High expression of GMNN predicts malignant progression and poor prognosis in ACC.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine neoplasm, which is characterized by poor prognosis and high recurrence rate. Novel and reliable prognostic and metastatic biomarkers are lacking for ACC patients. This study aims at screening potential prognostic biomarkers and therapeutic targets of ACC through bioinformatic methods and immunohistochemical (IHC) analysis. METHODS: In the present study, by using the Gene Expression Omnibus (GEO) database we identified differentially expressed genes (DEGs) in ACC and validated these DEGs in The Cancer Genome Atlas (TCGA) ACC cohort. A DEGs-based signature was additionally constructed and we assessed its prognosis and prescient worth for ACC by survival analysis and nomogram. Immunohistochemistry (IHC) was used to verify the relationship between hub gene-GMNN expressions and clinicopathologic outcomes in ACC patients. RESULTS: A total of 24 DEGs correlated with the prognosis of ACC were screened from the TCGA and GEO databases. Five DEGs were subsequently selected in a signature which was closely related to the survival rates of ACC patients and GMNN was identified as the core gene in this signature. Univariate and multivariate Cox regression showed that the GMNN was an independent prognostic factor for ACC patients (P < 0.05). Meanwhile, GMNN was closely related to the OS and PFI of ACC patients treated with mitotane (P < 0.001). IHC confirmed that GMNN protein was overexpressed in ACC tissues compared with normal adrenal tissues and significantly correlated with stage (P = 0.011), metastasis (P = 0.028) and Ki-67 index (P = 0.014). CONCLUSIONS: GMNN is a novel tumor marker for predicting the malignant progression, metastasis and prognosis of ACC, and may be a potential therapeutic target for ACC.

The CYP19A1 (TTTA)n Repeat Polymorphism May Affect the Prostate Cancer Risk: Evidence from a Meta-Analysis.

Abnormal aromatase (CYP19A1) expression may participate in prostate cancer (PCa) carcinogenesis. However, the results of studies on the CYP19A1 gene polymorphisms and PCa are conflicting. This meta-analysis aimed to systematically evaluate the associations between the CYP19A1 Arg264Cys polymorphism and the (TTTA)n repeat polymorphism and PCa. Electronic databases (PubMed, EmBase, ScienceDirect, and Cochrane Library) were comprehensively searched to identify eligible studies. The strength of the association between the Arg264Cys polymorphism and PCa was assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) in allelic, dominant, recessive, homozygous, and heterozygous genetic models. To analyze the impact of the (TTTA)n repeat polymorphism, we sequentially took the N-repeat allele (where N equals 7,8,10,11,12, and 13) as the minor allele and the sum of all the other alleles as the major allele. The ORs and 95% CIs were calculated in the allelic model; this analysis was performed individually for each repeat number. Pooled estimates of nine studies addressing the Arg264Cys polymorphism indicated that this polymorphism was not associated with PCa risk in the overall population or in the Caucasian or Asian subgroups. The 8-repeat allele in the (TTTA)n repeat polymorphism increased PCa risk in the overall population (OR = 1.34, 95% CI = 1.14-1.58, p = .001) and in the subgroup with population-based (PB) controls (OR = 1.41, 95% CI = 1.13-1.74, p = .002) as well as in the subgroup using capillary electrophoresis to identify this polymorphism (OR = 1.34, 95% CI = 1.09-1.65, p = .006).The meta-analysis indicated that the CYP19A1 (TTTA)n repeat polymorphism, but not the Arg264Cys polymorphism, may affect PCa risk.

Circular RNA circFNDC3B protects renal carcinoma by miR-99a downregulation.

Various circular RNAs (circRNAs) have been reported to involve in carcinoma. This study explored the role and mechanism of circRNA circFNDC3B (circFNDC3B) in renal carcinoma (RC). The detection indicators in this paper were viability, colony, and migration, which respectively investigated by Cell Counting Kit-8, colony formation, and migration assay. Reverse transcriptase quantitative polymerase chain reaction tested and cell transfection changed circFNDC3B and miR-99a expression. Moreover, western blot tested relate-proteins of proliferation, migration, and cell pathways were examined by western blot. circFNDC3B was upregulated at RC tissues. circFNDC3B enhanced cell viability, colony and migration, and miR-99a mimic played reverse impacts. Furthermore, circFNDC3B negatively regulated miR-99aand circFNDC3B restrained the janus kinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) and extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathways by miR-99a downregulation. Overexpression of circFNDC3B enhanced cell viability, colony formation and migration by miR-99a downregulation via JAK1/STAT3 and MEK/ERK pathways.

The circular RNA hsa-circ-0072309 plays anti-tumour roles by sponging miR-100 through the deactivation of PI3K/AKT and mTOR pathways in the renal carcinoma cell lines.

Aims: To explore the roles and regulatory mechanisms of the circular RNA (circRNA)-hsa-circ-0072309 in CAKI-1 and ACHN cells. Methods: CAKI-1 and ACHN cells were transfected with hsa-circ-0072309 overproduction vector (circRNA) and microRNA-100 (miR-100) mimic or the corresponding controls. Cell viability was detected with the CCK-8. The protein expression levels of p53, c-Myc, cleaved-caspase-3/9, matrix metalloproteinase (MMP)-2/9, vimentin, AKT, PI3K and mTOR were individually determined through western blot. qRT-PCR was used to examine the expressions of hsa-circ-0072309 and miR-100. The apoptotic rate and the migration or invasion rates were separately determined by the annexin v-FITC/PI with a flow cytometer and modified two-chamber migration assay or millicell hanging cell culture. Results: The hsa-circ-0072309 was poorly expressed in tumor tissue. Abundant hsa-circ-0072309 induced the inhibitions of cell proliferation, migration and invasion, as well as the PI3K/AKT and the mTOR cascades but enhancement of apoptosis. circRNA stimulated the down-regulation of miR-100, which was low-expressed in tumour tissue and whose overproduction abolished the impacts of circRNA on these elements mentioned above. Conclusion: The hsa-circ-0072309 played anti-tumour roles by targeting miR-100 by blocking the PI3K/AKT and mTOR cascades in the CAKI-1 and ACHN cell lines.

[Anatomic characteristics of the vessels in the spermatic cord of the varicocele patient: A laparoscopic study].

OBJECTIVE: To study the numbers and locations of spermatic veins, testicular arteries, and lymphatic vessels in the spermatic cord of the varicocele patient under the laparoscope. METHODS: Fifty-seven varicocele patients received laparoscopic ligation of spermatic veins, during which we recorded the numbers and observed the locations of spermatic veins, testicular arteries, and spermatic lymphatic vessels. RESULTS: During the surgery, we identified 3.3 ± 1.2 spermatic veins, 1.4 ± 0.9 testicular arteries, and 4.3 ± 1.1 spermatic lymphatic vessels. No statistically significant differences were observed between the two side in the numbers of the spermatic veins, testicular arteries and spermatic lymphatic vessels (P > 0.05). The testicular arteries were seen on the exterior of the spermatic veins and winding around them, while the spermatic lymphatic vessels mostly between the veins. CONCLUSION: The spermatic veins, testicular arteries, and lymphatic vessels in the spermatic cord of the varicocele patient have their specific anatomic characteristics. Laparoscopic identification of these vessels may contribute to the surgical treatment of varicocele.

Carotid stump syndrome: A case report.

Carotid stump syndrome (CSS) is known to be one of the causes of recurrent ipsilateral ischemic stroke following the occlusion of the internal carotid artery (ICA). The present study describes a case of left CSS in a 50-year-old patient presenting with a central retinal artery embolism following internal carotid and middle cerebral artery occlusion. The central retinal artery embolism was believed to be a consequence of microemboli, which originated from the stump of the occluded ICA, passing into the ophthalmic artery due to external carotid-internal carotid anastomotic channels, although the other possible pathophysiological causes of this condition are discussed. Digital subtraction angiography of the patient showed trickle flow in the occluded ICA during the venous phase, by which the stump emboli may have been transported to the ophthalmic artery. The patient was successfully treated with anticoagulation therapy without surgical or endovascular treatment.

The study of energy metabolism in bladder cancer cells in co-culture conditions using a microfluidic chip.

OBJECTIVES: This study aimed to systematically analyze changes in mitochondrial-related protein expression in bladder cancer cells and tumor-associated fibroblasts and to investigate the characteristics of bladder cancer cell energy metabolism. METHODS: In this study, we utilized the following techniques to achieve the objectives: (1) a co-culture system of bladder tumor cells and fibroblasts was built using a microfluidic chip as a three-dimensional culture system; (2) the concentration of lactic acid in the medium from the different groups was determined using an automatic micro-plate reader; (3) a qualitative analysis of mitochondria-related protein expression was performed by immunofluorescent staining; and (4) a quantitative analysis of mitochondrial-associated protein expression was conducted via Western blot. SPSS software was utilized to analyze the data. RESULTS: (1) Determination of lactic acid concentration: The lactic acid concentration was determined to be highest in the experimental group, followed by the T24 cell control group and then the fibroblast control group. (2) Qualitative results: In the control group, the mitochondrial-related protein fluorescence intensity was higher in the fibroblasts compared with the cancer cells, and the fluorescence intensity of the fibroblasts was reduced compared with the experimental group. The mitochondrial-related protein fluorescence intensity of the cancer cells was higher in the experimental group compared with the control group, and the opposite results were obtained with the fibroblasts. (3) Quantitative results: The expression of mitochondria-related proteins was higher in fibroblasts compared with cancer cells in the control group, and the opposite results were obtained in the experimental group (P<0.05). The expression of mitochondria-related proteins was increased in cancer cells in the experimental group compared with the control group; the opposite results were observed for the fibroblasts (P<0.05). CONCLUSIONS: The energy metabolism of bladder tumor cells does not parallel the "Warburg effect" because even under sufficient oxygen conditions, cancer cells still undergo glycolysis. Bladder cancer cells also have an efficient oxidative phosphorylation process wherein cancer cells promote glycolysis in adjacent interstitial cells, thereby causing increased formation of nutritional precursors. These high-energy metabolites are transferred to adjacent tumor cells in a specified direction and enter the Krebs Cycle. Ultimately, oxidative phosphorylation increases, and sufficient ATP is produced.

T-cell immunoglobulin mucin-3 expression in bladder urothelial carcinoma: Clinicopathologic correlations and association with survival.

BACKGROUND: T cell immunoglobulin mucin-3 (Tim-3) was initially recognized as a pivotal immune checkpoint inhibitor that maintains immune homeostasis and tolerance. Recently, Tim-3 has been demonstrated to play an important role in tumor-associated immune suppression and aberrant Tim-3 expression has been reported in several human malignancies. However, the role of Tim-3 in bladder urothelial carcinoma (BUC) remains largely unknown. The present study aims to investigate Tim-3 expression in BUC and analyze correlations with clinicopathologic outcomes and postoperative survival. METHODS: Tim-3 protein expressions were detected in paraffin embedded sections from 100 patients with BUC by immunohistochemistry. Expressions were correlated with clinicopathologic outcomes and postoperative survival. RESULTS: Tim-3 protein was over-expressed in bladder cancer cells, tumor infiltrating lymphocytes and endothelial cells from patients with BUC. The expression levels of Tim-3 were significantly correlated with advanced pathological grade and T stage. Moreover, another immune checkpoint molecule programmed death receptor-1(PD-1) was also over- expressed in BUC tissues and had a significant correlation with Tim-3. Multivariate analysis showed that Tim-3 expression, as well as PD-1 expression was both independent predictors of disease-free survival and overall survival in patients with BUC. CONCLUSION: Tim-3 over-expression implies adverse clinical outcomes for BUC, which suggests it is a potential prognostic biomarker and a novel therapeutic target in BUC.

B7-H1/PD-1 blockade therapy in urological malignancies: current status and future prospects.

The stimulatory and inhibitory coreceptors expressed by T lymphocytes are known to play critical roles in regulating cancer immunity. An array of inhibitory coreceptors involved in the inhibition of T-cell functions and the blockade of immune activation have been discovered in recent years, the most important of which are cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmmed death-1 (PD-1), and B7 homolog 1 (B7-H1). Immunotherapies targeting T-cell coinhibitory molecules have proved to be effective in cancer treatment. Several kinds of monoclonal antibodies have been tested in preclinical studies, with better outcomes than conventional therapies in many malignancies. Common urological malignancies including renal cell carcinoma, bladder cancer and prostate cancer are supposed to be immunogenic cancer types and not so sensitive to conventional therapies as other malignancies. This review will focus on B7-H1/PD-1 blockade therapy in urological malignancies, summarizing the results of clinical trials as well as the challenges and prospects of this emerging immunotherapy.

Recombinant bacillus Calmette-Guérin in urothelial bladder cancer immunotherapy: current strategies.

Bacillus Calmette-Guérin (BCG) has been used in the intravesical treatment of urothelial bladder cancer (UBC) for three decades. Despite its efficacy, intravesical BCG therapy is associated with some limitations such as side effects and BCG failure, which have inspired multiple ways to improve it. Recent advances have focused on recombinant BCG (rBCG) which provides a novel tactic for modification of BCG. To date, a number of rBCG strains have been developed and demonstrated to encourage efficacy and safety in preclinical and clinical studies. This review summarizes current rBCG strategies, concerns and future directions in UBC immunotherapy with an intention to encourage further research and eventually to inform clinical decisions.

Silencing B7-H1 enhances the anti-tumor effect of bladder cancer antigen-loaded dendritic cell vaccine in vitro.

OBJECTIVE: The aim of this study was to examine whether short hairpin RNA (shRNA) expressing lentiviral particles targeting B7-H1 infection could result in B7-H1 knockdown on dendritic cells (DCs) and to investigate whether B7-H1 silencing could augment the immune function of DCs and further elicit a more potent anti-tumor immune effect against bladder cancer cells in vitro. METHODS: Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells, were infected by a recombinant lentivirus containing shRNA sequence aimed at B7-H1. After that, the infected DCs were pulsed by tumor antigens and used to stimulate cytotoxic T lymphocytes-based anti-tumor effect in vitro. RESULTS: The lentivirus-mediated shRNA delivery method efficiently and effectively silenced B7-H1 in DCs. Furthermore, the B7-H1 silencing enhanced the stimulatory capacity and the secretion of interleukin-12, but down-regulated interleukin-10 secretion. And more importantly, the anti-tumor effect of bladder cancer antigen-loaded DC vaccine in vitro was also potentially augmented. CONCLUSION: This study suggests that a combination of B7-H1 knockdown and target antigen delivery could augment anti-tumor effects in vitro, which potentially provides a novel strategy in the immunotherapy of bladder cancer.

Quantitative risk stratification and individual comprehensive therapy for invasive bladder cancers in China.

BACKGROUND: To evaluate the risk factors for invasive bladder cancer and to develop a predictive model for the improvement of individual comprehensive therapy for invasive bladder cancers. MATERIALS AND METHODS: The records of 356 patients with invasive bladder cancer, operated on at three Chinese medical institutes, were reviewed. The Cox proportional hazards regression model was used to assess the clinical and pathological variables affecting disease-free survival (DFS). The regression coefficients determined by Cox regression analysis were used to construct a predictive index (PI). PI was used to categorize the patients into different risk groups. Kaplan-Meier survival curves followed with log-rank test were plotted to compare the difference. RESULTS: Tumor configuration (RR = 1.60, P = 0.01), multiplicity (RR = 1.41, P = 0.04), histological subtype (RR = 2.13, P < 0.01), tumor stage (RR = 2.50, P < 0.01), tumor grade (RR = 2.35, P < 0.01), node status (RR = 2.48, P < 0.01), and neoadjuvant chemotherapy (RR = 0.46, P = 0.02), had independent prognostic significance for DFS. PI = 0.47 x (configuration) + 0.34 x (multiplicity) + 0.76 x (tumor histological subtype) + 0.92 x (stage) + 0.86 x (grade) + 0.91 x (node status) - 0.79 x (neoadjuvant chemotherapy). The range of PI was -0.32 to 6.52, which was equally divided into three risk groups with significant differences on Kaplan-Meier curves and a log-rank test (P < 0.01). Meanwhile, the patient's probability of survival could be calculated by PI. CONCLUSIONS: Seven factors (tumor configuration, multiplicity, histological subtype, tumor stage, tumor grade, node status, neoadjuvant chemotherapy) affect the prognosis after radical cystectomy (RC) for invasive bladder cancer. PI can be used to optimize the individual comprehensive therapy. Given fewer perioperative complications, fast recovery from surgery and relatively satisfactory quality of life, ureterocutaneostomy, and ileal conduit are suitable for the patients with short expected life spans.

[Comparative study of transurethral electrovaporization of prostate versus transurethral resection of prostate on benign prostatic hyperplasia].

OBJECTIVES: To compare the efficacy of transurethral electrovaporization of prostate (TUVP) with transurethral resection of prostate (TURP). METHODS: 206 patients with symptomatic benign prostatic hyperplasia (BPH) whose prostatic sizes were all less than 60 grams were randomly divided into two groups. 97 cases were treated by TUVP while the other 109 cases were treated by TURP. The patients who underwent either TUVP or TURP were followed up for 12-34 months with an average of 20 months postoperatively. RESULTS: Both groups showed the significant decline in the mean IPSS (international prostatic symptom score) (P < 0.01), the mean PVR (Postovoiding Residual Volume) (P < 0.01), while increase in mean Qmax (Peak uroflow rate) (P < 0.01) in 12 months, 24 months after the operation. There were significant differences in the mean duration of operation or catheterization postoperatively (P < 0.05). The main complications of post-operation in the two groups were stress incontinence, TUR syndrome, urethral stricture, secondary bleeding. CONCLUSIONS: Both TUVP and TURP are effective treatment for the patient with BPH whose prostatic size is less than 60 grams. TUVP spends shorter time of the operation and postoperative catheterization than that of TURP.