Objective:To compare the efficacy and safety of hyperthermic intravesical chemotherapy(HIVEC)and intravesical chemotherapy(IVEC)in patients with intermediate and high risk nonmuscle-invasive bladder cancer(NMIBC)after...Objective:To compare the efficacy and safety of hyperthermic intravesical chemotherapy(HIVEC)and intravesical chemotherapy(IVEC)in patients with intermediate and high risk nonmuscle-invasive bladder cancer(NMIBC)after transurethral resection.Methods:We included 560 patients diagnosed with primary or recurrent NMIBC between April 2009 and December 2015 at 1 of 6 tertiary centers.We matched 364 intermediate or high risk cases and divided them into 2 groups:the HIVEC+IVEC group[chemohyperthermia(CHT)composed of 3 consecutive sessions followed by intravesical instillation without hyperthermia]and the IVEC group(intravesical instillation without hyperthermia).The data were recorded in the database.The primary endpoint was 2-year recurrence-free survival(RFS)in all NMIBC patients(n=364),whereas the secondary endpoints were the assessment of radical cystectomy(RC)and 5-year overall survival(OS).Results:There was a significant difference in the 2-year RFS between the two groups in all patients(n=364;HIVEC+IVEC:82.42%vs.IVEC:74.18%,P=0.038).Compared with the IVEC group,the HIVEC+IVEC group had a lower incidence of RC(P=0.0274).However,the 5-year OS was the same between the 2 groups(P=0.1434).Adverse events(AEs)occurred in 32.7%of all patients,but none of the events was serious(grades 3–4).No difference in the incidence or severity of AEs between each treatment modality was observed.Conclusions:This retrospective study showed that HIVEC+IVEC had a higher 2-year RFS and a lower incidence of RC than IVEC therapy in intermediate and high risk NMIBC patients.Both treatments were well-tolerated in a similar manner.展开更多
The aim of this study was to investigate the incidence of erectile dysfunction(ED)in nonmuscle-invasive bladder cancer(NMIBC)patients before and after transurethral resection(TUR)in China.Clinical data from 165 male p...The aim of this study was to investigate the incidence of erectile dysfunction(ED)in nonmuscle-invasive bladder cancer(NMIBC)patients before and after transurethral resection(TUR)in China.Clinical data from 165 male patients with NMIBC who received adjuvant intravesical chemotherapy after TUR in Neijiang First People’s Hospital(Neijiang,China)between January 2010 and June 2019 were retrospectively reviewed.The sexual function of these patients was evaluated before and 1.5 years after initial TUR by the International Index of Erectile Function-5(IIEF-5).An age-specific subanalysis was performed among the patients:<45 years old(Group 1,n=19)and≥45 years old(Group 2,n=146).Before and 1.5 years after TUR,the incidence rates of ED in Group 1 were 15.8%and 52.6%,and those in Group 2 were 54.1%and 61.0%,respectively.The difference between groups was statistically significant at the preoperative stage(15.8%vs 54.1%,P=0.002)but not at the postoperative stage(52.6%vs 61.0%,P=0.562).Compared with the preoperative stage,the incidence of ED at the postoperative stage was increased significantly in Group 1(15.8%vs 52.6%,P=0.017)but not in Group 2(54.1%vs 61.0%,P=0.345).In conclusion,the incidence of ED increased in male NMIBC patients under the age of 45 years after TUR in China.These patients should be offered professional counseling during the follow-up period.展开更多
Objectives: Surgical specimens obtained at the time of the last transurethral resection of bladder tumor (TURBT) for patients with nonmuscle-invasive bladder cancer (NMIBC) who underwent radical cystectomy were retros...Objectives: Surgical specimens obtained at the time of the last transurethral resection of bladder tumor (TURBT) for patients with nonmuscle-invasive bladder cancer (NMIBC) who underwent radical cystectomy were retrospectively evaluated in order to investigate the relationship between pathological variation and upstaging of NMIBC. Methods and Materials: Twenty patients (19 men, 1 woman;aged 69.4 ± 12.1 (mean ± SD) years) diagnosed with NMIBC underwent radical cystectomy during follow-up. Results: Five of the 20 patients (25%) had pathological upstaging in the radical cystectomy specimens. There was a statistical association between pathological upstaging and cancer death (p = 0.002). There were three patterns of pathological variation in the upstaged specimens: 1) in patients with BCG-resistant NMIBC, urothelial carcinoma invaded through the lamina propria;2) urothelial carcinoma showed diffuse invasion beyond the deep lamina propria, and the cancer cells had infiltrated as single cells and formed nodules;3) TURBT specimens showed a micropapillary variant. Conclusions: Since these pathological variations correlated with pathological upstaging, they may provide an indication for cystectomy in NMIBC patients.展开更多
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
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
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.
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
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: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
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
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: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
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
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
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
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
基金supported by the National Natural Science Foundation of China(Grant No.81972918)the Guangzhou Key Medical Discipline Construction Project Fund+1 种基金the Guangzhou Major Clinical Technology Program(Grant No.2019ZD16)the Guanzhou Municipal Special Clinical Technology Project(Grant No.2019TS40)。
文摘Objective:To compare the efficacy and safety of hyperthermic intravesical chemotherapy(HIVEC)and intravesical chemotherapy(IVEC)in patients with intermediate and high risk nonmuscle-invasive bladder cancer(NMIBC)after transurethral resection.Methods:We included 560 patients diagnosed with primary or recurrent NMIBC between April 2009 and December 2015 at 1 of 6 tertiary centers.We matched 364 intermediate or high risk cases and divided them into 2 groups:the HIVEC+IVEC group[chemohyperthermia(CHT)composed of 3 consecutive sessions followed by intravesical instillation without hyperthermia]and the IVEC group(intravesical instillation without hyperthermia).The data were recorded in the database.The primary endpoint was 2-year recurrence-free survival(RFS)in all NMIBC patients(n=364),whereas the secondary endpoints were the assessment of radical cystectomy(RC)and 5-year overall survival(OS).Results:There was a significant difference in the 2-year RFS between the two groups in all patients(n=364;HIVEC+IVEC:82.42%vs.IVEC:74.18%,P=0.038).Compared with the IVEC group,the HIVEC+IVEC group had a lower incidence of RC(P=0.0274).However,the 5-year OS was the same between the 2 groups(P=0.1434).Adverse events(AEs)occurred in 32.7%of all patients,but none of the events was serious(grades 3–4).No difference in the incidence or severity of AEs between each treatment modality was observed.Conclusions:This retrospective study showed that HIVEC+IVEC had a higher 2-year RFS and a lower incidence of RC than IVEC therapy in intermediate and high risk NMIBC patients.Both treatments were well-tolerated in a similar manner.
文摘The aim of this study was to investigate the incidence of erectile dysfunction(ED)in nonmuscle-invasive bladder cancer(NMIBC)patients before and after transurethral resection(TUR)in China.Clinical data from 165 male patients with NMIBC who received adjuvant intravesical chemotherapy after TUR in Neijiang First People’s Hospital(Neijiang,China)between January 2010 and June 2019 were retrospectively reviewed.The sexual function of these patients was evaluated before and 1.5 years after initial TUR by the International Index of Erectile Function-5(IIEF-5).An age-specific subanalysis was performed among the patients:<45 years old(Group 1,n=19)and≥45 years old(Group 2,n=146).Before and 1.5 years after TUR,the incidence rates of ED in Group 1 were 15.8%and 52.6%,and those in Group 2 were 54.1%and 61.0%,respectively.The difference between groups was statistically significant at the preoperative stage(15.8%vs 54.1%,P=0.002)but not at the postoperative stage(52.6%vs 61.0%,P=0.562).Compared with the preoperative stage,the incidence of ED at the postoperative stage was increased significantly in Group 1(15.8%vs 52.6%,P=0.017)but not in Group 2(54.1%vs 61.0%,P=0.345).In conclusion,the incidence of ED increased in male NMIBC patients under the age of 45 years after TUR in China.These patients should be offered professional counseling during the follow-up period.
文摘Objectives: Surgical specimens obtained at the time of the last transurethral resection of bladder tumor (TURBT) for patients with nonmuscle-invasive bladder cancer (NMIBC) who underwent radical cystectomy were retrospectively evaluated in order to investigate the relationship between pathological variation and upstaging of NMIBC. Methods and Materials: Twenty patients (19 men, 1 woman;aged 69.4 ± 12.1 (mean ± SD) years) diagnosed with NMIBC underwent radical cystectomy during follow-up. Results: Five of the 20 patients (25%) had pathological upstaging in the radical cystectomy specimens. There was a statistical association between pathological upstaging and cancer death (p = 0.002). There were three patterns of pathological variation in the upstaged specimens: 1) in patients with BCG-resistant NMIBC, urothelial carcinoma invaded through the lamina propria;2) urothelial carcinoma showed diffuse invasion beyond the deep lamina propria, and the cancer cells had infiltrated as single cells and formed nodules;3) TURBT specimens showed a micropapillary variant. Conclusions: Since these pathological variations correlated with pathological upstaging, they may provide an indication for cystectomy in NMIBC patients.
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.
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.
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.
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 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.
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.
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.
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.
