Copper affects virulence and diverse phenotypes of uropathogenic Proteus mirabilis.

BACKGROUND: Copper plays a role in urinary tract infection (UTI) and urinary copper content is increased during Proteus mirabilis UTI. We therefore investigated the effect of copper on uropathogenic P. mirabilis and the underlying mechanisms, focusing on the virulence associated aspects. METHODS: Mouse colonization, swarming/swimming assays, measurement of cell length, flagellin level and urease activity, adhesion/invasion assay, biofilm formation, killing by macrophages, oxidative stress susceptibility, OMPs analysis, determination of MICs and persister cell formation, RT-PCR and transcriptional reporter assay were performed. RESULTS: We found that copper-supplemented mice were more resistant to be colonized in the urinary tract, together with decreased swarming/swimming, ureases activity, expression of type VI secretion system and adhesion/invasion to urothelial cells and increased killing by macrophages of P. mirabilis at a sublethal copper level. However, bacterial biofilm formation and resistance to oxidative stress were enhanced under the same copper level. Of note, the presence of copper led to increased ciprofloxacin MIC and more persister cell formation against ampicillin. In addition, the presence of copper altered the outer membrane protein profile and triggered expression of RcsB response regulator. For the first time, we unveiled the pleiotropic effects of copper on uropathogenic P. mirabilis, especially for induction of bacterial two-component signaling system regulating fitness and virulence. CONCLUSION: The finding of copper-mediated virulence and fitness reinforced the importance of copper for prevention and therapeutic interventions against P. mirabilis infections. As such, this study could facilitate the copper-based strategies against UTI by P. mirabilis.

Infected calcium oxalate stone leading to pyogenic spondylodiscitis and bilateral lower limb weakness: a case report.

Introduction and importance: It is rare for calcium oxalate renal stone, presented mainly in sterile urine, to result in urinary tract infection. The stone-related infection could develop spondylodiscitis, causing neurological deficits. To date, there are no reports about calcium oxalate partial staghorn stone and spondylodiscitis. Case presentation: A 62-year-old male suffered from haematuria, fever, and flank pain. He came to the urology outpatient department, where acute pyelonephritis was diagnosed, and a left partial staghorn stone was seen on computed tomography. Oral antibiotics were prescribed with improvement. Two weeks after antibiotics treatment, he developed bilateral lower limb weakness and numbness under the nipple level. He was brought to the emergency department, where the spine MRI revealed T2-T3 spondylodiscitis with epidural abscess and spinal cord compression. He underwent T2-T3 spine operation with improvement in muscle power and hypesthesia. The culture of the surgical lesion yielded Citrobacter koseri, the same as the urine culture obtained at his first visit. Left-side percutaneous nephrolithotomy was performed 1 month after with successful stone removal and resolution of pyuria. Stone analyses reported calcium oxalate. Follow-up MRI showed marked improvement with resolution of spondylodiscitis. Clinical discussion: Urinary tract infection resulting from partial staghorn stone, with additional hematogenous spread causing spondylodiscitis, is scarcely discussed. The authors illustrated a case with calcium oxalate stone, belonging to sterile Jensen's classification type 1. However, a urinary tract infection could be seen in urine stasis or obstruction. Conclusion: With accurate diagnosis and essential interventions, the patient had immediate neurological improvement and reached disease-free status.

Estimated glomerular filtration rate-dip after medical target therapy associated with increased mortality and cardiovascular events in patients with primary aldosteronism.

OBJECTIVES: The correlation of the changes of estimated glomerular filtration rate (eGFR) with long-term cardiovascular complications in patients with primary aldosteronism (PA) following mineralocorticoid receptor antagonists (MRA) treatment remains ambiguous. This prospective study aims to determine factors associated with all-cause mortality and de novo cardiovascular events of PA patients against the eGFR-dip. METHODS: A total of 208 newly diagnosed PA patients were enrolled from January 2017 to January 2019. MRA was administered with at least a 6-month follow-up. The 'eGFR-dip' was defined as the difference between eGFR at 6 months after MRA treatment and respective baseline eGFR divided by the baseline eGFR. RESULTS: After a mean 5.7 years follow-up, an eGFR-dip more than 12%, which was detected in 99 (47.6%) of the 208 patients, was a significant independent risk factor predicting composite outcomes (all-cause mortality, de-novo three-point major adverse cardiovascular events, and/or congestive heart failure). Multivariable logistic regression showed that age [odds ratio (OR), 0.94; P = 0.003], pretreatment plasma aldosterone concentration (PAC; OR, 0.98; P  = 0.004), and initial eGFR (OR, 0.97; P  < 0.001) had a positive linkage with the eGFR-dip more than 12%. CONCLUSIONS: Nearly half of PA patients had an eGFR-dip more than 12% after 6 months of MRA treatment. They had a higher incidence of all-cause mortality and de novo cardiovascular events. Elder age, higher pretreatment PAC, or higher initial eGFR could be associated with an elevated risk of an eGFR-dip more than 12%.

New-onset diabetes mellitus risk associated with concurrent autonomous cortisol secretion in patients with primary aldosteronism.

Concurrent autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA patients) is not uncommon. This work aimed to determine the effect of cortisol levels on incident new-onset type 2 diabetes mellitus (NODM) in PA patients. Using the prospectively designed observational TAIPAI cohort, the PA patients were grouped by cortisol level after an overnight low-dose dexamethasone suppression test (1-mg DST). Of the 476 PA patients, 387 (43.7% men; mean age 52.8 years) did not have baseline DM. After a mean follow-up of 4.3 ± 2.9 years, 32 patients (8.3%) developed NODM. The cutoff value obtained via a generalized additive model showed that a serum cortisol level ≥ 2.65 µg/dL after 1-mg DST was a risk factor for developing NODM (HR, 3.5, p = 0.031) by Cox proportional- hazards model.. In PA patients with a higher body mass index (>25 kg/m2; HR, 3.16), lower estimated glomerular filtration rate (<90 ml/min/1.73 m2; HR, 3.18), longer hypertension duration (>7 years; HR, 3.34), and higher waist-to-hip ratio (>0.9; HR, 3.07), a concomitant cortisol level ≥ 2.65 µg/dL after 1-mg DST were more likely to develop NODM. The high-cortisol group of patients with aldosterone-producing adenoma (APA) using mineralocorticoid receptor antagonist (MRA) was associated with an increased risk of NODM (HR, 5.72). Our results showed that PA patients with a concomitant cortisol level ≥ 2.65 µg/dL after 1-mg DST, independent of the aldosterone level, had a higher incidence of NODM. Such PA patients should be carefully evaluated and managed to achieve better glucose control and prevent metabolic syndrome.

A post-trial follow-up study of pentosan polysulfate monotherapy on preventing recurrent urinary tract infection in women.

For women with recurrent urinary tract infection (UTI), previous U101 study has shown that pentosan polysulfate sodium (PPS) monotherapy for 16 weeks significantly reduced UTI episodes in the treatment group throughout the trial period. In this follow-up study, we aimed to assess whether the effects of PPS would last after completion of the trial to prevent recurrent UTIs. Conducted from 2018 to 2019, the U101 study was a multicenter, prospective, phase 2a, randomized trial, enrolling women with recurrent UTI to study the effects of a 16-week oral PPS monotherapy. After approximately two years, the follow-up was conducted by phone interview, obtaining data including self-reported UTI events, quality of life questionnaire, and adverse events. The primary endpoint of follow-up study was UTI recurrence-free survival and the secondary endpoints were quality of life and adverse events. Approximately two years after completion of the trial, the rate of recurrent UTI was 25% (3 of the 12 patients) in the PPS group and 85.7% (12 of the 14 patients) in the control group. Over the entire follow-up period, the UTI recurrence-free survival was significantly better in the PPS group than in the control group (log-rank test p < 0.001). The quality of life at two years was significantly improved in the PPS when compared to the control group (91.7 vs. 77.5, p < 0.001). No late adverse event was observed after cessation of the treatment. In this study, sixteen weeks of PPS monotherapy in women with recurrent UTI significantly reduced the numbers of recurrent UTI episodes during the 2-year follow-up.

The QseEF Two-Component System-GlmY Small RNA Regulatory Pathway Controls Swarming in Uropathogenic Proteus mirabilis.

Bacterial sensing of environmental signals through the two-component system (TCS) plays a key role in modulating virulence. In the search for the host hormone-sensing TCS, we identified a conserved qseEGF locus following glmY, a small RNA (sRNA) gene in uropathogenic Proteus mirabilis. Genes of glmY-qseE-qseG-qseF constitute an operon, and QseF binding sites were found in the glmY promoter region. Deletion of glmY or qseF resulted in reduced swarming motility and swarming-related phenotypes relative to the wild-type and the respective complemented strains. The qseF mutant had decreased glmYqseEGF promoter activity. Both glmY and qseF mutants exhibited decreased flhDC promoter activity and mRNA level, while increased rcsB mRNA level was observed in both mutants. Prediction by TargetRNA2 revealed cheA as the target of GlmY. Then, construction of the translational fusions containing various lengths of cheA 5'UTR for reporter assay and site-directed mutagenesis were performed to investigate the cheA-GlmY interaction in cheA activation. Notably, loss of glmY reduced the cheA mRNA level, and urea could inhibit swarming in a QseF-dependent manner. Altogether, this is the first report elucidating the underlying mechanisms for modulation of swarming motility by a QseEF-regulated sRNA GlmY, involving expression of cheA, rcsB and flhDC in uropathogenic P. mirabilis.

Preoperative %p2PSA and Prostate Health Index Predict Pathological Outcomes in Patients with Prostate Cancer Undergoing Radical Prostatectomy.

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.

The efficacy of pentosan polysulfate monotherapy for preventing recurrent urinary tract infections in women: A multicenter open-label randomized controlled trial.

BACKGROUND/PURPOSE: Pentosan polysulfate sodium (PPS), a semi-synthetic polysaccharide that adheres to bladder mucosa, is effective in treating interstitial cystitis. We evaluated the clinical benefit of PPS for the prevention of recurrent urinary tract infection (UTI) in women. METHODS: We conducted a multicenter, open-label, prospective, phase II, randomized controlled trial enrolling women with recurrent UTI ≥ 2 times in the past 6 months or ≥ 3 times in the past 12 months. Patients received oral PPS monotherapy for 16 weeks in treatment group. All patients were followed every 28 days until UTI recurrence or up to 112 days. The primary endpoint was the UTI recurrence-free survival. Adverse events were recorded as secondary endpoint. RESULTS: A total of 26 women were eligible for analysis. In the PPS group, none (0%) of the 12 patients had UTI recurrence during the study period. However, 9 (64%) of 14 patients had UTI recurrence in the control group. The UTI recurrence-free survival was significantly higher in the PPS group than in the control group (log-rank test p = 0.0004). One adverse event which led to discontinuation of the trial regimen was regarded as irrelevance of PPS treatment. The limitation was the small number of cases. CONCLUSION: Among women with recurrent UTI, 16-week PPS monotherapy significantly reduced UTI recurrence when compared with the control group.

Comparison of single and tandem ureteral stenting for malignant ureteral obstruction: a prospective study of 104 patients.

OBJECTIVES: The aim of this study was to compare single and tandem ureteral stenting in the management of malignant ureteral obstruction (MUO). METHODS: Our hospital's institutional review board approved this prospective study. Between November 2014 and June 2017, single ureteral stenting was performed in 56 patients (94 renal units) and tandem ureteral stenting in 48 patients (63 renal units) for MUO. A comparative analysis of the technical success rate, patient survival, stent patency, and complications was performed. RESULTS: Similar demographic data were observed in patients receiving either single or tandem ureteral stenting. The technical success rate was 93.6% (88/94) for single ureteral stenting and 95.2% (60/63) for tandem ureteral stenting. There was no difference in overall survival between patients receiving single or tandem ureteral stenting (p = 0.41), but the duration of stent patency in tandem ureteral stenting was significantly longer (p = 0.022). The mean patency time was 176.7 ± 21.3 days for single ureteral stenting, and 214.7 ± 21.0 days for tandem ureteral stenting. The complications of ureteral stenting were urinary tract infection (n = 18), lower urinary tract symptoms (n = 5), haematuria (n = 3), and stent migration (n = 1). CONCLUSIONS: Tandem ureteral stenting is a safe and feasible treatment for MUO, and had better efficacy compared to single ureteral stenting. KEY POINTS: • Ureteral stenting is an established treatment for the management of malignant ureteral obstruction (MUO) • Prospective single-centre study showed that tandem ureteral stenting is a safe and feasible treatment for MUO • Tandem ureteral stenting provides longer stent patency compared to single ureteral stenting in patient with MUO.

The application of p2PSA% and prostate health index in prostate cancer detection: A prospective cohort in a Tertiary Medical Center.

BACKGROUND/PURPOSE: Prostate specific antigen (PSA) with low specificity that causes unnecessary prostate biopsies increases clinical morbidities, psychological stress, and medical expenses. We aimed to test the accuracy and cutoff value of Prostate Health Index (PHI) in men for prostate cancer detection. METHODS: We prospectively enrolled 213 men who underwent prostate biopsy with PSA≦10 ng/ml or abnormal findings on digital rectal examination. Total PSA (tPSA), free PSA (fPSA) and p2PSA levels were measured by serum samples before prostate biopsy. PHI was calculated as (p2PSA/fPSA) × âˆštPSA. Multivariable logistic regression analyses were used to predict the risk of cancer and detect clinically significant prostate cancer. RESULTS: 33 (27.0%) patients were confirmed with the diagnoses of prostate cancer by prostate biopsy. The levels of p2PSA, %p2PSA, and PHI showed statistically significant differences between prostate cancer patients and non-cancer patients. %p2PSA and PHI had the highest area under the receiver operating characteristic curve (AUC) of 0.723 and 0.772 (both p < 0.001), respectively, predicting cancer detection at biopsy than other predictors (tPSA, fPSA, %fPSA, and PSA density (AUC: 0.544, 0.538, 0.593, and 0.664, respectively). In multivariable logistic regression, %p2PSA had a statistical significant odds ratio 8.51 (p = 0.003) and PHI had an odds ratio with marginal significance 4.18 (p = 0.06). CONCLUSION: %p2PSA and PHI increased the diagnostic accuracy with significantly greater sensitivity and specificity than tPSA. We determined an optimal cut-off value of PHI among Taiwanese population. These findings support the usefulness in the decisional process of prostate biopsy.

Recurrence pattern and TP53 mutation in upper urinary tract urothelial carcinoma.

TP53 mutation patterns are associated with prognosis of various cancers. This study was designed to investigate the association between TP53 mutation patterns and recurrence patterns in upper urinary tract urothelial carcinoma (UTUC) patients. A total of 165 consecutive UTUC patients who underwent nephroureterectomies were enrolled for measuring mutation patterns of TP53 gene from exome 2 to 11. Bladder recurrence, contralateral UTUC recurrence, and metastases were compared among groups by using log-rank test and Cox proportional hazard model. Single base substitution as an A:T to T:A transversion was noted in 55 (33.3%) patients (AT group). Forty-two (25.5%) patients had TP53 mutations with only other than A:T to T:A transversion (NAT group), and 68 patients (41.2%) had wide-type TP53 (WT group). AT group was predominately female (64%, 52%, 29%, respectively), had a higher incidence of end-stage renal disease (24%, 14%, 10%, respectively), and had more high-grade tumors (82%, 74%, 62%, respectively) compared to NAT and WT groups. With adjustment of tumor grade/stages, bladder and contralateral UTUC recurrence-free survival duration was shortest in NAT (p < 0.001) and AT group (p < 0.001), respectively. NAT group had a shorter metastasis-free survival duration than the other two groups combined (p = 0.018). As a result, A:T to T:A transversion increased contralateral UTUC recurrence risk, but other mutations in TP53 raised the hazard of bladder recurrence and metastases. Therefore, TP53 mutation pattern may be a useful biomarker to predict recurrence patterns of UTUC patients.

Malignant Ureteral Obstruction: Functional Duration of Metallic versus Polymeric Ureteral Stents.

BACKGROUND: Ureteral obstruction caused by extrinsic compression is often associated with intra-abdominal cancers. Internal drainage with ureteral stents is typically the first-line therapy to relieve such obstructions. Novel designs of ureteral stents made of different materials have been invented to achieve better drainage. In this study, we described the functional outcomes of a Resonance metallic ureteral stent (Cook Medical, Bloomington, Indiana, USA) in patients with malignant ureteral obstruction and compare the functional duration of Resonance stents with regular polymeric stents in the same cohort. METHODS: Cancer patients who received polymeric stents and subsequent Resonance stents for ureteral obstruction between July 2009 and November 2012 were included in a chart review. Stent failure was detected by clinical symptoms, imaging studies, and renal function tests. The functional durations of each stent were calculated, and possible factors affecting stent patency were investigated. RESULTS: A total of 50 stents were successfully inserted into 50 ureteral units in 42 patients with malignant ureteral obstruction. There were 7 antegrade stents and 43 retrograde stents. There were no major complications. Stent-related symptoms were similar in both kinds of stents. After polymeric stents were replaced with Resonance metallic stents, hydronephrosis subsided or remained stable in 90% (45/50) of the ureteral units. Serum creatinine decreased or remained stable in 90% (38/42) of these patients. The Resonance stent exhibited a mean increase in functional duration of 4 months compared with the polymeric stents (p<0.0001), and 50% (25/50) of the Resonance stents exhibited a significant increase in functional duration (more than 3 months). Pre-operative serum creatinine < 2 was associated with a substantial increase in stent duration. CONCLUSIONS: Resonance stents are effective and safe in relieving malignant ureteral obstructions after polymeric stents failure. Resonance stents can provide a longer functional duration than polymeric stents and should be offered as an option for internal drainage.

Corrigendum to "an emerging translational model to screen potential medicinal plants for nephrolithiasis, an independent risk factor for chronic kidney disease".

[This corrects the article DOI: 10.1155/2014/972958.].

An emerging translational model to screen potential medicinal plants for nephrolithiasis, an independent risk factor for chronic kidney disease.

Pharmacological therapy for urolithiasis using medicinal plants has been increasingly adopted for the prevention of its recurrence. A Drosophila melanogaster model developed for translational research of urolithiasis was applied to evaluate agents with potential antilithic effects and calcium oxalate (CaOx) formation. Potential antilithic herbs were prepared in a mixture of food in a diluted concentration of 5,000 from the original extract with 0.5% ethylene glycol (EG) as the lithogenic agent. The control group was fed with food only. After 3 weeks, flies (n ≥ 150 for each group) were killed using CO2 narcotization, and the Malpighian tubules were dissected, removed, and processed for polarized light microscopy examination of the crystals. The crystal formation rate in the EG group was 100.0%. In the study, 16 tested herbal drugs reached the crystal formation rate of 0.0%, including Salviae miltiorrhizae, Paeonia lactiflora, and Carthami flos. Scutellaria baicalensis enhanced CaOx crystal formation. Two herbal drugs Commiphora molmol and Natrii sulfas caused the death of all flies. Our rapid screening methods provided evidence that some medicinal plants have potential antilithic effects. These useful medicinal plants can be further studied using other animal or human models to verify their effects.

Effect of Flos carthami Extract and α 1-Adrenergic Antagonists on the Porcine Proximal Ureteral Peristalsis.

Traditional Chinese medicine (TCM) has been proposed to prevent urolithiasis. In China, Flos carthami (FC, also known as Carthamus tinctorius) (Safflower; Chinese name: Hong Hua/) has been used to treat urological diseases for centuries. We previously performed a screening and confirmed the in vivo antilithic effect of FC extract. Here, ex vivo organ bath experiment was further performed to study the effect of FC extract on the inhibition of phenylepinephrine (PE) (10(-4) and 10(-3) M) ureteral peristalsis of porcine ureters with several α 1-adrenergic antagonists (doxazosin, tamsulosin, and terazosin) as experimental controls. The results showed that doxazosin, tamsulosin, and terazosin dose (approximately 4.5 × 10(-6) - 4.5 × 10(-1) µg/mL) dependently inhibited both 10(-4) and 10(-3) M PE-induced ureteral peristalsis. FC extract achieved 6.2% ± 10.1%, 21.8% ± 6.8%, and 24.0% ± 5.6% inhibitions of 10(-4) M PE-induced peristalsis at doses of 5 × 10(3), 1 × 10(4), and 2 × 10(4) µg/mL, respectively, since FC extract was unable to completely inhibit PE-induced ureteral peristalsis, suggesting the antilithic effect of FC extract is related to mechanisms other than modulation of ureteral peristalsis.

Metallic ureteral stents in malignant ureteral obstruction: clinical factors predicting stent failure.

PURPOSE: To provide clinical outcomes of the Resonance metallic ureteral stent in patients with malignant ureteral obstruction, as well as clinical factors predicting stent failure. METHODS: Cancer patients who have received Resonance stents from July 2009 to March 2012 for ureteral obstruction were included for chart review. Stent failure was detected by clinical symptoms, image studies, and renal function tests. Survival analysis for stent duration was used to estimate patency rate and factors predicting stent failure. RESULTS: A total of 117 stents were inserted successfully into 94 ureteral units in 79 patients. There were no major complications. These stents underwent survival analysis and proportional hazard regression. The median duration for the stents was 5.77 months. In multivariate analysis, age (P=0.043), preoperative serum creatinine level (P=0.0174), and cancer type (P=0.0494) were significant factors associated with stent failure. Cancer treatment before and after stent insertion had no effect on stent duration. CONCLUSIONS: Resonance stents are effective and safe in relieving malignant ureteral obstructions. Old age and high serum creatinine level are predictors for stent failure. Stents in patients with lower gastrointestinal cancers have longer functional duration.

Effects of commercial citrate-containing juices on urolithiasis in a Drosophila model.

Diet modification plays an important role in nephrolithiasis. Development of an easy, ready-to-use beverage such as a commercial juice drink to use as a preventive treatment for renal calculi formation would be widely welcomed. We previously developed a novel Drosophila model for the study of nephrolithiasis. It provides a new well-established drug discovery platform for this common disease. In our current study, we used the Drosophila model to investigate the preventive effects of various commercial juices as potential treatments for nephrolithiasis. Our results showed that apple, cranberry, orange, and pomegranate juices failed to reduce calcium oxalate (CaOx) crystal formation, whereas our positive control-potassium citrate (K-citrate)-significantly prevented CaOx crystal formation. Unlike the commercial fruit juices that were tested, the administration of K-citrate significantly ameliorated the ethylene glycol (EG)-induced life-span reduction in treated flies. These results indicate that EG-induced CaOx nephrolithiasis in Drosophila can be prevented by K-citrate, but not by commercial citrate-containing juices. However, the inhibitory capability of citrate-containing juices to reduce renal stone formation in humans requires further elucidation.

CCL2 increases αvß3 integrin expression and subsequently promotes prostate cancer migration.

BACKGROUND: Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family which is associated with the disease status and outcomes of cancers. Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. However, the effect of CCL2 on human prostate cancer cells is largely unknown. The aim of this study was to examine the role of CCL2 in integrin expression and migratory activity in prostate cancers. METHODS: Prostate cancer migration was examined using Transwell, wound healing, and invasion assay. The PKCδ and c-Src phosphorylations were examined by using western blotting. The qPCR was used to examine the mRNA expression of integrins. A transient transfection protocol was used to examine AP-1 activity. RESULTS: Stimulation of prostate cancer cell lines (PC3, DU145, and LNCaP) induced migration and expression of integrin αvß3. Treatment of cells with αvß3 antibody or siRNA abolished CCL2-increased cell migration. CCL2-increased migration and integrin expression were diminished by CCR2 but not by CCR4 inhibitors, suggesting that the CCR2 receptor is involved in CCL2-promoted prostate cancer migration. CCL2 activated a signal transduction pathway that includes PKCδ, c-Src, and AP-1. Reagents that inhibit specific components of this pathway each diminished the ability of CCL2 to effect cell migration and integrin expression. CONCLUSIONS: Interaction between CCL2 and CCR2 enhances migration of prostate cancer cells through an increase in αvß3 integrin production. GENERAL SIGNIFICANCE: CCL2 is a critical factor of prostate cancer metastasis.

Solifenacin improves double-J stent-related symptoms in both genders following uncomplicated ureteroscopic lithotripsy.

The objective of this study is to evaluate the effects of solifenacin on double-J stent-related symptoms following uncomplicated ureterosocpic lithotripsy (URSL). A total of 70 patients who underwent double-J ureteral stent insertion following URSL were consecutively recruited and received solifenacin postoperatively. Another 70 age- and sex-matched subjects without solifenacin therapy were enrolled as a control group. The clinical data including stone and stent characteristics were collected. All subjects completed the brief-form Ureteral Symptom Score Questionnaire (Chinese-version) to assess the lower urinary tract symptoms, stent-related body pain and hematuria 2 weeks after operation. The severity of stent-related symptoms was compared between two groups. The mean age was 53.8 in solifenacin group and 53.4 years in the control group (p = 0.87). The stone characteristics, stent size, position and curl completeness were similar in both groups. Compared to the control group, solifenacin group had significantly lower total symptom score, urgency and urge incontinence scores. As for stent-related body pain, solifenacin group had significantly less flank, abdominal, urethral pain and hematuria scores (all p < 0.05). The solifenacin versus control group showed significant benefits in lower urinary tract symptoms, stent-related pain and hematuria in both genders (all p < 0.05). Four subjects encountered minor adverse events (5.7 %) and one had urinary retention (1.4 %) in solifenacin group. For patients undergoing URSL and double-J stent indwelling, postoperative solifenacin use was effective and well-tolerated for the treatment of lower urinary tract symptoms, stent-related body pain and hematuria irrespective of genders.

Aristolochic acid-induced upper tract urothelial carcinoma in Taiwan: clinical characteristics and outcomes.

Aristolochic acid (AA), a component of all Aristolochia-based herbal medicines, is a potent nephrotoxin and human carcinogen associated with upper urinary tract urothelial carcinoma (UUC). To investigate the clinical and pathological characteristics of AA-induced UUC, this study included 152 UUC patients, 93 of whom had been exposed to AA based on the presence of aristolactam-DNA adducts in the renal cortex. Gene sequencing was used to identify tumors with A:T-to-T:A transversions in TP53, a mutational signature associated with AA. Cases with both aristolactam-DNA adducts and A:T-to-T:A transversions in TP53 were defined as AA-UUC, whereas patients lacking both of these biomarkers were classified as non-AA-UUC. Cases with either biomarker were classified as possible-AA-UUC. Forty (26%), 60 (40%), and 52 (34%) patients were classified as AA-UUC, possible-AA-UUC and non-AA-UUC, respectively. AA-UUC patients were younger (median ages: 64, 68, 68 years, respectively; p=0.189), predominately female (65%, 42%, 35%, respectively; p=0.011), had more end-stage renal disease (28%, 10%, 12%, respectively; p=0.055), and were infrequent smokers (5%, 22%, 33%, respectively; p=0.07) compared to possible-AA-UUC and non-AA-UUC patients. All 14 patients who developed contralateral UUC had aristolactam-DNA adducts; ten of these also had signature mutations. The contralateral UUC-free survival period was shorter in AA-UUC compared to possible- or non-AA-UUC (p=0.019 and 0.002, respectively), whereas no differences among groups were observed for bladder cancer recurrence. In conclusion, AA-UUC patients tend to be younger and female, and have more advanced renal disease. Notably, AA exposure was associated with an increased risk for developing synchronous bilateral and metachronous contralateral UUC.