Body mass weighted PSA levels, new markers to predict locally advanced prostate cancer after prostatectomy.

BACKGROUND: PSA remains the most useful marker for screening, risk categorization, and follow-up in patients with prostate cancer. In the obese population, several studies have revealed that obesity may not only inversely interfere with the concentration of PSA, but also increase the risk of prostate cancer. Thus, we considered using the Body mass weighted PSA levels, presented as serum PSA concentration multiplied by body weight or BMI, instead of traditional PSA concentration, as potential markers to predict locally advanced prostate cancer after prostatectomy. METHODS: We retrospectively collected and analyzed data acquired from a single institute at which robot-assisted laparoscopic radical prostatectomy was performed. A total of 174 patients underwent radical prostatectomy, and the collected data included age, PSA level, body weight, BMI, and pathology results. RESULTS: A total of 174 patients diagnosed with adenocarcinoma of the prostate by needle biopsy, and most (N=165) were considered to have localized disease on preoperative multi-parameter magnetic resoanace imaging. After prostatectomy, 73% (N=127) of the patients remained in the localized disease group (group A) and 27%(N=47) of the patients were reclassified to the locally advanced prostate cancer (group B). The value of PSA was higher in Group B (16.9 vs 11.2 ng/dL; p= 0.062), but there was no statistically significant difference between the two groups. After using the numerical values of PSA x body weight and PSA x BMI, a statistically significant difference emerged between the two groups (p= 0.0198 in PSA × BW; p=0.0110 in PSA × BMI). CONCLUSION: The Body mass weighted PSA levels, instead of the traditional PSA concentration, may be better markers for predicting non-organ-confined disease after surgery. It may also be useful in screening and risk categorization.

Unusual presentation of penile giant condyloma acuminatum with spontaneous prepuce perforation: A case report.

BACKGROUND: Giant condyloma acuminatum (GCA) is an uncommon condition affecting the anogenital area. CASE SUMMARY: Here, we report an 88-year-old male patient who presented with a 5-year history of a progressive appearance of multiple cauliflower-like warts over his penile shaft, pubis region, and groin as well as urine leakage along the distal penile shaft. Physical examination revealed an ulcerative skin perforation with pus discharge under the distal prepuce base, which was initially suspected to be a urethral fistula. However, during surgery, it was discovered that the perforation was caused by a giant condyloma lesion that had obliterated the prepuce opening, with infection and high pressure causing subsequent skin perforation. He underwent circumcision and wide excision with electrocauterization of the warts. He was discharged after the surgery, and the residual lesion was treated with imiquimod and low-dose oral tegafur-uracil. CONCLUSION: Penile GCA can cause prepuce perforation and can be postoperatively treated with imiquimod and low-dose oral tegafur-uracil.

Circulating Tumor Cells Predict Response of Neoadjuvant Chemotherapy in Patients with Bladder Cancer: A Preliminary Study.

This study aimed to explore the existence of circulating tumor cells (CTCs) in patients with muscle-invasive bladder cancer (MIBC) and their predictive potential for response to neoadjuvant chemotherapy (NAC). From 33 blood samples of MIBC patients, CTCs were isolated by cell surface markers and enriched by the IsoFlux™ device, followed by morphological and immunofluorescent identification. CTCs were detected at baseline in all samples. Immunofluorescence confirmed the tumor origin. MIBC patients were stratified by NAC response into the disease control (DC) and progressive disease (PD) groups. In the DC group, the number of CTCs decreased significantly after four courses of NAC (p < 0.0001). CTC counts in 7.5 mL after four NAC cycles were highly correlated with postoperative pathological T stage (p < 0.0001). Our study demonstrated that CTCs might represent a valuable predictive marker for NAC response in MIBC. CTC detection in MIBC patients could allow early arrangement of radical cystectomy for NAC non-responders to prevent disease progression while receiving the NAC courses.

Endoscopic Combined Intrarenal Surgery Versus Percutaneous Nephrolithotomy for Complex Renal Stones: A Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopic combined intrarenal surgery (ECIRS) adds ureteroscopic vision to percutaneous nephrolithotomy (PCNL), which can be helpful when dealing with complex renal stones. Yet, there is still no consensus on the superiority of ECIRS. We aimed to critically analyze the available evidence of studies comparing efficacy, safety, bleeding risk, and efficiency of ECIRS and PCNL. METHODS: We searched for studies comparing efficacy (initial and final stone-free rate), safety (postoperative fever, overall and severe complications), efficiency (operative time and hospital stay) and bleeding risk between ECIRS and PCNL. Meta-analysis was performed. RESULTS: Seven studies (919 patients) were identified. ECIRS provided a significantly higher initial stone-free rate, higher final stone-free rate, lower overall complications, lower severe complications, and lower rate of requiring blood transfusion. There was no difference between the two groups in terms of postoperative fever, hemoglobin drop, operative time, and hospital stay. In the subgroup analysis, both minimally invasive and conventional ECIRS were associated with a higher stone-free rate and lower complication outcomes. CONCLUSIONS: When treating complex renal stones, ECIRS has a better stone-free rate, fewer complications, and requires fewer blood transfusions compared with PCNL. Subgroups either with minimally invasive or conventional intervention showed a consistent trend.

The Study of 3D Printing-Assisted Electrospinning Technology in Producing Tissue Regeneration Polymer-Fibroin Scaffold for Ureter Repair.

OBJECTIVE: Long segment ureteral lesion with obstruction is a clinically difficult issue for recovering and maintaining organ or tissue function. Regeneration medicine using various biomaterials as a scaffold in supporting tissue regrowth is emerging. We developed this customized scaffold using electrospinning and 3-dimensional assistance and expected that it may provide an alternative biomaterial for ureter defect repair. MATERIAL AND METHODS: Our study synthesized polycaprolactone and silk fibroin combination as biomaterial scaffolds. The differences in physicochemical properties and biocompatibility of polycaprolactone-silk fibroin bio-scaffolds prepared by electrospinning alone and 3-dimensional printing combined with electrospinning in proper ratios were compared and characterized. SV-HUC-1 uroepithelial cells cultured in polycaprolactone-silk fibroin (4 : 6) scaffolds were observed under a scanning electron microscope and using calcein-acetomethoxy and propidium iodide stain. The ex vivo resected healthy human ureteral segment tissue was anastomosed with the polycaprolactone-silk fibroin scaffolds and cultured in an ex vivo bath for 2 weeks. The cellular growth on the polycaprolactone-silk fibroin scaffold was observed microscopically. In the New Zealand white rabbit model, we performed a 1/5 ratio (2 cm out of 10 cm) defect replacement of the unilateral ureter. After 7 weeks, the rabbits were sacrificed and the implanted ureter scaffolds were resected for tissue sectioning and the cellular growth was observed by hematoxylin and eosin and Masson staining. RESULTS: When the proportion of silk fibroin was increased and the 3-dimensional electrospinning method was used, both the size and diameter of nanofiber holes were increased in the polycaprolactone-silk fibroin scaffold. Scanning electron microscope and fluorescent stain revealed that cultured 3T3 and SV-HUC-1 uroepithelial cells could electively penetrate inside the polycaprolactone-silk fibroin (4 : 6) nanofibrous scaffolds in 3 days. The polycaprolactone-silk fibroin scaffold anastomosis in an ex vivo bath showed cellular growth stably along the scaffold for 2 weeks, and most of the cells grow along with the outboard of the scaffold in layers. In an animal model, different layered cells can be observed to grow along with the outboard of the scaffold with mucosa, submucosa, muscular layer, and the serosa layer order after 7 weeks. Mucosa and muscular layer growth along the scaffold inner wall were seen simultaneously. CONCLUSION: 3-dimensional electrospinning synthesized 4 : 6 polycaprolactone-silk fibroin nanofiber scaffolds that are feasible for tissue growth and achieve the purpose of ureteral reconstruction in animal experiments. This new form of 3-dimensional electrospinning constructed polycaprolactone-silk fibroin nanofiber scaffold may be considered as a clinical urinary tract tissue reconstruction alternative in the future.

DNA Hypomethylation Is Associated with the Overexpression of INHBA in Upper Tract Urothelial Carcinoma.

Urothelial carcinoma includes upper urinary tract cancer (UTUC) and bladder cancer. Although nephroureterectomy is the standard treatment for UTUC, the recurrence rate is approximately half and the tumor is associated with poor prognoses. Metastases are the most devastating and lethal clinical situation in urothelial carcinoma. Despite its clinical importance, few potential diagnostic biomarkers are suitable for early UC detection. We compared high-stage/high-grade urothelial carcinoma tissues to adjacent normal urothelial tissues using methyl-CpG binding domain protein capture for genome-wide DNA methylation analysis. Based on our findings, inhibin ßA (INHBA) might be associated with carcinogenesis and metastasis. Further, clinical UC specimens had significant INHBA hypomethylation based on pyrosequencing. INHBA was detected by real-time PCR and immunohistochemistry staining, and was found to be highly expressed in clinical tissues and cell lines of urothelial carcinoma. Further, INHBA depletion was found to significantly reduce BFTC-909 cell growth and migration by INHBA-specific small interfering RNA. Interestingly, a positive correlation was found between SMAD binding and extracellular structure organization with INHBA using gene set enrichment analysis and gene ontology analysis. Together, these results are the first evidence of INHBA promoter hypomethylation and INHBA overexpression in UTUC. INHBA may affect urothelial carcinoma migration by reorganizing the extracellular matrix through the SMAD pathway.

Long Noncoding RNA LINC02470 Sponges MicroRNA-143-3p and Enhances SMAD3-Mediated Epithelial-to-Mesenchymal Transition to Promote the Aggressive Properties of Bladder Cancer.

Bladder cancer progression and metastasis have become major threats in clinical practice, increasing mortality and therapeutic refractoriness; recently, epigenetic dysregulation of epithelial-to-mesenchymal transition (EMT)-related signaling pathways has been explored. However, research in the fields of long noncoding RNA (lncRNA) and competing endogenous RNA (ceRNA) regulation in bladder cancer progression is just beginning. This study was designed to determine potential EMT-related ceRNA regulation in bladder cancer progression and elucidate the underlying mechanisms that provoke aggressiveness. After screening the intersection of bioinformatic pipelines, LINC02470 was identified as the most upregulated lncRNA during bladder cancer initiation and progression. Both in vitro and in vivo biological effects indicated that LINC02470 promotes bladder cancer cell viability, migration, invasion, and tumorigenicity. On a molecular level, miR-143-3p directly targets and reduces both LINC02470 and SMAD3 RNA expression. Therefore, the LINC02470-miR-143-3p-SMAD3 ceRNA axis rescues SMAD3 translation upon LINC02470 sponging miR-143-3p, and SMAD3 consequently activates the TGF-ß-induced EMT process. In conclusion, this is the first study to demonstrate that LINC02470 plays a pivotally regulatory role in the promotion of TGF-ß-induced EMT through the miR-143-3p/SMAD3 axis, thereby aggravating bladder cancer progression. Our study warrants further investigation of LINC02470 as an indicatively prognostic marker of bladder cancer.

Determining programmed cell death ligand 1 expression in circulating tumor cells of patients with clear cell renal cell carcinoma and its correlation with response to programmed cell death protein 1 inhibitors.

OBJECTIVE: There is a great interest in determining whether the expression of the programmed cell death ligand 1 is correlated with the efficacy of immune checkpoint inhibitors in patients with clear cell renal cell carcinoma; however, primary tumor biopsies can only provide limited information. Therefore, we explored the expression of programmed cell death ligand 1 on circulating tumor cells, which is a potential predictor of therapeutic response. METHODS: Circulating tumor cells were isolated from 20 clear cell renal cell carcinoma patients based on cell surface markers targeting clear cell renal cell carcinoma using IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. Programmed cell death ligand 1 expression status and clinical correlations were also analyzed. RESULTS: Before treatment with programmed cell death protein 1 inhibitors, circulating tumor cells were detected in all patients, ranging from 1 to 22 (median 7), with 75% (15/20) of the patients having programmed cell death ligand 1 + circulating tumor cells. Circulating tumor cell programmed cell death ligand 1 expression did not correlate with the immunohistochemical staining of programmed cell death ligand 1 in primary tumors. During treatment with programmed cell death protein 1 inhibitors, the disease control rate was much higher in the patients harboring programmed cell death ligand 1 + circulating tumor cells (73%, 11/15) than others (20%, 1/5). We also found that changes in total circulating tumor cell numbers and programmed cell death ligand 1 + circulating tumor cell counts correlated well with the disease outcome. CONCLUSION: We showed that the presence of programmed cell death ligand 1 + circulating tumor cells before programmed cell death protein 1 inhibition treatment could be a prognosis predictive factor and that the dynamic changes in circulating tumor cell numbers may be used to monitor the therapeutic response. Our study confirms the possibility of programmed cell death ligand 1 + circulating tumor cell detection in clear cell renal cell carcinoma patients' blood samples, which can potentially be used as an individualized immunotherapy molecular biomarker for real-time exploration.

Detection of circulating tumor cells as therapeutic markers in patients with penile squamous cell carcinoma: A preliminary study.

BACKGROUND: This study aimed to investigate the presence of circulating tumor cells (CTCs) in patients with penile squamous cell carcinoma (PSCC). METHODS: CTCs were isolated from 14 patients with PSCC, 6 patients with balanoposthitis, and 6 healthy individuals. CTCs were enriched based on cell surface markers and filtered through the IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. RESULTS: CTCs were found in all PSCC blood samples but not in balanoposthitis samples and samples from healthy individuals. Immunofluorescence studies confirmed the tumor origin. When the patients with PSCC were stratified according to metastatic inguinal lymph node status, a statistically significant difference was observed in the number of detected CTCs. CONCLUSION: Our study showed that CTCs in PSCC may represent a valuable marker for differentiating PSCC from other tumors. Based on the correlation with some clinical parameters, CTC analysis is possibly relevant for noninvasive monitoring of disease progression and prognosis. The results also suggested a potential role of CTCs in preventing overtreatment, such as inguinal lymph node dissection.

Rare case of pancreatic adenocarcinoma with spermatic cord and testicular metastasis.

Male gonadal metastases from pancreatic carcinomas are extremely rare, with fewer than 20 cases documented in the literature. Herein, we report a man in his 50s who presented at the genitourinary outpatient department with an enlarged scrotum (right side) that had developed progressively over several weeks. He also reported mild upper abdominal discomfort. Scrotal sonography revealed a hydrocele on the right side without testicular lesions. A mass pancreatic tail lesion with invasion of the spleen and left adrenal gland was identified through abdominal CT and MRI. Endoscopic ultrasound fine needle biopsy and right radical orchiectomy were performed. Moderately differentiated adenocarcinoma of the pancreatic tail with hematogenous metastasis to the right testis, epididymis and spermatic cord was verified on the basis of the pathology report. Disease progression occurred despite the patient receiving palliative chemoradiation therapy.

Effects of robot-assisted versus hand-assisted nephroureterectomy on circulating tumor cells for upper urinary tract urothelial carcinoma.

To compare perioperative circulating tumor cells (CTC) in primary upper tract urothelial carcinoma (UTUC) patients who underwent hand-assisted retroperitoneoscopic nephroureterectomy (HANU) or robotic-assisted nephroureterectomy (RANU). A total of 29 patients received RANU (n = 10) or HANU (n = 19). Peripheral blood samples were collected before, 24 h after surgery (POh24) and on postoperative day 28 (POD28). The demographic and pathologic data are similar in both groups. RANU had a longer operative time (p = 0.031), less bleeding volume (p = 0.004), and comparable pain sore (p = 0.169). The mean CTC numbers before surgery (2.4 vs. 2.3, p = 0.482), POh24 (2.4 vs. 1.9, p = 0.668) and POD28 (0.5 vs. 0.6, p = 0.280) were not significant different among groups. The amount of CTCs in both groups decreased and reached similar level on POD28. No significant difference of overall and intravesical recurrence rate between the two approaches. In comparison to RANU, more surgical manipulation does not affect tumor cell translocation into the bloodstream in UTUC patients who received HANU. However, a longer follow-up would be needed for the final comparison of tumor recurrence.

Increased incidence of neurogenic bladder after radical hysterectomy for cervical cancer: A nationwide population-based cohort study.

BACKGROUND: The effect of radical hysterectomy for patients with cervical cancer on voiding function remains controversial. The purpose of this study was to examine the association between radical hysterectomy for patients with cervical cancer and the odds of developing neurogenic bladder by using data from the National Health Insurance Research Database (NHIRD) in Taiwan. METHODS: We identified 17 936 patients who underwent radical hysterectomy for cervical cancer between 2000 and 2013 among inpatients registered in the Longitudinal Health Insurance Database in Taiwan. Of the patients, those diagnosed as having cervical cancer without radical hysterectomy were selected and compared as a matched control group. Patients diagnosed as having cervical cancer before the index date, those with neurogenic bladder dysfunction before tracking, and those aged <20 years were excluded. The hazard ratios (HRs) of neurogenic bladder and other variants of interest were further calculated using a multivariate Cox regression analysis. The cutoff p value of <0.05 was regarded as statistically significant. RESULTS: The adjusted HR (aHR) of subsequent neurogenic bladder was higher in the hysterectomy group (aHR = 1.205; 95% CI, 1.086-1.440; p = 0.029) than in the control group during the follow-up period. As to the age subgroups, the patients aged 20 to 44 years (aHR = 3.321, p = 0.001) had a significantly increased risk of developing neurogenic bladder after radical hysterectomy as compared with those aged 45 to 64 years (aHR = 1.193, p = 0.012). CONCLUSION: Patients with cervical cancer undergoing radical hysterectomy have an increased risk of neurogenic bladder, which may result from nerve denervation caused by the operation. These patients should be informed of the potential risk of voiding dysfunction during discussion of the subsequent management for cervical cancer.

Programmed Cell Death Ligand 1 Expression in Circulating Tumor Cells as a Predictor of Treatment Response in Patients with Urothelial Carcinoma.

Programmed cell death ligand 1 (PD-L1) inhibitors are commonly used in treating advanced-stage urothelial carcinoma (UC). Therefore, this study evaluated the relationship between PD-L1 expression in circulating tumor cells (CTCs) and treatment response to PD-L1 inhibitors using blood samples collected from patients with UC (n = 23). Subsequently, PD-L1 expression and its clinical correlation were analyzed. All patients had CTCs before PD-L1 inhibitory treatment, of which 15 had PD-L1-positive CTCs. However, PD-L1-positive expression in CTCs was not correlated with PD-L1 expression in tumor biopsy samples. Patients with PD-L1-positive CTCs had better disease control (DC) rates than those without PD-L1-positive CTCs. Moreover, changes in the proportion of PD-L1-positive CTCs were associated with disease outcomes. Furthermore, the PD-L1-positive CTC count in 9 of 11 patients who achieved DC had significantly decreased (p = 0.01). In four patients with progressive disease, this was higher or did not change. PD-L1-positive CTCs at baseline could be used as a biomarker to identify patients suitable for PD-L1 blockade therapy. Dynamic changes in PD-L1-positive CTCs during the course of treatment are predictive factors of immunotherapy response and prognostic factors of disease control. Hence, PD-L1-positive CTCs could be employed as a real-time molecular biomarker for individualized immunotherapy.

Ellagic Acid Resensitizes Gemcitabine-Resistant Bladder Cancer Cells by Inhibiting Epithelial-Mesenchymal Transition and Gemcitabine Transporters.

Gemcitabine (GCB) resistance is a major issue in bladder cancer chemoresistance, but its underlying mechanism has not been determined. Epithelial-mesenchymal transition (EMT) has been shown to be comprehensively involved in GCB resistance in several other cancer types, but the direct connection between EMT and GCB remains unclear. This study was designed to elucidate the mechanism of EMT-related GCB resistance in bladder cancer and identify a potential phytochemical to modulate drug sensitivity. The biological effects of ellagic acid (EA) or its combined effects with GCB were compared in GCB-resistant cells and the GCB-sensitive line in terms of cell viability, apoptosis, motility, and in vivo tumorigenicity. The molecular regulation of EMT-related GCB resistance was evaluated at both the mRNA and protein expression levels. Our results indicated that TGF-ß/Smad induced the overactivation of EMT in GCB-resistant cells and reduced the expression of GCB influx transporters (hCNT1 and hENT1). Moreover, ellagic acid (EA) inhibited the TGF-ß signaling pathway both in vitro and in vivo by reducing Smad2, Smad3, and Smad4 expression and thereby resensitized GCB sensitivity. In conclusion, our results demonstrate that TGF-ß/Smad-induced EMT contributes to GCB resistance in bladder cancer by reducing GCB influx and also elucidate the novel mechanisms of EA-mediated inhibition of TGF-ß/Smad-induced EMT to overcome GCB resistance. Our study warrants further investigation of EA as an effective therapeutic adjuvant agent for overcoming GCB resistance in bladder cancer.

Decreased drug resistance of bladder cancer using phytochemicals treatment.

The aim of the study is to investigate the ability of phytochemicals to overcome the multiple drug resistance (MDR) of bladder cancer. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the cytotoxic sensitivity of T24-GCB cells, a GCB resistant cell line, to different phytochemicals, including capsaicin, quercetin, curcumin, and resveratrol, and their combination with gemcitabine. Western blot analysis was used to detect the expression of membranous ABCC2 and metabolic proteins, DCK, TK1, and TK2 in tumor cells. Animal models were used to confirm the treatment efficacy of phytochemicals in combination with gemcitabine to bladder cancer. The observed/expected ratio of cytotoxicity analysis revealed that capsaicin has synergistic effect with gemcitabine to T24-GCB cells in a dose-dependent pattern. Quercetin, curcumin, and resveratrol have additive effect with gemcitabine to T24-GCB cells. Capsaicin and quercetin alone and combination with gemcitabine decreased the expression of ABCC2 and DCK and TKs, in T24-GCB cells. On the contrary, resveratrol and curcumin alone and combination with gemcitabine increased the expression of ABCC2 but decreased cytoplasmic kinases simultaneously. In xenografted subcutaneous tumor model on nude mice, combination treatment of capsaicin and gemcitabine demonstrated the highest tumor suppression effect when compared to capsaicin or gemcitabine treatment alone. The MDR of bladder cancer is closely related to membranous ABCC2, cytoplasmic DCK, and TKs expression. Capsaicin owns the strongest synergistic cytotoxic effect of gemcitabine to T24-GCB cells. This combination regimen may provide as an adjunctive treatment for overcoming MDR in bladder cancer.

Exosome-Derived LINC00960 and LINC02470 Promote the Epithelial-Mesenchymal Transition and Aggressiveness of Bladder Cancer Cells.

Exosomes are essential for several tumor progression-related processes, including the epithelial-mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) comprise a major group of exosomal components and regulate the neoplastic development of several cancer types; however, the progressive role of exosomal lncRNAs in bladder cancer have rarely been addressed. In this study, we identified two potential aggressiveness-promoting exosomal lncRNAs, LINC00960 and LINC02470. Exosomes derived from high-grade bladder cancer cells enhanced the viability, migration, invasion and clonogenicity of recipient low-grade bladder cancer cells and activated major EMT-upstream signaling pathways, including ß-catenin signaling, Notch signaling, and Smad2/3 signaling pathways. Nevertheless, LINC00960 and LINC02470 were expressed at significantly higher levels in T24 and J82 cells and their secreted exosomes than in TSGH-8301 cells. Moreover, exosomes derived from LINC00960 knockdown or LINC02470 knockdown T24 cells significantly attenuated the ability of exosomes to promote cell aggressiveness and activate EMT-related signaling pathways in recipient TSGH-8301 cells. Our findings indicate that exosome-derived LINC00960 and LINC02470 from high-grade bladder cancer cells promote the malignant behaviors of recipient low-grade bladder cancer cells and induce EMT by upregulating ß-catenin signaling, Notch signaling, and Smad2/3 signaling. Both lncRNAs may serve as potential liquid biomarkers for the prognostic surveillance of bladder cancer progression.

IL-27/IL-27RA signaling may modulate inflammation and progression of benign prostatic hyperplasia via suppressing the LPS/TLR4 pathway.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common urologic disease affecting aging men. The pathogenesis of BPH is multi-factorial, and chronic inflammation (CI) might be the central mechanism. Interleukin (IL)-27 signaling has been suggested as a modulator in autoimmune and inflammatory conditions. In this study, we used microarray experiments to analyze gene expression and molecular phenotypic associated with BPH progression, with a particular focus on CI and IL-27/IL-27RA signaling, and verified the microarray data in cell biology experiments. METHODS: Thirty BPH patients' specimens and clinical parameters were analyzed. BPH patients were divided into two groups based on the average prostate volume (41.5 mL): group 1, ≤40 mL; and group 2, >40 mL. Microarray experiments were conducted to identify differentially expressed genes (DEGs) by applying appropriate biostatistics to normalize and analyze the dataset. The candidate gene (IL27RA) was validated by quantitative reverse transcriptase-PCR (qRT-PCR) and immunohistochemistry (IHC). The interaction of IL27RA with genes involved in canonical inflammation-associated pathways was investigated by cell biology experiments. RESULTS: Eighty-three percent of BPH specimens contained inflammatory infiltrates, and the predominant type was CI. The serum PSA levels and prevalence of CI were higher in group 2. Microarray experiments identified 361 DEGs between these 2 groups. IL27RA was down-regulated and associated with prominent CI in BPH tissues of group 2. Validated by qRT-PCR and IHC, the results showed IL-27RA might modulate CI and progression of BPH. Thus, we investigated the interaction of IL27RA with TLR4, IL6, and IL8, which were involved in inflammation-associated pathways. We found the activation of IL-27RA after IL-27 treatment led to phosphorylation of STAT1 and STAT3 in prostate epithelial cells. By comparative treatments with lipopolysaccharide (LPS), IL-27, or combination, we found that IL-27/IL-27RA signaling suppressed the production of inflammatory cytokines, IL-6 and IL-8, induced by LPS/TLR4 pathway. CONCLUSIONS: Our study revealed that down-regulation of IL27RA in prostate tissue was associated with higher prevalence of CI and BPH progression. IL-27/IL-27RA signaling suppressed the LPS/TLR4 pathway. We conclude the IL-27/IL-27RA signaling might modulate CI and provide potential therapeutic strategies to prevent BPH progression.

The modulation study of multiple drug resistance in bladder cancer by curcumin and resveratrol.

Gemcitabine (GCB), which functions via the inhibition of DNA synthesis, is commonly used in the treatment of bladder cancer; however, its response rate is not satisfactory due to the development of drug resistance. The potential for phytochemicals to reverse drug resistance in bladder cancer tumor cells was evaluated. A human bladder cancer cell line, T24, was cultured, and GCB-resistant cells (T24-GCB) were also established. The acquired resistance of T24-GCB to GCB was measured using an MTT assay. The gene expression of ATP-binding cassette (ABC) transporter protein family members was analyzed using reverse transcription-quantitative PCR analysis, and western blotting was performed to verify ABC family protein, cytoplasmic thymidine kinase (TK) and poly (ADP-ribose) polymerase (PARP) expression on whole cell lysates. Subsequently, resveratrol and curcumin were used to evaluate their modulation potential in decreasing the drug resistance of T24-GCB cells to GCB using MTT and migration assays. T24-GCB cells have increased drug resistance ability, with an 18.75-fold higher ID50 value compared with native T24 cells (105 vs. 5.6 nM). T24-GCB cells also exhibit increased cross resistance to mitomycin C and paclitaxel. The mRNA expression of ABCC2 in T24-GCB cells increased compared with that in native T24 cells. Via western blot analysis, it was determined that the expression of ABCC2 protein was also increased in T24-GCB cells. Conversely, the expression of ABCB1, ABCG2, deoxycytidine kinase (DCK), TK1 and TK2 decreased. Following curcumin and resveratrol treatment alone or combined with GCB, additive cytotoxic enhancement was observed, and the migratory abilities of T24-GCB cells were significantly decreased. Western blot analysis revealed that ABCC2 protein expression increased, and DCK, TK1 and TK2 expression decreased following co-treatment of T24-GCB cells with GCB + curcumin or resveratrol compared with GCB alone. Of note, there was a marked increase in cleaved-PARP expression in T24-GCB cells treated with a combination of GCB + curcumin or resveratrol. Both curcumin and resveratrol could reverse the drug resistance of T24-GCB cells in an additive pattern though PARP enhancement without changes in ABCC2 and DCK, TK1 and TK2 expression.

A rare case of extraluminal gastrointestinal stromal tumor of the ileum presenting with lower urinary tract symptoms: A case report.

INTRODUCTION: Benign prostatic hyperplasia, bladder outlet obstruction, and overactive bladder are major causes of lower urinary tract symptoms (LUTS). Tumor compression of the urinary bladder resulting in LUTS was clinically observed. Gastrointestinal stromal tumors (GISTs) presenting with LUTS have not been reported before. Herein, we report a patient with extraluminal GIST of the ileum who had LUTS without gastrointestinal symptoms during the clinical course. PATIENT CONCERNS: A 68-year-old man visited the genitourinary outpatient department because of frequent urination with mild dysuria. He also complained of poor appetite, fatigue, and body weight loss of 10 kg over 6 months. A large presacral solid mass lesion compressing the bladder and surrounded by the bowel with gas content was identified through abdominal computed tomography. DIAGNOSIS: GIST of the ileum with mesenteric invasion was revealed by pathological examination. INTERVENTIONS: Exploratory laparotomy with removal of the pelvic tumor and segmental resection of the ileum was performed. OUTCOMES: Now, he received adjuvant imatinib target therapy for 1 year with stable condition. CONCLUSION: Extravesical compression or invasion of the urinary bladder by a pelvic mass lesion is common but is rarely accompanied by GISTs of the ileum. Specific findings identified through imaging should alert the surgeon to this specific entity and prepare thoroughly before surgical intervention.