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Background: For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically. Results: The results indicated that Fe-doped chrysotile nanotubes (FeSiNTs) with a relatively uniform outer diameter (15–25 nm) and inner diameter (7–8 nm), and a length of several hundred nanometers, which delivered an siRNA against the SPAG5 oncogene (siSPAG5) efficiently. The nanomaterials were designed to prolong the half-life of siSPAG5 in blood, increase tumor cell-specific uptake, and maximize the efficiency of SPAG5 silencing. In vitro, FeSiNTs carrying siSPAG5 inhibited the growth, migration, and invasion of bladder cancer cells. In vivo, the FeSiNTs inhibited growth and metastasis in three models of bladder tumors (a tail vein injection lung metastatic model, an in-situ bladder cancer model, and a subcutaneous model) with no obvious toxicities. Mechanistically, we showed that FeSiNTs/siSPAG5 repressed PI3K/AKT/mTOR signaling, which suppressed the growth and progression of tumor cells. Conclusions: The results highlight that FeSiNTs/siSPAG5 caused no activation of the innate immune response nor any systemic toxicity, indicating the possible therapeutic utility of FeSiNTs/siSPAG5 to deliver siSPAG5 to treat bladder cancer. [ABSTRACT FROM AUTHOR]

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]

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]