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Chinese Medical Journal 2003年第12期116卷 1860-1863页

作者：朱朝辉邢诗安林晨张雪艳付明梁萧曾甫清鲁功成吴旻 Department of Urology Union Hospital Department of Urology Central Laboratory Union Hospital National Laboratory of Molecular Oncology

Objective To evaluate the antitumor efficacy of proliferating cell nuclear antigen antisense oligonucleotide (PCNA-ASO) in combination with recombinant adenovirus p53 (Ad-p53) against bladder cancer EJ and BIU-87 cells in vitro and in vivo. Methods Cells were transfected with Ad-p53 (100 MOI), and PCNA-ASO (1.6 μmol/L) was then introduced into the cells using a cationic lipid (lipofectamine, 20 μl/ml). In vitro and in vivo antitumor effects of combining PCNA-ASO with Ad-p53 were measured using the MTT assay, flow cytometry, clone formation, and a nude mice model. Results The combination of PCNA-ASO and Ad-p53 inhibited cell viability in both the EJ (89.3%) and BIU-87 (78.6%) cell lines. The ability of the cells to form foci was also reduced by 74.8% in EJ cells and by 67.5% in BIU-87 cells (Pbladder cancer with mutant p53 has important therapeutic potential, significantly suppressing the growth of human bladder cancer both in vitro and in vivo.

关键词： bladder cancer Ad-p53 proliferating cell nuclear antigen antisense oligonucleotide

bladder cancer and Arsenic Exposure: Differences in the Two Populations Enrolled in A Study in Southwest Taiwan

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Biomedical and Environmental Sciences 2003年第4期16卷 355-368页

作者： STEVENH.LAMM DANIELM.BYRD MICHAELB.KRUSE MANNINGFE1NLEIB SHENG-HANLAI ConsultantsinEpidemiologyandOccupationalHealth Inc.WashingtonDC20007USA UonsultantsinToxicology RiskAssessmentandProductSafetyWashingtonDC20024USA JohnsHopkinsUniversity-BloombergSchoolofPublicHealth BaltimoreMD21202USA

Objective Analyses of bladder cancer mortality in the Black Foot Disease (BFD) endemic area of southwest Taiwan conducted by Morales et al. showed a discontinuity in risk at 400μg/L arsenic in the drinking water in a stratified analysis and no discontinuity in a continuous analysis. As the continuous analysis presentation had been used by both the NRC and the EPA to assess the carcinogenic risk from arsenic ingestion, an explanation of the discontinuity was sought. Methods Review of 40 years of published health studies of the BFD-endemic area of SW Taiwan showed that earlier publications had limited their cancer associations with arsenic levels in artesian well waters and that the reports of Morales et al., NRC, and EPA failed to do so. Underlying data for the Morales et al. study were obtained from the appendix to the NRC report. bladder cancer mortality rates were calculated from case counts and person-years of observation for each study village. Villages were categorized by water source according to the descriptions from the underlying study. Graphic and regression analyses were conducted of the bladder cancer mortality rates using exposure as a continuous variable and simultaneously stratifying by water source. Results The median village well arsenic levels ranged from 350 to 934μg/L for villages solely dependent on artesian well water and from 10 to 717μg/L for villages not solely dependent on artesian well water. bladder cancer mortality rates were found to be dependent upon the arsenic level only for those villages that were solely dependent on artesian well water for their water source. bladder cancer mortality rates were found to be independent of arsenic level for villages with non-artesian well water sources. Conclusions The data indicate that arsenic exposure levels do not explain the bladder cancer mortality risk in SW Taiwan among villages not dependent upon artesian well water. The association for villages dependent upon artesian well water may be explained either by arsenic acting as a high-dose c

关键词： Arsenic ingestion bladder cancer Dose-response Non-linear SW Taiwan cancer risk

bladder cancer epidemiology and genetic susceptibility

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The Journal of Biomedical Research 2013年第3期27卷 170-178页

作者： Haiyan Chu Meilin Wang Zhengdong Zhang Department of Environmental Genomics Jiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCancer CenterNanjing Medical University Department of Genetic Toxicology the Key Laboratory of Modern Toxicology of Ministry of EducationSchool of Public HealthNanjing Medical University

bladder cancer is the most common malignancy of the urinary system. The incidence of bladder cancer of men is higher than that of women （approximately 4：1）. Here, we summarize the bladder cancer-related risk factors, in- cluding environmental and genetic factors. In recent years, although the mortality rate induced by bladder cancer has been stable or decreased gradually, the public health effect may be pronounced. The well-established risk fac- tors for bladder cancer are cigarette smoking and occupational exposure. Genetic factors also play important roles in the susceptibility to bladder cancer. A recent study demonstrated that hereditary non-polyposis colorectal cancer is associated with increased risk of bladder cancer. Since 2008, genome-wide association study （GWAS） has been used to identify the susceptibility loci for bladder cancer. Further gene-gene or gene-environment interaction stud- ies need to be conducted to provide more information for the etiology of bladder cancer.

关键词： bladder cancer molecular epidemiology risk factors genetic susceptibility

Characterization of Genes Associated with Different Phenotypes of Human bladder cancer Cells

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Acta Biochimica et Biophysica Sinica 2006年第9期38卷 602-610页

作者： Yu-Cong YANG Xu LI Wei CHEN Center for Experimental Medicine,the First Affiliated Hospital,School of Medicine,Xi’an Jiaotong University,Xi’an 710061,China Center for Experimental Medicine the First Affiliated Hospital School of Medicine Xi'an Jiaotong UniversityXi'an 710061 China

To identify genes associated with morphological phenotypes of human bladder transitional cellcarcinoma,we used suppression subtractive hybridization (SSH) to create a subtractive cDNA library of twoestablished cell lines,BLZ-211 and BLS-211,derived from a patient with transitional cell carcinoma of thebladder,then to screen for differentially expressed genes.Real-time reverse transcription-polymerase chainreaction was used to further confirm the selected differentially expressed genes.Forward and reverse subtractivecDNA libraries yielded 168 and 305 putative clones,and among them more than 90% contained the inserts.After differential screening,36 different transcripts were obtained from 64 cDNA clones of a forward andreverse subtraction library.Among them,17 were identified as known genes by homology,for example,Vimentin,Keratin 7,DDH and UCH-L1.The remaining 19 were unknown expressed genes,and were collectedas new expressed sequence tags by the GenBank dbEST database with the accession numbers DR008207,DR010178,DR159652-DR159660,DY230447-DY230448,and DY505708-DY505713.Their function willbe studied further.Thus,SSH appears to be a useful technique for identifying differentially expressed genesbetween cell lines or clones.Our results,as revealed by SSH,also suggest that differences in gene expressionof cytoskeletal proteins might contribute to the different morphologies in BLZ-211 and BLS-211 cells.

关键词： bladder cancer phenotypes suppression subtractive hybridization

Erdafitinib and checkpoint inhibitors for first-line and second-line immunotherapy of hepatic,gastrointestinal,and urinary bladder carcinomas:Recent concept

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World Journal of Hepatology 2024年第4期16卷 490-493页

作者： Mohamed Wishahi Department of Urology Theodor Bilharz Research InstituteCairo 12411Egypt

cancer immunotherapy is administered for first-line,second-line,neoadjuvant,or adjuvant treatment of advanced,metastatic,and recurrent cancer in the liver,gastrointestinal tract,and genitourinary tract,and other solid tumors.Erdafitinib is a fibroblast growth factor receptor(FGFR)inhibitor,and it is an adenosine triphosphate competitive inhibitor of FGFR1,FGFR2,FGFR3,and FGFR4.Immune checkpoint inhibitors are monoclonal antibodies that block programmed cell death protein 1(PD-1)and its ligand that exert intrinsic antitumor mechanisms.The promising results of first-line treatment of advanced and metastatic urothelial carcinoma with PD-1 blockades with single or combined agents,indicate a new concept in the treatment of advanced,metastatic,and recurrent hepatic and gastrointestinal carcinomas.cancer immunotherapy as first-line treatment will improve overall survival and provide better quality of life.Debate is arising as to whether to apply the cancer immunotherapy as first-line treatment in invasive carcinomas,or as second-line treatment in recurrent or metastatic carcinoma following the standard chemotherapy.The literature in the field is not definite,and so far,there has been no consensus on the best approach in this situation.At present,as it is described in this editorial,the decision is applied on a case-by-case basis.

关键词： Programmed cell death protein-ligand 1 Erdafitinib Liver cancer Fibroblast growth factor receptor inhibitors Checkpoint inhibitors bladder cancer Metastases

Caffeine Suppresses Apoptosis of bladder cancer RT4 Cells in Response to Ionizing Radiation by Inhibiting Ataxia Telangiectasia Mutated-Chk2-p53 Axis

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Chinese Medical Journal 2015年第21期128卷 2938-2945页

作者： Zhe-Wei Zhang Jing Xiao Wei Luo Bo-Han Wang Ji-Min Chen Department of Urology Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang 310009 China Ministry of Education Key Laboratory of cancer Prevention and Intervention Zhejiang University School of Medicine Hangzhou Zhejiang 310009 China

Background： Caffeine suppresses ataxia telangiectasia and Rad3 related and ataxia telangiectasia mutated （ATM） activities; ATM is the major kinase for DNA damage detection. This study aimed to investigate the effects of caffeine on DNA damage responses in cells from the bladder cancer cell line RT4 those were exposed to ionizing radiation （IR）. Methods： Immunofluorescent staining was performed to investigate changes in the proteins involved in DNA damage responses with or without caffeine. A mouse xenograft model was used to study the effects of caffeine on the DNA damage responses. Western blotting was used to investigate the effects of caffeine pretreatment on the ATM-Chk2-p53-Puma axis, while real-time polymerase chain reaction （RT-PCR） assessed changes in messenger RNA levels of p53 and downstream targets responding to IR. Finally, terminal deoxynucleotidyl transferase-dUTP nick end labeling assay. Western blotting and colony formation assay were used to measure the effects of caffeine on radiation-related apoptosis. All of the data were analyzed with a two-tailed Student＇s t-test. Results： lmmunofluorescent staining showed that caffeine pretreatment profoundly suppressed the formation ofyH2AXand p53-binding protein 1 foci in RT4 cells in response to irradiation. Cellular and animal experiments suggested that this suppression was mediated by suppression of the ATM-Chk2-p53-Puma DNA damage-signaling axis. RT-PCR indicated caffeine also attenuated transactivation of p53 and p53-inducible genes. The colony formation assay revealed that caffeine displayed radioprotective effects on RT4 cells in response to low-dose radiation compared to the radiosensitization effects on T24 cells. Conclusion： Caffeine may inhibit IR-related apoptosis of bladder cancer RT4 cells by suppressing activation of the ATM-Chk2-p53-Puma axis.

关键词： Apoptosis Ataxia Telangiectasia Mutated bladder cancer Caffeine p53

Exosomes in bladder cancer:novel biomarkers and targets

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2021年第5期22卷 341-347,I0001页

作者： Hao GENG Qingchen ZHOU Wenhao GUO Ling LU Liangkuan BI Yi WANG Jie MIN Dexin YU Zhaofeng LIANG Department of Urology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230032China Department of Urology the First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Jiangsu Key Laboratory of Medical Science and Laboratory Medicine School of MedicineJiangsu UniversityZhenjiang 212013China Department of Child Healthcare Women and Children Health Hospital of ZhenjiangZhenjiang 212001China

Exosomes are nanometer-sized vesicles that contain various types of biologically active components,including proteins,nucleic acids,carbohydrates,and lipids,which vary with the type and physiological state of the cell.In recent years,several studies have showed that exosomes can provide new non-invasive diagnostic and prognostic biomarkers in patients affected by cancers,including bladder cancer(BC),and the lipid bilayer membrane structure makes exosomes as promising delivery vehicles for therapeutic applications.Exosomes have the characteristics of high abundance,high stability,tissue specificity,and wide distribution in body fluids,and are secreted as various types by cells in different states,thereby possessing great potential as biomarkers for BC.Herein,we briefly summarize the functions and roles of exosomes in the occurrence and development of BC and the current progress of research on exosomes in BC,while focusing on potential clinical applications of the diagnosis,treatment,and prognosis of BC.

关键词： Exosome bladder cancer Function Clinical application Biomarker

Effect of internal iliac artery chemotherapy after transurethral resection of bladder tumor for muscle invasive bladder cancer

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Chinese Journal of cancer Research 2014年第5期26卷 558-563页

作者： Jianxing Li Qi Wang Bo Xiao Xin Zhang Department of Urology Beijing Tsinghua Changgung HospitalMedical CentreTsinghua University Department of Urology Xuanwu HospitalCapital Medical University

Objective： To evaluate the clinical effect of transurethral resection of bladder tumor（TUR-BT） combined with internal iliac artery chemotherapy and intravesical instillation therapy for muscle invasive bladder cancer（MIBC）.Methods： From February 2007 to April 2014, 62 patients with MIBC were treated with TUR-BT combined with intravesical instillation therapy, with or without internal iliac artery chemotherapy, and the chemotherapy regimen is gemcitabine and cisplatin（GC）. The bladder preservation and survival rate as well as cancer-specific survival（CSS） rate and overall survival（OS） rate of the two groups were compared.Results： Sixty-two patients were followed-up for 26-102 months with an average of 58.4±3.1 months. Recurrence-free survival（RFS） at 2-year for TUR ＋ GC group and TUR group were 77.8% and 53.8%, respectively. bladder preserved rate（BPR） at 3-year for TUR ＋ GC group and TUR group were 94.4% and 80.8%. CSS rate at 2-year for TUR ＋ GC group and TUR group were 94.4% and 84.6%. The diseasefree survival（DFS） at 1-year for TUR ＋ GC group and TUR group were 83.3% and 61.5%, and 77.8% and 53.8% for the 2nd year. OS at 2-year for TUR ＋ GC group and TUR group were 88.9% and 92.3%.Conclusions： TUR-BT and intravesical instillation therapy combined with internal iliac artery chemotherapy for MIBC had a better outcome at RFS, BPR and DFS than the treatment without internal iliac artery chemotherapy, and no difference in OS and CSS.

关键词： Transurethral resection internal artery chemotherapy bladder cancer

Does urothelial cancer of bladder behave differently in young patients？

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Chinese Medical Journal 2012年第15期125卷 2643-2648页

作者： WANG Zhi-hua LI You-yuan HU Zhi-quan ZHU Hui ZHUANG Qian-yuan QI Yong YE Zhang-qun Department of Urology Tongji Hospital affiliated Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 China Department of Urology University Hospitals Case Medical CenterCase Westem Reserve University School of Medicine ClevelandOH 44106 USA

Background bladder urothelial cancer has been diagnosed at an increasing rate among young adults in China while the clinical outcomes remain highly controversial. To optimize the management of young patients with bladder cancer, we examined whether bladder urothelial cancer in young patients behaved differently from that in the elder patients. Methods From 1994 to 2008, a database of bladder urothelial cancer patients at a major tertiary medical center was retrospectively reviewed. The clinical and pathological parameters of patients who were less than 40 years of age and a series of patients older than 40 years of age as the control group during the same period were compared. A survival analysis was performed using the Kaptan-Meier method and log-rank test, and Cox regression was performed to identify clinical parameters that affected the clinic outcomes. Results Young bladder cancer patients had a lower male-to-female ratio and were less likely to have advanced stages and high-grade cancers at the initial diagnosis. Tumors in young bladder cancer patients tended to be less multifocal at diagnosis. In addition, young patients had a lower recurrence rate and longer recurrence interval than older patients. The Kaplan-Meier curve and Log-rank test showed that young patients had significantly better cancer specific survival than old patients. The univariate and multivariate Cox regression analysis revealed that tumor grade is the sole predictor for tumor recurrence in young patients. Conclusions Young patients with bladder cancer have favorable pathological features and clinical outcomes than older patients. These findinqs ar.que for more conservative management approaches for young patients with bladder cancer.

关键词： bladder cancer young adults pathology prognosis

Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1

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Acta Pharmaceutica Sinica B 2021年第12期11卷 4045-4054页

作者： Na Kong Xiaying Chen Jiao Feng Ting Duan Shuiping Liu Xueni Sun Peng Chen Ting Pan Lili Yan Ting Jin Yu Xiang Quan Gao Chengyong Wen Weirui Ma Wencheng Liu Mingming Zhang Zuyi Yang Wengang Wang Ruonan Zhang Bi Chen Tian Xie Xinbing Sui Wei Tao College of Pharmacy and Department of Medical Oncology the Affiliated Hospital of Hangzhou Normal UniversitySchool of MedicineHangzhou Normal UniversityHangzhou 311121China Key Laboratory of Elemene Class Anti-cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou 311121China Center for Nanomedicine and Department of Anesthesiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation.Currently,the therapeutic role of ferroptosis on cancer is gaining increasing interest.Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types;however,the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown.In the study,we investigated the effect of baicalin on bladder cancer cells5637 and KU-19-19.As a result,we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells.Subsequently,we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo,accompanied by reactive oxygen species(ROS) accumulation and intracellular chelate iron enrichment.The ferroptosis inhibitor deferoxamine but not necrostatin-1,chloroquine(CQ),N-acetyl-L-cysteine,L-glutathione reduced,or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone(Z-VAD-FMK) rescued baicalin-induced cell death,indicating ferroptosis contributed to baicalin-induced cell death.Mechanistically,we show that ferritin heavy chain1(FTH1) was a key determinant for baicalin-induced ferroptosis.Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells.Taken together,our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis,which will hopefully provide a prospective compound for bladder cancer treatment.

关键词： Baicalin Ferroptosis bladder cancer FTH1 Deferoxamine