Bladder Cancer Research Research Articles

A bibliometric analysis of bladder cancer and microRNA research: Trends and advances from 2008 to 2022.

Bladder cancer (BC) is a significant global health issue with high incidence and mortality rates. MicroRNAs (miRNAs) play a crucial role in regulating gene expression and have been found to be dysregulated in BC. Understanding the role of miRNAs in BC development could lead to targeted therapies and improved patient management. Our study presents a thorough examination of the correlation between BC and miRNA research from 2008 to 2022. With the help of 3 powerful methods, including VOSviewer, Biblioshiny, and CiteSpace software, we analyzed the retrieved documents from "Core Collection databases online" on the Web of Science. In total, 798 articles were extracted from the Web of Science, and the number of published papers showed an upward trend from 2008 to 2019. The total number of citations was 21,233, of which the highest paper was a review article written by Chan Jiajia et al in 2018 with 752 citations. Based on the result of the coauthor analysis, Seki Naohiko was the most productive writer and China had the highest volume of published articles. Co-citation analysis was used to reveal the knowledge structure of the research field. In addition to the keywords "Bladder cancer" and "miRNA," "Proliferation," "Biomarkers," and "Apoptosis" were the high-frequency used keywords. Recently, increasingly researchers have paid more attention to the field about BC and miRNA around the worldwide. Through in-depth communication and close collaboration, the veil of miRNA in BC has gradually been unveiled. Bibliometric analysis helps to identify hotspots in research and areas for future investigation.

Stable laminar shear stress induces G1 cell cycle arrest and autophagy in urothelial carcinoma by a torque sensor-coupled cone-and-plate device

The microenvironments of urinary systems play crucial roles in the development and metastasis of cancers due to their generation of complex temporal and spatial fluidic profiles. Because of their versatility in creating desired biomimetic flow, cone-and-plate bioreactors offer great potential for bladder cancer research. In this study, we construct a biocompatible cone-and-plate device coupled with a torque sensor, enabling the application and real-time monitoring of stable shear stress up to 50 dyne/cm². Under a stable shear stress stimulation at 12 dyne/cm2, bladder cancer cell BFTC-905 is arrested at the G1 phase with decreased cell proliferation after 24-hour treatment. This effect is associated with increased cyclin-dependent kinase inhibitors p21 and p27, inhibiting cyclin D1/CDK4 complex with dephosphorylation of serine 608 on the retinoblastoma protein. Consequently, an increase in cyclin D3 and decreases in cyclin A2 and cyclin E2 are observed. Moreover, we demonstrate that the shear stress stimulation upregulates the expression of autophagy-related proteins Beclin-1, LC3B-I and LC3B-II, while caspase cleavages are not activated under the same condition. The design of this system and its application shed new light on flow-induced phenomena in the study of urothelial carcinomas.

A review of urinary bladder microbiome in patients with bladder cancer and its implications in bladder pathogenesis.

The recent discovery of the urinary microbiome has led to an emerging field of investigation about the potential role of microorganisms in the pathogenesis of urinary bladder cancer. Few preliminary data have been reported so far implicating urobiome as causative and prognostic factor of bladder tumorigenesis. In the present study, a review of the current evidence is presented about microbiome composition among patients with bladder cancer and healthy individuals as well as possible implications of microbiome on urothelial carcinoma of the bladder. A literature review was conducted using PubMed/MEDLINE, Scopus, and the Cochrane library until December 2023. Search algorithm was constructed using the following terms and their associated Mesh terms and Boolean operators: "urinary microbiome" and "urinary microbiota". Studies written in English language, identifying, and comparing urinary microbiome among bladder cancer patients and healthy control group were included in the review. A total of 2,356 reports were identified. From this total 16 articles complied with the inclusion criteria were selected for analysis. These articles represent a total of about 486 bladder cancer patients. Recent studies revealed the colonization of the urinary tract and the bladder by micro-organisms using both enhanced culture- and molecular-based techniques for microbial characterization. However, several limitations exist in the literature decreasing the reliability of the current reports. As a result, urinary microbiome consist an ambitious era in bladder cancer research with an increasing number of evidence about its potential pathogenetic, prognostic and therapeutic role.

Integrated analysis of patients with bladder cancer from prospective transcription factor activity: Implications for personalized treatment approaches

Transcription factors are a specialized group of proteins that play important roles in regulating gene expression in human. These proteins control the transcription and translation of genes by binding to specific sites on DNA, thereby regulating key biological processes such as cell differentiation, proliferation, immune response, and neural development. Moreover, transcription factors are also involved in apoptosis and the pathogenesis of various diseases. By investigating transcription factors, researchers can uncover the mechanisms of gene regulation in organisms and develop more effective methods for preventing and treating human diseases. In the present study, the Virtual Inference of Protein-activity by Enriched Regulon algorithm was utilized to calculate the protein activity of transcription factors, and the metabolic-related protein activity were used for classifying bladder cancer patients into different subtype. To identify chemotherapy drugs with clinical benefits, the differences in prognosis and drug sensitivity between two distinct subtypes of bladder cancer patients were investigated. Simultaneously, the master regulators that display varying levels of transcription factor activity between two different bladder cancer subtypes were explored. Additionally, the potential transcriptional regulatory mechanisms and targets of these factors were investigated, thereby generating novel insights into bladder cancer research at the transcriptional regulation level.

Digital spatial profiling of the microenvironment of muscle invasive bladder cancer

Muscle invasive bladder cancer (MIBC) is a molecularly diverse disease with varied clinical outcomes. Molecular studies typically employ bulk sequencing analysis, giving a transcriptomic snapshot of a section of the tumour. However, tumour tissues are not homogeneous, but are composed of distinct compartments such as the tumour and stroma. To investigate the molecular profiles of bladder cancer, whilst also maintaining the spatial complexity of the tumours, we employed whole transcriptome Digital Spatial Profiling (DSP). With this method we generated a dataset of transcriptomic profiles of tumour epithelium, stroma, and immune infiltrate. With these data we investigate the spatial relationship of molecular subtype signatures and ligand signalling events. We find that Basal/Squamous and Classical subtypes are mostly restricted to tumour regions, while the stroma-rich subtype signatures are abundant within the stroma itself. Additionally, we identify ligand signalling events occurring between tumour, stroma, and immune infiltrate regions, such as immune infiltrate derived GPNMB, which was highly correlated with VEGFA expression within the tumour. These findings give us new insights into the diversity of MIBC at a molecular level and provide a dataset with detailed spatial information that was not available before in bladder cancer research.

Advances in Liquid Biopsy for Diagnosis of Bladder Cancer.

Bladder cancer (BCa) is the most common malignancy of the urinary system. It has a high recurrence rate and requires longterm follow-up. Significant advances in BCa research have been made in recent years; however, the initial diagnosis and follow-up of BCa relies on cystoscopy, which is an invasive and expensive procedure. Over the past decade, liquid biopsies (e.g., blood and urine) have proven to be highly efficient methods for the discovery of BCa biomarkers. This noninvasive sampling method is used to analyze unique tumor components released into body fluids and enables serial sampling and longitudinal monitoring of tumor progression. Several liquid biopsy biomarkers have been studied extensively and have shown promising results in the clinical applications of BCa, including early detection, microscopic residual disease detection, recurrence prediction, and treatment response. Therefore, this review aims to provide an update on various new liquid biopsy markers and the advantages and current limitations of liquid biopsy in the diagnosis of BCa.

Abstract IA022: AI in bladder cancer pathology and research: What can we expect and what not?

Abstract Artificial intelligence (AI) applications are rapidly evolving, disruptive technologies that recently attracted tremendous public awareness including euphoria, bull runs at stock exchanges but also criticism and skepticism. Pathology, a crucial clinical diagnostic discipline, faces significant challenges despite its critical role and broad scope. A notable issue is the declining interest among medical graduates in pursuing further training in Surgical Pathology and Molecular Pathology. This disinterest is compounded by a trend towards part-time work and the aging demographic in Western industrial nations, which increases the demand for precise cancer diagnoses, molecular pathology and advanced oncological treatments. As the need for skilled pathologists grows, the availability of these professionals is steadily decreasing. Furthermore, political policies in heavily regulated healthcare systems (e.g., Germany) are exacerbating the shortage by limiting residency and specialist training positions despite the growing need. Adding to the reluctance among medical graduates to consider pathology as discipline is the looming “threat”” of replacing the field with Artificial Intelligence (AI) technologies. However, historical precedents suggest that necessity often spurs significant innovation. AI's role in pathology is expanding, reshaping the field with new technological advancements. AI, broadly encompassing various computational algorithms designed to perform tasks typically requiring human intelligence such as learning, reasoning, and pattern recognition, is now being applied extensively across different domains including medical diagnostics. Recent implementations in pathology include AI-driven algorithms that automate processes such as the Gleason grading of prostate biopsies, lymph node metastasis detection, detection of molecular bladder cancer subtypes or grading of kidney cancer showing high accuracy levels, speed and reproducibility in delivering results. These tools, while they do not replace pathologists, significantly reduce their workload by automating routine tasks, thus freeing up time for more complex diagnostic activities or simply dealing with the increasing workload. Despite the exciting possibilities, the use of AI in predicting molecular alterations, such as FGFR3 mutations in bladder cancer, faces limitations due to insufficient sensitivity and specificity, indicating that such technologies are not yet suitable for screening purposes. In conclusion, AI is increasingly vital in addressing the challenges of modern pathology, particularly in compensating for the shortage of pathologists. As technology advances, its integration into clinical practice offers promising solutions to enhance diagnostic accuracy and efficiency in uropathology, paving the way for more personalized and effective patient care. Citation Format: Markus Eckstein. AI in bladder cancer pathology and research: What can we expect and what not? [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr IA022.

Arab world's impact on bladder cancer research and opportunities for growth: A bibliometric review study.

Bladder Cancer (BC) is a widespread form of cancer that affects over 1.6 million people globally. The majority of cases are diagnosed as urothelial carcinoma, with a higher likelihood of diagnosis in men and with increasing age. The Arab world (AW) is one of the regions with the highest incidence and mortality rates of BC, and the average age of diagnosis is between 40 and 49 years in North Africa and the Middle East. This study aims to assess the activity and distribution of BC publications in the AW. A systematic search across MEDLINE and Embase databases spanning 2007 to 2021 identified 1208 English-language articles on bladder cancer with Arab affiliations. The dataset was normalized against the average population and GDP (2007-2020) for 22 Arab countries. Statistical analyses via SPSS and visualizations with VOSviewer unveiled collaboration patterns and thematic trends in Arab bladder cancer research. A total of 1208 BC publications were published in the AW, representing 0.24% of all biomedical publications. Egypt topped the list with the highest number of publications. The co-authorship analysis generated by VOSviewer revealed that out of 4766 authors, 161 met the minimum threshold of 5 publications. The findings reveal that Egypt and Jordan are at the forefront of BC research in the region, while other Arab countries are lagging behind despite being heavily impacted by the disease. To drive progress in the field, it's important to uncover the obstacles impeding BC research in these countries and implement effective solutions to overcome them.

Exploring Darunavir, Rilpivirine and Etravirine as Potential Therapies for Bladder Cancer: Efficacy and Synergistic Effects.

This research explores the therapeutic efficacy of Darunavir (DRV), Rilpivirine (RPV), and Etravirine (ETV) against UM-UC-5 bladder cancer cells, addressing the critical need for innovative treatments in bladder cancer research. Through a comprehensive assessment of their individual and combined effects across diverse time intervals, ETV emerges as the most potent drug, with a lowest IC50 of 5.9 µM, closely followed by RPV (lowest IC50 of 9.6 µM), while DRV exhibits the least effectiveness (lowest IC50 of 25.6 µM). Notably, a significant synergistic effect is evident in the ETV and RPV combination, especially at 48 and 72 h for low concentrations. Synergies are also observed with ETV and DRV, albeit to a lesser extent and primarily at 48 h. Conversely, the DRV and RPV combination yields minimal effects, predominantly additive in nature. In summary, this pre-clinical investigation underscores the promising therapeutic potential of ETV and RPV, both as standalone treatments and in combination, hinting at repurposing opportunities in bladder cancer therapy, which could give a new treatment method for this disease that is faster and without as severe side effects as anticancer drugs. These findings represent a substantial stride in advancing personalized medicine within cancer research and will be further scrutinized in forthcoming studies.

Redox System and Oxidative Stress-Targeted Therapeutic Approaches in Bladder Cancer.

Bladder cancer (BCa) is the most common genitourinary malignancy, with a high global incidence and recurrence rate that is paired with an increasing caregiver burden and higher financial cost, in addition to increasing morbidity and mortality worldwide. Histologically, BCa is categorized into non-muscle invasive, muscle invasive, and metastatic BCa, on the basis of which the therapeutic strategy is determined. Despite all innovations and recent advances in BCa research, conventional therapies such as chemotherapy, immunotherapy, radiotherapy, and surgery fall short in the complete management of this important malignancy. Besides this worrying trend, the molecular basis of BCa development also remains poorly understood. Burgeoning evidence from experimental and clinical studies suggests that oxidative stress resulting from an imbalance between reactive oxygen species (ROS) generation and the body's antioxidant production plays an integral role in BCa development and progression. Hence, ROS-induced oxidative stress-related pathways are currently under investigation as potential therapeutic targets of BCa. This review focuses on our current understanding regarding ROS-associated pathways in BCa pathogenesis and progression, as well as on antioxidants as potential adjuvants to conventional BCa therapy.

Urinary Bladder Cancer Induced by N-Butyl-N-(4-Hydroxybutyl)-Nitrosamine.

Urinary bladder cancer is the tenth most common cancer worldwide with high morbidity and mortality. The majority of bladder cancers are urothelial carcinomas. More than half are papillomas or the papillary urothelial carcinomas (stages Ta and T1), which have a relatively good prognosis. Squamous cell carcinomas have a variable survival rate, while carcinomas in situ (Tis) can progress to muscle-invasive urothelial carcinomas (T2) with a poor prognosis. The most challenging feature of bladder cancer is its high recurrence rate, ranging from 50% to 90% of cases. The N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) model is an invaluable experimental tool for bladder cancer research, as BBN-induced bladder cancer in rodents resembles human bladder cancer in its morphological, biological, and molecular features. We present here a detailed protocol for the treatment of mice and the main expected results.

Eligibility and Endpoints for Clinical Trials in Trimodality Therapy for Bladder Cancer.

Trimodality therapy (TMT) is a viable option for muscle-invasive localized bladder cancer, providing an alternative to radical cystectomy in properly selected patients. The approval of novel therapeutics in different stages of bladder cancer treatment has sparked interest in exploring concurrent systemic therapies with radiation in clinical trials to enhance long-term outcomes. Achieving uniformity in trial eligibility criteria and endpoint definitions is imperative in describing clinical significance, comparing trials, and changing standard of care guidelines. To delineate eligibility criteria and appropriate endpoints for TMT clinical trials in an attempt to achieve uniformity in trial eligibility criteria and endpoint definitions which will then help move the field of bladder preservation forward and improve the current standard of care. An expert panel, comprising individuals with extensive experience in bladder cancer clinical trials, clinical practice focused on bladder cancer treatment, and patient advocacy, was assembled. The panel systematically reviewed phase II/III clinical trials previously published and assessing the role of radiation in definitive therapy with the specific goal of preserving native bladder function during bladder cancer treatment. Recommendations were summarized based on review of these trials and past experiences of the investigators. To ensure a holistic perspective, the summary was further subjected to rigorous reevaluation by a patient advocate, who added valuable insights from a patient's standpoint. The resulting consensus statements were summarized in this publication to contribute to the evolving landscape of bladder cancer research and treatment. The eligibility criteria for TMT should be pragmatic to encompass patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, bladder cancer stage T2-T4a N0±N1M0, unilateral tumor-associated hydronephrosis, attempted maximal transurethral resection of bladder tumor (TURBT), both pure urothelial carcinoma and/or mixed histologic subtypes (excluding rare and aggressive small cell variants) and patients who are non- cystectomy candidates. Bladder intact event-free survival (BIEFS) is proposed as a suitable endpoint for registration trials designed to compare two different treatment interventions, defined as the time from randomization to muscle-invasive or locoregional recurrence, systemic recurrence, radical cystectomy from any cause, or death from any cause. Overall survival is deemed an appropriate secondary endpoint or a co-primary end point as recent improvements in systemic therapy can produce significant improvement in long-term outcomes. Primary and secondary endpoints should be supported with patient-reported quality of life assessments, when available. The standardization of clinical trial design, eligibility criteria, and endpoints is essential for expediting progress in the field. Inclusivity, patient-centricity, and clinically meaningful endpoints will facilitate the analysis, comparison, and meta-analysis of different trials, fostering advancements in bladder cancer treatment.

Cell Line-Based Human Bladder Organoids with Bladder-like Self-Organization-A New Standardized Approach in Bladder Cancer Research.

Three-dimensional tumor models have gained significant importance in bladder cancer (BCa) research. Organoids consisting of different cell types better mimic solid tumors in terms of 3D architecture, proliferation, cell-cell interaction and drug responses. We developed four organoids from human BCa cell lines with fibroblasts and smooth muscle cells of the bladder, aiming to find models for BCa research. The organoids were characterized in terms of cytokeratins, vimentin, α-actin and KI67 by immunoreactivity. Further, we studied ligand-dependent activation of the Wnt/β-catenin pathway and investigated the responses to anti-tumor therapies. The organoids mimicked the structure of an inverse bladder wall, with outside urothelial cells and a core of supportive cells. The cytokeratin staining patterns and proliferation rate were in conjunction with the origins of the BCa cells. RT-112 even showed stratification of the epithelium. Treatment with Wnt10B led to increased β-catenin (active) levels in high-grade organoids, but not in low-grade BCa cells. Doxorubicin treatment resulted in clearly reduced viability (10-30% vs. untreated). In contrast, the effectivity of radiotherapy depended on the proliferation status of BCa cells. In conclusion, cell-line-based organoids can form bladder-like structures and reproduce in vivo features such as urothelial differentiation and stratification. Thus, they can be useful tools for functional studies in BCa and anti-cancer drug development.

Conditional Reprogramming Modeling of Bladder Cancer for Clinical Translation.

The use of advanced preclinical models has become increasingly important in drug development. This is particularly relevant in bladder cancer, where the global burden of disease is quite high based on prevalence and a relatively high rate of lethality. Predictive tools to select patients who will be responsive to invasive or morbid therapies (chemotherapy, radiotherapy, immunotherapy, and/or surgery) are largely absent. Patient-derived and clinically relevant models including patient-derived xenografts (PDX), organoids, and conditional reprogramming (CR) of cell cultures efficiently generate numerous models and are being used in both basic and translational cancer biology. These CR cells (CRCs) can be reprogrammed to maintain a highly proliferative state and reproduce the genomic and histological characteristics of the parental tissue. Therefore, CR technology may be a clinically relevant model to test and predict drug sensitivity, conduct gene profile analysis and xenograft research, and undertake personalized medicine. This review discusses studies that have utilized CR technology to conduct bladder cancer research.

Guidance on Therapeutic Strategies for Metastatic Urothelial Cancer

Guidance on Therapeutic Strategies for Metastatic Urothelial Cancer

Research in bladder cancer: translation into the clinic—report of 13th annual meeting of the German Research Group on Bladder Cancer (DFBK) in Berlin

Research in bladder cancer: translation into the clinic—report of 13th annual meeting of the German Research Group on Bladder Cancer (DFBK) in Berlin

MP63-11 ADVANCED AGE (>70 YEARS) DOES NOT AFFECT ONCOLOGICAL OUTCOMES IN NON-MUSCLE INVASIVE BLADDER CANCER PATIENTS TREATED WITH ADEQUATE BACILLUS CALMETTE-GUERIN: A COMPETING RISK ANALYSIS FROM a TERTIARY CARE CENTER.

You have accessJournal of UrologyCME1 Apr 2023MP63-11 ADVANCED AGE (>70 YEARS) DOES NOT AFFECT ONCOLOGICAL OUTCOMES IN NON-MUSCLE INVASIVE BLADDER CANCER PATIENTS TREATED WITH ADEQUATE BACILLUS CALMETTE-GUERIN: A COMPETING RISK ANALYSIS FROM a TERTIARY CARE CENTER. Roberto Contieri, Valentina Grajales, Wei Shen Tan, Kelly Bree, Patrick Hensley, Charles C. Guo, Graciela M. Nogueras-Gonzalez, Neema Navai, Colin P. Dinney, and Ashish M. Kamat Roberto ContieriRoberto Contieri More articles by this author , Valentina GrajalesValentina Grajales More articles by this author , Wei Shen TanWei Shen Tan More articles by this author , Kelly BreeKelly Bree More articles by this author , Patrick HensleyPatrick Hensley More articles by this author , Charles C. GuoCharles C. Guo More articles by this author , Graciela M. Nogueras-GonzalezGraciela M. Nogueras-Gonzalez More articles by this author , Neema NavaiNeema Navai More articles by this author , Colin P. DinneyColin P. Dinney More articles by this author , and Ashish M. KamatAshish M. Kamat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003321.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: According to the newly released European Association of Urology (EAU) prognostic factor risk groups, age over 70 should be considered an additional clinical risk factor for progression amongst patients with non-muscle invasive bladder cancer (NMIBC). However, this statement is based on an analysis of patients who did not receive intravesical BCG therapy. Herein, we aim to evaluate the impact of age on oncological outcomes in NMIBC patients treated with adequate BCG. METHODS: We performed an IRB approved retrospective study analyzing patients with NMIBC treated with adequate BCG at our institution from 2000 to 2020. Based on EAU guidelines, patients were stratified into two groups according to age ( <70 yrs and>70 yrs). Primary endpoint was cancer-specific mortality (CSM). The cumulative incidence method was used to estimate the risk of CSM, high-grade (HG) recurrence and progression to muscle-invasive BC or metastatic disease after accounting for other causes of death (OCD) as a competing risk event; curves were compared with the Pepe-Mori test. Multivariate competing-risks regression analyses were used to predict HG recurrence and progression according to age after accounting for OCD. RESULTS: A total of 632 patients treated with adequate BCG were identified (355 <70 yrs versus 277>70 yrs). The median follow-up was 64.6 months (Interquartile range: 35.3–99.4) . Older patients were more likely to have a concomitant CIS (29.0% vs. 35.7%, p=0.072), and less likely to undergo second resection (reTUR) (66.2% vs. 56.5%, p=0.013). Despite this, at multivariate competing-risk regression analyses, age>70 did not emerge as an independent predictor of HG recurrence or progression (SHR 1.07, 95% CI: 0.78–1.46; p=0.687 and SHR: 1.60; 95% CI: 0.89–2.89; p=0.118). OS at 5 (94.2% vs. 78.5%) and 10 years (81.1% vs 42.3%) was considerably lower in the>70 yrs group. However, the 5-yr CSM overlap between the age groups (5.1% 95% CI: 2.7-8.7 vs. 2.0% 95% CI: 0.8–4.2). CONCLUSIONS: Age >70 was not associated with significantly worse oncological outcomes in NMIBC patients treated with adequate BCG Source of Funding: This research was supported by the Wayne B. Duddlesten Professorship in Cancer Research, the Raymond and Maria Floyd Bladder Cancer Research Foundation Grant, NIH/NCI UTMD Anderson SPORE in Genitourinary Cancer (p50CA091846), the Cancer Center Support Grant (NCI Grant P30 CA016672). © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e875 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Roberto Contieri More articles by this author Valentina Grajales More articles by this author Wei Shen Tan More articles by this author Kelly Bree More articles by this author Patrick Hensley More articles by this author Charles C. Guo More articles by this author Graciela M. Nogueras-Gonzalez More articles by this author Neema Navai More articles by this author Colin P. Dinney More articles by this author Ashish M. Kamat More articles by this author Expand All Advertisement PDF downloadLoading ...

3D Tumor Models in Urology.

Three-dimensional tumor models have become established in both basic and clinical research. As multicellular systems consisting of tumor and tumor-associated cells, they can better represent tumor characteristics than monocellular 2D cultures. In this review, we highlight the potential applications of tumor spheroids and organoids in the field of urology. Further, we illustrate the generation and characteristics of standardized organoids as well as membrane-based 3D in vitro models in bladder cancer research. We discuss the technical aspects and review the initial successes of molecular analyses in the three major urologic tumor entities: urinary bladder carcinoma (BCa), prostate carcinoma (PCa), and renal cell carcinoma (RCC).

Differential Occupancy and Regulatory Interactions of KDM6A in Bladder Cell Lines.

Epigenetic deregulation is a critical theme which needs further investigation in bladder cancer research. One of the most highly mutated genes in bladder cancer is KDM6A, which functions as an H3K27 demethylase and is one of the MLL3/4 complexes. To decipher the role of KDM6A in normal versus tumor settings, we identified the genomic landscape of KDM6A in normal, immortalized, and cancerous bladder cells. Our results showed differential KDM6A occupancy in the genes involved in cell differentiation, chromatin organization, and Notch signaling depending on the cell type and the mutation status of KDM6A. Transcription factor motif analysis revealed HES1 to be enriched at KDM6A peaks identified in the T24 bladder cancer cell line; moreover, it has a truncating mutation in KDM6A and lacks a demethylase domain. Our co-immunoprecipitation experiments revealed TLE co-repressors and HES1 as potential truncated and wild-type KDM6A interactors. With the aid of structural modeling, we explored how truncated KDM6A could interact with TLE and HES1, as well as RUNX and HHEX transcription factors. These structures provide a solid means of studying the functions of KDM6A independently of its demethylase activity. Collectively, our work provides important contributions to the understanding of KDM6A malfunction in bladder cancer.

The status of bladder cancer research worldwide, a bibliometric review and recommendations

ABSTRACT Background Healthcare system costs associated with bladder cancer treatment are among the highest of curable malignancies, and prognosis in advanced disease remains poor. This scoping review examines the worldwide status of bladder cancer research by systematically mapping publications, exploring research topics, support, gaps and limitations that need to be addressed. Methods We searched the Web of Science database for publications using controlled vocabulary. Results were limited between 2000–2020, and were included in our study based on pre-specified eligibility criteria. Data used for analysis included author’s names, country of affiliation, language, journal, citations, and funding. Analysis was conducted using Biblioshiny R and SPSS. Research topics were identified according to sub-filters of title words and strings pre-determined by authors. Results 40,657 results were retrieved, of which 19,976 original articles and reviews met the pre-specified criteria. 92% of the publications originated from 20 countries and were included in the analysis. Trends show an increase across the world, most of which is due to increasing contributions from USA and China. An increase by 1000% in funded publications has been achieved. Studies focused on Surgery, Pathology, and Diagnosis, while Radiotherapy, Palliative care, quality of life and Epidemiology were the least described. Genetics had the most increase while being the most funded. GDP, incidence, prevalence and mortality were each significantly positively correlated with overall bladder cancer research output. Conclusion This review described the evolution of bladder cancer research. It also identified significant gaps and limitations that need to be highlighted as priority areas for research investment.