-
Phytotherapy Research : PTR Jan 2024Ursolic acid (UA) is a naturally occurring pentacyclic triterpenoid widely found in fruits and vegetables. It has been reported that UA has anti-inflammatory effects....
Ursolic acid (UA) is a naturally occurring pentacyclic triterpenoid widely found in fruits and vegetables. It has been reported that UA has anti-inflammatory effects. However, its efficacy and mechanism of action in the treatment of chronic prostatitis (CP) remain unclear. This study aimed to investigate the efficacy of UA treatment in CP and further explore the underlying mechanism. CP rat and pyroptosis cell models were established in vivo and in vitro, respectively. The efficacy of UA in inhibiting CP was evaluated via haematoxylin-eosin (HE) staining and measurement of inflammatory cytokines. RNA sequencing and molecular docking were used to predict the therapeutic targets of UA in CP. The expression of pyroptosis-related proteins was examined using various techniques, including immunohistochemistry, immunofluorescence, and flow cytometry. UA significantly ameliorated pathological damage and reduced the levels of proinflammatory cytokines in the CP model rats. RNA sequencing analysis and molecular docking suggested that NLRP3, Caspase-1, and GSDMD may be key targets. We also found that UA decreased ROS levels, alleviated oxidative stress, and inhibited p-NF-κB protein expression both in vivo and in vitro. UA improved pyroptosis morphology as indicated by electron microscope and inhibited the expression of the pyroptosis-related proteins NLRP3, Caspase-1, ASC, and GSDMD, reversed the levels of IL-1β, IL-18, and lactate dehydrogenase in vivo and in vitro. UA can mitigate CP by regulating the NLRP3 inflammasome-mediated Caspase-1/GSDMD pathway. Therefore, UA may be a potential for the treatment of CP.
Topics: Humans; Male; Rats; Animals; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Ursolic Acid; Pyroptosis; Caspase 1; Prostatitis; Molecular Docking Simulation; Gasdermins; Phosphate-Binding Proteins
PubMed: 37807970
DOI: 10.1002/ptr.8034 -
Advanced Science (Weinheim,... Mar 2024The extracellular matrix (ECM) undergoes substantial changes during prostate cancer (PCa) progression, thereby regulating PCa growth and invasion. Herein, a... (Meta-Analysis)
Meta-Analysis
The extracellular matrix (ECM) undergoes substantial changes during prostate cancer (PCa) progression, thereby regulating PCa growth and invasion. Herein, a meta-analysis of multiple PCa cohorts is performed which revealed that downregulation or genomic loss of ITGA1 and ITGA2 integrin genes is associated with tumor progression and worse prognosis. Genomic deletion of both ITGA1 and ITGA2 activated epithelial-to-mesenchymal transition (EMT) in benign prostate epithelial cells, thereby enhancing their invasive potential in vitro and converting them into tumorigenic cells in vivo. Mechanistically, EMT is induced by enhanced secretion and autocrine activation of TGFβ1 and nuclear targeting of YAP1. An unbiased genome-wide co-expression analysis of large PCa cohort datasets identified the transcription factor TEAD1 as a key regulator of ITGA1 and ITGA2 expression in PCa cells while TEAD1 loss phenocopied the dual loss of α1- and α2-integrins in vitro and in vivo. Remarkably, clinical data analysis revealed that TEAD1 downregulation or genomic loss is associated with aggressive PCa and together with low ITGA1 and ITGA2 expression synergistically impacted PCa prognosis and progression. This study thus demonstrated that loss of α1- and α2-integrins, either via deletion/inactivation of the ITGA1/ITGA2 locus or via loss of TEAD1, contributes to PCa progression by inducing TGFβ1-driven EMT.
Topics: Male; Humans; Prostate; Cell Line, Tumor; Prostatic Neoplasms; Signal Transduction; Integrin alpha2; TEA Domain Transcription Factors
PubMed: 38169150
DOI: 10.1002/advs.202305547 -
Pain Research & Management 2023Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases of the male urological system while the etiology and treatment of CP/CPPS... (Review)
Review
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases of the male urological system while the etiology and treatment of CP/CPPS remain a thorny issue. Cumulative research suggested a potentially important role of glial cells in CP/CPPS. This narrative review retrospected literature and grasped the research process about glial cells and CP/CPPS. Three types of glial cells showed a crucial connection with general pain and psychosocial symptoms. Microglia might also be involved in lower urinary tract symptoms. Only microglia and astrocytes have been studied in the animal model of CP/CPPS. Activated microglia and reactive astrocytes were found to be involved in both pain and psychosocial symptoms of CP/CPPS. The possible mechanism might be to mediate the production of some inflammatory mediators and their interaction with neurons. Glial cells provide a new insight to understand the cause of complex symptoms of CP/CPPS and might become a novel target to develop new treatment options. However, the activation and action mechanism of glial cells in CP/CPPS needs to be further explored.
Topics: Humans; Animals; Male; Chronic Disease; Prostatitis; Pelvic Pain; Central Nervous System; Neuroglia; Chronic Pain
PubMed: 38023826
DOI: 10.1155/2023/2061632 -
The Journal of Pathology Sep 2023Club cells are a type of bronchiolar epithelial cell that serve a protective role in the lung and regenerate damaged lung epithelium. Single-cell RNA sequencing...
Club cells are a type of bronchiolar epithelial cell that serve a protective role in the lung and regenerate damaged lung epithelium. Single-cell RNA sequencing (scRNA-seq) of young adult human prostate and urethra identified cell populations in the prostatic urethra and collecting ducts similar in morphology and transcriptomic profile to lung club cells. We further identified club cell-like epithelial cells by scRNA-seq of prostate peripheral zone tissues. Here, we aimed to identify and spatially localize club cells in situ in the prostate, including in the peripheral zone. We performed chromogenic RNA in situ hybridization for five club cell markers (CP, LTF, MMP7, PIGR, SCGB1A1) in a series of (1) nondiseased organ donor prostate and (2) radical prostatectomy specimens from individuals with prostate cancer. We report that expression of club cell genes in the peripheral zone is associated with inflammation and limited to luminal epithelial cells classified as intermediate cells in proliferative inflammatory atrophy (PIA). Club-like cells were enriched in radical prostatectomy specimens compared to nondiseased prostates and associated with high-grade prostate cancer. We previously reported that luminal epithelial cells in PIA can rarely harbor oncogenic TMPRSS2:ERG (ERG+) gene fusions, and we now demonstrate that club cells are present in association with ERG+ PIA that is transitioning to early adenocarcinoma. Finally, prostate epithelial organoids derived from prostatectomy specimens demonstrate that club-like epithelial cells can be established in organoids and are sensitive to anti-androgen-directed treatment in vitro in terms of decreased androgen signaling gene expression signatures compared to basal or hillock cells. Overall, our study identifies a population of club-like cells in PIA and proposes that these cells play an analogous role to that of club cells in bronchiolar epithelium. Our results further suggest that inflammation drives lineage plasticity in the human prostate and that club cells in PIA may be prone to oncogenic transformation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Male; Young Adult; Humans; Prostate; Prostatic Neoplasms; Epithelial Cells; Inflammation; Atrophy
PubMed: 37550827
DOI: 10.1002/path.6149 -
International Journal of Molecular... Jul 2023Prostate cancer is one of the most common malignant diseases in men, and it contributes significantly to the increased mortality rate in men worldwide. This study aimed... (Review)
Review
Prostate cancer is one of the most common malignant diseases in men, and it contributes significantly to the increased mortality rate in men worldwide. This study aimed to review the roles of p300 and TMPRSS2 (transmembrane protease, serine 2) in the AR (androgen receptor) pathway as they are closely related to the development and progression of prostate cancer. This paper represents a library-based study conducted by selecting the most suitable, up-to-date scientific published articles from online journals. We focused on articles that use similar techniques, particularly those that use prostate cancer cell lines and immunohistochemical staining to study the molecular impact of p300 and TMPRSS2 in prostate cancer specimens. The fusion is considered relevant to prostate cancer, but its association with the development and progression as well as its clinical significance have not been fully elucidated. On the other hand, high p300 levels in prostate cancer biopsies predict larger tumor volumes, extraprostatic extension of disease, and seminal vesicle involvement at prostatectomy, and may be associated with prostate cancer progression after surgery. The inhibition of p300 has been shown to reduce the proliferation of prostate cancer cells with (E26 transformation-specific) fusions, and combining p300 inhibitors with other targeted therapies may increase their efficacy. Overall, the interplay between the p300 and TMPRSS2 pathways is an active area of research.
Topics: Humans; Male; Biopsy; Oncogene Proteins, Fusion; Prostate; Prostatic Neoplasms; Serine Endopeptidases; Transcriptional Regulator ERG; p300-CBP Transcription Factors
PubMed: 37511059
DOI: 10.3390/ijms241411299 -
JNCI Cancer Spectrum Aug 2023Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score,...
BACKGROUND
Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score, T stage (based on digital rectal exam), and prostate-specific antigen (PSA). In this study a novel prognostic test, the Decipher Prostate Genomic Classifier (GC), was used to stratify risk of prostate cancer progression in a US national database of men with prostate cancer.
METHODS
Records of prostate cancer cases from participating SEER (Surveillance, Epidemiology, and End Results) program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the GC prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy-tested cohort and postoperative radiotherapy in the GC-tested cohort as well as adverse pathological findings after prostatectomy.
RESULTS
A total of 572 545 patients were included in the analysis, of whom 8927 patients underwent GC testing. GC biopsy-tested patients were more likely to undergo active active surveillance or watchful waiting than untested patients (odds ratio [OR] =2.21, 95% confidence interval [CI] = 2.04 to 2.38, P < .001). The highest use of active surveillance or watchful waiting was for patients with a low-risk GC classification (41%) compared with those with an intermediate- (27%) or high-risk (11%) GC classification (P < .001). Among National Comprehensive Cancer Network patients with low and favorable-intermediate risk, higher GC risk class was associated with greater use of local therapy (OR = 4.79, 95% CI = 3.51 to 6.55, P < .001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathological findings (OR = 2.94, 95% CI = 1.38 to 6.27, P = .005). Use of radiation after prostatectomy was statistically significantly associated with higher GC risk groups (OR = 2.69, 95% CI = 1.89 to 3.84).
CONCLUSIONS
There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of postoperative radiotherapy.In this study the Decipher Prostate Genomic Classifier (GC) was used to analyze a US national database of men with prostate cancer. Use of the GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a 3-fold higher chance of having worrisome findings in surgical specimens.
Topics: Male; Humans; United States; Risk Assessment; Prostatic Neoplasms; Prostate-Specific Antigen; Prostate; Genomics
PubMed: 37525535
DOI: 10.1093/jncics/pkad052 -
Radiologic Clinics of North America Jan 2024Multiparametric MR imaging of the prostate is an essential diagnostic study in the evaluation of prostate cancer. Several entities including normal anatomic structures,... (Review)
Review
Multiparametric MR imaging of the prostate is an essential diagnostic study in the evaluation of prostate cancer. Several entities including normal anatomic structures, benign lesions, and posttreatment changes can mimic prostate cancer. An in depth understanding of the pitfalls is important for accurate interpretation of prostate MR imaging.
Topics: Male; Humans; Prostate; Magnetic Resonance Imaging; Prostatic Neoplasms; Pelvis
PubMed: 37973245
DOI: 10.1016/j.rcl.2023.07.001 -
The Journal of Urology Oct 2023We studied whether adding percent free PSA to total PSA improves prediction of clinically significant prostate cancer and fatal prostate cancer.
PURPOSE
We studied whether adding percent free PSA to total PSA improves prediction of clinically significant prostate cancer and fatal prostate cancer.
MATERIALS AND METHODS
A total of 6,727 men within the intervention arm of PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial) had baseline percent free PSA. Of this cohort, 475 had clinically significant prostate cancer and 98 had fatal prostate cancer. Cumulative incidence and Cox analyses were conducted to evaluate the association between percent free PSA/PSA and clinically significant prostate cancer/fatal prostate cancer. Harrell's C index evaluated predictive ability. Kaplan-Meier analysis assessed survival.
RESULTS
Median follow-up was 19.7 years, median baseline PSA was 1.19 ng/mL, median percent free PSA was 18%. Cumulative incidence of fatal prostate cancer for men with baseline PSA ≥2 ng/mL and percent free PSA ≤10 was 3.2% and 6.1% at 15 and 25 years, respectively, compared to 0.03% and 1.1% for men with percent free PSA >25%. In younger men (55-64 years) with baseline PSA 2-10 ng/mL, C index improved from 0.56 to 0.60 for clinically significant prostate cancer and from 0.53 to 0.64 for fatal prostate cancer with addition of percent free PSA. In older men (65-74 years), C index improved for clinically significant prostate cancer from 0.60 to 0.66, with no improvement in fatal prostate cancer. Adjusting for age, digital rectal exam, family history of prostate cancer, and total PSA, percent free PSA was associated with clinically significant prostate cancer (HR 1.05, < .001) per 1% decrease. Percent free PSA improved prediction of clinically significant prostate cancer and fatal prostate cancer for all race groups.
CONCLUSIONS
In a large U.S. screening trial, the addition of percent free PSA to total PSA in men with baseline PSA ≥2 ng/mL improved prediction of clinically significant prostate cancer and fatal prostate cancer. Free PSA should be used to risk-stratify screening and decrease unnecessary prostate biopsies.
Topics: Male; Humans; Aged; Prostate-Specific Antigen; Mass Screening; Early Detection of Cancer; Prostatic Neoplasms; Prostate
PubMed: 37384841
DOI: 10.1097/JU.0000000000003603 -
International Braz J Urol : Official... 2024
Topics: Male; Humans; Prostate; Prostatitis; Tuberculosis, Male Genital
PubMed: 37624660
DOI: 10.1590/S1677-5538.IBJU.2023.0299 -
The Journal of Urology Jul 2024
Topics: Humans; Prostatic Hyperplasia; Male; Embolization, Therapeutic; Prostate
PubMed: 38703386
DOI: 10.1097/JU.0000000000003976