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A study published in the journal Clinical & Translational Medicine presents a novel risk stratification model for detecting residual tumors in patients with non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumors (TURBT). The model is based on urinary DNA methylation and incorporates clinical features such as tumor grade, presence of multiple tumors, maximum tumor size, histologic variants, and lymphatic-vascular invasion. The study found that the model achieved high accuracy in detecting residual tumors, with a sensitivity of 95.83%. By accurately identifying high-risk patients, unnecessary re-TURBT procedures can be reduced, thereby reducing patient distress and associated costs. [Extracted from the article]

Due to the poor stability and adverse effects of chemotherapy drugs, such as gemcitabine, the current effectiveness of traditional chemotherapy is minimal. Some patients also show a low response rate to immunotherapy. Therefore, a novel material PD‐L1‐GEMs is designed and synthesized with targeted specificity. PD‐L1‐GEMs specifically bind to bladder cancer cells. Free gemcitabine cleaved by a phosphatase enters bladder cancer cells through the macropinocytosis pathway and induces cytotoxicity. PD‐L1‐GEMs show good stability, binding specificity, and significant inhibitory effects in vitro. Two bladder tumor models (subcutaneous model and in situ model) show inhibition of growth and progression in PD‐L1‐GEMs treatment, as well as good biosafety in vivo. The PD‐L1 aptamer blocks the binding of PD‐L1 on the tumor cell surface to PD‐1 on T lymphocytes, restoring their immune function, inducing cytokine production and aggregation, and exerting an immune killing role on bladder cancer cells. PD‐L1‐GEMs represent a successful chemotherapy–immunotherapy strategy for bladder cancer. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in cancer tumorigenesis and progression. TMPO antisense RNA 1 (TMPO-AS1) has been found to be involved in several cancers by acting as a competing endogenous RNA. However, the potential roles of TMPO-AS1 in bladder cancer (BC) and the potential interactions with proteins remain poorly understood. Methods: The expression of the lncRNA TMPO-AS1 was evaluated via bioinformatic analysis and further validated by quantitative real-time PCR (qRT-PCR). Loss- and gain-of-function assays were performed to determine the biological functions of TMPO-AS1 in BC cell proliferation, migration, and invasion. Moreover, chromatin immunoprecipitation, Western blotting, and fluorescence in situ hybridization, as well as RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays, were conducted to explore the upstream and downstream molecules interacting with TMPO-AS1. Results: TMPO-AS1 is upregulated in BC. Functional experiments demonstrated that TMPO-AS1 promotes cell proliferation, migration, and invasion in BC and inhibits cell apoptosis in vivo and in vitro. Mechanically, E2F1 is responsible for TMPO-AS1 upregulation. Additionally, TMPO-AS1 facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), leading to E2F1 deubiquitination and stabilization; therefore, TMPO-AS1 promotes BC malignant phenotypes. Furthermore, rescue experiments showed that TMPO-AS1 promotes BC growth in an E2F1-dependent manner. Conclusions: Our study is the first to uncover the novel TMPO-AS1/E2F1 positive regulatory loop important for the promotion of BC malignant behaviors. The TMPO-AS1/E2F1 loop should be considered in the quest for new BC therapeutic options. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer is an epidemic and life-threating urologic carcinoma. Anoikis is a unusual type of programmed cell death which plays a vital role in tumor survival, invasion and metastasis. Nevertheless, the relationship between anoikis and bladder cancer has not been understood thoroughly. Methods: We downloaded the transcriptome and clinical information of BLCA patients from TCGA and GEO databases. Then, we analyzed different expression of anoikis-related genes and established a prognostic model based on TCGA database by univariate Cox regression, lasso regression, and multivariate Cox regression. Then the Kaplan–Meier survival analysis and receiver operating characteristic (ROC) curves were performed. GEO database was used for external validation. BLCA patients in TCGA database were divided into two subgroups by non-negative matrix factorization (NMF) classification. Survival analysis, different gene expression, immune cell infiltration and drug sensitivity were calculated. Finally, we verified the function of S100A7 in two BLCA cell lines. Results: We developed a prognostic risk model based on three anoikis-related genes including TPM1, RAC3 and S100A7. The overall survival of BLCA patients in low-risk groups was significantly better than high-risk groups in training sets, test sets and external validation sets. Subsequently, the checkpoint and immune cell infiltration had significant difference between two groups. Then we identified two subtypes (CA and CB) through NMF analysis and found CA had better OS and PFS than CB. Besides, the accuracy of risk model was verified by ROC analysis. Finally, we identified that knocking down S100A7 gene expression restrained the proliferation and invasion of bladder cancer cells. Conclusion: We established and validated a bladder cancer prognostic model consisting of three genes, which can effectively evaluate the prognosis of bladder cancer patients. Additionally, through cellular experiments, we demonstrated the significant role of S100A7 in the metastasis and invasion of bladder cancer, suggesting its potential as a novel target for future treatments. [ABSTRACT FROM AUTHOR]

Objective: To date, only a few studies have demonstrated the prognostic value of pretreatment serum albumin in bladder urothelial carcinoma (BUC). The aim of this study was to evaluate the association between the pretreatment albumin/globulin ratio (AGR) and the survival of patients with BUC treated with radical cystectomy (RC).Materials and Methods: Data from 296 patients with BUC who underwent RC between June 2000 and June 2013 were analyzed. The AGR was calculated as follows: albumin/(total protein-albumin). The AGR was divided into 2 groups for receiver operating characteristics curve analysis. Survival was estimated using Kaplan-Meier analysis and compared using the log rank test. Cox proportional hazards models were used for univariate and multivariate survival analyses.Results: Patients in the high AGR group (AGR≥1.60) had a lower 5-year recurrence-free mortality rate compared with those in the low AGR group (AGR<1.60) (87.0% vs. 48.0%, P<0.001). The median cancer-specific survival (CSS) time was 71.1 months for low AGR patients and 156.0 months for the high AGR patients (P<0.001). After adjusting for confounding variables, the AGR remained an independent predictor of recurrence-free survival (RFS) (hazard rate = 0.356; 95% CI: 0.170-0.748; P = 0.006) and CSS (hazard rate = 0.280; 95% CI: 0.115-0.683; P = 0.005). Moreover, in the subset of 167 patients with normal serum albumin (albumin of≥40.0g/l), serum AGR continues to be an independent predictor of RFS (P = 0.012) and CSS (P = 0.008).Conclusions: High AGR is a strong independent predictor of long-term RFS and CSS in patients with BUC undergoing RC. Additionally, among patients with normal albumin (≥40g/l) levels, patients with higher globulin, but lower AGR have worse survival. The pretreatment AGR is an easily accessible and cheap to use for predicting mortality in patients with BUC treated by RC. [ABSTRACT FROM AUTHOR]

• The first report of the use of a CD71 and CD44 aptamer as a drug carrier to target and eliminate both CSCs and non-CSCs. • The first report of the use of dual-aptamer based drug delivery system to treat bladder cancer. • CD71-CD44-GEMs exerted obvious anticancer effect in three types of tumor xenograft mice models. • CD71-CD44-GEMs showed excellent biosafety in three types of tumor xenograft mice models. Conventional chemotherapy lacks the ability to specifically target cancer cells, thus although it eliminates tumor tissues to some extent, it also damages normal tissues and organs. Meanwhile, cancer stem cells (CSCs)-induced tumor regrowth and drug resistance limits the application of some chemotherapy drugs. In this study, the CD71/CD44 dual-aptamer-gemcitabine (CD71-CD44-GEMs) conjugate was designed to treat bladder cancer through the co-targeting by CD71 of bladder cancer cells and by CD44 of bladder CSCs. A series of studies were used to evaluate the binding specificity and the in vitro and in vivo anti-cancer effects. We observed that CD71-CD44-GEMs selectively bound to and exerted a high inhibitory effect on bladder cancer in vitro and in vivo. Besides, CD71-CD44-GEMs can inhibit the formation of the tumorsphere and demonstrated a higher binding affinity and inhibitory efficacy than CD71-GEMs or CD44-GEMs (GEM delivered by a single target aptamer) in bladder cancer. Hence, CD71-CD44-GEMs represents a promising approach to treating bladder cancer for its high efficacy in drug delivery and ability to eliminate both bladder cancer cells and CSCs. [ABSTRACT FROM AUTHOR]