Sub-Staging-Specific Differences in Recurrence-Free, Progression-Free, and Cancer-Specific Survival for Patients with T1 Bladder Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: The efficiency of the T1 sub-staging system on categorizing bladder cancer (BC) patients into subgroups with different clinical outcomes was unclear. We summarized relevant evidences, including recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS), to analyze the prognostic significance of T1 sub-stage. METHODS: Systematic literature searches of MEDLINE, EMBASE, and the Cochrane Library were performed. We pooled data on recurrence, progression, and CSS from 35 studies. RESULTS: The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) indicated the difference in RFS between T1a sub-stage and T1b sub-stage (HR 1.28, 95% CI 1.14-1.43, p < 0.001). The significant difference was observed in PFS between the 2 arms (HR 2.18, 95% CI 1.95-2.44, p < 0.001). Worse CSS was found in T1b patients than in T1a patients (HR 1.36, 95% CI 1.21-1.54, p < 0.001). CONCLUSIONS: T1 sub-staging system based on the invasion depth into muscularis mucosae can be a significant prognostic factor for RFS, PFS, and CSS of patients with T1 BC. Urologists and pathologists are encouraged to work together to give a precise sub-stage classification of T1 BC, and T1 sub-staging system should be a routine part of any histopathological report when possible. Different treatment strategies need to be developed for both T1a BC and T1b BC.

Transurethral Enucleation of Bladder Leiomyoma: A Series of Six Cases and Review of the Literature.

OBJECTIVES: To investigate the feasibility and initial surgical outcomes of transurethral enucleation for 6 patients with bladder leiomyoma. MATERIALS: Six patients (mean age 50.2, range [34-67]) with bladder leiomyoma underwent transurethral enucleation. In each case, the resectoscope was inserted into the bladder. A resecting loop was used to incise the urothelium along the surgical margin of the bladder tumor, and a push was given through the resecting loop to further separate the tumor until it was shelled off the bladder wall. The intact mass was then cut into pieces and flushed out. After the operation, irrigation therapy was given. RESULTS: Surgery was performed successfully in all 6 patients. The mean size of the tumor was 3.9 cm (1.8-6.7 cm). The mean operation time was 60 min (30-100 min). The mean follow-up period was 14.8 months (2-30 months), and no evidence of recurrence was found in all cases. CONCLUSION: Transurethral enucleation is a safe, reliable, and effective surgical technique for selected patients with well-encapsulated tumors and is well suited for further pathological diagnosis and radical treatment.

Comprehensive analysis of necroptosis-related lncRNA signature with potential implications in tumor heterogeneity and prediction of prognosis in clear cell renal cell carcinoma.

BACKGROUND: Necroptosis has been reported to play a critical role in occurrence and progression of cancer. The dysregulation of long non-coding RNAs (lncRNAs) is associated with the progression and metastasis of clear cell renal cell carcinoma (CCRCC). However, research on necroptosis-related lncRNAs in the tumor heterogeneity and prognosis of CCRCC is not completely unclear. This study aimed to analysis the tumor heterogeneity among CCRCC subgroups and construct a CCRCC prognostic signature based on necroptosis-related lncRNAs. METHODS: Weighted gene co-expression network analysis (WGCNA) was performed to identify necroptosis-related lncRNAs. A preliminary classification of molecular subgroups was performed by non-negative matrix factorization (NMF) consensus clustering analysis. Comprehensive analyses, including fraction genome altered (FGA), tumor mutational burden (TMB), DNA methylation alterations, copy number variations (CNVs), and single nucleotide polymorphisms (SNPs), were performed to explore the potential factors for tumor heterogeneity among the three subgroups. Subsequently, we constructed a predictive signature by multivariate Cox regression. Nomogram, calibration curves, decision curve analysis (DCA), and time-dependent receiver-operating characteristics (ROC) were used to validate and evaluate the signature. Finally, immune correlation analyses, including immune-related signaling pathways, immune cell infiltration status and immune checkpoint gene expression level, were also performed. RESULTS: Seven necroptosis-related lncRNAs were screened out by WGCNA, and three subgroups were classified by NMF consensus clustering analysis. There were significant differences in survival prognosis, clinicopathological characteristics, enrichments of immune-related signaling pathway, degree of immune cell infiltration, and expression of immune checkpoint genes in the various subgroups. Most importantly, we found that 26 differentially expressed genes (DEGs) among the 3 subgroups were not affected by DNA methylation alterations, CNVs and SNPs. On the contrary, these DEGs were associated with the seven necroptosis-related lncRNAs. Subsequently, the identified RP11-133F8.2 and RP11-283G6.4 by multivariate Cox regression analysis were involved in the risk model, which could serve as an independent prognostic factor for CCRCC. Finally, qRT-PCR confirmed the differential expression of the two lncRNAs. CONCLUSIONS: These findings contributed to understanding the function of necroptosis-related lncRNAs in CCRCC and provided new insights of prognostic evaluation and optimal therapeutic strategy for CCRCC.

Thymoquinone suppresses invasion and metastasis in bladder cancer cells by reversing EMT through the Wnt/ß-catenin signaling pathway.

Epithelial mesenchymal transformation plays a crucial role in the metastasis of bladder cancer, which makes bladder cancer difficult to cure. Bladder cancer is the most common malignancy of the urinary system, and distant metastasis is the leading cause of death. Therefore, finding a bioactive drug that can specifically inhibit epithelial mesenchymal transformation may be a new direction for bladder cancer treatment in the future. Thymoquinone (TQ), the major active compound isolated from black seed oil (Nigella sativa), has been reported to exhibit anti-inflammatory and anticancer abilities. TQ can exhibit its antitumor effect by inhibiting the proliferation and metastasis of cancer cells. However, the underlying mechanism of TQ as a tumor inhibitor in bladder cancer remains poorly understood. First, in this research, we demonstrate that TQ can reverse EMT by upregulating epithelial markers, such as E-cadherin, and downregulating mesenchymal markers, such as N-cadherin and vimentin. Furthermore, we demonstrate that TQ can suppress the activation of the Wnt/ß-catenin signaling pathway and inhibit the expression of ß-catenin target genes, such as MYC, Axin-2, MMP7, CyclinD1 and MET, which play crucial roles in EMT and cancer progression. Additionally, we demonstrate that TQ can inhibit the growth of xenografts and restrict the formation of tumor metastatic foci in the lung. Taken together, our findings confirm the antimetastatic effect of TQ in bladder cancer cells for the first time and also provide new evidence for the development of TQ as a novel treatment for metastatic bladder cancer.

Bladder cancer cells interact with vascular endothelial cells triggering EGFR signals to promote tumor progression.

Although important progress has been made in elucidating the role of the tumor microenvironment in the development of bladder cancer, little is currently known regarding the interactions with vascular endothelial cells (ECs) that promote cancer progression. In the present study, it is reported that epidermal growth factor receptor ligands induced by the upregulation of vascular endothelial growth factor (VEGF)­A and VEGF­C via the VEGF receptor (R)2/nuclear factor­κB signaling pathway in ECs, may trigger EGFR signaling in bladder cancer cells and promote bladder cancer progression. Furthermore, the interaction between bladder cancer cells and ECs enhanced EC recruitment though the CXCL1/CXCL5/CXCL8­CXCR2 pathway. Western blotting was used to evaluate the presence of VEGFR, EGFR and nuclear factor­κB, and reverse transcription­quantitative polymerase chain reaction was used to evaluate the expression of VEGFR ligands and EGFR ligands. The present results indicate the mechanism by which the indirect interplay between bladder cancer cells and vascular ECs promotes cancer progression, through the VEGFR2 signaling pathway in vascular ECs and through the EGFR signaling pathway in bladder cancer cells.

A Molecular Beacon Based Surface-Enhanced Raman Scattering Nanotag for Noninvasive Diagnosis of Bladder Cancer.

Current techniques responsible for bladder cancer diagnosis and monitoring are insensitive and invasive. Here, we report a surface-enhanced Raman scattering nanotag for the sensitive diagnosis of bladder cancer using urine samples as a noninvasive approach. The sea-urchin-like Au nanoclusters used in this work exhibit excellent surface-enhanced Raman scattering ability with an enhancement factor of 3.44 × 107. Molecular beacons labeled with Cy3 are covalently anchored to the surface of Au nanoclusters, which serve as a specific recognition site for survivin mRNA. Further a polyethylene glycol coating provides stability and completes the final functionalization. This surface-enhanced Raman scattering nanotag has good efficiency (equilibrium time: 10 min) with high sensitivity (detection threshold: 19.4 nM), high specificity (capable of single-base mismatch recognition) and good stability against nucleases. All these features are also verified in the fluorescence modality. Furthermore, its function was highly maintained in clinical samples from 13 patients with bladder cancer, as evidenced by a sensitivity up to 91.7% and a specificity up to 100%. The nanotag demonstrates its superiority over cytology and has its great clinical value even for early bladder cancer diagnosis. Thus, the nanotag is promising for noninvasive and sensitive diagnosis of bladder cancer.

Thymoquinone induces apoptosis in bladder cancer cell via endoplasmic reticulum stress-dependent mitochondrial pathway.

BACKGROUND: Thymoquinone (TQ), the major active compound isolated from black seed oil (Nigella sativa), has been reported to exhibit anti-inflammatory and anticancer abilities. However, the exact molecular mechanism underlying the anticancer effect of TQ is still poorly understood, especially in regard to TQ's effect on endoplasmic reticulum stress-mediated apoptosis. METHODS: The cytotoxicity of TQ on T24 and 253J bladder cancer cells was analyzed by MTT assay, colony formation assay and Annexin V-FITC/PI staining, while SV-HUC-1, the SV-40 immortalized human uroepithelial cell line, was used as a normal control. The change in mitochondrial membrane potential was assessed by JC-1 staining. mRNA expression and protein expression were detected by qPCR and western blotting. Caspase-3 activity was detected by colorimetric assay. KEY FINDING: TQ has a significant cytotoxicity on bladder cancer cells and can inhibit their proliferation and induce apoptosis. The protein changes of Bcl-2, Bax, cytochrome c and endoplasmic reticulum stress-related proteins (GRP78, CHOP, and caspase-12) revealed that the anticancer effect of TQ was associated with mitochondrial dysfunction and the endoplasmic reticulum stress pathway. Pretreatment with a pan-caspase inhibitor, Z-VAD-fmk, or an ER stress inhibitor, 4-PBA, or knockdown of CHOP by shRNA can partly reverse the pro-apoptotic effect of TQ by enhancing the expression of the anti-apoptotic protein Bcl-2, blocking the release of cytochrome c and the translocation of Bax from the cytoplasm to mitochondria. SIGNIFICANCE: Our findings provide the first demonstration of the anticancer effect of TQ on bladder cancer, and the relationship between ER stress and mitochondrial dysfunction was clearly understood when the apoptosis progressed is revealed.

[PAHs concentrations in aquatic products and food safety evaluation in the coupled mangrove planting-aquaculture ecological system].

In order to know about the PAHs concentration in aquatic products from mangrove planting-aquaculture ecological system and to make sure of food quality and food safety, HPLC was used to determine concentrations of 13 polycyclic aromatic hydrocarbons (PAHs) in the Tilapia mossambica, Mugil cephalu and Concha ostreae from coupled mangrove planting-aquaculture ponds, food safety in aquatic products was also evaluated. The 13 PAHs were Fluorene (Flu), Phenanthrene (Phe), Anthracene (Ant), Fluoranthene (Fla), Pyrene (Pyr), Benz[a] anthraces (BaA), Chrysene (Chr), Benzo[b] fluoranthene (BbF), Benzo[k] fluoranthene (BkF), Benzo[a] Pyrene (BaP), Dibenzo [a, h] anthercene (DahA), Benzo [g, h, i] perylene (BghiP) and Indeno [1,2,3-c, d] pyrene (InP). Concentrations of PAHs were the highest in Concha ostreae which were in the range of 89.79-98.49 microg x kg(-1) dry weight, while those were in the range of 25.97-34.64 microg x kg(-1) in Mugil cephalu and 12.31-14.41 microg x kg(-1) in Tilapia mossambica. The content of fat affected the levels of PAHs content in different aquatic products. The individual composition of PAHs was characterized by 3 rings in samples with the range of 41.58% - 83.35%. Comparing with other areas, PAHs pollution of aquatic products in the studied area was in the mild level. Values of the total BaP(eq) concentration ranged from 0.0689 microg x kg(-1) to 1.0373 microg x kg(-1), which were lower than the maximum level set by European Union.