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Clinical Drug Investigation Aug 2022Prostate carcinoma is a highly prevalent biologically and clinically diverse disease, generally associated with a consistent elevation of prostate-specific antigen... (Review)
Review
Prostate carcinoma is a highly prevalent biologically and clinically diverse disease, generally associated with a consistent elevation of prostate-specific antigen levels. Castration-resistant prostate cancer represents a heterogeneous clinical setting that ranges from patients with an asymptomatic prostate-specific antigen elevation after hormone blockade failure and good performance status to patients with significant debilitating symptoms and rapidly progressive disease, leading to death. Nonmetastatic castration-resistant prostate cancer is a transient disease stage defined over specific criteria established within a sensitive time period. The majority of the patients with nonmetastatic castration-resistant prostate cancer will eventually develop metastatic lesions, associated with prostate cancer-specific morbidity and mortality. However, progression to metastatic disease is a heterogeneous process still not fully understood, with studies suggesting that younger age, high Gleason score (> 7), high prostate-specific antigen levels, reduced prostate-specific antigen doubling time (< 6 months), and a rapid alkaline phosphatase rise as potentially associated factors. Although the nonmetastatic castration-resistant prostate cancer treatment landscape has substantially evolved in recent years, the disease heterogeneity makes treatment decisions for this population challenging in the effort to achieve a balance between the risk of disease progression and the toxicity of new treatments in patients who often have associated comorbidities, yet are generally asymptomatic. The present article addresses the current main challenges in nonmetastatic castration-resistant prostate cancer management, including in diagnosis, owing to the development of new imaging modalities with a direct impact in disease detection, prognostic classification, as a result of the traditionally oversimplified definition of disease aggressiveness (mainly based on prostate-specific antigen doubling time), and patient selection for the most adequate treatment.
Topics: Humans; Male; Neoplasm Grading; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant
PubMed: 35829924
DOI: 10.1007/s40261-022-01178-y -
Urology Journal 2011To discuss the issue of screening for prostate cancer in elderly individuals. The impact of life expectancy on the choice of treatment in both patients and health care... (Review)
Review
PURPOSE
To discuss the issue of screening for prostate cancer in elderly individuals. The impact of life expectancy on the choice of treatment in both patients and health care providers has been investigated as well.
MATERIALS AND METHODS
We identified studies published from 1990 onwards by searching the MEDLINE database of the National Library of Medicine. Initial search terms were "localized prostate cancer" and "early stage prostate cancer" combined with "elderly patients, life expectancy, palliative, curative, quality of life, watchful waiting, radical prostatectomy, brachytherapy, and external beam radiotherapy".
RESULTS
Despite the decrease in prostate carcinoma-specific mortality, the use of prostate-specific antigen (PSA) has been shown to increase the prostate cancer detection rate with a shift to detection at earlier and less invasive pathological stages, overriding concerns about over-diagnosis and over treating. However, PSA screening is mainly offered to younger individuals, and older patients are more likely to have progressive disease and high-risk prostate cancer at diagnosis. Given that PSA screening diagnoses mainly curable, early prostate cancer, screening decision could be offered to otherwise healthy elderly patients who are likely to benefit from aggressive treatment.
CONCLUSION
Prostate-specific antigen screening is not officially recommended and most scientific associations promote shared decision making. While PSA screening decision is currently based on physician's judgment, it is clear that a strict age cut-off of 75 years reduces over-screening, but also prohibits screening in healthy older men with a long life expectancy.
Topics: Age Factors; Aged; Aged, 80 and over; Humans; Life Expectancy; Male; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 21656465
DOI: No ID Found -
Swiss Medical Weekly Nov 2009
Topics: Coronary Disease; Humans; Prostate-Specific Antigen; Stents
PubMed: 19950030
DOI: 10.4414/smw.2009.12941 -
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 -
Cancer Feb 2018
Topics: Aged; Early Detection of Cancer; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 29231972
DOI: 10.1002/cncr.31140 -
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 -
BMJ Open Mar 2022The objective of our study was to use laboratory data to describe prostate-specific antigen (PSA) testing trends for primary healthcare (PHC) services from a single...
Retrospective analysis to describe trends in first-ever prostate-specific antigen (PSA) testing for primary healthcare facilities in the Gauteng Province, South Africa, between 2006 and 2016.
OBJECTIVES
The objective of our study was to use laboratory data to describe prostate-specific antigen (PSA) testing trends for primary healthcare (PHC) services from a single province. PHC is a basic package of services offered to local communities, serving as the first point of contact within the health system. These services are offered at clinics and community health centres (CHC), the latter providing additional maternity, accident and emergency services.
DESIGN
The retrospective descriptive study design was used.
METHODS
We analysed national laboratory data between 2006 and 2016 for men ≥30 years in the Gauteng Province. We used the probabilistic matching algorithm to create first-ever PSA cohort. We used the hot-deck imputation to assign missing race group values and the district health information system facility descriptors to identify PHC testing. We reported patient numbers by calendar year, age category and race group as well as descriptive statistics. We used multivariable logistic regression to assess any association for race group and age with a PSA ≥4 µg/L.
RESULTS
Between 2006 and 2016, numbers of men tested increased from 1782 to 67 025, respectively, with 186 984/239 506 (78.1%) tests were from clinics. The majority of testing was for men in the 50-59 age category (31.5%) and Black Africans (86.4%). We reported a median of 0.9 µg/L that increased with age. A PSA ≥4 µg/L was reported for 11.7% of men, increasing to 35.5% for the ≥70 age category. The logistic regression reported that the adjusted odds of having a PSA ≥4 µg/L was significantly lower for Indian/Asians, multiracials and whites than for Black Africans (p value<0.0001).
CONCLUSIONS
Our study has shown a marked increase in PSA testing from clinics and CHC suggestive of screening for prostate cancer. The approaches reported in this study can be extended for national data.
Topics: Humans; Male; Primary Health Care; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; South Africa; Adult
PubMed: 35314469
DOI: 10.1136/bmjopen-2021-050646 -
Journal of Proteomics Apr 2021Early detection of prostate cancer may lead to the overdiagnosis and overtreatment of patients as well as missing significant cancers. The current diagnostic approach...
Early detection of prostate cancer may lead to the overdiagnosis and overtreatment of patients as well as missing significant cancers. The current diagnostic approach uses elevated serum concentrations of prostate-specific antigen (PSA) as an indicator of risk. However, this test has been widely criticized as it shows poor specificity and sensitivity. In order to improve early detection and diagnosis, several studies have investigated whether different PSA proteoforms are correlated to prostate cancer. Until now, studies and methodologies for the comprehensive characterization of PSA proteoforms from biofluids are scarce. For this purpose, we developed an intact protein assay to analyze PSA by capillary electrophoresis-electrospray ionization-mass spectrometry after affinity purification from patients' urine. Here, we determined six proteolytic cleavage variants. In regard to glycosylation, tri-, di-, mono- and non-sialylated complex-type N-glycans were found on non-cleaved PSA, as well as the non-glycosylated variant. The performance of the intact protein assay was assessed using a pooled sample, obtaining an inter-day variability of 15%. Furthermore, urinary patient samples were analyzed by intact protein analysis and a bottom-up approach (glycopeptide analysis). This combined approach revealed complimentary information on both levels, demonstrating the benefit of using two orthogonal techniques to provide a thorough profile of urinary PSA. SIGNIFICANCE: The detection of clinically relevant prostate cancer requires a more specific and sensitive biomarker and, in this case, several PSA proteoforms may be able to aid or improve the current PSA test. However, a comprehensive analysis of the intact PSA proteoform profile is still lacking. This study investigated the PSA proteoforms present in urine and, in particular, determined the relative contribution of cleaved PSA and non-cleaved PSA forms to the total glycosylation profile. Importantly, intact protein analysis did not require further sample treatment before being measured by CE-ESI-MS. Furthermore, its glycosylation was also assessed in a bottom-up approach to provide complementary information. Overall, these results represent an important basis for future characterization and biomarker studies.
Topics: Electrophoresis, Capillary; Glycopeptides; Glycosylation; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 33618028
DOI: 10.1016/j.jprot.2021.104148 -
The Oncologist 2012The findings of the National Institutes of Health State-of-the-Science Conference on the role of active surveillance in the management of men with localized prostate...
The findings of the National Institutes of Health State-of-the-Science Conference on the role of active surveillance in the management of men with localized prostate cancer are examined.
Topics: Female; Humans; Male; Neoplasms; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 22302229
DOI: 10.1634/theoncologist.2012-0004 -
The International Journal of Biological... Aug 2018Total PSA (tPSA) and free PSA (fPSA) are the most commonly used biomarkers for early detection of prostate cancer. Despite standardization efforts, many available PSA...
INTRODUCTION
Total PSA (tPSA) and free PSA (fPSA) are the most commonly used biomarkers for early detection of prostate cancer. Despite standardization efforts, many available PSA assays may still produce discordant results. In the present study, we compared four PSA assays calibrated to the WHO standards 96/670 and 96/668 for tPSA and fPSA, respectively.
METHODS
Within the scope of the Prostate Cancer Early Detection Study Based on a ''Baseline'' PSA Value in Young Men (PROBASE), we tested tPSA and fPSA in serum samples from 50 patients in the four different PROBASE sites using four WHO-calibrated assays from Roche (Elecsys, Cobas), Beckman-Coulter (Access-II) and Siemens (ADVIA Centaur). The comparison was performed using the Passing-Bablok regression method.
RESULTS
Compared to Access, the median tPSA levels for Centaur, Elecsys, and Cobas were +3%, +11%-20%, and +17%-23%, respectively, while for median fPSA levels the differences for Centaur, Elecsys, and Cobas were +49%, +29%-31%, and +22%, respectively.
DISCUSSION
Despite all investigated assays being WHO-calibrated, the Elecsys and Cobas tPSA assays produced considerably higher results than the Access and Centaur assays. Differences in fPSA-recovery between all investigated assays were even more pronounced. When applying the tPSA cutoff of 3.1 μg/L recommended for WHO-calibrated assays, the use of higher calibrated assays may lead to unnecessary prostate biopsies. Conversely, if the historical threshold of 4 μg/L is applied when using WHO-calibrated assays, it could lead to falsely omitted prostate biopsies.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Early Detection of Cancer; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Reference Standards; World Health Organization
PubMed: 29734838
DOI: 10.1177/1724600818754750