Ferroptosis,a type of regulated cell death driven by iron-dependent lipid peroxidation,is mainly initiated by extramitochondrial lipid peroxidation due to the accumulation of iron-dependent reactive oxygen species.Fer...Ferroptosis,a type of regulated cell death driven by iron-dependent lipid peroxidation,is mainly initiated by extramitochondrial lipid peroxidation due to the accumulation of iron-dependent reactive oxygen species.Ferroptosis is a prevalent and primitive form of cell death.Numerous cellular metabolic processes regulate ferroptosis,including redox homeostasis,iron regulation,mitochondrial activity,amino acid metabolism,lipid metabolism,and various disease-related signaling pathways.Ferroptosis plays a pivotal role in cancer therapy,particularly in the eradication of aggressive malignancies resistant to conventional treatments.Multiple studies have explored the connection between ferroptosis and bladder cancer,focusing on its incidence and treatment outcomes.Several biomolecules and tumor-associated signaling pathways,such as p53,heat shock protein 1,nuclear receptor coactivator 4,RAS-RAF-MEK,phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin,and the Hippo-tafazzin signaling system,exert a moderating influence on ferroptosis in bladder cancer.Ferroptosis inducers,including erastin,artemisinin,conjugated polymer nanoparticles,and quinazolinyl-arylurea derivatives,hold promise for enhancing the effectiveness of conventional anticancer medications in bladder cancer treatment.Combining conventional therapeutic drugs and treatment methods related to ferroptosis offers a promising approach for the treatment of bladder cancer.In this review,we analyze the research on ferroptosis to augment the efficacy of bladder cancer treatment.展开更多
Introduction:Bladder cancer(BC)has a high incidence and mortality rate worldwide.Suppressor anaphasepromoting complex domain containing 2(SAPCDC2)is over-expressed in a variety of tumors.Objectives:This study investig...Introduction:Bladder cancer(BC)has a high incidence and mortality rate worldwide.Suppressor anaphasepromoting complex domain containing 2(SAPCDC2)is over-expressed in a variety of tumors.Objectives:This study investigated the effects of SAPCD2 knockdown on BC cells.Methods:T24 and UMUC3 cell models and the xenografted BC tumor model with SAPCD2 knockdown were established to observe the malignant phenotype of BC cells by cell counting kit-8 assay,colony formation test,wound healing,and Transwell assay,mRNA and proteins expressions were measured with quantitative real-time polymerase chain reaction,western blotting,and tissue immunohistochemistry.Lithium chloride agonist on the Wnt/β-catenin pathway was used to clarify the molecular mechanism of SAPCD2 knockdown.Results:SAPCD2 expression was significantly higher in BC cell lines than in SVHUC-1 cells.SAPCD2 knockdown inhibited viability and cloning,hindered the G0/G1 phase of the cell cycle in UMUC3 and T24 cells,and decreased the migration and invasiveness of BC cells.SAPCD2 knockdown inhibited expression levels of cyclin D1,cyclin B1,N-cadherin,vimentin,Snail,β-catenin,c-Myc,and cyclin-dependent kinase 4,while the P21 and E-cadherin were raised by SAPCD2 knockdown.Furthermore,lithium chloride reversed the effects of SAPCD2 knockdown on the expression levels of the above proteins in UMUC3 and T24 cells.In vivo,SAPCD2 knockdown inhibited the volume,weight,and expression of Ki-67 andβ-catenin in tumors and increased the E-cadherin expression.Conclusion:SAPCD2 knockdown inhibits the malignant phenotype of BC via a pathway involvingβ-catenin.展开更多
BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained...BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.展开更多
Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects...Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle advancement.Their results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell cycle.This research gives a novel direction and concept for targeted therapy of BC.展开更多
BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for ...BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer.As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients,we examined American College of Surgeons National Surgical Quality Improvement Program(NSQIP)database to determine if there was higher morbidity among the neo-adjuvant group within the 30-day post-operative period.We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity.AIM To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery.METHODS A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity(bile leak,infection rate,rate of converting to open surgery,etc.)compared to the group who only had surgery.To calculate the odds ratio for the primary and secondary outcomes,a crude logistic regression was performed.RESULTS Of the 452 patients,52 patients received NACT prior to surgery.There were no statistically significant differences in the odds of morbidity between the two groups,including bile leak[odds ratio(OR),0.69;95%confidence interval(95%CI):0.16-2.10;P=0.55],superficial wound infection(OR,0.58;95%CI:0.03-3.02;P=0.61),and organ space wound infection(OR,0.63;95%CI:0.18-1.63;P=0.61).CONCLUSION There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.展开更多
Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management...Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.展开更多
BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patie...BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patients with bladder cancer,meanwhile,predict the sensitivity of patients to chemotherapy and immunotherapy.METHODS Bladder cancer information data was obtained from The Cancer Genome Atlas and GSE32894.The CIBERSORT was used to calculate the immune score of each sample.Weighted gene co-expression network analysis was used to find genes that will have the same or similar expression patterns.Subsequently,multivariate cox regression and lasso regression was used to further screen prognosis-related genes.The prrophetic package was used to predict phenotype from gene expression data,drug sensitivity of external cell line and predict clinical data.RESULTS The stage and risk scores are independent prognostic factors in patients with BUC.Mutations in FGFR3 lead to an increase in Tregs percolation and affect the prognosis of the tumor,and additionally,EMP1,TCHH and CNTNAP3B in the model are mainly positively correlated with the expression of immune checkpoints,while CMTM8,SORT1 and IQSEC1 are negatively correlated with immune checkpoints and the high-risk group had higher sensitivity to chemotherapy drugs.CONCLUSION Prognosis-related models of bladder tumor patients,based on Treg and NK cell percolation in tumor tissue.In addition to judging the prognosis of patients with bladder cancer,it can also predict the sensitivity of patients to chemotherapy and immunotherapy.At the same time,patients were divided into high and low risk groups based on this model,and differences in genetic mutations were found between the high and low risk groups.展开更多
Gall bladder cancer(GBC)is becoming a very devastating form of hepatobiliary cancer in India.Every year new cases of GBC are quite high in India.Despite recent advanced multimodality treatment options,the survival of ...Gall bladder cancer(GBC)is becoming a very devastating form of hepatobiliary cancer in India.Every year new cases of GBC are quite high in India.Despite recent advanced multimodality treatment options,the survival of GBC patients is very low.If the disease is diagnosed at the advanced stage(with local nodal metastasis or distant metastasis)or surgical resection is inoperable,the prognosis of those patients is very poor.So,perspectives of targeted therapy are being taken.Targeted therapy includes hormone therapy,proteasome inhibitors,signal transduction and apoptosis inhibitors,angiogenesis inhibitors,and immunotherapeutic agents.One such signal transduction inhibitor is the specific short interfering RNA(siRNA)or short hairpin RNA(shRNA).For developing siRNAmediated therapy shRNA,although several preclinical studies to evaluate the efficacy of these key molecules have been performed using gall bladder cells,many more clinical trials are required.To date,many such genes have been identified.This review will discuss the recently identified genes associated with GBC and those that have implications in its treatment by siRNA or shRNA.展开更多
Objective:The imbalance of antioxidants and pro-oxidants plays a crucial role in the carcinogenesis of bladder cancer(BC).This study aimed to evaluate serum antioxidant status in patients with BC and determine its pot...Objective:The imbalance of antioxidants and pro-oxidants plays a crucial role in the carcinogenesis of bladder cancer(BC).This study aimed to evaluate serum antioxidant status in patients with BC and determine its potential use in the diagnosis and progression potential considerations following histopathological assessment.Methods:A cross-sectional study included 90 patients with BC,divided into Ta,T1,and T2eT4 stage subgroups,and according to cancer progression potential,into low-grade(LG)and highgrade(HG)subgroups.The control group(CG)included 30 healthy volunteers.Antioxidant status was determined using the spectrophotometric method and standard laboratory tests.Results:Serum superoxide dismutase activity was significantly higher in BC patients regarding cancer stage in comparison to the CG(p<0.001).Catalase activity was highest in T2eT4 subgroup and was significantly higher compared to the Ta(p<0.01)and T1(p<0.05)subgroups.Serum albumin level was significantly lower in the BC group compared to the CG(p<0.001).In addition,it was significantly lower in T2eT4 subgroup compared to T1 and Ta subgroups(p<0.01).A significant negative correlation was found between tumor size and serum albumin level only(r=0.386,p<0.01).Catalase activity was higher in HG subgroup(p=0.009),while bilirubin level was higher in LG subgroup(p=0.035).The optimal cut-off value of catalase activity in differentiating patients with LG and HG BC subgroups was 11.96 IU/L,and the specificity and sensitivity were 51.1% and 82.2%,respectively.Bilirubin level,for a calculated optimal cut-off value of 11.95 mmol/L,had a specificity of 44.1%and sensitivity of 80.0%.Conclusion:More invasive stages of BC with greater progression potential are associated with an increase in enzymatic antioxidant activity and a decrease in non-enzymatic antioxidant capacity.It may suggest a possible role of antioxidants in the prediction and monitoring of illness trajectory.展开更多
Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide ...Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.展开更多
Objective: The interplay between chemokine C-X-C motif ligand 12(CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently,targ...Objective: The interplay between chemokine C-X-C motif ligand 12(CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently,targeting this signaling axis has emerged as a potential strategy in cancer therapy. However, the precise role of CXCL12 in clinical therapy, especially in immunotherapy for bladder cancer(BCa), remains poorly elucidated.Methods: We gathered multiple omics data from public databases to unveil the clinical relevance and tumor immune landscape associated with CXCL12 in BCa patients. Univariate and multivariate Cox regression analyses were employed to assess the independent prognostic significance of CXCL12 expression and formulate a nomogram. The expression of CXCL12 in BCa cell lines and clinical tissue samples was validated using enzymelinked immunosorbent assays(ELISA) and immunohistochemistry(IHC).Results: While transcriptional expression of CXCL12 exhibited a decrease in nearly all tumor tissues, CXCL12 methylation expression was notably increased in BCa tissues. Single-cell RNA analysis highlighted tissue stem cells and endothelial cells as the primary sources expressing CXCL12. Abnormal CXCL12 expression, based on transcriptional and methylation levels, correlated with various clinical characteristics in BCa patients. Functional analysis indicated enrichment of CXCL12 and its co-expression genes in immune regulation and cell adhesion. The immune landscape analysis unveiled a significant association between CXCL12 expression and M2 macrophages(CD163~+ cells) in BCa tissues. Notably, CXCL12 expression emerged as a potential predictor of immunotherapy response and chemotherapy drug sensitivity in BCa patients.Conclusions: Taken together, these findings suggest aberrant production of CXCL12 in BCa tissues,potentially influencing the treatment responses of affected individuals.展开更多
Objective Cisplatin(CDDP)-based chemotherapy is a first-line,drug regimen for muscle-invasive bladder cancer(BC)and metastatic bladder cancer.Clinically,resistance to CDDP restricts the clinical benefit of some bladde...Objective Cisplatin(CDDP)-based chemotherapy is a first-line,drug regimen for muscle-invasive bladder cancer(BC)and metastatic bladder cancer.Clinically,resistance to CDDP restricts the clinical benefit of some bladder cancer patients.AT-rich interaction domain 1A(ARID1A)gene mutation occurs frequently in bladder cancer;however,the role of CDDP sensitivity in BC has not been studied.Methods We established ARID1A knockout BC cell lines using CRISPR/Cas9 technology.IC50 determination,flow cytometry analysis of apoptosis,and tumor xenograft assays were performed to verify changes in the CDDP sensitivity of BC cells losing ARID1A.qRT-PCR,Western blotting,RNA interference,bioinformatic analysis,and ChIP-qPCR analysis were performed to further explore the potential mechanism of ARID1A inactivation in CDDP sensitivity in BC.Results It was found that ARID1A inactivation was associated with CDDP resistance in BC cells.Mechanically,loss of ARID1A promoted the expression of eukaryotic translation initiation factor 4A3(EIF4A3)through epigenetic regulation.Increased expression of EIF4A3 promoted the expression of hsa_circ_0008399(circ0008399),a novel circular RNA(circRNA)identified in our previous study,which,to some extent,showed that ARID1A deletion caused CDDP resistance through the inhibitory effect of circ0008399 on the apoptosis of BC cells.Importantly,EIF4A3-IN-2 specifically inhibited the activity of EIF4A3 to reduce circ0008399 production and restored the sensitivity of ARID1A inactivated BC cells to CDDP.Conclusion Our research deepens the understanding of the mechanisms of CDDP resistance in BC and elucidates a potential strategy to improve the efficacy of CDDP in BC patients with ARID1A deletion through combination therapy targeting EIF4A3.展开更多
The number of studies in the literature that diagnose cancer with machine learning using genome data is quite limited.These studies focus on the prediction performance,and the extraction of genomic factors that cause ...The number of studies in the literature that diagnose cancer with machine learning using genome data is quite limited.These studies focus on the prediction performance,and the extraction of genomic factors that cause disease is often overlooked.However,finding underlying genetic causes is very important in terms of early diagnosis,development of diagnostic kits,preventive medicine,etc.The motivation of our study was to diagnose bladder cancer(BCa)based on genetic data and to reveal underlying genetic factors by using machine-learning models.In addition,conducting hyper-parameter optimization to get the best performance from different models,which is overlooked in most studies,was another objective of the study.Within the framework of these motivations,C4.5,random forest(RF),artificial neural networks(ANN),and deep learning(DL)were used.In this way,the diagnostic performance of decision tree(DT)-based models and black box models on BCa was also compared.The most successful model,DL,yielded an area under the curve(AUC)of 0.985 and a mean square error(MSE)of 0.069.For each model,hyper-parameters were optimized by an evolutionary algorithm.On average,hyper-parameter optimization increased MSE,root mean square error(RMSE),LogLoss,and AUC by 30%,17.5%,13%,and 6.75%,respectively.The features causing BCa were extracted.For this purpose,entropy and Gini coefficients were used for DT-based methods,and the Gedeon variable importance was used for black box methods.The single nucleotide polymorphisms(SNPs)rs197412,rs2275928,rs12479919,rs798766 and rs2275928,whose BCa relations were proven in the literature,were found to be closely related to BCa.In addition,rs1994624 and rs2241766 susceptibility loci were proposed to be examined in future studies.展开更多
BACKGROUND The purpose of the present study was to examine retrospectively the contribution of 18Fluorodeoxyglucose positron emission tomography computed tomography(18FDG-PET/CT)to the evaluation of response to first-...BACKGROUND The purpose of the present study was to examine retrospectively the contribution of 18Fluorodeoxyglucose positron emission tomography computed tomography(18FDG-PET/CT)to the evaluation of response to first-line gemcitabine plus cispla-tin-based chemotherapy in patients with metastatic bladder cancer.AIM To evaluate the response to Gemcitabine plus Cisplatin-based chemotherapy using 18FDG-PET/CT imaging in patients with metastatic bladder cancer.METHODS Between July 2007 and April 2019,79 patients underwent 18FDG-PET/CT imaging with the diagnosis of Metastatic Bladder Carcinoma(M-BCa).A total of 42 pa-tients(38 male,4 female)were included in the study,and all had been admi-nistered Gemcitabine plus Cisplatin-based chemotherapy.After completion of the therapy,the patients underwent a repeat 18FDG-PET/CT scan and the results were compared with the PET/CT findings before chemotherapy according to European Organisation for the Research and treatment of cancer criteria.Mean age was 66.1 years and standard deviation was 10.7 years(range:41–84 years).RESULTS Of the patients,seven(16.6%)were in complete remission,17(40.5%)were in partial remission,six(14.3%)had a stable disease,and 12(28.6%)had a pro-gressive disease.The overall response rate was 57.1 percent.CONCLUSION 18FDG-PET/CT can be considered as a successful imaging tool in evaluating response to first-line chemotherapy for metastatic bladder cancer.Anatomical and functional data obtained from PET/CT scans may be useful in the planning of secondline and thirdline chemotherapy.展开更多
BACKGROUND Acquired haemophilia(AH)is a serious autoimmune haematological disease caused by the production of auto-antibodies against coagulation factor VIII.In some patients,AH is associated with a concomitant malign...BACKGROUND Acquired haemophilia(AH)is a serious autoimmune haematological disease caused by the production of auto-antibodies against coagulation factor VIII.In some patients,AH is associated with a concomitant malignancy.In case of surgical intervention,AH poses a high risk of life-threatening bleeding.CASE SUMMARY A 60-year-old female patient with multiple recurrences of non-muscle invasive bladder cancer underwent transurethral tumour resection.A severe haematuria developed postoperatively warranting two endoscopic revisions;however,no clear source of bleeding was identified in the bladder.Subsequent haematological examination established a diagnosis of AH.Treatment with factor VIII inhibitor bypass activity and immunosuppressive therapy was initiated immediately.The patient responded well to the therapy and was discharged from the hospital 21 d after the primary surgery.At the 38-mo follow-up,both AH and bladder cancer remained in complete remission.CONCLUSION AH is a rare,life-threatening haematological disease.AH should be considered in patients with persistent severe haematuria or other bleeding symptoms,especially if combined with isolated activated partial thromboplastin time prolongation.展开更多
Bladder cancer is the second most common tumor in the urinary system after prostate cancer.It is highly heterogeneous and its developmental mechanism involves abnormal alterations in the structure and function of mult...Bladder cancer is the second most common tumor in the urinary system after prostate cancer.It is highly heterogeneous and its developmental mechanism involves abnormal alterations in the structure and function of multiple genomes.Researching the molecular classification of bladder cancer by using molecular biology techniques is important for defining the pathogenesis of the disease and selecting therapeutic schedule.This paper will review the progress of molecular classification studies of bladder cancer.展开更多
Objective:To investigate the expression and significance of ADAM12 in bladder cancer.Methods:Transcriptome data and clinical data of bladder cancer and normal samples from TCGA database were downloaded to analyze the ...Objective:To investigate the expression and significance of ADAM12 in bladder cancer.Methods:Transcriptome data and clinical data of bladder cancer and normal samples from TCGA database were downloaded to analyze the expression level and prognosis of ADAM12 in bladder cancer and normal tissues,and analyze its clinical correlation.Bladder cancer wax block samples were collected to detect the expression level of ADAM12 protein in cancer and adjacent cancer by immunohisto-chemistry.In vitro experiments,the experiments were divided into siNC group and siADAM12 group by transfection interference sequence,and the effect of knockdown ADAM12 on the proliferation and migration of bladder cancer cells was evaluated by CCK8,Transwell and scratch experiments.Western Blot was used to detect the expression level of EMT-related protein in each group of bladder cancer cells.Bioinformatics was used to explore the potential mechanism of ADAM12 in influencing the progression of bladder cancer.Results:ADAM12 expression in bladder cancer tissue is higher than normal tissue(P<0.05).Compared with the low expression group,the prognosis of high-expression ADAM12 was worse(P=0.007),and it was related to tumor stage,depth of invasion and lymph node metastasis(P<0.05).The immunohistochemical results showed that ADAM12 was expressed higher in bladder cancer tissues than in neighboring tissues(P<0.05).The results of in vitro experiments showed that knocking down ADAM12 could inhibit the proliferation and migration of bladder cancer cells compared with the control group.Compared with the NC group,the Western Blot test results showed that the expression of E-cadherin was increased in the siADAM12 group,while the expression of N-cadherin and Vimentin was decreased.Overexpression leads to the opposite.Bioinformatics analysis showed that ADAM12 may be involved in multiple cancer-related signaling pathways and is associated with the infiltration of various immune cell(P<0.05).Conclusion:ADAM12 is highly expressed in bladder cancer tissues and is associated with tumor immune cell infiltration and promotes the migration of bladder cancer cells by regulating EMT,which may be a prognostic marker and biotherapeutic target for bladder cancer.展开更多
Prostate and bladder cancers are the two prevalent urological cancers, and several therapeutic options are currently available but the outcomes have not been satisfactory. To find the better therapeutic option, we inv...Prostate and bladder cancers are the two prevalent urological cancers, and several therapeutic options are currently available but the outcomes have not been satisfactory. To find the better therapeutic option, we investigated if the bioactive extracts of monk fruit, mogrosides, with potential anticancer activity might have anticancer effect against prostate and bladder cancer cells. Four of commercial products made of mogrosides known as Lakanto<sup>ò</sup> (LKT) products, LK1, LK2, LLE, and MOG, were then tested. A dose-dependent study at given concentrations of four products showed that LK1 and LK2 had little effects, while LLE and MOG showed a significant cell viability reduction in both PC-3 and T24 cells. To explore the anticancer mechanism of such products, cell cycle analysis was first performed. Such analysis revealed that LLE and MOG, not LK1 and LK2, led to a G<sub>1</sub> cell cycle arrest. Potential induction of endoplasmic reticulum (ER) stress was next examined because it is known to be linked to a cell cycle arrest. The three key regulators involved in ER stress were all up-regulated with LLE or MOG, indicating induction of ER stress. As ER stress is also known to induce apoptosis, this possibility was tested. The two apoptotic regulators were modulated in a specific manner with LLE or MOG, indicating induction of apoptosis. Lastly, to validate anticancer effect of LLE or MOG, anticancer effect of four chemotherapeutic drugs was also assessed in comparison with that of LLE/MOG. None of drugs had any effects but two products showed significant anticancer effect. In conclusion, two monk fruit products, LLE and MOG, demonstrated anticancer activity against PC-3 and T24 cells, significantly reducing cell viability and ultimately inducing apoptosis. Therefore, these two LKT products with few side effects may have clinical implications in the treatment of urological cancers.展开更多
Objective:To investigate the effects of Schisandra B on proliferation,migration,invasion of bladder cancer and to further investigate its molecular mechanism.Methods:Bladder cancer cells were subjected to different co...Objective:To investigate the effects of Schisandra B on proliferation,migration,invasion of bladder cancer and to further investigate its molecular mechanism.Methods:Bladder cancer cells were subjected to different concentrations of Schisandra B solution(0,20,40,80μmol/L).CCK-8 assay was used to detect the effect of schisandra B on bladder cancer cell proliferation.Transwell migration assay and wound healing assay were used to detect the effect of Schisandra B on the migration of bladder cancer cells.Transwell invasion assay was used to detect the effect of schisandra B on invasion ability of bladder cancer cells.The expression levels of intracellularβ-catenin and c-myc protein were measured by western blot.Results:Schisandra B inhibited the proliferation of T24 and UM-UC-3 cells in a concentration and time dependent manner(P<0.05).The rate of wound healing and number of migration and invasion cells decreased with the increase of Schisandra B concentration(P<0.05).The expression ofβ-catenin and c-myc decreased after treatment with Schisandra B in bladder cancer cells(P<0.05).Conclusion:Schisandra B can inhibit the proliferation,migration and invasion of human bladder cancer T24 and UM-UC-3 cells,and the main mechanism for its inhibitory effect may be related to the inactivation of the Wnt/β-catenin signaling pathway.展开更多
Background:This study aimed to select compounds with unique inhibitory effects on muscle-invasive bladder cancer(MIBC)from coumarone derivatives with similar parent nuclear structures and to reveal their tumor-suppres...Background:This study aimed to select compounds with unique inhibitory effects on muscle-invasive bladder cancer(MIBC)from coumarone derivatives with similar parent nuclear structures and to reveal their tumor-suppressive effects using various approaches.Methods:Bladder cancer cell lines SW780 and T24,as well as human normal bladder epithelial cell line SV-HUC-1 were selected as the study model,and these urinary system cells were co-incubated with various concentrations of(S,E)-4-(4-methylbenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-isocyanobenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-fluorobenzylidene)-3-phenylchroman-3-ol(FPO),and(S,E)-3-phenyl-4-(4-(trifluoromethoxy)benzylidene)chroman-3-ol.Cell activity was detected using cell counting kit-8.FPO showed the strongest inhibitory effect on MIBC cells;therefore,it was selected for further experiments.We monitored the FPO-induced T24 cell morphological changes with an inverted microscope.The FPO-inhibited migration of T24 cells was examined using a cell scratch assay.We detected the clonogenic ability of T24 cells through a clone formation test and evaluated their proliferative ability using a 5-ethynyl-2’-deoxyuridine fluorescence staining kit.The inhibitory effect of FPO against the cell cycle was monitored using flow cytometry,and its suppressive effect on the DNA replication ability of T24 cells was detected using double fluorescence staining(Ki67 and phalloidin).Results:Among the four candidate coumarone derivatives,FPO showed the most significant inhibitory effect on MIBC cells and was less toxic to normal urothelial cells.FPO inhibited T24 cell growth in time and dose-dependent manners(the half-inhibitory concentration is 8μM).FPO significantly repressed the proliferation,migration,and clonogenic ability of bladder cancer T24 cells.Cell mobility was significantly inhibited by FPO:30μM FPO almost completely repressed migration occurred at after 24 h treatment.Moreover,FPO significantly suppressed the clonogenicity of bladder cancer cells in a dose-dependent manner.Mechanistically,FPO targeted the cell cycle,arresting the S and G2 phases on bladder cancer T24 cells.Conclusion:We discovered a novel anticancer chemical,FPO,and proposed a potential mechanism,through which it suppresses MIBC T24 cells by repressing the cell cycle in the S and G2 phases.This study contributes to the development of novel anticancer drugs for MIBC.展开更多
基金supported by the Postdoctoral Scientific Research Developmental Fund of Heilongjiang(No.LBH-Q21130)the Beijing Medical Award Foundation(No.YXJL-2020-1207-0811).
文摘Ferroptosis,a type of regulated cell death driven by iron-dependent lipid peroxidation,is mainly initiated by extramitochondrial lipid peroxidation due to the accumulation of iron-dependent reactive oxygen species.Ferroptosis is a prevalent and primitive form of cell death.Numerous cellular metabolic processes regulate ferroptosis,including redox homeostasis,iron regulation,mitochondrial activity,amino acid metabolism,lipid metabolism,and various disease-related signaling pathways.Ferroptosis plays a pivotal role in cancer therapy,particularly in the eradication of aggressive malignancies resistant to conventional treatments.Multiple studies have explored the connection between ferroptosis and bladder cancer,focusing on its incidence and treatment outcomes.Several biomolecules and tumor-associated signaling pathways,such as p53,heat shock protein 1,nuclear receptor coactivator 4,RAS-RAF-MEK,phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin,and the Hippo-tafazzin signaling system,exert a moderating influence on ferroptosis in bladder cancer.Ferroptosis inducers,including erastin,artemisinin,conjugated polymer nanoparticles,and quinazolinyl-arylurea derivatives,hold promise for enhancing the effectiveness of conventional anticancer medications in bladder cancer treatment.Combining conventional therapeutic drugs and treatment methods related to ferroptosis offers a promising approach for the treatment of bladder cancer.In this review,we analyze the research on ferroptosis to augment the efficacy of bladder cancer treatment.
基金supported by the Medical and Health Science and Technology Program of Zhejiang Province(No.2021KY367).
文摘Introduction:Bladder cancer(BC)has a high incidence and mortality rate worldwide.Suppressor anaphasepromoting complex domain containing 2(SAPCDC2)is over-expressed in a variety of tumors.Objectives:This study investigated the effects of SAPCD2 knockdown on BC cells.Methods:T24 and UMUC3 cell models and the xenografted BC tumor model with SAPCD2 knockdown were established to observe the malignant phenotype of BC cells by cell counting kit-8 assay,colony formation test,wound healing,and Transwell assay,mRNA and proteins expressions were measured with quantitative real-time polymerase chain reaction,western blotting,and tissue immunohistochemistry.Lithium chloride agonist on the Wnt/β-catenin pathway was used to clarify the molecular mechanism of SAPCD2 knockdown.Results:SAPCD2 expression was significantly higher in BC cell lines than in SVHUC-1 cells.SAPCD2 knockdown inhibited viability and cloning,hindered the G0/G1 phase of the cell cycle in UMUC3 and T24 cells,and decreased the migration and invasiveness of BC cells.SAPCD2 knockdown inhibited expression levels of cyclin D1,cyclin B1,N-cadherin,vimentin,Snail,β-catenin,c-Myc,and cyclin-dependent kinase 4,while the P21 and E-cadherin were raised by SAPCD2 knockdown.Furthermore,lithium chloride reversed the effects of SAPCD2 knockdown on the expression levels of the above proteins in UMUC3 and T24 cells.In vivo,SAPCD2 knockdown inhibited the volume,weight,and expression of Ki-67 andβ-catenin in tumors and increased the E-cadherin expression.Conclusion:SAPCD2 knockdown inhibits the malignant phenotype of BC via a pathway involvingβ-catenin.
基金Supported by National Natural Science Foundation of China,No.82260785.
文摘BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.
文摘Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle advancement.Their results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell cycle.This research gives a novel direction and concept for targeted therapy of BC.
文摘BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer.As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients,we examined American College of Surgeons National Surgical Quality Improvement Program(NSQIP)database to determine if there was higher morbidity among the neo-adjuvant group within the 30-day post-operative period.We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity.AIM To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery.METHODS A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity(bile leak,infection rate,rate of converting to open surgery,etc.)compared to the group who only had surgery.To calculate the odds ratio for the primary and secondary outcomes,a crude logistic regression was performed.RESULTS Of the 452 patients,52 patients received NACT prior to surgery.There were no statistically significant differences in the odds of morbidity between the two groups,including bile leak[odds ratio(OR),0.69;95%confidence interval(95%CI):0.16-2.10;P=0.55],superficial wound infection(OR,0.58;95%CI:0.03-3.02;P=0.61),and organ space wound infection(OR,0.63;95%CI:0.18-1.63;P=0.61).CONCLUSION There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.
基金suppor ted by the National Key Research and Development Plan of China(Technology helps Economy 2020,2016YFC0106300)the National Natural Science Foundation of China(82174230)the Major Program Fund of Technical Innovation Project of Department of Science and Technology of Hubei Province(2016ACAl52)。
文摘Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.
文摘BACKGROUND Regulatory T cells(Tregs)and natural killer(NK)cells play an essential role in the development of bladder urothelial carcinoma(BUC).AIM To construct a prognosis-related model to judge the prognosis of patients with bladder cancer,meanwhile,predict the sensitivity of patients to chemotherapy and immunotherapy.METHODS Bladder cancer information data was obtained from The Cancer Genome Atlas and GSE32894.The CIBERSORT was used to calculate the immune score of each sample.Weighted gene co-expression network analysis was used to find genes that will have the same or similar expression patterns.Subsequently,multivariate cox regression and lasso regression was used to further screen prognosis-related genes.The prrophetic package was used to predict phenotype from gene expression data,drug sensitivity of external cell line and predict clinical data.RESULTS The stage and risk scores are independent prognostic factors in patients with BUC.Mutations in FGFR3 lead to an increase in Tregs percolation and affect the prognosis of the tumor,and additionally,EMP1,TCHH and CNTNAP3B in the model are mainly positively correlated with the expression of immune checkpoints,while CMTM8,SORT1 and IQSEC1 are negatively correlated with immune checkpoints and the high-risk group had higher sensitivity to chemotherapy drugs.CONCLUSION Prognosis-related models of bladder tumor patients,based on Treg and NK cell percolation in tumor tissue.In addition to judging the prognosis of patients with bladder cancer,it can also predict the sensitivity of patients to chemotherapy and immunotherapy.At the same time,patients were divided into high and low risk groups based on this model,and differences in genetic mutations were found between the high and low risk groups.
文摘Gall bladder cancer(GBC)is becoming a very devastating form of hepatobiliary cancer in India.Every year new cases of GBC are quite high in India.Despite recent advanced multimodality treatment options,the survival of GBC patients is very low.If the disease is diagnosed at the advanced stage(with local nodal metastasis or distant metastasis)or surgical resection is inoperable,the prognosis of those patients is very poor.So,perspectives of targeted therapy are being taken.Targeted therapy includes hormone therapy,proteasome inhibitors,signal transduction and apoptosis inhibitors,angiogenesis inhibitors,and immunotherapeutic agents.One such signal transduction inhibitor is the specific short interfering RNA(siRNA)or short hairpin RNA(shRNA).For developing siRNAmediated therapy shRNA,although several preclinical studies to evaluate the efficacy of these key molecules have been performed using gall bladder cells,many more clinical trials are required.To date,many such genes have been identified.This review will discuss the recently identified genes associated with GBC and those that have implications in its treatment by siRNA or shRNA.
文摘Objective:The imbalance of antioxidants and pro-oxidants plays a crucial role in the carcinogenesis of bladder cancer(BC).This study aimed to evaluate serum antioxidant status in patients with BC and determine its potential use in the diagnosis and progression potential considerations following histopathological assessment.Methods:A cross-sectional study included 90 patients with BC,divided into Ta,T1,and T2eT4 stage subgroups,and according to cancer progression potential,into low-grade(LG)and highgrade(HG)subgroups.The control group(CG)included 30 healthy volunteers.Antioxidant status was determined using the spectrophotometric method and standard laboratory tests.Results:Serum superoxide dismutase activity was significantly higher in BC patients regarding cancer stage in comparison to the CG(p<0.001).Catalase activity was highest in T2eT4 subgroup and was significantly higher compared to the Ta(p<0.01)and T1(p<0.05)subgroups.Serum albumin level was significantly lower in the BC group compared to the CG(p<0.001).In addition,it was significantly lower in T2eT4 subgroup compared to T1 and Ta subgroups(p<0.01).A significant negative correlation was found between tumor size and serum albumin level only(r=0.386,p<0.01).Catalase activity was higher in HG subgroup(p=0.009),while bilirubin level was higher in LG subgroup(p=0.035).The optimal cut-off value of catalase activity in differentiating patients with LG and HG BC subgroups was 11.96 IU/L,and the specificity and sensitivity were 51.1% and 82.2%,respectively.Bilirubin level,for a calculated optimal cut-off value of 11.95 mmol/L,had a specificity of 44.1%and sensitivity of 80.0%.Conclusion:More invasive stages of BC with greater progression potential are associated with an increase in enzymatic antioxidant activity and a decrease in non-enzymatic antioxidant capacity.It may suggest a possible role of antioxidants in the prediction and monitoring of illness trajectory.
基金The current study was supported by the National Natural Science Foundation of China(Grant Nos.82130096 and 82373537)Collaborative Innovation Center for Cancer Personalized Medicine and Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).
文摘Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.
基金supported by the Research fund of Anhui Institute of Translational Medicine (No. 2021zhyx-C62)。
文摘Objective: The interplay between chemokine C-X-C motif ligand 12(CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently,targeting this signaling axis has emerged as a potential strategy in cancer therapy. However, the precise role of CXCL12 in clinical therapy, especially in immunotherapy for bladder cancer(BCa), remains poorly elucidated.Methods: We gathered multiple omics data from public databases to unveil the clinical relevance and tumor immune landscape associated with CXCL12 in BCa patients. Univariate and multivariate Cox regression analyses were employed to assess the independent prognostic significance of CXCL12 expression and formulate a nomogram. The expression of CXCL12 in BCa cell lines and clinical tissue samples was validated using enzymelinked immunosorbent assays(ELISA) and immunohistochemistry(IHC).Results: While transcriptional expression of CXCL12 exhibited a decrease in nearly all tumor tissues, CXCL12 methylation expression was notably increased in BCa tissues. Single-cell RNA analysis highlighted tissue stem cells and endothelial cells as the primary sources expressing CXCL12. Abnormal CXCL12 expression, based on transcriptional and methylation levels, correlated with various clinical characteristics in BCa patients. Functional analysis indicated enrichment of CXCL12 and its co-expression genes in immune regulation and cell adhesion. The immune landscape analysis unveiled a significant association between CXCL12 expression and M2 macrophages(CD163~+ cells) in BCa tissues. Notably, CXCL12 expression emerged as a potential predictor of immunotherapy response and chemotherapy drug sensitivity in BCa patients.Conclusions: Taken together, these findings suggest aberrant production of CXCL12 in BCa tissues,potentially influencing the treatment responses of affected individuals.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81974396,No.81874091,No.82072840,and No.82102734)the Natural Science Foundation of Hubei Province(No.2020CFB829)the Health Commission of Hubei Province Scientific Research Project(No.WJ2021F081).
文摘Objective Cisplatin(CDDP)-based chemotherapy is a first-line,drug regimen for muscle-invasive bladder cancer(BC)and metastatic bladder cancer.Clinically,resistance to CDDP restricts the clinical benefit of some bladder cancer patients.AT-rich interaction domain 1A(ARID1A)gene mutation occurs frequently in bladder cancer;however,the role of CDDP sensitivity in BC has not been studied.Methods We established ARID1A knockout BC cell lines using CRISPR/Cas9 technology.IC50 determination,flow cytometry analysis of apoptosis,and tumor xenograft assays were performed to verify changes in the CDDP sensitivity of BC cells losing ARID1A.qRT-PCR,Western blotting,RNA interference,bioinformatic analysis,and ChIP-qPCR analysis were performed to further explore the potential mechanism of ARID1A inactivation in CDDP sensitivity in BC.Results It was found that ARID1A inactivation was associated with CDDP resistance in BC cells.Mechanically,loss of ARID1A promoted the expression of eukaryotic translation initiation factor 4A3(EIF4A3)through epigenetic regulation.Increased expression of EIF4A3 promoted the expression of hsa_circ_0008399(circ0008399),a novel circular RNA(circRNA)identified in our previous study,which,to some extent,showed that ARID1A deletion caused CDDP resistance through the inhibitory effect of circ0008399 on the apoptosis of BC cells.Importantly,EIF4A3-IN-2 specifically inhibited the activity of EIF4A3 to reduce circ0008399 production and restored the sensitivity of ARID1A inactivated BC cells to CDDP.Conclusion Our research deepens the understanding of the mechanisms of CDDP resistance in BC and elucidates a potential strategy to improve the efficacy of CDDP in BC patients with ARID1A deletion through combination therapy targeting EIF4A3.
文摘The number of studies in the literature that diagnose cancer with machine learning using genome data is quite limited.These studies focus on the prediction performance,and the extraction of genomic factors that cause disease is often overlooked.However,finding underlying genetic causes is very important in terms of early diagnosis,development of diagnostic kits,preventive medicine,etc.The motivation of our study was to diagnose bladder cancer(BCa)based on genetic data and to reveal underlying genetic factors by using machine-learning models.In addition,conducting hyper-parameter optimization to get the best performance from different models,which is overlooked in most studies,was another objective of the study.Within the framework of these motivations,C4.5,random forest(RF),artificial neural networks(ANN),and deep learning(DL)were used.In this way,the diagnostic performance of decision tree(DT)-based models and black box models on BCa was also compared.The most successful model,DL,yielded an area under the curve(AUC)of 0.985 and a mean square error(MSE)of 0.069.For each model,hyper-parameters were optimized by an evolutionary algorithm.On average,hyper-parameter optimization increased MSE,root mean square error(RMSE),LogLoss,and AUC by 30%,17.5%,13%,and 6.75%,respectively.The features causing BCa were extracted.For this purpose,entropy and Gini coefficients were used for DT-based methods,and the Gedeon variable importance was used for black box methods.The single nucleotide polymorphisms(SNPs)rs197412,rs2275928,rs12479919,rs798766 and rs2275928,whose BCa relations were proven in the literature,were found to be closely related to BCa.In addition,rs1994624 and rs2241766 susceptibility loci were proposed to be examined in future studies.
文摘BACKGROUND The purpose of the present study was to examine retrospectively the contribution of 18Fluorodeoxyglucose positron emission tomography computed tomography(18FDG-PET/CT)to the evaluation of response to first-line gemcitabine plus cispla-tin-based chemotherapy in patients with metastatic bladder cancer.AIM To evaluate the response to Gemcitabine plus Cisplatin-based chemotherapy using 18FDG-PET/CT imaging in patients with metastatic bladder cancer.METHODS Between July 2007 and April 2019,79 patients underwent 18FDG-PET/CT imaging with the diagnosis of Metastatic Bladder Carcinoma(M-BCa).A total of 42 pa-tients(38 male,4 female)were included in the study,and all had been admi-nistered Gemcitabine plus Cisplatin-based chemotherapy.After completion of the therapy,the patients underwent a repeat 18FDG-PET/CT scan and the results were compared with the PET/CT findings before chemotherapy according to European Organisation for the Research and treatment of cancer criteria.Mean age was 66.1 years and standard deviation was 10.7 years(range:41–84 years).RESULTS Of the patients,seven(16.6%)were in complete remission,17(40.5%)were in partial remission,six(14.3%)had a stable disease,and 12(28.6%)had a pro-gressive disease.The overall response rate was 57.1 percent.CONCLUSION 18FDG-PET/CT can be considered as a successful imaging tool in evaluating response to first-line chemotherapy for metastatic bladder cancer.Anatomical and functional data obtained from PET/CT scans may be useful in the planning of secondline and thirdline chemotherapy.
基金Supported by conceptual development of research organization,Ministry of Health,Czech Republic,No.FNOs/2023.
文摘BACKGROUND Acquired haemophilia(AH)is a serious autoimmune haematological disease caused by the production of auto-antibodies against coagulation factor VIII.In some patients,AH is associated with a concomitant malignancy.In case of surgical intervention,AH poses a high risk of life-threatening bleeding.CASE SUMMARY A 60-year-old female patient with multiple recurrences of non-muscle invasive bladder cancer underwent transurethral tumour resection.A severe haematuria developed postoperatively warranting two endoscopic revisions;however,no clear source of bleeding was identified in the bladder.Subsequent haematological examination established a diagnosis of AH.Treatment with factor VIII inhibitor bypass activity and immunosuppressive therapy was initiated immediately.The patient responded well to the therapy and was discharged from the hospital 21 d after the primary surgery.At the 38-mo follow-up,both AH and bladder cancer remained in complete remission.CONCLUSION AH is a rare,life-threatening haematological disease.AH should be considered in patients with persistent severe haematuria or other bleeding symptoms,especially if combined with isolated activated partial thromboplastin time prolongation.
基金National Natural Science Foundation of China (No.82060461)Innovation Research Team Project of Hainan Nature Foundation (No.820CXTD447)Clinical Medical Center construction project of Hainan Province.
文摘Bladder cancer is the second most common tumor in the urinary system after prostate cancer.It is highly heterogeneous and its developmental mechanism involves abnormal alterations in the structure and function of multiple genomes.Researching the molecular classification of bladder cancer by using molecular biology techniques is important for defining the pathogenesis of the disease and selecting therapeutic schedule.This paper will review the progress of molecular classification studies of bladder cancer.
基金Natural Science Foundation of Anhui Province(No.1808085MH293)。
文摘Objective:To investigate the expression and significance of ADAM12 in bladder cancer.Methods:Transcriptome data and clinical data of bladder cancer and normal samples from TCGA database were downloaded to analyze the expression level and prognosis of ADAM12 in bladder cancer and normal tissues,and analyze its clinical correlation.Bladder cancer wax block samples were collected to detect the expression level of ADAM12 protein in cancer and adjacent cancer by immunohisto-chemistry.In vitro experiments,the experiments were divided into siNC group and siADAM12 group by transfection interference sequence,and the effect of knockdown ADAM12 on the proliferation and migration of bladder cancer cells was evaluated by CCK8,Transwell and scratch experiments.Western Blot was used to detect the expression level of EMT-related protein in each group of bladder cancer cells.Bioinformatics was used to explore the potential mechanism of ADAM12 in influencing the progression of bladder cancer.Results:ADAM12 expression in bladder cancer tissue is higher than normal tissue(P<0.05).Compared with the low expression group,the prognosis of high-expression ADAM12 was worse(P=0.007),and it was related to tumor stage,depth of invasion and lymph node metastasis(P<0.05).The immunohistochemical results showed that ADAM12 was expressed higher in bladder cancer tissues than in neighboring tissues(P<0.05).The results of in vitro experiments showed that knocking down ADAM12 could inhibit the proliferation and migration of bladder cancer cells compared with the control group.Compared with the NC group,the Western Blot test results showed that the expression of E-cadherin was increased in the siADAM12 group,while the expression of N-cadherin and Vimentin was decreased.Overexpression leads to the opposite.Bioinformatics analysis showed that ADAM12 may be involved in multiple cancer-related signaling pathways and is associated with the infiltration of various immune cell(P<0.05).Conclusion:ADAM12 is highly expressed in bladder cancer tissues and is associated with tumor immune cell infiltration and promotes the migration of bladder cancer cells by regulating EMT,which may be a prognostic marker and biotherapeutic target for bladder cancer.
文摘Prostate and bladder cancers are the two prevalent urological cancers, and several therapeutic options are currently available but the outcomes have not been satisfactory. To find the better therapeutic option, we investigated if the bioactive extracts of monk fruit, mogrosides, with potential anticancer activity might have anticancer effect against prostate and bladder cancer cells. Four of commercial products made of mogrosides known as Lakanto<sup>ò</sup> (LKT) products, LK1, LK2, LLE, and MOG, were then tested. A dose-dependent study at given concentrations of four products showed that LK1 and LK2 had little effects, while LLE and MOG showed a significant cell viability reduction in both PC-3 and T24 cells. To explore the anticancer mechanism of such products, cell cycle analysis was first performed. Such analysis revealed that LLE and MOG, not LK1 and LK2, led to a G<sub>1</sub> cell cycle arrest. Potential induction of endoplasmic reticulum (ER) stress was next examined because it is known to be linked to a cell cycle arrest. The three key regulators involved in ER stress were all up-regulated with LLE or MOG, indicating induction of ER stress. As ER stress is also known to induce apoptosis, this possibility was tested. The two apoptotic regulators were modulated in a specific manner with LLE or MOG, indicating induction of apoptosis. Lastly, to validate anticancer effect of LLE or MOG, anticancer effect of four chemotherapeutic drugs was also assessed in comparison with that of LLE/MOG. None of drugs had any effects but two products showed significant anticancer effect. In conclusion, two monk fruit products, LLE and MOG, demonstrated anticancer activity against PC-3 and T24 cells, significantly reducing cell viability and ultimately inducing apoptosis. Therefore, these two LKT products with few side effects may have clinical implications in the treatment of urological cancers.
基金Guangdong Provincial Basic and Applied Basic Research Fund(No.2022A1515012195)Guangdong Provincial Bureau of Traditional Chinese Medicine Research Project(No.20211221,No.20222099)Guangdong Medical University Research Fund(No.4SG20158G)。
文摘Objective:To investigate the effects of Schisandra B on proliferation,migration,invasion of bladder cancer and to further investigate its molecular mechanism.Methods:Bladder cancer cells were subjected to different concentrations of Schisandra B solution(0,20,40,80μmol/L).CCK-8 assay was used to detect the effect of schisandra B on bladder cancer cell proliferation.Transwell migration assay and wound healing assay were used to detect the effect of Schisandra B on the migration of bladder cancer cells.Transwell invasion assay was used to detect the effect of schisandra B on invasion ability of bladder cancer cells.The expression levels of intracellularβ-catenin and c-myc protein were measured by western blot.Results:Schisandra B inhibited the proliferation of T24 and UM-UC-3 cells in a concentration and time dependent manner(P<0.05).The rate of wound healing and number of migration and invasion cells decreased with the increase of Schisandra B concentration(P<0.05).The expression ofβ-catenin and c-myc decreased after treatment with Schisandra B in bladder cancer cells(P<0.05).Conclusion:Schisandra B can inhibit the proliferation,migration and invasion of human bladder cancer T24 and UM-UC-3 cells,and the main mechanism for its inhibitory effect may be related to the inactivation of the Wnt/β-catenin signaling pathway.
基金supported by National Nature Science Foundation of China(82172978)Taishan Scholars Program of Shandong Province(Grant No.tsqn201909147)+1 种基金the Key Project at Central Government Level:the ability establishment of sustainable use for valuable Chinese medicine resources(2060302)the Student Innovation Training Program in Jining Medical University(cx2021116).
文摘Background:This study aimed to select compounds with unique inhibitory effects on muscle-invasive bladder cancer(MIBC)from coumarone derivatives with similar parent nuclear structures and to reveal their tumor-suppressive effects using various approaches.Methods:Bladder cancer cell lines SW780 and T24,as well as human normal bladder epithelial cell line SV-HUC-1 were selected as the study model,and these urinary system cells were co-incubated with various concentrations of(S,E)-4-(4-methylbenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-isocyanobenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-fluorobenzylidene)-3-phenylchroman-3-ol(FPO),and(S,E)-3-phenyl-4-(4-(trifluoromethoxy)benzylidene)chroman-3-ol.Cell activity was detected using cell counting kit-8.FPO showed the strongest inhibitory effect on MIBC cells;therefore,it was selected for further experiments.We monitored the FPO-induced T24 cell morphological changes with an inverted microscope.The FPO-inhibited migration of T24 cells was examined using a cell scratch assay.We detected the clonogenic ability of T24 cells through a clone formation test and evaluated their proliferative ability using a 5-ethynyl-2’-deoxyuridine fluorescence staining kit.The inhibitory effect of FPO against the cell cycle was monitored using flow cytometry,and its suppressive effect on the DNA replication ability of T24 cells was detected using double fluorescence staining(Ki67 and phalloidin).Results:Among the four candidate coumarone derivatives,FPO showed the most significant inhibitory effect on MIBC cells and was less toxic to normal urothelial cells.FPO inhibited T24 cell growth in time and dose-dependent manners(the half-inhibitory concentration is 8μM).FPO significantly repressed the proliferation,migration,and clonogenic ability of bladder cancer T24 cells.Cell mobility was significantly inhibited by FPO:30μM FPO almost completely repressed migration occurred at after 24 h treatment.Moreover,FPO significantly suppressed the clonogenicity of bladder cancer cells in a dose-dependent manner.Mechanistically,FPO targeted the cell cycle,arresting the S and G2 phases on bladder cancer T24 cells.Conclusion:We discovered a novel anticancer chemical,FPO,and proposed a potential mechanism,through which it suppresses MIBC T24 cells by repressing the cell cycle in the S and G2 phases.This study contributes to the development of novel anticancer drugs for MIBC.
