The published article titled“Puerarin inhibits proliferation and induces apoptosis by upregulation of miR-16 in bladder cancer cell line T24”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1227–1234.
BACKGROUNDΒ-elemene is widely used to treat a variety of cancers,including bladder cancer(BLCA).However,the anti-cancer target,effective constituents and mechanism was unclear.AIM To investigate the therapeutic effec...BACKGROUNDΒ-elemene is widely used to treat a variety of cancers,including bladder cancer(BLCA).However,the anti-cancer target,effective constituents and mechanism was unclear.AIM To investigate the therapeutic effect and underlying mechanism ofβ-elemene in BLCA.METHODS We first mined the GEPIA2 database to explore the association between the GM3(ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5,GM3,ST3GAL5)gene and BLCA.Second,we performed in vitro experiments using BLCA cells to verify the inhibitory effect and targets therapy ofβ-elemene on BLCA.RESULTS Our results revealed a significantly reduced expression of GM3 in BLCA tissues.Notably,BLCA patients with higher GM3 expression exhibited prolonged overall survival and disease-free survival.In vitro studies demonstrated thatβ-elemene significantly affected BLCA cell viability,leading to a marked upregulation of GM3 expression,increased apoptotic cell populations,and a notable reduction in cell migration and invasion.WB analysis showed thatβ-elemene enhanced GM3 protein expression while simultaneously decreasing phosphorylated epidermal growth factor receptor(p-EGFR)levels.Additionally,overexpression or RNAi of GM3 in BLCA cells resulted in corresponding changes in epidermal growth factor receptor and p-EGFR expression levels.CONCLUSION This study provides preliminary evidence for further investigation into the molecular mechanisms ofβ-elemene in the treatment of BLCA.展开更多
Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of ...Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of PANoptosis in BLCA heterogeneity and its impact on clinical outcomes and immunotherapy response while establishing a robust prognostic model based on PANoptosis-related features.Methods:Gene expression profiles and clinical data were collected from public databases.Spatial heterogeneity of cell death pathways in BLCA was evaluated.Consensus clustering was performed based on identified PANoptosis genes.Cell death pathway scores,molecular,and pathway activation differences between different groups were compared.Protein-protein interaction(PPI)network construction was constructed,and immune-related gene sets,tumor immune dysfunction and exclusion(TIDE)scores,and SubMap analysis were used to evaluate immunomodulator expression and immunotherapy efficacy.Ten machine learning algorithms were utilized to develop the most accurate predictive risk model,and a nomogram was created for clinical application.Results:BLCA demonstrated a spatially heterogeneous distribution of pyroptosis,apoptosis,and necroptosis.Notably,T effector cells significantly colocalized with total apoptosis.Two PANoptosis modes were identified:high PANoptosis(high.PANO)and low PANoptosis(low.PANO).High.PANO was associated with worse clinical outcomes and advanced tumor stage,and increased activation of immune-related and cell death pathways.It also showed increased infiltration of immune cells,elevated expression of immunomodulatory factors,and enhanced responsiveness to the immunotherapy.The PANoptosis-related machine learning prognostic signature(PMLS)exhibited strong predictive power for outcomes in BLCA.CSPG4 was identified as a key gene underlying prognostic and therapeutic differences.Conclusion:PANoptosis shapes distinct prognostic and immunological phenotypes in BLCA.PMLS offers a reliable prognostic tool.CSPG4 may represent a potential therapeutic target in PANoptosis-driven BLCA.展开更多
Bladder cancer(BLCA)is a highly invasive malignancy with limited targeted therapies.Lu et al reveal the oncogenic role of HOXC6 in BLCA by showing its elevated mRNA and protein levels in cancerous tissues.Silencing HO...Bladder cancer(BLCA)is a highly invasive malignancy with limited targeted therapies.Lu et al reveal the oncogenic role of HOXC6 in BLCA by showing its elevated mRNA and protein levels in cancerous tissues.Silencing HOXC6 sig-nificantly inhibits BLCA cell proliferation,migration and invasion,induces apo-ptosis and arrests the cell cycle at G0/G1.In addition,HOXC6 also regulates pa-thways related to chemical carcinogenesis and reactive oxygen species,with a strong association with the target gene TIMELESS,supported by binding signals in its promoter region.Here,we discuss the role of HOXC6 as a potential bio-marker and therapeutic target,contributing to a deeper understanding of the HOXC6-TIMELESS axis and its implications for advancing BLCA research and therapy.展开更多
Gall bladder cancer(GBC)remains a highly aggressive disease,with an overall 5-year dismal survival rate of 15%-20%.Its asymptomatic nature in very early stages and non-specific clinical presentations pose significant ...Gall bladder cancer(GBC)remains a highly aggressive disease,with an overall 5-year dismal survival rate of 15%-20%.Its asymptomatic nature in very early stages and non-specific clinical presentations pose significant challenges to timely detection.Consequently,GBC often presents late,making it one of the most challenging cancers to manage.Surgery offers the best chance for long-term survival;however,only 10%of GBC patients are candidates for upfront resection,with the majority presenting in locally advanced or metastatic stages.Further-more,GBC is generally resistant to chemotherapy and radiotherapy,limiting the effectiveness of systemic therapy.Therefore,early diagnosis is crucial to offer the best treatment through surgical resection and to improve the outcome.Recent advancements in imaging technologies,biomarker discovery,and molecular diagnostics offer promising avenues for enhancing detection rates.Though non-invasive,most of them lack specificity,and the majority fail as an early diagnostic tool.This review examines the current status of early detection strategies for GBC,addresses the limitations of existing approaches,and explores the newer emer-ging diagnostic tools and techniques and how they can be exploited in future for its early detection.展开更多
Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in ...Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in tumor diagnosis and treatment.Given the critical role of molecular subtyping in the BCa treatment,acquiring a comprehensive understanding is imperative for guiding treatment decisions,optimizing risk assessment systems,and ultimately improving patient prognosis.Methods:In this review,we provide a comprehensive overview of the research progress in molecular subtyping of BCa,with a primary focus on discussing its utility in guiding various treatment modalities including neoadjuvant chemotherapy,neoadjuvant immunotherapy,and targeted therapy.In addition,this review also covers the trimodality treatment,antibody-drug conjugates,and the treatment of small cell BCa.Results:We present a comprehensive overview of the responsiveness or resistance of different molecular subtypes of BCa to various therapeutic modalities.The basal subtype demonstrates favorable sensitivity to neoadjuvant chemotherapy across multiple classification systems,whereas the luminal infiltrated subtype exhibits potential susceptibility to immunotherapy.In terms of targeted therapy,the basal-like and the basal/squamous subtypes in some classifications have shown notable responsiveness to epidermal growth factor receptor-targeted therapy.Moreover,the luminal subtype in the University of Texas M.D.Anderson Cancer Center classification,the luminal papillary subtypes according to the Cancer Genome Atlas Research Network classification in 2017,and the luminal unstable type in the 2019 Molecular Subtyping classification show potential for the fibroblast growth factor receptor 3-targeted treatment.Conclusion:The significance and impact of BCa molecular subtyping in guiding treatment,evaluating progression,and predicting prognosis are increasingly acknowledged.Accurate subtyping and broad application can bring good benefits to clinical decision-making,risk assessment,and prognostic evaluation.展开更多
Introduction:Radical cystectomy with pelvic node dissection remains the standard of care for muscle-invasive bladder carcinoma(MIBC);however,there is a growing interest in bladder preservation alternatives among the e...Introduction:Radical cystectomy with pelvic node dissection remains the standard of care for muscle-invasive bladder carcinoma(MIBC);however,there is a growing interest in bladder preservation alternatives among the elderly population.Guidelines indicate that partial cystectomy(PC)combined with pelvic node dissection(LND)can be considered as an alternative in carefully selected individuals.Using the National Cancer Database,we analyzed the overall survival(OS)between PC with and without LND among octogenarians.Methods:We identified octogenarians with localized muscle-invasive bladder carcinoma(cT2-3N0M0)and urothelial histology who underwent PC with or without LND between 2004 and 2018.Based on the number of lymph nodes removed(LNR),the LND group was further subdivided into<10 and>=10 lymph node groups.A propensity-matched Kaplan-Meier survival analysis was performed to compare OS between these groups.Results:Among 2573 patients who underwent PC,492 octogenarians met our selection criteria.208(42.2%)had LND,while 284(57.8%)had no LND.Within the LND group,53(25.5%)had<10 LNR,and 155(74.5%)had>=10 LNR.The median OS for the matched LND and non-LND groups was 36.9 and 33.4 months(p=0.96),respectively.Similarly,<10 LNR and>=10 LNR had 36.9 and 43.5 months(p=0.42),respectively.Multivariate Cox regression analysis revealed no difference in the risk of mortality.Conclusion:Among octogenarians who underwent PC,there was no significant difference in OS between those with or without LND,and between<10 or>=10 LNR groups.Therefore,the role and extent of LND after PC need further exploration in this subset of the population.展开更多
Objective: To explore the current status and influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery, and to provide a reference for the development of targeted inter...Objective: To explore the current status and influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery, and to provide a reference for the development of targeted intervention strPan ategies. Methods: A general data questionnaire and supportive care needs scale were used to investigate 107 patients with muscle-invasive bladder cancer after surgery. Results: The total score of supportive care needs in patients with muscle-invasive bladder cancer after surgery was (98.48 ± 9.07). Multiple linear regression analysis showed that age, primary caregiver, medical payment method, number of hospitalizations and postoperative time were important influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery (P Conclusion: The supportive care needs of patients with muscle-invasive bladder cancer after surgery are at a low level. Medical staff should identify them early, pay more attention to young patients, patients without medical insurance and patients with multiple hospitalizations, and provide targeted nursing measures to meet their supportive care needs.展开更多
Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predi...Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predict BCa molecular subtypes.Method:We developed a predictive model for BCa molecular subtypes using machine learning(ML)and pathomics derived from Hematoxylin-Eosin stained pathological slides.A cohort of 353 patients from TCGA was employed,and image features were extracted for analysis.Pathomic signatures were constructed using the LASSO Cox regression algorithm,and a pathomic-clinical nomogram was developed and validated in training and testing cohorts.Results:Seventy distinct image features were identified from 150 pathomic signatures.The model demonstrated robust predictive ability,with AUCs of 0.833 and 0.822 in the training and validation cohorts,respectively.The addition of pathomic score,N stage,and M stage improved the model’s discrimination,achieving AUCs of 0.877 and 0.794 in the training and validation cohorts.Limitations include the lack of an external validation cohort.Conclusion:Our ML-based pathomics model shows promise in predicting BCa molecular subtypes and has the potential to enhance prognosis prediction and inform treatment strategies,marking a significant step towards precision medicine for BCa.展开更多
Objective:To determine the safety and the role of modulating cytokines and proteases in the immune response to intravesical Bacillus Calmette-Guérin(BCG)when primed with systemic intradermal BCG.Methods:Phase 1 a...Objective:To determine the safety and the role of modulating cytokines and proteases in the immune response to intravesical Bacillus Calmette-Guérin(BCG)when primed with systemic intradermal BCG.Methods:Phase 1 and mechanistic longitudinal,prospective,single-blind randomized study(NCT04806178).Twenty-one non-muscle invasive urothelial bladder cancer patients undergoing intravesical adjuvant BCG after transurethral resection of bladder tumor(TURBT)in a teaching hospital between September 2021 and April 2023 were randomized to 0.1 mL of intradermal BCG vaccine or placebo(0.9%saline)administered 15 days before the start of intravesical BCG therapy.Blood samples were evaluated mechanistically regarding eight cytokines serum levels interferon-induced transmembrane protein 3 Gene(IFITM3),Interleukin 1 beta(IL1-BETA),interleukin-2 receptor alpha chain(IL2 RA),Interleukin 6(IL 6),Interleukin 10(IL 10),Tumor necrosis factor alpha(TNF-α),Interferon-β,AXL,and one protease CASPASE 8.Results:After 1 exclusion,twenty patients were randomized to intradermal BCG(n=11)and intradermal placebo(n=9).There was no difference in adverse effects emerging from the intravesical Onco-BCG therapy,and no difference in the expression of the cytokines and proteases analyzed between control and intervention,and over time.Conclusions:Intradermal BCG administration before intravesical application was safe,with no increase in adverse effects.It also does not seem to change the analyzed targets during the intravesical induction-phase BCG.Other immune targets should be explored in the future.The Brazilian tuberculosis-endemic status,where BCG vaccination is mandatory,might have affected the results.展开更多
Bladder cancer remains a significant global health challenge,requiring repeated treatments and surveillance and potentially morbid therapies,particularly in advanced and recurrent stages.Exosomes,small extracellular v...Bladder cancer remains a significant global health challenge,requiring repeated treatments and surveillance and potentially morbid therapies,particularly in advanced and recurrent stages.Exosomes,small extracellular vesicles central to intercellular communication,have emerged as innovative tools in cancer diagnostics,prognosis,and therapy.Their role in modulating the immune response and the tumor microenvironment makes them particularly attractive for cancer immunotherapy.This review provides a comprehensive overview of exosome biology,with a focus on their role in immune modulation and potential therapeutic applications.We explore the progress and challenges of exosome-based immunotherapy in cancer,followed by a discussion on the current state of bladder cancer immunotherapy.Additionally,we highlight the roles of exosomes in bladder cancer,emphasizing their diagnostic and prognostic applications.Despite promising preclinical studies and a growing number of clinical trials in other cancers,exosome-based therapies remain underexplored in bladder cancer.We discuss the current clinical trials related to exosomes in bladder cancer and propose their potential future role in immunotherapy.Finally,we address the challenges and opportunities in translating exosome-based therapies from bench to bedside,emphasizing the need for further preclinical and clinical investigations.This review emphasized the potential of exosome-based immunotherapy as a transformative approach for bladder cancer diagnosis and treatment.展开更多
BACKGROUND Bladder cancer(BLCA)is a common urological tumor.Homeobox C6(HOXC6)is an HOX family gene that has an oncogenic effect in various malignancies.AIM To investigate the expression and function of HOXC6 in BLCA....BACKGROUND Bladder cancer(BLCA)is a common urological tumor.Homeobox C6(HOXC6)is an HOX family gene that has an oncogenic effect in various malignancies.AIM To investigate the expression and function of HOXC6 in BLCA.METHODS This study employed immunohistochemistry,along with global chip and sequencing data for BLCA,to comprehensively evaluate the protein and mRNA expression of HOXC6 in BLCA.RNA interference technology was employed to knock down the mRNA expression of HOXC6 in BLCA cells,and the impact of reduced HOXC6 expression on cellular function was assessed.Additionally,we explored the potential mechanisms of HOXC6 in BLCA by aggregating HOXC6 chromatin immunoprecipitation sequencing data.RESULTS The immunohistochemistry results,sequencing data,and microarray data revealed that both the mRNA and protein expressions of HOXC6 in BLCA were notably greater than the expressions in non-cancerous tissues.Knocking down the expression of HOXC6 considerably limited the function of cell proliferation,migration,and invasion abilities of BLCA cells,elevated cell apoptosis,and triggered the G0/G1 phase blockade.The potential target genes of HOXC6 were enriched in pathways such as chemical carcinogenesis and reactive oxygen species.A notable positive correlation between HOXC6 mRNA expression and its target gene timeless circadian regulator(TIMELESS)was revealed.Notable binding peak signals for HOXC6 were identified in the promoter region of TIMELESS.CONCLUSION HOXC6 is upregulated in BLCA and may influence the cellular functions of BLCA by regulating the expression of the target gene TIMELESS.展开更多
Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine.Here...Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine.Here,we introduce pyropheophorbide a-bisaminoquinoline conjugate lipid nanoparticles(PPBC LNPs)as a bimodal system for image-guided phototherapy in bladder cancer treatment.PPBC LNPs not only demonstrate both powerful photodynamic and photothermal effects upon light activation,but also exhibit potent autophagy blockage,effectively inducing bladder cancer cell death.Furthermore,PPBC LNPs possess remarkable photoacoustic(PA)and fluorescence(FL)imaging capabilities,enabling imaging with high-resolution,deep tissue penetration and high sensitivity for tracking drug biodistribution and phototherapy efficacy.Specifically,PA imaging confirms the efficient accumulation of PPBC LNPs within tumor and predicts therapeutic outcomes of photodynamic therapy,while FL imaging confirms their prolonged retention at the tumor site for up to 6 days.PPBC LNPs significantly suppress bladder tumor growth,with several tumors completely ablated following just two doses of the nanoparticles and laser treatment.Additionally,PPBC LNPs were formulated with lipid-based excipients and assembled using microfluidic technology to enhance biocompatibility,stability,and scalability,showing potential for clinical translation.This versatile nanoparticle represents a promising candidate for further development in bladder cancer therapy.展开更多
Objectives:Bladder Cancer(BC)is one of the most commonly diagnosed malignancies worldwide,with high rates of mortality and morbidity.It can be classified as non-muscle invasive bladder cancer(NMIBC)or muscle-invasive ...Objectives:Bladder Cancer(BC)is one of the most commonly diagnosed malignancies worldwide,with high rates of mortality and morbidity.It can be classified as non-muscle invasive bladder cancer(NMIBC)or muscle-invasive bladder cancer(MIBC),with radical cystectomy being the treatment for MIBC,which significantly reduces quality of life.MicroRNAs(miRs)act as critical genetic regulators,with both oncogenic and tumor-suppressive roles.MiR-10a is described as a tumor suppressor in various neoplasms,but its role in BC is controversial.This study aims to assess the activity of miR-10a in cellular invasion and proliferation in two distinct BC cell lines.Methods:The study used high-grade T24 and low-grade RT4 bladder cell lines.Cells were transfected with miR-10a mimic or a non-targeting control.Transfection efficiency was validated by qPCR.Cell proliferation was cultured for 10–14 days.Cell migration and invasion were evaluated using Matrigel.All assays were conducted in triplicate.Results:The T24 cells transfected with miR-10a presented decreased cellular proliferation and invasion compared to the Scramble(p=0.0481 and p<0.0001,respectively).In the RT4 cell line,there was only a significant reduction in cellular proliferation after miR-10a transfection(p=0.0029).Conclusions:Our findings suggest that miR-10a has a tumoral suppressor role in BC,demonstrating higher efficacy in high-grade cells.展开更多
Bladder cancer(BC)is a common malignancy and among the leading causes of cancer death worldwide.Analysis of BC cells is of great significance for clinical diagnosis and disease treatment.Current approaches rely mainly...Bladder cancer(BC)is a common malignancy and among the leading causes of cancer death worldwide.Analysis of BC cells is of great significance for clinical diagnosis and disease treatment.Current approaches rely mainly on imaging-based technology,which requires complex staining and sophisticated instrumentation.In this work,we develop a label-free method based on artificial intelligence(AI)-assisted impedance-based flow cytometry(IFC)to differentiate between various BC cells and epithelial cells at single-cell resolution.By applying multiple-frequency excitations,the electrical characteristics of cells,including membrane and nuclear opacities,are extracted,allowing distinction to be made between epithelial cells,low-grade,and high-grade BC cells.Through the use of a constriction channel,the electro-mechanical properties associated with active deformation behavior of cells are investigated,and it is demonstrated that BC cells have a greater capability of shape recovery,an observation that further increases differentiation accuracy.With the assistance of a convolutional neural network-based AI algorithm,IFC is able to effectively differentiate various BC and epithelial cells with accuracies of over 95%.In addition,different grades of BC cells are successfully differentiated in both spiked mixed samples and bladder tumor tissues.展开更多
Objectives:Intravesical Bacillus Calmette-Guérin(BCG)therapy is a gold standard for patients with high-risk non-muscle invasive bladder cancer(NMIBC).Although a long-lasting therapeutic response is observed in mo...Objectives:Intravesical Bacillus Calmette-Guérin(BCG)therapy is a gold standard for patients with high-risk non-muscle invasive bladder cancer(NMIBC).Although a long-lasting therapeutic response is observed in most patients,BCG failure occurs in 30%–50%of patients and a progression to muscle-invasive disease is found in 10%–15%.Therefore,predicting high-risk patients who might not benefit from BCG treatment is critical.The purpose of this study was to identify,whether the presence of specific oncogenic mutations might be indicative of BCG treatment response.Methods:Nineteen high-grade NMIBC patients who received intravesical BCG were retrospectively enrolled and divided into“responders”and“non-responders”groups.Tissue samples from transurethral resection of bladder cancer were performed before starting therapy and were examined using a multigene sequencing panel.Results:Mutations in TP53,FGFR3,PIK3CA,KRAS,CTNNB1,ALK and DDR2 genes were detected.TP53 and FGFR3 were found to be the most frequently mutated genes in our cohort(31.6%and 26.3%,respectively),followed by PIK3CA(15.8%).In the BCG-responsive patient group,90%of samples were found to have mutated genes,with almost 50%of them showing mutations in tyrosine kinase receptors and CTNNB1 genes.On the other hand,in the BCG-unresponsive group,we found mutations in 44.4%of samples,mainly in TP53 gene.Conclusions:Our findings suggest that a Next-Generation Sequencing(NGS)multigene panel is useful in predicting BCG response in patients with NMIBC.展开更多
Background:The burden of common urologic diseases,including benign prostatic hyperplasia(BPH),urinary tract infections(UTI),urolithiasis,bladder cancer,kidney cancer,and prostate cancer,varies both geographically and ...Background:The burden of common urologic diseases,including benign prostatic hyperplasia(BPH),urinary tract infections(UTI),urolithiasis,bladder cancer,kidney cancer,and prostate cancer,varies both geographically and within specific regions.It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases.Methods:We obtained data on incidence,prevalence,mortality,and disability-adjusted life-years(DALYs)for the aforementioned urologic diseases by age,sex,location,and year from the Global Burden of Disease(GBD)2021.We analyzed the burden associated with urologic diseases based on socio-demographic index(SDI)and attributable risk factors.The trends in burden over time were assessed using estimated annual percentage changes(EAPC)along with a 95%confidence interval(CI).Results:In 2021,BPH and UTI were the leading causes of age-standardized incidence rate(ASIR)and age-standardized prevalence rate(ASPR),with rates of 5531.88 and 2782.59 per 100,000 persons,respectively.Prostate cancer was the leading cause of both age-standardized mortality rate(ASMR)and age-standardized DALYs rate(ASDR),with rates of 12.63 and 217.83 per 100,000 persons,respectively.From 1990 to 2021,there was an upward trend in ASIR,ASPR,ASMR,and ASDR for UTI,while urolithiasis showed a downward trend.The middle and low-middle SDI quintile levels exhibited higher incidence,prevalence,mortality,and DALYs related to UTI,urolithiasis,and BPH,while the high and high-middle SDI quintile levels showed higher rates for the three cancers.The burden of these 6 urologic diseases displayed diverse age and sex distribution patterns.In 2021,a high body mass index(BMI)contributed to 20.07%of kidney cancer deaths worldwide,while smoking accounted for 26.48%of bladder cancer deaths and 3.00%of prostate cancer deaths.Conclusions:The global burden of 6 urologic diseases presents a significant public health challenge.Urgent international collaboration is essential to advance the improvement of urologic disease management,encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies.展开更多
The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characte...The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.展开更多
Bladder cancer(BC)ranks as the tenth most common cancer globally.Histopathologically,BC is broadly categorized into urothelial and non-urothelial BC.Urothelial carcinoma represents over 90%of BC in most regions worldw...Bladder cancer(BC)ranks as the tenth most common cancer globally.Histopathologically,BC is broadly categorized into urothelial and non-urothelial BC.Urothelial carcinoma represents over 90%of BC in most regions worldwide.The standard treatment procedure for diagnosing and treating non-muscle-invasive bladder cancer(NMIBC)is transurethral resection of bladder tumors(TURBT).Currently,the standard of care for muscle-invasive bladder cancer(MIBC)is neoadjuvant chemotherapy followed by radical cystectomy.Cryoablation therapy is a medical technique that uses extremely low temperatures to destroy diseased tissue.This treatment serves as a therapeutic tool for both benign and malignant diseases in organs such as the kidney,prostate gland,lung,liver,and breast,and is particularly effective for unresectable tumors,offering less trauma,quick recovery,good tolerability,and symptom control.However,cryoablation has its limitations.Over the past few years,cryoablation therapy has emerged as a new method for treating early BC.This treatment is minimally invasive,precise,and offers quick recovery,providing patients with a new treatment option.Although randomized studies are still limited,increasing evidence suggests its potential application in bladder cancer combined with transurethral resection(TURBT)or medication.Cryoablation is not standard therapy for bladder cancer.Treatment decisions should be discussed by a multidisciplinary team of urologists,oncologists,and interventional physicians and require more randomized controlled trials to define patient selection criteria and treatment approaches.展开更多
Objective This study aimed to investigate the role of the long noncoding RNA(lncRNA)maternally expressed gene 3(MEG3)in the epithelial-mesenchymal transition(EMT)of bladder cancer cells and the potential mechanisms.Me...Objective This study aimed to investigate the role of the long noncoding RNA(lncRNA)maternally expressed gene 3(MEG3)in the epithelial-mesenchymal transition(EMT)of bladder cancer cells and the potential mechanisms.Methods Cell invasion,migration,and wound healing assays were conducted to assess the effects of MEG3 on the invasive and migratory capabilities of bladder cancer cells.The expression levels of E-cadherin were measured using Western blotting,RT-qPCR,and dual luciferase reporter assays.RNA immunoprecipitation and pull-down assays were performed to investigate the interactions between MEG3 and its downstream targets.Results MEG3 suppressed the invasion and migration of bladder cancer cells and modulated the transcription of E-cadherin.The binding of MEG3 to the zinc finger region of the transcription factor Snail prevented its ability to transcriptionally repress E-cadherin.Additionally,MEG3 suppressed the phosphorylation of extracellular regulated protein kinase(ERK),c-Jun N-terminal kinase(JNK),and P38,thereby decreasing the expression of Snail and stimulating the expression of E-cadherin.Conclusion MEG3 plays a vital role in suppressing the EMT in bladder cancer cells,indicating its potential as a promising therapeutic target for the treatment of bladder cancer.展开更多
文摘The published article titled“Puerarin inhibits proliferation and induces apoptosis by upregulation of miR-16 in bladder cancer cell line T24”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1227–1234.
基金Supported by the Zhejiang Provincial Traditional Chinese Medicine Foundation,No.2021ZA021 and No.2022ZZ005.
文摘BACKGROUNDΒ-elemene is widely used to treat a variety of cancers,including bladder cancer(BLCA).However,the anti-cancer target,effective constituents and mechanism was unclear.AIM To investigate the therapeutic effect and underlying mechanism ofβ-elemene in BLCA.METHODS We first mined the GEPIA2 database to explore the association between the GM3(ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5,GM3,ST3GAL5)gene and BLCA.Second,we performed in vitro experiments using BLCA cells to verify the inhibitory effect and targets therapy ofβ-elemene on BLCA.RESULTS Our results revealed a significantly reduced expression of GM3 in BLCA tissues.Notably,BLCA patients with higher GM3 expression exhibited prolonged overall survival and disease-free survival.In vitro studies demonstrated thatβ-elemene significantly affected BLCA cell viability,leading to a marked upregulation of GM3 expression,increased apoptotic cell populations,and a notable reduction in cell migration and invasion.WB analysis showed thatβ-elemene enhanced GM3 protein expression while simultaneously decreasing phosphorylated epidermal growth factor receptor(p-EGFR)levels.Additionally,overexpression or RNAi of GM3 in BLCA cells resulted in corresponding changes in epidermal growth factor receptor and p-EGFR expression levels.CONCLUSION This study provides preliminary evidence for further investigation into the molecular mechanisms ofβ-elemene in the treatment of BLCA.
基金supported by grants from the National Natural Science Foundation of China(No.82172741)Shanghai Municipal Health Bureau(No.2020CXJQ03).
文摘Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of PANoptosis in BLCA heterogeneity and its impact on clinical outcomes and immunotherapy response while establishing a robust prognostic model based on PANoptosis-related features.Methods:Gene expression profiles and clinical data were collected from public databases.Spatial heterogeneity of cell death pathways in BLCA was evaluated.Consensus clustering was performed based on identified PANoptosis genes.Cell death pathway scores,molecular,and pathway activation differences between different groups were compared.Protein-protein interaction(PPI)network construction was constructed,and immune-related gene sets,tumor immune dysfunction and exclusion(TIDE)scores,and SubMap analysis were used to evaluate immunomodulator expression and immunotherapy efficacy.Ten machine learning algorithms were utilized to develop the most accurate predictive risk model,and a nomogram was created for clinical application.Results:BLCA demonstrated a spatially heterogeneous distribution of pyroptosis,apoptosis,and necroptosis.Notably,T effector cells significantly colocalized with total apoptosis.Two PANoptosis modes were identified:high PANoptosis(high.PANO)and low PANoptosis(low.PANO).High.PANO was associated with worse clinical outcomes and advanced tumor stage,and increased activation of immune-related and cell death pathways.It also showed increased infiltration of immune cells,elevated expression of immunomodulatory factors,and enhanced responsiveness to the immunotherapy.The PANoptosis-related machine learning prognostic signature(PMLS)exhibited strong predictive power for outcomes in BLCA.CSPG4 was identified as a key gene underlying prognostic and therapeutic differences.Conclusion:PANoptosis shapes distinct prognostic and immunological phenotypes in BLCA.PMLS offers a reliable prognostic tool.CSPG4 may represent a potential therapeutic target in PANoptosis-driven BLCA.
基金Supported by National Key R&D Program of China,No.2023YFC2507904Hubei Strategic Science and Technology Talent Plan,No.2024DJA037+1 种基金National Natural Science Foundation of China,No.32270768,No.82273970 and No.82370715Innovation Group Project of Hubei Province No.2023AFA026.
文摘Bladder cancer(BLCA)is a highly invasive malignancy with limited targeted therapies.Lu et al reveal the oncogenic role of HOXC6 in BLCA by showing its elevated mRNA and protein levels in cancerous tissues.Silencing HOXC6 sig-nificantly inhibits BLCA cell proliferation,migration and invasion,induces apo-ptosis and arrests the cell cycle at G0/G1.In addition,HOXC6 also regulates pa-thways related to chemical carcinogenesis and reactive oxygen species,with a strong association with the target gene TIMELESS,supported by binding signals in its promoter region.Here,we discuss the role of HOXC6 as a potential bio-marker and therapeutic target,contributing to a deeper understanding of the HOXC6-TIMELESS axis and its implications for advancing BLCA research and therapy.
文摘Gall bladder cancer(GBC)remains a highly aggressive disease,with an overall 5-year dismal survival rate of 15%-20%.Its asymptomatic nature in very early stages and non-specific clinical presentations pose significant challenges to timely detection.Consequently,GBC often presents late,making it one of the most challenging cancers to manage.Surgery offers the best chance for long-term survival;however,only 10%of GBC patients are candidates for upfront resection,with the majority presenting in locally advanced or metastatic stages.Further-more,GBC is generally resistant to chemotherapy and radiotherapy,limiting the effectiveness of systemic therapy.Therefore,early diagnosis is crucial to offer the best treatment through surgical resection and to improve the outcome.Recent advancements in imaging technologies,biomarker discovery,and molecular diagnostics offer promising avenues for enhancing detection rates.Though non-invasive,most of them lack specificity,and the majority fail as an early diagnostic tool.This review examines the current status of early detection strategies for GBC,addresses the limitations of existing approaches,and explores the newer emer-ging diagnostic tools and techniques and how they can be exploited in future for its early detection.
基金supported by the grants from the National Natural Science Foundation of China(82273132 to Liu B).
文摘Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in tumor diagnosis and treatment.Given the critical role of molecular subtyping in the BCa treatment,acquiring a comprehensive understanding is imperative for guiding treatment decisions,optimizing risk assessment systems,and ultimately improving patient prognosis.Methods:In this review,we provide a comprehensive overview of the research progress in molecular subtyping of BCa,with a primary focus on discussing its utility in guiding various treatment modalities including neoadjuvant chemotherapy,neoadjuvant immunotherapy,and targeted therapy.In addition,this review also covers the trimodality treatment,antibody-drug conjugates,and the treatment of small cell BCa.Results:We present a comprehensive overview of the responsiveness or resistance of different molecular subtypes of BCa to various therapeutic modalities.The basal subtype demonstrates favorable sensitivity to neoadjuvant chemotherapy across multiple classification systems,whereas the luminal infiltrated subtype exhibits potential susceptibility to immunotherapy.In terms of targeted therapy,the basal-like and the basal/squamous subtypes in some classifications have shown notable responsiveness to epidermal growth factor receptor-targeted therapy.Moreover,the luminal subtype in the University of Texas M.D.Anderson Cancer Center classification,the luminal papillary subtypes according to the Cancer Genome Atlas Research Network classification in 2017,and the luminal unstable type in the 2019 Molecular Subtyping classification show potential for the fibroblast growth factor receptor 3-targeted treatment.Conclusion:The significance and impact of BCa molecular subtyping in guiding treatment,evaluating progression,and predicting prognosis are increasingly acknowledged.Accurate subtyping and broad application can bring good benefits to clinical decision-making,risk assessment,and prognostic evaluation.
文摘Introduction:Radical cystectomy with pelvic node dissection remains the standard of care for muscle-invasive bladder carcinoma(MIBC);however,there is a growing interest in bladder preservation alternatives among the elderly population.Guidelines indicate that partial cystectomy(PC)combined with pelvic node dissection(LND)can be considered as an alternative in carefully selected individuals.Using the National Cancer Database,we analyzed the overall survival(OS)between PC with and without LND among octogenarians.Methods:We identified octogenarians with localized muscle-invasive bladder carcinoma(cT2-3N0M0)and urothelial histology who underwent PC with or without LND between 2004 and 2018.Based on the number of lymph nodes removed(LNR),the LND group was further subdivided into<10 and>=10 lymph node groups.A propensity-matched Kaplan-Meier survival analysis was performed to compare OS between these groups.Results:Among 2573 patients who underwent PC,492 octogenarians met our selection criteria.208(42.2%)had LND,while 284(57.8%)had no LND.Within the LND group,53(25.5%)had<10 LNR,and 155(74.5%)had>=10 LNR.The median OS for the matched LND and non-LND groups was 36.9 and 33.4 months(p=0.96),respectively.Similarly,<10 LNR and>=10 LNR had 36.9 and 43.5 months(p=0.42),respectively.Multivariate Cox regression analysis revealed no difference in the risk of mortality.Conclusion:Among octogenarians who underwent PC,there was no significant difference in OS between those with or without LND,and between<10 or>=10 LNR groups.Therefore,the role and extent of LND after PC need further exploration in this subset of the population.
文摘Objective: To explore the current status and influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery, and to provide a reference for the development of targeted intervention strPan ategies. Methods: A general data questionnaire and supportive care needs scale were used to investigate 107 patients with muscle-invasive bladder cancer after surgery. Results: The total score of supportive care needs in patients with muscle-invasive bladder cancer after surgery was (98.48 ± 9.07). Multiple linear regression analysis showed that age, primary caregiver, medical payment method, number of hospitalizations and postoperative time were important influencing factors of supportive care needs in patients with muscle-invasive bladder cancer after surgery (P Conclusion: The supportive care needs of patients with muscle-invasive bladder cancer after surgery are at a low level. Medical staff should identify them early, pay more attention to young patients, patients without medical insurance and patients with multiple hospitalizations, and provide targeted nursing measures to meet their supportive care needs.
基金supported by the Guangzhou Municipal Basic Research Program Jointly Funded by City,University,and Enterprise Special Project(2024A03J0907)the Natural Science Foundation of Guangdong Province(2024A1515013201)+1 种基金the National Natural Science Foundation of China(82203720,82203188,82002682,81972731,81773026,81972383)the Science and Technology Project of Zhongshan Municipality(No.2024B1032).
文摘Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predict BCa molecular subtypes.Method:We developed a predictive model for BCa molecular subtypes using machine learning(ML)and pathomics derived from Hematoxylin-Eosin stained pathological slides.A cohort of 353 patients from TCGA was employed,and image features were extracted for analysis.Pathomic signatures were constructed using the LASSO Cox regression algorithm,and a pathomic-clinical nomogram was developed and validated in training and testing cohorts.Results:Seventy distinct image features were identified from 150 pathomic signatures.The model demonstrated robust predictive ability,with AUCs of 0.833 and 0.822 in the training and validation cohorts,respectively.The addition of pathomic score,N stage,and M stage improved the model’s discrimination,achieving AUCs of 0.877 and 0.794 in the training and validation cohorts.Limitations include the lack of an external validation cohort.Conclusion:Our ML-based pathomics model shows promise in predicting BCa molecular subtypes and has the potential to enhance prognosis prediction and inform treatment strategies,marking a significant step towards precision medicine for BCa.
基金National Council for Scientific and Technological Development,CNPq,Research Productivity,grant numbers:304747/2018-1/310135/2022-2(Reis LO).
文摘Objective:To determine the safety and the role of modulating cytokines and proteases in the immune response to intravesical Bacillus Calmette-Guérin(BCG)when primed with systemic intradermal BCG.Methods:Phase 1 and mechanistic longitudinal,prospective,single-blind randomized study(NCT04806178).Twenty-one non-muscle invasive urothelial bladder cancer patients undergoing intravesical adjuvant BCG after transurethral resection of bladder tumor(TURBT)in a teaching hospital between September 2021 and April 2023 were randomized to 0.1 mL of intradermal BCG vaccine or placebo(0.9%saline)administered 15 days before the start of intravesical BCG therapy.Blood samples were evaluated mechanistically regarding eight cytokines serum levels interferon-induced transmembrane protein 3 Gene(IFITM3),Interleukin 1 beta(IL1-BETA),interleukin-2 receptor alpha chain(IL2 RA),Interleukin 6(IL 6),Interleukin 10(IL 10),Tumor necrosis factor alpha(TNF-α),Interferon-β,AXL,and one protease CASPASE 8.Results:After 1 exclusion,twenty patients were randomized to intradermal BCG(n=11)and intradermal placebo(n=9).There was no difference in adverse effects emerging from the intravesical Onco-BCG therapy,and no difference in the expression of the cytokines and proteases analyzed between control and intervention,and over time.Conclusions:Intradermal BCG administration before intravesical application was safe,with no increase in adverse effects.It also does not seem to change the analyzed targets during the intravesical induction-phase BCG.Other immune targets should be explored in the future.The Brazilian tuberculosis-endemic status,where BCG vaccination is mandatory,might have affected the results.
基金funded by start-up funds from the University of Chicago.
文摘Bladder cancer remains a significant global health challenge,requiring repeated treatments and surveillance and potentially morbid therapies,particularly in advanced and recurrent stages.Exosomes,small extracellular vesicles central to intercellular communication,have emerged as innovative tools in cancer diagnostics,prognosis,and therapy.Their role in modulating the immune response and the tumor microenvironment makes them particularly attractive for cancer immunotherapy.This review provides a comprehensive overview of exosome biology,with a focus on their role in immune modulation and potential therapeutic applications.We explore the progress and challenges of exosome-based immunotherapy in cancer,followed by a discussion on the current state of bladder cancer immunotherapy.Additionally,we highlight the roles of exosomes in bladder cancer,emphasizing their diagnostic and prognostic applications.Despite promising preclinical studies and a growing number of clinical trials in other cancers,exosome-based therapies remain underexplored in bladder cancer.We discuss the current clinical trials related to exosomes in bladder cancer and propose their potential future role in immunotherapy.Finally,we address the challenges and opportunities in translating exosome-based therapies from bench to bedside,emphasizing the need for further preclinical and clinical investigations.This review emphasized the potential of exosome-based immunotherapy as a transformative approach for bladder cancer diagnosis and treatment.
基金Supported by the Science and Technology Major Project of Guangxi,No.AA22096030 and No.AA22096032the Yongjiang Program of Nanning+3 种基金the Creative Research Development from The First Affiliated Hospital of Guangxi Medical University,No.Medical Excellence Award 202303Guangxi Medical University Undergraduate Education and Teaching Reform Project,No.2024XJGYC20Guangxi Medical University Student Innovation and Entrepreneurship Training Program Project,No.202310598002X,No.202310598041,No.202410598039X,and No.202410598044the“Future Academic Star”of the Guangxi Medical University,No.WLXSZX24096.
文摘BACKGROUND Bladder cancer(BLCA)is a common urological tumor.Homeobox C6(HOXC6)is an HOX family gene that has an oncogenic effect in various malignancies.AIM To investigate the expression and function of HOXC6 in BLCA.METHODS This study employed immunohistochemistry,along with global chip and sequencing data for BLCA,to comprehensively evaluate the protein and mRNA expression of HOXC6 in BLCA.RNA interference technology was employed to knock down the mRNA expression of HOXC6 in BLCA cells,and the impact of reduced HOXC6 expression on cellular function was assessed.Additionally,we explored the potential mechanisms of HOXC6 in BLCA by aggregating HOXC6 chromatin immunoprecipitation sequencing data.RESULTS The immunohistochemistry results,sequencing data,and microarray data revealed that both the mRNA and protein expressions of HOXC6 in BLCA were notably greater than the expressions in non-cancerous tissues.Knocking down the expression of HOXC6 considerably limited the function of cell proliferation,migration,and invasion abilities of BLCA cells,elevated cell apoptosis,and triggered the G0/G1 phase blockade.The potential target genes of HOXC6 were enriched in pathways such as chemical carcinogenesis and reactive oxygen species.A notable positive correlation between HOXC6 mRNA expression and its target gene timeless circadian regulator(TIMELESS)was revealed.Notable binding peak signals for HOXC6 were identified in the promoter region of TIMELESS.CONCLUSION HOXC6 is upregulated in BLCA and may influence the cellular functions of BLCA by regulating the expression of the target gene TIMELESS.
文摘Rational design of multifunctional nanoplatforms capable of combining therapeutic effects with real-time monitoring of drug distribution and tumor status is emerging as a promising approach in cancer nanomedicine.Here,we introduce pyropheophorbide a-bisaminoquinoline conjugate lipid nanoparticles(PPBC LNPs)as a bimodal system for image-guided phototherapy in bladder cancer treatment.PPBC LNPs not only demonstrate both powerful photodynamic and photothermal effects upon light activation,but also exhibit potent autophagy blockage,effectively inducing bladder cancer cell death.Furthermore,PPBC LNPs possess remarkable photoacoustic(PA)and fluorescence(FL)imaging capabilities,enabling imaging with high-resolution,deep tissue penetration and high sensitivity for tracking drug biodistribution and phototherapy efficacy.Specifically,PA imaging confirms the efficient accumulation of PPBC LNPs within tumor and predicts therapeutic outcomes of photodynamic therapy,while FL imaging confirms their prolonged retention at the tumor site for up to 6 days.PPBC LNPs significantly suppress bladder tumor growth,with several tumors completely ablated following just two doses of the nanoparticles and laser treatment.Additionally,PPBC LNPs were formulated with lipid-based excipients and assembled using microfluidic technology to enhance biocompatibility,stability,and scalability,showing potential for clinical translation.This versatile nanoparticle represents a promising candidate for further development in bladder cancer therapy.
基金supported by grants from the São Paulo Research Foundation(FAPESP)to ThaináRodrigues(2021/04603-8).
文摘Objectives:Bladder Cancer(BC)is one of the most commonly diagnosed malignancies worldwide,with high rates of mortality and morbidity.It can be classified as non-muscle invasive bladder cancer(NMIBC)or muscle-invasive bladder cancer(MIBC),with radical cystectomy being the treatment for MIBC,which significantly reduces quality of life.MicroRNAs(miRs)act as critical genetic regulators,with both oncogenic and tumor-suppressive roles.MiR-10a is described as a tumor suppressor in various neoplasms,but its role in BC is controversial.This study aims to assess the activity of miR-10a in cellular invasion and proliferation in two distinct BC cell lines.Methods:The study used high-grade T24 and low-grade RT4 bladder cell lines.Cells were transfected with miR-10a mimic or a non-targeting control.Transfection efficiency was validated by qPCR.Cell proliferation was cultured for 10–14 days.Cell migration and invasion were evaluated using Matrigel.All assays were conducted in triplicate.Results:The T24 cells transfected with miR-10a presented decreased cellular proliferation and invasion compared to the Scramble(p=0.0481 and p<0.0001,respectively).In the RT4 cell line,there was only a significant reduction in cellular proliferation after miR-10a transfection(p=0.0029).Conclusions:Our findings suggest that miR-10a has a tumoral suppressor role in BC,demonstrating higher efficacy in high-grade cells.
基金financial support from the National Natural Science Foundation of China(NSFC Grant No.22076138)the National Natural Science Foundation of China(NSFC Grant No.62174119).
文摘Bladder cancer(BC)is a common malignancy and among the leading causes of cancer death worldwide.Analysis of BC cells is of great significance for clinical diagnosis and disease treatment.Current approaches rely mainly on imaging-based technology,which requires complex staining and sophisticated instrumentation.In this work,we develop a label-free method based on artificial intelligence(AI)-assisted impedance-based flow cytometry(IFC)to differentiate between various BC cells and epithelial cells at single-cell resolution.By applying multiple-frequency excitations,the electrical characteristics of cells,including membrane and nuclear opacities,are extracted,allowing distinction to be made between epithelial cells,low-grade,and high-grade BC cells.Through the use of a constriction channel,the electro-mechanical properties associated with active deformation behavior of cells are investigated,and it is demonstrated that BC cells have a greater capability of shape recovery,an observation that further increases differentiation accuracy.With the assistance of a convolutional neural network-based AI algorithm,IFC is able to effectively differentiate various BC and epithelial cells with accuracies of over 95%.In addition,different grades of BC cells are successfully differentiated in both spiked mixed samples and bladder tumor tissues.
文摘Objectives:Intravesical Bacillus Calmette-Guérin(BCG)therapy is a gold standard for patients with high-risk non-muscle invasive bladder cancer(NMIBC).Although a long-lasting therapeutic response is observed in most patients,BCG failure occurs in 30%–50%of patients and a progression to muscle-invasive disease is found in 10%–15%.Therefore,predicting high-risk patients who might not benefit from BCG treatment is critical.The purpose of this study was to identify,whether the presence of specific oncogenic mutations might be indicative of BCG treatment response.Methods:Nineteen high-grade NMIBC patients who received intravesical BCG were retrospectively enrolled and divided into“responders”and“non-responders”groups.Tissue samples from transurethral resection of bladder cancer were performed before starting therapy and were examined using a multigene sequencing panel.Results:Mutations in TP53,FGFR3,PIK3CA,KRAS,CTNNB1,ALK and DDR2 genes were detected.TP53 and FGFR3 were found to be the most frequently mutated genes in our cohort(31.6%and 26.3%,respectively),followed by PIK3CA(15.8%).In the BCG-responsive patient group,90%of samples were found to have mutated genes,with almost 50%of them showing mutations in tyrosine kinase receptors and CTNNB1 genes.On the other hand,in the BCG-unresponsive group,we found mutations in 44.4%of samples,mainly in TP53 gene.Conclusions:Our findings suggest that a Next-Generation Sequencing(NGS)multigene panel is useful in predicting BCG response in patients with NMIBC.
基金supported(in part)by the National Key Research and Development Program(2022YFC3600700)the Fundamental Research Funds for the Central Universities(2042024YXA008)the Young Top-Notch Talent Cultivation Program of Hubei Province(for Prof.Xian-Tao Zeng).
文摘Background:The burden of common urologic diseases,including benign prostatic hyperplasia(BPH),urinary tract infections(UTI),urolithiasis,bladder cancer,kidney cancer,and prostate cancer,varies both geographically and within specific regions.It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases.Methods:We obtained data on incidence,prevalence,mortality,and disability-adjusted life-years(DALYs)for the aforementioned urologic diseases by age,sex,location,and year from the Global Burden of Disease(GBD)2021.We analyzed the burden associated with urologic diseases based on socio-demographic index(SDI)and attributable risk factors.The trends in burden over time were assessed using estimated annual percentage changes(EAPC)along with a 95%confidence interval(CI).Results:In 2021,BPH and UTI were the leading causes of age-standardized incidence rate(ASIR)and age-standardized prevalence rate(ASPR),with rates of 5531.88 and 2782.59 per 100,000 persons,respectively.Prostate cancer was the leading cause of both age-standardized mortality rate(ASMR)and age-standardized DALYs rate(ASDR),with rates of 12.63 and 217.83 per 100,000 persons,respectively.From 1990 to 2021,there was an upward trend in ASIR,ASPR,ASMR,and ASDR for UTI,while urolithiasis showed a downward trend.The middle and low-middle SDI quintile levels exhibited higher incidence,prevalence,mortality,and DALYs related to UTI,urolithiasis,and BPH,while the high and high-middle SDI quintile levels showed higher rates for the three cancers.The burden of these 6 urologic diseases displayed diverse age and sex distribution patterns.In 2021,a high body mass index(BMI)contributed to 20.07%of kidney cancer deaths worldwide,while smoking accounted for 26.48%of bladder cancer deaths and 3.00%of prostate cancer deaths.Conclusions:The global burden of 6 urologic diseases presents a significant public health challenge.Urgent international collaboration is essential to advance the improvement of urologic disease management,encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies.
文摘The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.
基金This work was supported by the 2023 Guangzhou Basic and Applied Basic Research Project(2023A04J2132).
文摘Bladder cancer(BC)ranks as the tenth most common cancer globally.Histopathologically,BC is broadly categorized into urothelial and non-urothelial BC.Urothelial carcinoma represents over 90%of BC in most regions worldwide.The standard treatment procedure for diagnosing and treating non-muscle-invasive bladder cancer(NMIBC)is transurethral resection of bladder tumors(TURBT).Currently,the standard of care for muscle-invasive bladder cancer(MIBC)is neoadjuvant chemotherapy followed by radical cystectomy.Cryoablation therapy is a medical technique that uses extremely low temperatures to destroy diseased tissue.This treatment serves as a therapeutic tool for both benign and malignant diseases in organs such as the kidney,prostate gland,lung,liver,and breast,and is particularly effective for unresectable tumors,offering less trauma,quick recovery,good tolerability,and symptom control.However,cryoablation has its limitations.Over the past few years,cryoablation therapy has emerged as a new method for treating early BC.This treatment is minimally invasive,precise,and offers quick recovery,providing patients with a new treatment option.Although randomized studies are still limited,increasing evidence suggests its potential application in bladder cancer combined with transurethral resection(TURBT)or medication.Cryoablation is not standard therapy for bladder cancer.Treatment decisions should be discussed by a multidisciplinary team of urologists,oncologists,and interventional physicians and require more randomized controlled trials to define patient selection criteria and treatment approaches.
基金supported by the National Natural Science Foundation of China(Nos.82273443,81602234 and 81802538)the Natural Science Foundation of Hubei Province(Nos.2017CFB637 and 2023AFB1041).
文摘Objective This study aimed to investigate the role of the long noncoding RNA(lncRNA)maternally expressed gene 3(MEG3)in the epithelial-mesenchymal transition(EMT)of bladder cancer cells and the potential mechanisms.Methods Cell invasion,migration,and wound healing assays were conducted to assess the effects of MEG3 on the invasive and migratory capabilities of bladder cancer cells.The expression levels of E-cadherin were measured using Western blotting,RT-qPCR,and dual luciferase reporter assays.RNA immunoprecipitation and pull-down assays were performed to investigate the interactions between MEG3 and its downstream targets.Results MEG3 suppressed the invasion and migration of bladder cancer cells and modulated the transcription of E-cadherin.The binding of MEG3 to the zinc finger region of the transcription factor Snail prevented its ability to transcriptionally repress E-cadherin.Additionally,MEG3 suppressed the phosphorylation of extracellular regulated protein kinase(ERK),c-Jun N-terminal kinase(JNK),and P38,thereby decreasing the expression of Snail and stimulating the expression of E-cadherin.Conclusion MEG3 plays a vital role in suppressing the EMT in bladder cancer cells,indicating its potential as a promising therapeutic target for the treatment of bladder cancer.
