American journal of clinical and experimental urology最新文献

{"title":"Impact of race-based calculations of eGFR on the management of muscle invasive bladder cancer.","authors":"Amir Khan, Shu Wang, Kathryn Hughes Barry, Eberechukwu Onukwugha, Michael Phelan, Rehan Choudhry, Mohummad Minhaj Siddiqui","doi":"10.62347/DOCH1460","DOIUrl":"10.62347/DOCH1460","url":null,"abstract":"<p><strong>Purpose: </strong>The estimated glomerular filtration rate (eGFR) has historically been calculated with a race-coefficient multiplier (RCM); however, the RCM has been broadly criticized as inaccurate and a potential contributor to exacerbating disparities. We evaluated the impact of the RCM on eGFR and examined the 30-day post-cystectomy complications in a muscle-invasive bladder cancer cohort.</p><p><strong>Materials and methods: </strong>We retrospectively analyzed patients diagnosed with MIBC who underwent cystectomy in the ACS NSQIP database from 2006 to 2020 using CPT and ICD codes. The eGFR was computed using the Modification of Diet in Renal Diseases equation which has RCM = 1.212 for black patients. Using the race data field, patients were categorized into Black and non-Black. The eGFR cut-off of 60 mL/min/1.73 m² was chosen for patient stratification because it represents a key clinical threshold in the classification of chronic kidney disease and influences various care decisions such as chemotherapy choice. Subsequently, we examined the 30-day post-cystectomy cardiovascular and pulmonary (CV&P) complications in these patients stratified by their eGFR using descriptive statistics and a multivariable logistic regression model.</p><p><strong>Results: </strong>The application of the RCM to estimate eGFR in the Black cohort increased the mean eGFR from 57.8 to 70.0 ml/min/1.73 m² (P = 0.001) which led to a 17.3% (45.6% vs 62.9%, P = 0.001) increase in the proportion of Black patients with eGFR≥60 ml/min/1.73 m². The rate of CV&P complications post-cystectomy among this group of 17.3% of patients in the Black cohort was 7.6% compared to a 4.3% complication rate among a non-Black cohort matched for similar eGFR for whom RCM was not applied (P = 0.06). Black patients in this RCM-dependent category of eGFR≥60 mL/min/1.73 m² had higher adjusted odds of developing 30-day post cystectomy CV&P complications compared to eGFR-matched non-Black patients (OR = 2.2, 95% CI = 1.13-4.31, P = 0.02).</p><p><strong>Conclusion: </strong>In this study, we found that inclusion of RCM in the eGFR significantly increases the proportion of Black patients with eGFR≥60. This RCM might also be associated with higher post-cystectomy CV&P complications; therefore, future studies are needed to evaluate the implications of race-based algorithms on outcomes.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"12 6","pages":"389-398"},"PeriodicalIF":1.5,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOX2 control activation of dormant prostate cancer cells in bone metastases by promoting CCNE2 gene expression.","authors":"Min Deng, Pei-Zheng Huang, Ze-Yu Huang, Ting-Ting Chen, Xing Luo, Chao-Yu Liao, Wen-Hao Xu, Jiang Zhao, Qing-Jian Wu, Ji Zheng","doi":"10.62347/ASCY2532","DOIUrl":"10.62347/ASCY2532","url":null,"abstract":"<p><strong>Background: </strong>Cancer stem cells (CSCs) have a powerful tumor initiation ability, which can promote the early dissemination of single disseminated tumor cells (DTCs), leading to tumor progression. SOX2, a pluripotent inducible transcription factor, is key to maintaining self-renewal and pluripotency of prostate cancer stem cells. However, there is a lack of comprehensive understanding of how SOX2 regulates DTCs dormancy and proliferation in the bone marrow microenvironment.</p><p><strong>Methods and results: </strong>By constructing a mouse bone metastasis model to simulate the progression of prostate cancer with bone metastasis, the bone tissue immunofluorescence showed that SOX2 expression increased with the progression of prostate cancer in the bone marrow microenvironment. We validated this phenomenon with publicly available single-cell and transcriptome datasets and found that SOX2 is involved in multiple phenotypes associated with prostate cancer dormancy, proliferation, and invasion. Further, CCNE2, a potential target downstream of SOX2, was identified through multiple transcription factor databases and protein interaction networks.</p><p><strong>Conclusion: </strong>The expression of SOX2 affects multiple phenotypes related to dormancy, proliferation and invasion of prostate cancer, and may indirectly activate the dormant prostate cancer cells through the downstream target gene CCNE2, thus affecting the progression and bone metastasis of prostate cancer.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"12 6","pages":"375-388"},"PeriodicalIF":1.5,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of cell plasticity on prostate tumor heterogeneity and therapeutic response.","authors":"Maddison Archer, Kevin M Lin, Kaushik P Kolanukuduru, Joy Zhang, Reuben Ben-David, Leszek Kotula, Natasha Kyprianou","doi":"10.62347/YFRP8901","DOIUrl":"10.62347/YFRP8901","url":null,"abstract":"<p><p>Epithelial-mesenchymal transition (EMT) is a dynamic process of lineage plasticity in which epithelial cancer cells acquire mesenchymal traits, enabling them to metastasize to distant organs. This review explores the current understanding of how lineage plasticity and phenotypic reprogramming drive prostate cancer progression to lethal stages, contribute to therapeutic resistance, and highlight strategies to overcome the EMT phenotype within the prostate tumor microenvironment (TME). Emerging evidence reveals that prostate tumor cells can undergo lineage switching, adopting alternative growth pathways in response to anti-androgen therapies and taxane-based chemotherapy. These adaptive mechanisms support tumor survival and growth, underscoring the need for deeper insights into the processes driving prostate cancer differentiation, including neuroendocrine differentiation and lineage plasticity. A comprehensive understanding of these mechanisms will pave the way for innovative therapeutic strategies. Effectively targeting prostate cancer cells with heightened plasticity and therapeutic vulnerability holds promise for overcoming treatment resistance and preventing tumor recurrence. Such advancements are critical for developing effective approaches to prostate cancer treatment and improving patient survival outcomes.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"12 6","pages":"331-351"},"PeriodicalIF":1.5,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic features of bladder cancer based on five neddylation-related genes.","authors":"Jiang Guo, Yuanning Zhang, Lei He, Xiaojun Wang, Zhangyan Chen, Can Yao","doi":"10.62347/RWCH7802","DOIUrl":"10.62347/RWCH7802","url":null,"abstract":"<p><strong>Background: </strong>Nedylation and tumours are closely linked. The role of nedylation in bladder cancer (BCa) has rarely been reported and this study aims to explore its potential impact on the pathogenesis and progression of BCa.</p><p><strong>Methods: </strong>Leveraging gene expression data from the TCGA database, this research employs the limma software package and WGCNA for gene module identification and analysis. Subsequent steps include the construction of a PPI network, the conduct of LASSO and univariate Cox regression analyses, and utilizing GSEA and single-cell sequencing to examine the influence of hub genes in bladder cancer-related biological pathways.</p><p><strong>Results: </strong>The investigation revealed 11,361 genes with significant differential expression between normal and tumour tissues, and identified 1,500 hub genes through analysis. LASSO regression identified eight critical genes. Univariate Cox regression analysis revealed that COMMD9, GPS1, PSMB5, VHL, and WDR5 are independent prognostic factors for BCa. GSEA and single-cell sequencing highlight the potential of these genes to modulate immune responses and interactions between tumour and immune cells. Meanwhile, GSEA demonstrated that GPS1 can activate the NF-κB signalling pathway, leading to an increase in influenza virus polymerase activity.</p><p><strong>Conclusion: </strong>This study identifies COMMD9, GPS1, PSMB5, VHL, and WDR5 as significant prognostic markers in BCa, thereby underscoring their roles in immune regulation and tumour-immune cell dynamics.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"12 5","pages":"240-254"},"PeriodicalIF":1.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased expression of <i>LncRNA CRYM-AS1</i> promotes apoptosis through the Hippo-YAP1 signaling pathway leading to diabetic erectile dysfunction.","authors":"Ze-Bo Zhang, Ying Chen, Zhan-Sen Huang, Zi-Jun Du, Wei Wang, Bo-Wen Tang, Su-Shun Yuan, Di-Ling Chen, Shu-Guang Zhu, Jun Chen","doi":"10.62347/YZGC6734","DOIUrl":"10.62347/YZGC6734","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) primarily engage with mRNA, DNA, proteins, and microRNAs (miRNAs), thereby regulating gene expression; however, its specific role in diabetic erectile dysfunction (DED) has not been studied. This study aims to investigate the effects and mechanisms of <i>LncRNA CRYM-AS1</i> in DED. The differential target gene <i>LncRNA CRYM-AS1</i> was identified in the penile tissues of rats with DED through bioinformatics analyses. A KEGG signaling pathway enrichment analysis suggested a potential association between <i>LncRNA CRYM-AS1</i> and the Hippo-YAP1 pathway. Real-time fluorescent quantitative PCR (RT-qPCR) results indicated a significantly lower expression of <i>LncRNA CRYM-AS1</i> in the penile tissue of DED rats compared to the control group. Western Blot and immunohistochemistry (IHC) staining results demonstrated significantly elevated protein expression levels of YAP1, Caspase3, BAX, and Bcl-2, with a decreased Bcl-2/BAX ratio. CCK8 cell viability results showed a significant decrease in cell viability in the high glucose group at 4 days of modeling, and compared with the normal glucose group, RT-qPCR results showed that the expression of <i>LncRNA CRYM-AS1</i> in the high glucose group in human umbilical vein endothelial cells (HUVECs) was significantly reduced; Western Blot results showed that the protein expression of YAP1, Cleaved-caspase3 and BAX was significantly up-regulated, and the protein expression of Bcl-2 was significantly down-regulated in the high glucose group. Compared with the empty vector group, RT-qPCR results after transfection of si<i>LncRNA CRYM-AS1</i> showed that the expression of <i>LncRNA CRYM-AS1</i> was down-regulated, the mRNA and protein expression of YAP1, Caspase3, Cleaved-caspase3, BAX, and Bcl-2 were significantly up-regulated, and the Bcl-2/BAX ratio decreased. Flow cytometry results showed that the apoptosis rate of HUVECs increased after interference. Low expression of <i>LncRNA CRYM-AS1</i> may activate the Hippo-YAP1 signaling pathway to regulate apoptosis in HUVECs, leading to ED development, and the discovery of new target genes may provide new therapeutic targets to regulate diabetic erectile disfunction.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"12 5","pages":"226-239"},"PeriodicalIF":1.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmembrane prostatic acid phosphatase: a therapeutic target in advanced prostate cancer.","authors":"Alexander Kirschenbaum, Pamela Cheung, Vinodh Rajagopalan, Shen Yao, Lucas Milgrim, Natasha Kyprianou, Alice C Levine","doi":"10.62347/DZIU5992","DOIUrl":"10.62347/DZIU5992","url":null,"abstract":"<p><p>Prostate cancer (PCa) is the most common cancer and second leading cause of cancer death in American men. Most patients with metastatic disease respond initially to androgen deprivation therapy (ADT), but almost inevitably progress to castration resistant prostate cancer (CRPC). Identification of markers and drivers of mCRPC that (a) represent a progenitor-type cancer cell population (b) persist in castration resistant disease (c) are actionable targets expressed on the cell surface, and (d) are induced by hypoxia, is required to facilitate the development of novel targeted therapies. We identified prostatic acid phosphatase (PAP), particularly the transmembrane form (TMPAP), as one such potential target. PAP is both a phosphatase and a 5'ectonucleotidase that generates adenosine. We herein demonstrate that PAP is expressed early on during fetal development and persists in castration-resistant disease. The VCaP and VCaP-enzalutamide-resistant PCa cell lines express secretory (sPAP) and TMPAP. Androgens downregulate while hypoxia upregulates PAP expression. In vivo, PAP persists in hypoxic areas of castration-resistant tumors. Knockdown of PAP decreases VCaP migration and colony formation. Finally, treatment of VCaP tumor-bearing mice with inhibitors of adenosine receptors reduces tumor growth. This data demonstrates that TMPAP is a novel therapeutic target in advanced prostate cancer.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"12 5","pages":"255-265"},"PeriodicalIF":1.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N4-acetyl-sulfamethoxazole stone in a patient on chronic trimethoprim/sulfamethoxazole therapy: a case report and literature review.","authors":"Kevin Morgan, William Donelan, Mitsu Andre, Jennifer Janelle, Benjamin Canales, Vincent G Bird","doi":"10.62347/PIXS5642","DOIUrl":"10.62347/PIXS5642","url":null,"abstract":"<p><p>Though early antibiotic sulfonamides had poor urine solubility and resulted in urine crystalluria and urolithiasis, sulfamethoxazole urolithiasis is a rare phenomenon. In our case report, we describe a patient with N4-acetyl-sulfamethoxazole (metabolite of sulfamethoxazole) urolithiasis that developed after prolonged exposure to trimethoprim/sulfamethoxazole (TMP-SMX). Prior to stone formation, our patient had a total colectomy and end ileostomy created after an episode of toxic megacolon secondary <i>Clostridium difficile</i>. He also had benign prostatic hypertrophy and chronic urinary retention. These specific metabolic conditions, including dehydration leading to higher urinary concentration, urinary stasis, and low urinary pH may have predisposed our patient to this rare condition. Our patient's stones were then imaged under light microscopy and scanning electron microscopy (SEM). It was found to be comprised of rectangular shaped crystals. To our knowledge, this is the first time these stone crystals have been imaged with SEM.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"12 5","pages":"296-300"},"PeriodicalIF":1.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Hodgkin's primary lymphoma involving the genitourinary tract: histopathological experience from two tertiary hospitals, Western region, Saudi Arabia.","authors":"Haneen Al-Maghrabi, Jaudah Al-Maghrabi","doi":"10.62347/GFNJ2400","DOIUrl":"10.62347/GFNJ2400","url":null,"abstract":"<p><strong>Background: </strong>Urinary tract and male genital organ lymphoid neoplasms are uncommon, accounting for less than 5% of all primary extranodal lymphomas. There have only been a few small case series and isolated case reports describing the primary sites and subtypes of these neoplasms. The aim of the study is to investigate the pathological characteristics of patients diagnosed with primary Genitourinary (GU) lymphoma in at two major hospitals.</p><p><strong>Material and methods: </strong>We obtained cases that were diagnosed with primary GU lymphomas between 2005 and 2020. Pathology and immunohistochemistry slides were retrieved and reviewed, additional immunohistochemical markers were done on selected cases.</p><p><strong>Result: </strong>Herein we present a study of 11 patients. The mean age at diagnosis time was 46 years (range 24-71 years). Among urinary bladder, and ureter lymphomas, a slight female predominance was noted (3:2). Pathologic lymphoma subtype observed in our study were diffuse large B-cell lymphoma (DLBCL) (36%); mucosa-associated lymphoid tissue (MALT) lymphoma (18%); acute lymphoblastic lymphoma (B-LBL) (9%); high-grade B-cell lymphomas (27%) one of them with histomorphology of Burkitt-like large cell type, and a case of high-grade lymphoma, unclassifiable (9%). At the initial time of presentation, patients were commonly presented with non-specific signs and symptoms.</p><p><strong>Conclusion: </strong>Even though this study reaffirms the prevalence of DLBCL in GU system, it also sheds light on the variable range of lymphomas that can arise in these sites. The variety of subtypes highlights the significance of thoroughly characterizing lymphoma classifications through ancillary studies such as immunohistochemistry and other molecular/cytogenetic tests if needed, as they are crucial for achieving an accurate pathology diagnosis.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"12 5","pages":"288-295"},"PeriodicalIF":1.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prioritizing precision: detection of prostate cancer using mri guided fusion needle biopsy across the pennsylvania urologic regional collaborative.","authors":"Dennis Head, Ako A Ako, Serge Ginzburg, Eric Singer, Bruce Jacobs, Claudette Fonshell, Adam Reese, Edouard Trabulsi, Jeffrey Tomaszewski, John Danella, Laurence Belkoff, Robert Uzzo, Jay D Raman","doi":"10.62347/BPCP1813","DOIUrl":"10.62347/BPCP1813","url":null,"abstract":"<p><strong>Purpose: </strong>Targeted prostate biopsies are increasingly being performed by urologists in the United States including those in the Pennsylvania Urologic Regional Collaborative, a physician-led data-sharing and quality improvement collaborative. To evaluate the performance of MRI guided fusion needle prostate biopsies in the collaborative, we analyzed the variability by practice in rates of detection of clinically significant prostate cancer and patient characteristics associated with detection of clinically significant prostate cancer.</p><p><strong>Methods: </strong>We analyzed 857 first-time MRI fusion biopsy procedures performed at five practices (minimum 20 procedures) between 2015 and 2019. We used chi-square analysis for baseline patient characteristics and Grade Group (GG) ≥ 3 tumor detection rates by practice. Multivariable logistic regression was used to estimate the odds of clinically significant cancer detection when adjusting for baseline patient characteristics.</p><p><strong>Results: </strong>Approximately 15% of men undergoing targeted MRI guided biopsy were ≤ 59 years old. Median prostate specific antigen (PSA) was 6.8 ng/ml. Detection rates for GG ≥ 3 tumors ranged from 14.3% to 28.3% (P = 0.02) across practices. However, the odds of GG ≥ 3 tumor detection did not differ significantly between practices after adjusting for clinical and radiographic factors. Overall, increased likelihood of detecting a GG ≥ 3 tumor was associated with increased age, DRE abnormalities, higher PSA, smaller gland volume and PI-RADS ≥ 4 MRI lesions. There was an 81% concordance rate between PI-RADS ≥ 4 and Gleason grade ≥ 3 prostate cancer.</p><p><strong>Conclusion: </strong>We demonstrate the value of obtaining pre-biopsy MRI given high concordance between presence of suspicious lesions and MRI-targeted biopsy detection of clinically significant prostate cancer. Variability of baseline patient characteristics among practices may account for the observed differences in clinically significant cancer detection rates. These findings can aid standardization and quality improvement efforts within the collaborative.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"12 5","pages":"323-330"},"PeriodicalIF":1.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitin C-terminal hydrolase L1 is a regulator of tumor growth and metastasis in double-negative prostate cancer.","authors":"Shiqin Liu, Fernando Jose Garcia-Marques, Michelle Shen, Abel Bermudez, Sharon J Pitteri, Tanya Stoyanova","doi":"10.62347/JNBR1463","DOIUrl":"10.62347/JNBR1463","url":null,"abstract":"<p><p>Prostate cancer is the second leading cause of cancer-related deaths among men worldwide. With heavy androgen deprivation therapies, prostate cancer may shift to androgen receptor negative and neuroendocrine negative subtype of castration resistant prostate cancer, defined as double-negative prostate cancer. Double-negative prostate cancer is associated with poor prognosis and disease mortality. The molecular mechanisms underlying the emergence of double-negative prostate cancer remain poorly understood. Here, we demonstrate that Ubiquitin C-Terminal Hydrolase L1 (UCH-L1), is negatively correlated with androgen receptor levels in prostate cancer patients. UCH-L1 plays a functional role in tumorigenesis and metastasis in double-negative prostate cancer. Knock-down of UCH-L1 decreases double-negative prostate cancer colony formation <i>in vitro</i> and tumor growth <i>in vivo</i>. Moreover, decrease of UCH-L1 significantly delays cell migration <i>in vitro</i> and spontaneous metastasis and metastatic colonization <i>in vivo</i>. Proteomic analysis revealed that mTORC1 signaling, androgen response signaling and MYC targets are the top three decreased pathways upon UCH-L1 decrease. Further, treatment with LDN-57444, a UCH-L1 small molecule inhibitor, impairs double-negative prostate cancer cell colony formation, migration <i>in vitro</i>, and metastatic colonization <i>in vivo</i>. Our study reveals that UCH-L1 is an important regulator of double-negative prostate cancer tumor growth and progression, providing a promising therapeutic target for this subtype of metastatic prostate cancer.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"12 5","pages":"306-322"},"PeriodicalIF":1.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}