Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal ...Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal strategies.Methods:We established GC(Gemcitabine and Cisplatin)-resistant T24-R and UC3-R cell lines from T24 and UM-UC-3(UC3)cells.Transcriptomic and proteomic analyses identified differentially expressed molecules.Apoptosis and cell viability were assessed by flow cytometry and CCK-8(Cell Counting Kit-8)assays,while RT-qPCR(Reverse Transcription Quantitative Polymerase Chain Reaction)and Western blot analyzed gene and protein expression.Immunofluorescence evaluated FAK(Focal Adhesion Kinase)phosphorylation,and a xenograft mouse model validated the findings in vivo.Results:Integrated transcriptomic and proteomic analysis identified FN1(fibronectin)as a consistently upregulated top candidate in resistant cells(T24-R transcript log_(2)FC=2.8,protein log_(2)FC=0.9;UC3-R transcript log_(2)FC=3.7;all p<0.001).Knockdown of FN1 reduced chemoresistance(Resistance Index:5.2 in T24-R and 2.0 in UC3-R cells,p<0.001)and enhanced apoptosis(approximately 4.5-fold in T24-R and 7.5-fold in UC3-R,p<0.001).ITGB4(Integrin Subunit Beta 4)was upregulated in resistant cells(transcript log_(2)FC:4.2 in T24-R and 3.03 in UC3-R;protein log_(2)FC:0.67 in T24-R;all p<0.01).Critically,ITGB4 knockdown abolished the chemoresistance promoted by exogenous FN1,which was associated with increased FAK(Y397)phosphorylation.Conclusion:Our results demonstrate that the FN1-ITGB4 axis drives chemoresistance in bladder cancer via FAK signaling.Targeting this axis represents a promising strategy to overcome chemoresistance.展开更多
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inhibits proliferation and induces apoptosis by upregulation of miR-16 in bladder cancer cell line T24”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1227–1234.
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
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
Immune checkpoint inhibitors(ICIs)play a significant role in tumor treatment,but the immune-related adverse events(irAEs),which brings about have also attracted much attention.Among them,toxic epidermal necrolysis(TEN...Immune checkpoint inhibitors(ICIs)play a significant role in tumor treatment,but the immune-related adverse events(irAEs),which brings about have also attracted much attention.Among them,toxic epidermal necrolysis(TEN)is one of the most severe skin toxic reactions.This article reports a case of a bladder cancer patient who developed TEN after receiving ICIs treatment.The male patient was diagnosed with bladder cancer in November 2023.On April 29,2024,he was admitted to the Third Hospital of Changsha for antitumor treatment.In May 2024,he developed immune-related myocarditis after treatment with toripalimab.On July 6,2024,the patient switched to envafolimab treatment,and on July 16,he developed rashes and eventually progressed to TEN.After treatment with glucocorticoids and related symptomatic measures,the patient improved.TEN is a rare but serious irAE in ICIs treatment.Suspected patients should be intervened early,and patients who have already developed it should be actively treated,in order to enhance the understanding and management of TEN caused by ICIs treatment.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
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
Objective:Cisplatin-based chemotherapy is a cornerstone for bladder cancer treatment,but the development of resistance remains a major clinical challenge.Curcumol,a bioactive sesquiterpenoid derived from Curcumae Rhiz...Objective:Cisplatin-based chemotherapy is a cornerstone for bladder cancer treatment,but the development of resistance remains a major clinical challenge.Curcumol,a bioactive sesquiterpenoid derived from Curcumae Rhizoma,has shown anti-tumor potential.This study investigated the efficacy of curcumol in overcoming cisplatin resistance and elucidated its underlying molecular mechanisms in bladder cancer progression.Methods:Clinical correlation was assessed in patients receiving neoadjuvant chemotherapy with or without Curcumae Rhizoma.The anti-tumor effects of curcumol were evaluated in both cisplatin-sensitive and cisplatinresistant bladder cancer cells.Multi-omics approaches,including RNA sequencing,proteomics and metabolomics,were employed.Key mechanisms involving H3K9 lactylation(H3K9la)were explored via Western blotting,immunohistochemistry,and cleavage under targets and tagmentation(CUT&Tag)assays.The role of the identified target ORC6 was validated through genetic knockout and overexpression.Finally,ferroptosis was confirmed by measuring lipid peroxidation[malondialdehyde(MDA)],total iron levels,and ferroptosis-related protein markers in vitro.Results:Clinical data indicated that patients administered Curcumae Rhizoma exhibited enhanced responses to neoadjuvant chemotherapy.In addition,curcumol suppressed the proliferation,migration,and invasion of both bladder cancer cells and cisplatin-resistant cells.Mechanistically,proteomic analysis and non-targeted metabolomics revealed that curcumol suppresses glycolysis and lactate production.Subsequently,Western blotting analysis demonstrated a marked reduction in H3K9la levels in both T24 and 5637 cells following curcumol treatment.This decrease in H3K9la was also observed in patient tumor tissues via immunohistochemistry staining.CUT&Tag analysis identified that H3K9la is enriched with the highest number of reads at the ORC6 promoter region.Combined in vitro and in vivo experiments indicated that OCR6 exerted a tumor-promoting effect on bladder cancer.Its knockout induced G0/G1 phase arrest and enhanced apoptosis,while its expression contributed to cancer progression by enhancing invasive and migratory capabilities.Furthermore,ORC6 overexpression correlated with ferroptosis scores and ferroptosis-related genes.In vitro,OCR6 knockout promoted ferroptosis via DNA damage,characterized by elevated MDA content,decreased expression of core ferroptosis-related proteins(GPX4 and SLC7A11),increased percentage ofγH2AX-positive cells and longer DNA tails.Finally,we performed rescue experiments using a ferroptosis inhibitor in ORC6 knockout cells,which indicated that ferroptosis inhibitor could weaken the effect of ORC6 knockout on the invasive,migratory,and proliferative capacities.Conclusions:Our findings demonstrated that curcumol effectively counteracted cisplatin resistance and inhibited bladder cancer progression by targeting the glycolysis-H3K9la-ORC6 axis to induce ferroptosis.This study established a critical link between metabolic reprogramming,histone lactylation,and ferroptosis,providing a novel therapeutic avenue for treating chemoresistant bladder cancer.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
Objective:This study aimed to explore the anticancer potential of Cannabis sativa(C.sativa)strains,specifically PARIS,Dairy Queen(DQ),and super cannabidiol(sCBD),on bladder cancer cells.Given the increasing interest i...Objective:This study aimed to explore the anticancer potential of Cannabis sativa(C.sativa)strains,specifically PARIS,Dairy Queen(DQ),and super cannabidiol(sCBD),on bladder cancer cells.Given the increasing interest in cannabinoids like cannabichromene(CBC)and delta-9-tetrahydrocannabinol(THC)for their therapeutic properties,we evaluated their cytotoxic effects on urothelial carcinoma(UC)cell lines and their ability to inhibit cell migration and induce apoptosis in both two-dimensional cell models and three-dimensional ex vivo organ cultures(EVOCs).Methods:C.sativa strains were screened for their cytotoxicity against UC cell lines(HTB-4 and HTB-9)using XTT assays.Their phytocannabinoid content was analyzed using high-performance liquid chromatography.We employed fluorescence-activated cell-sorting to determine apoptosis and cell cycle,migration assays to determine cell migration,and EVOCs to evaluate the cytotoxic effect on UC.Gene expression was determined by quantitative polymerase chain reaction.Results:Three commercial C.sativa strains,PARIS,DQ,and sCBD,were found to have the most potent anticancer effects on bladder cancer cells.All extracts contain CBC and THC at different concentrations.In XTT assays on UC cell lines,PARIS had a half-maximal inhibitory concentration(IC50)of 21.58 mg/mL,while DQ and sCBD had similar cytotoxic activity with IC_(50) values for 48-h treatment of 17.99 mg/mL and 17.88 mg/mL,respectively.DQ and sCBD extracts were found to significantly reduce cell migration and increase the percentage of cells in S phase and G_(2)/M phase within the cell population.In EVOCs,the extracts initiated cell death with the expression of apoptosis-related genes increased following exposure to treatment.Conclusion:The findings suggest that C.sativa strains PARIS,DQ,and sCBD,containing CBC and THC,exhibit significant anticancer activity against UC cell lines and ex vivo models.These results underscore the therapeutic potential of CBC-and THC-rich C.sativa extracts in bladder cancer treatment.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:Pelvic organ-sparing surgery aims to preserve vital reproductive and sexual organs,enhancing quality of life,especially in premenopausal women.Pelvic organ preservation for female patients undergoing radical...Objective:Pelvic organ-sparing surgery aims to preserve vital reproductive and sexual organs,enhancing quality of life,especially in premenopausal women.Pelvic organ preservation for female patients undergoing radical cystectomy is now emphasized for sexual and hormonal function.Recent screening studies show no survival advantage despite early diagnosis of ovarian cancer,but opportunistic salpingectomy could reduce high-grade serous carcinoma risk.The aim of this review was to analyze the incidence of metachronous or delayed ovarian cancer in patients undergoing radical cystectomy for bladder cancer.Methods:PubMed,Scopus,Web of Science,ClinicalTrials.gov,and Cochrane Library were searched systematically for English-language articles up to June 2024.The selection was done first by title and abstract screening and then by full-text assessment for eligibility.This review has been registered in PROSPERO(CRD42024561902).Results:This review included two retrospective studies(2211 patients).Most patients had local or regional advanced disease,with a minority having distant disease.Only one study reported direct pelvic organ involvement from urothelial cancer,with no ovarian involvement found.Among patients who had organ-sparing surgery or pelvic exenteration,only two developed ovarian cancer post-surgery.No mean follow-up time or side effects from pelvic organ removal were reported in either study.Conclusion:When oncologically safe,ovarian-sparing surgery with salpingectomy should be considered in female bladder cancer patients undergoing radical cystectomy.Opportunistic salpingectomy should be encouraged during abdominal urological surgeries,with thorough preoperative counseling guiding decisions.Further studies are needed to define the role of preventive gynecologic surgery in urologic procedures.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
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
Given the critical shortage of antibody-drug conjugates(ADCs)for bladder cancer(BCa),we developed a novel FGFR3-targeted ADC,LZU-WZLYFG001,composed of a humanized anti-FGFR3 IgG1 monoclonal antibody,a cleavable GGFG l...Given the critical shortage of antibody-drug conjugates(ADCs)for bladder cancer(BCa),we developed a novel FGFR3-targeted ADC,LZU-WZLYFG001,composed of a humanized anti-FGFR3 IgG1 monoclonal antibody,a cleavable GGFG linker,and the payload DXD.The antibody was engineered in 293 cells and conjugated via thiol-based chemistry,achieving a drug-to-antibody ratio(DAR)of eight.Comprehensive preclinical assessments,including in vitro and in vivo studies using BCa cells,organoids,cell-derived xenograft and patient-derived xenograft(PDX)models,were conducted to evaluate efficacy,targeting ability,mechanism,safety and tissue distribution.LZU-WZLYFG001 demonstrated high purity,targeting specificity and low endotoxin levels,and it significantly inhibited BCa cell proliferation,migration and invasion at nanomolar concentrations,with efficacy strongly associated with FGFR3 expression levels.Mechanistic studies showed binding to FGFR3,internalization and lysosomal release of LZU-WZLYFG001.In organoid and xenograft models,LZU-WZLYFG001 exhibited superior efficacy compared with the gemcitabine+cisplatin(GC)regimen,particularly in GC-resistant PDX tumors,while also showing robust 3D penetration,a bystander effect,and no significant short-term toxicity.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
基金supported by grants from the National Natural Science Foundation of China(82372881 to Weiyang He)the Chongqing Biomedicine Key R&D Project(CSTB2021TIAD-KPX0041 to Weiyang He).
文摘Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal strategies.Methods:We established GC(Gemcitabine and Cisplatin)-resistant T24-R and UC3-R cell lines from T24 and UM-UC-3(UC3)cells.Transcriptomic and proteomic analyses identified differentially expressed molecules.Apoptosis and cell viability were assessed by flow cytometry and CCK-8(Cell Counting Kit-8)assays,while RT-qPCR(Reverse Transcription Quantitative Polymerase Chain Reaction)and Western blot analyzed gene and protein expression.Immunofluorescence evaluated FAK(Focal Adhesion Kinase)phosphorylation,and a xenograft mouse model validated the findings in vivo.Results:Integrated transcriptomic and proteomic analysis identified FN1(fibronectin)as a consistently upregulated top candidate in resistant cells(T24-R transcript log_(2)FC=2.8,protein log_(2)FC=0.9;UC3-R transcript log_(2)FC=3.7;all p<0.001).Knockdown of FN1 reduced chemoresistance(Resistance Index:5.2 in T24-R and 2.0 in UC3-R cells,p<0.001)and enhanced apoptosis(approximately 4.5-fold in T24-R and 7.5-fold in UC3-R,p<0.001).ITGB4(Integrin Subunit Beta 4)was upregulated in resistant cells(transcript log_(2)FC:4.2 in T24-R and 3.03 in UC3-R;protein log_(2)FC:0.67 in T24-R;all p<0.01).Critically,ITGB4 knockdown abolished the chemoresistance promoted by exogenous FN1,which was associated with increased FAK(Y397)phosphorylation.Conclusion:Our results demonstrate that the FN1-ITGB4 axis drives chemoresistance in bladder cancer via FAK signaling.Targeting this axis represents a promising strategy to overcome chemoresistance.
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.
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.
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 Research Project of Health Commission of Hunan Province,China(D202313016450)。
文摘Immune checkpoint inhibitors(ICIs)play a significant role in tumor treatment,but the immune-related adverse events(irAEs),which brings about have also attracted much attention.Among them,toxic epidermal necrolysis(TEN)is one of the most severe skin toxic reactions.This article reports a case of a bladder cancer patient who developed TEN after receiving ICIs treatment.The male patient was diagnosed with bladder cancer in November 2023.On April 29,2024,he was admitted to the Third Hospital of Changsha for antitumor treatment.In May 2024,he developed immune-related myocarditis after treatment with toripalimab.On July 6,2024,the patient switched to envafolimab treatment,and on July 16,he developed rashes and eventually progressed to TEN.After treatment with glucocorticoids and related symptomatic measures,the patient improved.TEN is a rare but serious irAE in ICIs treatment.Suspected patients should be intervened early,and patients who have already developed it should be actively treated,in order to enhance the understanding and management of TEN caused by ICIs treatment.
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 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supports of Science and Technology Plan Basic Project of Guizhou Province(No.ZK[2022]General 446)the Natural Science Fundation of Zhejiang Province(No.Q24H160134)+4 种基金Science and Technology Project of Zhejiang Health Commission(No.2024660542)Clinical Research Plan for TCM of Administration of Traditional Chinese Medicine of Zhejiang Province(No.2025075369)Bijie City Science and Technology Plan Project(No.[2025]No.60)National Health Commission of the People’s Republic of China-Zhejiang Province Jointly Constructed ProjectZhejiang Province Medical and Health Science and Technology Plan(No.WKJ-ZJ-2517)。
文摘Objective:Cisplatin-based chemotherapy is a cornerstone for bladder cancer treatment,but the development of resistance remains a major clinical challenge.Curcumol,a bioactive sesquiterpenoid derived from Curcumae Rhizoma,has shown anti-tumor potential.This study investigated the efficacy of curcumol in overcoming cisplatin resistance and elucidated its underlying molecular mechanisms in bladder cancer progression.Methods:Clinical correlation was assessed in patients receiving neoadjuvant chemotherapy with or without Curcumae Rhizoma.The anti-tumor effects of curcumol were evaluated in both cisplatin-sensitive and cisplatinresistant bladder cancer cells.Multi-omics approaches,including RNA sequencing,proteomics and metabolomics,were employed.Key mechanisms involving H3K9 lactylation(H3K9la)were explored via Western blotting,immunohistochemistry,and cleavage under targets and tagmentation(CUT&Tag)assays.The role of the identified target ORC6 was validated through genetic knockout and overexpression.Finally,ferroptosis was confirmed by measuring lipid peroxidation[malondialdehyde(MDA)],total iron levels,and ferroptosis-related protein markers in vitro.Results:Clinical data indicated that patients administered Curcumae Rhizoma exhibited enhanced responses to neoadjuvant chemotherapy.In addition,curcumol suppressed the proliferation,migration,and invasion of both bladder cancer cells and cisplatin-resistant cells.Mechanistically,proteomic analysis and non-targeted metabolomics revealed that curcumol suppresses glycolysis and lactate production.Subsequently,Western blotting analysis demonstrated a marked reduction in H3K9la levels in both T24 and 5637 cells following curcumol treatment.This decrease in H3K9la was also observed in patient tumor tissues via immunohistochemistry staining.CUT&Tag analysis identified that H3K9la is enriched with the highest number of reads at the ORC6 promoter region.Combined in vitro and in vivo experiments indicated that OCR6 exerted a tumor-promoting effect on bladder cancer.Its knockout induced G0/G1 phase arrest and enhanced apoptosis,while its expression contributed to cancer progression by enhancing invasive and migratory capabilities.Furthermore,ORC6 overexpression correlated with ferroptosis scores and ferroptosis-related genes.In vitro,OCR6 knockout promoted ferroptosis via DNA damage,characterized by elevated MDA content,decreased expression of core ferroptosis-related proteins(GPX4 and SLC7A11),increased percentage ofγH2AX-positive cells and longer DNA tails.Finally,we performed rescue experiments using a ferroptosis inhibitor in ORC6 knockout cells,which indicated that ferroptosis inhibitor could weaken the effect of ORC6 knockout on the invasive,migratory,and proliferative capacities.Conclusions:Our findings demonstrated that curcumol effectively counteracted cisplatin resistance and inhibited bladder cancer progression by targeting the glycolysis-H3K9la-ORC6 axis to induce ferroptosis.This study established a critical link between metabolic reprogramming,histone lactylation,and ferroptosis,providing a novel therapeutic avenue for treating chemoresistant bladder cancer.
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Objective:This study aimed to explore the anticancer potential of Cannabis sativa(C.sativa)strains,specifically PARIS,Dairy Queen(DQ),and super cannabidiol(sCBD),on bladder cancer cells.Given the increasing interest in cannabinoids like cannabichromene(CBC)and delta-9-tetrahydrocannabinol(THC)for their therapeutic properties,we evaluated their cytotoxic effects on urothelial carcinoma(UC)cell lines and their ability to inhibit cell migration and induce apoptosis in both two-dimensional cell models and three-dimensional ex vivo organ cultures(EVOCs).Methods:C.sativa strains were screened for their cytotoxicity against UC cell lines(HTB-4 and HTB-9)using XTT assays.Their phytocannabinoid content was analyzed using high-performance liquid chromatography.We employed fluorescence-activated cell-sorting to determine apoptosis and cell cycle,migration assays to determine cell migration,and EVOCs to evaluate the cytotoxic effect on UC.Gene expression was determined by quantitative polymerase chain reaction.Results:Three commercial C.sativa strains,PARIS,DQ,and sCBD,were found to have the most potent anticancer effects on bladder cancer cells.All extracts contain CBC and THC at different concentrations.In XTT assays on UC cell lines,PARIS had a half-maximal inhibitory concentration(IC50)of 21.58 mg/mL,while DQ and sCBD had similar cytotoxic activity with IC_(50) values for 48-h treatment of 17.99 mg/mL and 17.88 mg/mL,respectively.DQ and sCBD extracts were found to significantly reduce cell migration and increase the percentage of cells in S phase and G_(2)/M phase within the cell population.In EVOCs,the extracts initiated cell death with the expression of apoptosis-related genes increased following exposure to treatment.Conclusion:The findings suggest that C.sativa strains PARIS,DQ,and sCBD,containing CBC and THC,exhibit significant anticancer activity against UC cell lines and ex vivo models.These results underscore the therapeutic potential of CBC-and THC-rich C.sativa extracts in bladder cancer treatment.
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.
文摘Objective:Pelvic organ-sparing surgery aims to preserve vital reproductive and sexual organs,enhancing quality of life,especially in premenopausal women.Pelvic organ preservation for female patients undergoing radical cystectomy is now emphasized for sexual and hormonal function.Recent screening studies show no survival advantage despite early diagnosis of ovarian cancer,but opportunistic salpingectomy could reduce high-grade serous carcinoma risk.The aim of this review was to analyze the incidence of metachronous or delayed ovarian cancer in patients undergoing radical cystectomy for bladder cancer.Methods:PubMed,Scopus,Web of Science,ClinicalTrials.gov,and Cochrane Library were searched systematically for English-language articles up to June 2024.The selection was done first by title and abstract screening and then by full-text assessment for eligibility.This review has been registered in PROSPERO(CRD42024561902).Results:This review included two retrospective studies(2211 patients).Most patients had local or regional advanced disease,with a minority having distant disease.Only one study reported direct pelvic organ involvement from urothelial cancer,with no ovarian involvement found.Among patients who had organ-sparing surgery or pelvic exenteration,only two developed ovarian cancer post-surgery.No mean follow-up time or side effects from pelvic organ removal were reported in either study.Conclusion:When oncologically safe,ovarian-sparing surgery with salpingectomy should be considered in female bladder cancer patients undergoing radical cystectomy.Opportunistic salpingectomy should be encouraged during abdominal urological surgeries,with thorough preoperative counseling guiding decisions.Further studies are needed to define the role of preventive gynecologic surgery in urologic procedures.
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.
基金supported by the Major Science and Technology Special Project of Gansu Province(24ZDFA002)the National Natural Science Foundation of China(82060459)+1 种基金the Key Research and Development Program of Gansu Province(23YFFA0007)the Joint Research Fund of Gansu Province(23JRRA1511)。
文摘Given the critical shortage of antibody-drug conjugates(ADCs)for bladder cancer(BCa),we developed a novel FGFR3-targeted ADC,LZU-WZLYFG001,composed of a humanized anti-FGFR3 IgG1 monoclonal antibody,a cleavable GGFG linker,and the payload DXD.The antibody was engineered in 293 cells and conjugated via thiol-based chemistry,achieving a drug-to-antibody ratio(DAR)of eight.Comprehensive preclinical assessments,including in vitro and in vivo studies using BCa cells,organoids,cell-derived xenograft and patient-derived xenograft(PDX)models,were conducted to evaluate efficacy,targeting ability,mechanism,safety and tissue distribution.LZU-WZLYFG001 demonstrated high purity,targeting specificity and low endotoxin levels,and it significantly inhibited BCa cell proliferation,migration and invasion at nanomolar concentrations,with efficacy strongly associated with FGFR3 expression levels.Mechanistic studies showed binding to FGFR3,internalization and lysosomal release of LZU-WZLYFG001.In organoid and xenograft models,LZU-WZLYFG001 exhibited superior efficacy compared with the gemcitabine+cisplatin(GC)regimen,particularly in GC-resistant PDX tumors,while also showing robust 3D penetration,a bystander effect,and no significant short-term toxicity.
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.
