American journal of clinical and experimental urology最新文献

{"title":"Single-cell RNA-Seq identifies factors necessary for the regenerative phenotype of prostate luminal epithelial progenitors.","authors":"Daniel C Moline, Morgan L Zenner, Alex Burr, Jordan E Vellky, Larisa Nonn, Donald J Vander Griend","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Benign prostate hyperplasia and prostate cancer are common diseases that involve the overgrowth of prostatic tissue. Although their pathologies and symptoms differ, both diseases show aberrant activation of prostate progenitor cell phenotypes in a tissue that should be relatively quiescent. This phenomenon prompts a need to better define the normal prostate progenitor cell phenotype and pursue the discovery of causal networks that could yield druggable targets to combat hyperplastic prostate diseases. We used single-cell (sc) RNA-Seq analysis to confirm the identity of a luminal progenitor cell population in both the hormonally intact and castrated mouse prostate. Using marker genes from our scRNA-Seq analysis, we identified factors necessary for the regeneration phenotype of prostate organoids derived from mice and humans <i>in vitro</i>. These data outline potential factors necessary for prostate regeneration and utilization of scRNA-Seq approaches for the identification of pharmacologic strategies targeting critical cell populations that drive prostate disease.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"10 6","pages":"425-439"},"PeriodicalIF":1.2,"publicationDate":"2022-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9831919/pdf/ajceu0010-0425.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10631838","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":"Modeling development of genitourinary birth defects to understand disruption due to changes in gene dosage.","authors":"Victor A Ruthig, Dolores J Lamb","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Genitourinary development is a delicately orchestrated process that begins in the embryo. Once complete, the genitourinary system is a collection of functionally disparate organs spread throughout the abdominal and pelvic regions. These distinct organs are interconnected through an elaborate duct system which aggregates the organs' products to a common exit point. The complicated nature of the genitourinary system makes it highly susceptible to developmental disruptions that produce anomalies. In fact, genitourinary anomalies are among the most common class of human birth defects. Aside from congenital anomalies of the kidney and urinary tract (CAKUT), for males, these birth defects can also occur in the penis (hypospadias) and testis (cryptorchism), which impact male fertility and male mental health. As genetic technology has advanced, it has become clear that a subset of cases of genitourinary birth defects are due to gene variation causing dosage changes in critical regulatory genes. Here we first review the parallels between human and mouse genitourinary development. We then demonstrate how translational research leverages mouse models of human gene variation cases to advance mechanistic understanding of causation in genitourinary birth defects. We close with a view to the future highlighting upcoming technologies that will provide a deeper understanding of gene variation affecting regulation of genitourinary development, which should ultimately advance treatment options for patients.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"10 6","pages":"412-424"},"PeriodicalIF":1.5,"publicationDate":"2022-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9831917/pdf/ajceu0010-0412.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9113941","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":"Activation of ONECUT2 by RB1 loss in castration-resistant prostate cancer.","authors":"Chen Qian, Qian Yang, Stephen J Freedland, Dolores Di Vizio, Leigh Ellis, Sungyong You, Michael R Freeman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Functional loss of the two major tumor repressors, TP53 and RB1, is frequently involved in the emergence and progression of castration-resistant prostate cancer (CRPC). Inactivating mutations in <i>TP53</i> and <i>RB1</i> promote lineage variants that suppress the androgen receptor axis and enhance therapy resistance. The present study provides the first evidence that RB1 loss, and not TP53 loss, is sufficient to activate the master regulator transcription factor ONECUT2 (OC2) in mCRPC. OC2 upregulation is common in CRPC and drives metastasis and lineage plasticity, particularly neuroendocrine differentiation, in model systems. Pharmacologic inhibition of OC2 was reported to suppress established human CRPC metastases in mice. Here we show that RB1 silencing in human and mouse prostate cancer models is sufficient to upregulate OC2, at least in part through epigenetic regulation. OC2 expression downregulated TP53 transcription and inactivated RB1 via phosphorylation. OC2 expression and activation in human CRPC correlated with bi- or single-allelic loss of <i>RB1</i> and inversely with RB1 expression and activity. A small molecule OC2 inhibitor blocked enzalutamide-induced lineage plasticity in vitro. These findings indicate that activation of OC2 in CRPC occurs in response to RB1 inactivation, and that biomarkers of RB1 activity may be useful for stratifying patients refractory to hormone therapy where OC2 is targeted pharmacologically.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"10 6","pages":"397-407"},"PeriodicalIF":1.5,"publicationDate":"2022-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9831918/pdf/ajceu0010-0397.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286775","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":"Increased COX-1 expression in benign prostate epithelial cells is triggered by mitochondrial dysfunction.","authors":"Chandler N Hudson, Kai He, Laura E Pascal, Teresa Liu, Livianna K Myklebust, Rajiv Dhir, Pooja Srivastava, Naoki Yoshimura, Zhou Wang, William A Ricke, Donald B DeFranco","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Prostatic inflammation is closely linked to the development and progression of benign prostatic hyperplasia (BPH). Clinical studies of non-steroidal anti-inflammatory drugs, which inhibit cyclooxygenase-2 (COX-2), targeting prostate inflammation patients with symptomatic BPH have demonstrated conflicting results, with some studies demonstrating symptom improvement and others showing no impact. Thus, understanding the role of the cyclooxygenases in BPH and prostatic inflammation is important.</p><p><strong>Methods: </strong>The expression of COX-1 was analyzed in a cohort of donors and BPH patients by immunohistochemistry and compared to previously determined characteristics for this same cohort. The impact of mitochondrial dysfunction on COX-1 and COX-2 was determined in experiments treating human benign prostate epithelial cell lines BPH-1 and RWPE-1 with rotenone and MitoQ. RWPE-1 cells were transfected with small interfering RNA specific to complex 1 gene NDUFS3.</p><p><strong>Results: </strong>COX-1 expression was increased in the epithelial cells of BPH specimens compared to young healthy organ donor and normal prostate adjacent to BPH and frequently co-occurred with COX-2 alteration in BPH patients. COX-1 immunostaining was associated with the presence of CD8+ cytotoxic T-cells, but was not associated with age, prostate size, COX-2 or the presence of CD4+, CD20+ or CD68+ inflammatory cells. In cell line studies, COX protein levels were elevated following treatment with inhibitors of mitochondrial function. MitoQ significantly decreased mitochondrial membrane potential in RWPE-1 cells. Knockdown of NDUFS3 stimulated COX-1 expression.</p><p><strong>Conclusion: </strong>Our findings suggest COX-1 is elevated in BPH epithelial cells and is associated with increased presence of CD8+ cytotoxic T-cells. COX-1 can be induced in benign prostate epithelial cells in response to mitochondrial complex I inhibition, and knockdown of the complex 1 protein NDUFS3. COX-1 and mitochondrial dysfunction may play more of a role than previously recognized in the development of age-related benign prostatic disease.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"10 4","pages":"234-245"},"PeriodicalIF":1.2,"publicationDate":"2022-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428567/pdf/ajceu0010-0234.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9921137","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":"Acute graft thrombosis in patients who underwent renal transplant and received anticoagulant or antiplatelet agents. A systematic review and meta-analysis.","authors":"Rodrigo Guerra,&nbsp;Paulo Roberto Kawano,&nbsp;Marcelo Petean Amaro,&nbsp;Hamilto Akihissa Yamamoto,&nbsp;Fernando Ferreira Gomes Filho,&nbsp;João Luiz Amaro,&nbsp;Regina Paolucci El Dib,&nbsp;Herney Andres Garcia-Perdomo,&nbsp;Leonardo Oliveira Reis","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>Thrombosis is a major cause of early allograft loss in renal transplantation. Herein, we assessed the frequency of acute graft thrombosis in patients who underwent renal transplant and received anticoagulant or antiplatelet agents.</p><p><strong>Methods: </strong>We performed a systematic review of all available case series studies of anticoagulant and/or antiplatelet prophylaxis of thrombosis in renal transplantation. The data were pooled in a proportional meta-analysis.</p><p><strong>Results: </strong>Twenty-one case series were identified from 7,160 retrieved titles. A total of 3,246 patients were analyzed (1,718 treated with antiplatelet and/or anticoagulant agents and 1,528 non-treated control subjects). Allograft thrombosis occurred in 7.24% (95% CI 3.45 to 12.27%) of the patients receiving no intervention compared with 3.38% (95% CI 1.45 to 6.1%), 1.2% (95% CI 0.6 to 2.1%) and 0.47% (95% CI 0.001 to 1.79%) of the patients in the anticoagulant, aspirin, and aspirin + anticoagulant groups, respectively. The bleeding complication rate for anticoagulants was significantly higher than in the other groups.</p><p><strong>Conclusions: </strong>Our data suggests that anticoagulants, and aspirin, either alone or in association with an anticoagulant, seem to have a low frequency of acute allograft thrombosis after kidney transplantation. Higher hemorrhagic complication rates might occur when anticoagulants are used.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"10 3","pages":"129-141"},"PeriodicalIF":1.2,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301061/pdf/ajceu0010-0129.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40621907","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":"Role of prostate stem cells and treatment strategies in benign prostate hyperplasia.","authors":"Kalyan J Gangavarapu,&nbsp;Peter F Jowdy,&nbsp;Barbara A Foster,&nbsp;Wendy J Huss","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Benign prostate hyperplasia (BPH) is a progressive disease with a direct correlation between incidence and age. Since the treatment and management of BPH involve harmful side effects and decreased quality of life for the patient, the primary focus of research should be to find better and longer-lasting therapeutic options. The mechanisms regulating prostate stem cells in development can be exploited to decrease prostate growth. BPH is defined as the overgrowth of the prostate, and BPH is often diagnosed when lower urinary tract symptoms (LUTS) of urine storage or voiding symptoms cause patients to seek treatment. While multiple factors are involved in the hyperplastic growth of the stromal and epithelial compartments of the prostate, the clonal proliferation of stem cells is considered one of the main reasons for BPH initiation and regrowth of the prostate after therapies for BPH fail. Several theories explain possible reasons for the involvement of stem cells in the development, progression, and pathogenesis of BPH. The aim of the current review is to discuss current literature on the fundamentals of prostate development and the role of stem cells in BPH. This review examines the rationale for the hypothesis that unregulated stem cell properties can lead to BPH and therapeutic targeting of stem cells may reduce treatment-related side effects and prevent the regrowth of the prostate.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"10 3","pages":"154-169"},"PeriodicalIF":1.2,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301063/pdf/ajceu0010-0154.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40621910","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":"Fasting and 24-h urine pH in patients with urolithiasis using potassium citrate.","authors":"Isabela Bertanholi Leme da Silva,&nbsp;Carmen Petean Amaro,&nbsp;João Luiz Amaro,&nbsp;Natália Baraldi Cunha,&nbsp;Matheus Augusto Callegari,&nbsp;Hamilto Akihissa Yamamoto,&nbsp;Rodrigo Guerra,&nbsp;Juliany Gomes Quitzan,&nbsp;Leonardo O Reis,&nbsp;Paulo Roberto Kawano","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the correlation between the pH readings in 24-h urine and the random fasting specimen in patients with urolithiasis using 2 methods.</p><p><strong>Methods: </strong>A total of 114 patients with urinary lithiasis using potassium citrate were prospectively analyzed. All patients collected 24-h urine and an additional sample, after nocturnal fasting, collected on the day they brought the 24-h sample at the lab. Two different methods (test strip and digital meter) were used to determine pH values.</p><p><strong>Results: </strong>The pH analysis using strips in the 24-h urine presented a mean value similar to the one obtained in the fasting sample (6.07 ± 0.74 vs. 6.02 ± 0.82, respectively; P > 0.05). The same behavior was seen considering the readings with a digital pH meter (5.8 ± 0.78 vs. 5.75 ± 0.83; P > 0.05). However, readings conducted in the same specimen with pH meter and test strip were dissonant (P < 0.05), suggesting that the colorimetric method is not reliable in the assessment of urinary pH in this population.</p><p><strong>Conclusion: </strong>pH assessment in a random urinary specimen proved as efficient as the 24-h urine standard method to monitor patients with kidney stones in the use of potassium citrate. Classical test strip analysis is not sensitive enough to evaluate the urine pH in this population and digital pH meter reading is preferred.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"10 3","pages":"188-193"},"PeriodicalIF":1.2,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301065/pdf/ajceu0010-0188.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40621909","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":"Scrotal calcinosis: a case report and literature review.","authors":"Dawen Ye,&nbsp;Xueping Ma,&nbsp;Xuezhen Yang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>To understand the clinical features of idiopathic scrotal calcium deposits, to improve the understanding of the disease, and to discuss its etiology, pathogenesis and scrotal reconstruction strategies in the course of diagnosis and treatment.</p><p><strong>Methods: </strong>To analyze the diagnosis and treatment of one case of idiopathic calcium salt deposition in the scrotum and to review the relevant literature.</p><p><strong>Results: </strong>The patient was a 55-year-old male with multiple yellowish-white nodules of varying sizes in the scrotum for more than 20 years, with hard nodules and no tenderness or ulcerative manifestations. Under subarachnoid anesthesia, the scrotum was reconstructed after surgical excision of all diseased nodes, and postoperative pathology was consistent with scrotal calcium salt deposition.</p><p><strong>Conclusion: </strong>Scrotal idiopathic calcium deposits is a rare skin conditions caused by insoluble calcium salts deposited in the scrotal skin tissue, for which surgical excision of the lesion is the main treatment modality with remarkable results. It needs to be differentiated from epidermoid cysts, multiple lipodystrophies of the scrotum, and scabies nodules.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"10 3","pages":"194-198"},"PeriodicalIF":1.2,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301062/pdf/ajceu0010-0194.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40621911","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":"Long non-coding RNA in prostate cancer.","authors":"Christine An,&nbsp;Ian Wang,&nbsp;Xin Li,&nbsp;Rong Xia,&nbsp;Fangming Deng","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostate cancer is the most frequently diagnosed cancer in males and its development and progression remains an important area of study. Recently, long non-coding RNAs (lncRNAs) have been evidenced as key players in cancer pathogenesis. Specifically, dysregulation of long non-coding RNA (lncRNA) expression has shown to affect tumor proliferation and metastasis, acting as either tumor suppressors or oncogenes. However, its specific mechanisms and functions in prostate cancer remain unclear. This review provides an overview of currently available information on prostate cancer-related lncRNAs, including <i>GAS5, GAS-007, MEG3, PCA3, PCAT14, PCAT1, PVT1, UCA1, SChLAP1, MALAT1, HOTAIR,</i> and <i>NEAT1</i>. Notable tumor growth inhibitors include GAS5 and MEG3. GAS5 is evidenced to interfere with the AKT/MTOR signaling pathway through targeting microRNA mir-103. MEG3, however, is proposed to inhibit the cycle, sponge miR-9-5p, and induce gene silencing. PCAT1, PVT1, and UCA1 are important tumor growth promoters. PCAT1 is indicated to be a transcriptional repressor, a mir-145-5P sponge, and a P13K/AKT pathway activator. Studies suggest that PVT1 acts via microRNA targeting and regulating proliferating cell nuclear antigen. UCA1 may sponge miR-204 and miR-331-3p as well as regulate myosin VI. Thorough understanding of these lncRNAs may elucidate new aspects of prostate cancer pathology and serve a pivotal role in developing novel diagnostic and prognostic techniques.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"10 3","pages":"170-179"},"PeriodicalIF":1.2,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301060/pdf/ajceu0010-0170.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40621908","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":"Role of prostate and bone stromal cells on prostate cancer progression.","authors":"Sofia Karkampouna,&nbsp;Marianna Kruithof-de Julio,&nbsp;George N Thalmann","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostate cancer is a highly heterogeneous disease, often manifesting in a metastatic form to the bone. Complex tumour cells and surrounding microenvironment interactions are important determinants of disease progression and therapy resistance. Here, we provide an overview of some of the early studies that recognized the pro-tumourigenic role of prostate stroma, particularly fibroblasts, bone stromal components, and its permissive tumour properties. This article is written in memory of Prof. Dr LWK Chung and his contributions. Prostate and bone metastasis stroma concepts emerging from his work are now more actively being pursued by the authors of this article and others in the field.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"10 3","pages":"180-187"},"PeriodicalIF":1.2,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301059/pdf/ajceu0010-0180.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40621912","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}