Bladder cancer (BC) is one of the most lethal genitourinary malignancies owing to its propensity for recurrence and poor survival. The biochemical pathway, signal transducer and activator of transcription 3 (STAT3), has gained significance as a molecular pathway that promotes proliferation, invasion, and chemoresistance. In this study, we explored the targeting of STAT3 with TTI-101 and SH5-07 in bladder cancer (BCa) and elucidated the mechanisms in three-dimensional (3D) spheroid and tumoroid models. We optimized the growth of spheroids from human, rat, and mouse BCa cell lines (J82, NBT-II, and MB49, respectively), and tumoroids from BBN (N-butyl-N-(4-hydroxybutyl)-nitrosamine) induced rat bladder tumors. Cell viability was assessed using MTT and trypan blue assays. ATP production, ROS production, and calcium AM (CA)/EtBr staining were used to measure the spheroid and organoid inhibition and mitochondrial function. Western blot analysis was performed to evaluate the pharmacodynamic markers involved in cell proliferation, apoptosis, cancer stem cells (CSCs), and STAT3 signaling in BCa. We found that targeting STAT3 (using TTI-101 and SH5-07) significantly reduced the proliferation of BCa spheroids, and tumoroids, which was accompanied by decreased expression of pSTAT3, Cyclin D1, and PCNA. Our data also demonstrated that treatment with STAT3 inhibitors induced ROS production and cell death in BCa spheroids and organoids. STAT3 inhibition induced cell death was associated with the activation of caspase 3/7 and PARP cleavage. Moreover, TTI-101 and SH5-07 targets cancer stem cells by downregulating the expression of CD44 and CD133 in 3D models. This study provides the first evidence for the prevention of bladder cancer with small-molecule inhibitors TTI101 and SH5-07 via suppression of CSCs and STAT3 signaling.

Chemoradiation-based bladder preservation therapy (BPT) is currently a curative option for non-metastatic muscle-invasive bladder cancer (MIBC) patients at favorable risk or an alternative to radical cystectomy (RC) for those who are unfit for RC. In BPT, only patients who achieve complete response (CR) after chemoradiation have favorable prognosis and quality of life with preserved functional bladder. Thus, predicting CR and favorable prognosis is important for optimal patient selection for BPT. We reviewed biomarkers for predicting clinical outcomes of chemoradiation-based BPT. Biomarkers studied were categorized into those related to apoptosis, cell proliferation, receptor tyrosine kinases, DNA damage response genes, hypoxia, molecular subtype, and others. Among these biomarkers, Ki-67 labeling index (Ki-67 LI) and meiotic recombination 11 may be used for selecting BPT or RC. Ki-67 LI and erythroblastic leukemia viral oncogene homolog 2 (erbB2) may be used for predicting both chemoradiation response and prognosis of patients on BPT. Concurrent use of trastuzumab and a combination of carbogen and nicotinamide can overcome chemoradiation resistance conferred by erbB2 overexpression and tumor hypoxia. Further studies are needed to confirm the practical utility of these biomarkers for progress on biomarker-directed personalized management of MIBC patients.

Human urinary bladder cancer has similar development that invasive urothelial cancer that happens spontaneously in dogs. Then, research of these malignant tumors associated with the advances of new treatment drive to the specific fight of the urothelial tumor cell, is highly valuably related to efficiency and reduction of side effects of treatments, even extrapolating to humans. Thus, a review of the most important aspects on new advances on canine bladder cancer was achieved. Many forms of therapies are being reported; one of them, of highly promising feature is the treatment with immunomodulators. The resemblance between spontaneous urothelial cancer in canines and urinary bladder cancer in humans makes this canine tumor relevant animal model to research and advances of treatment that may be more efficient in management of tumor with less unfavorable effects. Immunomodulators exhibit important outcomes when used in the therapy of bladder cancer in dogs. Nanomaterials that are possible carriers of some kinds of drugs to the target tumor significantly raise the efficiently of the therapy. Therefore, the advancement of immunomodulator combined with nanoparticles can disrupt the therapy of bladder cancer in dogs and thereafter in humans.

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute - Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and ran exome sequencing. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade.

The overwhelming majority of bladder cancers are transitional cell carcinomas. Albeit mostly monotonous, carcinomas in the bladder may occasionally display a broad spectrum of histological features that should be recognized by pathologists because some of them represent a diagnostic problem and/or lead prognostic implications. Sometimes these features are focal in the context of conventional transitional cell carcinomas, but some others are generalized across the tumor making its recognition a challenge. For practical purposes, the review distributes the morphologic spectrum of changes in architectural and cytological. So, nested and large nested, micropapillary, myxoid stroma, small tubules and adenoma nephrogenic-like, microcystic, verrucous, and diffuse lymphoepithelioma-like, on one hand, and plasmacytoid, signet ring, basaloid-squamous, yolk-sac, trophoblastic, rhabdoid, lipid/lipoblastic, giant, clear, eosinophilic (oncocytoid), and sarcomatoid, on the other, are revisited. Key histological and immunohistochemical features useful in the differential diagnosis are mentioned. In selected cases, molecular data associated with the diagnosis, prognosis, and/or treatment are also included.

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 car-cinoma 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.

Epigenetic alterations are known contributors to cancer development and aggressiveness. Additional to alterations in cancer cells, aberrant epigenetic marks are present in cells of the tumor microenvironment, including lymphocytes and tumor-associated macrophages, which are often overlooked but known to be a contributing factor to a favorable environment for tumor growth. Therefore, the main aim of this review is to give an overview of the epigenetic alterations affecting immune cells in the tumor microenvironment to provoke an immunosuppressive function and contribute to cancer development. Moreover, immunotherapy is briefly discussed in the context of epigenetics, describing both its combination with epigenetic drugs and the need for epigenetic biomarkers to predict response to immune checkpoint blockage. Combining both topics, epigenetic machinery plays a central role in generating an immunosuppressive environment for cancer growth, which creates a barrier for immunotherapy to be successful. Furthermore, epigenetic-directed compounds may not only affect cancer cells but also immune cells in the tumor microenvironment, which could be beneficial for the clinical response to immunotherapy. Thus, modulating epigenetics in combination with immunotherapy might be a promising therapeutic option to improve the success of this therapy. Further studies are necessary to (1) understand in-depth the impact of the epigenetic machinery in the tumor microenvironment; (2) how the epigenetic machinery can be modulated according to tumor type to increase response to immunotherapy and (3) find reliable biomarkers for a better selection of patients eligible to immunotherapy.

Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates patient frailty and impaired physical function. Sarcopenia can be caused by multiple factors, including advanced age, lack of exercise, poor nutritional status, inflammatory diseases, endocrine diseases, and malignancies. Recently, growing evidence has indicated the importance of sarcopenia in the management of patients with various cancers. Sarcopenia is associated with not only higher rates of treatment-related complications but also worse prognosis in cancer-bearing patients. In this article, we conducted a systematic literature review regarding the significance of sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent studies focusing on the prognostic role of changes in skeletal muscle mass during the course of treatment in bladder cancer patients.

Patients with pT1 high-grade (HG) bladder cancer (BC) and a very high risk of progression might benefit from immediate radical cystectomy (RC), but this option remains controversial. Validation of a standardized method to evaluate the extent of lamina propria (LP) invasion (with recognized prognostic value) in transurethral resections (TURBT) specimens is still needed. The Rete Oncologica Lombarda (ROL) system showed a high predictive value for progression after TURBT in recent retrospective studies. Our aim was to validate ROL system on a large mono-institutional prospective series of primary urothelial carcinomas. From 2016 to 2020, we adopted ROL for all patients with pT1 HG BC on TURBT. We employed a 1.0-mm threshold to stratify tumors in ROL1 and ROL2. A total of 222 pT1HGBC were analyzed. Median age was 74 years, with male predominance (73.8%). ROL was feasible in all cases: 91 cases were ROL1 (41%) and 131 ROL2 (59%). At a median follow up of 26.9 months (IQR 13.8-40.6), we registered 80 recurrences and 40 progressions. ROL was a significant predictor of tumor progression at both univariable (HR 3.53; CI 95% 1.56 – 7.99; p<0.01) and multivariable (HR 2.90; CI 95% 1.25 – 6.75; p=0.01) Cox regression analyses. At Kaplan-Meier estimates, ROL showed correlation with both PFS (p=0.0012) and RFS (p=0.0167). Our results confirmed the strong predictive value of ROL for progression on a large prospective series. We encourage the application of ROL for reporting the extent of LP invasion, substaging T1 HG BC, and improving risk tables for urological decision making.

(1) Background: Intravesical Chemotherapy is standard of care in intermediate risk non-muscle-invasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost and practice patterns. Epirubicin (EPI), one of these agents is used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability is still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: A systematic search of PUBMED, Webofscience, clinicaltrials.gov, and Google Scholar databases was performed on December 31, 2023. We reviewed 28 studies that included patients treated EPI after TURBT (transurethral resection of bladder tumors) for NMIBC and who compared oncological outcomes such as recurrence and progression to other adjuvant treatment such as Mitomycin C (MMC), Gemcitabine (GEM) and BCG. Further, we looked at the safety profile of EPI at room temperature under hyperthermia intravesically and at the oncological outcomes when administrated with hyperthermia; (3) Results: When compared to other chemotherapeutics (MMC/GEM), EPI seemed to be equally effective; however, EPI seems less effective in preventing disease management recurrence compared to BCG intravesical. The most common adverse events of EPI include cystitis, dysuria, and pollakiuria. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are promising newcomers.

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying non-invasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small non-coding RNA such as microRNA and transfer RNA-derived fragments (tRF). Here we performed small-RNA next-generation sequencing for urine EVs, serum EVs and serum supernatant from 41 patients with non-muscle invasive BC (27 stage Ta, 14 stage T1) and 15 non-cancer patients (NCP) with benign cystoscopy findings. Serum and urine samples were collected before transurethral resection of bladder tumors (TUR-b) and at routine postsurgery check-ups. Expression levels of tRFs in presurgery samples were compared to those at postsurgery check-ups and to NCPs. To strengthen the reliability of our results, samples from 10 patients with stage T1 disease were resequenced. When comparing tRF expression in urine EVs between BC patients with stage T1 disease and NCPs, 14 differentially expressed tRFs (DEtRFs) were identified. In serum supernatant, six DEtRFs were identified among stage T1 patients when comparing presurgery to postsurgery samples, and four DEtRFs were found when comparing presurgery samples to NCPs. By performing a blast search, we found that sequences of DEtRFs aligned with genomic sequences pertaining to processes relevant to cancer development, such as enhancers, regulatory elements and CpG islands. Our findings display a number of tRFs that may hold potential as biomarkers for the diagnosis and recurrence-free survival of BC.

Urinary bladder cancer (UBC) is the most common malignancy of the urinary tract in humans, with an estimated global prevalence of 1.1 million cases over 5 years¹. Due to high rates of recurrence and resistance to chemotherapy, UBC is one of the most expensive cancers to treat, resulting in significant health care costs. There is, therefore, a critical need to develop innovative molecular and cellular tools to refine patient stratification and help predict response to treatment. Urine is an underused resource of biological components shed from bladder tumors, such as exfoliated cells and extracellular vesicles, that could serve as molecular fingerprints and provide valuable biological insights into tumor phenotype and mechanisms of resistance to chemotherapy. Additionally, characterization of urine-derived extracellular vesicles and cells could be used as reliable biomarkers for prediction of response to neoadjuvant therapy.

Background: Ubiquitination is an important post-transcriptional modification crucial for maintaining cell homeostasis. As a deubiquitination enzyme, ubiquitin-specific protease 1 (USP1) is associated with tumor progression; however, its role in bladder cancer is unknown. This study was aimed to analyze USP1 expression and study its roles in bladder cancer. Methods: The web server GEPIA was used to analyze the USP1 expression. To explore USP1 function in bladder cancer, we constructed USP1-knockout cell lines in UMUC3 cells. A FLAG-USP1 (WT USP1) plasmid and a plasmid FLAG-USP1 C90S (catalytic-inactive mutant) used to overexpress USP1 in T24 cells. CCK8, colony formation, and transwell assays were used to assess cell viability, proliferation and migration. RNA sequencing (RNA-seq) and dual-luciferase reporter assays were performed to screen the pathway. Coimmunoprecipitation and immunofluorescence were used to explore the interaction between USP1 and c-MYC. Xenograft mouse model was used to study the role of USP1 in bladder cancer. Results: USP1 expression is upregulated in human bladder cancer cells and correlated with poor patient prognosis. USP1 overexpression promoted cell proliferation, clone formation, and migration; this was attenuated by genetic ablation of USP1. Furthermore, we observed that USP1- deficiency inhibited tumor formation in vivo. Mechanistically, the c-MYC pathway was remarkably activated compared with the other pathways. Furthermore, USP1 could directly interact with c-MYC. and increase c-MYC stability depending on the catalytic activity of USP1. Conclusions: Our results suggest that high expression of USP1 promotes bladder cancer progression by stabilizing c-MYC; hence, USP1 it may serve as a novel therapeutic target for treating bladder cancer.

Bladder cancer (BLCA) is the sixth most common type of cancer and has a dismal prognosis if diagnosed late. To identify treatment options for BLCA, we systematically evaluated data from the Broad Institute DepMap project. We found that urothelial BLCA cell lines are among the most sensitive to microtubule assembly inhibition by paclitaxel treatment. Strikingly, we unveiled that the top dependencies in BLCA cell lines include genes encoding proteins involved in microtubule assembly, thus highlighting the importance of microtubule network dynamics as a major vulnerability in human BLCA. In cancers, such as ovarian and breast, where paclitaxel is the golden standard of care, resistance to paclitaxel treatment has been linked to p53-inactivating mutations. To study the response of BLCA to microtubule assembly inhibition and its mechanistic link with the mutational status of p53 protein, we treated a collection of BLCA cell lines with a dose range of paclitaxel and performed a detailed characterization of the response. We herein discovered that BLCA cell lines are significantly sensitive to low concentrations of paclitaxel, independently of their p53 status. Paclitaxel induced a G2/M cell cycle arrest and growth inhibition, followed by robust activation of apoptosis. Most importantly, we revealed that paclitaxel triggered a robust DNA-damage response and apoptosis program without activating the p53 pathway. Integration of transcriptomics, epigenetic and dependency data demonstrated that the response of BLCA to paclitaxel is independent of p53 mutational signatures, but strongly depends on the expression of DNA-repair genes. Our work highlights urothelial BLCA as an exceptional candidate for paclitaxel treatment and paves the way for the rational use of a combination of paclitaxel and DNA-repair inhibitors as an effective, novel therapeutic strategy.

The purpose of this review is to present the current knowledge about the diagnostic and treatment options in bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). In this review compaction of CT and MRI performance in preoperative prediction of lymph node invasion (LNI) in BCa patients was presented, along with other diagnostic methods. Most scientific societies do not distinguish cN+ patients in their guidelines, recommendations concern muscle-invasive bladder cancer (MIBC) and differ between associations. Currently, the standard treatment of patients with MIBC is radical cystectomy (RC) with bilateral pelvic lymph node dis-section (PLND). The template of PLND and its therapeutic value remain debatable. Moreover, most guidelines recommend neoadjuvant chemotherapy (NAC). However, there is still lack of definitive evidence of the superiority of neoadjuvant chemotherapy over adjuvant chemotherapy. Nevertheless, the curative treatment that provides the best long-term survival in cN+ patients is a multimodal approach with a combination of chemotherapy and RC. Recent studies demonstrate the growing importance of immunotherapy. Special attention should be paid to cN+ BCa patients as the oncological outcomes are significantly worse for this group.

Background: Glutathione and its related enzymes constitute one of the most important antioxidant defense mechanisms against oxidative stress and cancer formation in the body. Bladder cancer is the second most common urological malignancy after prostate cancer. Oxidative stress plays a significant role in the development and prognosis of bladder cancer. The aim of this study was to examine the effect of glutathione on the prognosis of non-muscle-invasive bladder cancer. Methods: The 98 patients with bladder tumors were those with T1G3 pathology who had undergone intravesical Bacillus Calmette-Guérin therapy, while the 30 controls were healthy individuals with no history of transitional cell carcinoma of the bladder. The 128 participants were divided into four groups: Group 1 comprised 41 patients who did not experience recurrence during follow-up, Group 2 included 28 patients who had recurrent tumors, Group 3 consisted of 29 patients who progressed to muscle-invasive stages, and Group 4 was composed of 30 healthy volunteers. Blood samples were collected from all participants. Glutathione levels were measured, and statistical analysis were performed. Results: There was a statistically significant difference in reduced glutathione levels among the groups (p < 0.001), attributed to Group 4 exhibiting higher reduced glutathione levels compared to Groups 1, 2, and 3 (p < 0.001). No significant differences were observed in reduced glutathione levels between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 (p > 0.999). Total glutathione levels varied significantly among the groups (p < 0.001), with Group 4 having higher levels than Groups 1, 2, and 3 (p < 0.001). However, there were no significant differences between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 in terms of total glutathione levels (p = 0.473, p = 0.747, and p > 0.999, respectively). Regarding oxidized glutathione levels, a significant difference was observed (p < 0.001), with Group 4 showing lower levels than the remaining three groups (p < 0.001). No significant differences were found between Groups 1 and 2, Groups 1 and 3, or Groups 2 and 3 in relation to oxidized glutathione levels (p > 0.999, p = 0.171, and p > 0.999, respectively). Conclusions: The current study revealed that glutathione is a factor influencing the development of new bladder cancer but did not affect its prognosis. Nevertheless, we recommend that future studies with larger bladder cancer patient cohorts should be conducted to comprehensively determine the effect of glutathione on the prognosis of bladder cancer.

Men are more likely to develop cancer than women. In fact, male predominance is one of the most consistent cancer epidemiology findings. Additionally, men have a poorer prognosis and an increased risk of secondary malignancies compared to women. These differences have been investigated in order to better understand cancer and to better treat both men and women. In this review, we discuss factors that may cause this gender difference, focusing on urothelial bladder cancer (UBC) pathogenesis. We consider physiological factors that may cause higher male cancer rates, including differences in X chromosome gene expression. We discuss how androgens may promote bladder cancer development directly by stimulating bladder urothelium and indirectly by suppressing immunity. We are particularly interested in natural killer (NK) cells because they are important, but often overlooked anti-cancer lymphocytes.

Bacillus Calmette-Guérin (BCG) immunotherapy has been a cornerstone treatment for non-muscle invasive bladder cancer for decades and still faces challenges, such as severe immune adverse reactions, which reduce its use as a first-line treatment. This review examines BCG therapy’s history, mechanisms, and current status, highlighting how nanotechnology and bioengineering are revitalizing its application. We discuss novel nanocarrier systems aimed at enhancing BCG's efficacy while mitigating specific side effects. These approaches promise improved tumor targeting, better drug loading, and enhanced stimulation of anti-tumor immune responses. Key strategies involve using functional BCG cell wall components and co-delivering BCG with chemotherapeutics to achieve synergistic effects. While most studies remain experimental, this research direction offers hope for overcoming BCG's limitations and advancing bladder cancer immunotherapy. Further elucidation of BCG's mechanisms and rigorous safety evaluations of new delivery systems will be crucial for translating these innovations into clinical practice.

Cyclin E2, a member of the cyclin family, is a key cell cycle-related protein. This protein plays essential roles in cancer progression, and as such, an inhibitor of cyclin E2 has been approved to treat several types of cancers. Even so, mechanisms underlying how to regulate cyclin E2 expression in cancer remain largely unknown. The current study found that miR-3687 is up-regulated in clinical bladder cancer (BC) tumor tissues, TCGA database and human BC cell lines. Inhibition of miR-3687 expression significantly reduces human BC cell proliferation in vitro and tumor growth in vivo, which are concurrently with the induction of G0/G1 cell cycle arrest and downregulation of cyclin E2 protein expression. Interestingly, overexpression of cyclin E2 reversed the inhibition of BC proliferation induced by miR-3687. Mechanistic studies suggest that miR-3687 could bind to the 3'-UTR of foxp1 mRNA, downregulates FOXP1 protein expression, and in turn promotes the transcription of cyclin E2, thereby promoting the growth of BC cells. Collectively, the current study not only establishes a novel regulatory axis of miR-3687/FOXP1 in regard to regulation of cyclin E2 expression in BC cells, but also provides strong suggestive evidence that miR-3687 and FOXP1 may be potentially promising targets in therapeutic strategies of human BC.

Carboxypeptidase A4 (CPA4) has shown the potential possibility as a biomarker in the early diagnosis for certain cancers. However, no previous research has linked CPA4 to therapeutic or prognostic significance in bladder cancer. Using data from The Cancer Genome Atlas (TCGA) database, we set out to determine the full extent of the link between CPA4 and BLCA. We further analyzed the interacting proteins of CPA4 and infiltrated immune cells via TIMER2，STRING and GEPIA2 databases. The expression of CPA4 in tumor and normal tissues was compared using the TCGA+GETx database. The connection between CPA44 expression and clinicopathologic characteristics and overall survival (OS) was investigated using multivariate methods and Kaplan-Meier survival curves. The potential functions and pathways were investigated via gene set enrichment analysis. Furthermore, we analyze the associations between CPA4 expression and infiltrated immune cells with their respective gene marker sets using the ssGSEA, TIMER2, and GEPIA2 databases. Compared to matching normal tissues, human CPA4 was found to be substantially expressed. We confirmed that overexpression of CPA4 is linked with shorter OS, DSF, PFI, and increased diagnostic potential using Kaplan-Meier and ROC analysis. The expression of CPA4 is related to T-bet, IL12RB2, CTLA4, and LAG3, among which T-bet and IL12RB2 are Th1 marker genes, while CTLA4 and LAG3 are related to T cell exhaustion, which may be used to guide the application of checkpoint blockade and the adoption of T cell transfer therapy.

Abstract Background: Small Cajal body-specific RNAs (scaRNAs) are a specific subset of small nucleolar RNAs (snoRNAs) that have recently been emerged as pivotal contributors in diverse physiological and pathological processes. However, their defined roles in carcinogenesis remain largely elusive. This study aims to explore the potential function and mechanism of SCARNA12 in bladder cancer (BLCA) and to provide a theoretical basis for further investigations into the biological functionalities of scaRNAs. Materials and Methods: TCGA, GEO and GTEx data sets were used to analyze the expression of SCARNA12 and its clinicopathological significance in BLCA. Quantitative real-time PCR (qPCR) and in situ hybridization were applied to validate the expression of SCARNA12 in both BLCA cell lines and tissues. RNA sequencing (RNA-seq) combined with bioinformatics analyses were conducted to reveal the changes of gene expression patterns and functional pathways in BLCA patients with different expression of SCARNA12 and T24 cell lines upon SCARNA12 knockdown. Single-cell mass cytometry (CyTOF) was then used to evaluate the tumor-related cell cluster affected by SCARNA12. Moreover, SCARNA12 was stably knocked down in T24 and UMUC3 cell lines by lentivirus-mediated CRISPR/Cas9 approach. The biological effects of SCARNA12 on the proliferation, clonogenic, migration, invasion, cell apoptosis, cell cycle and tumor growth were assessed by in vitro MTT, colony formation, wound healing, transwell, flow cytometry assays and in vivo nude mice xenograft models, respectively. Finally, chromatin isolation by RNA purification (ChIRP) experiment were further conducted to delineate the potential mechanisms of SCARNA12 in BLCA. Results: The expression of SCARNA12 was significantly up-regulated in both BLCA tissues and cell lines. RNA-seq data elucidated that SCARAN12 may play a potential role in cell adhesion and extracellular matrix (ECM) related signaling pathways. CyTOF results further showed that an ECM-related cell cluster with vimentin+, CD13+, CD44+, CD47+ was enriched in BLCA patients with high SCARNA12 expression. Additionally, SCARNA12 knockdown significantly inhibited the proliferation, colony formation, migration, and invasion abilities in T24 and UMUC3 cell lines. SCARNA12 knockdown prompted cell arrest in the G0/G1 and G2/M phase, and promoted the apoptosis in T24 and UMUC3 cell lines. Furthermore, SCARNA12 knockdown could suppress the in vivo tumor growth in nude mice. ChIRP experiment further suggested that SCARNA12 may combine transcription factors H2AFZ to modulate transcription program and then affect BLCA progression. Conclusion: Our study is the first to propose aberrant alteration of SCARNA12 and elucidate its potential oncogenic roles in BLCA via the modulation of ECM signaling. The interaction of SCARNA12 with the transcriptional factor H2AFZ emerges as a key contributor to the carcinogenesis and progression of BLCA. These findings suggest SCARNA12 may serve as a diagnostic biomarker and potential therapeutic target for the treatment of BLCA.

Background: Bladder cancer (BC) development is highly related to immune cell infiltration and inflammation. This study aimed to construct a new classification of bladder cancer (BC) molecular subtypes based on immune cells-associated CpG sites. Methods: The genes of 28 types of immune cells were obtained from previous studies. Then methylation sites corresponding to immune cells-associated genes were acquired. Differentially methylation sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylation sites was performed to divide into several subtypes. Then the potential mechanism of different subtypes was exploded. Result: Bladder cancer patients were divided into three groups. Cluster 3 (methylation-L) subtype had the best prognosis. Cluster 1 (methylation-M) had the worst prognosis. The distribution of immune cells, level expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC_co_inhibition, APC_co_stimulation, HLA, MHC_class_I, Type_I_IFN_Reponse, and Type_II_IFN_Reponse were significant difference among three subgroups. The distribution of genomic alterations was different among them. Conclusion: The classification was accurate and stable. BC patients could be divided into three subtypes based on the immune cells-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were various among three subgroups. High level immune infiltration was a correlation with high level methylation. The lower RNAss score was associated with higher immune infiltration and higher level expression of CD274.

The aim of this study was to evaluate the usefulness of cystoscopic injection of Botulinum-A toxin (BTX) in the detrusor wall in the treatment of children with decreased bladder capacity due to neurogenic bladder. The prospective, randomized non placebo controlled trial is conducted in our institution since year 2006 with the approval of the local Ethics Committee. 556 cystoscopic injections of BTX were performed in 141 children with neurogenic bladder in age 1 to 18 years. In all cases decreased bladder capacity and bladder overactivity with urine incontinence were estimated. The pre-and post-treatment evaluations included determination of urinary continence status, bladder function in frequency/volume chart of catheterized urine and in urodynamic studies. Parameters measured in urodynamic investigations included maximal cystometric capacity, detrusor reflex volume, maximal detrusor pressure. Parameters were analyzed before the cystoscopy and during the follow-up examinations in 5 age groups. Values of all measured parameters improved significantly and equally after therapy in every from 5 age groups. The results obtained from the study confirmed that endoscopic administration of BTX improves function of urinary bladder in children with neurogenic bladder, and the method represents an alternative approach to conservative treatment and surgical augmentation.

Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle invasive bladder cancer (NMIBC) faces limitations in efficacy and significant side effects, aggravated by a recent global shortage. In this prospective clinical study, we report outcomes of sequential intravesical adminis-tration of gemcitabine and docetaxel (Gem/Doce) as the first-line treatment in BCG-naïve patients with high-risk NMIBC (HR NMIBC). From October 2019 until April 2022, we enrolled 52 patients and followed treatment protocol set by the University of Iowa. Follow-up assessments were con-ducted every 3 months. In this cohort, 25 (48.1%) patients were diagnosed with T1HG bladder cancer, 10 (19.2%) patients had carcinoma in situ (CIS), and 17 (32.7%) patients had a combination of CIS+T1HG. Median time to first recurrence in T1HG, CIS and T1HG+CIS groups was 11, 10.5 and 8.8 months, respectively. The recurrence-free survival was 98.1%, 94.2% and 80.8% at 6, 9 and 12 months, respectively. The rate of progression-free survival was 100%, 98.1% and 92.3% at 6, 9 and 12 months, respectively. We demonstrated the safety and efficacy of Gem/Doce therapy in BCG-naïve patients with HR NMIBC during a one-year follow-up. Further research with extended follow-up, as well as direct comparison of Gem/Doce and other anticancer agents, are essential.

Spondyloptosis is a condition where there is complete dislocation of L5 over sacrum. It is a form of spinal dislocation in which one spinal segment is lodged in the anterior or posterior space of another or advanced spondylolisthesis [1]. Treatment is usually spinal fusion depending on the level of lesion [2]. This clinical case is of a 15 year old male with a history of fall from auto-rickshaw followed by a blunt trauma from a heavy iron rod falling over his abdomen. There was no history of loss of consciousness, but the patient had an excruciating pain over back immediately after the incident. Patient is now paraplegic with loss of sensation below L5 along with loss bladder and bowel control since the time of injury. The T1 weighted MRI of spine revealed grade 5 anterior lysthesis of L5 over S1 level with complete spinal cord transaction. The patient was operated to restore the vertebral alignment with pedicle screws and rods. After 3 months, patient is now treated for neuro-musculoskeletal , genitourinary and genitointestinal function with biofeedback, pelvic floor exercises and timed voiding [3]. When a patient has issues with urine retention, Valsalva manoeuvres, Crede's method, suprapubic tapping, and anal stretching are employed to help them void more effortlessly [4].

Background: a 17 years-old girl with a Mitrofanoff appendicovesicostomy developed a large bladder clot due to hematuria after a surgical cystolithotomy in an augmented bladder. Trans-urethral approaches were not feasible due to a previous surgical closure of the bladder neck. Methods: after an unsuccessful trans-appendicovesicostomy bladder washing, the endoscopic evaluation was performed using a 14 Ch rigid cystoscope, surrounded by its own urethral sheath. The clot was progressively fragmented through the cystoscope and a urethral catheter under direct vision. Clot fragments were aspirated obtaining a complete evacuation; Results: the urethral sheath prevented damages to the appendicovesicostomy, allowing at the same time repeated accesses of the cystoscope into the neobladder and ensuring the success of the procedure; Conclusions: the use of urethral sheath 14 Ch though an appendicovesicostomy preserves both the stoma and the channel, making possible endoscopic procedures as blood clot evacuation into the neobladder.

Sinulariolide, a natural product extracted from cultured-type soft coral Sinularia flexibilis, possesses bioactivity against the movement of several types of cancer cell. However, the molecular pathway of its effects on human bladder cancer remain poorly understood. Using a human bladder cancer cell line as an in vitro model, this study investigated the underlying mechanism of sinulariolide against cell migration/invasion in TSGH-8301 cells. We found that sinulariolide inhibited TSGH-8301 cell migration/invasion, and the effect was concentration-dependent. Furthermore, the protein expressions of matrix metalloproteinases (MMPs) MMP-2 and MMP-9, as well as urokinase, were significantly decreased after 24-h sinulariolide treatment. Meanwhile, the increased expressions of tissue inhibitors of metalloproteinases (TIMPs) TIMP-1 and TIMP-2 were in parallel with an increased concentration of sinulariolide. Finally, the expressions of several key phosphorylated proteins in the mTOR signaling pathway were also downregulated by sinulariolide treatment. Our results demonstrated that sinulariolide has significant effects against TSGH-8301 cell migration/invasion, and its effects were associated with decreased levels of MMP-2/-9 and urokinase expression, as well as increased TIMP-1/TIMP-2 expression. The inhibitory effects were mediated by reducing phosphorylation proteins of the PI3K, AKT and mTOR signaling pathway. The findings suggested that sinulariolide is a good candidate for advanced investigation with the aim of developing a new drug for the treatment of human bladder cancer.

Human papillomavirus (HPV) infections, primarily transmitted through sexual contact, have been linked to various cancers, including cervical, penile, anal, oropharynx, breast, and prostate cancers. This study presents a unique case of concurrent high-risk HPV35, HPV45, and HPV59 infections in both prostate and bladder cancer tissues from a single patient, representing the first documented instance worldwide with identical HPV types detected in two adjacent organs of the same individual. Employing a multiplex-PCR approach, gel electrophoresis, and Sanger sequencing, we confirmed the presence of these high-risk HPV types. Additionally, Western blot analysis using an HPV E7 antibody demonstrated the active expression of HPV oncoproteins in both cancer types. This discovery underscores the potential for HPV intra-organ transmission and necessitates further exploration of alternative transmission routes. The implications of our results offer new insights into the complex dynamics of HPV transmission in cancer pathogenesis.

Treatment of bladder cancer remains a critical unmet need and requires advanced approaches, particularly the development of local drug delivery systems. The physiology of the urinary bladder causes the main difficulties in the local treatment of bladder cancer: regular voiding prevents the maintenance of optimal concentration of the instilled drugs, while poor permeability of the urothelium limits the penetration of the drugs into the bladder wall. Therefore, much research effort is spent to overcome these hurdles, thereby improving the efficacy of available therapies. The explosive development of nanotechnology, polymer science and related fields has contributed to the emergence of a number of nanostructured vehicles (nano- and micro scale) applicable for intravesical drug delivery. Moreover, the engineering approach has facilitated the design of several macro-sized depot systems (centimeter scale) capable of remaining in the bladder for weeks and months. In this article, the main rationales and strategies for improved intravesical delivery are reviewed. Here, we focused on analysis of colloidal nano- and micro-sized drug carriers, and indwelling macro-scale devices which were evaluated for applicability in local therapy of bladder cancer in vivo.

The article aims to find potential biomarker for the detection of tubular damage in pediatric neurogenic bladder (NB) by investigating urinary levels of liver-type fatty acid-binding protein (uL-FABP). This prospective analysis was conducted on two groups: 42 children with NB and 18 healthy children. The uL-FABP concentrations were measured using ELISA methods. The children’s medical charts were analyzed to determine age, sex, anthropometric measurements, activity assessment using Hoffer’s scale and renal function parameters. The results revealed that the uL-FABP/creatinine ratio was higher in the studied group compared with the reference group. A significant positive correlation between uL-FABP and proteinuria was found. Children with a history of vesicoureteral reflux (VUR) tended to have elevated uL-FABP. In conclusion, uL-FABP may be considered a potential tubular damage biomarker in children with NB. Proteinuria and history of VUR may be the factors influencing uL-FABP.

Background. TRPA1-related drugs alter sensation, particularly in conditions of inflammation. To further characterize the role of these drugs in bladder sensation, the TRPA1 agonist cinnamaldehyde (CMA) and oral true cinnamon spice were examined in preclinical models of bladder pain. Methods. Female, adult rats with and without acute zymosan-induced cystitis, were anesthetized and visceromotor (VMR) and cystometric responses to urinary bladder distension (UBD) determined following either the intravesical administration of CMA/vehicle solutions or the oral administration of true cinnamon/vehicle. ELISA measures of bladder TRPA1 content were also determined. Results. Acute cystitis resulted in increases in bladder TRPA1 content and produced an increased vigor of the VMRs to UBD and a lowering of micturition volume thresholds for activation of a micturition response. Intravesical CMA produced a robust inhibition of VMRs to UBD in rats with cystitis, but not in those without. Micturition volume thresholds were lowered by CMA in rats without cystitis, but had no additional effect in rats with cystitis. Oral cinnamon also produced a robust inhibition of VMRs to UBD in rats with cystitis and a mild augmentation of VMRs to UBD in rats without cystitis. Conclusions. A potentially analgesic effect of the spice, true cinnamon, in the treatment of the pain of acute cystitis was suggested by these preclinical studies. Human studies are indicated.

Cisplatin (CDDP) remains a key drug for patients with advanced bladder cancer (BC), despite the emergence of new therapeutic agents. Identifying factors contributing to treatment resistance to CDDP is crucial. The acidity of the tumor microenvironment has been reported to be associated with treatment resistance and poor prognosis across various cancer types. Our objective was to investigate the effects of an acidic environment on BC cells and elucidate the mechanisms behind CDDP resistance. Our findings show that BC cells cultured in acidic conditions developed resistance to cisplatin as acidity increased. Notably, CDDP administered to BC cells in a pH 6.0 environment required twice the concentration compared to pH 7.5 to achieve equivalent toxicity. Using chloroquine and navitoclax, we identified the involvement of Bcl-2 and LC3B pathways in the acquisition of CDDP resistance under acidic conditions. Western blot analysis revealed that the activation of Bcl-2 and XIAP expression appears to inhibit both apoptotic and autophagic cell death. These results suggest that alleviating the acidity of the tumor microenvironment in clinical settings might enhance BC sensitivity to CDDP.

Research studies related to neuroplastic changes that occur secondary to a bout of cystitis at a critical neonatal period of development in female rats (P14-16) are reviewed. They reveal that neonatal bladder inflammation (NBI) leads to an adult phenotype with many of the features of the human disorder, interstitial cystitis. Neurochemical, behavioral and neurophysiological differences between rats which experienced NBI and control animals are discussed and new data presented.

Following spinal cord injury (SCI), pathological reflexes develop that result in altered bladder function and sphincter dis-coordination, with accompanying changes in the detrusor. Bladder chemodenervation is known to ablate the pathological reflexes, but the resultant effects on the bladder tissue are poorly defined. In a rodent model of contusion SCI, we examined the effect of early bladder chemodenervation with botulinum toxin A (BoNT-A) on bladder histopathology and collagen deposition. Adult female Long Evans rats were given a severe contusion SCI at spi-nal level T9. The SCI rats immediately underwent open laparotomy and received detrusor injec-tions of either BoNT-A (10 U/animal) or saline. At 8 weeks post injury, the bladders were col-lected, weighed, and examined histologically. BoNT-A injected bladders of SCI rats (SCI-BoNT-A) weighed significantly less than saline injected bladders of SCI rats (SCI-saline) (241 ± 25 mg vs. 183 ± 42 mg; p<0.05). Histological analyses showed that SCI resulted in significantly thicker bladder walls due to detrusor hypertrophy and fibrosis compared to bladders from uninjured animals (339 ± 89.0 m vs. 193 ± 47.9 m; p<0.0001). SCI-BoNT-A animals had significantly thinner bladder walls compared to SCI-saline animals (202 ± 55.4 m vs. 339 ± 89.0 m; p<0.0001). SCI-BoNT-A animals had collagen organization in the bladder walls similar to that of uninjured animals. Detrusor chemodenervation soon after SCI appears to preserve bladder tissue integrity, by reducing the development of detrusor fibrosis and hypertrophy associated with SCI.

This study investigated the risk of lung and bladder cancers in people residing in proximity of a coal-oil-fired thermal power plant in an area of north-eastern Italy, covered by a population-based cancer registry. Incidence rate ratios (IRR) by sex, age, and histology were computed according to tertiles of residential exposure to benzene, nitrogen dioxide (NO2), particular matter, and sulfur dioxide (SO2) among 1076 incident cases of lung and 650 cases of bladder cancers. In men of all ages and in women under 75 years of age, no significant associations were observed. Conversely, in women aged >75 years significantly increased risks of lung and bladder cancers were related to high exposure to benzene (IRR for highest vs. lowest tertile: 2.00 for lung cancer and 1.94 for bladder cancer) and NO2 (IRR: 1.72 for lung cancer; and 1.94 for bladder cancer). In these women, a 1.71-fold higher risk of lung cancer was also related to a high exposure to SO2. The findings of this descriptive study indicated that air pollution may have a role with regard to the risk of lung and bladder cancers, limited to women aged ≥ 75 years. Such increased risk warrants further analytical investigations.

Abstract We aim to describe the diagnosis and surgical management of urinary tract endometriosis (UTE). We detail current diagnostic tools including advanced transvaginal ultrasound, magnetic resonance imaging, and surgical diagnostic tools such as cystourethroscopy. While discussing surgical treatment options, we emphasize the importance of an interdisciplinary team, for complex cases that involve the urinary tract. While bladder DE is more straightforward in its surgical treatment, ureteral DE requires a high level of surgical skill. Specialists should be aware of the important entity of UTE due to the serious health implications for women. When UTE exists, it is important to work within a interdisciplinary radiological and surgical team.

Background: Chronic pelvic pain is a debilitating condition affecting quality of life. Endometriosis is one of the leading causes of CPP, but recent studies highlighted the role of interstitial cystitis/bladder pain syndrome (IC/PBS) in causing CPP. Only some studies addressed the coexistence between these two conditions, which seems more frequent than what is supposed, leading to diagnostic delays and unnecessary surgeries. This systematic review aimed to evaluate the estimate of the coexistence of endometriosis and IC/PBS. Methods: We performed a systematic review of the literature indexed on PubMed, Scopus, ISI Web of Science, and Cochrane using a combination of keywords and text words represented by “painful bladder syndrome”, “endometriosis”, “interstitial cystitis”, “bladder pain syndrome”. We performed a meta-analysis of the results. Results: Meta-analysis shows that the coexistence of endometriosis and IC/PBS in women with CPP ranges between 15,5-78,3%, which is higher than the prevalence of IC/PBS in the general population. Conclusions: Women with CPP need a multidisciplinary approach and a referral to centers with specific expertise. In cases of endometriosis unresponsive to treatment, other reasons for CPP need to be ruled out, above all in women not responsive to treatment.

Background: Estrogen homeostasis is crucial for bladder function, and estrogen deprivation resulting from ovarian removal or ovarian dysfunction may lead to various bladder dysfunctions. However, the specific mechanisms are not fully understood. Methods: We simulated estrogen deprivation using a rat ovariectomy model and supplemented estrogen through subcutaneous injections. The metabolic characteristics of bladder tissue were analyzed using non-targeted metabolomics, followed by bioinformatics analysis to preliminarily reveal the association between estrogen deprivation and bladder function. Results: We successfully established a rat model with estrogen deprivation and, through multivariate analysis and validation, identified several promising biomarkers represented by 3, 5-tetradecadiencarnitine, lysoPC (15:0), and cortisol. Furthermore, we explored estrogen deprivation-related metabolic changes in the bladder primarily characterized by amino acid metabolism imbalance. Conclusions: This study, for the first time, depicted the metabolic profile of bladder resulting from estrogen deprivation, providing an important experimental basis for future research on bladder dysfunctions caused by estrogen deprivation.

Our previous study found that intravesical perfusion metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel for-mulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong in-hibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and expression of tumour biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPK/mTOR signalling pathway compared with metformin alone. These findings highlighted the potential of this novel formulation as an efficient candidate for managing BC via intravesical ad-ministration.

Catheter-associated urinary tract infections (CAUTI) are a recurring problem for individuals with neurogenic bladder who rely on frequent intermittent catheterization. Dysbiosis of the urine microbiome, characterized by the presence of pathogenic organisms and insufficient levels of Lactobacilli, is common in this population. We propose that introducing beneficial Lactobacilli via a catheter lubricant could act as a prophylactic "live barrier" to enhance beneficial bacteria in the urethra. The IC TF1 Catheter Lubricant gel discussed in this study is a freshly prepared viscous gel composed of sterile gelling components and a dry Lactobacillus Rhamnosus spp. powder. The gel prepared on- site by simple mixing, is usable for 24 hours with predictable and precise viability counts. Our investigation focuses on the design, physical attributes, manufacturability with quality control criteria, stability of probiotic viability, antimicrobial properties, cellular toxicity, and tissue compatibility of the IC TF1 gel. The gel demonstrates promising physical properties and biocompatibility, leading to the need for further pre-clinical and human trials to assess its safety and effectiveness in reducing pathogenic urethral colonization.The localized delivery of probiotic supplementation through catheter lubrication has the potential to enhance the well-being of individuals with neurogenic bladder and aid in the management of CAUTI.

The problems of modeling the human bladder and its stress-strain state under external static influence were considered. A method for identification of the anisotropic biomechanical characteristics of bladder tissue was proposed. A FEM model was created, which accepts into regard that the bladder is surrounded by fiber and affected by surrounding organs, and partially protected by pelvic bones. The model considered the presence of constant hydrostatic pressure on the walls of the bladder when it is full. It has been shown that isotropic mechanical characteristics of biological tissue can be used for studying the deformed state of a filled bladder if the filled bladder 300 ml is considered as initial non-deformed stage. This was shown by modeling and verification the effect of the external static force on the bladder. Numerical experiments were conducted based on the constructed model. To validate the results obtained, a series of natural experiments on the effect of external pressure on the bladder under ultrasound control was conducted. In the future, it is planned to use the constructed model to study rupture deformations of the bladder under the influence of static and dynamic loads.

This study introduces a compact Raman spectrometer with a 1064 nm excitation laser coupled with a fiber probe and an inexpensive motorized stage, offering a promising alternative to widely used Raman imaging instruments with 785 nm excitation lasers. The benefits of 1064 nm excitation for biomedical applications include further suppression of fluorescence background and deeper tissue penetration. The performance of the 1064 nm instrument in detecting cancer in human bladder resectates is demonstrated. Raman images with 1064 nm excitation were collected ex vivo from 10 human tumor and non-tumor bladder specimens and the results are compared to previously published Raman images with 785 nm excitation. K-Means cluster (KMC) analysis is used after pre-processing to identify Raman signatures of control, tumor, necrosis, and lipid-rich tissues. Hierarchical cluster analysis (HCA) groups the KMC centroids of all specimens as input. The tools for data processing and hyperspectral analysis were compiled in an open source Python library called SpectraMap (SpMap). In conclusion, the 1064 nm Raman system can differentiate between tumor and non-tumor bladder tissues in a similar way to 785 nm Raman spectroscopy. These findings hold promise for future clinical hyperspectral imaging.

Background: Quality of life (QoL) in IC/BPS patients is an evidence gap in guidelines, because studies are limited and outdated. Therefore, guidelines might not reflect the current situation accurately, and no possible improvements in QoL of these patients. Secondly, guidelines suggest multimodal approach in therapy, however unknown is how the efficacy of these therapies are perceived by the patient themselves. The aim of this study is to investigate the perception of IC/BPS patients on their QoL and to determine which treatments they received and how they evaluate the efficacy of these various (alternative) therapies.Methods: Quantitative retrospective database study in IC/BPS patients, compiled of existing patient survey data (n=217) from July 2021. Results: The QoL of patients is affected significantly by IC/BPS. This is evident from the substantial self-reported impact by patients, the various affected domains on EQ-5D 5L. The QoL was not negatively affected by delayed diagnosis, but there were differences between female and males. Secondly, there was the wide array of (alternative) treatments utilized, although some have doubtful results and high dropout rates. Conclusion: QoL is considerably impaired in IC/BPS patients. Coagulation therapy and intravesical GAG therapy were most appreciated treatments. The diverse responses and adherence to various treatments warrant a personalized approach (phenotype-oriented therapy). To achieve improvement in the QoL, it is important to incorporate the patient’s perspective in treatment guidelines.

Glycosaminoglycans (GAGs) with unique structures from marine animals show intriguing pharmacological activities and negligible biological risks, providing more options for us to explore safer agents. Swim bladder is a tonic food and folk medicine, and its GAGs show good anticoag-ulant activity. In this study, two GAGs SJG-1.0 and GMG-1.0 have been extracted and isolated from the swim bladder of Sphyraena jello and Gadus morhua. The physicochemical properties, pre-cise structural characteristics, and anticoagulant activities of these GAGs were determined. The analysis results of the SJG-1.0 and GMG-1.0 showed that they were chondroitin sulfate (CS)/dermatan sulfate (DS) hybrid chains with molecular weights of 109.32 kDa and 123.13 kDa, respectively. They were mainly composed of the repeating disaccharide unit of -{IdoA-α1,3-GalNAc4S-β1,4-}- (DS-A). The DS-B disaccharide unit of -{IdoA2S-α1,3-GalNAc4S-β1,4-}- also existed in both SJG-1.0 and GMG-1.0. SJG-1.0 had a higher proportion of CS-O disaccharide unit -{-GlcA-β1,3-GalNAc-β1,4-}-, while GMG-1.0 contained higher proportion of CS-E disaccha-ride unit -{-GlcA-β1,3-GalNAc4S6S-β1,4-}-. The disaccharide compositions of the GAGs varied in a species-specific manner. Anticoagulant activity assay revealed that both SJG-1.0 and GMG-1.0 had potent anticoagulant activity, which can significantly prolong activated partial thrombosis time. GMG-1.0 also can prolong the thrombin time. SJG-1.0 showed no intrinsic tenase inhibition ac-tivity, while GMG-1.0 can obviously inhibit intrinsic tenase with EC50 of 58 nM. Their significantly different anticoagulant activities may be due to their different disaccharide structural units and proportions. These findings suggested that the swim bladder CS/DS hybrid chains with well-defined structure may be safer anticoagulants with low bleeding risk.

Bladder cancer is one of the most common malignant diseases in the urinary system and a highly aggressive neoplasm. The prognosis is not favourable usually and its evolution for particular patients is very difficult to find out. In this paper we propose a dynamic mathematical model that describes the bladder tumor growth and the immune response evolution. This model is customized for a single patient, determining appropriate model parameter values via model calibration. Due to the uncertainty of the tumor evolution, using the calibrated model parameters, we predict the tumor size and the immune response evolution over the next few months assuming three different scenarios: favourable, neutral and unfavourable. In the former, the cancer disappears; in the second a 5mm tumor is expected around the middle of August 2018; in the worst scenario, a 5mm tumor is expected around the end of May 2018. The patient has been cited around June 15th, 2018, to check the tumor size, if it exists.

Transitional cell carcinoma of the bladder is currently a very representative model of development in basic, pathogenic and therapeutic research within the framework of modern clinical oncology. The article aims to present a clinical case of transitional cell carcinoma of the bladder, a diagnostic approach that takes into consideration the combination of clinical imaging methods, for which a 67-year-old white male patient with a history of macroscopic hematuria is presented, which is why which is treated and placed under follow-up, demonstrating that a successful diagnostic approach has been, is and will always be a fascinating intellectual challenge for doctors, and an inexhaustible source of satisfaction in their professional life, as long as its bases and procedures are mastered. . , this serves as the uniqueness and novelty of the work that is presented.

The microbiome, once considered peripheral, is emerging as a relevant player in the intricate web of factors contributing to cancer development and progression. These often overlooked microorganisms, in the context of urological malignancies, have been investigated primarily focusing on the gut microbiome, while exploration of urogenital microorganisms remains limited. In light of this, our systematic review delves into the complex role of these understudied actors in various neoplastic conditions, including prostate, bladder, kidney, penile, and testicular cancers. Our analysis found a total of 37 studies, with prostate cancer-12, bladder cancer-20, kidney cancer-4, penile/testicular cancer-1, which reveals distinct associations specific to each condition, hinting at potential therapeutic avenues and future biomarker discoveries. It becomes evident that further research is imperative to unravel the complexities of this domain and provide a more comprehensive understanding.

Urological cancers include a spectrum of malignancies affecting organs of the reproductive and/or urinary systems, such as prostate, kidney, bladder, and testis. Despite improved primary prevention, detection and treatment, urological cancers are still characterized by an increasing incidence and mortality worldwide and although advances have been made toward understanding the molecular basis of these diseases, a complete insight of the pathogenic mechanisms is still a research challenge for defining safer pharmacological therapies and prognostic factors, especially for the metastatic stage of these neoplasms for which no effective therapies exist. Glyoxalases are enzymes that catalyzes the glutathione-dependent metabolism of cytotoxic methylglyoxal (MG), thus protecting against cellular damage and apoptosis. They are generally overexpressed in numerous cancers as a survival strategy by providing a safeguard through enhancement of MG detoxification. Increasing evidence suggest that glyoxalases, especially Glo1, would act as oncogenes in urological malignancies and be central to their initiation, growth and progression. In this review, we highlight the critical role of glyoxalases as regulators of tumorigenesis in the prostate through modulation of various critical signaling pathways, and provide an overview of the current knowledge on glyoxalases in bladder, kidney and testis cancers. We also discuss the promise and challenges for Glo1 inhibitors as future anti-PCa therapeutics and the potential of glyoxalases as biomarkers for PCa diagnosis.

Since decades, oxybutynin hydrochloride is prescribed to improve bladder control in cases of incontinence and excessive urination frequency. This review summarizes synthetic methods enabling preparation of the racemic drug and, in a detailed manner, preparation of (S)-2-cyclohexyl-2-hydroxy-2-phenylacetic acid, a key intermediate in the synthesis of (S)-oxybutynin. Mode of action and metabolism are briefly commented in order to explain the main adverse effects associated with its use and to justify the evolution observed in the diverse commercial formulations. Repositioning opportunities are discussed in terms of clinical trials for the management of hyperhidrosis, hot flashes, and obstructive sleep apnea.

Caudal regression syndrome (CRS) is a congenital abnormality characterized by an incomplete development of the spinal cord (SC) and other abnormalities. We studied a 9-months old CRS child presenting: interruption of SC at L2-L3 level, sacral agenesis, lack of innervation of the inferior limbs (flaccid paraplegia) and neurogenic bladder and bowel. Given the effects of growth hormone (GH) on the proliferation, differentiation and migration of neural stem cells (NSCs), we treated him with GH and rehabilitation, trying to induce the recovery of main sequelae. GMFM-88 test score was 12.31%. After a blood analysis, GH treatment (0.3 mg/day, 5 days/week, 3 months and then 15 days without GH) and rehabilitation commenced. This protocol was followed during 5 years, being the last GH dose 1 mg/day. Blood analysis and physical exams were performed every 3 months initially and every 6 months later. Six months after commencing the treatment GMFM-88 score increased to 39.48%. Responses to sensitive stimuli appeared in most of the territories explored; 18 months later sensitive innervation was complete and the patient moved any muscle over the knees and controlled his sphincters. Three years later he walked with the help of canes, there was plantar flexion and GMFM-88 score was 78.48%. In summary, GH plus rehabilitation may be useful for innervating distal territories, below the level of the incomplete spinal cord in CRS. Most likely, GH acts on ependymal SC NSCs, as the hormone does in the neurogenic niches in the brain.

One of the most common complications of neurogenic bladder secondary to spinal cord injury (SCI) is urinary incontinence, possibly related to bladder-emptying methods and changes in quality of life. This study aimed to identify the occurrence of this complication in adults with SCI and analyze its relationship with bladder-emptying methods, satisfaction, and lifestyle. This is a quantitative, exploratory, cross-sectional study. The variables were collected using the Bowel and Bladder Treatment Index during a telephone interview with 290 participants from February to November 2021. According to the results, 70% of the participants were male and 74.1% performed clean intermediate catheterization (CIC) as the main bladder-emptying method. Moreover, 55.6% were considered incontinent in the last year. Emptying by normal urination and bladder reflex triggering had a statistically significant relationship with urinary incontinence. A statistical association was observed between all the variables of satisfaction and lifestyle with urinary incontinence. Although CIC reduced urine leakage, a considerable number of participants still presented with frequent urine leakage. Urinary incontinence negatively altered satisfaction with the bladder-emptying method, effectiveness of bladder management, quality of life, and personal and social relationships.

Urinary tract infections (UTIs) are the second most common bacterial infection with high recurrence rates. A major causative agent of UTIs is uropathogenic Escherichia coli (UPEC), which can form persistent biofilms on urothelial surfaces and/or urinary catheters. Biofilms are inherently tolerant to antimicrobials, making them difficult to eradicate. Ciprofloxacin hybrids functionalised with nitroxides have previously shown enhanced biofilm eradication activity in vitro. Here, we evaluate a ciprofloxacin di-nitroxide hybrid (CDN11), previously reported to have antibiofilm activity against UPEC, as a potential UTI therapeutic in various infection models. We report potent CDN11 activity against mature biofilms formed by cystitis strain UTI89 inside polyethylene catheters. In infected human bladder cell monolayers, CDN11 afforded a 3-log reduction in UPEC colony forming units (CFU) compared to controls, including intracellular bacteria. Infected mouse bladders carrying biofilm-like intracellular UPEC reservoirs had reduced bacterial burdens following treatment with CDN11 ex vivo. Activity trends for CDN11 were comparable throughout all models, indicating that our testing pipeline was robust. New antimicrobial development is arduous and requires large investments of time and money. The pipeline described here could be readily used in testing new compounds, fast tracking the development of novel UTI therapeutics.

Lower urinary tract symptoms (LUTS) and hematuria are common symptoms in men with benign prostatic hyperplasia (BPH) and prostate cancer (PCa) mainly affecting the elderly population. Prostatic arterial embolization (PAE) is a minimally invasive pro-cedure that has shown promising results in managing massive intractable prostatic he-maturia in patients with BPH and PCa. A few studies, however, have provided valuable insights into the durability and efficacy of PAE focusing on the long-term effectiveness, quality of life, and cancer-specific control of hemostasis and urinary symptoms. As a result of concomitant cardiovascular conditions, these patients often take anticoagulants or antithrombotics, which can worsen their hematuria and clinical status. Transurethral resection of the prostate (TURP) is considered a very high-risk procedure even without massive bleeding, and requires discontinuation of Vitamin K antagonists and antiplate-let therapies. Such patients usually have their surgery postponed, and PAE should be considered a safe alternative treatment. We aimed to report a narrative review from 1976 to June 2023 of the current state of PAE for massive and intractable hematuria highlighting recent developments in this technique, including prospective cohort stud-ies and focusing on long-term outcome, safety, and complication management in PCa patients with significant hemorrhagic symptoms. As an additional contribution, we propose a simple algorithm for treating intractable bleeding associated with prostate cancer in a 92-year-old man with LUTS.

Background: Micro-RNAs (miRNA) are emerging as biomarkers in the detection and prognosis of cancers due to their inherent stability and resilience. Methods: To summarize evidence regarding urinary miRNA (umiRNAs) role in the detection, prognosis and therapeutic management of urological cancers, we performed a systematic review of the most important scientific databases using the following keywords: (urinary mir-na)AND(prostate cancer); (urinary mirna)AND(bladder cancer); (urinary mirna)AND(renal cancer); (urinary mirna)AND(testicular cancer); (urinary mirna)AND(urothelial cancer). Results: Of all, 1364 articles were initially selected. Only original studies in the English language on human specimens were considered for inclusion in our systematic review. Thus, a convenient sample of 60 original articles was identified. Urinary miRNA (UmiRNAs) are downregulated in prostate cancers and may serve as potential non-invasive molecular biomarkers. Several umiR-NAs have been identified as diagnostic biomarkers of urothelial carcinoma and bladder cancer (BCa), allowing to discriminate malignant from non-malignant forms of haematuria. UmiRNAs could serve as therapeutic targets or recurrence markers of non-muscle invasive BCa and could predict the aggressivity and prognosis of muscle-invasive BCa. In renal cell carcinoma, miRNAs have been identified as predictors of tumour detection, aggressiveness, and progression to metastasis. Conclusion: umiRNAs could play an important role in the diagnosis, prognosis, and therapy of urological cancers.

Nowadays molecular research is essential for the better understanding of tumor cells pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’ therefore it is possible to discover complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs which comprises seven members: STAT1, STAT2, STAT3, STAT5A, STAT5B, STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration and angiogenesis. Inhibition of this transcription factor inhibits previously mentioned effects in cancer cells whereas normal cells are not affected. Hence STAT3 might be a viable target for cancer therapy.

To examine the association of clinical, treatment, and dose parameters with late urinary toxicity after low-dose-rate brachytherapy (LDR-BT) for prostate cancer, we retrospectively studied patients with prostate cancer who underwent LDR-BT from January 2007 through December 2016. Urinary toxicity was assessed using the International Prostate Symptom Score (IPSS) and Overactive Bladder (OAB) Symptom Score (OABSS). Severe and moderate lower urinary tract symptoms (LUTS) were defined as IPSS ≥ 20 and ≥ 8, respectively; OAB was defined as a nocturnal frequency of ≥ 2 and a total OABSS of ≥ 3. In total, 203 patients (median age, 66 years) were included, with a mean follow-up of 8.4 years after treatment. The IPSS and OABSS worsened after 3 months of treatment; these scores improved to pretreatment levels after 18–36 months in most patients. Patients with a higher baseline IPSS and OABSS had a lower frequency of moderate and severe LUTS and OAB at 24 and 60 months, respectively. LUTS and OAB at 24 and 60 months were not correlated with the dosimetric factors of LDR-BT. Although the rate of long-term urinary toxicities assessed using IPSS and OABSS was low, the baseline scores were related to long-term function. Refining patient selection may further reduce long-term urinary toxicity.

As an uncommon cause of spinal cord infarction, anterior spinal cord syndrome can manifest with motor paralysis, loss of pain, and temperature sensation distal to the site of the lesion. The main pathogenesis of this syndrome is the disruption of blood flow in the anterior spinal artery. Mortality and morbidity differ with the etiology of the syndrome. So knowing the etiology of blood flow disruption is essential for patient management. This review article highlights the important clinical manifestation of Anterior spinal artery syndrome. Also describes etiology, pathogenesis, diagnosis, prognosis, possible management, and complications.

Renal artery thrombosis is a sporadic serious clinical condition which potentially cause renal infarction. Diagnosis of renal infarction can be delayed or missed due to non specific clinical presentation and overlapping appearance of medical and surgical phenomena. Early diagnosis supported by biochemical and radiological findings while appropriate management potentially improve morbidity and mortality. Persistent abdominal or flank pain with raised LDH and proteinuria on background of thromboembolism risk factors supports the diagnosis. Despite the rarity of the disease rapid identification with prompt medical or endovascular intervention could prevent irreversible renal parenchymal damage.