Role Of PSA Research Articles

PSA controls hepatic lipid metabolism by regulating the NRF2 signaling pathway.

The activity of proteinase is reported to correlate with the development and progression of nonalcoholic fatty liver disease (NAFLD). Puromycin-sensitive aminopeptidase (PSA/NPEPPS) is an integral nontransmembrane enzyme that functions to catalyze the cleavage of amino acids near the N-terminus of polypeptides. A previous study suggested that this enzyme acts as a regulator of neuropeptide activity; however, the metabolic function of this enzyme in the liver has not been explored. Here, we identified the novel role of PSA in hepatic lipid metabolism. Specifically, PSA expression was lower in fatty livers from NAFLD patients and mice (HFD, ob/ob, and db/db). PSA knockdown in cultured hepatocytes exacerbated diet-induced triglyceride accumulation through enhanced lipogenesis and attenuated fatty acid β-oxidation. Moreover, PSA mediated activation of the master regulator of antioxidant response, nuclear factor erythroid 2-related factor 2 (NRF2), by stabilizing NRF2 protein expression, which further induced downstream antioxidant enzymes to protect the liver from oxidative stress and lipid overload. Accordingly, liver-specific PSA overexpression attenuated hepatic lipid accumulation and steatosis in ob/ob mice. Furthermore, in human liver tissue samples, decreased PSA expression correlated with the progression of NAFLD. Overall, our findings suggest that PSA is a pivotal regulator of hepatic lipid metabolism and its antioxidant function occurs by suppressing NRF2 ubiquitination. Moreover, PSA may be a potential biomarker and therapeutic target for treating NAFLD.

Prostate cancer screening and the role of PSA: A UK perspective.

Prostate cancer screening and the role of PSA: A UK perspective.

Role of PSA in Diagnosis of Chronic Prostatitis

Background: Prostatitis is the poor cousin of prostatic cancer and Benign hyperplasia. The prevalence of prostatitis in general population was estimated to be 0.5 to 14.2% in developed countries. Publishing in Iraq was concern mainly with treatment of prostatitis.Objective: This work was carried out to comment on the concept of prostatitis in clinical practice.Method: A total of 275 males was included in this study. They were complaining of urinary symptoms (frequency, urgency, hesitancy, straining, difficulty in initiation urinary stream).All cases were confirmed to have chronic prostatic after excluding prostatic carcinoma by abdominal ultrasound, free to total PSA and urinary Prostatic carcino-antigen-3. Their age was 45.6 ± 9.6 year. Urine samples were proceeded immediately after collection. Centrifuged and non-centrifuged specimen were examined.Results: PSA was affected significantly by age (p = 0.002). A significant high level was observed among those complaining of pain during ejaculation (p = 0.0001).Those showed epithelial cells in urine had significant high level of PSA (p = 0.0001). Uric acid in urine was associated with significant high level of PSA (p = 0,03).Conclusion: The diagnosis of CP / CPPS might be outside the traditional urologic practice and might consider PSA level too.

UP43 - Diagnostic performance of biparametric prostate MRI in the detection of prostate cancer: focus on role of PSA, tumor volume and ADC in PI-RADS >= 4 nodules

UP43 - Diagnostic performance of biparametric prostate MRI in the detection of prostate cancer: focus on role of PSA, tumor volume and ADC in PI-RADS >= 4 nodules

SC306 - Diagnostic performance of biparametric prostate MRI in the detection of prostate cancer: Focus on role of PSA, tumor volume and ADC in PI-RADS ≥ 4 nodules

SC306 - Diagnostic performance of biparametric prostate MRI in the detection of prostate cancer: Focus on role of PSA, tumor volume and ADC in PI-RADS ≥ 4 nodules

ST8SIA4-Dependent Polysialylation is Part of a Developmental Program Required for Germ Layer Formation from Human Pluripotent Stem Cells.

Polysialic acid (PSA) is a carbohydrate polymer of repeating α-2,8 sialic acid residues that decorates multiple targets, including neural cell adhesion molecule (NCAM). PST and STX encode the two enzymes responsible for PSA modification of target proteins in mammalian cells, but despite widespread polysialylation in embryonic development, the majority of studies have focused strictly on the role of PSA in neurogenesis. Using human pluripotent stem cells (hPSCs), we have revisited the developmental role of PST and STX and show that early progenitors of the three embryonic germ layers are polysialylated on their cell surface. Changes in polysialylation can be attributed to lineage-specific expression of polysialyltransferase genes; PST is elevated in endoderm and mesoderm, while STX is elevated in ectoderm. In hPSCs, PST and STX genes are epigenetically marked by overlapping domains of H3K27 and H3K4 trimethylation, indicating that they are held in a "developmentally-primed" state. Activation of PST transcription during early mesendoderm differentiation is under control of the T-Goosecoid transcription factor network, a key regulatory axis required for early cell fate decisions in the vertebrate embryo. This establishes polysialyltransferase genes as part of a developmental program associated with germ layer establishment. Finally, we show by shRNA knockdown and CRISPR-Cas9 genome editing that PST-dependent cell surface polysialylation is essential for endoderm specification. This is the first report to demonstrate a role for a glycosyltransferase in hPSC lineage specification. Stem Cells 2016;34:1742-1752.

315 Prospective randomized controlled study of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening program for early diagnosis of prostate cancer

315 Prospective randomized controlled study of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening program for early diagnosis of prostate cancer

Abstract 262: The PROFILE feasibility study: Genetic prostate cancer risk stratification for targeted screening

Abstract Introduction & Objectives: Prostate cancer (PC) screening is controversial and a better assessment of individualized PC risk is needed. Several single nucleotide polymorphisms (SNPs) conferring a cumulative risk of PC have been identified. We have explored the potential role of genetic markers for targeted screening in a population with increased risk of PC due to family history (FH). Material & Methods: PROFILE was developed as a pilot study to determine the feasibility of targeted PC screening using prostatic biopsy (PB) and its association with specific genetic profiles in men with FH. We also evaluated the role of PSA and Diffusion Weighted MRI (DW-MRI) as screening tools. 116 men aged 40-69 with FH of PC were enrolled between October 2009 and December 2012. Cumulative SNP risk scores were calculated by summing 59 risk alleles for each locus using the weighted effect (log-additive model). DW-MRI was performed in 50 patients. Participants were asked to undergo a 10 core PB regardless of baseline PSA. Results: Median age 53 yrs (40-69) and median PSA was 1.15. One hundred and two men accepted to undergo a PB as primary PC screening. Twenty-three tumours were found (22.5% of biopsies) as well as seven men diagnosed with atypical small acinar proliferation (ASAP) (6.8%) and 8 men with high-grade prostatic intraepithelial neoplasia (HG-PIN) (7.8%). In total 37.1% received an abnormal result. Of those diagnosed with PC, 41% were intermediate or high risk and required treatment (compared to 24% in general population screening). The predictive performance of DW-MRI, PSA, genetic model and genetic model plus PSA measured by AUC were: 0.85, 0.73, 0.57 and 0.74, respectively. The genetic model performed best in men with a ‘normal’ PSA (<3 ng/ml - AUC 0.63). Analyses of a 78 SNP profile incorporating the new 23 recently identified SNPs is underway. Conclusions: Our results indicate that PB used for PC screening in men with FH of PC identified a higher proportion of clinically significant PCs. The high AUC for DW-MRI would warrant a larger study. The incidence of ASAP is higher in this group than the general population.The SNP risk score was more predictive in men with PSA<3 where PB would not normally be undertaken, therefore an expanded study to investigate the role of genetic profiling in directing PB in PC screening is indicated. Citation Format: Rosalind Eeles, Zsofia Kote-Jarai, Antonis Antoniou, Pardeep Kumar, Christos Mikropoulos, Tokhir Dadaev, Natalie Taylor, Elizabeth Bancroft. The PROFILE feasibility study: Genetic prostate cancer risk stratification for targeted screening. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 262. doi:10.1158/1538-7445.AM2014-262

The PROFILE feasibility study: Genetic prostate cancer risk stratification for targeted screening.

22 Background: Prostate cancer (PC) screening is controversial and a better assessment of individualized PC risk is needed. Several single nucleotide polymorphisms (SNPs) conferring a cumulative risk of PC have been identified. We have explored the potential role of genetic markers for targeted screening in a population with increased risk of PC due to family history (FH). Methods: PROFILE was developed as a pilot study to determine the feasibility of targeted PC screening using prostatic biopsy (PB) and its association with specific genetic profiles in men with FH. We also evaluated the role of PSA and Diffusion Weighted MRI (DW-MRI) as screening tools. One hundred sixteen men age 40 to 69 with FH of PC were enrolled between October 2009 and December 2012. Cumulative SNP risk scores were calculated by summing 59 risk alleles for each locus using the weighted effect (log-additive model). DW-MRI was performed in 50 patients. Participants were asked to undergo a 10 core PB regardless of baseline PSA. Results: Median age 53 (40 to 69) and median PSA was 1.15. One hundred and two men accepted to undergo a PB as primary PC screening. Twenty-three tumours were found (22.5% of biopsies) as well as seven men diagnosed with atypical small acinar proliferation (ASAP) (6.8%) and eight men with high-grade prostatic intraepithelial neoplasia (HG-PIN) (7.8%). In total 37.1% received an abnormal result. Out of the diagnosed PC 41% were intermediate or high risk and requiring treatment, which compares with 24% in general population screening. The predictive performance of DW-MRI, PSA, genetic model and genetic model plus PSA measured by AUC were: 0.85, 0.73, 0.57 and 0.74, respectively. The genetic model performed best in men with a normal PSA of <3(AUC 0.63). Analyses of a 78 SNP profile from the recent COGS results are underway. Conclusions: Ourresults indicate that PB is acceptable for PC screening in men with FH of PC. The significant AUC for DW-MRI would warrant a larger study. The incidence of ASAP is higher in this group than the general population.The SNP risk score was more predictive in men with PSA less than three where PB would not normally be undertaken, therefore an expanded study to investigate the role of genetic profiling in directing PB in PC screening is indicated.

Cancer de la prostate : les niveaux de preuve des biomarqueurs de la détection précoce

As part of an overall review on the role of PSA and other emerging biomarkers in the detection, diagnosis and treatment of prostate cancer, we present here a part of a review of the literature made by the working group Biologie de la Prostate (AFU, CNBH, SFBC, SFMN) on the use of PSA and other biomarkers in the early detection of prostate cancer with an assessment of the level of evidence.

Recommandations en onco-urologie 2013 du CCAFU : Cancer de la prostate

IntroductionThe sub Comittee prostate of the CCAFU established guidelines for diagnostic, treatment, evaluation and standart of care of prostate cancer. MethodsGuidelines 2010 were updated based on systematic literature search performed by the sub-Comittee in Medline and PubMed databases to evaluate references, levels of evidence and grade of recommandation. ResultsPathological examination of the tissue specimens was defined specifically for Gleason score according to ISP 2005 recommandations. Prostate and pelvis RMN became the reference in terms of radiological exam. Individual and early diagnosis of prostate cancer was defined and role of PSA was precised. Active surveillance became one of the standart of care of low-risk tumors, radical prostatectomy remained one of the options for all risk group tumors, length of hormonotherapy in association with radiotherapy was precised according to the risk group. Side effects of hormonotherapy treament needed specific supervision ; hormonotherapy had no indication in case of non metastatic tumors and intermittent hormonotherapy in metastatic tumors. New hormonal drugs in pre and post chemotherapy and bone target drugs opened new therapeutics pathways. ConclusionFrom 2010 to 2013, standarts of care of prostate cancer were modified because of results of prospective studies and new therapeutics. They allowed precise treatments for each specific clinical situation. In the future, multidisciplinary treatments for high risk tumors, time of adjuvant treatment and sequencies of new hormonal treatment had to be defined.

Profile study: Genetic prostate cancer risk stratification for targeted screening.

5054 Background: Prostate cancer (PC) screening is controversial and better approaches are needed, including a better assessment of individualized PC risk. Several studies have identified a number of common single nucleotide polymorphisms (SNPs) that confer a cumulative risk of PC. We have explored the potential role of genetic markers in identifying men who should be selectively targeted for screening in a population with increased risk of PC due to family history (FH) of the disease. Methods: PROFILE has been developed as a pilot study. The primary aim is to determine the feasibility of targeted PC screening using prostatic biopsy (PB) and its association with specific genetic profiles in men with FH. Secondary aims are to evaluate the role of PSA and Diffusion Weighted MRI (DW-MRI) as screening tools in this population. From December 2010 men aged 40-69 with FH of PC were invited into the study until 100 men were enrolled. Blood samples were provided for PSA and DNA extraction. The cumulative SNP risk scores for each patient were calculated by summing 59 risk alleles for each locus using the weighted effect as estimated in previous studies (log-additive model). DW-MRI was performed in 50 patients. All participants were asked to undergo a 10 core PB regardless of baseline PSA. Those who declined PB have been excluded from this analysis. Data on side effects and cancer worry were also collected. Results: 35% of invited men entered the study. Median age was 53 yrs (40-69) and median PSA was 1.15. Ninety men accepted to undergo a PB as primary PC screening. Twenty-two tumours were found and 45% of them were clinically significant [Median age 64yrs (47-69), median PSA 5.4 (0.91-9.3)]. The predictive performance of DW-MRI, PSA, genetic model and genetic model plus PSA measured by AUC were: 0.85, 0.73, 0.57 and 0.74, respectively. The genetic model performed better in men with PSA<3(AUC 0.63). No severe side effect or adverse psychosocial variables were noted. Conclusions: Our results indicate that PB is acceptable as a means of PC screening in men with FH of PC. Overall, DW-MRI and PSA were more predictive of PC than the genetic risk score. As more SNPs are found, a larger study is warranted to evaluate their role in the PC screening algorithm.

10 Prospective randomized controlled trial of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening programme for prostate cancer

10 Prospective randomized controlled trial of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening programme for prostate cancer

P051 Prospective randomized controlled trial of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening programme for prostate cancer

P051 Prospective randomized controlled trial of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening programme for prostate cancer

Abstract 2828: Characterization of protein substrates of PSA: effect of PSA stimulating peptides

Abstract Increased proteolytic activity is associated with cancer, where proteases play a major role in tumor spread and formation of metastases. However, proteases may also inhibit tumor growth. The prostate produces several proteases, the most abundant one being prostate-specific antigen (PSA or kallikrein-related peptidase-3, KLK3). The role of PSA in the prostate, and in particular in prostate cancer, is not well known. However, several functions have been proposed, most of which are based on the protein substrates, which PSA cleaves in vitro. These include both tumor growth promoting and inhibiting activities, e.g., antiangiogenic activity of PSA. We have previously used phage display technology to develop peptides, the synthetic analogs of which stimulate the activity of PSA. These peptides are useful for studying the significance of PSA-activity and potentially for prostate cancer treatment. We analyzed the cleavage of different protein substrates of PSA and found that physiological substrates, semenogelin-1 and −2, are cleaved much more efficiently than other substrates, such as IGFBP-3, fibronectin and galectin-3. The peptides increased the proteolytic activity of PSA towards these protein substrates, but the extent of stimulation and the relative efficiency of peptides were different than with small peptide substrates. We conclude that the peptides can be used to stimulate the activity of PSA towards natural protein substrates. Thus, they may be potential lead molecules for drug development. As most of the studied protein substrates are cleaved with very low efficiency, their relevance as PSA substrates is questionable, especially as prostate produces several other highly active proteases, including several kallikreins and trypsin. As compared to other substrates, semenogelins are very efficiently cleaved by PSA, highlighting the substrate specificity of PSA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2828. doi:1538-7445.AM2012-2828

P108 Phenotypic changes in Pseudomonas aeruginosa (Psa) populations during exacerbations in adult Cystic Fibrosis patients infected with non-epidemic strains

BackgroundChronic infection with Psa in most CF patients is due to single unique strains, which over time accumulate mutations resulting in mucoid conversion, loss of motility, auxotrophy and increased antibiotic...

Fast Facts: Benign Prostatic Hyperplasia (sixth edition)

1 2 3 8 B J U I N T E R N A T I O N A L © 2 0 1 0 B J U I N T E R N A T I O N A L | 1 0 6 , 1 2 3 8 | doi:10.1111/j.1464-410X.2010.09783.x covers, with the appropriate level of detail, all aspects of BPH starting with a well-illustrated chapter on the pathophysiology. The second chapter tackles diagnosis, including relevant aspects of history, physical examination and investigations. There is an important discussion on the role of PSA including an upto-date summary on the screening debate. The chapter concludes with a guideline algorithm for the basic management of LUTS in men. Management of BPH is divided into three further chapters. Chapter three addresses medical management and includes the latest data on 5 α -reductase inhibitors and combined therapy in addition to the wellestablished α -blockers and other medical options. Traditional surgical treatments are described in chapter four with emphasis on complications and outcomes as well as more recent modifications such as bipolar appliances and resection in saline. Chapter five deals with minimally invasive treatment options, most of which are still in their infancy and are regarded as investigational. The penultimate chapter addresses considerations that influence treatment decisions; with excellent tables summarising and comparing outcomes and adverse effects of the different treatments. The closing chapter briefly outlines future issues and trends.

UP-1.121: The Role of PSA in Diagnosis of Prostate Cancer: Does the Predictive Value of PSA Changes for the Secondary Prostate Biopsy?

UP-1.121: The Role of PSA in Diagnosis of Prostate Cancer: Does the Predictive Value of PSA Changes for the Secondary Prostate Biopsy?

Role of PSA as a predictor of bone metastases among the different racial groups with prostate cancer in KwaZulu Natal, South Africa

Journal of Men's HealthVol. 6, No. 3 WCMH AbstractsRole of PSA as a predictor of bone metastases among the different racial groups with prostate cancer in KwaZulu Natal, South Africa22E.H. Abdel Goad and Poovan GovenderE.H. Abdel GoadSearch for more papers by this author and Poovan GovenderSearch for more papers by this authorPublished Online:21 Nov 2013https://doi.org/10.1016/j.jomh.2009.08.024AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Role of PSA as a predictor of bone metastases among the different racial groups with prostate cancer in KwaZulu Natal, South Africa." Journal of Men's Health, 6(3), p. 234FiguresReferencesRelatedDetails Volume 6Issue 3Sep 2009 InformationWPMH GmbHTo cite this article:E.H. Abdel Goad and Poovan Govender.Role of PSA as a predictor of bone metastases among the different racial groups with prostate cancer in KwaZulu Natal, South Africa.Journal of Men's Health.Sep 2009.234-234.http://doi.org/10.1016/j.jomh.2009.08.024Published in Volume: 6 Issue 3: November 21, 2013PDF download

UP-03.13: The role of PSA in predicting TURP specimen weight

UP-03.13: The role of PSA in predicting TURP specimen weight