Circular STAG2 RNA Modulates Bladder Cancer Progression via miR-145-5p/TAGLN2 and Is Considered as a Biomarker for Recurrence.

The current study aimed to elucidate the regulatory mechanisms of the circRNA hsa_circ_0139697 (circSTAG2(16-25)) in BCa and to consider the opportunity of using circSTAG2(16-25) isolated from BCa patient urine as a marker for disease development prediction. The selection of this circRNA was determined by the special role of its parental gene STAG2 in BCa biology. The circRNA hsa_circ_0139697 was chosen from 25 STAG2 circRNAs due to its differential expression in the urine of BCa patients and healthy volunteers. Higher levels of circSTAG2(16-25) were detected in urine samples obtained from patients with recurrent tumors. A higher expression of circSTAG2(16-25) was also detected in more tumorigenic BCa cell lines. The overexpression of circSTAG2(16-25) in BCa cells induced the elevation of proliferation, motility, and invasion. To study the mechanisms of circSTAG2(16-25) activity, we confirmed that circSTAG2(16-25) can bind miR-145-5p in vitro as was predicted by bioinformatic search. miR-145-5p was shown to suppress some genes that promoted BCa progression. One of these genes, TAGLN2, encodes the protein Transgelin 2, which plays a role in BCa cell motility and invasion. Therefore, the possible mechanism of action of circSTAG2(16-25) could be sponging the tumor suppressor miR-145-5p, which results in activation of TAGLN2. In addition, circSTAG2(16-25) might be considered as a potential biomarker for recurrence prediction.

Organoid model of urothelial cancer: establishment and applications for bladder cancer research.

3D cancer cell models are suitable for drug evaluation because they more precisely mimic tissue architecture than 2D cultures. To study cytotoxicity of anticancer agents, the most sensitive CellTiter-Glo 3D assay is used. However, this is an end point assay, so it is not possible to consider the variance of the starting material amount in the final reading. It is difficult to maintain an even plating density of 3D organoids for cytotoxicity analysis. We present a simple, 3D bladder cancer culture that can be maintained, cryopreserved and used for molecular and drug response studies. We applied a simple modification of the drug response assay for 3D cultures by measuring the background signal with the CellTiter Blue assay before drug application.

Highly active antiretroviral therapy dysregulates proliferation and differentiation of human pre-adipocytes.

AIM: To investigate the mechanism(s) by which potential effects of multi-drug highly-active antiretroviral therapy contributes to lipodystrophy syndrome. METHODS: Preadipocytes from healthy donors were assessed for proliferation and differentiation in the presence of nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) individually and in combination. Effects on proliferation were assessed with a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and effects on differentiation were assessed from glycerol-3-phosphate dehydrogenase (GP DH) activity and quantitation of Oil Red O staining for intracellular lipid. Data were analyzed with a randomized block ANOVA with post-hoc Fisher's Least Significant Difference test. RESULTS: Preadipocyte proliferation was inhibited by a combination of NNRTI + NRTI (14% at 48 h, P < 0.001) and PI + NRTI (19% at 48 h, P < 0.001) with additional suppression when ritonavir (RTV) was added (26% at 48 h). The drug combination of atazanavir (ATV) + RTV + emtricitabine (FTC) + tenofovir (TDF) had the greatest inhibitory effect on proliferation at 48 h. Preadipocyte differentiation was most significantly reduced by the efavirenz + FTC + TDF assessed either by GPDH activity (64%) or lipid accumulation (39%), P < 0.001. Combining NRTIs with a PI (ATV + FTC + TDF) significantly suppressed differentiation (GPDH activity reduced 29%, lipid accumulation reduced by 19%, P < 0.01). This effect was slightly greater when a boosting amount of RTV was added (ATV + FTC + TDF + RTV, P < 0.001). CONCLUSION: Although combination antiretroviral therapy is clinically more efficacious than single drug regimens, it also has a much greater inhibitory effect on preadipocyte proliferation and differentiation.

5 Years Experience With Drug Eluting and Bare Metal Stents as Primary Intervention in Transplant Renal Artery Stenosis.

BACKGROUND: Transplant renal artery stenosis (TRAS) is a common vascular complication after kidney transplantation and is associated with refractory hypertension, volume overload, and graft injury or loss. This article describes 5-year outcomes of endovascular intervention for TRAS with bare metal and drug eluting stents (DES). METHODS: We investigated, as a prospective cohort study, patient and graft outcomes after the targeted use of DES for vessel diameter less than 5 mm and bare metal stents (BMS) for vessel diameter greater than 5 mm as the primary management for TRAS. RESULTS: From March 2008 to November 2014, 57 patients were stented for hemodynamically significant TRAS; 29 received DES, 26 received BMS, and 2 patients received both stent types. They were followed up for a mean of 35.1 ± 22.8 months; a subset of these patients who all received DES were followed up for 61.7 ± 17.5 months. Mean serum creatinine declined from 2.87 ± 1.5 mg/dL at the time of intervention to 1.98 ± 0.76 mg/dL (P < 0.001) at one month follow-up and was 1.96 ±0.92 mg/dL (P < 0.001) at 35.1 ± 22.8 months. Mean systolic blood pressure declined from 159.05 ± 19.68 mm Hg at time of intervention to 135.65 ± 15.10 mm Hg (P < 0.001) at most recent visit. Clinically driven restenosis requiring repeat revascularization occurred in 15.7% of patients. CONCLUSIONS: Primary stenting with DES and BMS is both successful in the initial treatment of TRAS and also produced an immediate and long-term reduction in serum creatinine and systolic blood pressure.

Renal Artery Pseudoaneurysm in Kawasaki Disease.

Whereas coronary aneurysms are commonly associated with Kawasaki disease, involvement of the renal vasculature is exceedingly rare. Genitourinary involvement in patients with Kawasaki disease is typically limited to sterile pyuria and proteinuria. In this case, a 13-year-old girl who presented with right flank pain and microhematuria was found to have an intraparenchymal hemorrhagic mass on computerized tomography scan. Renal arteriography confirmed the diagnosis of pseudoaneurysm in a lower pole segmental artery branch and complete occlusion was achieved with endovascular embolization.

Different Management Options for Transplant Ureteral Obstructions within an Inguinal Hernia.

Ureteral obstruction secondary to an inguinal hernia with transplant ureteral component is an extremely rare entity with only several case reports found in literature. In all previously reported cases, management of the obstruction involved temporary drainage with ureteral stenting or nephrostomy tube placements followed by delayed definitive repair. We present two case reports, here one being the first one managed by immediate definitive repair via ureteral reimplant and herniorrhaphy and a second case by delayed definitive repair after percutaneous nephrostomy tube placement. Both patients continued to do well postoperatively with normalization of renal function on follow-up.

Urologic considerations and complications in kidney transplant recipients.

Urologic considerations during the kidney transplantation process, starting with initial recipient evaluation and continuing through the post-transplant, long-term follow-up, are critical for minimizing urologic complications and improving graft survival. Appropriate, targeted, preoperative urologic evaluation of the recipient allows for an optimized urinary tract to accept the graft, whereas post-transplant urologic follow-up and monitoring decrease the risk of graft lost secondary to a urologic cause, particularly in patients with a urologic reason for their kidney failure and in those patients with concomitant urologic diagnoses. Urologic complications comprise the second most common adverse post-transplant event, occurring in 2.5% to 14% of patients and are associated with high morbidity, graft loss, and mortality. Early and late urologic complications, including hematuria, hematoma, lymphocele, urine leak, ureteral stricture, nephrolithiasis, and vesicoureteral reflux, and their causes and treatment options are explored. A multidisciplinary team approach to kidney transplantation, including transplant surgery, urology, and nephrology, optimizes outcomes and graft survival. Although the current role of the urologist in kidney transplantation varies greatly by institution, appropriate consultation, participation, and monitoring in select patients is essential.

Alemtuzumab with corticosteroid minimization for pediatric deceased donor renal transplantation: a seven-yr experience.

Alemtuzumab is a monoclonal antibody targeting CD52 receptors on B and T lymphocytes and is an effective induction agent in pediatric renal transplantation. We report a seven-yr experience using alemtuzumab induction and steroid-free protocol in the pediatric population as safe and effective. Twenty-one pediatric deceased donor renal transplants were performed at a single academic institution. All received induction with single-dose alemtuzumab and were maintained on a steroid-free protocol using TAC and MMF immunosuppression. There were 15 males and six females in the study whose ages ranged from one to 19 yr. The average follow-up was 32 months (range from 12 to 78.2 months and median 33.7 ± 23.7 months). All patients had immediate graft function. Graft survival was 95%, and patient survival was 100%. Mean 12 and 36 months eGFR were 63.33 ± 21.01 and 59.90 ± 15.27 mL/min/1.73m(2), respectively. Three patients developed acute T-cell-mediated rejection due to non-adherence while no recipients developed cytomegalovirus infection, PTLD, or polyoma BK viral nephropathy. Steroid avoidance with single-dose alemtuzumab induction provides adequate and safe immunosuppression in pediatric deceased donor renal transplant recipients receiving TAC and low-dose MMF maintenance therapy.

Partial nephrectomy for a large renal lymphatic malformation in a child presenting with hypertension.

A 9-year-old girl had hypertension (systolic blood pressure of 125 mm Hg) noted at an annual well child visit. An ultrasound study demonstrated a large right renal cystic mass. A partial nephrectomy was performed. The surgical specimen was 9.7 × 9.4 × 6.4 cm and weighed 413.2 g. The tumor stained diffusely positive for smooth muscle actin and focally positive for factor VIII. Final histologic diagnosis was primary intrarenal lymphatic malformation. The case is unusual because of the presentation, size of the mass, as well as the therapeutic approach of partial nephrectomy.

Effect of ritonavir and atazanavir on human subcutaneous preadipocyte proliferation and differentiation.

Protease inhibitors (PIs) have been implicated in the development of HIV-associated lipodystrophy through a reduction in the differentiation of preadipocytes. While atazanavir (ATV) is associated with fewer clinical metabolic abnormalities in the short-term, the effects of long-term exposure are not known. ATV effects on preadipocyte replication or differentiation would indicate the potential for long-term problems. This study compared ritonavir (RTV) and ATV effects on preadipocyte replication and differentiation in human primary cultures. Preadipocytes from subcutaneous fat were studied in the presence of therapeutic concentrations of RTV and ATV for replication, differentiation, and adipokine secretion. The effects of the drugs on the expression of PPARgamma and related genes during differentiation were also assessed by real-time quantitative PCR. RTV induced a significant inhibition of preadipocyte proliferation, differentiation and adiponectin secretion. ATV at concentrations within the range of therapeutic levels did not affect differentiation or adiponectin secretion, but did have inhibitory effects on preadipocyte proliferation. Inhibition of differentiation by PIs was associated with decreased expression of PPARgamma, C/EBPalpha, and aP2 genes. In summary, although ATV at therapeutic levels has a smaller impact on adipogenesis, alterations in preadipocyte proliferation suggest the potential for adverse effects with long-term use.

Diagnosis of bladder cancer with microelectromechanical systems-based cystoscopic optical coherence tomography.

OBJECTIVES: To examine the utility and potential limitations of microelectromechanical systems-based spectral-domain cystoscopic optical coherence tomography (COCT) so as to improve the diagnosis of early bladder cancer. METHODS: An optical coherence tomography catheter was integrated into the single instrument channel of a 22F cystoscope to permit white-light-guided COCT over a large field of view (4.6 mm wide and 2.1 mm deep per scan at 8 frames/s) and 10-microm resolution. Intraoperative COCT diagnosis was performed in 56 patients, with a total of 110 lesions examined and compared with biopsied histology. RESULTS: The overall sensitivity of COCT (94%) was significantly higher than cystoscopy (75%, P = .02) and voided cytology (59%, P = .005); the major enhancement over cystoscopy was for low-grade pTa-1 cancer and carcinoma in situ (P < .018). The overall specificity of COCT (81%) was comparable to voided cytology (88.9%, P = .49), but significantly higher than cystoscopy (62.5%, P = .02). CONCLUSIONS: The microelectromechanical systems-based COCT, owing to its high resolution and detection sensitivity and large field of view, offers great potential for "optical biopsy" to enhance the diagnosis of nonpapillary bladder tumors and their recurrences and to guide bladder tumor resection.

High body mass index in muscular patients and flank position are risk factors for rhabdomyolysis: case report after laparoscopic live-donor nephrectomy.

BACKGROUND AND PURPOSE: Rhabdomyolysis is well known after traumatic crush injuries or ischemia involving muscles. Postoperatively, it most likely is secondary to surgical positioning and patient muscle mass. We report a case after laparoscopic live-donor nephrectomy. CASE REPORT: A muscular 35-year-old man underwent elective left laparoscopic live-donor nephrectomy in a 70 degrees flank position with four ports. He was in the right-side lying position with hip flexion (flank position) for approximately 4 hours. A kidney bridge had been placed between the iliac crest and the rib cage. Postoperatively, the patient had light-pinkish urine and low urine output. There was marked induration of the buttocks and significant pedal and scrotal edema. With judicious use of alkalinization and diuretics, the patient did not require dialysis, and renal function returned to base level by postoperative day 20. The recipient of the kidney had a normal postoperative course. CONCLUSION: Rhabdomyolysis is a syndrome of muscle necrosis and release of intracellular components into the circulation. Acute renal failure secondary to myoglobinuria is a common complication. We currently use little flexion of the table during donor nephrectomy and bring the table to a neutral position immediately after kidney retrieval. Postoperatively, one needs a high index of suspicion for rhabdomyolysis to avoid or at least promptly recognize this rare but potentially serious condition after any operation lasting >or=4 hours.