Modulation of Potential-Limiting Steps in Lithium-Sulfur Batteries by Catalyst Synergy.

Electrocatalysis is considered to be an effective method to solve the sluggish kinetics of lithium-sulfur batteries. However, a single catalyst cannot simultaneously catalyze multi-step sulfur reductions. And once the catalyst surface is covered by the initially deposited solid products, the subsequent catalytic activity will significantly deteriorate. Here, microporous ZIF-67 and its derivative nano-metallic Co0 are used as dual-catalyst aiming to address these drawbacks. The dual catalytic center effectively cooperates the adsorption and electron transfer for multi-steps of sulfur reductions, transforming the potential-limited step (Li2S4→Li2S2/Li2S) into a thermodynamic spontaneous reaction. ZIF-67 first adsorbs soluble Li2S4 to form a coordination structure of ZIF-Li2S4. Then nano-metallic Co0 attracts uncoordinated S atoms in ZIF-Li2S4 and facilitates the breaking of S-S bonds to form transient reductive ZIF-Li2S2 and Co-S2 via. spontaneous electron transfer. These intermediates facilitate continuous conversion to Li2S with reduced formation energy, which is beneficial to the regeneration of the catalyst. As a result, the cathode with ZIF@CNTs/Co@CNFs synergetic catalyst achieves initial areal capacity of 4.7 mAh cm-2 and maintains 3.5 mAh cm-2 at low electrolyte/sulfur ratio (E/S) of 5 µL mg-1. This study provides valuable guidance for improving the electrochemical performance of lithium-sulfur batteries through catalyst synergistic strategies for multi-step reactions.

Role of glucocorticoid signaling in urothelial tumorigenesis: Inhibition by prednisone presumably through inducing glucocorticoid receptor transrepression.

Glucocorticoids, including dexamethasone (DEX) and prednisone (PRED), have been prescribed in patients with neoplastic disease as cytotoxic agents or comedications. Nonetheless, it remains uncertain whether they have an impact on the development of bladder cancer. We, therefore, assessed the functional role of the glucocorticoid-mediated glucocorticoid receptor (GR) signaling in urothelial tumorigenesis. Tumor formation was significantly delayed in xenograft-bearing mice with implantation of control bladder cancer UMUC3 cells or nonneoplastic urothelial SVHUC cells undergoing malignant transformation induced by a chemical carcinogen 3-methylcholanthrene (MCA), compared with respective GR knockdown xenografts. Using the in vitro system with MCA-SVHUC cells, we screened 11 GR ligands, including DEX, and found significant inhibitory effects of PRED on their neoplastic transformation. The effects of PRED were restored by a GR antagonist RU486 in GR-positive MCA-SVHUC cells, while PRED failed to inhibit the neoplastic transformation of GR knockdown cells. Significant decreases in the expression levels of oncogenes (c-Fos/c-Jun) and significant increases in those of a tumor suppressor UGT1A were seen in MCA-SVHUC-control cells (vs GR-short hairpin RNA) or PRED-treated MCA-SVHUC-control cells (vs mock). In addition, N-butyl-N-(4-hydroxybutyl) nitrosamine induced bladder cancer in all of eight mock-treated mice vs seven (87.5%) of DEX-treated (P = .302) or four (50%) of PRED-treated (P = .021) animals. Finally, DEX was found to considerably induce both transactivation (activation of glucocorticoid-response element mediated transcription and expression of its targets) and transrepression (suppression of nuclear factor-kappa B transactivation and expression of its regulated genes) of GR in SVHUC cells, while PRED more selectively induced GR transrepression. These findings suggest that PRED could prevent urothelial tumorigenesis presumably via inducing GR transrepression.

Genome Evolution Analysis of Recurrent Testicular Malignant Mesothelioma by Whole-Genome Sequencing.

BACKGROUND/AIMS: Malignant mesothelioma of the tunica vaginalis testis is a rare and lethal disease. The genomic characteristics and genetic changes of tumor cells during the progression of this disease are unknown. METHODS: we performed whole-genome sequencing of four successive tumor samples derived from surgery and a blood sample in a single patient. RESULTS: All tumors were found to have significant C-to-T and T-to-C mutations, and amplification of copy number in chromosomes 1 and 12 were notified in all tumor samples. Subclone analysis revealed a parallel evolution of the tumor in this patient. We also identified some mutations in mesothelioma-associated genes such as KIF25, AHNAK, and PRDM2. CONCLUSIONS: The results showed a comprehensive genomic change in malignant mesothelioma of the tunica vaginalis testis and provide a better understanding of the clonal evolution during tumor recurrence and metastasis.

Adjustable single-incision mini-slings (Ajust®) versus other slings in surgical management of female stress urinary incontinence: a meta-analysis of effectiveness and complications.

BACKGROUND: Adjustable single-incision mini-sling (SIMS) is a new category of SIMS for stress urinary incontinence (SUI). The aim of this study was to compare the efficacy and safety of adjustable single-incision mini-sling with other slings. METHODS: Literature search in databases such as Pubmed, and Conchrane Library was performed up to December, 2015. The outcomes including cure rate, operation time, postoperative pain score and complications were reanalyzed. The pooled relative risk (RR) and mean difference (MD) with their 95% confidence interval (95% CI) were calculated by RevMan v5.0. RESULTS: Eight studies with 1093 SUI female patients were included. There was no significant difference between adjustable SIMS and other slings (transobturator slings and MiniArc) in patients subjective cure rate and objective cure rate. In addition, adjustable SIMS was associated with a significantly shorter operative time and lower postoperative pain score when comparing adjustable SIMS with transobturator tape (MD = - 1.35; 95%CI: -2.24 to - 0.46, P = 0.003). For the complications, there was also no significant difference between adjustable SIMS and transobturator slings. CONCLUSIONS: Adjustable SIMS had equally efficacy for SUI compared with transobturator slings and MiniArc. However, the significantly shorter operative time and lower postoperative pain score than transobturator tape supported the clinical application of adjustable SIMS.

A novel Y chromosome microdeletion potentially associated with defective spermatogenesis identified by custom array comparative genome hybridization.

Male infertility is a major health problem worldwide. Oligospermia and azoospermia are the most common symptoms of this disorder. Despite recent advances, the aetiopathogenesis of defective spermatogenesis remains largely uncertain. The aim of this study is to discover unknown or novel chromosome aberrations associated with male reproductive failure. We developed a high-resolution custom array comparative genomic hybridization for initial screening of copy number variations in 10 patients with idiopathic oligozoospermia and azoospermia and eight normal fertile men. We found that deletions were mainly located in the deleted-in-azoospermia subregion and were confined to patients. More importantly, an interesting microdeletion of the Y chromosome designated as D01 was detected in four out of 10 patients with oligozoospermia and azoospermia. We validated this recurrent deletion in nine out of 100 additional infertile men using polymerase chain reaction assays, whereas, it was not present in 100 proven fertile controls(P = 0.002). Furthermore, a bioinformatics analysis demonstrated that the 5' terminal of D01 is situated proximal to several conserved transcription factor binding sites within the Y chromosome. Our study indicated that this newly identified Y chromosome deletion might be potentially associated with impaired spermatogenesis and it is worthy of further investigations in larger cohorts.

Silodosin inhibits prostate cancer cell growth via ELK1 inactivation and enhances the cytotoxic activity of gemcitabine.

BACKGROUND: Biological significance of ELK1, a transcriptional factor whose phosphorylation is necessary for c-fos proto-oncogene activation, in prostate cancer remains far from fully understood. In this study, we aim to investigate the role of ELK1 in tumor growth as well as the efficacy of a selective α1A-adrenergic blocker, silodosin, in ELK1 activity in prostate cancer cells. METHODS: We first immunohistochemically determined the levels of phospho-ELK1 (p-ELK1) expression in radical prostatectomy specimens. We then assessed the effects of ELK1 knockdown via short hairpin RNA and silodosin on cell proliferation, migration, and invasion in prostate cancer lines. RESULTS: The levels of p-ELK1 expression were significantly higher in carcinoma than in benign (P < 0.001) or high-grade prostatic intraepithelial neoplasia (HGPIN) (P = 0.002) as well as in HGPIN than in benign (P < 0.001). Kaplan-Meier and log-rank tests revealed that moderate-strong positivity of p-ELK1 in carcinomas tended to correlate with biochemical recurrence after radical prostatectomy (P = 0.098). In PC3 and DU145 expressing ELK1 (mRNA/protein) but no androgen receptor (AR), ELK1 silencing resulted in considerable decreases in the expression of c-fos as well as in cell migration/invasion and matrix metalloproteinase-2 expression, but not in cell viability. Silodosin treatment reduced the expression/activity of ELK1 in these cells as well as the viability of AR-positive LNCaP and C4-2 cells and the migration of both AR-positive and AR-negative cells, but not the viability of AR-negative or ELK1-negative cells. Interestingly, silodosin significantly increased sensitivity to gemcitabine, but not to cisplatin or docetaxel, even in AR-negative cells. CONCLUSIONS: ELK1 is likely to be activated in prostate cancer cells and promote tumor progression. Furthermore, silodosin that inactivates ELK1 in prostate cancer cells not only inhibits their growth but also enhances the cytotoxic activity of gemcitabine. Thus, ELK1 inhibition has the potential of being a therapeutic approach for prostate cancer.

Cyclosporine A and tacrolimus inhibit urothelial tumorigenesis.

The functional role of nuclear factor of activated T-cells (NFAT), while it has been extensively investigated in the immune system, remains uncertain in bladder cancer development. We here aim to assess the effects of cyclosporine A (CsA) and tacrolimus (FK506), immunosuppressants known to specifically inactivate the NFAT pathway in immune cells, on neoplastic transformation of urothelial cells. Immunohistochemistry revealed that the expression levels of NFATc1, a NFAT isoform shown to function as an oncogene in a sarcoma model, were elevated in urothelial neoplasms, compared with non-neoplastic urothelial tissues, and in low-grade and high-grade papillary urothelial carcinomas, compared with papillary urothelial neoplasms of low malignant potential. In an immortalized normal urothelial cell line SVHUC, CsA and FK506 reduced NFATc1 expression, NFAT transcriptional activity, and the expression of c-myc, a downstream target of NFATc1 signals. Treatment with CsA or FK506 in the SVHUC cells undergoing neoplastic transformation induced by exposure to a chemical carcinogen 3-methylcholanthrene resulted in strong inhibition in colony formation in vitro as well as tumor formation in NOD-SCID mice. CsA and FK506 were additionally found to up-regulate the expression of several molecules that play a protective role in bladder tumorigenesis, including p53, p21, and p27, and down-regulate that of oncogenic genes, such as cyclin D1, cyclin D3, and cyclin E, in SVHUC cells with the carcinogen challenge. Thus, CsA and FK506 likely inhibit urothelial tumorigenesis. These findings offer a potential chemopreventive approach for urothelial tumors using NFAT inhibitors.

[Establishment of a screening method for AZF microdeletions by capillary technology and a clinical trial].

OBJECTIVE: To establish an accurate, fast and simple screening method for AZF microdeletions using capillary technology and use it for clinical testing. METHODS: For each pair of primers, the 5' end of either forward or reverse primer was labeled with a FAM, JOE or TAMRA fluorescence dyes to establish multiplex quantitative fluorescence PCR systems for the establishment of a screening method of Y chromosome AZF microdeletions by capillary technology. The detection of Y chromosome AZF microdeletion was carried out on 725 cases of non-obstructive azoospermia, oligospermia or asthenospermia. RESULTS: A screening method for Y chromosome AZF microdeletions using capillary technology was established. Thirty eight cases of AZF microdeletions were found among 725 cases of non-obstructive azoospermia, oligospermia or asthenospermia, which gave a deletion rate of 5.24%. Y chromosomal microdeletions were found in 8.62% of the azoospermia group, 6.75% of the oligozoospermic group, and 2.23% of the asthenospermia group. CONCLUSION: An accurate, fast and simple screening method of Y chromosome AZF microdeletions by capillary technology has been established, which may have an important clinical value.

[Research progress on the effect of glucocorticoid receptor signaling pathways in bladder cancer].

Glucocorticoid receptor (GR) is identified as a member of nuclear receptor family. To exert its biological action, the ligand bound GR is translocated from the cytoplasm into the nucleus by regulating transcriptional signals of related genes. In clinical practice, the effects of glucocorticoid are often mediated by GR signaling pathways. An increasing number of studies have indicated that GR signaling pathways play an essential role in the proliferation, invasion and prognosis of bladder cancer. Meanwhile, the new-generation selective GR activator improves its anti-tumor effects, and at the same time reduces the adverse reactions of hormones, which probably raises the prospect for the treatment of bladder cancer.

[Influence of semen preservation and processing methods on sperm DNA integrity].

OBJECTIVE: To investigate the influence of different methods of semen preservation and processing on sperm DNA integrity. METHODS: We collected semen samples from 100 normozoospermic male volunteers and, following homogeneous mixing, preserved them by means of snap freezing, slow freezing, or at the room temperature for 4 and 24 hours. Meanwhile we processed the semen by washing, swim-up, and density gradient centrifugation (DGC). Then we obtained the sperm DNA fragmentation index (DFI) by sperm chromatin dispersion test and measured total sperm motility and DFI after cultured for 24 hours following processing. RESULTS: The sperm DFIs after 4 hours of preservation by snap freezing, slow freezing, and at the room temperature were (27.3 ± 6.4)%, (26.9 ± 6.1)%, and (24.7 ± 6.8)%, respectively, and that after preserved at the room temperature for 24 hours was (35.6 ± 9.0)%, with statistically significant differences between the first three and the 24-hour room temperature preservation groups (P < 0.05) but not among the former three groups (P > 0.05). The sperm DFI was significantly higher in the samples processed by washing ([13.7 ± 2.0]%) than in those processed by swim-up ([9.1 ± 1.3]%) and DGC ([8.0 ± 2.5]%) (P < 0.05), and it was the lowest in the DGC group after 24-hour culture ([11.5 ± 4.2]%) as compared with the other groups (P < 0.05). CONCLUSION: Sperm DNA integrity is influenced by different semen preservation conditions and processing methods.

The role of NFATc1 in prostate cancer progression: cyclosporine A and tacrolimus inhibit cell proliferation, migration, and invasion.

BACKGROUND: The functional role of nuclear factor of activated T-cells (NFAT), a well-characterized regulator of the immune response, in prostate cancer progression remains largely unknown. We aim to investigate biological significance of NFATc1, a NFAT isoform shown to function as an oncogene in a sarcoma model, in human prostate cancer. METHODS: We first determined the expression levels of NFAT in prostate cell lines and tissue specimens. We then assessed the effects of NFAT inhibition via NFATc1-small interfering RNA (siRNA) as well as immunosuppressants including cyclosporine A (CsA) and tacrolimus (FK506) on prostate cancer cell proliferation, apoptosis, migration, and invasion in vitro and in vivo. RESULTS: Immunohistochemistry revealed that the expression levels of NFATc1 were significantly elevated in prostatic carcinomas, compared with non-neoplastic prostate or high-grade prostatic intraepithelial neoplasia tissues, and in high-grade (Gleason scores ≥7) tumors. NFATc1 positivity in carcinomas, as an independent prognosticator, also correlated with the risk of biochemical recurrence after radical prostatectomy. In prostate cancer cell lines, CsA and FK506 inhibited NFATc1 expression and its nuclear translocation, NFAT transcriptional activity, and the expression of c-myc, a downstream target of NFAT. NFAT silencing or treatment with these NFAT inhibitors resulted in decreases in cell viability/colony formation and cell migration/invasion, as well as increases in apoptosis, in androgen receptor (AR)-negative, AR-positive/androgen-sensitive, and AR-positive/castration-resistant lines. No significant additional inhibition in the growth of NFAT-siRNA cells by CsA and FK506 was seen, whereas these agents, especially FK506, further inhibited their invasion. In xenograft-bearing mice, CsA and FK506 significantly retarded tumor growth. CONCLUSIONS: Our results suggest that NFATc1 plays an important role in prostate cancer outgrowth. Thus, NFATc1 inactivation, especially using CsA and FK506, has the potential of being a therapeutic approach for not only hormone-naïve but also castration-resistant prostate cancers.

Expression of UDP-glucuronosyltransferase 1A in bladder cancer: association with prognosis and regulation by estrogen.

Although UDP-glucuronosyltransferase 1A (UGT1A) plays an important role in preventing bladder cancer initiation by detoxifying carcinogenic compounds, its contribution to bladder cancer progression is poorly understood. We immunohistochemically stained for UGT1A in bladder specimens. UGT1A was positive in 130/145 (90%; 28 [19%] weak, 53 [37%] moderate, and 49 [34%] strong) urothelial neoplasms, which was significantly weaker than in matched non-neoplastic urothelial tissues (100/101 [99%]; 2 [2%] weak, 17 [17%] moderate, and 81 [80%] strong). Fifty (98%) of 51 low-grade/79 (99%) of 80 non-muscle-invasive tumors were immunoreactive to UGT1A, whereas 80 (85%) of 94 high-grade/51 (78%) of 65 muscle-invasive tumors were UGT1A-positive. Kaplan-Meier analysis showed strong associations between lower UGT1A expression versus the risk of recurrence in high-grade non-muscle-invasive tumors (P = 0.038) or disease-specific mortality in muscle-invasive tumors (P = 0.016). Multivariate analysis further revealed UGT1A loss as an independent prognosticator for disease-specific mortality in patients with muscle-invasive tumor (P = 0.010). Additionally, the expression of UGT1A was positively and negatively correlated with those of estrogen receptor-α and estrogen receptor-ß, respectively. We then assessed UGT1A/Ugt1a levels in human cell lines/mouse tissues. 17ß-Estradiol increased and decreased UGT1A expression in normal urothelium and bladder cancer lines, respectively, and an anti-estrogen abolished these effects. Ovariectomy in mice resulted in down-regulation of Ugt1a subtypes. These results suggest the involvement of UGT1A in not only bladder carcinogenesis but tumor progression. Moreover, UGT1A is likely regulated by estrogens in non-neoplastic urothelium versus bladder tumor in opposite manners, which could be underlying mechanisms of gender-specific differences in bladder cancer incidence and progression.

Function of NEK2 in clear cell renal cell carcinoma and its effect on the tumor microenvironment.

BACKGROUND: Previous studies have revealed the critical functions of NEK2 in controlling the cell cycle which is linked to poor prognosis in multiple tumor types, but less research has been devoted to clear cell renal cell carcinoma (ccRCC). METHODS: We downloaded clinical data from the gene expression omnibus (GEO) and TCGA databases together with transcriptional and mutational datasets. Strongly coexpressed genes with NEK2 were extracted from TCGA-KIRC cohort, and were submitted to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional analyses. According to NEK2 levels, the survival status, mutational characteristics, response to immunotherapy and sensitivity to drugs of the patients were studied. The potential correlations between NEK2 levels and immune cell state as well as immune cell infiltration were examined using the GEPIA, TIMER and TISIDB databases. Double immunofluorescence (IF) was performed to identify the NEK2 overexpression and relationship with CD8 in ccRCC. RESULTS: The NEK2 gene was overexpressed and would enhance the nuclear division and cell cycle activities in ccRCC. ccRCC patients with high NEK2 expression had worse clinical outcomes, higher mutation burden and better therapeutic response. Moreover, NEK2 gene overexpression was positively related to various immune cell marker sets, which was also proved by validation cohort, and more infiltration of various immune cells. CONCLUSION: ccRCC patients with NEK2 high expression have a poorer prognosis than those with NEK2 low expression, resulting from its function of promoting proliferation, accompanied by increased infiltration of CD8 + T cells and Tregs and T-cell exhaustion and will respond better to proper treatments.

Androgen receptor signals regulate UDP-glucuronosyltransferases in the urinary bladder: a potential mechanism of androgen-induced bladder carcinogenesis.

UDP-glucuronosyltransferases (UGTs), major phase II drug metabolism enzymes, play an important role in urinary bladder cancer initiation by detoxifying carcinogens. We aimed to determine if androgens regulate UGT expression via the androgen receptor (AR) pathway in the bladder. Real-time reverse transcription-polymerase chain reaction and Western blot analyses were used to assess UGT1A levels in the normal urothelium SVHUC cell line stably expressed with AR and in bladder tissues from AR knockout (ARKO) and castrated male mice. Immunohistochemistry was also performed in radical cystectomy specimens. Dihydrotestosterone (DHT) treatment in SVHUC-AR reduced mRNA expression of all the UGT1A subtypes (19-75% decrease), and hydroxyflutamide antagonized the DHT effects. In contrast, DHT showed only marginal effects on UGT1A expression in SVHUC-Vector. Of note were higher expression levels of UGT1As in SVHUC-Vector than in SVHUC-AR. In ARKO mice, all the Ugt1a subtypes were up-regulated, compared to wild-type littermates. In wild-type male mice, castration increased the expression of Ugt1a8, Ugt1a9, and Ugt1a10. Additionally, wild-type female mice had higher levels of Ugt1a than wild-type males. Immunohistochemical studies showed strong (3+) UGT1A staining in 11/24 (46%) cancer tissues, which was significantly lower than in corresponding benign tissues [17/18 (94%) cases (P = 0.0009)]. These results suggest that androgen-mediated AR signals promote bladder carcinogenesis by down-regulating the expression of UGTs in the bladder.

A Case of Primary Lymphoepithelioma-Like Carcinoma of the Bladder With Review.

Lymphoepithelioma-like carcinoma (LELC) was characterized by epithelial neoplastic cells developing in solid or incohesive sheets mixed with a noticeable lymphoid infiltration. Lymphoepithelioma-like carcinoma of the bladder (LELCB), which was first described by Zukerberg, is a rare variant of LELC. Here we reported a new case of LELCB occurring in a 70-year-old woman presenting with hematuria. Computed tomography (CT) and cystoscopy revealed a tumor on the left upper wall of the bladder. A partial cystectomy was finally performed. Pathological and immunohistochemical analysis revealed LELCB. After receiving systemic adjuvant chemotherapy, the patient conducted a 25-month follow-up without experiencing a recurrence.

Giant Adrenal Cyst: A Case Report.

Giant adrenal cysts are rare lesions, most often discovered incidentally. In this case report, a patient presenting with nonspecific abdominal distension is described. Imaging studies revealed a vast cystic mass closely attached to the left adrenal gland. Neither routine laboratory tests nor endocrine function tests revealed abnormalities. By performing open surgery, the cystic mass was completely removed. According to the pathological results, the wall of the cystic mass has an endothelial structure and some vascular components. Comprehensive analysis indicated that this case was an angiomatous adrenal endothelial cyst which was an extremely uncommon form of an adrenal cyst. Over a one-year follow-up, no evidence of recurrence was observed in the patient postoperatively. Through this case, we wish to raise awareness of this disease.

DeepTAP: An RNN-based method of TAP-binding peptide prediction in the selection of tumor neoantigens.

The transport of peptides from the cytoplasm to the endoplasmic reticulum (ER) by transporters associated with antigen processing (TAP) is a critical step in the intracellular presentation of cytotoxic T lymphocyte (CTL) epitopes. The development and application of computational methods, especially deep learning methods and new neural network strategies that can automatically learn feature representations with limited knowledge, provide an opportunity to develop fast and efficient methods to identify TAP-binding peptides. Herein, this study presents a comprehensive analysis of TAP-binding peptide sequences to derive TAP-binding motifs and preferences for N-terminal and C-terminal amino acids. A novel recurrent neural network (RNN)-based method called DeepTAP, using bidirectional gated recurrent unit (BiGRU), was developed for the accurate prediction of TAP-binding peptides. Our results demonstrated that DeepTAP achieves an optimal balance between prediction precision and false positives, outperforming other baseline models. Furthermore, DeepTAP significantly improves the prediction accuracy of high-confidence neoantigens, especially the top-ranked ones, making it a valuable tool for researchers studying antigen presentation processes and T-cell epitope screening. DeepTAP is freely available at https://github.com/zjupgx/deeptap and https://pgx.zju.edu.cn/deeptap.

Biocompatible Gallium Nanodots against Drug-Resistant Bacterial Pneumonia and Liver Abscess.

Resistant bacterial infection remains a severe public health threat, and conventional antibiotic drugs work poorly in effectively treating infectious diseases. Here, we developed gallium-based nanodots (Ga NDs), consisting of specific disruption of bacterial iron ability, to treat multidrug-resistant (MDR) Gram-negative bacteria-infected diseases. The Ga NDs significantly suppress the proliferation of two typical MDR bacteria strains (P. aeruginosa and ESBL E. coli) compared with clinically used antibacterial drugs, including penicillin and levofloxacin. Ga NDs could also disrupt the biofilms of these two bacterial strains. In P. aeruginosa infected pneumonia and ESBL E. coli infected acute liver abscess models, the Ga NDs enable substantial inhibition of bacterial growth and reduce the organs' inflammation that resulted in significant improvement of survival. Further, the Ga NDs demonstrated excellent biocompatibility and biosafety characteristics. Together, we believe that our gallium containing nanotherapeutics are expected to be developed into promising alternative therapies to combat drug-resistant bacterial infection.

Expression of androgen and oestrogen receptors and its prognostic significance in urothelial neoplasm of the urinary bladder.

UNLABELLED: What's known on the subject? and What does the study add? Steroid hormone receptor signals have been implicated in bladder tumourigenesis and tumour progression. The expression of androgen and/or oestrogen receptors has been assessed in bladder cancer, leading to conflicting data of expression levels and their relationship to histopathological characteristics of the tumours. We simultaneously analyze three receptors in non-neoplastic bladder tissues as well as in primary and metastatic bladder tumour specimens. Our data demonstrate that the expression status correlates with tumour grades/stages and patients' outcomes. OBJECTIVE: To assess the expression of the androgen receptor (AR) and oestrogen receptors (ERs) in bladder tumours because recent studies have shown conflicting results and the prognostic significance of their expression remains unclear. PATIENTS AND METHODS: We investigated the expression of AR, ERα and ERß in 188 bladder tumour specimens, as well as matched 141 non-neoplastic bladder and 14 lymph node metastasis tissues, by immunohistochemistry. We then evaluated the relationships between their expression and the clinicopathological features available for the present patient cohort. RESULTS: AR/ERα/ERß was positive in 80%/50%/89% of benign urothelium, 50%/67%/41% of benign stroma, 42%/27%/49% of primary tumours and 71%/64%/71% of metastatic tumours. Significantly lower expression of AR/ERα was found in high-grade tumours (36%/23%) and tumours invading muscularis propria (33%/19%) compared to low-grade tumours (55%; P= 0.0232/38%; P= 0.0483) and tumours not invading muscularis propria (51%; P= 0.0181/35%; P= 0.0139), respectively. Significantly higher expression of ERß was found in high-grade tumours (58%) and tumours invading muscularis propria (67%) compared to low-grade tumours (29%; P= 0.0002) and tumours not invading muscularis propria (34%; P < 0.0001), respectively. Kaplan-Meier and log-rank tests further showed that positivity of ERß (but not AR or ERα) was associated with the recurrence of low-grade tumours (P= 0.0072); the progression of low-grade tumours (P= 0.0005), high-grade tumours not invading muscularis propria (P= 0.0020) and tumours invading muscularis propria (P= 0.0010); or disease-specific mortality in patients with tumours invading muscularis propria (P= 0.0073). CONCLUSIONS: Compared to benign bladders, a significant decrease in the expression of AR, ERα or ERß in bladder cancer was seen. Loss of AR or ERα was strongly associated with higher grade/more invasive tumours, whereas ERß expression was increased in high-grade/invasive tumours and predicted a worse prognosis.

Expression of semenogelins I and II and its prognostic significance in human prostate cancer.

BACKGROUND: Little is known about the role of semenogelins, seminal plasma proteins that play critical roles in semen clotting and subsequent liquefaction in the presence of zinc and prostate-specific antigen, in human malignancies. METHODS: We investigated the expression of semenogelins in four human prostate cancer lines by RT-PCR and Western blotting as well as in 70 radical prostatectomy specimens by immunohistochemistry. Effects of semenogelin overexpression on prostate cancer cell proliferation were also assessed. RESULTS: mRNA/protein signals for semenogelins I (SgI) and II (SgII) were detected only in androgen-sensitive LNCaP cells cultured with zinc. Transfection of SgI/SgII increased/decreased cell growth of androgen receptor (AR)-positive/semenogelin-negative CWR22Rv1 in the presence of zinc, whereas it showed marginal effects in AR-negative/semenogelin-negative PC-3 and DU145. Immunohistochemical studies showed that SgI and SgII stain positively in 55 (79%) and 31 (44%) cancer tissues, respectively, which was significantly higher than in corresponding benign tissues [SgI-positive in 13 (19%) cases (P < 0.0001) and SgII-positive in 15 (21%) cases (P = 0.0066)]. Among the histopathological parameters available for our patient cohort, there was an inverse association only between Gleason score (GS) and SgII expression (GS ≤ 7 vs. GS ≥ 8: P = 0.0150; GS7 vs. GS ≥ 8: P = 0.0111). Kaplan-Meier and log-rank tests further revealed that patients with SgI-positive/SgII-negative tumor have the highest risk for biochemical recurrence (P = 0.0242). CONCLUSIONS: These results suggest the involvement of semenogelins in prostate cancer and their prognostic values in predicting cancer progression after radical prostatectomy. Additional functional analyses of semenogelins are necessary to determine their biological significance in prostate cancer.