IMPORTANCE OF PROSTATIC SPECIFIC ANTIGEN (PSA) IN CLINICAL PRACTICE : OUR EXPERIENCE.
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ABSTRACT:
SUBMITTER: Chopra GS
PROVIDER: S-EPMC5531575 | biostudies-other | 1998 Jul
REPOSITORIES: biostudies-other
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Project description:PurposeStudies of genetic variation in the prostate-specific antigen (PSA) gene have improved the diagnostic accuracy of PSA for diagnosing prostate diseases in Caucasians. However, the reference ranges and pharmacokinetics of PSA differ significantly according to race. Therefore, we evaluated the association between genetic variations in the PSA promoter area and benign prostatic hyperplasia (BPH) phenotypes in Korean BPH patients.Materials and methodsOne hundred twenty-one men were enrolled. The initial serum PSA level, prostate size, and PSA changes at 3 months after treatment with dutasteride were determined. We amplified the promoter region of the PSA gene (nucleotide positions -158 to -356 and -5217 to -5429) and sequenced the products.ResultsThree relatively well characterized single-nucleotide polymorphisms (SNPs; rs3760722, rs266867, and rs266868), six uncharacterized SNPs (rs17554958, rs266882, rs4802754, rs2739448, rs2569733, and rs17526278), and one novel SNP (nucleotide position -5402) were found. There were no statistically significant correlations between any of the SNPs of the PSA promoter area and age-adjusted prostate sizes, initial PSA levels, or PSA variations after 3 months of dutasteride treatment.ConclusionsSNPs in the PSA promoter area were not associated with BPH phenotypes. We could not predict serum PSA changes after dutasteride treatment on the basis of PSA promoter genotype in Korean patients with BPH.
| S-EPMC3016427 | biostudies-literature
Project description:ObjectivesCross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa).Setting, participants and outcome measuresPatient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man's age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study.ResultsThe 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45-49 years to 53.0% for men aged 65-69 years (p for trend <0.001). For those with a PSA level ≥3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%, respectively).ConclusionA high proportion of men aged 45-69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa.Trial registration numberISRCTN20141297,NCT02044172.
| S-EPMC5665300 | biostudies-literature
Project description:Prostate-specific antigen (PSA or kallikrein-related peptidase-3, KLK3) exerts chymotrypsin-like proteolytic activity. The main biological function of PSA is the liquefaction of the clot formed after ejaculation by cleavage of semenogelins I and II in seminal fluid. PSA also cleaves several other substrates, which may explain its putative functions in prostate cancer and its antiangiogenic activity. We compared the proteolytic efficiency of PSA towards several protein and peptide substrates and studied the effect of peptides stimulating the activity of PSA with these substrates. An endothelial cell tube formation model was used to analyze the effect of PSA-degraded protein fragments on angiogenesis. We showed that PSA degrades semenogelins I and II much more efficiently than other previously identified protein substrates, e.g., fibronectin, galectin-3 and IGFBP-3. We identified nidogen-1 as a new substrate for PSA. Peptides B2 and C4 that stimulate the activity of PSA towards small peptide substrates also enhanced the proteolytic activity of PSA towards protein substrates. Nidogen-1, galectin-3 or their fragments produced by PSA did not have any effect on endothelial cell tube formation. Although PSA cleaves several other protein substrates, in addition to semenogelins, the physiological importance of this activity remains speculative. The PSA levels in prostate are very high, but several other highly active proteases, such as hK2 and trypsin, are also expressed in the prostate and may cleave protein substrates that are weakly cleaved by PSA.
| S-EPMC4169579 | biostudies-literature
Project description:BackgroundProstate-specific antigen (PSA) is used for diagnosing prostate cancer, but does not reflect the characteristics of prostate cancer cells to allow assessment of cancer progression. PSA mRNA and circulating tumor cells (CTCs) could be potential biomarkers. However, the relationship between serum PSA levels and PSA mRNA in CTCs is unclear, and this study aimed to investigate this relationship.MethodsHealthy donors (HD, n = 9), and patients with local non-metastatic stage prostate cancer (n = 30), metastatic hormone-sensitive prostate cancer (mHSPC, n = 10), and metastatic castration-resistant prostate cancer (mCRPC, n = 75), were included. The expression of PSA mRNA in CTCs was measured by droplet digital PCR. Serum PSA (ng/mL) levels and PSA mRNA (copies/μL) in CTCs were then compared using Spearman correlation coefficients.ResultsPSA mRNA expression in CTCs was observed in 30% (9/30) of patients with localized cancer, 60.0% (6/10) among patients with mHSPC, 65.3% (49/75) among patients with mCRPC, and 0% among patients with HD, indicating that the detection rate of PSA mRNA increased with cancer stage. PSA mRNA expression in CTCs also increased from localized to metastatic stages. PSA mRNA levels rapidly increased in the mHSPC and mCRPC stages. Interestingly, PSA mRNA expression in CTCs was not correlated with serum PSA levels at the localized stage (R = 0.064, P = 0.512). However, there were significant correlations between serum PSA levels and PSA mRNA expression in mHSPC (R = 0.532, P = 0.041) and mCRPC (R = 0.566, P = 0.025). The number of CTCs isolated from mHSPC and mCRPC was not proportional to serum PSA and PSA mRNA levels.ConclusionCTC PSA mRNA has the potential to be used as a biomarker to complement serum PSA protein analysis or replace serum PSA in metastatic stages of prostate cancer.
| S-EPMC8844604 | biostudies-literature
Project description:The prostate-specific antigen (PSA) assays currently employed for the detection of prostate cancer (PCa) lack the specificity needed to differentiate PCa from benign prostatic hyperplasia and have high false positive rates. The PSA calibrants used to create calibration curves in these assays are typically purified from seminal plasma and contain many molecular forms (intact PSA and cleaved subforms). The purpose of this study was to determine if the composition of the PSA molecular forms found in these PSA standards contribute to the lack of PSA test reliability. To this end, seminal plasma purified PSA standards from different commercial sources were investigated by western blot (WB) and in multiple research grade PSA ELISAs. The WB results revealed that all of the PSA standards contained different mass concentrations of intact and cleaved molecular forms. Increased mass concentrations of intact PSA yielded higher immunoassay absorbance values, even between lots from the same manufacturer. Standardization of seminal plasma derived PSA calibrant molecular form mass concentrations and purification methods will assist in closing the gaps in PCa testing measurements that require the use of PSA values, such as the % free PSA and Prostate Health Index by increasing the accuracy of the calibration curves.
| S-EPMC4766849 | biostudies-other
Project description:Prostate specific antigen (PSA/KLK3) is known to be the chief executor of the fragmentation of semenogelins, dissolution of semen coagulum, thereby releasing sperm for active motility. Recent research has found that semenogelins also play significant roles in sperm fertility by affecting hyaluronidase activity, capacitation and motility, thereby making PSA important for sperm fertility beyond simple semen liquefaction. PSA level in semen has been shown to correlate with sperm motility, suggesting that PSA level/activity can affect fertility. However, no study investigating the genetic variations in the KLK3/PSA gene in male fertility has been undertaken. We analyzed the complete coding region of the KLK3 gene in ethnically matched 875 infertile and 290 fertile men to find if genetic variations in KLK3 correlate with infertility. Interestingly, this study identified 28 substitutions, of which 8 were novel (not available in public databases). Statistical comparison of the genotype frequencies showed that five SNPs, rs266881 (OR = 2.92, P < 0.0001), rs174776 (OR = 1.91, P < 0.0001), rs266875 (OR = 1.44, P = 0.016), rs35192866 (OR = 4.48, P = 0.025) and rs1810020 (OR = 2.08, P = 0.034) correlated with an increased risk of infertility. On the other hand, c.206 + 235 T > C, was more freuqent in the control group, showing protective association. Our findings suggest that polymorphisms in the KLK3 gene correlate with infertility risk.
| S-EPMC5593825 | biostudies-literature
Project description:To report experience with fingolimod in clinical practice.Patients in an academic medical center who were prescribed fingolimod from October 2010 to August 2011 were identified through the electronic medical record and followed for 12 months after fingolimod initiation. Adverse effects (AEs), clinical measures, MRI data, and quality of life measures were assessed.Three hundred seventeen patients started fingolimod. Eleven patients were treatment naïve (3.5%) and 76 (24.0%) had remote disease modifying therapy (DMT) use prior to fingolimod. One hundred fifty-one (47.6%) switched because of patient preference and 79 (24.9%) switched because of breakthrough disease. About 11.6% transitioned from natalizumab. Follow-up data were available for 306 patients (96.5%) with mean follow-up time 332 days. Fingolimod was discontinued in 76 of 306 patients (24.8%) at mean 248 days after fingolimod start. Discontinuation most often was due to AEs (n = 40) or breakthrough disease (n = 22). Among patients who started fingolimod with available 12 month follow-up data, 267 (87.3%) remained relapse free and 256 (83.7%) had no relapses or gadolinium enhancement. Time to first relapse occurred at mean 282 days after fingolimod initiation. Quality of life measures remained stable at follow-up.Fingolimod was discontinued at a higher rate in clinical practice than in clinical trials. Discontinuation was primarily due to AEs or breakthrough disease. Disease activity was adequately controlled in most patients who started fingolimod. This clinical practice cohort is consistent with efficacy data from phase 3 trials and describes the most common tolerability issues in clinical practice.
| S-EPMC4414718 | biostudies-literature
Project description:ObjectiveThe influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies.MethodsConsecutive patients with a prostate-specific antigen (PSA) level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis.ResultsThe median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60-69, 70-79 and ?80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0-10.0 ng/ml to detect 90% of all PCa.ConclusionsThe effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population.
| S-EPMC4474838 | biostudies-literature
Project description:Galectin-3 is a multivalent carbohydrate-binding protein involved in cell adhesion, cell cycle control, immunomodulation, and cancer progression, including prostate cancer. Galectin-3 function is regulated by proteolytic cleavage that destroys galectin-3 multivalency while preserving carbohydrate-binding activity. In human semen, galectin-3 is present in seminal plasma and is also associated with prostasomes, exosome-like vesicles secreted by the prostate. In the current study, we characterized the proteolytic activity that cleaves galectin-3 in human seminal plasma.An in vitro assay was developed to investigate galectin-3 cleavage in seminal plasma. The effect of protease inhibitors, divalent ion chelators, and Zn(2+) on the cleavage activity was determined. Proteases enriched from seminal plasma were tested for their ability to cleave galectin-3. Affinity purification and microsequence analysis were used to identify the cleavage site in galectin-3.Galectin-3 was identified in human seminal plasma in an intact and truncated form. Gelatinases enriched from seminal plasma did not cleave galectin-3. Inhibitor studies indicated that the galectin-3 cleavage activity in seminal plasma is a Zn(2+) sensitive, serine protease. Prostate specific antigen (PSA) was demonstrated to cleave galectin-3 between tyrosine¹??-glycine¹?? and produce a functionally active, monovalent lectin.PSA is a chymotrypsin-like serine protease secreted by the prostatic epithelium and normally functions in liquefaction of semen following ejaculation. Furthermore, PSA is implicated in the promotion of localized prostate tumors and bone metastases by its roles in immunomodulation, invasion, and apoptosis. Our results indicate that PSA regulates galectin-3 in human semen and may regulate galectin-3 function during prostate cancer progression.
| S-EPMC3606048 | biostudies-literature
Project description:ObjectiveThe aim was to determine the effects of chronic intermittent hypobaric hypoxia (CIHH) on prostate-specific antigen (PSA) levels in Chilean miners who work at different altitudes.MethodsA cross-sectional study was conducted between April and July 2019. Miners from five mines (N=338) at different altitudes were evaluated. We recorded sociodemographic, working and altitude information. Haemoglobin oxygen saturation (SaO2) and haemoglobin (Hb) were measured in situ, while PSA and testosterone were analysed at a low level. Linear mixed-effect models were used to evaluate the association between PSA level and two CIHH exposures: composite CIHH (with four descriptors) and ChileStd-CIHH (CIHH Chilean standard; based on the Chilean technical guide for occupational exposure to CIHH). All models were adjusted by age, body mass index and day of the work the samples were taken.ResultsHighest and lowest PSA levels were found in mines ≥3000 m above sea level (mine 3: median=0.75, IQR=-0.45; mine 4: median=0.46, IQR=-0.35). In the multilevel models, the wider altitude difference between mining operation and camp showed lower PSA levels (model D: βPSA=-0.93 ng/mL, βlogPSA=-0.07, p<0001), adjusted for other CIHH descriptors, SaO2, Hb and testosterone. The descriptors of composite CIHH explained better PSA variations than ChileStd-CIHH (model D: marginal R2=0.090 vs model A: marginal R2=0.016).ConclusionsOccupational health regulations and high altitude medicine should consider these results as initial evidence on the inclusion of new descriptors for CIHH and the possible effect of this exposure on PSA levels in this male-dominated occupational sector.
| S-EPMC8448907 | biostudies-literature