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Male Urogenital Diseases - Top 30 Publications

MtDNA depletion influences the transition of CD44 subtypes in human prostate cancer DU145 cells.

Our earlier study revealed that long-term ethidium bromide application causes mitochondrial DNA depletion in human prostate cancer DU145 cell line (DU145(MtDP)), and this DU145(MtDP) subline appears to have expanded CD44(Bright) cell population than its parental wild type DU145 cells (DU145(WT)). Increasing evidence suggests that CD44(Bright) cells are highly cancer stem cell like, but it is not clear about their dynamic transition between CD44(Dim) and CD44(Bright) phenotypes in prostate cancer cells, and how it is affected by mitochondrial DNA depletion. To address these questions, four cell subpopulations were isolated from both DU145(WT) and DU145(MtDP) cell lines based on their CD44 expression level and mitochondrial membrane potential. The cell motility and colony formation capability of the fluorescence activated cell sorting-sorted cell subpopulations were further examined. It was discovered in the DU145(WT) cells that CD44(Dim) cells could transit into both CD44(Dim) and CD44(Bright) phenotypes and that CD44(Bright) cells were prone to sustain their CD44(Bright) phenotype as renewal. However, such transition principle was altered in the DU145(MtDP) cells, in which CD44(Bright) cells showed similar capability to sustain a CD44(Bright) phenotype, while the transition of CD44(Dim) cells to CD44(Bright) were suppressed. It is concluded that mitochondrial DNA depletion in the human prostate cancer DU145 cells influences their renewal and CD44 subphenotype transition. Such alterations may be the driving force for the enrichment of CD44(Bright) DU145 cells after the mitochondrial DNA depletion, although the molecular mechanisms remain unclear.

Comment on "Predicting postnatal renal function of prenatally detected posterior urethral valves using fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient determination".

The association between caudal anesthesia and increased risk of postoperative surgical complications in boys undergoing hypospadias repair: Comment on data sparsity.

Letter to the editor regarding "The association between caudal anesthesia and increased risk of postoperative surgical complications in boys undergoing hypospadias repair".

Acute Kidney Injury in Patients with Cancer.

Acute Kidney Injury in Patients with Cancer.

Acute Kidney Injury in Patients with Cancer.

The susceptibility of FSHB -211G > T and FSHR G-29A, 919A > G, 2039A > G polymorphisms to men infertility: an association study and meta-analysis.

Male infertility is a complex disorder caused by genetic, developmental, endocrine, or environmental factors as well as unknown etiology. Polymorphisms in the follicle stimulating hormone beta subunit (FSHB) (rs10835638, c.-211G > T) and follicle stimulating hormone receptor (FSHR) (rs1394205, c.-29G > A; rs6165, c.919A > G; rs6166, c.2039 A > G) genes might disturb normal spermatogenesis and affect male reproductive ability.

Optimising assessment of kidney function when managing localised renal masses.

Increased early and incidental detection, improved surgical techniques and technological advancement mean that the management of renal mass lesions is constantly evolving. The treatment of choice for renal mass lesions has historically been radical nephrectomy. Partial nephrectomy is now recommended for localised renal masses, owing to favourable renal functional outcomes. Ablative renal surgery confers a significant risk of chronic kidney disease. There are few studies assessing long term outcomes of nephrectomy on renal outcomes, and virtually no studies assessing long term outcomes for less invasive therapies such as ablation. Unless a renal mass is clearly benign on imaging, management decisions will be made with an assumption of malignancy. The content of this review applies to both benign and malignant renal mass lesions. We advocate for improved strategies for kidney function assessment and risk stratification, early targeted referral, and regular screening for chronic kidney disease for all patients after surgery.

Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial.

Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain.

Abdominal mass revealing xanthogranulomatous pyelonephritis in an infant.

Xanthogranulomatous pyelonephritis (XGP) is a chronic pyelonephritis observed in children and exceptionally in infants. Symptomatology is vague and may delay diagnosis and patient's management. Treatment is based on medical therapy but most often on surgery with poor renal prognosis. We report the case of a 15-month old infant with isolated mass in the left flank. He had no fever or alteration of general state and urine cultures were sterile. Radiological evaluation (renal ultrasound, uroscan and renal scintigraphy) highlighted left non-functioning kidney with "hydropyonephrosis" evoking the diagnosis of XGP. The indication for total nephrectomy by lombotomy was posed and definitive anatomo-pathological examination confirmed the diagnosis of diffuse XGP. This observation emphasizes the importance of suspect PXG in patients with renal mass or malformative uropathy with recurrent urinary tract infections whose treatment should be rigorous and codified.

Cascade Fumarate Hydratase mutation screening allows early detection of kidney tumour: a case report.

Fumarate hydratase (FH) deficiency is a rare autosomal recessive disorder which results in a major defect in cellular metabolism. It presents in infancy with progressive encephalopathy, hypotonia, seizures and failure to thrive and is often fatal in childhood. It is caused by mutations in the FH gene (1q42.1) that result in deficiency of the citric acid cycle enzyme fumarate hydratase, resulting in accumulation of fumaric acid. Heterozygous germline mutations in the FH gene predispose to an aggressive autosomal dominant inherited early-onset kidney cancer syndrome: hereditary leiomyomatosis and renal cell cancer (HLRCC).

Anticancer effect of Saussurea lappa extract via dual control of apoptosis and autophagy in prostate cancer cells.

To demonstrate the mechanisms of the curative effect of Saussurea lappa ethanol extract (SLE) against prostate cancer, we evaluated the effect of SLE on the induction of apoptosis and autophagy and investigated whether SLE-induced autophagy exerts a pro-survival or pro-apoptotic effect in lymph node carcinoma of the prostate (LNCaP) prostate cancer cells. SLE was prepared using 100% ethanol and added to LNCaP cells for 24 hours. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell apoptosis was evaluated by Tali assay. The expression of apoptosis-related mRNA and proteins was analyzed by quantitative real-time RT-PCR and western blotting. SLE treatment decreased the viability of LNCaP cells and increased Bax expression while suppressing the expression of pro-caspases-8/9/3, PARP, Bid, and Bcl-2, thereby inducing apoptosis in LNCaP cells. Cell proliferation related proteins, including p-Akt, androgen receptor, and prostate-specific antigen, were suppressed by SLE treatment. SLE also induced autophagy in LNCaP cells, and inhibition of autophagy enhanced the apoptosis induced by SLE treatment. These results suggest that SLE exerts anticancer effects through the induction of both cellular apoptosis and autophagy, and apoptotic cell death can be facilitated by blocking autophagy in SLE-treated LNCaP cells. Therefore, SLE might be a potential anticancer agent for the treatment of prostate cancer.

Comparing common doses (double-dose vs usual-dose) of atorvastatin for preventing contrast-induced acute kidney injury and mortality after coronary angiography.

High-dose atorvastatin pretreatment was proved reducing the risk of contrast-induced acute kidney injury (CI-AKI), especially in patients with high C-reactive protein (CRP) levels. We evaluated the effects of common atorvastatin doses (double vs usual) on the risk of CI-AKI and mortality.We recorded outcomes from 1319 patients who were administered periprocedural common doses of atorvastatin. The risks of CI-AKI and mortality between double-dose (40 mg/d) and usual-dose atorvastatin (20 mg/d) were compared using multivariable regression models in all patients or CRP tertile subgroups.Seventy-six (5.8%) patients developed CI-AKI. Double-dose atorvastatin compared with usual-dose did not further reduce the risk of CI-AKI (adjusted odds ratio [OR]: 2.28, 95% confidence interval [CI]: 0.92-5.62, P = .074), even for patients in the highest CRP tertile (>8.33 mg/L; adjusted OR: 3.76, 95% CI: 0.83-17.05, P = .086). Similar results were observed in reducing mortality in all patients (adjusted hazard ratio: 0.47, 95% CI: 0.10-2.18; P = .339) and in the highest CRP tertiles (P = .424). In the subgroup analysis, double-dose atorvastatin increased risk of CI-AKI in patients with creatinine clearance (CrCl) < 60 mL/min, anemia, contrast volume > 200 mL and > 2 stents implanted (P = .046, .009, .024, and .026, respectively).Daily periprocedural double-dose atorvastatin was not associated with a reduced risk of CI-AKI compared with usual-dose, and did not provide an improved long-term prognosis, even in patients with high CRP levels. However, it increased the risk of CI-AKI in patients with a high contrast volume/CrCl.

Plumbagin-loaded aptamer-targeted poly D,L-lactic-co-glycolic acid-b-polyethylene glycol nanoparticles for prostate cancer therapy.

Plumbagin inhibits the growth, metastasis, and invasion of prostate cancer (PCa). However, its lower bioavailability limits biopharmaceutical properties due to insolubility in water. Prostate-specific membrane antigen (PSMA) aptamer-targeted nanoparticles (NPs) significantly enhanced cytotoxicity in prostate epithelial cells. This study aimed to investigate the effects of plumbagin-loaded prostate-specific membrane antigen (PSMA) aptamer-targeted poly D,L-lactic-co-glycolic acid-b-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) on prostate cancer (PCa) in vitro.PLGA-PEG with a terminal carboxylic acid group (PLGA-PEG-COOH) was synthesized, and plumbagin was loaded on PLGA-PEG-COOH NPs using the nanoprecipitation method and characterized by field emission scanning electron microscopy (SEM), transmission electron microscopy (TEM), and laser light scattering. The uptake and distribution of plumbagin-NPs in human PCa LNCaP cells were investigated by fluorescent labeling. Subsequently, PSMA antibody-targeted PLGA-PEG-COOH NPs (targeted NPs) were prepared by covalent binding and characterized by x-ray photoelectron spectroscopy. Furthermore, the anticancer activity of plumbagin-loaded, targeted NPs was compared with that of nontargeted NPs in LNCaP cells in vitro.Plumbagin-NPs (diameter of 189.4 ± 30.6 nm and zeta potential of -17.1 ± 3.7 mV) were optimized based on theoretical drug loading of 5% and a ratio of water:acetone of 3:1. During the first 2 hours, the cumulative release rate of the drug was 66.4 ± 8.56%. Moreover, plumbagin-targeted NPs with nitrogen atoms were prepared. The uptake rate was 90% at 0.5 hours for targeted and nontargeted NPs. The IC50 of targeted NPs and nontargeted NPs was 32.59 ± 8.03 μM and 39.02 ± 7.64 μM, respectively.Plumbagin-loaded PSMA aptamer-targeted NPs can be used in targeted chemotherapy against PCa.

Improved Outcomes in Men with Advanced Prostate Cancer.

Preoperative High Neutrophil-to-Lymphocyte Ratio Is Associated with High-grade Bladder Cancer.

To evaluate the correlation between the neutrophil-to-lymphocyte ratio (NLR) and histopathological characteristics of bladder cancer.

Analysis of Clinicopathological Features and Prognostic Factors in 39 Cases of Bladder Neuroendocrine Carcinoma.

Through analysis and summarization of clinicopathological features, immunohistochemical expression, pathological diagnostic criteria, prognostic and other factors in patients suffering from bladder neuroendocrine carcinoma (BNEC), a better understanding of BNEC could be achieved to provide solid evidence for clinicopathology and prognosis.

Reduced Expression of Metastasis Suppressor-1 (MTSS1) Accelerates Progression of Human Bladder Uroepithelium Cell Carcinoma.

Metastasis suppressor 1 (MTSS1) is a multi-functional cytoskeletal protein. Recent research showed that MTSS1 is a potential tumor suppressor in many types of cancer cells, including kidney and bladder cancer cells. However, the clinical implication of MTSS1 in human bladder uroepithelium cell carcinoma (BUCC) and its potential in suppressing BUCC tumorigenesis remains undetermined. In the present study, the expression of MTSS1 in human BUCC tissue samples, and correlations between MTSS1 and pathological grade and stage of the tumors were examined in BUCC specimens. The function of MTSS1 in BUCC progression was explored.

High HIV incidence in men who have sex with men following an early syphilis diagnosis: is there room for pre-exposure prophylaxis as a prevention strategy?

HIV pre-exposure prophylaxis (PrEP) is becoming a pivotal strategy for HIV prevention. Understanding the impact of risk factors for HIV transmission to identify those at highest risk would favour the implementation of PrEP, currently limited by costs. In this service evaluation, we estimated the incidence of bacterial STIs in men who have sex with men (MSM) diagnosed with early syphilis attending a London sexual health clinic according to their HIV status. In addition, we estimated the incidence of HIV infection in HIV-negative MSM, following a diagnosis of early syphilis.

The tradition algorithm approach underestimates the prevalence of serodiagnosis of syphilis in HIV-infected individuals.

Currently, there are three algorithms for screening of syphilis: traditional algorithm, reverse algorithm and European Centre for Disease Prevention and Control (ECDC) algorithm. To date, there is not a generally recognized diagnostic algorithm. When syphilis meets HIV, the situation is even more complex. To evaluate their screening performance and impact on the seroprevalence of syphilis in HIV-infected individuals, we conducted a cross-sectional study included 865 serum samples from HIV-infected patients in a tertiary hospital. Every sample (one per patient) was tested with toluidine red unheated serum test (TRUST), T. pallidum particle agglutination assay (TPPA), and Treponema pallidum enzyme immunoassay (TP-EIA) according to the manufacturer's instructions. The results of syphilis serological testing were interpreted following different algorithms respectively. We directly compared the traditional syphilis screening algorithm with the reverse syphilis screening algorithm in this unique population. The reverse algorithm achieved remarkable higher seroprevalence of syphilis than the traditional algorithm (24.9% vs. 14.2%, p < 0.0001). Compared to the reverse algorithm, the traditional algorithm also had a missed serodiagnosis rate of 42.8%. The total percentages of agreement and corresponding kappa values of tradition and ECDC algorithm compared with those of reverse algorithm were as follows: 89.4%,0.668; 99.8%, 0.994. There was a very good strength of agreement between the reverse and the ECDC algorithm. Our results supported the reverse (or ECDC) algorithm in screening of syphilis in HIV-infected populations. In addition, our study demonstrated that screening of HIV-populations using different algorithms may result in a statistically different seroprevalence of syphilis.

Comparison of postoperative pain between laparoscopic and robot-assisted partial nephrectomies for renal tumors: A propensity score matching analysis.

Robot-assisted partial nephrectomy (RAPN) has emerged as an alternative to laparoscopic partial nephrectomy (LPN) for removal of renal tumors. Several advantages of robotic surgery have been reported, but there is no comparative study on postoperative pain between the 2 techniques. Therefore, we compared the postoperative numerical rating scale (NRS) of pain intensity between patients who underwent LPN and those who underwent RAPN.We included 705 patients who underwent either LPN (n = 200) or RAPN (n = 505) for renal tumors between January 2000 and September 2016. After 1:1 propensity score matching, the final analysis included 142 patients each in the LPN and RAPN groups. The primary endpoint was postoperative NRS of pain intensity. The secondary endpoints were opioid requirement, opioid-related complications, and duration of hospital stay.Preoperative and intraoperative values of propensity score matched patients (n = 284) were not significantly different between the LPN and RAPN groups. There was no significant difference in NRS of pain intensity between the 2 groups. Opioid requirement was different between the 2 groups on postoperative day (POD) 0 (12.4 vs 11.3 mg of morphine-equivalent dose), but not from POD 1 to POD 4. The incidence of opioid-related complications and duration of hospital stay were not significantly different between the 2 groups.Postoperative pain was not significantly different between patients who underwent RAPN and those who underwent LPN. This result provides a potentially useful knowledge of postoperative pain characteristics in RAPN and LPN.

Advanced Renal Cell Carcinoma: Role of the Radiologist in the Era of Precision Medicine.

For the past decade, advanced renal cell carcinoma (RCC) has been at the forefront of oncologic innovation. Our rapidly evolving understanding of the molecular and genetic basis of RCC has revolutionized the management of advanced RCC; 10 novel molecular targeted agents and immune checkpoint inhibitor have received U.S. Food and Drug Administration approval for treatment of advanced RCC in a little over a decade. Amid this progress, imaging has assumed a central role in metastatic surveillance and follow-up of advanced RCC. State-of-the-art knowledge of the molecular basis of RCC and its treatment and imaging will help ensure that the radiology community remains relevant and central in the care of patients with advanced RCC. This article will review developments in management of advanced RCC from a radiologist's perspective to highlight our clinical role. It will describe how the underlying molecular mechanisms of RCC provide specific targets for novel anticancer agents. The relationship between the mechanisms of action of these novel anticancer agents and the imaging appearance of tumor response will be discussed, along with the available tumor response criteria and their strengths and weaknesses, thus assisting radiologists in response assessment in the setting of clinical trials or routine practice. The class- and drug-specific toxicities and complications associated with the novel anticancer agents will be summarized, since these are frequently missed or misinterpreted and require the radiologist's input in prompt detection and management. The potential role of radiogenomics and texture analysis in the management of advanced RCC will also be discussed. (©) RSNA, 2017.

Exosomes and Exosomal MicroRNAs in Prostate Cancer Radiation Therapy.

Despite current risk stratification systems using traditional clinicopathologic factors, many localized and locally advanced prostate cancers fail radical treatment (ie, radical prostatectomy, radiation therapy with or without androgen deprivation therapy). Therefore, a pressing need exists for enhanced methods of disease stratification through novel prognostic and predictive tools that can reliably be applied in clinical practice. Exosomes are 50- to 150-nm small vesicles released by cancer cells that reflect the genetic and nongenetic materials of parent cancer cells. Cancer cells can contain distinct sets of microRNA profiles, the expression of which can change owing to stress such as radiation therapy. These alterations or distinctions in contents allow exosomes to be used as prognostic and/or predictive biomarkers and to monitor the treatment response. Additionally, microRNAs have been shown to influence multiple processes in prostate tumorigenesis, including cell proliferation, induction of apoptosis, migration, oncogene inhibition, and radioresistance. Thus, comparative exosomal microRNA profiling at different levels could help portray tumor aggressiveness and response to radiation therapy. Although technical challenges persist in exosome isolation and characterization, recent improvements in microRNA profiling have evolved toward in-depth analyses of the exosomal cargo and its functions. We have reviewed the role of exosomes and exosomal microRNAs in biologic processes of prostate cancer progression and radiation therapy response, with a particular focus on the development of clinical assays for treatment personalization.

Long-Term Quality of Life in Prostate Cancer Patients Treated With Cesium-131.

To evaluate long-term patient-reported quality of life (QOL) scores in men with prostate cancer treated at our institution with (131)Cs prostate brachytherapy.

External Beam Radiation Therapy With a Brachytherapy Boost Versus Radical Prostatectomy in Gleason Pattern 5 Prostate Cancer: A Population-Based Cohort Study.

Patients with prostate cancer (PCa) containing Gleason pattern (GP) 5 disease experience a greater and earlier incidence of prostate cancer-specific mortality (PCSM) than general PCa patients. This affords the statistical power to compare PCSM outcomes among different treatment modalities even when restricting the analysis to patients treated in the modern era. The purpose of the present study was to compare the survival outcomes among patients with GP 5 PCa on needle core biopsy or transurethral resection of the prostate who underwent extremely dose-escalated radiation therapy (RT; exemplified by external beam RT with a brachytherapy boost [EBRT + BT]) versus radical prostatectomy (RP) in the modern era.

Effect of Eischens Yoga During Radiation Therapy on Prostate Cancer Patient Symptoms and Quality of Life: A Randomized Phase II Trial.

A randomized phase II study was performed to measure the potential therapeutic effects of yoga on fatigue, erectile dysfunction, urinary incontinence, and overall quality of life (QOL) in prostate cancer (PCa) patients undergoing external beam radiation therapy (RT).

Inhibitory effect of Par-4 combined with cisplatin on human Wilms' tumor cells.

Wilms' tumor is associated with a high treatment success rate, but there is still a risk of recurrence. Cisplatin, which is one of the chemotherapeutic agents used for its treatment, is associated with a very high rate of resistance. Par-4 (prostate apoptosis response 4) is a tumor suppressor, which is capable of sensitizing tumor cells to chemotherapy. Therefore, the aim of this study was to determine whether combined treatment with Par-4 and cisplatin is effective for inhibiting growth of Wilms' tumor. Wilms' tumor and control cell samples were collected and analyzed by immunofluorescence assay and immunohistochemistry. Total proteins extracted from cultured cells were analyzed using western blotting and flow cytometry. In addition, a mouse xenograft model was established. We discovered significantly low expression of Par-4 in the tumor tissue, which was positively correlated with high expression of GRP78 (glucose-regulated protein 78). In addition, we found that ectopic Par-4 co-localized with cell surface GRP78 and induced high expression of the endoplasmic reticulum proteins ATF4 and BAX, which activated the endoplasmic reticulum apoptosis pathway. Moreover, treatment with ectopic Par-4 and cisplatin suppressed xenograft growth in nude mice. In conclusion, our results showed that Par-4 overexpression and cisplatin had a synergistic effect on SK-NEP-1 cells, as a result of which cell growth was inhibited and cellular apoptosis was induced. Thus, in vitro and in vivo upregulation of Par-4 expression is indispensable for the trafficking of GRP78 to the cell membrane and subsequent apoptosis of cancer cells.

MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene.

MiR-139-5p has been reported to be overexpressed in many types of cancers, but its role in bladder cancer has not been elucidated yet. Here, we report that miR-139-5p functions as a tumor suppressor in bladder cancer and inhibits the cancer stem cell self-renewal by targeting Bmi1 directly. We found that miR-139-5p expression was significantly downregulated in the bladder cancer specimens compared with that in adjacent normal tissues. In vitro, restoration of miR-139-5p expression significantly inhibited the proliferation of bladder cancer cells. Mechanism analysis revealed that miR-139-5p could decrease Bmi1 protein levels by binding to the 3' untranslated region of Bmi1 messenger RNA. Stem cell-related proteins such as c-MYC, NANOG, OCT4, and KLF4 and signaling pathways such as Wnt signaling were suppressed by restoration of miR-139-5p in bladder cancer cells. In addition, miR-139-5p expression also blocked self-renewal of bladder cancer stem cells by inhibiting Bmi1. In summary, our study supports that miR-139-5p acts as a tumor suppressor in bladder cancer development and suppresses cancer stem cell property of bladder cancer. Our study also suggests that miR-139-5p has the potential to be used as a therapeutic molecule for bladder cancer treatment.

Long non-coding RNA CCAT2 promotes cell proliferation and invasion through regulating Wnt/β-catenin signaling pathway in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common urologic malignancy. Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) has been suggested as serving pivotal roles in tumorigenesis. However, the clinical significance and biological role of CCAT2 in ccRCC remains elusive. The purpose of this study is to identify the function of CCAT2 in ccRCC and its possible molecular mechanism. Expression of CCAT2 was analyzed in 61 ccRCC tissues and two ccRCC cell lines (786-O and ACHN) by quantitative reverse transcription polymerase chain reaction. The functional roles of CCAT2 in ccRCC were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, Transwell assay, and flow cytometric analysis. The influence of CCAT2 on tumorigenesis was monitored by in vivo mice xenograft model. The activation of Wnt/β-catenin signaling pathway was evaluated by the TOP/FOP Wnt luciferase reporter assay and western blot assay. CCAT2 expression was markedly higher in ccRCC cell lines and tissues, being positively associated with tumor size and tumor stage in ccRCC patients. Patients with higher CCAT2 expression had a markedly poorer overall survival than did patients with low CCAT2 expression. Knocking down CCAT2 expression led to reduced cell proliferation and increased apoptosis of ccRCC cells in vitro as well as the activation of Wnt/β-catenin signaling pathway, and CCAT2 overexpression remarkably enhanced these oncogenic properties. In vivo mice xenograft model also showed that knocking CCAT2 expression inhibited the growth of ccRCC xenografts. In conclusion, these results indicated that CCAT2 may play a critical role in ccRCC progression and will be further considered as a biomarker for predicting the survival of ccRCC patients and a potential therapeutic target for ccRCC intervention.