This study aimed to understand the barriers to nurse-physician collaboration in implementing preoperative stoma site marking using qualitative research methods following Theoretical Domain Framework.

A qualitative descriptive study using semi-structured interviews was conducted from March to June 2023 in the urology departments of nine tertiary hospitals in China. Twelve urologists and eight enterostomal therapists (ETs) were recruited using purposive sampling. Audio recordings were transcribed verbatim and data were analyzed using content analysis.

Five themes were identified in the study: shortage of manpower and stoma care products, lack of standard and regulations, lack of motivation and intention, inconsistency of expectation on consequences, and difficulties in cooperation.

This study indicated that the barriers to implementation of preoperative urostomy localization among urologists and ETs. Institutions, resources, clear career plans, and performance feedback can increase motivation and intention. In addition, the lack of cooperation between urologists and ETs is a key factor for poor urostomy localization implementation, which calls for effective and equal communication between doctors and nurses.

Bladder cancer has a high recurrence rate, which indicates that the therapeutic effects of advanced bladder cancers are still limited. In this study, we combined vorinostat and cyproheptadine as a new treatment for bladder cancer. When combining the two drugs, an additive to synergistic effect is discovered. Furthermore, we modified the structure of vorinostat using cyproheptadine tricyclic ring to get compounds 8 C and O8C, which keep HDAC inhibitory activity and have IC50 lower than 10 μM in 5637, BFTC 905, and MB49 cells. In in vitro assay, vorinostat, 8 C and O8C increased the percentage of cell cycle in G2/M in 5637, while G0/G1 arrest in BFTC 905. Apoptosis was seen in 5637 and slightly in BFTC 905 by the Annexin V-PI staining assay, and a minor rescued cell viability after Z-VAD-FMK pretreatment in 5637. 8 C and O8C slightly decreased MMP, and increased ROS levels. Among different ROS scavenger treatments, only N-acetyl-L-cysteine shows a minor viability rescue, indicating ROS may not take an important role in 8C- and O8C-induced cell death. In the in vivo assay, mice underwent intraperitoneal injection of 8 C, delaying tumor growth compared to cyproheptadine, vorinostat, and O8C individually. Because the water solubility of 8 C is not good, we use its salt form 8C-HCl for further in vivo study. Mice underwent gavage of 8C-HCl, which resulted in delaying tumor growth. In conclusion, 8 C and 8C-HCl, from structure modification of vorinostat by cyproheptadine tricyclic ring, enhance tumor suppressive effect in vitro and in vivo.

There is a lack of clinical evidence on whether further clinical strategies are needed after TURBT combined with immediate bladder instillation. This study intends to establish a reliable quantitative assay for active urinary cancer cells (AUCC) and to investigate the clinical efficacy of continuous saline bladder irrigation (CSBI) as a feasible option by analyzing the perioperative AUCC changes in TURBT.

An AUCC assay was developed and its reliability was verified by single-cell whole genome sequencing. Bladder cancer patients (N = 324) diagnosed by cystoscopy and pathologic biopsy and control individuals (N = 92) were included from 2021 to 2023 in the study. Enrolled patients with non-muscle invasive bladder cancer (NMIBC) underwent TURBT followed by immediate bladder instillation of epirubicin, after subgroups received CSBI or not, and AUCCs were tested on the first and fifth postoperative day. The patients were followed up for two years for postoperative recurrence.

The AUCC assay achieved good detection accuracy, with a sensitivity of 0.821 and specificity of 0.902. AUCC increased on the first day after TURBT in combination with immediate bladder instillation, regardless of whether or not the patient received CSBI. However, AUCCs decreased more rapidly on the fifth day in patients treated with CSBI, and patients with concomitant risk factors benefited more from CSBI. The two-year follow-up results showed that high-risk patients with complex surgeries could benefit significantly from CSBI.

We pioneered a quantitative assay for AUCC and provided laboratory evidence that TURBT causes tumor cell dissemination and CSBI can be a further clinical strategy to reduce the risk of potential recurrence.

Mitotic catastrophe is well-known as a major pathway of endogenous tumor death, but the prognostic significance of its heterogeneity regarding bladder cancer (BLCA) remains unclear.

Our study focused on digging deeper into the TCGA and GEO databases. Through differential expression analysis as well as Weighted Gene Co-expression Network Analysis (WGCNA), we identified dysregulated mitotic catastrophe-associated genes, followed by univariate cox regression as well as ten machine learning algorithms to construct robust prognostic models. Based on prognostic stratification, we revealed intergroup differences by enrichment analysis, immune infiltration assessment, and genomic variant analysis. Subsequently by multivariate cox regression as well as survshap(t) model we screened core prognostic gene and identified it by Mendelian randomization. Integration of qRT-PCR, immunohistochemistry, and single-cell analysis explored the core gene expression landscape. In addition, we explored the ceRNA axis containing upstream non-coding RNAs after detailed analysis of pathway activation, immunoregulation, and methylation functions of the core genes. Finally, we performed drug screening and molecular docking experiments based on the core gene in the DSigDB database.

Our efforts culminated in the establishment of an accurate prognostic model containing 16 genes based on Coxboost as well as the Random Survival Forest (RSF) algorithm. Detailed analysis from multiple perspectives revealed a strong link between model scores and many key indicators: pathway activation, immune infiltration landscape, genomic variant landscape, and personalized treatment. Subsequently ANLN was identified as the core of the model, and prognostic analysis revealed that it portends a poor prognosis, further corroborated by Mendelian randomization analysis. Interestingly, ANLN expression was significantly upregulated in cancer cells and specifically clustered in epithelial cells and provided multiple pathways to mediate cell division. In addition, ANLN regulated immune infiltration patterns and was also inseparable from overall methylation levels. Further analysis revealed potential regulation of the MIR4435-2HG, hsa-miR-15a-5p, ANLN axis and highlighted a range of potential therapeutic agents including Phytoestrogens.

The model we developed was a powerful predictive tool for BLCA prognosis and revealed the impact of mitotic catastrophe heterogeneity on BLCA in multiple dimensions, which then guided clinical decision-making. Furthermore, we highlighted the potential of ANLN as a BLCA target.

Bladder cancer (BLCa) metastasis is a predominant cause of death for bladder cancer patients. Histone demethylase KDM3A specifically removes the repressive mono- or di-methyl marks from H3K9 and thus contributes to the activation of gene transcription. However, the underlying mechanisms of KDM3A in bladder cancer are poorly understood. Here, we report that high levels of KDM3A are associated with bladder cancer clinical progression. KDM3A silencing inhibits bladder cancer cell growth, cell migration and invasion in vitro and in vivo. Mechanistically, we identify that non-classic deubiquitinase USP13 interacts with KDM3A to promote its degradation in cytoplasm via the proteasome-specific pathway. USP13 was significantly down-regulated in bladder cancer tissues and negatively associated with KDM3A expression. Furthermore, we show in bladder injected-liver metastasis xenograft model that USP13 inhibits bladder cancer metastasis through destabilizing cytoplasmic KDM3A. Collectively, our findings identify KDM3A is an important regulator of bladder cancer cell growth and metastasis and targeting USP13/KDM3A complex could be a valuable strategy to ameliorate bladder cancer progression and metastasis.

Background/Objectives: Bladder cancer (BC), a highly heterogeneous and mutation-prone malignancy, remains a significant therapeutic challenge due to its propensity for recurrence, metastasis, and drug resistance. Natural products, particularly paeonol, a bioactive compound derived from Moutan Cortex in traditional Chinese medicine, have shown promising potential in cancer therapy. This study aims to evaluate the anti-BC effects of paeonol and elucidate its underlying molecular mechanisms. Methods: In vitro experiments were conducted using T24 and J82 BC cell lines to assess paeonol's effects on cell viability, migration, apoptosis, and cell cycle progression via CCK-8, scratch, flow cytometry, RT-qPCR, and Western blot analyses. In vivo efficacy was evaluated using a xenograft mouse model, with tumor growth monitored and histopathological analysis performed. Results: Paeonol significantly inhibited BC cell proliferation and migration in a dose- and time-dependent manner, with IC50 values of 225 μg/mL (T24) and 124 μg/mL (J82) at 48 h. It induced apoptosis and arrested the cell cycle at the G1 phase, accompanied by upregulation of pro-apoptotic proteins (BID, BAX, BIM, and p53). In vivo, paeonol reduced tumor volume and weight without histopathological abnormalities in vital organs. Conclusions: Paeonol exhibits potent anti-BC activity by apoptotic pathways and by arresting the cell cycle at the G1 phase and inhibiting tumor growth. Its favorable safety profile and multi-target mechanisms highlight its potential as a promising therapeutic candidate for BC. These findings provide a foundation for further clinical development of paeonol-based therapies.

X-linked inhibitor of apoptosis protein (XIAP), a member of the IAP family, is overexpressed in a variety of tumors and plays an important role in tumor progression. Increasing evidence suggests that XIAP promotes metastasis of bladder cancer but the underlying mechanism is not very clear. The RNA N6-methyladenosine (m6A) reader YTHDC1 regulates RNA splicing, nuclear transport, and mRNA stability and is a potential tumor target; however, its ubiquitin E3 ligase has not been described. In this study, screening of proteins that specifically interact with XIAP identified YTHDC1 as its degradation substrate. Ectopic overexpression of XIAP promoted degradation of YTHDC1, and knockout of XIAP upregulated YTHDC1, which inhibited metastasis of bladder cancer. Furthermore, YTHDC1 reduced the expression of matrix metalloproteinase-2 (MMP-2) by destabilizing its mRNA. These experiments revealed that XIAP promotes ubiquitination of YTHDC1, positively regulating expression of the MMP-2 and promoting metastasis of bladder cancer. Collectively, these findings demonstrate that XIAP is a critical regulator of YTHDC1 and pinpoint the XIAP/YTHDC1/MMP-2 axis as a promising target for the treatment of bladder cancer.

Describe real-world epidemiology, treatment patterns, health care resource utilization, and costs of locally advanced or metastatic urothelial carcinoma (la/mUC) in France.

Retrospective study including all adults with la/mUC diagnosis during January 2017 to December 2020 in the PMSI database.

Annual prevalence and incidence ranged from 36.4 to 38.9 and 16.4 to 18.5 cases per 100,000 people, respectively. Of the 25,314 patients with incident la/mUC, 37.6% did not receive first-line systemic treatment. Of the 14,656 patients who started first-line systemic treatment, 66.6%, 22.5%, and 10.9% received 1, 2, and 3 lines of therapy, respectively. Annual per-patient costs in second-/third-line setting ranged from €8803 to €16,012.

The substantial disease burden of la/mUC in France highlights the unmet need for new therapies.

PurposeWe aimed to exploit a urine exosomal long non-coding RNAs (lncRNAs) fingerprint to facilitate the early diagnosis of bladder cancer.MethodsMicroarray differential expression profiling of lncRNAs was for the first time employed in urine exosomes from 10 non-muscle-invasive bladder cancer (NMIBC) patients and 10 healthy controls to screen out candidate exosomal lncRNA biomarkers, which were then verified by quantitative real-time polymerase chain reaction in three independent phases including bladder cancer cells, culture fluid and 200 NMIBC participants. Logistic regression was performed to construct a diagnostic model-the diagnostic potency of which was assessed.ResultsThe profile of three exosome-derived lncRNAs (CCDC148-AS1, XLOC_006419, and RP5-1148A21.3) was screened and further verified to be notably over-expressed in NMIBC patients and bladder cancer cell lines, and exhibited area under the receiver-operating characteristic curve values of 0.873, 0.825, and 0.834, respectively, in training, validation, and double-blind validation phases. The profile was superior to urinary cytology in discriminating NMIBC from healthy controls (P < 0.0001). A significant correlation existed between a higher level of CCDC148-AS1 and a higher tumor grade (P < 0.001), and up-regulated CCDC148-AS1 as well as XLOC_006419 were statistically related with tumor node metastasis stage (P = 0.004 and P = 0.031, respectively). These three identified lncRNAs were confirmed to originate from bladder cancer cells and be packaged within exosomes, thus staying sufficiently stable in urine.ConclusionsTumor-originated urine exosomal lncRNAs, as fingerprint in NMIBC, exhibited satisfying clinical significance in early diagnosis of bladder cancer.

Given the changing treatment landscape for locally advanced or metastatic urothelial carcinoma (la/mUC), this study aimed to describe real-world treatments, overall survival (OS), health care resource utilization (HCRU), and costs among US patients with la/mUC receiving first-line therapy.

This retrospective study was conducted using 100% Medicare claims data (2015-2020). Patients with la/mUC were selected; initiation of first-line therapy was the index date. Treatments and OS were assessed during follow-up (index date to the earliest of end of data availability, health plan coverage, or death). All-cause HCRU and costs (2021 USD) were assessed during the first-line treatment period (index date to the earliest of first-line discontinuation, switch to second-line therapy, end of follow-up, or death). Outpatient pharmacy costs were not included. All-cause OS from start of first-line therapy was estimated using the Kaplan-Meier approach. The HCRU, cost, and OS analyses were stratified by 3 index treatment groups-platinum-based chemotherapy, non-platinum-based chemotherapy, and programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor monotherapy-and adjusted for baseline characteristics.

Of 9,939 patients included, 77.1% were men and mean age was 76 years. In total, 5,050 (50.8%) received platinum-based chemotherapy, 1,361 (13.7%) received non-platinum-based chemotherapy, and 3,242 (32.6%) received PD-1/L1 inhibitor monotherapy for first-line la/mUC. Median OS was 12.9, 12.9 (P = 0.960), and 9.0 months (P < 0.001) with platinum-based chemotherapy (reference), non-platinum-based chemotherapy, and PD-1/L1 inhibitor monotherapy, respectively. Most (> 99%) patients had ≥ 1 outpatient visit during the treatment period; mean number of visits per patient was 13.1 with platinum-based chemotherapy, 10.5 with non-platinum-based chemotherapy, and 18.3 with PD-1/L1 inhibitor monotherapy. In general, HCRU was significantly lower for patients receiving PD-1/L1 inhibitor monotherapy versus platinum-based chemotherapy. However, costs were significantly higher with PD-1/L1 inhibitor monotherapy versus platinum-based chemotherapy. Mean total monthly cost per patient was $10,285 for platinum-based chemotherapy, $8,982 for non-platinum-based chemotherapy, and $18,147 for PD-1/L1 inhibitor monotherapy.

From 2015 to 2020, patients with la/mUC had substantial HCRU and costs and short survival, regardless of first-line treatment. More effective therapies were needed to prolong survival and reduce the economic burden of la/mUC.

Insomnia characterised by difficulties in falling asleep and maintaining sleep, and early awaking, is a prevalent worldwide sleep disorder. While previous studies have suggested an association between insomnia and adverse glycaemic control, the evidence remains inconclusive. Therefore, this meta-analysis aims to explore this association.

Insomnia was assessed based on defined criteria, including related symptoms such as poor sleep quality and low sleep efficiency. Glycaemic control was evaluated using indicators such as fasting plasma glucose, haemoglobin A1c, and the presence of diabetes. A literature search was performed in PubMed, Web of Science, and Scopus. The quality of the included studied was assessed using The Newcastle-Ottawa Scale. Effect sizes, including odds ratio, relative risk, mean difference, and standard mean difference, were chosen based on data type. Forest plots visually displayed pooled effect sizes and corresponding 95% confidence intervals, while the I2 test calculated heterogeneity. Meta-regression and subgroup analysis explored potential sources of heterogeneity. Leave-one-out sensitivity analysis assessed result robustness, and Begg's and Egger's tests evaluated publication bias.

Ninety-one articles, comprising 84 are cross-sectional studies, (five are case-control studies, and two are cohort studies) with 2 217 521 participants, were included. Ten separate meta-analyses were conducted based on variable type (binary/continuous), study design (cross-sectional, case-control, or cohort), and measurement of exposures/outcomes. All meta-analyses indicated a positive association between insomnia (related symptoms) and adverse glycaemic control. However, three meta-analyses showed significant heterogeneity, and three lacked robustness. No publication bias was detected across any of the analyses.

Insomnia is likely associated with adverse glycaemic control. As the included studies are observational, future research should prioritise diverse methodologies and robust study designs to further explore this complex relationship.

insomnia, insomnia related symptoms, glycaemic control, systematic review, meta-analysis.

PROSPERO CRD42024491688.

Bladder cancer (BC) is a malignant tumor characterized by a high incidence of urinary system diseases. The complex pathogenesis of BC has long been a focal point in medical research. With the robust development of epigenetics, the crucial role of epigenetic modifications in the occurrence and progression of BC has been elucidated. These modifications not only affect gene expression but also impact critical biological behaviors of tumor cells, including proliferation, differentiation, apoptosis, invasion, and metastasis. Notably, DNA methylation, an important epigenetic regulatory mechanism, often manifests as global hypomethylation or hypermethylation of specific gene promoter regions in BC. Alterations in this methylation pattern can lead to increased genomic instability, which profoundly influences the expression of proto-oncogenes and tumor suppressor genes. MiRNAs, as noncoding small RNAs, participate in various biological processes of BC by regulating target genes. Consequently, this work aims to explore the interaction mechanisms between DNA methylation and miRNAs in the occurrence and development of BC. Research has demonstrated that DNA methylation not only directly influences the expression of miRNA genes but also indirectly affects the maturation and functionality of miRNAs by modulating the methylation status of miRNA promoter regions. Simultaneously, miRNAs can regulate DNA methylation levels by targeting key enzymes such as DNA methyltransferases (DNMTs), thereby establishing a complex feedback regulatory network. A deeper understanding of the crosstalk mechanisms between DNA methylation and miRNAs in BC will contribute to elucidating the complexity and dynamics of epigenetic modifications in this disease, and may provide new molecular targets and strategies for the early diagnosis, treatment, and prognostic evaluation of BC.

Bladder cancer poses significant clinical challenges due to its high metastatic potential and poor prognosis, especially when it progresses to muscle-invasive stages. Here, we show that the m6A reader YTHDC1 is downregulated in muscle-invasive bladder cancer and is negatively correlated with the expression of epithelial‒mesenchymal transition genes. The functional inhibition or depletion of YTHDC1 increased the migration and invasion of urothelial cells. Integrative analysis of multimodal sequencing datasets provided detailed insights into the molecular mechanisms mediating YTHDC1-dependent phenotypes and identified SMAD6 as a key transcript involved in the invasiveness of urothelial carcinoma of the bladder. Notably, SMAD6 mRNA colocalized less with YTHDC1 in tumoral tissues than in paratumoral tissues, indicating disrupted binding during cancer progression. Our findings establish YTHDC1-dependent m6A reading as a critical epitranscriptomic mechanism regulating bladder cancer invasiveness and provide a paradigm for the epitranscriptomic deregulation of cancer-associated networks.

Plasma membrane tension-related genes (MTRGs) are known to play a crucial role in tumor progression by influencing cell migration and adhesion. However, their specific mechanisms in bladder cancer (BLCA) remain unclear.

Transcriptomic, clinical and mutation data from BLCA patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Clusters associated with MTRGs were identified by consensus unsupervised cluster analysis. The genes of different clusters were analyzed by GO and KEGG gene enrichment analysis. Differentially expressed genes (DEGs) were screened from different clusters. Consensus cluster analysis of prognostic DEGs was performed to identify gene subtypes. Patients were then randomly divided into training and validation groups, and MTRG scores were constructed by logistic minimum absolute contraction and selection operator (LASSO) and Cox regression analysis. We assessed changes in clinical outcomes and immune-related factors between different patient groups. The single-cell RNA sequencing (scRNA-seq) dataset for BLCA was collected and analyzed from the Tumor Immune Single-cell Hub (TISCH) database. Biological functions were investigated using a series of experiments including quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), wound healing, transwell, etc.

Our MTRG score is based on eight genes (HTRA1, GOLT1A, DCBLD2, UGT1A1, FOSL1, DSC2, IGFBP3 and TAC3). Higher scores were characterized by lower cancer stem cell (CSC) indices, as well as higher tumor microenvironment (TME) stromal and immune scores, suggesting that high scores were associated with poorer prognosis. In addition, some drugs such as cisplatin, paclitaxel, doxorubicin, and docetaxel exhibited lower IC50 values in the high MTRG score group. Functional experiments have demonstrated that downregulation of DCBLD2 affects tumor cell migration, but not proliferation.

Our study sheds light on the prognostic significance of MTRGs within the TME and their correlation with immune infiltration patterns, ultimately impacting patient survival in BLCA. Notably, our findings highlight DCBLD2 as a promising candidate for targeted therapeutic interventions in the clinical management of BLCA.

Bladder cancer is one of the most prevalent malignancies, and the mechanisms underlying its progression and the role of the tumor microenvironment (TME) are unclear. Recent advancements in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) enable detailed analysis of the cellular heterogeneity, gene expression, and cell-cell interactions in bladder diseases.

We conducted a comprehensive search for recent articles that have investigated bladder diseases using scRNA-seq and ST.

scRNA-seq and ST have led to significant discoveries in bladder disease research. These technologies have enabled the identification of multiple molecular subtypes within individual tumors and of the mechanisms of treatment resistance. Additionally, molecular differences based on gender have been explored, explaining the heterogeneity of the incidence and progression of bladder cancer. These findings deepen our understanding of the pathology of bladder diseases and highlight the transformative potential of scRNA-seq and ST in identifying novel biomarkers and therapeutic targets.

Integrating scRNA-seq and ST has considerably enhanced our understanding of tumor heterogeneity and the tumor microenvironment within tissues. These insights may lead to the development of personalized therapies and the improvement of patient outcomes. Several challenges, such as technical limitations and access difficulties, need to be addressed for the future clinical application of these technologies.

Diagnosis of primary and relapsed bladder carcinomas is accomplished by urethrocystoscopy, an invasive procedure, combined with urinary cytology, with limited sensitivity, resulting in a substantial burden. Thus, noninvasive biomarkers have been investigated, among which DNA methylation has shown promise. This systematic review and meta-analysis sought to assess the diagnostic accuracy of DNA methylation biomarkers reported in the literature for bladder cancer detection, pinpointing the most informative one.

The search for this systematic review and meta-analysis was conducted on PubMed, Scopus, and Cochrane Library for relevant studies published until December 31, 2022. A meta-analysis was performed using a random-effect model, to compute the pooled sensitivity and specificity of the markers. PROSPERO's registration ID for the study is CRD42023397703.

Out of the 2297 studies retrieved, 68 were included in the final analysis, despite considerable heterogeneity. These involved 12 696 participants, of whom 5557 were diagnosed with bladder cancer. Using diagnostic odds ratio (DOR) as a comparative measure, the five most promising markers (pooled sensitivity, specificity, and DOR) were SALL3 (61%, 97%, and 55.67, respectively), PENK (77%, 93%, and 47.90, respectively), ZNF154 (87%, 90%, and 45.07, respectively), VIM (82%, 90%, and 44.81, respectively), and POU4F2 (81%, 89%, and 34.89, respectively). Urinary cytology identified bladder cancer with 55% sensitivity, 92% specificity, and 14.37 DOR.

DNA methylation biomarkers disclose high accuracy for bladder cancer detection in urine. Nonetheless, validation studies in different clinical settings are scarce, hampering clinical use. The identified biomarkers should be prioritized in future validation studies.

In this meta-analysis, we include previously published studies that used urine samples of bladder cancer patients' from all around the globe. We were able to compare the diagnostic accuracy of noninvasive markers across different populations. We were able to conclude on the most promising DNA methylation markers to detect bladder cancer using urine.

The efficacy of immunotherapy is heavily influenced by T cell activity. This study aimed to examine how T cell proliferation regulators can predict the prognosis and response to immunotherapy in patients with bladder cancer (BCa).

T cell proliferation-related subtypes were determined by employing the non-negative matrix factorization (NMF) algorithm that analyzed the expression patterns of T cell proliferation regulators. Subtypes were assessed for variations in prognosis, immune infiltration, and functional behaviors. Subsequently, a risk model related to T cell proliferation was created through Cox and Lasso regression analyses in the TCGA cohort and then confirmed in two GEO cohorts and an immunotherapy cohort.

BCa patients were categorized into two subtypes (C1 and C2) according to the expression profiles of 31 T cell proliferation-related genes (TRGs) with distinct prognoses and immune landscapes. The C2 subtype had a shorter overall survival (OS), with higher levels of M2 macrophage infiltration, and the activation of cancer-related pathways than the C1 subtype. Following this, thirteen prognosis-related genes that were involved in T cell proliferation were utilized to create the prognostic signature. The model's predictive accuracy was confirmed by analyzing both internal and external datasets. Individuals in the high-risk category experienced a poorer prognosis, increased immunosuppressive factors in the tumor microenvironment, and diminished responses to immunotherapy. Additionally, the immunotherapeutic prediction efficacy of the model was further confirmed by an immunotherapy cohort (anti-PD-L1 in the IMvigor210 cohort).

Our study characterized two subtypes linked to T cell proliferation in BCa patients with distinct prognoses and tumor microenvironment (TME) patterns, providing new insights into the heterogeneity of T cell proliferation in BCa and its connection to the immune landscape. The signature has prospective clinical implications for predicting outcomes and may help physicians to select prospective responders who prioritize current immunotherapy.

Non-muscle-invasive bladder cancer (NMIBC) prognosis varies significantly due to the biological and clinical heterogeneity. High-risk stage T1-G3, comprising 15-20% of NMIBCs, involves the lamina propria and is associated with higher rates of recurrence, progression, and cancer-specific mortality. In the present study, we have evaluated the enumeration of tumour-derived extracellular vesicles (tdEVs) and circulating tumour cells (CTCs) in high-risk NMIBC patients and their correlation with survival outcomes such as time to progression (TTP), and cancer-specific survival (CSS). Eighty-three high-risk T1-G3 NMIBC patients treated between September 2010 and January 2013 were included. Blood samples were collected before a transurethral resection of the bladder (TURB) and analysed using the CellSearch® system. The presence of at least one CTC was associated with a shorter TTP and CSS. Extending follow-up to 120 months and incorporating automated tdEV evaluation using ACCEPT software demonstrated that tdEV count may additionally stratify patient risk. Combining tdEVs and CTCs improves risk stratification for NMIBC progression, suggesting that tdEVs could be valuable biomarkers for prognosis and disease monitoring. Further research is needed to confirm these findings and establish the clinical significance of tdEVs in early-stage cancers.

Bladder cancer (BC), the predominant urological malignancy in men, exhibits complex molecular underpinnings contributing to its progression. This investigation aims to elucidate the expression dynamics of calcium-binding protein 39 (CAB39) in both healthy and cancerous tissues and to explore its functional role in the epithelial-mesenchymal transition (EMT) within human bladder cancer contexts. Utilizing immunohistochemistry and quantitative reverse transcription analyses, we assessed CAB39 expression across BC specimens and cell lines. Further, we implemented wound healing, cell invasion, and CCK-8 proliferation assays in CAB39-knockdown cell lines, alongside a nude mouse xenograft model, to gauge the impact of diminished CAB39 expression on the invasive, migratory, and proliferative capacities of BC cells. Our gene set enrichment analysis probed into the repertoire of genes augmented by increased CAB39 expression in BC cells, with subsequent validation via western blotting. Our findings reveal a pronounced overexpression of CAB39 in both BC tissues and cellular models, inversely correlated with disease prognosis. Remarkably, the oncogenic trajectory of bladder cancer was mitigated upon the establishment of shRNA-mediated CAB39 knockdown in vitro and in vivo, effectively reversing the cancer's invasive and metastatic behaviors and curbing tumorigenesis in xenograft models. Hence, CAB39 emerges as a critical biomarker for bladder cancer progression, significantly implicated in facilitating EMT via the upregulation of neural cadherin (N-cadherin) and the suppression of epithelial cadherin through NF-κB signaling pathways. CU-T12-9 effectively overturned the downregulation of p65-NF-kB and N-cadherin, key elements involved in EMT and cell motility, induced by CAB39 knockdown. This study underscores CAB39's pivotal role in bladder cancer pathophysiology and its potential as a therapeutic target.

Little is known about the prospective association between autosomal mosaic chromosomal alterations (mCAs), a group of large-scale somatic mutations on autosomes, and bladder cancer. Here we utilized data from 99,877 participants who were free of physician-diagnosed cancer at baseline (2004-2008) of the China Kadoorie Biobank to estimate the associations between autosomal mCAs and bladder cancer (ICD-10: C67). A total of 2874 autosomal mCAs events among 2612 carriers (2.6%) were detected. After a median follow-up of 12.4 years, we discovered that participants with all autosomal mCAs exhibited higher risks of bladder cancer, with a multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of 2.60 (1.44, 4.70). The estimate of such association was even stronger for mosaic loss events (HR [95% CI]: 6.68 [2.92, 15.30]), while it was not significant for CN-LOH events. Both expanded (cell fraction ≥10%) and non-expanded autosomal mCAs, as well as mosaic loss, were associated with increased risks of bladder cancer. Of interest, physical activity (PA) significantly modified the associations of autosomal mCAs and mosaic loss (Pinteraction = 0.038 and 0.012, respectively) with bladder cancer. The increased risks of bladder cancer were only observed with mCAs and mosaic loss among participants with a lower level of PA (HR [95% CI]: 5.11 [2.36, 11.09] and 16.30 [6.06, 43.81]), but not among participants with a higher level of PA. Our findings suggest that peripheral leukocyte autosomal mCAs may represent a novel risk factor for bladder cancer, and PA may serve as a potential intervention target for mCAs carriers.

The poor 5-year survival rate for bladder cancers is associated with the lack of efficient diagnostic and treatment techniques. Despite cystoscopy-assisted photomedicine and external radiation being promising modalities to supplement or replace surgery, they remain invasive or fail to provide real-time navigation. Here, we report non-invasive fractionated photodynamic therapy of bladder cancer with full-course real-time near-infrared-II imaging based on engineered X-ray-activated nanotransducers that contain lanthanide-doped nanoscintillators with concurrent emissions in visible and the second near-infrared regions and conjugated photosensitizers. Following intravesical instillation in mice with carcinogen-induced autochthonous bladder tumours, tumour-homing peptide-labelled nanotransducers realize enhanced tumour regression, robust recurrence inhibition, improved survival rates, and restored immune homeostasis under X-ray irradiation with accompanied near-infrared-II imaging. On-demand fractionated photodynamic therapy with customized doses is further achieved based on quantifiable near-infrared-II imaging signal-to-background ratios. Our study presents a promising non-invasive strategy to confront the current bladder cancer dilemma from diagnosis to treatment and prognosis.

To assess CD276 expression and explore its relationship with the clinicopathological characteristics and prognosis of patients with bladder cancer.

In total, RNA-sequencing data and clinical profiles of 436 bladder cancer cases from The Cancer Genome Atlas (TCGA) were assessed using the University of California Santa Cruz Xena (UCSC) platform. We compared the CD276 levels in cancerous and adjacent normal tissues and used the R software for statistical association with the clinical stage, grade, and survival (the overall survival, disease-specific survival, and progression-free survival). A single-gene GSEA analysis on TCGA-BLCA data was performed to explore potential pathways through which CD276 might influence bladder cancer. Additionally, CD276 expression was analyzed by comparing data from 9 cancerous tissues and 3 adjacent normal tissues in the GEO dataset GSE7476. Furthermore, we analyzed 133 cancerous bladder and adjacent tissue samples from the Soochow University Hospital, collected between January 1, 2016, and September 30, 2022, to assess the CD276 protein expression using immunohistochemistry. We examined the relationship between tumor CD276 levels and clinical outcomes and prognosis of bladder cancer.

Bioinformatic analysis revealed elevated CD276 expression in tumors compared to that in adjacent tissues (p<0.05), correlating with poor survival. GSEA revealed that CD276 was significantly involved in extracellular matrix-related pathways. Immunohistochemistry confirmed CD276 overexpression in tumor tissues, with higher levels linked to advanced pathological grades and worse prognosis.

CD276 is markedly upregulated in bladder cancer and associated with severe pathological features, advanced disease, potential for metastasis, and diminished survival rates. It may promote bladder cancer development and progression by influencing extracellular matrix-related-related pathways, making it a viable diagnostic and prognostic biomarker for bladder cancer.

A rare histological variant of transitional cell urothelial carcinoma, the plasmacytoid variant, was recently included in the World Health Organization classification of urothelial tract tumors. This variant has a morphological resemblance to other tumors, which poses a diagnostic challenge for identifying this tumor and may often lead to misdiagnosis. Vigilant histopathological analysis and immunostaining are required to delineate the correct diagnosis. The plasmacytoid variant of urothelial carcinoma is an aggressive tumor with a poor prognosis, making correct diagnosis essential for early and appropriate treatment. This paper presents the case of a 46-year-old male with a plasmacytoid variant of high-grade urothelial carcinoma who underwent transurethral resection of a bladder tumor, received chemotherapy, and is currently undergoing follow-up.

Exposure to environmental pollutants and human microbiome composition are important predisposition factors for tumour development1,2. Similar to drug molecules, pollutants are typically metabolized in the body, which can change their carcinogenic potential and affect tissue distribution through altered toxicokinetics3. Although recent studies demonstrated that human-associated microorganisms can chemically convert a wide range of xenobiotics and influence the profile and tissue exposure of resulting metabolites4,5, the effect of microbial biotransformation on chemical-induced tumour development remains unclear. Here we show that the depletion of the gut microbiota affects the toxicokinetics of nitrosamines, which markedly reduces the development and severity of nitrosamine-induced urinary bladder cancer in mice6,7. We causally linked this carcinogen biotransformation to specific gut bacterial isolates in vitro and in vivo using individualized bacterial culture collections and gnotobiotic mouse models, respectively. We tested gut communities from different human donors to demonstrate that microbial carcinogen metabolism varies between individuals and we showed that this metabolic activity applies to structurally related nitrosamine carcinogens. Altogether, these results indicate that gut microbiota carcinogen metabolism may be a contributing factor for chemical-induced carcinogenesis, which could open avenues to target the microbiome for improved predisposition risk assessment and prevention of cancer.

Bladder cancer (BLCA) was recognized as a significant public health challenge due to its high incidence and mortality rates. The influence of molecular subtypes on treatment outcomes was well-acknowledged, necessitating further exploration of their characterization and application. This study was aimed at enhancing the understanding of BLCA by mapping its molecular heterogeneity and developing a robust prognostic model using single-cell and bulk RNA sequencing data. Additionally, immunological characteristics and personalized treatment strategies were investigated through the risk score.

Single-cell RNA sequencing (scRNA-seq) data from GSE135337 and bulk RNA-seq data from several sources, including GSE13507, GSE31684, GSE32894, GSE69795, and TCGA-BLCA, were utilized. Molecular subtypes, particularly the basal-squamous (Ba/Sq) subtype associated with poor prognosis, were identified. A prognostic model was constructed using LASSO and Cox regression analyses focused on genes linked with the Ba/Sq subtype. this model was validated across internal and external datasets to ensure predictive accuracy. High- and low-risk groups based on the risk score derived from TCGA-BLCA data were analyzed to examine their immune-related molecular profiles and treatment responses.

Six molecular subtypes were identified, with the Ba/Sq subtype being consistently associated with poor prognosis. The prognostic model, based on basal-squamous subtype-related genes (BSSRGs), was shown to have strong predictive performance across diverse clinical settings with AUC values at 1, 3, and 5 years indicating robust predictability in training, testing, and entire datasets. Analysis of the different risk groups revealed distinct immune infiltration and microenvironments. Generally higher tumor mutation burden (TMB) scores and lower tumor immune dysfunction and exclusion (TIDE) scores were exhibited by the low-risk group, suggesting varied potentials for systemic drug response between the groups. Finally, significant differences in potential systemic drug response rates were also observed between risk groups.

The study introduced and validated a new prognostic model for BLCA based on BSSRGs, which was proven effective in prognosis prediction. The potential for personalized therapy, optimized by patient stratification and immune profiling, was highlighted by our risk score, aiming to improve treatment efficacy. This approach was promised to offer significant advancements in managing BLCA, tailoring treatments based on detailed molecular and immunological insights.

Bladder cancer (BLCA) poses a significant global health challenge due to its high incidence, poor prognosis, and limited treatment options.

This study aims to investigate the association between two specific polymorphisms, CYP1A2-163 C/A and CYP1A2-3860G/A, within the Cytochrome P450 1A2 (CYP1A2) gene and susceptibility to BLCA.

The study employed a case-control design, genotyping 340 individuals using Polymerase Chain Reaction-High-Resolution Melting Curve (PCR-HRM). Various genetic models were applied to evaluate allele and genotype frequencies. Genetic linkage analysis was facilitated using R packages.

The study reveals a significant association with the - 163 C/A allele, particularly in the additive model. Odds ratio (OR) analysis links CYP1A2-163 C/A (rs762551) and CYP1A2-3860G/A(rs2069514) polymorphisms to BLCA susceptibility. The rs762551 C/A genotype is prevalent in 55% of BLCA cases and exhibits an OR of 2.21. The A/A genotype has an OR of 1.54. Regarding CYP1A2-3860G/A, the G/A genotype has an OR of 1.54, and the A/A genotype has an OR of 2.08. Haplotype analysis shows a predominant C-C haplotype at 38.2%, followed by a C-A haplotype at 54.7%, and a less frequent A-A haplotype at 7.1%. This study underscores associations between CYP1A2 gene variants, particularly rs762551 (CYP1A2-163 C/A), and an increased susceptibility to BLCA. Haplotype analysis of 340 individuals reveals a predominant C-C haplotype at 38.2%, followed by a C-A haplotype at 54.7%, and a less frequent A-A haplotype at 7.1%.

In conclusion, the - 163 C/A allele, C/A genotype of rs762551, and G/A genotype of rs2069514 emerge as potential genetic markers associated with elevated BLCA risk.

Patients with cancer are at an increased risk of developing a hypercoagulative phenotype and venous thromboembolism. However, no clinical trial has yet confirmed that anticoagulant therapy improves cancer prognosis, and the mechanism underlying hypercoagulation in patients with bladder cancer is not well understood.

We hypothesized that the prognostic genes affect tumor progression via tumor-mediated coagulation.

We detected the most significant prognostic genes of bladder cancer with The Cancer Genome Atlas dataset and validated them in 2 Gene Expression Omnibus datasets and 1 ArrayExpress dataset. Immunohistochemical tests were performed on a cohort of 80 individuals to further examine the prognostic genes. For the most reliable prognostic gene, its influence on coagulation was evaluated with gene knockdown followed by next-generation sequencing and cellular and animal experiments.

Depletion of microtubule interacting and trafficking domain containing 1 (MITD1), a major prognostic gene of bladder cancer, significantly increased the tissue factor (TF) expression. MITD1 deficiency led to cytokinesis arrest, which, in turn, promoted the TF expression via unfolded protein response and c-Jun. The knockdown of IRE1, an essential kinase of unfolded protein response or the inactivation of c-Jun using c-Jun N-terminal kinase inhibitors weakened MITD1 deficiency- or dithiothreitol-induced TF upregulation. Cells lacking MITD1 promoted coagulation and metastasis in the experimental metastasis assay.

Our findings suggest the novel role of tumor prognostic genes upon the development of hypercoagulative phenotype and venous thromboembolism, thereby underlining the importance of anticoagulant therapy and shedding light on the therapeutic value of targeting MITD1 in bladder cancer.

Urinary bladder cancer (BC) inflicts a significant impairment of life quality and poses a high mortality risk. Schistosoma haematobium infection can cause BC, and the urinary microbiota of BC patients differs from healthy controls. Importantly, intravesical instillation of the bacterium Bacillus Calmette-Guerin stands as the foremost therapy for non-muscle invasive BC. Hence, studying the receptors and signaling molecules orchestrating bacterial recognition and the cellular response in the context of BC is of paramount importance. Thus, we challenged Toll-like receptor 4 (Tlr4) and myeloid differentiation factor 88 (Myd88) knock-out (KO) mice with N-butyl-N-(4-hydroxylbutyl)-nitrosamine (BBN), a well-known urinary bladder carcinogen. Gut microbiota, gene expression, and urinary bladder pathology were followed. Acute exposure to BBN did not reveal a difference in bladder pathology despite differences in the animal's ability to recognize and react to bacteria. However, chronic treatment resulted in reduced cancer invasiveness among Myd88KO mice while the absence of functional Tlr4 did not influence BC development or progression. These differences correlate with a heightened abundance of the Faecalibaculum genus and the lowest microbial diversity observed among Myd88KO mice. The presented data underscore the important role of microbiota composition and MyD88-mediated signaling during bladder carcinogenesis.

Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes despite the prevalent recurrence and progression among many patients. In particular, flat urothelial carcinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new-generation photosensitizer, 5-Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes.

Chimeric antigen receptor engineered T (CAR T) cell therapy has developed rapidly in recent years, leading to profound developments in oncology, especially for hematologic malignancies. However, given the pressure of immunosuppressive tumor microenvironments, antigen escape, and diverse other factors, its application in solid tumors is less developed. Urinary system tumors are relatively common, accounting for approximately 24% of all new cancers in the United States. CAR T cells have great potential for urinary system tumors. This review summarizes the latest developments of CAR T cell therapy in urinary system tumors, including kidney cancer, bladder cancer, and prostate cancer, and also outlines the various CAR T cell generations and their pathways and targets that have been developed thus far. Finally, the current advantages, problems, and side effects of CAR T cell therapy are discussed in depth, and potential future developments are proposed in view of current shortcomings.

The objective was to evaluate the incidence and degree of double-J ureteral stent (DJUS) migration. Additionally, we aimed to investigate the risk factors associated with stent migration in the orthotopic neobladder group. In this retrospective study, 61 consecutive patients were included; 35 patients (45 DJUS placements) underwent radical cystectomy with orthotopic neobladder and 26 patients (35 DJUS placements) underwent urinary bladder without cystectomy between July 2021 and March 2023. All the patients were treated with a DJUS for ureteric strictures. The technical success rate was 100% in each group. The DJUS migration was significantly higher in the orthotopic neobladder group, with 22 of 45 cases (48.9%), compared to the urinary bladder group, which had 4 of 35 cases (11.4%) (P ≤ .001). Among the patients in the orthotopic neobladder group who experienced DJUS migration, stent dysfunction occurred in 18 cases (81.8%), which was statistically significant (P = .003). Multivariate logistic regression analysis revealed that only the size of the DJUS was significantly and positively associated with migration (odds ratio:10.214, P = .010). DJUS migration can easily occur in patients undergoing radical cystectomy and orthotopic neobladder, and smaller stent sizes are associated with a higher incidence of migration.

Bladder cancer (BC) is a common malignant tumor of urinary system, which can be divided into muscle-invasive BC (MIBC) and nonmuscle-invasive BC (NMIBC). The number of BC patients has been gradually increasing currently. At present, bladder tumours are diagnosed and followed-up using a combination of cystoscopic examination, cytology and histology. However, the detection of early grade tumors, which is much easier to treat effectively than advanced stage disease, is still insufficient. It frequently recurs and can progress when not expeditiously diagnosed and monitored following initial therapy for NMIBC. Treatment strategies are totally different for different stage diseases. Therefore, it is of great practical significance to study new biomarkers for diagnosis and prognosis. In this review, we summarize the current state of biomarker development in BC diagnosis and prognosis prediction. We retrospectively analyse eight diagnostic biomarkers and eight prognostic biomarkers, in which CK, P53, PPARγ, PTEN and ncRNA are emphasized for discussion. Eight molecular subtype systems are also identified. Clinical translation of biomarkers for diagnosis, prognosis, monitoring and treatment will hopefully improve outcomes for patients. These potential biomarkers provide an opportunity to diagnose tumors earlier and with greater accuracy, and help identify those patients most at risk of disease recurrence.

This systematic review and meta-analysis will review randomized control trials for localized bladder cancer, evaluating surgical and pathologic outcomes of ORC versus RARC.

Randomized studies evaluating adults with non-metastatic bladder cancer who underwent a radical cystectomy. Randomized trials were selected for final review. Data was extracted and analyzed with Revman 5 software. The primary outcome was complication rates within 90 days. Secondary outcomes included postoperative quality of life, estimated intraoperative blood loss, and other perioperative outcomes. Continuous variables were reported using mean difference with 95% confidence intervals, and dichotomous variables were reported using risk difference with 95% confidence intervals with RARC as the experimental group and ORC as the reference group.

Of 134 articles screened, six unique randomized studies were selected. For Grade I-II complications, the risk ratio (RR) was 0.92 (95% CI [0.79,1.08], p = 0.33), and for Grade III-V complications, RR 0.93 (95% CI [0.73,1.18], p = 0.59). RARC resulted in decreased blood loss (95% CI [-438.08, -158.44], p < 0.00001) and longer operative time (95% CI [55.23, 133.13], p < 0.00001). Quality of life using the EORTC-QLQ-30 global health score at 3 months post-op appeared to favor RARC with a mean difference of 4.46 points (95% CI [1.78, 7.15], p = 0.001). Pathologic outcomes neither statistically nor clinically favored one modality, as there was no significant difference between mean lymph node yield (p = 0.49), positive lymph nodes (p = 1.00), and positive surgical margins (p = 0.85) between the surgical modalities.

Although one surgical modality is not overtly superior, the choice may be decided by mitigating individual operative risk factors like intraoperative blood loss, operative time, post-operative quality of life, as well as institutional costs and learning curve among surgeons.

The in-depth exploration of long non-coding RNAs (lncRNAs) reveals their pivotal and diverse roles in various disorders, particularly cancer. Within this intricate landscape, thymopoietin-antisense RNA-1 (TMPO-AS1) emerges as a noteworthy instigator of oncogenesis in humans. This exhaustive review seeks to intricately unravel the present understanding of TMPO-AS1, emphasizing its molecular foundations and highlighting its clinical applications in the realm of cancer research. TMPO-AS1 consistently exhibits heightened expression across a spectrum of cancer types, encompassing lung, colorectal, breast, cervical, bladder, pancreatic, hepatocellular, gastric, ovarian, and osteosarcoma. Elevated levels of TMPO-AS1 are intricately linked to unfavorable prognoses, accompanied by distinctive clinical and pathological characteristics. Functionally, TMPO-AS1 showcases its prowess in enhancing cancer cell migration, invasion, proliferation, and orchestrating epithelial-mesenchymal transition (EMT) through a myriad of molecular mechanisms. These mechanisms entail intricate interactions with proteins, microRNAs, and intricate signaling pathways. Furthermore, TMPO-AS1 is intricately involved in regulating critical cellular processes, including apoptosis and the cell cycle. The mounting evidence converges towards the potential of TMPO-AS1 serving as a diagnostic and prognostic biomarker, further entwined with its potential role in influencing chemoresistance in cancer. This potential is underscored by its consistent associations with clinical outcomes and treatment responses. This comprehensive investigation not only consolidates our existing knowledge of TMPO-AS1's multifaceted roles but also sheds illuminating insights on its profound significance in the intricate landscape of cancer biology, paving the way for potential applications in clinical practice.