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High-throughput glycopeptide profiling of prostate-specific antigen from seminal plasma by MALDI-MS.Talanta Jan 2021An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen...
An altered total seminal plasma glycosylation has been associated with male infertility, and the highly abundant seminal plasma glycoprotein prostate-specific antigen (PSA) plays an important role in fertilization. However, the exact role of PSA glycosylation in male fertility is not clear. To understand the involvement of PSA glycosylation in the fertilization process, analytical methods are required to study the glycosylation of PSA from seminal plasma with a high glycoform resolution and in a protein-specific manner. In this study, we developed a novel, high-throughput PSA glycopeptide workflow, based on matrix-assisted laser desorption/ionization-mass spectrometry, allowing the discrimination of sialic acid linkage isomers via the derivatization of glycopeptides. The method was successfully applied on a cohort consisting of seminal plasma from infertile and fertile men (N = 102). Forty-four glycopeptides were quantified in all samples, showing mainly complex-type glycans with high levels of fucosylation and sialylation. In addition, N,N-diacetyllactosamine (LacdiNAc) motives were found as well as hybrid-type and high mannose-type structures. Our method showed a high intra- and interday repeatability and revealed no difference in PSA glycosylation between fertile and infertile men. Next to seminal plasma, the method is also expected to be of use for studying PSA glycopeptides derived from other biofluids and/or in other disease contexts.
Topics: Glycopeptides; Glycosylation; Humans; Male; Polysaccharides; Prostate-Specific Antigen; Semen; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 33167210
DOI: 10.1016/j.talanta.2020.121495 -
International Journal of Cancer Dec 2020This review discusses evidence for population-based screening with contemporary screening tools. In Europe, prostate-specific antigen (PSA)-based screening led to a... (Review)
Review
This review discusses evidence for population-based screening with contemporary screening tools. In Europe, prostate-specific antigen (PSA)-based screening led to a relative reduction of prostate cancer (PCa) mortality, but also to a substantial amount of overdiagnosis and unnecessarily biopsies. Risk stratification based on a single variable (a clinical variable or based on the presence of a lesion on prostate imaging) or based on multivariable approaches can aid in reducing unnecessary prostate biopsies and overdiagnosis by selecting men who can benefit from further clinical assessment. Multivariable approaches include clinical variables, and biomarkers, often combined in risk calculators or nomograms. These risk calculators can also incorporate the result of MRI imaging. In general, as compared to a purely PSA based approach, the combination of relevant prebiopsy information results in superior selection of men at higher risk of harboring clinically significant prostate cancer. Currently, it is not possible to draw any conclusions on the superiority of these multivariable risk-based approaches since head-to-head comparisons are virtually lacking. Recently initiated large population-based screening studies in Finland, Germany and Sweden, incorporating various multivariable risk stratification approaches will hopefully give more insight in whether the harm-benefit ratio can be improved, that is, maintain (or improving) the ability to reduce metastatic disease and prostate cancer mortality while reducing harm caused by unnecessary testing and overdiagnosis including related overtreatment.
Topics: Early Detection of Cancer; Humans; Magnetic Resonance Imaging; Male; Multivariate Analysis; Precision Medicine; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Assessment
PubMed: 32394421
DOI: 10.1002/ijc.33045 -
Bioorganic & Medicinal Chemistry Letters Jun 2020Disulfiram in conjunction with copper has been shown to be a potent anticancer agent. However, disulfiram's therapeutic potential in prostate cancer is hindered by...
Disulfiram in conjunction with copper has been shown to be a potent anticancer agent. However, disulfiram's therapeutic potential in prostate cancer is hindered by off-target effects due to its reactive and nucleophilic thiol-containing component, diethyldithiocarbamate (DTC). To minimize undesirable reactivity, we have strategically blocked the thiol moiety in DTC with a cleavable p-aminobenzyl (pAB) group linked to peptide substrates recognized by prostate specific antigen (PSA). Here we report the synthesis and evaluation in cancer cell models of two PSA-activatable prodrugs: HPD (Ac-HSSKLQL-pAB-DTC and RPD (RSSYYSL-pAB-DTC). In vitro exposure to PSA was found to trigger activation of HPD and RPD to release diethyldithiocarbamate, and both prodrugs were found to induce toxicity in prostate cancer cells, with HPD showing the most promising selectivity. With copper supplementation, the IC of HPD was 1.4 µM in PSA-expressing LNCaP cells, and 11 µM in PC3 cells that do not express PSA. These studies demonstrate the utility of using peptide recognition handles to direct the activity of dithiocarbamate prodrugs for selective cytotoxicity of cancer cells.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Copper; Humans; Male; Prodrugs; Prostate-Specific Antigen; Prostatic Neoplasms; Thiocarbamates
PubMed: 32253061
DOI: 10.1016/j.bmcl.2020.127148 -
American Journal of Men's Health 2022A community-based prostate cancer screening program was conducted to assess the morbidity and associated factors for prostate cancer among the subpopulation of men aged...
A community-based prostate cancer screening program was conducted to assess the morbidity and associated factors for prostate cancer among the subpopulation of men aged ≥50 years in Taizhou, China. Taizhou Integrated Prostate Screening (TIPS) is a large, observational, population-based study of prostate cancer screening data based on serum prostate-specific antigen (PSA) concentrations. A pilot census of all male residents aged 50 years or older was conducted in Luqiao District, one of the field sites of the TIPS cohort in the city of Taizhou, Zhejiang. The interviewer-administered questionnaire evaluated demographic characteristics and environmental exposure factors. A total of 1,806 out of 3,516 participants completed the questionnaire. The overall prevalence of PSA ≥4 ng/mL was 11.5%, and included participants at low risk (9.2%), moderate risk (1.7%), and high risk (0.6%). Participants aged 60-69, 70-79, and ≥80 years had a 2.7-fold, 4.2-fold, and 6.5-fold higher risk of elevated PSA, respectively, in comparison with those aged 50 to 59 years ( < .001). Eighteen patients were diagnosed with prostate cancer, of whom 11 (61.1%) underwent radical surgery. This community-based PSA screening program indicated the results for early detection of prostate cancer among men aged ≥50 years. Early screening and appropriate clinical therapy for the management of prostate cancer are essential in this subpopulation.
Topics: Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Early Detection of Cancer; Prostate; Mass Screening
PubMed: 36412060
DOI: 10.1177/15579883221138192 -
Clinical Chemistry and Laboratory... Sep 2019Background Prostate-specific antigen (PSA) remains as the most used biomarker in the detection of early prostate cancer (PCa). Clinical practice guidelines (CPGs) are... (Review)
Review
Background Prostate-specific antigen (PSA) remains as the most used biomarker in the detection of early prostate cancer (PCa). Clinical practice guidelines (CPGs) are produced to facilitate incorporation of evidence into clinical practice. This is particularly useful when PCa screening remains controversial and guidelines diverge among different medical institutions, although opportunistic screening is not recommended. Methods We performed a systematic review of guidelines about PCa screening using PSA. Guidelines published since 2008 were included in this study. The most updated version of these CPGs was used for the evaluation. Results Twenty-two guidelines were selected for review. In 59% of these guidelines, recommendations were graded according to level of evidence (n = 13), but only 18% of the guidelines provided clear algorithms (n = 4). Each CPG was assessed using a checklist of laboratory issues, including pre-analytical, analytical, and post-analytical factors. We found that laboratory medicine specialists participate in 9% of the guidelines reviewed (n = 2) and laboratory issues were frequently omitted. We remarked that information concerning the consequences of World Health Organization (WHO) standard in PSA testing was considered by only two of 22 CPGs evaluated in this study. Conclusions We concluded that the quality of PCa early detection guidelines could be improved properly considering the laboratory issues in their development.
Topics: Clinical Laboratory Techniques; Early Detection of Cancer; Humans; Male; Mass Screening; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 31120856
DOI: 10.1515/cclm-2018-1252 -
Minerva Urology and Nephrology Feb 2021Prostate specific membrane antigen (PSMA) positron emission tomography (PET) with computed tomography (CT) is a promising molecular imaging technique for prostate cancer... (Review)
Review
Prostate specific membrane antigen positron emission tomography/computed tomography and staging high risk prostate cancer: a non-systematic review of high clinical impact literature.
INTRODUCTION
Prostate specific membrane antigen (PSMA) positron emission tomography (PET) with computed tomography (CT) is a promising molecular imaging technique for prostate cancer (PCa). Although not yet included in international guidelines, PSMA PET/CT is commonly used in clinical practice to stage patients with newly diagnosed PCa. This review focuses on the most up-to-date literature on staging high-risk prostate cancer with PSMA PET/CT.
EVIDENCE ACQUISITION
An online based literature research encompassing original studies, reviews and meta-analysis was performed in the month of November of 2019. The most relevant and impactful research was then extracted based on the expertise of the authors, with the specific focus of highlighting the clinical impact and appropriateness of PSMA PET/CT in staging PCa.
EVIDENCE SYNTHESIS
The use of PSMA PET/CT is appropriate in all high-risk patients with newly diagnosed PCa as it will often have a significant clinical impact. Although preliminary findings are promising, there is still a scarcity of data regarding the performance of PSMA PET/CT vs. other modalities in defining disease within the prostate gland. There is good evidence suggesting that PSMA PET/CT may be superior to every other imaging modality in assessing loco-regional and distant metastatic disease.
CONCLUSIONS
PSMA PET/CT has the potential to become a gold standard in staging high risk prostate cancer, providing clinicians with accurate information on the extent of disease within the prostate and the presence of loco-regional and distant metastatic disease within a single scan.
Topics: Humans; Male; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 32550630
DOI: 10.23736/S2724-6051.20.03739-X -
Journal of Cellular and Molecular... Sep 2020Current treatments including androgen deprivation fail to prevent prostate cancer (PrCa) from progressing to castration-resistant PrCa (CRPC). Accumulating evidence...
Current treatments including androgen deprivation fail to prevent prostate cancer (PrCa) from progressing to castration-resistant PrCa (CRPC). Accumulating evidence highlights the relevance of prostate-specific antigen (PSA) in the development and progression of PrCa. The underlying mechanism whereby PSA functions in PrCa, however, has yet been elucidated. We demonstrated that PSA knockdown attenuated tumorigenesis and metastasis of PrCa C4-2 cells in vitro and in vivo, whereas promoted the apoptosis in vitro. To illuminate the comprehensive role of PSA in PrCa, we performed an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to explore the proteomic change induced by PSA knockdown. Among 121 differentially expressed proteins, 67 proteins were up-regulated, while 54 proteins down-regulated. Bioinformatics analysis was used to explore the mechanism through which PSA exerts influence on PrCa. Protein-protein interaction analysis showed that PSA may mediate POTEF, EPHA3, RAD51C, HPGD and MCM4 to promote the initiation and progression of PrCa. We confirmed that PSA knockdown induced the up-regulation of MCM4 and RAD51C, while it down-regulated POTEF and EPHA3; meanwhile, MCM4 was higher in PrCa para-cancerous tissue than in cancerous tissue, suggesting that PSA may facilitate the tumorigenesis by mediating MCM4. Our findings suggest that PSA plays a comprehensive role in the development and progression of PrCa.
Topics: Cell Line, Tumor; Disease Progression; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Interaction Maps; Proteome; Proteomics; Up-Regulation
PubMed: 33107155
DOI: 10.1111/jcmm.15634 -
Lakartidningen Apr 2024Prostate-specific antigen (PSA) based screening is controversial, even though randomised trials show that screening can reduce prostate cancer mortality. The main reason... (Review)
Review
Prostate-specific antigen (PSA) based screening is controversial, even though randomised trials show that screening can reduce prostate cancer mortality. The main reason is that screening leads to overdiagnosis of indolent cancers that would never have surfaced clinically in the absence of screening. Recently, several large studies have shown that magnetic resonance imaging (MRI) improves prostate cancer diagnostics. With MRI, up to half of all men with elevated PSA values can be spared a biopsy. When a biopsy is needed, the needles can be directed towards the suspicious area in the prostate, which increases the detection of clinically significant tumors. In Sweden, regional programmes with organised prostate cancer testing were introduced in 2020. These programmes aim to make prostate cancer testing more standardized, efficient, and equitable. In the future, biomarkers and AI-based systems will likely be important to further improve prostate cancer diagnostics.
Topics: Humans; Prostatic Neoplasms; Male; Prostate-Specific Antigen; Early Detection of Cancer; Magnetic Resonance Imaging; Sweden; Mass Screening; Biopsy; Biomarkers, Tumor
PubMed: 38647107
DOI: No ID Found -
Urology Dec 2022To evaluate how blood levels of prostate-specific antigen (PSA) relate to prostate volume of benign tissue, Gleason pattern 3 (GP3) and Gleason pattern 4 (GP4) cancer.
OBJECTIVE
To evaluate how blood levels of prostate-specific antigen (PSA) relate to prostate volume of benign tissue, Gleason pattern 3 (GP3) and Gleason pattern 4 (GP4) cancer.
METHODS
The cohort included 2209 consecutive men undergoing radical prostatectomy at 2 academic institutions with pT2N0, Grade Group 1-4 prostate cancer and an undetectable postoperative PSA. Volume of benign, GP3, and GP4 were estimated. The primary analysis evaluated the association between PSA and volume of each type of tissue using multivariable linear regression. R, a measure of explained variation, was calculated using a multivariable model.
RESULTS
Estimated contribution to PSA was 0.04/0.06 ng/mL/cc for benign, 0.08/0.14 ng/mL/cc for GP3, and 0.62/0.80 ng/ml/cc for GP4 for the 2 independent cohorts, respectively. GP4 was associated with 6 to 8-fold more PSA per cc compared to GP3 and 15-fold higher compared to benign tissue. We did not observe a difference between PSA per cc for GP3 vs. benign tissue (P = 0.2). R decreased only slightly when removing age (0.006/0.018), volume of benign tissue (0.051/0.054) or GP3 (0.014/0.023) from the model. When GP4 was removed, R decreased 0.051/0.310. PSA density (PSA divided by prostate volume) was associated with volume of GP4 but not GP3, after adjustment for benign volume.
CONCLUSION
Gleason pattern 4 cancer contributes considerably more to PSA and PSA density per unit volume compared to GP3 and benign tissue. Contributions from GP3 and benign are similar. Further research should examine the utility of determining clinical management recommendations by absolute volume of GP4 rather than the ratio of GP3 to GP4.
Topics: Humans; Male; Neoplasm Grading; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms
PubMed: 35987380
DOI: 10.1016/j.urology.2022.08.014 -
The British Journal of Radiology Apr 2023Bone and soft tissue sarcomas are a group of rare malignant tumours with major histological and anatomical varieties. In a metastatic setting, sarcomas have a poor... (Review)
Review
Bone and soft tissue sarcomas are a group of rare malignant tumours with major histological and anatomical varieties. In a metastatic setting, sarcomas have a poor prognosis due to limited response rates to chemotherapy. Radioligand therapy targeting prostate-specific membrane antigen (PSMA) may offer a new perspective. PSMA is a type II transmembrane glycoprotein which is present in all prostatic tissue and overexpressed in prostate cancer. Despite the name, PSMA is not prostate-specific. PSMA expression is also found in a multitude of non-prostatic diseases including a subgroup of sarcomas, mostly in its neovascular endothelial cells. On PET/CT imaging, multiple sarcomas have also shown intense PSMA-tracer accumulation. PSMA expression and PSMA-tracer uptake seem to be highest in patients with aggressive and advanced sarcomas, who are also in highest need of new therapeutic options. Although these results provide a good rationale for the future use of PSMA-targeted radioligand therapy in a selection of sarcoma patients, more research is needed to gain insight into optimal patient selection methods, PSMA-targeting antibodies and tracers, administered doses of radioligand therapy, and their efficacy and tolerability. In this review, mRNA expression of the FOLH1 gene which encodes PSMA, PSMA immunohistochemistry, PSMA-targeted imaging and PSMA-targeted therapy in sarcomas will be discussed.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Endothelial Cells; Prostatic Neoplasms; Sarcoma; Prostate-Specific Antigen; Molecular Imaging
PubMed: 36728839
DOI: 10.1259/bjr.20220886