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Bladder cancer (BC) is one of the most prevalent and life-threatening cancers among the male population worldwide. Sex determining region Y-box protein 5 (SOX5) plays important roles in a variety of human cancers. However, little research has been conducted on the function and underlying mechanism of SOX5 in BC. In the present study, we first reveal the increased expression of SOX5 in BC tissues and

BACKGROUND: Keratinizing squamous metaplasia (KSM) is a clinically heterogeneous disease that lacks research that provide definitive recurrent risk factors. Therefore, we identified the recurrence factors in patients with KSM of the bladder after transurethral resection (TUR). We also attempted to investigate the association between KSM and bladder cancer. METHODS: Clinical information of 257 patients diagnosed with KSM who underwent TUR in Xiangya Hospital from January 2010 to November 2018 were retrospectively collected. Clinical information was available for follow-up of 223 patients. To determine the risk factors for recurrence, we conducted univariate and multivariate cox regression analysis respectively. To explore the association between KSM and bladder cancer, we used clinical follow-up data. RESULTS: The median follow-up time is 49 (IQR, 12–121) months. Five-year recurrence-free rate (RFR) and 1-year RFR were 86.1% and 91.9%, respectively. Thirty-one patients (13.9%) relapsed of KSM after a median follow-up of 49 months (range, 12–121 months), and none of them developed subsequent bladder cancer. Univariate Cox analysis indicated that urinary tract infection [hazard ratio (HR) =2.111; 95% confidence interval (CI): 1.043–4.271; P=0.038], and atypical urothelial hyperplasia of the bladder (HR =4.191; 95% CI: 2.006–8.756; P

To parallelly compare the efficacy of neoadjuvant immunotherapy (tislelizumab), neoadjuvant chemotherapy (gemcitabine and cisplatin), and neoadjuvant combination therapy (tislelizumab + GC) in patients with muscle-invasive bladder cancer (MIBC) and explore the efficacy predictors, we perform a multi-center, real-world cohort study that enrolls 253 patients treated with neoadjuvant treatments (combination therapy: 98, chemotherapy: 107, and immunotherapy: 48) from 15 tertiary hospitals. We demonstrate that neoadjuvant combination therapy achieves the highest complete response rate and pathological downstaging rate compared with neoadjuvant immunotherapy or chemotherapy. We develop and validate an efficacy prediction model consisting of pretreatment clinical characteristics, which can pinpoint candidates to receive neoadjuvant combination therapy. We also preliminarily reveal that patients who achieve pathological complete response after neoadjuvant treatments plus maximal transurethral resection of the bladder tumor may be safe to receive bladder preservation therapy. Overall, this study highlights the benefit of neoadjuvant combination therapy based on tislelizumab for MIBC.

The limited effect of adjuvant therapy for advanced bladder cancer (BCa) leads to a poor prognosis. Increasing evidence has shown that RNA N6-methyladenosine (m

The tumor mutational burden (TMB) calculated by whole-exome sequencing (WES) is a promising biomarker for the response to immune checkpoint inhibition (ICIs) in solid tumors. However, WES is not feasible in the routine clinical setting. In addition, the characteristics of the TMB in Chinese urothelial carcinoma (UC) are unclear. The aim of this study was to demonstrate the reliability of an Acornmed 808 panel and analyze the characteristics of the TMB in Chinese UC. An Acornmed 808 panel was designed and virtually validated using UC data from the cancer genome atlas (TCGA). Comprehensive analysis of sequencing and clinical data was performed to explore the characteristics of the TMB for 143 Chinese UC patients. Compared to the TMB calculated with random 808-, 500-, and 250-gene panels, the TMB calculated with the Acornmed 808 panel was closer to that calculated by WES. There were marked disparities in the mutational landscape and TMB between Chinese and TCGA UC data. The TMB was negatively associated with copy number variation (CNV). In contrast, the TMB was positive correlation with numbers of mutated DDR genes. Exposure to aristolochic acid signature was observed only in the TMB-high groups. The Acornmed 808 panel is a clinically practical method to assess the TMB. The TMB was associated with the DDR gene status and CNV counts and might be a biomarker for further stratification of UC patients. The study suggested that patients with high TMB may have a unique carcinogenic mechanism.

N6-methylation of adenosine (m6A), a post-transcriptional regulatory mechanism, is the most abundant nucleotide modification in almost all types of RNAs. The biological function of m6A in regulating the expression of oncogenes or tumor suppressor genes has been widely investigated in various cancers. However, recent studies have addressed a new role of m6A modification in the anti-tumor immune response. By modulating the fate of targeted RNA, m6A affects tumor-associated immune cell activation and infiltration in the tumor microenvironment (TME). In addition, m6A-targeting is found to affect the efficacy of classical immunotherapy, which makes m6A a potential target for immunotherapy. Although m6A modification together with its regulators may play the exact opposite role in different tumor types, targeting m6A regulators has been shown to have wide implications in several cancers. In this review, we discussed the link between m6A modification and tumor with an emphasis on the importance of m6A in anti-tumor immune response and immunotherapy.

While androgens may function via nuclear androgen receptor (nAR) to increase bladder cancer (BCa) progression, the impact of androgens on muscle invasive BCa, which contains nearly 80% nAR-negative cells, remains unclear. To dissect the androgens potential impacts on these nAR-negative muscle invasive BCa, we first found that the androgens, dihydrotestosterone (DHT) might function via a novel membrane AR (mAR-SLC39A9) to increase nAR-negative BCa cell migration and invasion. Mechanism dissection revealed that DHT/mAR-SLC39A9 might function by altering Gαi protein-mediated MAPK/MMP9 intracellular signaling to increase nAR-negative BCa cell migration and invasion. Preclinical studies using multiple in vitro nAR-negative BCa cell lines and an in vivo mouse model all demonstrated that targeting this newly identified DHT/mAR-SLC39A9/Gαi/MAPK/MMP9 signaling with small molecules mAR-SLC39A9-shRNA or Gαi-shRNA, and not the classic antiandrogens including enzalutamide, bicalutamide, or hydroxyflutamide, could suppress nAR-negative BCa cell invasion. Results from human clinical samples surveys also indicated the positive correlation of this newly identified DHT/mAR signaling with BCa progression and prognosis. Together, these results suggest that androgens may not only function via the classic nAR to increase the nAR-positive BCa cell invasion, they may also function via this newly identified mAR-SLC39A9 to increase the nAR-negative/mAR-positive BCa cell invasion.

To compare the perioperative and functional outcomes of holmium laser enucleation of the prostate (HoLEP) and thulium laser enucleation of the prostate (ThuLEP) for the treatment of large-volume benign prostatic hyperplasia (BPH) (> 80 ml). A total of 116 consecutive patients with BPH were randomized to be treated surgically with either HoLEP (n = 58) or ThuLEP (n = 58), following the classical three-lobe enucleation technique. Follow-up was assessed at 1, 3, 6, 12 and 18 months after surgery. At 18 months, the lower urinary tract symptom index was improved significantly in both groups compared with the baseline values. The operative time (78.4 ± 8.0 vs. 71.4 ± 6.4 min) and enucleation time (61.2 ± 5.4 vs. 56.4 ± 8.4 min) were significantly shorter for ThuLEP compared to HoLEP (both p 0.05). The HoLEP and ThuLEP groups had equivalent International Prostate Symptom Scores (3 [3–3] vs. 3 [3–3], p = 0.776), quality of life (1 [1–2] vs. 2 [1–2], p = 0.809), Qmax (25.3 ± 4.8 ml/s vs. 24.7 ± 4.4 ml/s, p = 0.470), postvoid residual urine (PVR) (6.1 [2.6–20.8] vs. 7.7 [3.1–22.8] ml, p = 0.449) and PSA (0.84 ± 0.32 vs. 0.90 ± 0.34 ml, p = 0.309) at 18 months postoperatively. Both HoLEP and ThuLEP relieve lower urinary tract symptoms in a comparable way with high efficacy and safety. ThuLEP was statistically superior to HoLEP in operation time and enucleation time, although the differences were clinically negligible.

In this study, a combined process of alkaline pressure oxidative leaching (APOL) and Na2S leaching was proposed to extract arsenic and antimony from high arsenic smelter ash. The arsenic was selectively dissolved into the leachate during APOL, while the antimony was separated into the residue as insoluble NaSb(OH)6. The effects of different process parameters on the extraction of arsenic and antimony were investigated based on thermodynamic calculation. The results indicated that the extraction of arsenic was as high as 96% after APOL process under the conditions: 2 mol/L of NaOH concentration, 95 °C of leaching temperature, 90 min of leaching time, 1.5 MPa of oxygen partial pressure, 10:1 of liquid-to-solid ratio. The NaSb(OH)6 generated after APOL could be converted to Na3SbS4·10H2O and thus was leached out by Na2S leaching. The optimum conditions were established as: 2.75 mol/L of Na2S concentration, 95 °C of leaching temperature, 120 min of leaching time and 10:1 of liquid-to-solid ratio, under which the extraction of antimony was as high as 97.01%. A series of tests indicated that the leaching toxicity of the leaching residue met the Chinese identification standards.

Bladder cancer is one of the leading causes of cancer deaths worldwide. Early detection of lymph node metastasis of bladder cancer is essential to improve patients’ prognosis and overall survival. Current diagnostic methods are limited, so there is an urgent need for new specific biomarkers. Non-coding RNA and m6A have recently been reported to be abnormally expressed in bladder cancer related to lymph node metastasis. In this review, we tried to summarize the latest knowledge about biomarkers, which predict lymph node metastasis in bladder cancer and their mechanisms. In particular, we paid attention to the impact of non-coding RNA on lymphatic metastasis of bladder cancer and its specific molecular mechanisms, as well as some prediction models based on imaging, pathology, and biomolecules, in an effort to find more accurate diagnostic methods for future clinical application.

Background The clinical diagnostic method for bladder cancer is cystoscopy, an invasive, expensive and inconvenient clinical test. Using urinary cell-free DNA (cfDNA) to develop non-invasive test for bladder cancer was a promising liquid biopsy. Methods To improve the using rate of cfDNA template and decrease the PCR bias for liquid biopsy using urinary cfDNA, we developed a cell-free single-molecule unique primer extension resequencing (cf-SUPER) technology which was done for 29 matched urinary cfDNA and tumor DNA samples of bladder cancer patients to evaluate consistency of mutation profiles. Then, a 22 high mutational frequence genes was selected to form an uriprier panel, which was analyzed in 100 patients (47 bladder cancer cases and 53 controls) using cf-SUPER technology. This performance of the technology was evaluated using bioinformatic tools and clinical samples. Results The study showed that cf-SUPER technology can accurately detect mutations with allele fractions even low as 0.01% and the DNA input as low as 1 ng. The consistency of mutation profiles and clinical pathological diagnose between 29 matched urinary cfDNA and tumor DNA samples was respectively 82.76% and 89.66% by using cf-SUPER technology. Using cf-SUPER technology, the sensitivity and specificity were 98%, 94% respectively for uriprier panel in non-invasive test. Conclusions The preliminary work shows that cf-SUPER technology will be a promising method for liquid biopsy. Focusing urinary cfDNA, the non-invasive diagnose and monitoring of bladder cancer can come true by using cf-SUPER technology.

Background A high prevalence of osteoblastic bone metastases is characteristic of prostate cancer. Prostate‐specific antigen (PSA) is a serine protease uniquely produced by prostate cancer cells and is an important serological marker for prostate cancer. However, whether PSA modulates the osteogenic process remains largely unknown. In this study, we explored the effect of PSA on modulating the osteoblastic differentiation of mesenchymal stem cells (MSCs). In this study, we used flow cytometry, CCK‐8 assay, Alizarin red S (ARS) staining and quantification, alkaline phosphatase (ALP) activity and staining, Western blotting, and quantitative real‐time PCR (qRT‐PCR) to explore the effect of PSA on osteogenic differentiation of MSCs. Results We first demonstrated that although PSA did not affect the proliferation, morphology, or phenotype of MSCs, it significantly promoted the osteogenic differentiation of MSCs in a concentration‐dependent manner. Furthermore, we demonstrated that PSA promoted the osteogenic differentiation of MSCs by elevating the expression of Cadherin 11 in MSCs and, thus, activating the Akt signaling pathway. Conclusions In conclusion, we demonstrated that PSA could promote the osteogenesis of MSCs through Akt signaling pathway activation by elevating the expression of cadherin‐11 in MSCs. These findings imply a possible role of PSA in osteoblastic bone metastases in prostate cancer.

The androgen receptor (AR) has been linked to bladder cancer (BCa) progression, but if this involves circular RNAs (circRNAs) remains unclear. Here, we find that AR alters the levels of circRNA‐FNTA (circFNTA) to increase BCa cell invasion and chemo‐resistance. Mechanistically, AR represses the RNA editing gene ADAR2 via direct binding to its 5′ promoter region to increase circFNTA levels, which then sponges the microRNA miR‐370‐3p to increase the expression of its host gene FNTA. This AR‐mediated ADAR2/circFNTA/miR‐370‐3p/FNTA pathway then activates KRAS signaling to alter BCa cell invasion and chemo‐sensitivity to cisplatin. A clinical BCa sample survey shows that circFNTA expression is elevated in BCa tissues, and results from a BCa mouse model indicate that depletion of circFNTA leads to the suppression of BCa metastases and increased cisplatin chemo‐sensitivity. Together, based on our results using multiple BCa cell lines and an in vivo mouse model we suggest that targeting this newly identified AR/ADAR2/circFNTA/miR‐370‐3p/FNTA/KRAS axis may lead to the development of therapies to suppress BCa metastasis and to increase its chemo‐sensitivity.

Additional file 1: Table S1. Primers list. Table S2. Average of unique reads for each sample. Table S3. The diagnostic parameters for the diagnostic model with increasing numbers of genes used. Table S4. AUC values for each gene, in discriminating cancer from controls. Table S5. Basic information of 12 false-negative samples. Table S6. The results of a consistent comparison in different cancer stage. Table S7. The results of a consistent comparison in different gender. Table S8. The results of a consistent comparison in different age. Table S9. The results of a consistent comparison for 5-gene model (Supernatant) and 7 gene model (Sediment).

Although early studies suggested that bladder cancer (BCa) is more prevalent in men than in women, muscle-invasive rates are higher in women than in men, suggesting that sex hormones might play important roles in different stages of BCa progression. In this work, we found that estrogen receptor beta (ERβ) could increase BCa cell proliferation and invasion via alteration of miR-92a-mediated DAB2IP (DOC-2⁄DAB2 interacting protein) signals and that blocking miR-92a expression with an inhibitor could partially reverse ERβ-enhanced BCa cell growth and invasion. Further mechanism dissection found that ERβ could increase miR-92a expression at the transcriptional level via binding to the estrogen-response-element (ERE) on the 5′ promoter region of its host gene C13orf25. The ERβ up-regulated miR-92a could decrease DAB2IP tumor suppressor expression via binding to the miR-92a binding site located on the DAB2IP 3′ UTR. Preclinical studies using an in vivo mouse model also confirmed that targeting this newly identified ERβ/miR-92a/DAB2IP signal pathway with small molecules could suppress BCa progression. Together, these results might aid in the development of new therapies via targeting of this ERβ-mediated signal pathway to better suppress BCa progression., Bladder cancer: stopping the spread Blocking the effects of the female hormone estrogen may increase the survival rate of women with bladder cancer (BCa). Although BCa is more common in men, tumors are more likely to invade neighboring tissues in women. Sex hormones and their receptors, which are known to affect progression of other cancers, may play a key role. A team led by Shuyuan Yeh at the University of Rochester Medical Center, USA, and Wang Long at Central South University, Changsha, China, investigated the role that estrogen receptor beta (ERβ) plays in BCa. They found that reducing ERβ levels made BCa cells less invasive. Further investigation revealed a way to block ERβ signaling, which made BCa tumors less likely to invade neighboring tissue in a mouse model. Understanding the ERβ signaling pathway may help to develop better treatments for BCa.

Recent studies indicated that the estrogen receptor beta (ERβ) could affect the progression of prostate and bladder tumors, however, its roles in the renal cell carcinoma (RCC), remain to be elucidated. Here, we provide clinical evidence that ERβ expression is correlated in a negative manner with the overall survival/disease-free survival in RCC patients. Mechanism dissection revealed that targeting ERβ with ERβ-shRNA and stimulating the transactivation of ERβ with 17β-estradiol or environmental endocrine disrupting chemicals, all resulted in altering the lncRNA HOTAIR expression. The ERβ-modulated HOTAIR is able to function via antagonizing several microRNAs, including miR-138, miR-200c, miR-204, or miR-217 to impact various oncogenes, including ADAM9, CCND2, EZH2, VEGFA, VIM, ZEB1, and ZEB2, to promote RCC proliferation and invasion. Together, the identification of the ERβ-HOTAIR axis may provide us new biomarkers and/or therapeutic targets to better suppress RCC progression in the future.

// Zhenyu Ou 1 , Yao He 1 , Lin Qi 1 , Xiongbin Zu 1 , Longxiang Wu 1 , Zhenzhen Cao 2 , Yuan Li 1 , Longfei Liu 1 , Daud Athanasius Dube 3 , Zhi Wang 1 and Long Wang 1 1 Department of Urology, Xiangya Hospital, Central South University, Changsha, China 2 Department of Gynecologic Oncology, The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China 3 Department of Urology, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe Correspondence to: Long Wang, email: doctorwanglong@163.com Keywords: benign prostatic hyperplasia, mast cell, proliferation, chemokine Received: October 19, 2016 Accepted: June 06, 2017 Published: July 22, 2017 ABSTRACT Early evidences have showed that mast cells could infiltrate into benign prostatic hyperplasia (BPH) tissues, but the exact role of mast cells in BPH development remains unclear. In this study, we identified more mast cells existing in human BPH tissues compared with that in the normal prostate. In the in vitro co-culture system, BPH-1 prostate cells promoted activation and migration of mast cells, and mast cells conversely stimulated BPH-1 cells proliferation significantly. Molecular analysis demonstrated that mast cell-derived interleukin 6 (IL-6) could activate STAT3/Cyclin D1 signals in BPH-1 cells. Blocking IL-6 or STAT3 partially reverse the capacity of mast cells to enhance BPH-1 cell proliferation. Our findings suggest that infiltrating mast cells in BPH tissues could promote BPH development via IL-6/STAT3/Cyclin D1 signals. Therefore, targeting infiltrating mast cells may improve the therapeutic effect of BPH.

Epidemiological studies show obvious gender differences in the incidence and the prognosis of bladder cancer (BCa). Estrogen receptor alpha (ERα) was recently shown to play a protective role in BCa. However, the mechanisms by which ERα mediates BCa progression need to be further elucidated. In the present study, we explored the mechanisms by which ERα inhibits BCa invasion by modulating circRNA levels. ERα suppressed BCa invasion by decreasing circ_0023642 expression. Chromatin immunoprecipitation (ChIP) and luciferase assays revealed that ERα reduced circ_0023642 expression by regulating the expression of its host gene, UVRAG, at the transcriptional level. ERα decreased circ_0023642 levels and subsequently increased miR-490-5p expression, resulting in decreased EGFR expression to suppress BCa cell invasion. Circ_0023642 was demonstrated to directly bind to miR-490-5p. Notably, miR-490-5p regulated EGFR expression by binding to the miR-490-5p-binding site located in the 3′-untranslated region (UTR) of the EGFR mRNA. Preclinical studies using an in vivo mouse model also confirmed that this ERα/circ_0023642/miR-490-5p/EGFR signaling pathway suppressed BCa progression. Altogether, this newly identified pathway may serve as the basis for developing novel therapeutic strategies to treat BCa.

Transforming growth factor-β1 (TGFβ1)-induced differentiation into and the activation of myofibroblasts have been regarded as critical events in benign prostatic hyperplasia (BPH); however, the underlying mechanisms of BPH pathogenesis remain unclear. Microarray profiling, STRING analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and Gene Ontology (GO) enrichment analysis were performed to confirm the candidate genes and long non-coding RNA (lncRNAs) related to BPH. Collagen Type III (COL3A1) was significantly upregulated by TGFβ1 in prostate stromal cells (PrSCs) and might be involved in DNM3OS function in myofibroblasts upon TGFβ1 stimulation. Upon TGFβ1 stimulation, COL3A1 protein was decreased by DNM3OS silencing. miR-29a and miR-29b could directly bind to the DNM3OS and COL3A1 3' untranslated region (UTR)s to negatively regulate their expression, and by serving as a competing endogenous RNAs (ceRNA), DNM3OS competed with COL3A1 for miR-29a/29b binding, therefore counteracting miR-29a/29b-mediated COL3A1 suppression. The effect of DNM3OS silencing on ECM components and TGFβ1 downstream signaling was similar to that of the TGFβ1 inhibitor SB431542. miR-361 could target DNM3OS and TGFβ1; DNM3OS competed for miR-361 binding to counteract miR-361-mediated TGFβ1 suppression. In conclusion, we identified DNM3OS as a specifically-upregulated lncRNA upon TGFβ1 stimulation in PrSCs; by serving as a ceRNA for the miR-29a/29b cluster and miR-361, DNM3OS eliminated miRNA-mediated suppression of COL3A1 and TGFβ1, thereby promoting TGFβ1-induced PrSC transformation into myofibroblasts.

To compare the perioperative and functional outcomes of holmium laser enucleation of the prostate (HoLEP) and thulium laser enucleation of the prostate (ThuLEP) for the treatment of large-volume benign prostatic hyperplasia (BPH) ( 80 ml).A total of 116 consecutive patients with BPH were randomized to be treated surgically with either HoLEP (n = 58) or ThuLEP (n = 58), following the classical three-lobe enucleation technique. Follow-up was assessed at 1, 3, 6, 12 and 18 months after surgery.At 18 months, the lower urinary tract symptom index was improved significantly in both groups compared with the baseline values. The operative time (78.4 ± 8.0 vs. 71.4 ± 6.4 min) and enucleation time (61.2 ± 5.4 vs. 56.4 ± 8.4 min) were significantly shorter for ThuLEP compared to HoLEP (both p 0.001). There were no significant differences between the two groups regarding morcellation time, resected weight, hemoglobin decrease, catheter time and hospital stay (p 0.05). The HoLEP and ThuLEP groups had equivalent International Prostate Symptom Scores (3 [3-3] vs. 3 [3-3], p = 0.776), quality of life (1 [1-2] vs. 2 [1-2], p = 0.809), Qmax (25.3 ± 4.8 ml/s vs. 24.7 ± 4.4 ml/s, p = 0.470), postvoid residual urine (PVR) (6.1 [2.6-20.8] vs. 7.7 [3.1-22.8] ml, p = 0.449) and PSA (0.84 ± 0.32 vs. 0.90 ± 0.34 ml, p = 0.309) at 18 months postoperatively.Both HoLEP and ThuLEP relieve lower urinary tract symptoms in a comparable way with high efficacy and safety. ThuLEP was statistically superior to HoLEP in operation time and enucleation time, although the differences were clinically negligible.

To evaluate the benefit of neoadjuvant chemotherapy (NAC) for survival in high-grade upper tract urothelial carcinoma (UTUC), a propensity score-based analysis was performed with high-grade UTUC patients from multiple urologic centers. From three urologic centers, 48 high-grade UTUC patients who received chemotherapy followed by surgery (NAC group) and 72 high-grade UTUC patients who underwent initial surgery (no-NAC group) were involved in a propensity score-based analysis. After propensity score-based (1:1) matching, 37 patients receiving NAC and 37 patients not receiving NAC were followed. The patients who received NAC had improved disease-free survival (DFS) and overall survival (OS), with a 3-year DFS rate of 78.4% and an OS rate of 86.5% versus a 3-year DFS rate of 51.4% and an OS rate of 62.2% for those treated with initial surgery (P = 0.018 and P = 0.02, respectively). In the multivariate analysis, the NAC group had a lower risk for mortality [DFS hazard ratio (HR) 0.25; 95% confidence interval (CI) 0.10–0.62; P = 0.003; OS HR 0.22; 95% CI 0.085–0.57; P = 0.002]. The analysis of patient survival in matched subgroups showed that NAC was beneficial in terms of the 3-year DFS for the group with a cT of 3 or higher (DFS HR 0.37; 95% CI 0.14–0.94; P = 0.036) and the group that had tumor with hydronephrosis (DFS HR 0.31; 95% CI 0.11–0.87; P = 0.026). The study showed that NAC may be considered as an effective addition to surgery for the treatment in high-grade UTUC patients.

While androgens may function via nuclear androgen receptor (nAR) to increase bladder cancer (BCa) progression, the impact of androgens on muscle invasive BCa, which contains nearly 80% nAR-negative cells, remains unclear. To dissect the androgens potential impacts on these nAR-negative muscle invasive BCa, we first found that the androgens, dihydrotestosterone (DHT) might function via a novel membrane AR (mAR-SLC39A9) to increase nAR-negative BCa cell migration and invasion. Mechanism dissection revealed that DHT/mAR-SLC39A9 might function by altering G

Early studies demonstrated that male melanoma patients have worse survival than female patients, yet the detailed mechanisms for this gender difference remain unclear. We analyzed around 100 cases of human melanoma and found that androgen receptor (AR) positive melanoma patients have worse survival outcomes compared with AR-negative melanoma patients. Here we report that AR can have positive roles to increase melanoma cell invasion in multiple cell lines in vitro and a mouse model in vivo. Mechanism dissection suggest that AR increases melanoma cell invasion via modulating the MITF-AXL signals via altering the miRNA-539-3p/USP13 signaling to increase MITF protein degradation through a reduction of de-ubiquitination. Restoring MITF can reverse AR-enhanced melanoma cell invasion. Together, our results demonstrate that AR can promote melanoma metastasis via altering the miRNA-539-3p/USP13/MITF/AXL signal and targeting this newly identified signal with AR degradation enhancer ASC-J9 may help us to better suppress the melanoma metastasis.

In this study, a combined process of Na2S leaching and NaCl-H2SO4 leaching was developed to extract antimony and bismuth from tin anode slime after soda roasting–alkaline leaching. The optimal conditions for the extraction of antimony have been established as: Na2S concentration of 0.7 mol/L, temperature of 85 °C, liquid-to-solid ratio (L/S) of 14:1, and leaching time of 120 min. Under the conditions, more than 98% of antimony was extracted from tin anode slime, wherein the antimony was converted to liquid sodium thioantimonate, which was then converted into Na3SbS4(H2O)9 crystal via evaporation-crystallization; for this process, the recovery of antimony reached 93.83% at 50% evaporation rate, and the crystallization rate of antimony was 95%. The residue obtained was subjected to NaCl-H2SO4 leaching. About 94.94% of bismuth was extracted under the optimum conditions: H2SO4 concentration of 1 mol/L, NaCl/H2SO4 mole ratio of 2.5:1, L/S of 12:1, temperature of 80 °C, and leaching time of 120 min. The leach solution was then hydrolyzed and precipitated to form BiOCl, which showed a precipitation rate of 95.91% and Bi recovery of 91.12% at the hydrolysis pH of 2.4.

To compare the efficacy and safety of video endoscopic inguinal lymphadenectomy through a hypogastric subcutaneous approach (VEIL-H) with a leg subcutaneous approach (VEIL-L) in the surgical management of penile cancer.Between October 2012 and October 2016, 72 penile cancer patients who underwent VEIL-H (n = 37) or VEIL-L (n = 35) by one experienced surgeon in our hospital were retrospectively included. Data associated with demographic characteristics and perioperative outcomes were evaluated and compared between two groups.No intraoperative complications occurred and no deaths were recorded. No difference was noted with respect to demographic and clinicopathological data, operative time, estimated blood loss, spare of the great saphenous vein, dissected inguinal lymph nodes, patients with inguinal lymph node metastasis, positive inguinal lymph nodes, duration of drain, postoperative hospital days, and postoperative complications between two groups (p 0.05). Two patients of each group received a bilateral laparoscopic pelvic lymphadenectomy in one session. The pathological results of all dissected pelvic lymph nodes were negative. Median follow-up was 16.2 months, during which time three patients in VEIL-L group and two patients in VEIL-H group developed regional or distant metastases.Hypogastric approach is as effective and safe as VEIL-L for penile cancer. Moreover, VEIL-H can avoid the operation on both the limb and abdomen if laparoscopic pelvic lymphadenectomy is required.

While B cells in the tumor microenvironment may play important roles in cancer progression, their impacts on the bladder cancer (BCa) metastasis remain unclear. Here we found from human clinical BCa samples that BCa tissues could recruit more B cells than the surrounding normal bladder tissues and the in vitro co-culture assay also demonstrated that B cells could be recruited more easily towards BCa cells compared to normal bladder cells. Chamber invasion and 3D invasion assays showed the recruited B cells could then significantly increase the BCa cell invasion. Mechanism dissection found that recruited B cells could increase IL-8/androgen receptor (AR) signals in BCa cells that could then promote the expression of metastasis genes including MMP1 and MMP13. Blocking the IL-8/AR/MMPs signals either by anti-IL-8 neutralizing antibody, AR-siRNA, or MMPs inhibitors all partially reversed the infiltrating B cells capacity to increase the BCa cell invasion. The in vivo data from orthotopically xenografted BCa mouse model also confirmed that infiltrating B cells could increase BCa cell invasion via increasing AR signals. Together, these results demonstrate the key roles of B cells within the bladder tumor microenvironment that increase the BCa metastasis and may help us to develop the potential therapies via targeting these newly identified IL-8/AR/MMPs signals to better battle the BCa progression.

Clinical data indicates that T cells can be recruited to bladder cancer (BCa), yet the impact of T cells on BCa progression remains unclear. In the present study, we found that T cells were recruited more to BCa tissues than to the surrounding normal bladder tissues. Results from an in vitro co-culture system also found that BCa recruited more CD4+ T cells than did normal bladder cells. The recruiting of T cells to BCa tissues may increase the proliferation and invasion of BCa cells. Mechanistic studies revealed that infiltrating T cells stimulate BCa estrogen receptor beta (ERβ) signaling and consequently increase the expression of MET proto-oncogene, receptor tyrosine kinase (c-MET), through either direct binding to its promoter or via modulation of IL-1 expression. Interruption of ERβ/c-MET or ERβ/IL-1/c-MET signaling via ERβ-shRNA, IL-1 antagonist, or the c-MET inhibitor, SU11274, could partially reverse the T cell-enhanced BCa cell invasion and proliferation. Finally, the mouse BCa model with xenografted BCa 5637 cells with T (HH) cells confirmed the results of in vitro co-culture studies showing that infiltrating T cells could promote BCa metastasis via modulation of the ERβ/c-MET or ERβ/IL-1/c-MET signaling pathways. These findings may provide a new therapeutic approach to better combat BCa progression via targeting these newly identified signaling pathways.

Tin anode slime, a secondary resource containing Sn, was used as a raw material in the preparation of CaSnO3 via the processes of soda roasting, alkaline leaching, and precipitation. The effects of roasting, leaching, and precipitation on the extraction of tin from slime were investigated in detail. The following optimum conditions were identified: Na2CO3/tin anode slime mass ratio of 1:1, roasting temperature of 1000 °C, roasting time of 45 min, charcoal powder dosage of 20%, NaOH concentration of 2 mol/L, liquid-to-solid ratio of 14:1, leaching temperature of 65 °C, leaching time of 90 min, CaO/Sn mole ratio of 3.5:1, precipitation temperature of 85 °C, and precipitation time of 120 min. Under these conditions, more than 95% of Sn was extracted from tin anode slime after roasting and leaching, in which Sn was converted into Na2SnO3, which enhanced Sn extraction. Furthermore, more than 99% of Sn was precipitated from the leach solution via the reaction with CaO. The proposed method exhibits advantages of low pollution, low cost, and high leaching rate, when compared with the conventional preparation of CaSnO3 or treatment of tin anode slime.