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 original version of this article was revised due to production error by the vendor.The author“Hua-min DING”is one of the co-authors,and the name should be labeled correctly as appears on PDF.The affiliation of“...The original version of this article was revised due to production error by the vendor.The author“Hua-min DING”is one of the co-authors,and the name should be labeled correctly as appears on PDF.The affiliation of“Yu-jun SHUAI”and“Chao HUANG”is“Department of Urology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China”,and both of them should be labeled as 1,as correctively appears on PDF.展开更多
Using anesthetic gel may not sufficiently exclude pain perception during and after cystoscopy in male patients.To evaluate the analgesic efficacy and safety of intramuscular parecoxib(40 mg)for outpatient-based rigid ...Using anesthetic gel may not sufficiently exclude pain perception during and after cystoscopy in male patients.To evaluate the analgesic efficacy and safety of intramuscular parecoxib(40 mg)for outpatient-based rigid cystoscopy,we performed a prospective,randomized and controlled study.Consecutive male patients requiring diagnostic cystoscopy in our hospital were divided into group A(1%tetracaine gel,n=50)and group B(parecoxib,n^5l)at random.Patients received intramuscular injections of either 2 mL sterile saline in group A or 40 mg parecoxib in group B 30 min before the procedure.Tetracaine gel was injected into the urethra 3 min before the procedure in group A,with patients receiving plain lubricant gel in group B at the same time.Cystoscopy-associated pain levels were evaluated using the Visual Analog Score(VAS)during the procedure.Post-procedure urethral pain and complications were recorded and analyzed.The results showed that male patients experienced significantly less pain in group B than in group A(2.70±1.36 V5.3.56±1.74,P=0.008).The percentage of patients with dysuria pain was not significantly different between the two groups.In addition,24 h after cystoscopy,the patients with no previous experience of cystoscopy were more likely to declare urethral pain(59.2%vs.33.3%,P=0.012,relative risk=1.78).No difference was observed in analgesic-related complications between the two groups.We conclude that intramuscular injection of 40 mg parecoxib may improve comfort for male patients undergoing rigid cystoscopy.展开更多
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 original version of this article was revised due to production error by the vendor.The author“Hua-min DING”is one of the co-authors,and the name should be labeled correctly as appears on PDF.The affiliation of“Yu-jun SHUAI”and“Chao HUANG”is“Department of Urology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China”,and both of them should be labeled as 1,as correctively appears on PDF.
文摘Using anesthetic gel may not sufficiently exclude pain perception during and after cystoscopy in male patients.To evaluate the analgesic efficacy and safety of intramuscular parecoxib(40 mg)for outpatient-based rigid cystoscopy,we performed a prospective,randomized and controlled study.Consecutive male patients requiring diagnostic cystoscopy in our hospital were divided into group A(1%tetracaine gel,n=50)and group B(parecoxib,n^5l)at random.Patients received intramuscular injections of either 2 mL sterile saline in group A or 40 mg parecoxib in group B 30 min before the procedure.Tetracaine gel was injected into the urethra 3 min before the procedure in group A,with patients receiving plain lubricant gel in group B at the same time.Cystoscopy-associated pain levels were evaluated using the Visual Analog Score(VAS)during the procedure.Post-procedure urethral pain and complications were recorded and analyzed.The results showed that male patients experienced significantly less pain in group B than in group A(2.70±1.36 V5.3.56±1.74,P=0.008).The percentage of patients with dysuria pain was not significantly different between the two groups.In addition,24 h after cystoscopy,the patients with no previous experience of cystoscopy were more likely to declare urethral pain(59.2%vs.33.3%,P=0.012,relative risk=1.78).No difference was observed in analgesic-related complications between the two groups.We conclude that intramuscular injection of 40 mg parecoxib may improve comfort for male patients undergoing rigid cystoscopy.