asian population were still inconclusive. We conducted a meta-analysis to ascertain the association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms with bladder cancer risk in Asian population. METHODOLOGY/PRINCIPAL FINDINGS: The association strength was measured with odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of 9 eligible studies, conducted in China, India and Japan, were identified. We observed a significant increased risk of bladder cancer in dominant model (OR = 1.199, 95% CI: 1.021,1.408, Pheterogeneity = 0.372), allele comparison (OR = 1.200, 95% CI: 1.057,1.362, Pheterogeneity = 0.107) of Arg194Trp, heterozygote comparison (OR = 1.869, 95% CI: 1.205,2.898, Pheterogeneity = 0.011) and dominant model (OR = 1.748, 95% CI: 1.054,2.900, Pheterogeneity = 0.01) of Arg280His. Pooled results estimated from adjusted ORs further validated these findings. No publication bias was detected. Subgroup analyses found that significant increased risk was only found among community-based studies not hospital-based studies. There was no evidence of publication bias. CONCLUSION: This is the first meta-analysis conducted in Asian investigating the correlation between XRCC1 polymorphisms and susceptibility to bladder cancer. Our meta-analysis shows that XRCC1 Arg194Trp and Arg280His polymorphisms are associated with a significantly increased risk of bladder cancer in Asian population.

Effect of microbubble-enhanced ultrasound on prostate permeability: a potential therapeutic method for prostate disease.

OBJECTIVE: To explore the effect of microbubble-enhanced therapeutic ultrasound (MEUS) on prostate permeability and the blood-prostate barrier. METHODS: Experimental rabbits were assigned to 5 separate groups; the MEUS group, the MEUS 24-hour group, and the 3 control groups. A therapeutic ultrasound device was used to treat the rabbit prostates in vivo in combination with intravenous injection of microbubbles (MBs). Evans blue (EB) and lanthanum (La) nitrate were injected to assess the prostate permeability using laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM). RESULTS: The MEUS group exhibited a significant increase in EB exudation and EB staining of the glandular parenchyma compared with the control groups. In the MEUS group, LSCM showed that a bright red fluorescence of EB was extensively distributed in the intercellular space of extravascular stroma and the glandular epithelium. In addition, TEM showed that the tight junction between vascular endothelial cells was opened, and the La particles used as tracers were seen in the stroma and glandular epithelium. The alterations in the MEUS group were significantly different from those in the groups exposed to MBs or ultrasound alone. These alterations were also not observed in the MEUS 24-hour group. CONCLUSION: MEUS enhanced the prostate permeability, and it effectively opened the blood-prostate barrier. Hence, MEUS may serve as a potential noninvasive therapy for targeted drug or gene delivery to the prostate. However, the relationship between the acoustic parameters of MEUS and prostate permeability or the bioeffects of MEUS needs to be evaluated in future studies.

Suture-free technique of extravesical ureteroneocystostomy with ring pin stapler: experimental study of canines. I. Preliminary results.

OBJECTIVES: To compare the mechanical and sutured ureteroneocystostomy in a canine model. METHODS: In 18 dogs, extravesical ureteroneocystostomy on 1 side was randomly assigned to end-to-side anastomosis performed with a titanium ring-pin stapler or interrupted absorbable sutures. To create the antireflux tunnel, the longitudinal line of the muscle layer was closed over the implanted ureter with titanium clips or sutures. At 3 months postoperatively, renal ultrasonography, intravenous urography, ascending cystography, the Whitaker test, and the macroscopic and microscopic results were assessed. RESULTS: The ureteroneocystostomy with the ring pin stapler and the antireflux tunnel construction with titanium clips had a 100% technical success rate. Compared with manual suturing anastomosis, the suture-free technique took a significantly shorter time and resulted in slightly, but not significantly, less ureteral obstruction after 3 months. One dog in group 2 had evidence of ureteral dilation and hydronephrosis compared with the normal contralateral side. No signs of stone formation, urinary cyst, or fistulas were found after either closure method. None of the 18 dogs demonstrated vesicoureteral reflux. Histologic examination showed no signs of acute inflammation or marked fibrosis in any of the 18 specimens. Moreover, the intrapelvic pressure in group 1 was approximately similar to that of the normal contralateral side. CONCLUSIONS: Ureteroneocystostomy performed with a titanium ring-pin stapler is feasible and faster than using conventional sutures. This suture-free technique is simple and safe, with possibly lower complication rates than a nonstented suture technique. Additional studies with a longer follow-up duration are needed to confirm these results.

Bladder regeneration by collagen scaffolds with collagen binding human basic fibroblast growth factor.

PURPOSE: Studies show that basic fibroblast growth factor can promote bladder regeneration. However, the lack of targeting delivery approaches limits its clinical application. We investigated a collagen based targeting system for bladder regeneration. A collagen binding domain was added to the native basic fibroblast growth factor N-terminal to allow it to bind to collagen. MATERIALS AND METHODS: Sprague-Dawley rats underwent partial cystectomy. Collagen scaffolds loaded with collagen binding domain basic fibroblast growth factor, native basic fibroblast growth factor or phosphate buffered saline were grafted to the remaining host bladders, respectively. At days 30 and 90 reconstructed bladders were evaluated by histological analysis and urodynamics. RESULTS: This targeting basic fibroblast growth factor delivery system induced satisfying bladder histological structures. It promoted more vascularization and smooth muscle cell ingrowth. Urodynamics revealed well accommodated bladder tissue with volume capacity and compliance. CONCLUSIONS: Results show that the targeting delivery system consisting of collagen binding domain basic fibroblast growth factor and collagen membranes induced better bladder regeneration at the injury site. Thus, this targeting delivery system may be an effective strategy for bladder regeneration with potential clinical applications.