Background: Although treatment options for metastatic castration-resistant prostate cancer (mCRPC) have been increasing since 2014, the actual treatment sequences of each drug in clinical practice in Japan have only been reported in a limited number of patients and facilities. The primary objective of this database study was to investigate the general situation and the transition of prior and post-mCRPC treatments.
Methods: Using Medical Data Vision's medical record database across Japan, patients diagnosed with mCRPC from January 2015 to December 2022 based on defined criteria were extracted. Treatment sequences before and after mCRPC diagnosis were analyzed.
Results: Analysis of 4967 patients revealed that the most common pretreatment for mCRPC was classical vintage hormone therapy (77.1%), followed by androgen receptor signaling inhibitors (ARSI), including enzalutamide (7.8%) and abiraterone (7.4%). The most common treatments for first-line mCRPC were enzalutamide (43.1%), abiraterone (28.3%), and docetaxel (10.7%). When the treatment prior to mCRPC was ARSI, docetaxel was the most common first-line treatment for mCRPC, but another ARSI that had not been used as treatment prior to mCRPC was also selected as first-line mCRPC treatment at a similar rate to docetaxel. Regarding annual changes, the proportion of vintage hormone therapy for mCRPC has been decreasing annually, and there has been a trend to replace it with ARSIs.
Conclusion: In terms of the treatment sequence for mCRPC in Japan, vintage hormone therapy was the most common pretreatment for mCRPC, and ARSIs were the most common first-line treatments for mCRPC.
背景：尽管转移性去势抵抗性前列腺癌（mCRPC）的治疗方案自2014年以来不断增加，但每种药物在日本临床实践中的实际治疗顺序仅在有限数量的患者和机构中报道。本数据库研究的主要目的是调查一般情况以及既往和后mcrpc治疗的转变。方法：使用Medical Data Vision的日本病历数据库，提取2015年1月至2022年12月根据定义标准诊断为mCRPC的患者。分析mCRPC诊断前后的治疗顺序。结果：4967例mCRPC患者的分析显示，最常见的预处理是经典的复古激素治疗（77.1%），其次是雄激素受体信号抑制剂（ARSI），包括恩杂鲁胺（7.8%）和阿比特龙（7.4%）。一线mCRPC最常见的治疗方法是恩杂鲁胺（43.1%）、阿比特龙（28.3%）和多西他赛（10.7%）。当mCRPC之前的治疗是ARSI时，多西他赛是mCRPC最常见的一线治疗，但在mCRPC之前未被用作治疗的另一种ARSI也被选择作为mCRPC的一线治疗，其比率与多西他赛相似。从年度变化来看，mCRPC的复古激素治疗比例逐年下降，并有被ARSIs替代的趋势。结论：从日本mCRPC的治疗顺序来看，vintage hormone therapy是最常见的mCRPC预处理，ARSIs是最常见的一线mCRPC治疗方案。
{"title":"Real-World Treatment Patterns Before and After Metastatic Castration-Resistant Prostate Cancer in Japan: Retrospective Analysis Using a Hospital-Based, Multicenter Database.","authors":"Masaki Shiota, Linghua Xu, Tomoyo Oguri, Masayuki Tanaka","doi":"10.1155/proc/9964591","DOIUrl":"10.1155/proc/9964591","url":null,"abstract":"<p><strong>Background: </strong>Although treatment options for metastatic castration-resistant prostate cancer (mCRPC) have been increasing since 2014, the actual treatment sequences of each drug in clinical practice in Japan have only been reported in a limited number of patients and facilities. The primary objective of this database study was to investigate the general situation and the transition of prior and post-mCRPC treatments.</p><p><strong>Methods: </strong>Using Medical Data Vision's medical record database across Japan, patients diagnosed with mCRPC from January 2015 to December 2022 based on defined criteria were extracted. Treatment sequences before and after mCRPC diagnosis were analyzed.</p><p><strong>Results: </strong>Analysis of 4967 patients revealed that the most common pretreatment for mCRPC was classical vintage hormone therapy (77.1%), followed by androgen receptor signaling inhibitors (ARSI), including enzalutamide (7.8%) and abiraterone (7.4%). The most common treatments for first-line mCRPC were enzalutamide (43.1%), abiraterone (28.3%), and docetaxel (10.7%). When the treatment prior to mCRPC was ARSI, docetaxel was the most common first-line treatment for mCRPC, but another ARSI that had not been used as treatment prior to mCRPC was also selected as first-line mCRPC treatment at a similar rate to docetaxel. Regarding annual changes, the proportion of vintage hormone therapy for mCRPC has been decreasing annually, and there has been a trend to replace it with ARSIs.</p><p><strong>Conclusion: </strong>In terms of the treatment sequence for mCRPC in Japan, vintage hormone therapy was the most common pretreatment for mCRPC, and ARSIs were the most common first-line treatments for mCRPC.</p>","PeriodicalId":20907,"journal":{"name":"Prostate Cancer","volume":"2026 ","pages":"9964591"},"PeriodicalIF":2.0,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378303","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}
Pub Date : 2026-02-24eCollection Date: 2026-01-01DOI: 10.1155/proc/9924021
Saphurah Nabaasa, Marvin Mwesigwa Mutakooha, Lawrence Amadile, Charles Nkubi Bagenda, Jolly Lydia Ninsiima, Abraham Birungi, Raymond Atwine, Hassan Wasswa, Richard Kasadha, Tibenderana Lauben, Frank Ssedyabane
Background: Both healthy and malignant prostate tissues express the glycoprotein marker known as prostate-specific antigen (PSA). When checking for prostate lesions, serum total PSA levels are a major factor. However, the exact levels to rely on are not explicit.
Objective: To ascertain the relationship between histopathological findings and serum levels of the PSA in patients in southwest Uganda.
Methods: This cross-sectional study involved 71 participants in southwestern Uganda from January to July 2023, who underwent histological examinations. Blood samples were taken off for total serum PSA level measurement. Stained formalin-fixed paraffin-embedded sections were examined. Histological results and PSA levels were correlated using Spearman's correlation coefficient.
Results: The study involved 74 participants with an average age of 74.20 ± 9.40 years and average Gleason score of 7.73 ± 1.04. Only 1/71 (1.41%) had prostatic intraepithelial neoplasia (PIN), 36/71 (50.70%) had benign prostate hyperplasia (BPH), and 34/71 (47.89%) had prostate adenocarcinoma (PAC). A significant correlation was observed between PSA levels above 100 ng/mL (p = 0.001, rho = 0.5955) and prostate cancer and between PSA levels up to 20 ng/mL (p = 0.010, rho = 0.03033). AUC of 0.85 (95% CI: 0.77-0.94) showed good predictive power of the test. PSA optimal cut off was 103.4 ng/mL, at sensitivity of 68% and specificity of 92% with maximum Youden index (J): 0.595.
Conclusion: There was a significant correlation between BPH with PSA levels up to 20 ng/mL and above 100 ng/mL for prostate adenocarcinoma. In some of the cases, however, total serum PSA levels were high for BPH and low for prostate adenocarcinoma. PSA test usefulness cannot be nullified, but its accuracy and specificity have to be ascertained in order to increase its reliability. Future researches are argued to focus more on how to refine PSA-based diagnostics through identifying any underlying unknown hereditary factors and probably better biomarkers that could be influencing PSA levels. With this, dependability increases and unnecessary biopsing reduces, thus alleviating anxiety in patients and probably their caregivers.
Contributions of this study: The study provides additional insights into the importance and clarity of total serum PSA levels in prostate screening and diagnosis.
{"title":"Correlating Histological Results and Total Serum Levels of the Prostate-Specific Antigen Among Patients in Southwestern Uganda.","authors":"Saphurah Nabaasa, Marvin Mwesigwa Mutakooha, Lawrence Amadile, Charles Nkubi Bagenda, Jolly Lydia Ninsiima, Abraham Birungi, Raymond Atwine, Hassan Wasswa, Richard Kasadha, Tibenderana Lauben, Frank Ssedyabane","doi":"10.1155/proc/9924021","DOIUrl":"10.1155/proc/9924021","url":null,"abstract":"<p><strong>Background: </strong>Both healthy and malignant prostate tissues express the glycoprotein marker known as prostate-specific antigen (PSA). When checking for prostate lesions, serum total PSA levels are a major factor. However, the exact levels to rely on are not explicit.</p><p><strong>Objective: </strong>To ascertain the relationship between histopathological findings and serum levels of the PSA in patients in southwest Uganda.</p><p><strong>Methods: </strong>This cross-sectional study involved 71 participants in southwestern Uganda from January to July 2023, who underwent histological examinations. Blood samples were taken off for total serum PSA level measurement. Stained formalin-fixed paraffin-embedded sections were examined. Histological results and PSA levels were correlated using Spearman's correlation coefficient.</p><p><strong>Results: </strong>The study involved 74 participants with an average age of 74.20 ± 9.40 years and average Gleason score of 7.73 ± 1.04. Only 1/71 (1.41%) had prostatic intraepithelial neoplasia (PIN), 36/71 (50.70%) had benign prostate hyperplasia (BPH), and 34/71 (47.89%) had prostate adenocarcinoma (PAC). A significant correlation was observed between PSA levels above 100 ng/mL (<i>p</i> = 0.001, rho = 0.5955) and prostate cancer and between PSA levels up to 20 ng/mL (<i>p</i> = 0.010, rho = 0.03033). AUC of 0.85 (95% CI: 0.77-0.94) showed good predictive power of the test. PSA optimal cut off was 103.4 ng/mL, at sensitivity of 68% and specificity of 92% with maximum Youden index (J): 0.595.</p><p><strong>Conclusion: </strong>There was a significant correlation between BPH with PSA levels up to 20 ng/mL and above 100 ng/mL for prostate adenocarcinoma. In some of the cases, however, total serum PSA levels were high for BPH and low for prostate adenocarcinoma. PSA test usefulness cannot be nullified, but its accuracy and specificity have to be ascertained in order to increase its reliability. Future researches are argued to focus more on how to refine PSA-based diagnostics through identifying any underlying unknown hereditary factors and probably better biomarkers that could be influencing PSA levels. With this, dependability increases and unnecessary biopsing reduces, thus alleviating anxiety in patients and probably their caregivers.</p><p><strong>Contributions of this study: </strong>The study provides additional insights into the importance and clarity of total serum PSA levels in prostate screening and diagnosis.</p>","PeriodicalId":20907,"journal":{"name":"Prostate Cancer","volume":"2026 ","pages":"9924021"},"PeriodicalIF":2.0,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12932906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147309519","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}
Pub Date : 2026-01-15eCollection Date: 2026-01-01DOI: 10.1155/proc/9996270
Alexander Yaney, Jonathan E Schoenhals, Yevgeniya Gokun, Andrew Stevens, Jack Wang, Jessica Aduwo, Ahmad Shabsigh, Shawn Dason, Akshay Sood, Evan Thomas, Jacob Eckstein, Russell Palm, Rebekah Young, Dayssy Alexandra Diaz Pardo, Douglas Martin, Shang-Jui Wang
<p><strong>Background: </strong>At the height of the COVID-19 pandemic, healthcare utilization among cancer patients, including those with prostate cancer, was limited due to inadequate healthcare resources and concern for disease transmission among patients and medical personnel. While publications with treatment recommendations during the pandemic exist, there is limited real-life data comparing prostate cancer management pre-COVID to during the pandemic.</p><p><strong>Objective: </strong>The primary aim of this study is to determine the effect of the COVID-19 pandemic on prostate cancer management at a tertiary medical center by comparing patients receiving treatment preceding the pandemic to those receiving treatment during the height of the pandemic.</p><p><strong>Methods: </strong>Prostate cancer patients treated with definitive intent (surgery, definitive radiation (RT), or salvage RT) in 2019-2020 were retrospectively reviewed. Analysis was performed with the following timeframes: pre-COVID as 1/3/19 to 2/28/20 and COVID as 3/1/20 to 9/30/20. Time-to-treatment (TT) for surgery and definitive RT was defined from the date of diagnosis (biopsy or decision to treat if active surveillance) to the date of surgery or RT start, respectively. TT for salvage RT was defined as the date of PSA failure to RT start. Descriptive statistics such as medians and interquartile ranges (IQRs) were reported for continuous variables, while frequency counts and percents were reported for categorical variables. Chi-squared tests (Fisher's exact when appropriate) along with Wilcoxon rank sum tests were used to compare two timeframes. Two adjusted binary logistic regressions assessed the associations of NCCN risk groups, as well as grade group (GG), on the outcome of receipt of treatment during COVID compared to those in pre-COVID timeframes.</p><p><strong>Results: </strong>This study sample included 565 prostate cancer patients treated with surgery (<i>n</i> = 303), definitive RT (<i>n</i> = 151), or salvage RT (<i>n</i> = 111). There was a statistically significant difference in TT by timeframe for all patients (median 111 days pre-COVID v 126.5 days COVID, <i>p</i> = 0.007). For patients who received definitive or salvage RT with ADT, there were significant differences in time from ADT initiation to treatment start between pre-COVID vs. COVID (definitive RT: median 78 days v 147 days, <i>p</i> = 0.001; salvage RT: median 67 days v 84 days, <i>p</i> = 0.004). A significantly higher proportion of patients received ADT prior to surgery in the COVID cohort compared to those in pre-COVID (9.8% v 0.5%, <i>p</i> < 0.001). Patients with clinically more aggressive prostate cancer had higher odds of being treated in the COVID timeframe (HR or VHR, adjusted OR [aOR] 1.62, 95% CI: 1.02-2.55).</p><p><strong>Conclusions: </strong>The COVID-19 pandemic changed prostate cancer management in various ways including longer TT, prolonged time from ADT initiation to RT, increased ut
{"title":"Change in Clinical Management of Localized Prostate Cancer Patients at a Tertiary Medical Center as a Result of SARS-CoV-2 (COVID-19).","authors":"Alexander Yaney, Jonathan E Schoenhals, Yevgeniya Gokun, Andrew Stevens, Jack Wang, Jessica Aduwo, Ahmad Shabsigh, Shawn Dason, Akshay Sood, Evan Thomas, Jacob Eckstein, Russell Palm, Rebekah Young, Dayssy Alexandra Diaz Pardo, Douglas Martin, Shang-Jui Wang","doi":"10.1155/proc/9996270","DOIUrl":"10.1155/proc/9996270","url":null,"abstract":"<p><strong>Background: </strong>At the height of the COVID-19 pandemic, healthcare utilization among cancer patients, including those with prostate cancer, was limited due to inadequate healthcare resources and concern for disease transmission among patients and medical personnel. While publications with treatment recommendations during the pandemic exist, there is limited real-life data comparing prostate cancer management pre-COVID to during the pandemic.</p><p><strong>Objective: </strong>The primary aim of this study is to determine the effect of the COVID-19 pandemic on prostate cancer management at a tertiary medical center by comparing patients receiving treatment preceding the pandemic to those receiving treatment during the height of the pandemic.</p><p><strong>Methods: </strong>Prostate cancer patients treated with definitive intent (surgery, definitive radiation (RT), or salvage RT) in 2019-2020 were retrospectively reviewed. Analysis was performed with the following timeframes: pre-COVID as 1/3/19 to 2/28/20 and COVID as 3/1/20 to 9/30/20. Time-to-treatment (TT) for surgery and definitive RT was defined from the date of diagnosis (biopsy or decision to treat if active surveillance) to the date of surgery or RT start, respectively. TT for salvage RT was defined as the date of PSA failure to RT start. Descriptive statistics such as medians and interquartile ranges (IQRs) were reported for continuous variables, while frequency counts and percents were reported for categorical variables. Chi-squared tests (Fisher's exact when appropriate) along with Wilcoxon rank sum tests were used to compare two timeframes. Two adjusted binary logistic regressions assessed the associations of NCCN risk groups, as well as grade group (GG), on the outcome of receipt of treatment during COVID compared to those in pre-COVID timeframes.</p><p><strong>Results: </strong>This study sample included 565 prostate cancer patients treated with surgery (<i>n</i> = 303), definitive RT (<i>n</i> = 151), or salvage RT (<i>n</i> = 111). There was a statistically significant difference in TT by timeframe for all patients (median 111 days pre-COVID v 126.5 days COVID, <i>p</i> = 0.007). For patients who received definitive or salvage RT with ADT, there were significant differences in time from ADT initiation to treatment start between pre-COVID vs. COVID (definitive RT: median 78 days v 147 days, <i>p</i> = 0.001; salvage RT: median 67 days v 84 days, <i>p</i> = 0.004). A significantly higher proportion of patients received ADT prior to surgery in the COVID cohort compared to those in pre-COVID (9.8% v 0.5%, <i>p</i> < 0.001). Patients with clinically more aggressive prostate cancer had higher odds of being treated in the COVID timeframe (HR or VHR, adjusted OR [aOR] 1.62, 95% CI: 1.02-2.55).</p><p><strong>Conclusions: </strong>The COVID-19 pandemic changed prostate cancer management in various ways including longer TT, prolonged time from ADT initiation to RT, increased ut","PeriodicalId":20907,"journal":{"name":"Prostate Cancer","volume":"2026 ","pages":"9996270"},"PeriodicalIF":2.0,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12808921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998900","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}
Pub Date : 2026-01-13eCollection Date: 2026-01-01DOI: 10.1155/proc/1399482
Fangming Wang, Yan Zhang, Meng Fu, Yuzhe Tang, Haifeng Song, Gang Zhang, Boxing Su, Jianxing Li
<p><strong>Background: </strong>Multiparametric magnetic resonance imaging (mpMRI) has been widely utilized in clinical practice for identifying clinically significant prostate cancer (csPCa). Although mpMRI demonstrates a pooled negative predictive value (NPV) of 90%, additional clinical parameters require evaluation to enhance this metric specifically for the Chinese population-given the rising incidence of PCa in China, as well as ethnic differences in average prostate volume (PV) and chronic prostatitis prevalence that may impact mpMRI's diagnostic performance.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 543 patients who underwent transrectal ultrasound-guided prostate biopsy at Beijing Tsinghua Changgung Hospital between November 2014 and March 2025. After applying exclusion criteria, 412 patients were enrolled, all of whom had completed prebiopsy mpMRI within 1 month prior to biopsy. Patients were stratified into four groups based on the results of MRI examination and the pathological outcomes of biopsy: MRI (-) PCa (-), MRI (+) PCa (-), MRI (-) PCa (+), and MRI (+) PCa (+) groups. Multivariate logistic regression analyses were used to assess the odd ratios (ORs) of potential predictors for csPCa, comparing the MRI (-) PCa (+) and MRI (-) PCa (-) groups. Receiver operating characteristic curves were generated to analyze the predictive values of total PSA (tPSA), free PSA (fPSA), free-to-total (f/t) PSA, PV, PSA density (PSAD), and adjusted PSAD (PSAD<sup>adj</sup>, defined as PSAD × weight) for csPCa in patients with negative MRI.</p><p><strong>Results: </strong>The patient distribution was as follows: MRI (-) PCa (-) group: 27.9% (115/412), MRI (+) PCa (-) group: 36.9% (152/412), MRI (-) PCa (+) group: 2.4% (10/412), and MRI (+) PCa (+) group: 32.8% (135/412). The NPV of MRI for csPCa was 92%. Multivariate analyses indicated that PV was negatively associated with the presence of csPCa (OR = 0.940, 95% CI: 0.896-0.986, <i>p</i> = 0.012), while PSAD and PSAD<sup>adj</sup> were positively associated with csPCa occurrence (OR = 10.288, 95% CI: 1.569-67.46, <i>p</i> = 0.015; OR = 1.027, 95% CI: 1.001-1.053, <i>p</i> = 0.043, respectively). For MRI-negative patients, PV > 55.25 mL (sensitivity = 100%, specificity = 63.2%), PSAD < 0.100 ng/mL<sup>2</sup> (sensitivity = 100%, specificity = 25.4%), or PSAD<sup>adj</sup> < 7.24 ng/mL (sensitivity = 100%, specificity = 28.1%) enhanced MRI's NPV to 100%, while PSAD < 0.205 ng/mL<sup>2</sup> (sensitivity = 77.8%, specificity = 71.9%) and PSAD<sup>adj</sup> < 24.97 ng/mL (sensitivity = 55.6%, specificity = 90.4%) improved NPV to 97.6% and 92.6%, respectively.</p><p><strong>Conclusion: </strong>In Chinese men with negative prostate MRIs, PV > 55.25 mL, PSAD < 0.100 ng/mL<sup>2</sup>, or PSAD<sup>adj</sup> < 7.24 ng/mL may elevate mpMRI's NPV from 92% to 100%, enabling safe avoidance of unnecessary biopsies. Prospective multicenter validation is required to confirm these find
{"title":"Reliability of Negative Prostate MRI for Biopsy Decision-Making in the Male Han Chinese Population.","authors":"Fangming Wang, Yan Zhang, Meng Fu, Yuzhe Tang, Haifeng Song, Gang Zhang, Boxing Su, Jianxing Li","doi":"10.1155/proc/1399482","DOIUrl":"10.1155/proc/1399482","url":null,"abstract":"<p><strong>Background: </strong>Multiparametric magnetic resonance imaging (mpMRI) has been widely utilized in clinical practice for identifying clinically significant prostate cancer (csPCa). Although mpMRI demonstrates a pooled negative predictive value (NPV) of 90%, additional clinical parameters require evaluation to enhance this metric specifically for the Chinese population-given the rising incidence of PCa in China, as well as ethnic differences in average prostate volume (PV) and chronic prostatitis prevalence that may impact mpMRI's diagnostic performance.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 543 patients who underwent transrectal ultrasound-guided prostate biopsy at Beijing Tsinghua Changgung Hospital between November 2014 and March 2025. After applying exclusion criteria, 412 patients were enrolled, all of whom had completed prebiopsy mpMRI within 1 month prior to biopsy. Patients were stratified into four groups based on the results of MRI examination and the pathological outcomes of biopsy: MRI (-) PCa (-), MRI (+) PCa (-), MRI (-) PCa (+), and MRI (+) PCa (+) groups. Multivariate logistic regression analyses were used to assess the odd ratios (ORs) of potential predictors for csPCa, comparing the MRI (-) PCa (+) and MRI (-) PCa (-) groups. Receiver operating characteristic curves were generated to analyze the predictive values of total PSA (tPSA), free PSA (fPSA), free-to-total (f/t) PSA, PV, PSA density (PSAD), and adjusted PSAD (PSAD<sup>adj</sup>, defined as PSAD × weight) for csPCa in patients with negative MRI.</p><p><strong>Results: </strong>The patient distribution was as follows: MRI (-) PCa (-) group: 27.9% (115/412), MRI (+) PCa (-) group: 36.9% (152/412), MRI (-) PCa (+) group: 2.4% (10/412), and MRI (+) PCa (+) group: 32.8% (135/412). The NPV of MRI for csPCa was 92%. Multivariate analyses indicated that PV was negatively associated with the presence of csPCa (OR = 0.940, 95% CI: 0.896-0.986, <i>p</i> = 0.012), while PSAD and PSAD<sup>adj</sup> were positively associated with csPCa occurrence (OR = 10.288, 95% CI: 1.569-67.46, <i>p</i> = 0.015; OR = 1.027, 95% CI: 1.001-1.053, <i>p</i> = 0.043, respectively). For MRI-negative patients, PV > 55.25 mL (sensitivity = 100%, specificity = 63.2%), PSAD < 0.100 ng/mL<sup>2</sup> (sensitivity = 100%, specificity = 25.4%), or PSAD<sup>adj</sup> < 7.24 ng/mL (sensitivity = 100%, specificity = 28.1%) enhanced MRI's NPV to 100%, while PSAD < 0.205 ng/mL<sup>2</sup> (sensitivity = 77.8%, specificity = 71.9%) and PSAD<sup>adj</sup> < 24.97 ng/mL (sensitivity = 55.6%, specificity = 90.4%) improved NPV to 97.6% and 92.6%, respectively.</p><p><strong>Conclusion: </strong>In Chinese men with negative prostate MRIs, PV > 55.25 mL, PSAD < 0.100 ng/mL<sup>2</sup>, or PSAD<sup>adj</sup> < 7.24 ng/mL may elevate mpMRI's NPV from 92% to 100%, enabling safe avoidance of unnecessary biopsies. Prospective multicenter validation is required to confirm these find","PeriodicalId":20907,"journal":{"name":"Prostate Cancer","volume":"2026 ","pages":"1399482"},"PeriodicalIF":2.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12798065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970905","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}
Pub Date : 2026-01-11eCollection Date: 2026-01-01DOI: 10.1155/proc/7871208
Fabienne Lehner, Souzan Salemi, Christopher Millan, Christoph Kündig, Daniel Eberli
Background: Most therapy options for castration-resistant prostate cancer (CRPCa) target the androgen axis. Human kallikrein-related peptidase (KLK) 2, a serine protease, is a downstream target gene of the androgen receptor (AR) involved in cancer progression, but also known to have an AR-independent function. Tissue KLKs, especially KLK2, are promising targets for therapy in advanced PCa because of their high PCa specificity and their correlation to the rising cancer grade and stage. By inhibition with the recombinant protease inhibitor MDPK67b targeting KLK2 and other trypsin-like KLKs including KLK4 and KLK14, we investigated the antitumor response and the influence on AR downstream target genes with MDPK67b in PCa cell lines in vitro.
Methods: Human PCa cells were cultured in a charcoal-stripped media and treated with MDPK67b (0.75 mg/mL). Cell viability was measured by CellTiter-Glo luminescent assay, cell death by flow cytometry. Gene analysis of AR, PSA, and PSMA was performed by qPCR. Correlating protein levels were evaluated by immunoblotting and confirmed by immunocytochemical staining.
Results: Treatment with 0.75 mg/mL MDPK67b led to a reduction of cell proliferation of 40% by day 5 in androgen-sensitive LNCaP cells. Immunostaining confirmed the decrease in cell proliferation by antibody labeling of Ki-67. Treatment induced apoptosis, which was visible by flow cytometry of annexin V in LNCaP cells. Further, MDPK67b induced a reduction in AR and PSA gene and protein expression but upregulated PSMA, a target for PCa imaging and therapy.
Conclusion: Treatment with MDPK67b demonstrates a significant antitumor effect by relevant reduction in cell proliferation and upregulation of apoptosis in LNCaP cells. Blockage of secreted KLKs can downregulate the AR and thereby influence its downstream target genes like PSA and PSMA. Upregulation of PSMA can lead to a theranostic, that is, therapeutic and diagnostic, advantage in clinics in a CR setting. Therefore, inhibition of KLKs represents a promising and AR-independent approach to treat advanced and CRPCa.
{"title":"Inhibition of Growth and Induction of Apoptosis of Human Prostate Cancer Cells by Enzymatic Blockage of Kallikreins.","authors":"Fabienne Lehner, Souzan Salemi, Christopher Millan, Christoph Kündig, Daniel Eberli","doi":"10.1155/proc/7871208","DOIUrl":"10.1155/proc/7871208","url":null,"abstract":"<p><strong>Background: </strong>Most therapy options for castration-resistant prostate cancer (CRPCa) target the androgen axis. Human kallikrein-related peptidase (KLK) 2, a serine protease, is a downstream target gene of the androgen receptor (AR) involved in cancer progression, but also known to have an AR-independent function. Tissue KLKs, especially KLK2, are promising targets for therapy in advanced PCa because of their high PCa specificity and their correlation to the rising cancer grade and stage. By inhibition with the recombinant protease inhibitor MDPK67b targeting KLK2 and other trypsin-like KLKs including KLK4 and KLK14, we investigated the antitumor response and the influence on AR downstream target genes with MDPK67b in PCa cell lines in vitro.</p><p><strong>Methods: </strong>Human PCa cells were cultured in a charcoal-stripped media and treated with MDPK67b (0.75 mg/mL). Cell viability was measured by CellTiter-Glo luminescent assay, cell death by flow cytometry. Gene analysis of AR, PSA, and PSMA was performed by qPCR. Correlating protein levels were evaluated by immunoblotting and confirmed by immunocytochemical staining.</p><p><strong>Results: </strong>Treatment with 0.75 mg/mL MDPK67b led to a reduction of cell proliferation of 40% by day 5 in androgen-sensitive LNCaP cells. Immunostaining confirmed the decrease in cell proliferation by antibody labeling of Ki-67. Treatment induced apoptosis, which was visible by flow cytometry of annexin V in LNCaP cells. Further, MDPK67b induced a reduction in AR and PSA gene and protein expression but upregulated PSMA, a target for PCa imaging and therapy.</p><p><strong>Conclusion: </strong>Treatment with MDPK67b demonstrates a significant antitumor effect by relevant reduction in cell proliferation and upregulation of apoptosis in LNCaP cells. Blockage of secreted KLKs can downregulate the AR and thereby influence its downstream target genes like PSA and PSMA. Upregulation of PSMA can lead to a theranostic, that is, therapeutic and diagnostic, advantage in clinics in a CR setting. Therefore, inhibition of KLKs represents a promising and AR-independent approach to treat advanced and CRPCa.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov ID: NCT04644770.</p>","PeriodicalId":20907,"journal":{"name":"Prostate Cancer","volume":"2026 ","pages":"7871208"},"PeriodicalIF":2.0,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12791160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966625","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}
Pub Date : 2025-12-31eCollection Date: 2025-01-01DOI: 10.1155/proc/9766669
Neal D Shore, Emmanuel S Antonarakis, Jason Hafron, Kelvin A Moses, Christopher Pieczonka, Benjamin Lowentritt, Nadeem Sheikh, Daniel J George, Tanya Barauskas Dorff
The first cellular cancer immunotherapy, sipuleucel-T, was approved for metastatic castration-resistant prostate cancer (mCRPC) patients 15 years ago. Since then, the therapeutic landscape of advanced prostate cancer has significantly evolved. Sipuleucel-T is a personalized, autologous immunotherapy that activates the patient's immune system to target prostatic acid phosphatase (PAP)-expressing tumor cells and has demonstrated survival benefit in patients with nonopioid requiring mCRPC. Subsequent clinical trials and abundant real-world data have provided further evidence of this novel immunotherapy's clinical benefit for patients with mCRPC, as well as demonstrating the numerous immune and biologic responses that sipuleucel-T induces. These data have also identified patient-specific factors associated with longer survival, including race, baseline disease burden, and treatment-induced immune responses. Despite the addition of multiple life-prolonging therapeutic modalities now available to treat patients with mCRPC, the mechanism of action of sipuleucel-T remains unique for patients with advanced prostate cancer. Therefore, maximizing the appropriate clinical utilization of sipuleucel-T in patients with mCRPC within current treatment paradigms is essential.
{"title":"Cellular Immunotherapy for Prostate Cancer: Lessons Learned From 15 Years of Sipuleucel-T.","authors":"Neal D Shore, Emmanuel S Antonarakis, Jason Hafron, Kelvin A Moses, Christopher Pieczonka, Benjamin Lowentritt, Nadeem Sheikh, Daniel J George, Tanya Barauskas Dorff","doi":"10.1155/proc/9766669","DOIUrl":"10.1155/proc/9766669","url":null,"abstract":"<p><p>The first cellular cancer immunotherapy, sipuleucel-T, was approved for metastatic castration-resistant prostate cancer (mCRPC) patients 15 years ago. Since then, the therapeutic landscape of advanced prostate cancer has significantly evolved. Sipuleucel-T is a personalized, autologous immunotherapy that activates the patient's immune system to target prostatic acid phosphatase (PAP)-expressing tumor cells and has demonstrated survival benefit in patients with nonopioid requiring mCRPC. Subsequent clinical trials and abundant real-world data have provided further evidence of this novel immunotherapy's clinical benefit for patients with mCRPC, as well as demonstrating the numerous immune and biologic responses that sipuleucel-T induces. These data have also identified patient-specific factors associated with longer survival, including race, baseline disease burden, and treatment-induced immune responses. Despite the addition of multiple life-prolonging therapeutic modalities now available to treat patients with mCRPC, the mechanism of action of sipuleucel-T remains unique for patients with advanced prostate cancer. Therefore, maximizing the appropriate clinical utilization of sipuleucel-T in patients with mCRPC within current treatment paradigms is essential.</p>","PeriodicalId":20907,"journal":{"name":"Prostate Cancer","volume":"2025 ","pages":"9766669"},"PeriodicalIF":2.0,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12767674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912803","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}
Pub Date : 2025-11-26eCollection Date: 2025-01-01DOI: 10.1155/proc/6500084
J N Stein, A M Deal, H Winslow, K Morgan, H Muthukrishnan, Y E Whang, M Charlot
Background: Prostate cancer is the second leading cause of cancer death among men, with a disproportionate burden on Black men. Racial disparities in care delivery for early-stage disease are well documented but less is known about racial gaps in advanced prostate cancer care, a stage where effective therapies can prolong life for years. We sought to evaluate potential treatment disparities among Black and White men with metastatic prostate cancer.
Methods: We performed a retrospective cohort study of patients with metastatic prostate cancer receiving treatment at a large public tertiary care health system between 2015 and 2020 using electronic health record data. We estimated the prevalence ratio (PR) of being prescribed each of the recommended treatment options for metastatic prostate cancer as per National Comprehensive Care Network guidelines, including androgen receptor pathway inhibitors (ARPIs) and other antiandrogens, chemotherapy, and bone protection, comparing Black men to White men.
Results: We identified 1166 patients with metastatic prostate cancer treated with androgen deprivation therapy (ADT); 370 (32%) were Black. Prescribing of systemic treatments did not differ by race, notably including ARPI (PR: 0.98 95% CI: 0.98-1.1, p=0.8). About 30% of both Black and White patients interacted with our patient navigation team, a group of oncology nurses focused on ensuring patients receive recommended care.
Conclusions: In a large public tertiary care health system, we did not observe racial disparities in the prescribing of guideline-recommended therapies for metastatic prostate cancer. High rates of insurance, a robust patient navigation program, and a well-developed pharmacy assistance program may have helped mitigate racial disparities in care. Future studies should prospectively evaluate the delivery of prostate cancer therapies across health systems and the influence of navigation and pharmacy assistance programs.
{"title":"Racial Disparities in the Prescribing of Guideline-Recommended Medications for Metastatic Prostate Cancer: A Retrospective Cohort Study.","authors":"J N Stein, A M Deal, H Winslow, K Morgan, H Muthukrishnan, Y E Whang, M Charlot","doi":"10.1155/proc/6500084","DOIUrl":"10.1155/proc/6500084","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer is the second leading cause of cancer death among men, with a disproportionate burden on Black men. Racial disparities in care delivery for early-stage disease are well documented but less is known about racial gaps in advanced prostate cancer care, a stage where effective therapies can prolong life for years. We sought to evaluate potential treatment disparities among Black and White men with metastatic prostate cancer.</p><p><strong>Methods: </strong>We performed a retrospective cohort study of patients with metastatic prostate cancer receiving treatment at a large public tertiary care health system between 2015 and 2020 using electronic health record data. We estimated the prevalence ratio (PR) of being prescribed each of the recommended treatment options for metastatic prostate cancer as per National Comprehensive Care Network guidelines, including androgen receptor pathway inhibitors (ARPIs) and other antiandrogens, chemotherapy, and bone protection, comparing Black men to White men.</p><p><strong>Results: </strong>We identified 1166 patients with metastatic prostate cancer treated with androgen deprivation therapy (ADT); 370 (32%) were Black. Prescribing of systemic treatments did not differ by race, notably including ARPI (PR: 0.98 95% CI: 0.98-1.1, <i>p</i>=0.8). About 30% of both Black and White patients interacted with our patient navigation team, a group of oncology nurses focused on ensuring patients receive recommended care.</p><p><strong>Conclusions: </strong>In a large public tertiary care health system, we did not observe racial disparities in the prescribing of guideline-recommended therapies for metastatic prostate cancer. High rates of insurance, a robust patient navigation program, and a well-developed pharmacy assistance program may have helped mitigate racial disparities in care. Future studies should prospectively evaluate the delivery of prostate cancer therapies across health systems and the influence of navigation and pharmacy assistance programs.</p>","PeriodicalId":20907,"journal":{"name":"Prostate Cancer","volume":"2025 ","pages":"6500084"},"PeriodicalIF":2.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12674856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678465","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}
Objectives: To assess the validity of magnetic resonance imaging-determined tumor contact area (MRI-TCA) as a predictive factor for pathological extraprostatic extension (EPE) in cT2N0M0 prostate cancer patients.
Methods: We retrospectively analyzed 72 cT2N0M0 prostate cancer patients who underwent multiparametric MRI (mpMRI) followed by robot-assisted laparoscopic prostatectomy (RARP) between February 2014 and April 2021. Patients whose MRI-based index lesion did not match the pathological specimens were excluded. MRI-TCA was approximated using an elliptical shape and calculated by two different methods: MRI-TCA1: Calculated using the tumor contact length (TCL) in the axial plane and the longer TCL in either the sagittal or coronal plane, capturing tumor dimensions across two planes. MRI-TCA2: Calculated using the TCL in the axial plane and tumor thickness derived from MRI slice data, reflecting the tumor's contact area within the MRI volume. We compared postoperative prostate-specific antigen (PSA) recurrence-free survival by stratifying patients based on the optimal thresholds of MRI-TCL, MRI-TCA1, MRI-TCA2, pathological-TCL, and pathological-TCA.
Results: Sixteen patients (22.2%) were pathologically positive for EPE. MRI-TCL, MRI-TCA1, and MRI-TCA2 were significantly greater in patients with EPE-positive (EPE+) tumors than in those with EPE-negative (EPE-) tumors (p < 0.0001, p < 0.0001, and p = 0.0026, respectively). No statistically significant differences were found between MRI-TCL and MRI-TCA1 (p = 0.914) or between MRI-TCL and MRI-TCA2 (p = 0.112) in predicting pathological EPE. A significant difference in postoperative PSA recurrence rate was observed in the stratified analysis based on pathological-TCA (p = 0.022).
Conclusion: Both MRI-TCA1 and MRI-TCA2 are clinically accessible and effective parameters for predicting pathological EPE in cT2N0M0 prostate cancer patients. However, neither method demonstrated clear superiority over MRI-TCL. Pathological-TCA was shown to be a significant predictor of both pathological EPE and postoperative PSA recurrence.
目的：评价磁共振成像确定肿瘤接触面积（MRI-TCA）作为cT2N0M0前列腺癌患者病理性前列腺外展（EPE）预测因素的有效性。方法：回顾性分析2014年2月至2021年4月期间接受多参数磁共振成像（mpMRI）和机器人辅助腹腔镜前列腺切除术（RARP）的72例cT2N0M0前列腺癌患者。排除mri指标病变与病理标本不匹配的患者。MRI-TCA使用椭圆形状近似，并通过两种不同的方法计算：MRI-TCA1：使用肿瘤接触长度（TCL）在轴向面和较长的TCL在矢状面或冠状面计算，捕获跨越两个平面的肿瘤尺寸。MRI- tca2：使用轴向面TCL和MRI切片数据导出的肿瘤厚度计算，反映肿瘤在MRI体积内的接触面积。我们根据MRI-TCL、MRI-TCA1、MRI-TCA2、病理- tcl和病理- tca的最佳阈值对患者进行分层，比较了术后前列腺特异性抗原（PSA）无复发生存率。结果：EPE病理阳性16例（22.2%）。EPE阳性（EPE+）肿瘤患者的MRI-TCL、MRI-TCA1和MRI-TCA2水平显著高于EPE阴性（EPE-）肿瘤患者（p < 0.0001, p < 0.0001, p = 0.0026）。MRI-TCL与MRI-TCA1预测病理性EPE的差异无统计学意义（p = 0.914）， MRI-TCL与MRI-TCA2预测病理性EPE的差异无统计学意义（p = 0.112）。在基于病理- tca的分层分析中，观察到术后PSA复发率的显著差异（p = 0.022）。结论：MRI-TCA1和MRI-TCA2是预测cT2N0M0前列腺癌患者病理EPE的临床可及的有效指标。然而，两种方法都没有显示出明显优于MRI-TCL。病理性tca被证明是病理性EPE和术后PSA复发的重要预测因子。
{"title":"MRI-Determined Tumor Contact Area as a Predictor of Pathological Extraprostatic Extension in Clinical T2 Prostate Cancer.","authors":"Masashi Tsujimoto, Yuta Inoue, Hideto Taga, Yumiko Saito, Masatomo Kaneko, Masatsugu Miyashita, Takeshi Yamada, Yasuhiro Yamada, Takashi Ueda, Atsuko Fujihara, Takumi Shiraishi, Masayoshi Okumi, Fumiya Hongo, Eiichi Konishi, Kaori Yamada, Kei Yamada, Osamu Ukimura","doi":"10.1155/proc/9165949","DOIUrl":"10.1155/proc/9165949","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the validity of magnetic resonance imaging-determined tumor contact area (MRI-TCA) as a predictive factor for pathological extraprostatic extension (EPE) in cT2N0M0 prostate cancer patients.</p><p><strong>Methods: </strong>We retrospectively analyzed 72 cT2N0M0 prostate cancer patients who underwent multiparametric MRI (mpMRI) followed by robot-assisted laparoscopic prostatectomy (RARP) between February 2014 and April 2021. Patients whose MRI-based index lesion did not match the pathological specimens were excluded. MRI-TCA was approximated using an elliptical shape and calculated by two different methods: MRI-TCA1: Calculated using the tumor contact length (TCL) in the axial plane and the longer TCL in either the sagittal or coronal plane, capturing tumor dimensions across two planes. MRI-TCA2: Calculated using the TCL in the axial plane and tumor thickness derived from MRI slice data, reflecting the tumor's contact area within the MRI volume. We compared postoperative prostate-specific antigen (PSA) recurrence-free survival by stratifying patients based on the optimal thresholds of MRI-TCL, MRI-TCA1, MRI-TCA2, pathological-TCL, and pathological-TCA.</p><p><strong>Results: </strong>Sixteen patients (22.2%) were pathologically positive for EPE. MRI-TCL, MRI-TCA1, and MRI-TCA2 were significantly greater in patients with EPE-positive (EPE+) tumors than in those with EPE-negative (EPE-) tumors (<i>p</i> < 0.0001, <i>p</i> < 0.0001, and <i>p</i> = 0.0026, respectively). No statistically significant differences were found between MRI-TCL and MRI-TCA1 (<i>p</i> = 0.914) or between MRI-TCL and MRI-TCA2 (<i>p</i> = 0.112) in predicting pathological EPE. A significant difference in postoperative PSA recurrence rate was observed in the stratified analysis based on pathological-TCA (<i>p</i> = 0.022).</p><p><strong>Conclusion: </strong>Both MRI-TCA1 and MRI-TCA2 are clinically accessible and effective parameters for predicting pathological EPE in cT2N0M0 prostate cancer patients. However, neither method demonstrated clear superiority over MRI-TCL. Pathological-TCA was shown to be a significant predictor of both pathological EPE and postoperative PSA recurrence.</p>","PeriodicalId":20907,"journal":{"name":"Prostate Cancer","volume":"2025 ","pages":"9165949"},"PeriodicalIF":2.0,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12580032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438995","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}
Prostate cancer is the most frequently diagnosed tumor of male reproductive system. Clinically, there is a lack of effective treatment drugs for prostate cancer. Previous studies have shown that AMPK inhibitor dorsomorphin was demonstrated to have potent antitumor effects. However, the effect of dorsomorphin on prostate cancer and its molecular mechanism are still unclear. In this study, the effects of dorsomorphin on the invasion and infiltration, epithelial-mesenchymal transition (EMT), and angiogenesis were investigated in two types of prostate cancer cells (DU145 and PC-3). In addition, nude mouse tumorigenic experiments were performed to confirm the antitumor effect of dorsomorphin. We found that dorsomorphin treatment concentration- and time-dependently inhibited the invasion and infiltration of DU145 and PC-3 cells. In addition, dorsomorphin reduced the expression levels of extracellular matrix components and angiogenesis-related proteins (HIF-1α and VEGF). Further study showed that dorsomorphin inhibited matrix deposition by antagonizing the EMT. Our results from nude mouse tumorigenic experiments further demonstrated dorsomorphin's tumor-growth inhibitory effect, whereas its antimetastatic potential is supported by in vitro invasion and EMT assays. Mechanistically, dorsomorphin treatment suppressed TGF-β1 expression and thereby inhibited the phosphorylation and nucleation of Smad2/3 signaling, which plays a key role in the regulation of EMT. Further study showed that dorsomorphin-triggered inactivation of JAK2/STAT3 and sonic hedgehog (Shh) signaling was involved in the inhibition of TGF-β1-mediated EMT. Interestingly, dorsomorphin inhibited the expression and nucleation of Gli1 and Gli3 but not affected the expression of Gli2. Thus, these findings reveal that the new mechanism of AMPK inhibitor dorsomorphin against prostate cancer metastasis is through synergistically antagonizing JAK2/STAT3 and Gli2-independent Shh activation.
{"title":"Dorsomorphin Suppresses EMT to Reduce AR-Negative Prostate Cancer Metastasis by Synergistically Antagonizing JAK2/STAT3 and Gli2-Independent Shh Activation.","authors":"Dongzhang Li, Guantao Lou, Wei Tian, Zujian Hu, Yongliang Chen, Wangjian Li","doi":"10.1155/proc/8843174","DOIUrl":"10.1155/proc/8843174","url":null,"abstract":"<p><p>Prostate cancer is the most frequently diagnosed tumor of male reproductive system. Clinically, there is a lack of effective treatment drugs for prostate cancer. Previous studies have shown that AMPK inhibitor dorsomorphin was demonstrated to have potent antitumor effects. However, the effect of dorsomorphin on prostate cancer and its molecular mechanism are still unclear. In this study, the effects of dorsomorphin on the invasion and infiltration, epithelial-mesenchymal transition (EMT), and angiogenesis were investigated in two types of prostate cancer cells (DU145 and PC-3). In addition, nude mouse tumorigenic experiments were performed to confirm the antitumor effect of dorsomorphin. We found that dorsomorphin treatment concentration- and time-dependently inhibited the invasion and infiltration of DU145 and PC-3 cells. In addition, dorsomorphin reduced the expression levels of extracellular matrix components and angiogenesis-related proteins (HIF-1<i>α</i> and VEGF). Further study showed that dorsomorphin inhibited matrix deposition by antagonizing the EMT. Our results from nude mouse tumorigenic experiments further demonstrated dorsomorphin's tumor-growth inhibitory effect, whereas its antimetastatic potential is supported by in vitro invasion and EMT assays. Mechanistically, dorsomorphin treatment suppressed TGF-β1 expression and thereby inhibited the phosphorylation and nucleation of Smad2/3 signaling, which plays a key role in the regulation of EMT. Further study showed that dorsomorphin-triggered inactivation of JAK2/STAT3 and sonic hedgehog (Shh) signaling was involved in the inhibition of TGF-β1-mediated EMT. Interestingly, dorsomorphin inhibited the expression and nucleation of Gli1 and Gli3 but not affected the expression of Gli2. Thus, these findings reveal that the new mechanism of AMPK inhibitor dorsomorphin against prostate cancer metastasis is through synergistically antagonizing JAK2/STAT3 and Gli2-independent Shh activation.</p>","PeriodicalId":20907,"journal":{"name":"Prostate Cancer","volume":"2025 ","pages":"8843174"},"PeriodicalIF":2.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252558","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}
Pub Date : 2025-09-16eCollection Date: 2025-01-01DOI: 10.1155/proc/8862153
Xiaoming Xu, Li Wang, Huafeng Pan, Tingitng Gu, Zhongliang Cheng, Tianjun Peng, Jianting Zhang, Jiaren Pan
Background: Fibroblast growth factor receptor 1 (FGFR1) signaling is activated by fibroblast growth factors (FGFs) during prostate cancer (PCa) progression. However, the mechanisms by which FGFR1 signaling regulates PCa progression are not fully understood. The objective of this study was to investigate the cross talk between autocrine FGF/FGFR1 loop and aerobic glycolysis in progression of advanced PCa. Method: DU145 cells were used as an advanced PCa model. FGFR1 expression was knockdowned by stable expression of anti-FGFR1 shRNA, and lactate dehydrogenase A (LDHA) levels were rescued by ectopic expression of LDHA cDNA. Protein expression was determined using Western blotting and immunohistochemistry. Tumorigenicity of DU145 cells was defined by cell growth, invasion, and survival in both cultures and xenografts in mice. Results: Here, we showed that DU145 cells in cultures expressed both FGF2 and FGFR1, and knockdown of FGFR1 expression or inactivation of FGFR1 signaling reduced LDHA expression or aerobic glycolysis, which was correlated with suppression of both cell proliferation and invasion, and with promotion of apoptosis. Ectopic expression of LDHA cDNA rescued LDHA levels in FGFR1-deficient cells, restoring their aerobic glycolysis, cell growth, and survival. Similarly, the growth rates of xenografted DU145 cells in mice were decreased by the loss of FGFR1 expression but were rescued by the ectopic expression of LDHA. Conclusion: Our data indicate autocrine FGF/FGFR1 signaling regulates aerobic glycolysis in PCa DU145 cells via LDHA, suggesting the potential of targeting FGFs/FGFRs-LDHA for the management of advanced PCa. The regulation of aerobic glycolysis by other growth factors in PCa remains further investigation.
{"title":"Autocrine Fibroblast Growth Factor Receptor 1 Signaling Activates Lactate Dehydrogenase A-Aerobic Glycolysis for Advanced Human Prostate Tumor Growth.","authors":"Xiaoming Xu, Li Wang, Huafeng Pan, Tingitng Gu, Zhongliang Cheng, Tianjun Peng, Jianting Zhang, Jiaren Pan","doi":"10.1155/proc/8862153","DOIUrl":"10.1155/proc/8862153","url":null,"abstract":"<p><p><b>Background:</b> Fibroblast growth factor receptor 1 (FGFR1) signaling is activated by fibroblast growth factors (FGFs) during prostate cancer (PCa) progression. However, the mechanisms by which FGFR1 signaling regulates PCa progression are not fully understood. The objective of this study was to investigate the cross talk between autocrine FGF/FGFR1 loop and aerobic glycolysis in progression of advanced PCa. <b>Method:</b> DU145 cells were used as an advanced PCa model. FGFR1 expression was knockdowned by stable expression of anti-FGFR1 shRNA, and lactate dehydrogenase A (LDHA) levels were rescued by ectopic expression of LDHA cDNA. Protein expression was determined using Western blotting and immunohistochemistry. Tumorigenicity of DU145 cells was defined by cell growth, invasion, and survival in both cultures and xenografts in mice. <b>Results:</b> Here, we showed that DU145 cells in cultures expressed both FGF2 and FGFR1, and knockdown of FGFR1 expression or inactivation of FGFR1 signaling reduced LDHA expression or aerobic glycolysis, which was correlated with suppression of both cell proliferation and invasion, and with promotion of apoptosis. Ectopic expression of LDHA cDNA rescued LDHA levels in FGFR1-deficient cells, restoring their aerobic glycolysis, cell growth, and survival. Similarly, the growth rates of xenografted DU145 cells in mice were decreased by the loss of FGFR1 expression but were rescued by the ectopic expression of LDHA. <b>Conclusion:</b> Our data indicate autocrine FGF/FGFR1 signaling regulates aerobic glycolysis in PCa DU145 cells via LDHA, suggesting the potential of targeting FGFs/FGFRs-LDHA for the management of advanced PCa. The regulation of aerobic glycolysis by other growth factors in PCa remains further investigation.</p>","PeriodicalId":20907,"journal":{"name":"Prostate Cancer","volume":"2025 ","pages":"8862153"},"PeriodicalIF":2.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138690","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}
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