Maternally Expressed Gene 3 (MEG3) is an imprinted gene that encodes a long non-coding RNA (lncRNA) associated with tumorigenesis. Autophagy is activated in cancer cells and contributes to tumor cell survival. However, little is known about whether MEG3 regulates bladder cancer development by controlling autophagy. In the study, we found that MEG3 levels were significantly reduced in bladder cancer tissues compared with normal controls, and autophagy activity was increased in bladder cancer tissues. A significant negative correlation was observed between MEG3 levels and LC3-II (autophagy marker) levels in vivo. We further demonstrated that MEG3 markedly suppressed autophagy activation, whereas MEG3 knockdown activated autophagy in human bladder cancer cell lines. Downregulated expression of MEG3 inhibited cell apoptosis, whereas autophagy inhibition increased MEG3-knockdown cell apoptosis. MEG3 knockdown also increased cell proliferation. More importantly, autophagy inhibition abrogated MEG3 knockdown-induced cell proliferation. These data demonstrated that downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer.

The aim of the study was to compare the clinical outcome and the cost-effectiveness between retrograde intra renal surgery (RIRS) and mini-percutaneous nephrolithotripsy (mPCNL) for the management of single renal stone of 2-3 cm in Chinese medical setting. From May 2005 to February 2011, 115 patients with solitary renal calculi were treated either by RIRS or mPCNL. 56 patients were in RIRS group while 59 were in mPCNL group. Patients' demographics between the two groups, in terms of gender, age, BMI, history of ESWL as well as stone side, stone location and stone size were comparable. Peri-operative course, clinical outcome, complication rates and medical cost were compared. The effective quotient (EQ) of two groups was calculated. Data were analyzed using Fisher's exact test, Chi-square test and Student's t test. EQ for RIRS and mPCNL were 0.52 and 0.90. The initial stone-free rate (SFR) of RIRS group and mPCNL group was 71.4 and 96.6 %, respectively (P = 0.000). The mean procedure number was 1.18 in RIRS group and 1.03 in mPCNL group, respectively (P = 0.035). The operative time for RIRS was longer (P = 0.000) while the mean hospital stay was shorter (P = 0.000). There was no statistical difference in peri-operative complications between the groups. The initial hospitalization cost, laboratory and radiology test cost of RIRS group were lower (P = 0.000). However, counting the retreatment cost in the two groups, the total medical expenditure including the overall hospitalization cost, overall laboratory and radiology test cost and post-operative out-patient department (OPD) visit cost was similar between two groups. In conclusion, with similar total medical cost, mPCNL achieved faster stone clearance and lower retreatment rate without major complications, which implied higher cost-effectiveness for the treatment of single renal stone of 2-3 cm in Chinese medical setting. RIRS is also a safe and reliable choice for patients having contraindications or preference against mPCNL.

Background Nearly a half million people around the world are diagnosed with bladder cancer each year, and an incomplete understanding of its pathogenicity and lack of efficient biomarkers having been discovered lead to poor clinical management of bladder cancer. Fat mass and obesity‐associated protein (FTO) is a critical player in carcinogenesis. We, here, explored the role of FTO and unraveled the mechanism of its function in bladder cancer. Methods Identification of the correlation of FTO with bladder cancer was based on both bioinformatics and clinical analysis of tissue samples collected from a cohort of patients at a hospital and microarray data. Gain‐of‐function and loss‐of‐function assays were conducted in vivo and in vitro to assess the effect of FTO on bladder carcinoma tumor growth and its impact on the bladder carcinoma cell viability. Moreover, the interactions of intermediate products were also investigated to elucidate the mechanisms of FTO function. Results Bladder tumor tissues had increased FTO expression which correlated with clinical bladder cancer prognosis and outcomes. Both in vivo and in vitro, it played the function of an oncogene in stimulating the cell viability and tumorigenicity of bladder cancer. Furthermore, FTO catalyzed metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) demethylation, regulated microRNA miR‐384 and mal T cell differentiation protein 2 (MAL2) expression, and modulated the interactions among these processes. Conclusions The interplay of these four clinically relevant factors contributes to the oncogenesis of bladder cancer. FTO facilitates the tumorigenesis of bladder cancer through regulating the MALAT/miR‐384/MAL2 axis in m6A RNA modification manner, which ensures the potential of FTO for serving as a diagnostic or prognostic biomarker in bladder cancer.

No abstract

HMGB1 might be a new molecular marker to predict the prognosis of patients with BC.

Purpose: Immunotherapy offers a second-line option for patients with metastatic urothelial carcinoma (mUC) who failed standard therapy, but the biomarkers for predicting response remain to be explored. This study aims to evaluate the safety, efficacy, and correlative biomarker of toripalimab in patients with previously treated mUC. Patients and Methods: Patients with mUC received toripalimab 3 mg/kg Q2W. Clinical response was assessed every 8 weeks by an independent review committee per RECIST v1.1. Tumor PD-L1 expression, tumor mutational burden (TMB), and other biomarkers were evaluated. Results: Among the intention-to-treat population (n = 151), 85% of the patients experienced treatment-related adverse event (TRAE) and 20% experienced grade 3 and above TRAE. The objective response rate (ORR) was 26% with a disease control rate (DCR) of 45%. The median duration of response, progression-free survival (PFS), and overall survival (OS) were 19.7 months [95% confidence interval (CI): 13.9–not estimable], 2.3 months (95% CI, 1.8–3.6), and 14.4 months (95% CI, 9.3–23.1), respectively. Both PD-L1+ and TMB-high (10 mutations/Mb as the cutoff) patients had better ORR than PD-L1− patients (42% vs. 17%, P = 0.002) and TMB-low patients (48% vs. 22%, P = 0.014), respectively. The TMB-high group also showed better PFS (12.9 vs. 1.8 months, P < 0.001) and OS (not reached versus 10.0 months, P = 0.018) than the TMB-low group. Conclusions: Toripalimab has demonstrated encouraging clinical activity in the second-line treatment of mUC with a manageable safety profile. PD-L1 expression and TMB were two independent biomarkers in the study.

Bladder cancer (BC) has become a serious health problem and represents the second most commonly diagnosed urological tumor. Curcumin is a principal active natural component of turmeric and has long been used in Asia as a traditional herbal medicine. Curcumin suppresses cell growth in various types of cancer, including BC, by regulating numerous molecular signaling pathways. The human trophoblast cell surface antigen 2 (Trop2) belongs to the tumor-associated calcium signal transducer gene family. Trop2 has been described as a cancer driver and is deregulated in various types of cancer. However, whether Trop2 is involved in curcumin-induced BC cell inhibition remains to be elucidated. The present study hypothesized that Trop2 may be a promising target of curcumin in BC cells. It was found that Trop2 was closely involved in curcumin-induced cell proliferation suppression, mobility inhibition, apoptosis, and cell cycle arrest in BC cells. Curcumin decreased the expression of Trop2 and its downstream target cyclin E1, and increased the level of p27. The overexpression of Trop2 enhanced the oncogenic activity of BC cells, whereas downregulation of the expression of Trop2 suppressed cell proliferation and mobility, increased apoptosis, and sensitized BC cells to curcumin treatment. Therefore, Trop2 may be a promising target of curcumin in BC cells and the inhibition of Trop2 may be an important method for the therapeutic management of patients with BC.

We have constructed a multifunctional nanoprobe with sensing and imaging properties by using hollow mesoporous silica coated upconversion nanoparticles (UCNPs) and Hg(2+) responsive ruthenium (Ru) complex. The Ru complex was loaded into the hollow mesoporous silica and the UCNPs acted as an energy donor, transferring luminescence energy to the Ru complex. Furthermore, polyethylenimine (PEI) was assembled on the surface of mesoporous silica to achieve better hydrophilic and bio-compatibility. Upon addition of Hg(2+), a blue shift of the absorption peak of the Ru complex is observed and the energy transfer process between the UCNPs and the Ru complex was blocked, resulting in an increase of the green emission intensity of the UCNPs. The un-changed 801 nm emission of the nanoprobe was used as an internal standard reference and the detection limit of Hg(2+) was determined to be 0.16 μM for this nanoprobe in aqueous solution. In addition, based on the low cytotoxicity as studied by CCK-8 assay, the nanoprobe was successfully applied for cell imaging and small animal imaging. Furthermore, when doped with Gd(3+) ions, the nanoprobe was successfully applied to in vivo magnetic resonance imaging (MRI) of Kunming mice, which demonstrates its potential as a MRI positive-contrast agent. Therefore, the method and results may provide more exciting opportunities to afford nanoprobes with multimodal bioimaging and multifunctional applications.