Prostate Cancer Disease Research Articles

Leptin levels are associated with coronary artery calcification in patients with advanced prostate cancer.

Convergent data suggest that advanced prostate cancer and coronary heart disease (CHD) share biological vulnerabilities that may be linked to adiposity. Here we explore whether leptin, as a marker and mediator of adiposity, could link prostate cancer to CHD. Patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in a phase II trial (NCT02703623) studying androgen deprivation therapy, abiraterone, prednisone, and apalutamide were eligible if they had plasma and a chest CT scan available. Coronary artery calcium (CAC) scores and adipokine levels were measured upon enrollment. Of 164 patients, 87% were white. The mean age was 65.6 ± 7.5 years, 88% were either overweight or obese, 59% had hypertension, 48% had hyperlipidemia (HLD), 20% had type 2 diabetes mellitus, and 41% were former or current smokers. Coronary calcifications were found in 115 patients (70%). Among 47 patients with non-contrast chest CT scans, the median total CAC score was 133 AU (IQR 22.6-704.6). Four patients (9%) had a score of 0 AU (low risk) and 24 (51%) scores ≥100 AU, associated with high risk for major adverse cardiovascular events. Leptin levels correlated positively with the right coronary artery (RCA) CAC score [Pearson correlation coefficient (ρ) = 0.3715 (P = .0142)]. In a multivariate logistic regression analysis, older age, HLD, and higher leptin levels were independently associated with RCA calcification and a higher number of calcified coronary arteries. Among men with mCRPC, there was a high burden of CHD, and higher leptin levels were associated with coronary atherosclerosis independently of traditional cardiac risk factors.

Abstract IA020: Deciphering the mechanisms of neutrophil immune response in bone metastatic prostate cancer

Abstract Metastatic disease of prostate cancer (PCa) is currently incurable. Bone is the most common tissue site for prostate cancer metastasis and progression in bone is largely dictated by tumor-stromal interactions in the bone microenvironment. We showed previously that bone marrow neutrophils inhibit bone metastatic PCa growth, however metastatic PCa becomes resistant to neutrophil response and progresses within the bone compartment. It is unclear how these findings translate to a clinical setting. Further, the mechanisms associated with tumor resistance to neutrophil immune response remain unknown and presents a new avenue for therapeutic intervention. Thus, the goals of this study were: 1) to define the impact of metastatic PCa on neutrophil function throughout prostate cancer progression and 2) to determine the potential of neutrophils as predictive biomarkers of PCa disease progression. To do this, peripheral blood polymorphonuclear neutrophils (PMNs) were collected from 4 patient cohorts (localized PCa, metastatic hormone-sensitive PCa (mHSPC), metastatic castration-resistant (mCRPC) and healthy men) and PMN molecular and functional properties assessed, including: cancer cell cytotoxicity and cell surface markers. There was a significant decrease with disease progression in PMN expression of CD10, a marker for differentiation, while in tandem, there was an increase in pro-inflammatory marker, CD88 (complement receptor) in mCRPC men compared to mHSPC. PMNs from all disease stages were equally cytotoxic to human PCa cell lines (LNCaP, C42B, and PC3). However, second generation androgen deprivation therapy (ADT) suppressed patient PMN cytotoxicity against mCRPC cells (C42B, PC3). This suppression was due to androgen receptor (AR)-mediated regulation of the pleotropic and immune suppressant cytokine, transforming growth factor beta receptor I (TβRI). PMNs from mCRPC patients who received 2nd generation ADT, expressed significantly more TβRI than patients who only received 1st line ADT. Further, we found that PMNs in CRPC patient bone metastases express more TβRI than PMNs in matched liver metastases, which express little to no TβRI. Treatment of mouse bone marrow neutrophils with enzalutamide, increased neutrophil TβRI expression in a dose dependent manner and blocked cytotoxicity against PCa cells. Exogenous testosterone treatment in vivo, pharmacologic inhibition (using Repsox, a small molecule kinase inhibitor of TβRI) or genetic deletion (using conditional TβRI knockout mice) rescued enzalutamide-mediated neutrophil suppression and restored neutrophil cytotoxicity. These data collectively suggest that AR inhibition suppresses anti-tumor neutrophil responses via TβRI however, this study highlights the ability to leverage standard-care ADT to generate neutrophil anti-tumor responses against bone metastatic PCa. Citation Format: Leah M Cook. Deciphering the mechanisms of neutrophil immune response in bone metastatic prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr IA020.

Establishment and validation of predictive model of prostate cancer

Prostate cancer is a prevalent malignant disease among middle-aged and elderly men. Its prevention and detection are significant public health issues. We aimed to construct an interpretable model for predicting death risk in prostate cancer patients. We performed model development using the Cancer Genome Atlas and the Genotype-Tissue Expression databases. In comparison among models, the SVM model has the highest prediction performance among the eight models. The SHAP method, sorted by importance, reveals the top eight predictors of prostate cancer disease. This effective computer-aided approach can facilitate frontline clinicians in the diagnosis and management of patients with prostate cancer.

Bibliometric analysis of scientific literature on the use of suppositories in the treatment of prostate cancer patients

Nowadays, cancer remains one of the main causes of death worldwide. Statistical data from various literary sources indicate that more than 130,000 people in Ukraine receive this diagnosis as a sentence every year. Cancer can affect any organs of the human body and, over time, the entire organism. In 2024, the agency of the World Health Organization on cancer and the International Agency of Cancer Research published the latest statistical estimates of this pathology in a global format, where prostate cancer is among the five most common oncological pathologies and takes the fourth place. Oncological diseases are one of the priority areas of healthcare development in accordance with the Order of the Ministry of Health of Ukraine No. 1832 dated 07.10.2022 “On Approval of Priority Areas of Healthcare Development for 2023–2025”. It was this fact that determined the choice of the direction of this research in the matter of finding information on the provision of pharmaceutical care, namely the use of a drug – a rectal suppository for the treatment of prostate cancer. The aim of the work is to carry out a bibliometric analysis and further generalize the data of the scientific literature to study the prognostic value and features of the prescription of suppositories in the treatment of prostate cancer. Materials and methods. The data search was conducted in the PubMed electronic database using the following key terms: “prostate cancer and suppositories”, “prostate cancer”. To monitor and analyze international scientific research, with the help of visualization tools and modern SciVal citation metrics using the online platform, bibliometric analysis can be performed. Using the VOSviewer functional program, bibliometric networks were constructed and visualized. Results. A map of the relationships between the most used keywords on the topics of “prostate cancer” and “prostate cancer and suppositories”, grouped into clusters for the period from 1986 to 2024, was built. The clustering of the most used keywords on the subject of “prostate cancer” for the specified period is summarized. According to the bibliographic analysis, interest in the above topic was highest in 2014 and 2021. Conclusions. According to the bibliographic analysis, the interest in the subject of the patients’ treatment with prostate cancer disease continues to grow from 1998 up to the present. The analysis of publication activity using the visualization tool of bibliometric networks VOSviewer for the period from 2014 to 2024 for the key words “prostate cancer” has shown the presence of 14 clusters. The largest cluster is devoted to modern methods of prostate cancer treatment, studies of gene rearrangement, target therapy, carcinogenesis.

Comprehensive review of cardiovascular disease in prostate cancer: epidemiology, risk factors, therapeutics and prevention strategies.

The prevalence of cardiovascular risk factors and disease is high in patients with newly diagnosed prostate cancer (PC). Survivorship of PC patients is often determined by cardiovascular disease (CVD). Our review synthesizes the most recent literature exploring the dynamics between PC and CVD across the disease trajectory and treatments. We review key ongoing clinical trials in the field and highlight avenues for future study. We conducted a comprehensive narrative review of the literature using various search strategies in three databases (PubMed, Web of Science, ClinicalTrials.gov), focusing on literature published between 2000 and 2024. We discuss the significance of CVD-related mortality in PC, review the risk factors, and highlight potential mechanisms for accelerated CVD in the androgen-deprivation setting. Furthermore, we summarize key literature of CVD and cardiotoxicity for various therapeutic approaches in PC, including orchiectomy, taxane-based chemotherapy, GnRH-axis targets, and next-generation hormonal agents and PARP inhibitors. Lastly, we discuss prevention strategies and the importance of multi-disciplinary care in this setting. CVD is a major cause of death in men with PC. Various novel therapeutic approaches have been pivotal in improving oncologic outcomes, but emerging data demonstrate a complex interplay between the androgen axis and CVD that is likely affected by modern treatment strategies. Given the prolonged PC survivorship, unraveling non-oncologic related causes of death and investigating prevention strategies are imperative (Fig.1). Fig. 1 LANDSCAPE OF PROSTATE CANCER.: Spectrum of prostate cancer disease states (red) and interventions (yellow) with the potential role for optimization (green) to improve cardiovascular outcomes in the future (blue).

Lycopene-Loaded Emulsions: Chitosan Versus Non-Ionic Surfactants as Stabilizers.

Lycopene is a natural carotenoid with well-known benefits due to its antioxidant properties, including an anti-inflammatory effect in colorectal cancer and anti-angiogenic effects along with a reduction in the risk of prostate cancer and coronary heart disease. Due to their poor water solubility, photosensitivity and heat sensitivity, their incorporation in cosmetic and food matrices should be through encapsulation systems. In the present work, lycopene-loaded emulsions were prepared using two different types of stabilizers: non-ionic surfactants, testing several ratios of Tween 80 and Span 80, and chitosan, using chitosans of different viscosities and molecular weights. Soybean oil was found to be a suitable candidate for O/W emulsion preparation. Lycopene encapsulation efficiency (EE) of 70-75% and loading capacities of 0.14 mg/g were registered in stable emulsions stabilized either by non-ionic surfactants or acidified chitosans. Therefore, chitosan is a good alternative as a sustainable stabilizer to partially replace traditional synthetic ingredients with a new biodegradable, renewable and biocompatible material which could contribute to reduce the environmental impact as well as the ingestion of synthetic toxic materials by humans, decreasing their risk of suffering from chronic and complex pathologies, among which several types of cancer stand out.

Advances in the diagnosis of prostate cancer based on image fusion

Image fusion currently plays an important role in the diagnosis of prostate cancer (PCa). Selecting and developing a good image fusion algorithm is the core task of achieving image fusion, which determines whether the fusion image obtained is of good quality and can meet the actual needs of clinical application. In recent years, it has become one of the research hotspots of medical image fusion. In order to make a comprehensive study on the methods of medical image fusion, this paper reviewed the relevant literature published at home and abroad in recent years. Image fusion technologies were classified, and image fusion algorithms were divided into traditional fusion algorithms and deep learning (DL) fusion algorithms. The principles and workflow of some algorithms were analyzed and compared, their advantages and disadvantages were summarized, and relevant medical image data sets were introduced. Finally, the future development trend of medical image fusion algorithm was prospected, and the development direction of medical image fusion technology for the diagnosis of prostate cancer and other major diseases was pointed out.

A landmark federal interagency collaboration to promote data science in health care: Million Veteran Program-Computational Health Analytics for Medical Precision to Improve Outcomes Now.

In 2016, the Department of Veterans Affairs (VA) and the Department of Energy (DOE) established an Interagency Agreement (IAA), the Million Veteran Program-Computational Health Analytics for Medical Precision to Improve Outcomes Now (MVP-CHAMPION) research collaboration. Oversight fell under the VA Office of Research Development (VA ORD) and DOE headquarters. An Executive Committee and 2 senior scientific liaisons work with VA and DOE leadership to optimize efforts in the service of shared scientific goals. The program supported centralized data management and genomic analysis including creation of a scalable approach to cataloging phenotypes. Cross-cutting methods including natural language processing, image processing, and reusable code were developed. The 79.6 million dollar collaboration has supported centralized data management and genomic analysis including a scalable approach to cataloging phenotypes and launched over 10 collaborative scientific projects in health conditions highly prevalent in veterans. A ground-breaking analysis on the Summit and Andes supercomputers at the Oak Ridge National Laboratory (ORNL) of the genetic underpinnings of over 2000 health conditions across 44 million genetic variants which resulted in the identification of 38270 independent genetic variants associating with one or more health traits. Of these, over 2000 identified associations were unique to non-European ancestry. Cross-cutting methods have advanced state-of-the-art artificial intelligence (AI) including large language natural language processing and a system biology study focused on opioid addiction awarded the 2018 Gordon Bell Prize for outstanding achievement in high-performance computing. The collaboration has completed work in prostate cancer, suicide prevention, and cardiovascular disease, and cross-cutting data science. Predictive models developed in these projects are being tested for application in clinical management. Eight new projects were launched in 2023, taking advantage of the momentum generated by the previous collaboration. A major challenge has been limitations in the scope of appropriated funds at DOE which cannot currently be used for health research. Extensive multidisciplinary interactions take time to establish and are essential to continued progress. New funding models for maintaining high-performance computing infrastructure at the ORNL and for supporting continued collaboration by joint VA-DOE research teams are needed.

Preparation and in vitro/in vivo evaluation of uniform-sized Goserelin-loaded sustained release microspheres

Sustained release microspheres loaded with goserelin are regarded as a promising candidate for treating prostate cancer and other sex hormone diseases. However, their widespread adoption has been hindered by issues such as wide particle size distribution and unstable release characteristics. To address these challenges, we employed a combination of the solid-in-oil-in-water microspheres preparation approach (S/O/W) and innovative premix membrane emulsification technology and deeply investigated the effects of four key parameters on the loaded performance of microspheres and the microscopic mechanisms behind them. With this approach, we successfully produced goserelin-loaded sustained release microspheres of narrow particle size distribution (Span 0.642), remarkable encapsulation efficiency (DL = 4.23 %, EE = 93.98 %), low initial burst release (about 0.50 % within 2 h), and compatibility with small injection needles (23-G, inner diameter 0.33 mm, outer diameter 0.64 mm, maximal force 59 N). In the animal model(administered dose, 2.4 mg·Kg−1), goserelin long-acting sustained release microspheres sustained release for over 32 days, maintaining effective concentrations above 2 ng·mL−1, and effectively reduced serum testosterone concentrations to castration levels (<1.0 ng·mL−1) by day 4, maintaining this inhibition for up to 21 days, exhibiting comparable efficacy to the positive control group. In vivo release kinetics analysis revealed that goserelin-loaded sustained release microspheres exhibited a release pattern dominated by diffusion with corrosion assistance in vivo. In summary, the systematic and comprehensive evaluation of uniform-sized goserelin-loaded sustained release microspheres has highlighted their excellent translational potential, and the study herein may provide new strategies and ideas for the development of microsphere dosage forms.

When You Get to the Fork in the Road, Take It: The Challenges in Managing Patients With Advanced Prostate Cancer.

As is the case with most solid tumors, the heterogeneity of the disease biology of prostate cancer presents clinicians managing this disease with daily challenges. However, in contrast to other common cancers such as breast, lung, and colorectal cancers, there are unique challenges in prostate cancer management, including the variety of clinicians who manage aspects of the disease (urologists, medical oncologist, radiation oncologists) and the striking absence of prospective comparative data to inform the optimal sequence of systemic therapy in patients with metastatic castration-resistant disease. The purpose of this review is to attempt to assist practicing oncologists with sorting through the myriad of prostate cancer disease subsets and the challenges in making therapeutic decisions in multiple data-free zones given the absence of level 1 comparative clinical trials in the metastatic hormone-sensitive and castration-resistant states.

Application value of magnetic resonance spectroscopy imaging in the diagnosis of prostate cancer.

Magnetic resonance spectroscopy (MRSI) can distinguish between benign and malignant prostate diseases. This study investigated the potential of MRSI for diagnosing prostate cancer and guiding prostate biopsy. We retrospectively reviewed 234 patients with suspected prostate cancer who underwent MRSI with targeted prostate biopsy. Patients were divided into two groups according to their puncture pathology: prostate cancer (n = 103, 44.02%) and benign prostatic disease (n = 131, 55.98%). The t-test, Mann-Whitney U test, or chi-square test was used to compare the groups. The diagnostic abilities of MRSI, prostate-specific antigen level, digital rectal examination, and magnetic resonance imaging without contrast for prostate cancer were compared using the area under the receiver operating characteristic curve (AUC-ROC); the ARC-ROC values were 0.831, 0.768, 0.692, and 0.656, respectively. The AUC-ROC value for diagnosing prostate cancer using the CC/c ratio was 0.853. CC/c ratio > 0.97 was identified as the optimal threshold for diagnosing prostate cancer (sensitivity, 86.5%; specificity, 78.6%; Youden index, 0.651). Spearman correlation analysis revealed a correlation between the CC/c ratio and Gleason score (r = 0.737, p < 0.001). Using the CC/c ratio of MRSI as an adjunct to targeted prostate biopsy can improve the detection rate of positive biopsies and evaluate prostate cancer invasiveness.

Abstract A035: Protein quantitative trait loci analysis in diverse prostate cancer patients: A focus on angiogenesis

Abstract Prostate cancer exhibits notable disparities in mortality rates between African American (AA) and European American (EA) populations, with genetic ancestry and the social environment influencing both disease risk and lethality. Angiogenesis, the process of new blood vessel formation, plays a critical role in tumor progression and metastasis. However, the germline genetic contribution to the physiological variation in levels of circulating angiogenic markers, and the angiogenic process, is largely unknown. This study aims to explore the genetic underpinnings of angiogenesis in prostate cancer patients through a protein quantitative trait loci (pQTL) analysis. We analyzed 30 blood-based angiogenesis-related immuno-oncology markers in a cohort of 2,437 men from Ghana and the United States, comprising 1,330 controls and 1,107 prostate cancer cases. A comprehensive evaluation of 4,301,332 single nucleotide polymorphisms (SNPs) was conducted to investigate their associations with these markers across 3 population groups (Ghanaian, African American, and European American men). In this genome-wide pQTL we identified loci that associated with the levels of 13 markers (p &amp;lt;1.2 x 10-9). Our findings reveal that germline genetic variants may contribute to the variability in circulating angiogenic marker levels, or the systemic angiogenesis-inducing potential, with specific loci showing population-specific associations. We further link these circulating angiogenic markers to prostate cancer disease characteristics. Thus, our results suggest that germline genetic factors influence circulating levels of circulating angiogenesis-related proteins and thereby systemic angiogenesis, with a relationship to prostate cancer. Citation Format: Ashlie Santaliz Casiano, Hunter Schaumloffel, Huaitian Liu, Brittany Jenkins-Lord, Tsion Minas, Tiffany Dorsey, Stefan Ambs. Protein quantitative trait loci analysis in diverse prostate cancer patients: A focus on angiogenesis [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A035.

The role of SRC-3 in prostate cancer progression and implications for therapeutic targeting: A systematic review

Context: Prostate cancer remains a significant global health concern, and understanding the molecular drivers of this disease is crucial for developing effective diagnostic and therapeutic strategies. Steroid receptor coactivator-3 (SRC-3), a member of the SRC family, has emerged as a key player in prostate cancer pathogenesis. Aims: To examine the role of SRC-3 in prostate cancer, encompassing molecular mechanisms, clinical implications, and therapeutic opportunities. Methods: A systematic literature search following PRISMA guidelines was conducted in PubMed, PMC, and other relevant databases to identify studies that investigate SRC-3 in prostate cancer. Results: 785 articles were retrieved from databases using specific keywords and MeSH terms related to SRC-3 and Prostate Cancer. After removing 461 duplicates, 260 articles were excluded based on title and abstract review. Subsequently, a comprehensive screening by three researchers resulted in 47 relevant articles for this systematic review. Evidence suggests that SRC-3 expression correlates with prostate cancer aggressiveness, disease recurrence, and poor patient outcomes. Its potential as a diagnostic biomarker and therapeutic target if explored, offers insights into personalized medicine approaches. Conclusions: SRC-3 plays a pivotal role in prostate cancer, influencing disease progression and clinical outcomes. Understanding the molecular intricacies of SRC-3 in prostate cancer offers new opportunities for precision medicine and innovative therapeutic approaches. This review provides a comprehensive overview of SRC-3's involvement in prostate cancer, emphasizing its clinical relevance and potential as a therapeutic target, ultimately contributing to improved patient care in the era of personalized oncology.

The role of gut microbiota in prostate cancer progression: A Mendelian randomization study of immune mediation.

The potential relationship between the gut microbiota and prostate cancer, possibly influenced by immune cells, remains unclear. This study employed the mediation Mendelian randomization (MR) technique to investigate the causal link between the gut microbiota, immune cells, and prostate cancer. Data on immune cell activity were sourced from Valeria Orrù's research, whereas the genome-wide association study outcome dataset was obtained from the Integrative Epidemiology Unit database. The bidirectional MR analysis utilized 5 different methods: inverse variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode. In addition, the mediating effect of immune cells on the gut microbiota and prostate cancer was explored using mediation analysis. Eighty-three single nucleotide polymorphisms associated with prostate cancer were screened as instrumental variables. In a positive MR analysis with gut microbiota as the exposure factor, IVW showed an association between 8 gut microbiota and prostate cancer. Additionally, 9 types of immune cells have been found to be associated with prostate cancer using methods such as IVW. MR analysis of the gut microbiota on immune cells (beta1) revealed a negative correlation between Bifidobacterium and CD39+ T regulatory cells (Tregs; odds ratio [OR] = 0.785, 95% confidence interval [CI] = 0.627-0.983, P = .03). Furthermore, MR analysis of immune cells in prostate cancer disease (beta2) showed that CD39+Tregs are a risk factor for prostate cancer (OR = 1.215, 95% CI = 1.027-1.354, P = .04). Moreover, MR analysis of gut microbiota in prostate cancer (total effect) indicated that Bifidobacterium is a protective factor for prostate cancer (OR = 0.905, 95% CI = 0.822-0.977, P = .04). The sensitivity analysis verified the robustness of the above results. Mediation analysis demonstrated that CD39+Tregs partially mediate the causal relationship between Bifidobacterium and prostate cancer. This study demonstrates that Bifidobacterium inhibits prostate cancer progression through CD39+Tregs as mediators, providing new ideas and approaches for the treatment and prevention of prostate cancer.

Perspectives on technology: Prostate Imaging-Reporting and Data System (PI-RADS) interobserver variability.

To explore the topic of Prostate Imaging-Reporting and Data System (PI-RADS) interobserver variability, including a discussion of major sources, mitigation approaches, and future directions. A narrative review of PI-RADS interobserver variability. PI-RADS was developed in 2012 to set technical standards for prostate magnetic resonance imaging (MRI), reduce interobserver variability at interpretation, and improve diagnostic accuracy in the MRI-directed diagnostic pathway for detection of clinically significant prostate cancer. While PI-RADS has been validated in selected research cohorts with prostate cancer imaging experts, subsequent prospective studies in routine clinical practice demonstrate wide variability in diagnostic performance. Radiologist and biopsy operator experience are the most important contributing drivers of high-quality care among multiple interrelated factors including variability in MRI hardware and technique, image quality, and population and patient-specific factors such as prostate cancer disease prevalence. Iterative improvements in PI-RADS have helped flatten the curve for novice readers and reduce variability. Innovations in image quality reporting, administrative and organisational workflows, and artificial intelligence hold promise in improving variability even further. Continued research into PI-RADS is needed to facilitate benchmark creation, reader certification, and independent accreditation, which are systems-level interventions needed to uphold and maintain high-quality prostate MRI across entire populations.

Cardiovascular Events and Androgen Receptor Signaling Inhibitors in Advanced Prostate Cancer

Cardiovascular (CV) events remain a substantial cause of mortality among men with advanced and metastatic prostate cancer (PCa). The introduction of novel androgen receptor signaling inhibitors (ARSI) has transformed the treatment landscape of PCa in recent years; however, their associated CV toxic effects remains unclear. To assess the incidence of CV events with addition of ARSI to standard of care (SOC) in locally advanced (M0) and metastatic (M1) PCa. Systematic searches of PubMed, Scopus, Web of Science, EMBASE, and ClinicalTrials.gov were performed from inception up to May 2023. Randomized clinical trials of ARSI agents (abiraterone, apalutamide, darolutamide, enzalutamide) that reported CV events among individuals with M0 and M1, hormone-sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC). A systematic review was performed in accordance with PRISMA guidance. Two authors screened and independently evaluated studies eligible for inclusion. Data extraction and bias assessment was subsequently performed. A random-effects meta-analysis was performed to estimate risk ratios for the incidence of all grade and grade 3 or higher CV events (primary outcomes), in addition to hypertension, acute coronary syndrome (ACS), cardiac dysrhythmia, CV death, cerebrovascular event, and venous thromboembolism (secondary outcomes). Sources of heterogeneity were explored using meta-regression. There were 24 studies (n = 22 166 patients; median age range, 63-77 years; median follow-up time range, 3.9-96 months) eligible for inclusion. ARSI therapy was associated with increased risk of all grade CV event (risk ratio [RR], 1.75; 95% CI, 1.50-2.04; P < .001) and grade 3 or higher CV events (RR, 2.10; 95%, 1.72-2.55; P < .001). ARSI therapy also was associated with increased risk for grade 3 or higher events for hypertension (RR, 2.25; 95% CI, 1.74-2.90; P < .001), ACS (RR, 1.93; 95% CI, 1.43-1.60; P < .01), cardiac dysrhythmia (RR, 1.64; 95% CI, 1.23-2.17; P < .001), cerebrovascular events (RR, 1.86; 95% CI, 1.34-2.59; P < .001) and for CV-related death (RR, 2.02; 95% CI, 1.32-3.10; P = .001). Subgroup analysis demonstrated increased risk of all CV events across the disease spectrum (M0 HSPC: RR, 2.26; 95% CI, 1.36-3.75; P = .002; M1 HSPC: RR, 1.85; 95% CI, 1.47-2.31; P < .001; M0 CRPC: RR, 1.79; 95% CI, 1.13-2.81; P = .01; M1 CRPC: RR, 1.46; 95% CI, 1.16-1.83; P = .001). This systematic review and meta-analysis found that the addition of ARSIs to traditional ADT was associated with increased risk of CV events across the prostate cancer disease spectrum. These results suggest that patients with prostate cancer should be advised about and monitored for the potential of increased risk of CV events with initiation of ARSI therapy alongside conventional hormonal therapy.

Prostate cancer and cardiovascular disease: Racial/ethnic disparities and role of chronic toxic stress/allostatic load

Prostate cancer and cardiovascular disease: Racial/ethnic disparities and role of chronic toxic stress/allostatic load

The association between inflammatory bowel disease and risk of prostate cancer: a population-based retrospective study based on Korean National Health Insurance Service database

BackgroundThe aim of this study was to determine whether inflammatory bowel disease (IBD) is associated with the risk of developing prostate cancer (PCa) through a population-based study. Materials and methodsMale patients aged ≥40 years, diagnosed with IBD from 2010 to 2013 and without IBD were identified and followed-up till 2019. A matched cohort of male patients with and without IBD in a ratio of 1:4 was created based on age, income level, and Charlson comorbidity index. Multivariate Cox regression analysis was conducted to evaluate the association of IBD with the prescence of PCa and PCa requiring definitive treatment within 1 year of diagnosis. The hazard ratio (HR) and 95% confidence interval (CI) were stratified by Crohn's disease, ulcerative colitis (UC), and subtypes. ResultsAfter matching, 15,751 IBD patients and 62,346 controls were analyzed. Over a median follow-up period of 96 months, the HR for PCa was significantly increased in patients with IBD (HR: 2.44; 95% CI: 2.08–2.86, P < 0.001). IBD was also associated with PCa requiring definitive treatment within 1 year (HR: 2.67; 95% CI: 2.09–3.42, P < 0.001). In subgroup analysis, UC (HR: 2.83; 95% CI: 2.18–3.69, P < 0.001) showed higher risk of PCa requiring definitive treatment than for Crohn's disease (HR: 2.21; 95% CI: 1.43–3.43, P = 0.0004). All-cause death in patient-diagnosed PCa was the highest in UC of pancolitis (HR: 2.26; 95% CI: 0.99–5.16, P = 0.054), and the lowest in ulcerative proctitis (HR: 0.35; 95% CI: 0.21–0.60, P = 0.0001). ConclusionIBD was associated with an increased incidence of PCa in our matched analysis.

Increased α2,3-sialyl N-glycosylated prostate-specific membrane antigen (PSMA) in post-DRE urine is associated with high grade group prostate cancer.

Aberrant glycosylation of proteins is an important hallmark in multiple cancers. Prostate-specific membrane antigen (PSMA), a highly glycosylated protein with 10 N-linked glycosylation sites, is an Food and Drug Administration approved theranostic for prostate cancer. However, glycosylation changes in PSMA that are associated with prostate cancer disease progression have not been fully characterized. We investigated whether urinary PSMA sialylation correlate with high-grade prostate cancer. Urine samples were collected from men after digital rectal examination (DRE) before prostate biopsy. Lectin-antibody enzyme-linked immunoassay was used to quantify α2,3-sialyl PSMA in post-DRE urine samples from subjects with benign prostate tumors, Grade Group 1 prostate cancer and those with Grade Group ≥2 disease. There are significant increases in α2,3-sialylated PSMA in patients with Grade Group ≥2 disease compared to benign (p = 0.0009) and those with Grade Group 1 disease (p = 0.0063). There were no significant differences in α2,3-sialyl PSMA levels between Grade Group 1 and benign prostate tumors (p = 0.7947). Our study shows that there are significant differences in the abundance of α2,3-sialylated PSMA in post-DRE urines from disease stratified prostate cancer patients, and the increase is correlated with progression and disease severity. The detection of increased PSMA sialyation in post-DRE urines from patients with higher Grade Group ≥2 disease states provides novel untapped potential for the development of prognostic biomarkers for prostate cancer. Specifically, quantitation of α2,3-sialylated PSMA shows potential for discriminating between benign to intermediate grade disease, which is a significant clinical challenge in staging and risk stratification of prostate cancer.

&lt;i&gt;In Silico&lt;/i&gt; Screening of Phytochemicals as an Approach against Tubulin Inhibitor in Prostate Cancer

Background: Millions of men worldwide are affected by the complicated disease of prostate cancer, which is most common in areas with high socioeconomic indices. There is growing proof indicating that not all cases of prostate tumors are the same as well as that monitoring techniques and prostate-specific localization therapies are harmless methods of dealing with this mild illness. Plant-based chemicals are believed to be an important reservoir of novel bioactive compounds with a range of different chemical motifs. Aim: The potential of tubulin-targeting medications to target Micro tubulin mechanisms and disrupt important cellular processes which include mitosis, cell signalling, cytoplasmic trafficking and angiogenesis is what makes them such effective cancer therapies. Methods: The current research uses a variety of applications for emphasizing the drug-like properties, toxicology testing, and in silico analysis of numerous phytochemicals in prostate cancer by using the NPACT (Naturally occurring plant-based anti-cancer compound) data bank, Auto dock, Biovia discovery studio for the preparation of target protein and interaction between targeted protein site and Phytocompounds. Result and Conclusion: outcomes of the in silico screening, such as the discovery of possible bioactive substances or interested targets. The nine phytochemicals exhibited the greatest docking results, proving they are potent inhibitors of prostate tumors. To verify the computational results, compare the in silico assumptions with empirical information or previously published literature. To reinforce the conclusions, illustrations such as modifications to conformation, binding ways, or sequences of interactions. This in silico study is a critical first step in realizing the enormous promise of plant-based constituents in the field of drugs.