Bladder Cancer最新文献

{"title":"SH3BP5-AS1/IGF2BP2/VDAC2 Axis Promotes the Apoptosis and Ferroptosis of Bladder Cancer Cells","authors":"Yong Shao, Yunhui Chan, Rong Zhao","doi":"10.3233/blc-211629","DOIUrl":"https://doi.org/10.3233/blc-211629","url":null,"abstract":"BACKGROUND: Bladder cancer (BC) is the most common malignant tumor in the urinary system with a high incidence, imposing a burden on the healthcare system worldwide. The participation of long non-coding RNAs (lncRNAs) in BC has attracted increasing attention. OBJECTIVE: The aim in the current study was to explore the potential mechanism involving SH3BP5-AS1 in modulating BC cell proliferation, apoptosis and ferroptosis. METHODS: qPCR and WB analysis measured the expression of RNAs and proteins. Functional and mechanism experiments were performed to investigate RNA impacts on cell proliferation, apoptosis and ferroptosis, and explore the correlation between RNA and protein expression. RESULTS: SH3BP5-AS1 was down-regulated in BC cells, and SH3BP5-AS1 overexpression could inhibit BC cell proliferation but facilitate the cell apoptosis. SH3BP5-AS1 was also found to facilitate the ferroptosis of BC cells. Additionally, SH3BP5-AS1 was confirmed to recruit IGF2BP2 to regulate VDAC2 expression in the m6A-dependent manner. VDAC2 was detected to be down-regulated in BC cells and was verified to inhibit BC cell growth. Moreover, it was indicated from rescue assays that SH3BP5-AS1 could modulate VDAC2 expression to promote the ferroptosis of BC cells. CONCLUSION: SH3BP5-AS1 could affect BC cell proliferation, apoptosis and ferroptosis via IGF2BP2/VDAC2, providing a novel molecular perspective for understanding BC.","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135822899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in the Classification of Bladder Cancer - Updates from the 5th Edition of the World Health Organization Classification of the Urinary and Male Genital Tumors.","authors":"Charles C Guo, Steven S Shen, Bogdan Czerniak","doi":"10.3233/BLC-220106","DOIUrl":"10.3233/BLC-220106","url":null,"abstract":"<p><strong>Background: </strong>The World Health Organization Classification (WHO) of Urinary and Male Genital Tumors has recently been updated to its 5th edition. The new edition presents a comprehensive approach to the classification of urinary and male genital tumors with an incorporation of morphologic, clinical, and genomic data.</p><p><strong>Objective: </strong>This review aims to update the new classification of bladder cancer in the 5th edition and to highlight important changes in nomenclatures, diagnostic criteria, and molecular characterization, as compared to the 4th edition.</p><p><strong>Methods: </strong>The pathologic classification of bladder cancer in the 5th edition of WHO Classification of Urinary and Male Genital Tumours was compared to that in the 4th edition. PubMed was searched using key words, including bladder cancer, WHO 1973, WHO 1998, WHO 2004, WHO 2016, histology, pathology, genomics, and molecular classification in the time frame from 1973 to August of 2022. Other relevant papers were also consulted, resulting in the selection of 81 papers as references.</p><p><strong>Results: </strong>The binary grading of papillary urothelial carcinoma (UC) is practical, but it may be oversimplified and contribute to \"grade migration\" in recent years. An arbitrary cutoff (5%) has been proposed for bladder cancers with mixed grades. The diagnosis of papillary urothelial neoplasm with low malignant potential has been dramatically reduced in recent years because of overlapping morphology and treatment with low-grade papillary UC. An inverted growth pattern should be distinguished from true (or destructive) stromal invasion in papillary UC. Several methods have been proposed for pT1 tumor substaging, but it is often challenging to substage pT1 tumors in small biopsy specimens. Bladder UC shows a high tendency for divergent differentiation, leading to several distinct histologic subtypes associated with an aggressive clinical behavior. Molecular classification based on the genomic analysis may be a useful tool in the stratification of patients for optimal treatment.</p><p><strong>Conclusions: </strong>The 5th edition of WHO Classification of Urinary and Male Genital Tumours has made several significant changes in the classification of bladder cancer. It is important to be aware of these changes and to incorporate them into routine clinical practice.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"1 1","pages":"1-14"},"PeriodicalIF":1.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41555692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Trials Corner Issue 8(4).","authors":"Piyush K Agarwal, Cora N Sternberg","doi":"10.3233/BLC-229008","DOIUrl":"https://doi.org/10.3233/BLC-229008","url":null,"abstract":"","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"8 4","pages":"423-425"},"PeriodicalIF":1.0,"publicationDate":"2022-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urethral Melanoma - Clinical, Pathological and Molecular Characteristics.","authors":"Roy Mano,&nbsp;Benedikt Hoeh,&nbsp;Renzo G DiNatale,&nbsp;Alejandro Sanchez,&nbsp;Nicole E Benfante,&nbsp;Ed Reznik,&nbsp;Mario M Leitao,&nbsp;Alexander N Shoushtari,&nbsp;Alvin Goh,&nbsp;S Machele Donat,&nbsp;Harry W Herr,&nbsp;Bernard H Bochner,&nbsp;Guido Dalbagni,&nbsp;Timothy F Donahue","doi":"10.3233/BLC-211633","DOIUrl":"https://doi.org/10.3233/BLC-211633","url":null,"abstract":"<p><strong>Background: </strong>Mucosal melanoma involving the urethra is a rare disease with distinct clinical and molecular characteristics and poor outcomes. Our current knowledge is limited by the small number of reports regarding this disease.</p><p><strong>Objective: </strong>To describe the clinical, pathological, and molecular characteristics of urethral melanoma.</p><p><strong>Methods: </strong>We summarized the clinicopathologic data for 31 patients treated for urethral melanoma from 1986-2017 at our institution. Genomic data from our institutional sequencing platform MSK-IMPACT (<i>n</i> = 5) and gene-specific PCR data on <i>BRAF</i>, <i>KIT</i>, and/or <i>NRAS</i> (<i>n</i> = 8) were compared to genomic data of cutaneous melanomas (<i>n</i> = 143), vulvar/vaginal melanomas (<i>n</i> = 24), and primary non-melanoma urethral tumors (<i>n</i> = 5) from our institutional database.</p><p><strong>Results: </strong>Twenty-three patients were diagnosed with localized disease, 7 had regional/nodal involvement and one had metastases. Initial treatment included surgery in 25 patients; seven had multimodal treatment. Median follow-up was 46 months (IQR 33-123). Estimated 5-year cancer-specific survival was 45%. No significant change in survival was observed based on a year of treatment.Primary urethral melanomas showed a higher frequency of <i>TP53</i> mutations compared to cutaneous (80.0% vs. 18.2%, <i>p</i> = 0.006) and vulvar/vaginal melanomas (80.0 vs. 25.0%, <i>p</i> = 0.04). <i>BRAF</i> mutations were absent in urethral primaries (0% vs. 46% in cutaneous melanoma, <i>p</i> = 0.02). Tumor mutation burden was higher in cutaneous than urethral melanomas (<i>p</i> = 0.04). Urethral melanomas had a higher number of somatic alterations compared to non-melanoma urethral tumors (median 11 vs. 5, <i>p</i> = 0.03).</p><p><strong>Conclusions: </strong>Our findings support a unique mutational landscape of urethral melanoma compared to cutaneous melanoma. Survival remains poor and is unchanged over the time studied.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"8 3","pages":"291-301"},"PeriodicalIF":1.1,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/e7/blc-8-blc211633.PMC9536426.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40567733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenging Cases in Urothelial Cancer: Case 25.","authors":"Mark S Soloway, Neil A Abrahams","doi":"10.3233/BLC-229005","DOIUrl":"10.3233/BLC-229005","url":null,"abstract":"","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"1 1","pages":"329-333"},"PeriodicalIF":1.0,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41517674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Sex Differences in Bladder Cancer: Evident and Elusive Sex-biasing Factors.","authors":"Christa M Lam, Zihai Li, Dan Theodorescu, Xue Li","doi":"10.3233/BLC-211658","DOIUrl":"10.3233/BLC-211658","url":null,"abstract":"<p><p>Bladder cancer incidence is drastically higher in males than females across geographical, racial, and socioeconomic strata. Despite potential differences in tumor biology, however, male and female bladder cancer patients are still clinically managed in highly similar ways. While sex hormones and sex chromosomes have been shown to promote observed sex differences, a more complex story lies beneath these evident sex-biasing factors than previously appreciated. Advances in genomic technology have spurred numerous preclinical studies characterizing elusive sex-biasing factors such as epigenetics, X chromosome inactivation escape genes, single nucleotide polymorphism, transcription regulation, metabolism, immunity, and many more. Sex-biasing effects, if properly understood, can be leveraged by future efforts in precision medicine based on a patient's biological sex. In this review, we will highlight key findings from the last half century that demystify the intricate ways in which sex-specific biology contribute to differences in pathogenesis as well as discuss future research directions.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"8 3","pages":"241-254"},"PeriodicalIF":1.0,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ce/59/blc-8-blc211658.PMC9536425.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40567734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Trials Corner Issue 8(2).","authors":"Piyush K Agarwal, Cora N Sternberg","doi":"10.3233/BLC-229004","DOIUrl":"https://doi.org/10.3233/BLC-229004","url":null,"abstract":"","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"8 2","pages":"233-235"},"PeriodicalIF":1.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Chromatin Modifying Complexes and Therapeutic Opportunities in Bladder Cancer.","authors":"Khyati Meghani, Lauren Folgosa Cooley, Andrea Piunti, Joshua J Meeks","doi":"10.3233/BLC-211609","DOIUrl":"10.3233/BLC-211609","url":null,"abstract":"<p><strong>Background: </strong>Chromatin modifying enzymes, mainly through post translational modifications, regulate chromatin architecture and by extension the underlying transcriptional kinetics in normal and malignant cells. Muscle invasive bladder cancer (MIBC) has a high frequency of alterations in chromatin modifiers, with 76% of tumors exhibiting mutation in at least one chromatin modifying enzyme [1]. Additionally, clonal expansion of cells with inactivating mutations in chromatin modifiers has been identified in the normal urothelium, pointing to a currently unknown role of these proteins in normal bladder homeostasis.</p><p><strong>Objective: </strong>To review current knowledge of chromatin modifications and enzymes regulating these processes in Bladder cancer (BCa).</p><p><strong>Methods: </strong>By reviewing current literature, we summarize our present knowledge of external stimuli that trigger loss of equilibrium in the chromatin accessibility landscape and emerging therapeutic interventions for targeting these processes.</p><p><strong>Results: </strong>Genetic lesions in BCa lead to altered function of chromatin modifying enzymes, resulting in coordinated dysregulation of epigenetic processes with disease progression.</p><p><strong>Conclusion: </strong>Mutations in chromatin modifying enzymes are wide-spread in BCa and several promising therapeutic targets for modulating activity of these genes are currently in clinical trials. Further research into understanding how the epigenetic landscape evolves as the disease progresses, could help identify patients who might benefit the most from these targeted therapies.</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"8 2","pages":"101-112"},"PeriodicalIF":1.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/6e/blc-8-blc211609.PMC9278011.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10686461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Functional Gene, Zinc Finger Protein 485 (ZNF485), is Involved in Bladder Cancer Proliferation","authors":"Yiao Tan, Fangfang Zhao, Shuhan Liu, Tao Huang, Chunbao Zang, Dan Sha, Lingsuo Kong, Fangfang Ge, Dabing Huang, Youguang Pu","doi":"10.3233/blc-211623","DOIUrl":"https://doi.org/10.3233/blc-211623","url":null,"abstract":"<h4><span>Abstract</span></h4><h3><span></span>BACKGROUND:</h3><p>Bladder cancer is the second most common urological cancer worldwide, with low early diagnosis and high mortality. The limited progress in diagnostics and treatment greatly impedes the survival of bladder cancer patients.</p><h3><span></span>OBJECTIVE:</h3><p>Potential therapeutic biomarkers are urgently needed for future clinical treatment.</p><h3><span></span>METHODS:</h3><p>We analyzed the sequencing data and corresponding clinicopathological features and survival information of bladder cancer patients in the TCGA database and identified a new zinc finger protein 485 gene, termed ZNF485, which is highly expressed in the tissues of bladder cancer patients and was verified in cells, animal models and tissue microarrays.</p><h3><span></span>RESULTS:</h3><p>We found that inhibition of ZNF485 in the bladder cancer cell lines T24 and 5637 obviously inhibited proliferation and promoted the apoptosis of cancer cells. Furthermore, wound healing and invasion assays showed that downregulation of ZNF485 significantly decreased the mobility and invasion of T24 and 5637 cells. In addition, ZNF485-shRNA transfection obviously inhibited tumor growth in nude mice. Immunohistochemical results of clinical samples showed that the expression level of ZNF485 protein in cancer tissues was higher than that in adjacent tissues. Mechanistic analysis identified possible downstream target genes.</p><h3><span></span>CONCLUSIONS:</h3><p>Taken together, the results provide evidence that ZNF485 is involved in bladder cancer proliferation and might be a potential therapeutic biomarker for the treatment of this disease</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"37 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2022-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138508134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 2 Study of S-588410 Maintenance Monotherapy for Platinum-Treated Advanced or Metastatic Urothelial Carcinoma","authors":"Nobuaki Shimizu, Syed A. Hussain, Wataru Obara, Toshinari Yamasaki, Satoru Takashima, Takahiro Hasegawa, Motofumi Iguchi, Kenji Igarashi, Osamu Ogawa, Tomoaki Fujioka","doi":"10.3233/blc-211592","DOIUrl":"https://doi.org/10.3233/blc-211592","url":null,"abstract":"<h4><span>Abstract</span></h4><h3><span></span>BACKGROUND:</h3><p>Effective maintenance therapy for urothelial carcinoma (UC) is needed to delay progression after first-line chemotherapy.</p><h3><span></span>OBJECTIVE:</h3><p>To evaluate S-588410, a cancer peptide vaccine containing five human leukocyte antigen (HLA)-A^*24:02-restricted epitope peptides derived from five cancer-testis antigens (DEPDC1, MPHOSPH1, URLC10, CDCA1, and KOC1) in chemotherapy-treated, clinically stable patients with advanced or metastatic UC</p><h3><span></span>MATERIALS AND METHODS:</h3><p>This open-label, international, phase 2 trial enrolled patients with UC who had completed≥4 cycles of first-line platinum-containing chemotherapy without disease progression. Forty-five HLA-A^*24:02-positive patients received subcutaneous injections of S-588410 (Montanide ISA 51 VG with 1 mg/mL of each peptide) weekly for 12 weeks then once every 2 weeks thereafter for up to 24 months. Thirty-six HLA-A^*24:02-negative patients did not receive S-588410 (observation group). The primary endpoint was the rate of cytotoxic T-lymphocyte (CTL) induction against≥1 of the peptides at 12 weeks.</p><h3><span></span>RESULTS:</h3><p>The CTL induction rate in the S-588410 group was 93.3% (<i>p</i> &lt; 0.0001, one-sided binomial test with a rate of≤50% as the null hypothesis). The antitumor response rate was 8.9% in the S-588410 group and 0% in the observation group; median progression-free survival was 18.1 versus 12.5 weeks and median overall survival was 71.0 versus 99.0 weeks, respectively. The most frequent treatment-emergent adverse event was injection-site reactions (47 events, grades 1–3) reported in 93.3% (<i>n</i> = 42/45) of participants.</p><h3><span></span>CONCLUSIONS:</h3><p>S-588410 demonstrated a high CTL induction rate, acceptable safety profile, and modest clinical response, as maintenance therapy in participants with advanced or metastatic UC who had received first-line platinum-based chemotherapy (EudraCT 2013-005274-22).</p>","PeriodicalId":54217,"journal":{"name":"Bladder Cancer","volume":"28 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2022-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138508129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}