{"title":"Prostate cancer autoantibodies - applications in diagnosis, prognosis, monitoring disease progression and immunotherapy.","authors":"Rahul Jayakrishnan, Cara Schafer, Shyh-Han Tan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although PSA testing is widely used in prostate cancer diagnosis, it remains an imperfect assay due to its lack of accuracy. While several urine or tissue-based gene expression assays are available to identify patients with higher risk of adverse disease and to aid in deciding treatment options, there is still a critical need for reliable biomarkers to monitor disease progression and treatment response. Autoantibodies (AAbs) produced by the humoral immune response against tumor associated antigens offer an attractive alternative, as they target a wide variety of prostate cancer specific antigens and can be collected by using clinically non-invasive methods. Herein, we review the transition from traditional methods that identify individual AAbs to high throughput approaches that detect multiple targets simultaneously in patient sera. We also discuss how these approaches improved the sensitivity and specificity of AAb detection and enhanced prostate cancer diagnosis and prognosis. Cancer vaccines offer potential as a novel therapeutic strategy in their ability to stimulate both cell-mediated and antibody-mediated cytotoxic responses. Ongoing efforts aim to identify immunotherapy targets that also stimulate a strong antibody response, since antibodies activated by the anti-cancer humoral response can eliminate cancer cells effectively via several distinct mechanisms. Autoantibodies are useful not only for the diagnosis of prostate cancer, predicting disease progression, and tracking response to treatment, but can also be harnessed as therapeutic agents for prostate cancer treatment.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 2","pages":"79-102"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165224/pdf/ajceu0011-0079.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823488","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":"Fibroepithelial stromal polyp of bladder-a mimicker of sarcoma or angiomyxoma at uncommon location.","authors":"Liping Li, Robert E Weiss, Debra Heller","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The fibroepithelial stromal polyp is a benign polypoid proliferation of the stroma with overlying epithelium. Because the lesion contains atypical stromal cells, sometimes it can be overdiagnosed as sarcoma or with myxoid stroma, it can be misdiagnosed as angiomyxoma. The reported locations are mainly in the lower female genital tract, urethra, and rarely extragenital sites, such as the breast, and are exceptionally rare in the bladder. We encountered a 65-year-old man who presented with two small velvety, erythematous patches on the posterior bladder wall. The final diagnosis is a fibroepithelial stromal polyp of the bladder. Familiarity with this lesion will prevent overinterpretation of this benign lesion as a malignancy.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 4","pages":"348-351"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461029/pdf/ajceu0011-0348.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10118302","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}
Mehdi Dadpour, Amir Mohammad Soltani, Mahyar Ghafoori, Abbas Basiri, Nasrin Borumandnia, Amirhossein Nayebzade, Behzad Narouie, Hamed Hasani, Nasser Shakhssalim
{"title":"Ultrasound/MRI-targeted biopsy versus saturated trans-rectal ultrasound guided biopsy of prostate in patients with primary negative conventional biopsy and still elevated PSA: a prospective randomized clinical trial.","authors":"Mehdi Dadpour, Amir Mohammad Soltani, Mahyar Ghafoori, Abbas Basiri, Nasrin Borumandnia, Amirhossein Nayebzade, Behzad Narouie, Hamed Hasani, Nasser Shakhssalim","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>To evaluate and compare the rate of cancer detection by two methods Saturated TRUS guided biopsy and ultrasound/magnetic resonance imaging (US/MRI)-targeted biopsy in patients with primary negative prostate cancer in standard 12 cores biopsy evaluation but still have elevated prostate specific antigen (PSA).</p><p><strong>Materials and methods: </strong>From 105 patients who met our inclusion criteria, 53 patients underwent US/MRI-targeted biopsy and 52 remaining patients underwent Saturated 20 core TRUS guided biopsy in a prospective randomized clinical trial.</p><p><strong>Results: </strong>The mean age (±SD) was 62.2 (±8.2) year. The mean PSA (±SD) was 11.8 (±7.5) ng/ml. The mean prostate volume was 56.1 (±24.8) ml. Adenocarcinoma of prostate was detected in 9/52 (17.3%) patients in groups saturated biopsy and 14/53 (26.4%) patients in US/MRI-targeted biopsy group and there was no difference in cancer detection rate between 2 groups (P=0.252). except four patients with fever (two in each group), there was no other serious complication (Clavien grade 3 or higher) occurred in the patients. In the multivariate analysis, higher pre-procedure PSA, lower size of the prostate, pathology of ASAP and presence of nodule in DRE were independent predictors for cancer detection in second biopsy (P=0.036, P<0.001, P=0.013 and P=0.031, respectively).</p><p><strong>Conclusion: </strong>We didn't find any superiority in cancer detection rate and any different in complication rate between these two methods saturated TRUS guided biopsy and US/MRI-targeted biopsy.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 4","pages":"312-319"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461031/pdf/ajceu0011-0312.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176404","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}
Hannah Ruetten, Simran K Sandhu, Olivia Fox, Jonathan Zhu, Jaskiran K Sandhu, Chad M Vezina
{"title":"The impact of short term, long term and intermittent <i>E. coli</i> infection on male C57BL/6J mouse prostate histology and urinary physiology.","authors":"Hannah Ruetten, Simran K Sandhu, Olivia Fox, Jonathan Zhu, Jaskiran K Sandhu, Chad M Vezina","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostatic inflammation and prostatic fibrosis are associated with lower urinary tract dysfunction in men. Prostatic inflammation arising from a transurethral uropathogenic <i>E. coli</i> infection is sufficient to increase prostatic collagen content in male mice. It is not known whether and how the sequence, duration and chronology of prostatic infection influence urinary function, prostatic inflammation and collagen content. We placed a transurethral catheter into adult male C57BL/6J mice to deliver uropathogenic <i>E. coli</i> UTI189 two-weeks prior to study endpoint (to evaluate the short-term impact of infection), 10-weeks prior to study endpoint (to evaluate the long-term impact of infection), or two-, six-, and ten-weeks prior to endpoint (to evaluate the impact of repeated intermittent infection). Mice were catheterized the same number of times across all experimental groups and instilled with sterile saline when not instilled with <i>E. coli</i> to control for the variable of catheterization. We measured bacterial load in free catch urine, body weight and weight of bladder and dorsal prostate; prostatic density of leukocytes, collagen and procollagen 1A1 producing cells, and urinary function. Transurethral <i>E. coli</i> instillation caused more severe and persistent bacteriuria in mice with a history of one or more transurethral instillations of sterile saline or <i>E. coli</i>. Repeated intermittent infections resulted in a greater relative bladder wet weight than single infections. However, voiding function, as measured by the void spot assay, and the density of collagen and ProCOL1A1+ cells in dorsal prostate tissue sections did not significantly differ among infection groups. The density of CD45+ leukocytes was greater in the dorsal prostate of mice infected two weeks prior to study endpoint but not in other infection groups compared to uninfected controls.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 1","pages":"59-68"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009312/pdf/ajceu0011-0059.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9497826","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}
Alfonso H Santos, Amer Belal, Sherif Badra, Hisham Ibrahim, Kawther Alquadan, Rohan Mehta, Muhannad A Leghrouz
{"title":"Common predictors of adverse outcomes in adult deceased donor kidney transplant recipients with varying sensitization.","authors":"Alfonso H Santos, Amer Belal, Sherif Badra, Hisham Ibrahim, Kawther Alquadan, Rohan Mehta, Muhannad A Leghrouz","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Our objective was to identify consistent predictors of multiple adverse outcomes of adult deceased donor (DD) kidney transplant recipients (KTRs) of varying sensitization status.</p><p><strong>Methods: </strong>We used the national transplant database in studying 62037 adult DD-KTRs between Dec. 2007 and Jun. 2015 stratified into sensitization cohorts based on calculated panel reactive antibody (CPRA) of <10%, 10%-79%, and ≥80%. We used multivariable logistic regressions for the analysis of risks for delayed graft function (DGF), and of acute rejection (AR) and hospitalization in the first year of transplant, and Cox hazard regression for 5-year overall graft loss (OAGL) and death.</p><p><strong>Results: </strong>The kidney donor risk index (KDRI) highest two quartiles ≥1.45 and 1.15-1.44 were the most consistent predictors for 100% of adverse outcomes (OAGL, death, DGF, AR, and hospitalization) with high significance (P<0.0001) across all sensitization cohorts. The two risk factors that were consistently associated with 80% of adverse outcomes across sensitization cohorts were: (1) pre-transplant dialysis duration >2 years was significantly associated with increased risks of overall graft loss, death, DGF, and hospitalization; and (2) Black KTR race was significantly associated with increased risks of DGF, AR, and hospitalization, and decreased risk of death. Diabetes and KTR age >65 (years) were significant risk factors for overall loss and death across sensitization cohorts.</p><p><strong>Conclusions: </strong>The two highest KDRI quartiles, pre-transplant dialysis duration >2 years, and African American recipient race are consistent predictors of multiple adverse outcomes in adult DDKTRs across sensitization strata and should be among the factors considered in clinical decision-making and research models in kidney transplantation.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 3","pages":"235-248"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333136/pdf/ajceu0011-0235.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9872401","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}
Dara J Lundon, Brian D Kelly, Caoimhe Casby, David Coyle, Rita A Flaherty, Sean Hynes, Teresa McHale, Garrett C Durkan
{"title":"A case report of mucinous tubular and spindle cell carcinoma of the kidney.","authors":"Dara J Lundon, Brian D Kelly, Caoimhe Casby, David Coyle, Rita A Flaherty, Sean Hynes, Teresa McHale, Garrett C Durkan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor that has only recently been described, with less than eighty cases in the literature. This was only recognized as a specific entity in the World Health Organization 2004 classification of Renal Cell Carcinoma (RCC). MTSCCs are polymorphic renal neoplasms characterized by small, elongated tubules lined by cuboidal cells with cords of spindled cells separated by pale mucinous stroma. We report the case of a 57 year old lady who had an incidental finding of a mass in her right kidney. The radiological features were consistent with a RCC and following a multidisciplinary team discussion she underwent a laparoscopic radical nephrectomy. Macroscopic examination revealed a well circumscribed 6.5 × 6 × 6.5 cm right lower pole mass. Histologically it was composed of elongated tubules, small tubules and papillary structures with a necrotic centre. The cells demonstrated cuboidal and spindle cell morphology. Histological grade was Fuhrman grade 2. The majority of MTSCCs are indolent, and there are only two reports of distant metastases which responded favorably to adjuvant sunitinib. To date there is no international consensus on long term surveillance of these patients. Due of the favorable prognosis with this type of tumor, MTSCC must be differentiated from papillary renal cell carcinoma to avoid administration of excessive adjuvant treatment to patients.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 1","pages":"75-78"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009310/pdf/ajceu0011-0075.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9117049","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}
Maryam Ahmadi, Adam Osman, Peng Lee, Fangming Deng, Guanghong Liao
{"title":"Clear cell adenocarcinoma of the urinary bladder: a case report and review of literature.","authors":"Maryam Ahmadi, Adam Osman, Peng Lee, Fangming Deng, Guanghong Liao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The most common histological type of urinary bladder cancer is urothelial carcinoma (UC). Clear cell adenocarcinoma (CCA) of the urinary bladder is a rare histologic subtype of adenocarcinoma in the urinary tract. The tumor primarily affects women and has histomorphological features resembling CCA of the female genital tract (or Müllerian origin). Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. Patients typically present with gross hematuria, dysuria, and discharge. In this study, we report a case of a 50-year-old male, presenting with gross hematuria, which was subsequently diagnosed with CCA at our pathology department. Furthermore, we provide a short systematic review of the literature for this rare histopathological entity and a brief discussion about its morphological and immunohistochemical (IHC) characteristics.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 4","pages":"344-347"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461038/pdf/ajceu0011-0344.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123418","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 pulse duration alterable laser ureterorenoscopic lithotripsy for upper urinary tract calculi.","authors":"Hideo Otsuki, Hironori Kojima, Tomohiro Hongo, Shunsuke Hori, Yukihide Matsui, Tomoya Yamasaki, Makoto Isono, Takeo Kosaka, Shinya Uehara, Kei Fujio","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To assess the effectiveness of a pulse duration alterable Holmium-YAG (Ho:YAG) laser on the stone-free rate (SFR) compared to a conventional pulse duration fixed laser after ureterorenoscopic lithotripsy (URSL). The medical records from patients with upper urinary tract calculi of ≥ 9 mm and < 30 mm were retrospectively investigated. URSL using a conventional Ho:YAG Laser (group C) or a pulse duration alterable Ho:YAG system (group A) was included. In total, 228 and 188 patients were enrolled in groups C and A, respectively. A 272 µm optical core bare-ended, reusable laser fiber was used, and the laser system was set to a standard 0.8 J and 10 Hz (8 W of average power) in both groups. URSL adopts active fragmentation using an extraction approach. SF was defined as the complete absence of stone fragments on computed tomography (CT) 1-2 months after URSL. Sex, BMI, stone length, stone volume, stone density, and the number of patients with positive preoperative urine cultures were not significantly different between the groups. However, age, rate of preoperative febrile urinary tract infection (fUTI), and pre-stenting were significantly higher in group A, and the operative times and incidence of postoperative fUTI were comparable. The SFRs were 71.5% and 80.3% in groups C and A, respectively (P = 0.035). Multivariate logistic regression revealed that the use of conventional laser was associated with non-SF (odds ratio [OR] 1.090, 95% confidence interval [CI] 1.01-1.18, P = 0.040). The present study revealed the superior performance of a pulse duration alterable Ho:YAG laser on the SFR after URSL compared to a conventional pulse duration fixed laser delivery system.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 4","pages":"328-333"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461037/pdf/ajceu0011-0328.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123416","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}
Emma Rosenbluth, Christine W Liaw, Jacob N Bamberger, Aisosa Omorogbe, Johnathan A Khusid, Raymond Khargi, Alan J Yaghoubian, Anna Ricapito, Blair Gallante, William M Atallah, Mantu Gupta
{"title":"The effects of continuing aspirin on blood loss and postoperative outcomes in percutaneous nephrolithotomy.","authors":"Emma Rosenbluth, Christine W Liaw, Jacob N Bamberger, Aisosa Omorogbe, Johnathan A Khusid, Raymond Khargi, Alan J Yaghoubian, Anna Ricapito, Blair Gallante, William M Atallah, Mantu Gupta","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Percutaneous nephrolithotomy (PCNL) is an effective surgery for complex kidney stones yet with inherent bleeding risks. It remains unclear whether aspirin should be discontinued prior to PCNL. We aimed to further substantiate the safety of continuing aspirin during PCNL surgery and to determine whether aspirin status affects postoperative outcomes following PCNL.</p><p><strong>Methods: </strong>We retrospectively queried our endourology database for patients who underwent PCNL from October 2017 to December 2022 at our high-volume tertiary referral center. The three groups were based on aspirin status at the time of PCNL: no aspirin (NA), discontinued aspirin (DA), and continued aspirin (CA). Data collected included demographics, preoperative characteristics, operative parameters, pre and postoperative lab values, transfusions, and complications.</p><p><strong>Results: </strong>A total 648 patients were divided into these study groups: 525 NA patients (81.0%), 55 DA (8.5%), and 68 CA (10.5%). The DA and CA groups were of similar comorbidities, and both were more comorbid at baseline than NA. Postoperative change in lab values and complications did not differ significantly. Rates of postoperative blood transfusion were higher in the CA and DA groups compared to NA and approached statistical significance. There were no significant differences in any postoperative outcomes between the DA and CA groups alone.</p><p><strong>Conclusions: </strong>In patients on chronic aspirin therapy, continuing aspirin appears equally safe to discontinuing aspirin prior to PCNL. Most patients should not forego the benefits of continuous aspirin for the theoretical risk of bleeding. Patients on prolonged aspirin therapy may be more likely than those who are not on chronic aspirin therapy to require blood transfusions. However, regardless of whether aspirin use is stopped, this may be caused by patient comorbidities rather than higher rates of blood loss.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 1","pages":"50-58"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009308/pdf/ajceu0011-0050.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9122060","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}
Laura E Pascal, Krystle A Frahm, Kegan O Skalitzky, Donald B DeFranco, Lora H Rigatti, Ray Lu, Teresa T Liu
{"title":"Genetic alterations in CREBRF influence prostate cancer survival and impact prostate tissue homeostasis in mice.","authors":"Laura E Pascal, Krystle A Frahm, Kegan O Skalitzky, Donald B DeFranco, Lora H Rigatti, Ray Lu, Teresa T Liu","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Risk factors for prostate cancer include age, environment, race and ethnicity. Genetic variants in cyclic-adenosine-monophosphate-response-element-binding protein 3 regulatory factor (CREBRF) gene are frequently observed in Pacific Islanders, a population with elevated prostate cancer incidence. CREBRF has been shown to play a role in other cancers, however its function in prostate homeostasis and tumorigenesis has not been previously explored. We determined the incidence of CREBRF alterations in publicly available databases and examined the impact of CREBRF deletion on the murine prostate in order to determine whether CREBRF impacts prostate physiology or pathophysiology.</p><p><strong>Methods: </strong>Alterations in CREBRF were identified in prostate cancer patients via in silico analysis of several publicly available datasets through cBioPortal. Male <i>Crebrf</i> knockout and wild-type littermate mice were generated and examined for prostate defects at 4 months of age. Immunohistochemical staining of murine prostate sections was used to determine the impact of <i>Crebrf</i> knockout on proliferation, apoptosis, inflammation and blood vessel density in the prostate. Serum adipokine levels were measured using a Luminex Multiplex Assay.</p><p><strong>Results: </strong>CREBRF alterations were identified in up to 4.05% of prostate tumors and the mutations identified were categorized as likely damaging. Median survival of prostate cancer patients with genetic alterations in CREBRF was 41.23 months, compared to 131 months for patients without these changes. In the murine model, the prostates of <i>Crebrf</i> knockout mice had reduced epithelial proliferation and increased TUNEL<sup>+</sup> apoptotic cells. Circulating adipokines PAI-1 and MCP-1 were also altered in <i>Crebrf</i> knockout mice compared to age-matched controls.</p><p><strong>Conclusions: </strong>Prostate cancer patients with genetic alterations in CREBRF had a significantly decreased overall survival suggesting that wild type CREBRF may play a role in limiting prostate tumorigenesis and progression. The murine knockout model demonstrated that CREBRF could modulate proliferation and apoptosis and macrophage density in the prostate. Serum levels of adipokines PAI-1 and MCP-1 were also altered and may contribute to the phenotypic changes observed in the prostates of <i>Crebrf</i> knockout mice. Future studies focused on populations susceptible to CREBRF mutations and mechanistic studies will be required to fully elucidate the potential role of CREBRF in prostate tumorigenesis.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 1","pages":"27-39"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009309/pdf/ajceu0011-0027.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9330770","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}