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Sample records for antigen psa failure

  1. PSA Nadir of <0.5 ng/mL Following Brachytherapy for Early-Stage Prostate Adenocarcinoma is Associated With Freedom From Prostate-Specific Antigen Failure

    SciTech Connect

    Ko, Eric C.; Stone, Nelson N.; Stock, Richard G.

    2012-06-01

    Purpose: Because limited information exists regarding whether the rate or magnitude of PSA decline following brachytherapy predicts long-term clinical outcomes, we evaluated whether achieving a prostate-specific antigen (PSA) nadir (nPSA) <0.5 ng/mL following brachytherapy is associated with decreased PSA failure and/or distant metastasis. Methods and Materials: We retrospectively analyzed our database of early-stage prostate adenocarcinoma patients who underwent brachytherapy, excluding those receiving androgen-deprivation therapy and those with <2 years follow-up. Median and mean pretreatment PSA were 6 ng/mL and 7.16 ng/mL, respectively. By clinical stage, 775 were low risk ({<=}T2a), 126 were intermediate risk (T2b), and 20 were high risk (>T2b). By Gleason score, 840 were low risk ({<=}6), 71 were intermediate risk (7), and 10 were high risk (>7). Patients were treated with brachytherapy only (I-125, n = 779, or Pd-103, n = 47), or brachytherapy + external-beam radiation therapy (n = 95). Median follow-up was 6.3 years. We noted whether nPSA <0.5 ng/mL was achieved and the time to achieve this nadir and tested for associations with pretreatment risk factors. We also determined whether this PSA endpoint was associated with decreased PSA failure or distant metastasis. Results: Absence of high-risk factors in clinical stage ({<=}T2b), Gleason score ({<=}7), and pretreatment PSA ({<=}20 ng/mL) was significantly associated with achieving nPSA <0.5 ng/mL. By Kaplan-Meier analysis, patients achieving nPSA <0.5 ng/mL had significantly higher long-term freedom from biochemical failure (FFBF) than nonresponders (5-year FFBF: 95.2 {+-} 0.8% vs. 71.5 {+-} 6.7%; p < 0.0005). Among responders, those who achieved nPSA <0.5 ng/mL in {<=}5 years had higher FFBF than those requiring >5 years (5-year FFBF: 96.7 {+-} 0.7% vs. 80.8 {+-} 4.6%; p < 0.0005). On multivariate analysis, patients who achieved nPSA <0.5 ng/mL in {<=}5 years had significantly higher FFBF than other

  2. Prostate-specific antigen (PSA) blood test

    MedlinePlus

    Prostate-specific antigen; Prostate cancer screening test; PSA ... special steps are needed to prepare for this test. ... Reasons for a PSA test: This test may be done to screen for prostate cancer. It is also used to follow people after prostate cancer ...

  3. Association between polymorphisms in the prostate-specific antigen (PSA) promoter and release of PSA.

    PubMed

    Sävblom, C; Giwercman, A; Malm, J; Halldén, C; Lundin, K; Lilja, H; Giwercman, Y

    2009-10-01

    Variations in serum prostate-specific antigen (PSA) have been ascribed to A/G nucleotide polymorphisms located at -158 bp (rs266882) and -4643 bp (rs925013), relative to the transcription start site within the promoter of the PSA gene. PSA is also an androgen receptor target (AR) gene and polymorphisms in AR gene are known to affect AR function. Our objective was to compare the impact of these A/G polymorphisms separately or in combination with AR CAG micro satellite on regulation of PSA secretion into seminal plasma and blood in young men. Leukocyte DNA was extracted from 291 conscripts and genotyping performed with the Sequenom Mass Array System. PSA was measured with an immunofluorometric assay. Linear regression analysis was used to test the association of polymorphism frequencies with serum and seminal plasma levels of PSA. PSA gene polymorphisms at -158 bp or -4643 bp did not alone influence total PSA (tPSA) levels in seminal plasma or in blood. Homozygotes for the A-allele at -158 bp in combination with CAG > 22 had significantly higher serum levels of tPSA than subjects carrying the G-allele (p = 0.01). In conclusion, the PSA gene polymorphisms did not importantly influence the levels of tPSA in seminal plasma or in blood. tPSA in serum was influenced by interactions between PSA promoter variants and AR CAG polymorphism.

  4. Prostate-Specific Antigen (PSA) Test

    MedlinePlus

    ... prostate cancer recurrence. However, a single elevated PSA measurement in a patient who has a history of ... than with BPH . One recently approved test combines measurement of a form of pro-PSA called [-2] ...

  5. Opium consumption is negatively associated with serum prostate-specific antigen (PSA), free PSA, and percentage of free PSA levels.

    PubMed

    Safarinejad, Mohammad Reza; Asgari, Seyyed Alaeddin; Farshi, Alireza; Iravani, Shahrokh; Khoshdel, Alireza; Shekarchi, Babak

    2013-01-01

    Addiction to opium continues to be a major worldwide medical and social problem. The study addressing the association between opium consumption and serum prostate-specific antigen (PSA) level is lacking. We determined the effects of opium consumption on serum PSA levels in opium-addict men. Our study subjects comprised 438 opium-addict men with a mean age of 52.2 ± 6.4 years (group 1). We compared these men with 446 men who did not indicate current or past opium use (group 2). Serum total PSA (tPSA), free PSA (fPSA), % fPSA, and sex hormones were compared between the 2 groups. The mean serum tPSA level was significantly lower in group 1 (1.05 ng/mL) than in controls (1.45 ng/mL) (P = 0.001). Opium consumption was also associated with lower fPSA (P = 0.001) and % fPSA (P = 0.001). Serum free testosterone level in opium-addict patients (132.5 ± 42 pg/mL) was significantly lower than that in controls (156.2 ± 43 pg/mL) (P = 0.03). However, no significant correlation existed between tPSA and free testosterone levels (r = 0.28, 95% CI, -0.036 to 0.51, P = 0.34). Among the patients with cancer in group 1, 35% were found to have high-grade tumor (Gleason score ≥ 7) compared with 26.7% in group 2 (P = 0.02). Total PSA and fPSA were strongly correlated with duration of opium use (r = -0.06, 95% CI, -0.04 to -0.08, P = 0.0001; and r = -0.05, 95% CI, -0.03 to -0.07, P = 0.0001, respectively). Opium consumption is independently and negatively associated with serum tPSA, fPSA, and % fPSA levels.

  6. Re-examining Prostate-specific Antigen (PSA) Density: Defining the Optimal PSA Range and Patients for Using PSA Density to Predict Prostate Cancer Using Extended Template Biopsy.

    PubMed

    Jue, Joshua S; Barboza, Marcelo Panizzutti; Prakash, Nachiketh S; Venkatramani, Vivek; Sinha, Varsha R; Pavan, Nicola; Nahar, Bruno; Kanabur, Pratik; Ahdoot, Michael; Dong, Yan; Satyanarayana, Ramgopal; Parekh, Dipen J; Punnen, Sanoj

    2017-07-01

    To compare the predictive accuracy of prostate-specific antigen (PSA) density vs PSA across different PSA ranges and by prior biopsy status in a prospective cohort undergoing prostate biopsy. Men from a prospective trial underwent an extended template biopsy to evaluate for prostate cancer at 26 sites throughout the United States. The area under the receiver operating curve assessed the predictive accuracy of PSA density vs PSA across 3 PSA ranges (<4 ng/mL, 4-10 ng/mL, >10 ng/mL). We also investigated the effect of varying the PSA density cutoffs on the detection of cancer and assessed the performance of PSA density vs PSA in men with or without a prior negative biopsy. Among 1290 patients, 585 (45%) and 284 (22%) men had prostate cancer and significant prostate cancer, respectively. PSA density performed better than PSA in detecting any prostate cancer within a PSA of 4-10 ng/mL (area under the receiver operating characteristic curve [AUC]: 0.70 vs 0.53, P < .0001) and within a PSA >10 mg/mL (AUC: 0.84 vs 0.65, P < .0001). PSA density was significantly more predictive than PSA in detecting any prostate cancer in men without (AUC: 0.73 vs 0.67, P < .0001) and with (AUC: 0.69 vs 0.55, P < .0001) a previous biopsy; however, the incremental difference in AUC was higher among men with a previous negative biopsy. Similar inferences were seen for significant cancer across all analyses. As PSA increases, PSA density becomes a better marker for predicting prostate cancer compared with PSA alone. Additionally, PSA density performed better than PSA in men with a prior negative biopsy. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Predictors of mortality after prostate-specific antigen failure

    SciTech Connect

    D'Amico, Anthony V. . E-mail: adamico@lroc.harvard.edu; Kantoff, Phillip; Loffredo, Marian; Renshaw, Andrew A.; Loffredo, Brittany; Chen Minghui

    2006-07-01

    Purpose: We identified factors associated with the length of survival after prostate-specific antigen (PSA) failure. Methods and Materials: The study cohort comprised 81 of 206 men enrolled on a randomized trial evaluating external-beam radiation therapy (RT) with or without androgen suppression therapy (AST) and who experienced PSA failure. Salvage AST was administered at a PSA level of {approx}10 ng/mL as per protocol. Cox regression was used to determine factors associated with length of survival after PSA failure. Results: A PSA DT (doubling time) <6 months (p = 0.04) and age at the time of PSA failure (p = 0.009) were significantly associated with length of survival. By 5 years, 35% and 65% of all-cause mortality was from prostate cancer in men whose age at PSA failure was 75 or higher vs. <75, respectively. Across all ages, 0%, 4%, as compared with 63% of men, were estimated to die of prostate cancer within 5 years after PSA failure if their PSA DT was >12, 6-12, or <6 months, respectively. Conclusions: Advanced age and a PSA DT <6 months at the time of PSA failure are associated with a significantly shorter survival.

  8. Molecular Form Differences Between Prostate-Specific Antigen (PSA) Standards Create Quantitative Discordances in PSA ELISA Measurements

    PubMed Central

    McJimpsey, Erica L.

    2016-01-01

    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. PMID:26911983

  9. Molecular Form Differences Between Prostate-Specific Antigen (PSA) Standards Create Quantitative Discordances in PSA ELISA Measurements

    NASA Astrophysics Data System (ADS)

    McJimpsey, Erica L.

    2016-02-01

    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.

  10. PSA nadir predicts biochemical and distant failures after external beam radiotherapy for prostate cancer: A multi-institutional analysis

    SciTech Connect

    Ray, Michael E. . E-mail: mray@umich.edu; Thames, Howard D.; Levy, Larry B.; Horwitz, Eric M.; Kupelian, Patrick A.; Martinez, Alvaro A.; Michalski, Jeff M.; Pisansky, Thomas M.; Shipley, William U.; Zelefsky, Michael J.; Zietman, Anthony L.; Kuban, Deborah A.

    2006-03-15

    Purpose: To determine the significance of prostate-specific antigen (PSA) nadir (nPSA) and the time to nPSA (T{sub nPSA}) in predicting biochemical or clinical disease-free survival (PSA-DFS) and distant metastasis-free survival (DMFS) in patients treated with definitive external beam radiotherapy (RT) for clinical Stage T1b-T2 prostate cancer. Methods and Materials: Nine participating institutions submitted data on 4839 patients treated between 1986 and 1995 for Stage T1b-T2cN0-NxM0 prostate cancer. All patients were treated definitively with RT alone to doses {>=}60 Gy, without neoadjuvant or planned adjuvant androgen suppression. A total of 4833 patients with a median follow-up of 6.3 years met the criteria for analysis. Two endpoints were considered: (1) PSA-DFS, defined as freedom from PSA failure (American Society for Therapeutic Radiology and Oncology definition), initiation of androgen suppression after completion of RT, or documented local or distant failure; and (2) DMFS, defined as freedom from clinically apparent distant failure. In patients with failure, nPSA was defined as the lowest PSA measurement before any failure. In patients without failure, nPSA was the lowest PSA measurement during the entire follow-up period. T{sub nPSA} was calculated from the completion of RT to the nPSA date. Results: A greater nPSA level and shorter T{sub nPSA} were associated with decreased PSA-DFS and DMFS in all patients and in all risk categories (low [Stage T1b, T1c, or T2a, Gleason score {<=}6, and PSA level {<=}10 ng/mL], intermediate [Stage T1b, T1c, or T2a, Gleason score {<=}6, and PSA level >10 but {<=}20 ng/mL, or Stage T2b or T2c, Gleason score {<=}6, and PSA level {<=}20 ng/mL, or Gleason score 7 and PSA level {<=}20 ng/mL], and high [Gleason score 8-10 or PSA level >20 ng/mL]), regardless of RT dose. The 8-year PSA-DFS and DMFS rate for patients with nPSA <0.5 ng/mL was 75% and 97%; nPSA {>=}0.5 but <1.0 ng/mL, 52% and 96%; nPSA {>=}1.0 but <2.0 ng/mL, 40

  11. PSA bounces after neoadjuvant androgen deprivation and external beam radiation: Impact on definitions of failure

    SciTech Connect

    Zietman, Anthony L. . E-mail: azietman@partners.org; Christodouleas, John P.; Shipley, William U.

    2005-07-01

    Purpose: To determine the characteristics of prostate specific antigen (PSA) bounces after external beam radiation therapy (EBRT) with neoadjuvant androgen deprivation and their impact on definitions of biochemical failure. Methods and Materials: Characteristics of bounce were calculated for all patients treated by EBRT with neoadjuvant androgen deprivation at our institution between 1992 and 1998 (preexclusion analysis). Calculations were repeated for the subgroup that satisfied additional inclusion/exclusion criteria (postexclusion analysis). The percentage of bounces scoring as false positives according to the ASTRO definition of biochemical failure was compared with those for three alternative definitions (Vancouver, Nadir-plus-two, and Nadir-plus-three) using McNemar's tests. Results: Thirty-nine percent (preexclusion cohort) and 56% (postexclusion cohort) of patients demonstrated a PSA bounce. Twenty percent (preexclusion analysis) and 25% (postexclusion analysis) of these bounces scored as biochemical failure according to the ASTRO definition. The Nadir-plus-three definition scored the smallest percentage of bounces as failure, but the difference between this definition and the ASTRO definition reached statistical significance in neither preexclusion nor postexclusion analyses (p {>=} 0.070). Conclusions: A substantial proportion of patients treated by EBRT with neoadjuvant deprivation experienced a PSA bounce. A large percentage of these bounces scored as biochemical failure according to the ASTRO definition. The Nadir-plus-three definition is less vulnerable to this bias.

  12. A population study of fasting time and serum prostate-specific antigen (PSA) level.

    PubMed

    Lau, Cheryl K; Guo, Maggie; Viczko, Jeannine A; Naugler, Christopher T

    2014-01-01

    Prostate cancer is one of the most common cancers in men. Traditional screening and diagnostic methods include digital rectal examinations (DREs), biopsies and serum prostate-specific antigen (PSA) tests, with the latter being the more popular. PSA is a biomarker for prostate cancer; however, it is highly sensitive to external factors as well as other prostate diseases. As such, the reliability of of the serum PSA level as a sole screening and diagnostic tool for prostate cancer is controversial. Recently, it has been shown that fasting extremes can affect concentrations of serum chemistry analytes, thus raising the question of whether or not fasting has an effect on the highly sensitive PSA biomarker. Patients testing for serum PSA levels are often concomitantly submitting to other tests that require fasting, subjecting certain patients to a fasting PSA level while others not. The objective of this study was to investigate whether this discrepancy in fasting state translates into an effect on serum PSA levels. Serum PSA levels and fasting time records for 157 276 men who underwent testing at Calgary Laboratory Services (CLS; Calgary, Alberta, Canada) between 01 January 2010 and 31 March 2013 were accessed. Linear regression models of mean PSA levels and fasting times revealed a statistically important relationship at certain fasting times. Applying a dynamic mathematical model to explore the clinical effect of fasting suggests minimal impact on serum PSA result interpretation. Thus, patients can be tested for serum PSA levels regardless of their fasting state.

  13. Free and complexed prostate-specific antigen (PSA) in the early detection of prostate cancer.

    PubMed

    Tello, F L; Prats, C H; González, M D

    2001-02-01

    We evaluated the analytical performance and diagnostic utility of complexed prostate-specific antigen (CPSA) and their ratios, complexed-to-total PSA (C/T PSA) and free-to-complexed PSA (F/C PSA), in comparison with the total PSA (TPSA) and free-to-total PSA ratio (F/T PSA) as means of diagnosing prostate cancer (PC). Samples (n=101) were drawn from men with no evidence of malignancy (n=80) and from men with PC (n=21) at biopsy. For determination of the F/T PSA ratio, the DPC Immulite-2000 method was used; and the Bayer Immuno-1 CPSA and TPSA assays were used to determine the C/T PSA ratio. The Bayer Immuno-1 CPSA assay provides accurate and precise CPSA values in human serum. The performance of the different forms and ratios was compared using receiver operating characteristic curve analysis. CPSA had the greatest area under the curve (AUC, 0.689) although it was not statistically different from the other parameters. A cut-off value of 4.66 ng/ml for CPSA provided a specificity of 38% and a sensitivity of 93%. The F/C PSA ratio maintained a sensitivity of 93% and had an increased specificity of 41%. The measurement of CPSA provides a slight increase in specificity compared with the use of the TPSA in the early detection of prostate cancer.

  14. [Use of prostatic specific antigen in primary care (PSA)].

    PubMed

    Panach-Navarrete, J; Gironés-Montagud, A; Sánchez-Cano, E; Doménech-Pérez, C; Martínez-Jabaloyas, J M

    2017-04-01

    In the literature it is shown that the use of PSA is occasionally wrong, by requesting this marker in very young or very old men, and repeated measurements in short periods of time. The main objective of this study was to describe the use of PSA in daily practice by primary care physicians in our area, dealing with aspects such as the importance of patient age, the value in the screening for prostate cancer, or the subjective beliefs about its usefulness. A secondary objective was the comparison of use, and beliefs among doctors who claim to know PSA well, and those who do not. A descriptive and comparative study was conducted using questionnaires that were handed to primary care doctors in all health centres in our area. A descriptive analysis was performed and response rates among doctors who thought they had enough information about PSA, and those who did not, were compared using the Chi-squared test. A total of 103 questionnaires were received from the physicians, with 83.5% claiming to have sufficient knowledge about the PSA. The professionals in this latter group request PSA at an earlier age (P=.029), with a higher frequency (P=.011) and have more doubts about its usefulness (P=.009) than those with less knowledge. Almost half (49.5%) said they request less than 50 determinations per year, and 33% between 50 and 100. More than half (53.4%) of doctors would not request the first PSA on a patient until their 50s, and up to 49% request it up to 80 years. The true value of PSA has been established many times by 64.1% of requesters, and 29.1% believe it is unhelpful in the diagnosis of cancer. In our study, 64% of primary care physicians have considered the true value of the PSA several times, and 29% believe it to be of little use in the diagnosis of prostate cancer. In addition, some data suggest it has limited use due to the fact that 50% made less than 50 PSA requests per years, and 28% of the professionals would never request it on a male without urinary

  15. A Diet, Physical Activity, and Meditation Intervention in Men With Rising Prostate-Specific Antigen (PSA)

    DTIC Science & Technology

    2005-05-01

    prostate cancer ( PrCA ), one in three patients will experience an elevation in serum prostate antigen (PSA) within 10 years. This rises to one in two...at 15 years. After such evidence of recurrence, the most common treatment is androgen ablation. We hypothesize that the host- PrCA balance in...asymptomatic men with biochemically recurrent PrCA , as reflected by the PSA rise, is favorably affected by an intensive, vegetable-based diet, plus physical

  16. Androgen ablation augments human HLA2.1-restricted T cell responses to PSA self antigen in transgenic mice

    PubMed Central

    Arredouani, Mohamed S.; Tseng-Rogenski, Stephanie S.; Hollenbeck, Brent K.; Escara-Wilke, June; Leander, Karen R.; Defeo-Jones, Deborah; Hwang, Clara; Sanda, MartinG.

    2010-01-01

    Background In recent years, there has been an increasing interest in targeting human prostate tumor-associated antigens (TAAs) for prostate cancer immunotherapy as an alternative to other therapeutic modalities. However, immunologic tolerance to TAA poses a significant obstacle to effective, TAA-targeted immunotherapy. We sought to investigate whether androgen deprivation would result in circumventing immune tolerance to prostate TAA by impacting CD8 cell responses. Methods To this end, we generated a transgenic mouse that expresses the human prostate specific antigen (PSA) specifically in the prostate, and crossed it to the HLA-A2.1 transgenic mouse. Results Our PSA transgenic mouse showed restricted expression of PSA in the prostate and detectable circulating PSA levels. Additionally, PSA expression was androgen-dependent with reduced PSA expression in the prostate within one week of castration, and undetectable PSA by day 42 after castration as evaluated by ELISA. Castration of the PSA/A2.1 hybrid mouse prior to immunization with a PSA-expressing recombinant vaccinia virus resulted in a significant augmentation of PSA-specific cytotoxic lymphocytes. Conclusions This humanized hybrid mouse model provides a well defined system to gain additional insight into the mechanisms of immune tolerance to PSA and to test novel strategies aiming at circumventing immune tolerance to PSA and other TAA for targeted prostate cancer immunotherapy. PMID:20209643

  17. Altered glycosylation pattern allows the distinction between prostate-specific antigen (PSA) from normal and tumor origins.

    PubMed

    Peracaula, Rosa; Tabarés, Glòria; Royle, Louise; Harvey, David J; Dwek, Raymond A; Rudd, Pauline M; de Llorens, Rafael

    2003-06-01

    Prostate-specific antigen (PSA) is a glycoprotein secreted by prostate epithelial cells. PSA is currently used as a marker of prostate carcinoma because high levels of PSA are indicative of a tumor situation. However, PSA tests still suffer from a lack of specificity to distinguish between benign prostate hyperplasia and prostate cancer. To determine whether PSA glycosylation could provide a means of differentiating between PSA from normal and tumor origins, N-glycan characterization of PSA from seminal fluid and prostate cancer cells (LNCaP cell line) by sequencing analysis and mass spectrometry was carried out. Glycans from normal PSA (that correspond to low and high pI PSA fractions) were sialylated biantennary complex structures, half of them being disialylated in the low pI PSA fraction and mostly monosialylated in the high pI PSA. PSA from LNCaP cells was purified to homogeneity, and its glycan analysis showed a significantly different pattern, especially in the outer ends of the biantennary complex structures. In contrast to normal PSA glycans, which were sialylated, LNCaP PSA oligosaccharides were all neutral and contained a higher fucose content. In 10-15% of the structures fucose was linked alpha1-2 to galactose, forming the H2 epitope absent in normal PSA. GalNAc was increased in LNCaP glycans to 65%, whereas in normal PSA it was only present in 25% of the structures. These carbohydrate differences allow a distinction to be made between PSA from normal and tumor origins and suggest a valuable biochemical tool for diagnosis and follow-up purposes.

  18. Prostate-Specific Antigen (PSA)–Based Population Screening for Prostate Cancer: An Economic Analysis

    PubMed Central

    Tawfik, A

    2015-01-01

    Background The prostate-specific antigen (PSA) blood test has become widely used in Canada to test for prostate cancer (PC), the most common cancer among Canadian men. Data suggest that population-based PSA screening may not improve overall survival. Objectives This analysis aimed to review existing economic evaluations of population-based PSA screening, determine current spending on opportunistic PSA screening in Ontario, and estimate the cost of introducing a population-based PSA screening program in the province. Methods A systematic literature search was performed to identify economic evaluations of population-based PSA screening strategies published from 1998 to 2013. Studies were assessed for their methodological quality and applicability to the Ontario setting. An original cost analysis was also performed, using data from Ontario administrative sources and from the published literature. One-year costs were estimated for 4 strategies: no screening, current (opportunistic) screening of men aged 40 years and older, current (opportunistic) screening of men aged 50 to 74 years, and population-based screening of men aged 50 to 74 years. The analysis was conducted from the payer perspective. Results The literature review demonstrated that, overall, population-based PSA screening is costly and cost-ineffective but may be cost-effective in specific populations. Only 1 Canadian study, published 15 years ago, was identified. Approximately $119.2 million is being spent annually on PSA screening of men aged 40 years and older in Ontario, including close to $22 million to screen men younger than 50 and older than 74 years of age (i.e., outside the target age range for a population-based program). A population-based screening program in Ontario would cost approximately $149.4 million in the first year. Limitations Estimates were based on the synthesis of data from a variety of sources, requiring several assumptions and causing uncertainty in the results. For example, where

  19. A lab-in-a-briefcase for rapid prostate specific antigen (PSA) screening from whole blood.

    PubMed

    Barbosa, Ana I; Castanheira, Ana P; Edwards, Alexander D; Reis, Nuno M

    2014-08-21

    We present a new concept for rapid and fully portable prostate specific antigen (PSA) measurements, termed "lab-in-a-briefcase", which integrates an affordable microfluidic ELISA platform utilising a melt-extruded fluoropolymer microcapillary film (MCF) containing an array of 10 200 μm internal diameter capillaries, a disposable multi-syringe aspirator (MSA), a sample tray pre-loaded with all of the required immunoassay reagents, and a portable film scanner for colorimetric signal digital quantification. Each MSA can perform 10 replicate microfluidic immunoassays on 8 samples, allowing 80 measurements to be made in less than 15 minutes based on semi-automated operation, without the need of additional fluid handling equipment. The assay was optimised for the measurement of a clinically relevant range of PSA of 0.9 to 60.0 ng ml(-1) in 15 minutes with CVs on the order of 5% based on intra-assay variability when read using a consumer flatbed film scanner. The PSA assay performance in the MSA remained robust in undiluted or 1 : 2 diluted human serum or whole blood, and the matrix effect could simply be overcome by extending sample incubation times. The PSA "lab-in-a-briefcase" is particularly suited to a low-resource health setting, where diagnostic labs and automated immunoassay systems are not accessible, by allowing PSA measurement outside the laboratory using affordable equipment.

  20. A Diet, Physical Activity, and Meditation Intervention in Men With Rising Prostate-Specific Antigen (PSA)

    DTIC Science & Technology

    2006-05-01

    Trial, Diet, Nutrition , Physical Activity, Meditation, Prevention , Circadian Rhythm, Epidemiology, Prostate-Specific Antigen (PSA) 16. SECURITY...other project staff. • A Project Coordinator trained in nutrition and exercise science was hired in August 2003. In the fall of 2004, the role of...other intervention studies in the Department of Epidemiology and Biostatistics. • Tom Hurley, biostatistian in the Statewide Cancer Prevention and

  1. PSA Bounce and Biochemical Failure After Brachytherapy for Prostate Cancer: A Study of 820 Patients With a Minimum of 3 Years of Follow-Up

    SciTech Connect

    Caloglu, Murat; Ciezki, Jay P.; Reddy, Chandana A.; Angermeier, Kenneth; Ulchaker, James; Chehade, Nabil; Altman, Andrew; Magi-Galuzzi, Christina; Klein, Eric A.

    2011-07-01

    Purpose: To determine clinical or dosimetric factors associated with a prostate-specific antigen (PSA) bounce, as well as an association between a PSA bounce and biochemical relapse-free survival (bRFS), in patients treated with iodine-125 brachytherapy. Methods and Materials: A variety of clinical and treatment factors were examined in 820 patients who had a minimum of 3 years of PSA follow-up with T1-T2cN0M0 prostate cancer. Four different PSA threshold values were used for defining a PSA bounce: a PSA rise of {>=}0.2, {>=}0.4, {>=}0.6, and {>=}0.8 ng/mL. Results: A PSA bounce of {>=}0.2, {>=}0.4, {>=}0.6, and {>=}0.8 ng/mL was noted in 247 patients (30.1%), 161 (19.6%), 105 (12.8%), and 78 (9.5%), respectively. The median time to the first PSA rise was 17.4, 16.25, 16.23, and 15.71 months, respectively, vs. 34.35 months for a biochemical failure (p < 0.0001). A PSA rise of {>=}0.2 ng/mL was the only definition for which there was a significant difference in bRFS between bounce and non-bounce patients. The 5-year bRFS rate of patients having a PSA bounce of {>=}0.2 was 97.7% vs. 91% for those who did not have a PSA bounce (p = 0.0011). On univariate analysis for biochemical failure, age, risk group, and PSAs per year had a statistically significant correlation with PSA bounce of {>=}0.2 ng/mL. On multivariate analysis, age and PSAs per year remained statistically significant (p < 0.0001 and p = 0.0456, respectively). Conclusions: A bounce definition of a rise {>=}0.2 ng/mL is a reliable definition among several other definitions. The time to first PSA rise is the most valuable factor for distinguishing between a bounce and biochemical failure.

  2. [The role of prostate specific antigen and its derivatives (age-specific PSA, PSA density, velocity, free/total PSA) in the diagnosis of prostate cancer].

    PubMed

    Di Silverio, F; D'Eramo, G; Buscarini, M; Sciarra, A; Casale, P; Di Nicola, S; Loreto, A

    1998-06-01

    PSA is the most useful tumor marker for the diagnosis and treatment of prostate cancer. Its clinical use, however, still lacks the necessary sensitivity and specificity to be considered as ideal. In fact PSA is not specific for adenocarcinoma of the prostate: an elevated serum level of the marker does not necessarily mean malignant growth and normal levels too often hide an occult and potentially lethal cancer. With the discovery of different molecular PSA forms in the serum, an improved discrimination between benign prostate hyperplasia (BPH) and prostate cancer appears possible. This may be particularly useful in cases with equivocal PSA values and unpalpable prostate neoplasm to reduce the number of unnecessary prostate biopsies and increase the number of biopsies in cases without palpable or ultrasonic visible anomalies. The clinical use of PSA age-referenced levels is discussed. Their use is invaluable in screening programs where the routine adoption of age-specific values can help to pick-up younger patients with potentially curable prostate cancer and older patients with BPH where additional tests would be unnecessary. The role of PSA velocity (PASAV) s also discussed. An elevation rate of PSA of 0.75 ng/ml over 18 months on 3 serial samples appears to be the best cut-off to distinguish BPH from prostate cancer. However, the use of PSAV seems to be less useful in patients with elevated PSA levels and negative biopsy results. Free to total PSA ratio is probably the best parameter to reduce the number of unnecessary biopsies in men with a serum total PSA of 4 to 10 ng/ml. The advantages and limitations for different levels of cut-off are shown. A flow chart illustrating the role of various PSA "derivatives" in screening and subsequent evaluation of men over 50 years of age is also presented.

  3. Extreme-Risk Prostate Adenocarcinoma Presenting With Prostate-Specific Antigen (PSA) >40 ng/ml: Prognostic Significance of the Preradiation PSA Nadir

    SciTech Connect

    Alexander, Abraham S.; Mydin, Aminudin; Jones, Stuart O.; Christie, Jennifer; Lim, Jan T.W.; Truong, Pauline T.; Ludgate, Charles M.

    2011-12-01

    Purpose: To examine the impact of patient, disease, and treatment characteristics on survival outcomes in patients treated with neoadjuvant androgen deprivation therapy (ADT) and radical external-beam radiotherapy (RT) for clinically localized, extreme-risk prostate adenocarcinoma with a presenting prostate-specific antigen (PSA) concentration of >40 ng/ml. Methods and Materials: A retrospective chart review was conducted of 64 patients treated at a single institution between 1991 and 2000 with ADT and RT for prostate cancer with a presenting PSA level of >40 ng/ml. The effects of patient age, tumor (presenting PSA level, Gleason score, and T stage), and treatment (total ADT duration and pre-RT PSA level) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were examined. Results: Median follow-up time was 6.45 years (range, 0.09-15.19 years). Actuarial bDFS, PCSS, and OS rates at 5 years were 39%, 87%, and 78%, respectively, and 17%, 64%, and 45%, respectively, at 10 years. On multivariate analysis, the pre-RT PSA level ({<=}0.1 versus >0.1 ng/ml) was the single most significant prognostic factor for bDFS (p = 0.033) and OS (p = 0.018) rates, whereas age, T stage, Gleason score, and ADT duration ({<=}6 versus >6 months) were not predictive of outcomes. Conclusion: In prostate cancer patients with high presenting PSA levels, >40 ng/ml, treated with combined modality, neoadjuvant ADT, and RT, the pre-RT PSA nadir, rather than ADT duration, was significantly associated with improved survival. This observation supports the use of neoadjuvant ADT to drive PSA levels to below 0.1 ng/ml before initiation of RT, to optimize outcomes for patients with extreme-risk disease.

  4. [Current role of protatic specific antigen (PSA) and its by-products in the diagnosis of prostate cancer].

    PubMed

    Placer, José; Planas, Jacques; Celma, Ana; Morote, Juan

    2015-04-01

    Incorporation of prostatic specific antigen (PSA) to clinical practice was a revolution in the diagnosis and modified the epidemiology of prostate cancer (PCa). Although it lacks of many characteristics of an ideal tumor marker, it is the marker most used for diagnosis and follow up of any kind of cancer. It represents the best clinical tool we have available today for screening and staging of PCa. On the contrary, its greatest limitation is the lack of tumor specificity. The use of PSA by-products and molecular isoforms tries to solve, at least partially, its limitations. Indeed, the use of FreePSA ratio (%fPSA) ad PSA density (PSAD) increase significantly the specificity of the diagnostic test and, the use of derivatives that evaluate time kinetics of PSA (PSA velocity (PSAV) and PSA doubling time (PSADT) represents a very useful tool for prognosis estimation during treatment and follow up of the disease. The greatest advance over the last years comes from the analysis of the predecessor isoform (-2) pPSA and the phi Index. Both markers have demonstrated to improve the sensitivity and specificity results obtained to date, resulting in a decrease of unnecessary biopsies. Probably, with the ongoing development of new markers for PCa , the role of PSA on disease diagnosis and staging would be modified in a few years.

  5. The effect of the frequency and duration of prostate specific antigen (PSA) measurement on PSA doubling time calculations in men with biochemically recurrent prostate cancer

    PubMed Central

    Paller, CJ; Olatoye, D; Xie, S; Zhou, X; Denmeade, SR; Eisenberger, MA; Antonarakis, ES; Carducci, MA; Rosner, GL

    2013-01-01

    Background Prostate specific antigen (PSA) doubling time (PSADT) is an attractive intermediate endpoint for assessing novel therapies in biochemically recurrent prostate cancer (BRPC). This study explores whether PSADT calculations are influenced by frequency/duration of PSA measurements, and whether statistical variability leads investigators to find false significant results. Methods In retrospective analyses of two BRPC cohorts: Johns Hopkins Hospital (JHH) patients who deferred therapy and placebo patients on a randomized clinical trial (RCT), we calculated changes in PSADT from early measurements to later measurements using subsets of available PSAs for patients with ≥6 and ≥9 PSAs. We simulated hypothetical single-arm trials using randomly selected, 50-patient subsets and simulated two-arm RCTs. Results JHH cohort (n=205) had median follow-up 58 months, median age 61 years, and median Gleason 7. PSA variability changed with duration of PSA measurement as median within-patient PSADT increases for men with >6 PSAs ranged from 1.0 to 1.4 months by PSA subset while increases for men with ≥9 PSAs ranged from 3.9 to 4.1 months. Frequency of measurement did not change PSA variability as PSADT increase was unchanged when odd values were used instead of all values. Approximately 30% of JHH men experienced >200% increases in PSADT. Up to 62% of 50-patient single-arm simulations detected significant PSADT change, whereas simulated RCTs did not. Results were supported in the RCT placebo cohort; 46% of patients experienced PSADT increases >200%. Conclusion These data suggest that calculated PSADT in BRPC may naturally increase over time in the absence of therapy and may be influenced by duration of PSA follow-up. As a result, single arm trials could show false significant increases despite the lack of active treatment of these patients. Placebo-controlled RCTs including clinical endpoints are recommended to screen novel agents in men with BRPC to mitigate bias

  6. A national multicenter phase 2 study of prostate-specific antigen (PSA) pox virus vaccine with sequential androgen ablation therapy in patients with PSA progression: ECOG 9802.

    PubMed

    DiPaola, Robert S; Chen, Yu-Hui; Bubley, Glenn J; Stein, Mark N; Hahn, Noah M; Carducci, Michael A; Lattime, Edmund C; Gulley, James L; Arlen, Philip M; Butterfield, Lisa H; Wilding, George

    2015-09-01

    E9802 was a phase 2 multi-institution study conducted to evaluate the safety and effectiveness of vaccinia and fowlpox prostate-specific antigen (PSA) vaccine (step 1) followed by combination with androgen ablation therapy (step 2) in patients with PSA progression without visible metastasis. To test the hypothesis that vaccine therapy in this early disease setting will be safe and have a biochemical effect that would support future studies of immunotherapy in patients with minimal disease burden. Patients who had PSA progression following local therapy were treated with PROSTVAC-V (vaccinia)/TRICOM on cycle 1 followed by PROSTVAC-F (fowlpox)/TRICOM for subsequent cycles in combination with granulocyte-macrophage colony-stimulating factor (step 1). Androgen ablation was added on progression (step 2). Step 1 primary end points included progression at 6 mo and characterization of change in PSA velocity pretreatment to post-treatment. Step 2 end points included PSA response with combined vaccine and androgen ablation. In step 1, 25 of 40 eligible patients (63%) were progression free at 6 mo after registration (90% confidence interval [CI], 48-75). The median pretreatment PSA velocity was 0.13 log(PSA)/mo, in contrast to median postregistration velocity of 0.09 log(PSA)/mo (p=0.02), which is an increase in median PSA doubling time from 5.3 mo to 7.7 mo. No grade ≥4 treatment-related toxicity was observed. In the 27 patients eligible and treated for step 2, 20 patients achieved a complete response (CR) at 7 mo (CR rate: 74%; 90% CI, 57-87). Although supportive of larger studies in the cooperative group setting, this study is limited by the small number of patients and the absence of a control group as in a phase 3 study. A viral PSA vaccine can be administered safely in the multi-institutional cooperative group setting to patients with minimal disease volume alone and combined with androgen ablation, supporting the feasibility of future phase 3 studies in this

  7. A National Multicenter Phase 2 Study of Prostate-specific Antigen (PSA) Pox Virus Vaccine with Sequential Androgen Ablation Therapy in Patients with PSA Progression: ECOG 9802

    PubMed Central

    DiPaola, Robert S.; Chen, Yu-Hui; Bubley, Glenn J.; Stein, Mark N.; Hahn, Noah M.; Carducci, Michael A.; Lattime, Edmund C.; Gulley, James; Arlen, Philip M.; Butterfield, Lisa H.; Wilding, George

    2014-01-01

    Background E9802 was a phase 2 multi-institution study conducted to evaluate the safety and effectiveness of vaccinia and fowlpox prostate-specific antigen (PSA) vaccine (step 1) followed by combination with androgen ablation therapy (step 2) in patients with PSA progression without visible metastasis. Objective To test the hypothesis that vaccine therapy in this early disease setting will be safe and have a biochemical effect that would support future studies of immunotherapy in patients with minimal disease burden. Design, setting, and participants Patients had PSA progression following local therapy were treated with PROSTVAC-V (vaccinia)/TRICOM on cycle 1 followed by PROSTVAC-F (fowlpox)/TRICOM for subsequent cycles in combination with granulocyte-macrophage colony-stimulating factor (step 1). Androgen ablation was added on progression (step 2). Outcome measurements and statistical analysis Step 1 primary end points included progression at 6 mo and characterization of change in PSA velocity pretreatment to post-treatment. Step 2 end points included PSA response with combined vaccine and androgen ablation. Results and limitations In step 1, 25 of 40 eligible patients (63%) were progression free at 6 mo after registration (90% confidence interval [CI], 48–75). The median pretreatment PSA velocity was 0.13 log(PSA)/mo, in contrast to median postregistration velocity of 0.09 log(PSA)/mo (p = 0.02), which is an increase in median PSA doubling time from 5.3 mo to 7.7 mo. No grade ≥4 treatment-related toxicity was observed. In the 27 patients eligible and treated for step 2, 20 patients achieved a complete response (CR) at 7 mo (CR rate: 74%; 90% CI, 57–87). Although supportive of larger studies in the cooperative group setting, this study is limited by the small number of patients and the absence of a control group as in a phase 3 study. Conclusions A viral PSA vaccine can be administered safely in the multi-institutional cooperative group setting to patients

  8. A Multi-Center Study of [−2]Pro-Prostate-Specific Antigen (PSA) in Combination with PSA and Free PSA for Prostate Cancer Detection in the 2.0 to 10.0 ng/mL PSA Range

    PubMed Central

    Catalona, William J.; Partin, Alan W.; Sanda, Martin G.; Wei, John T.; Klee, George G.; Bangma, Chris H.; Slawin, Kevin M.; Marks, Leonard S.; Loeb, Stacy; Broyles, Dennis L.; Shin, Sanghyuk S.; Cruz, Amabelle B.; Chan, Daniel W.; Sokoll, Lori J.; Roberts, William L.; van Schaik, Ron H.N.; Mizrahi, Isaac A.

    2011-01-01

    Purpose PSA and free PSA (fPSA) have limited specificity for detecting clinically significant, curable prostate cancer (PCa), leading to unnecessary biopsies and detection and treatment of some indolent tumors. [−2]proPSA (p2PSA) may improve specificity for detecting clinically significant PCa. Our objective was to evaluate p2PSA, fPSA, and PSA in a mathematical formula (prostate health index [phi] = [−2]proPSA / fPSA) × PSA1/2) to enhance specificity for detecting overall and high-grade PCa. Materials and Methods We enrolled 892 men in a prospective multi-institutional trial with no history of PCa, normal rectal examination, a PSA of 2–10 ng/mL, and ≥6- core prostate biopsy. We examined the relationship of serum PSA, %fPSA and phi with biopsy results. The primary endpoints were the specificity and AUC using phi to detect overall and Gleason ≥7 prostate cancer on biopsy compared with %fPSA. Results For the 2–10 ng/mL PSA range, at 80–95% sensitivity, the specificity and AUC (0.703) of phi exceeded those of PSA and %fPSA. Increasing phi was associated with a 4.7-fold increased risk of PCa and 1.61-fold increased risk of Gleason ≥7 disease on biopsy. The AUC for phi (0.724) exceeded that of %fPSA (0.670) in discriminating between PCa with Gleason ≥ 4+3 vs. lower grade disease or negative biopsies. Phi results were not associated with age and prostate volume. Conclusions Phi may be useful in PCa screening to reduce unnecessary biopsies in men age ≥50 years with PSA 2–10 ng/mL and negative DRE, with minimal loss in sensitivity. PMID:21419439

  9. Prostate-specific antigen (PSA) best practice policy. American Urological Association (AUA).

    PubMed

    2000-02-01

    Prostate cancer is one of the most common forms of noncutaneous cancer in men in the United States. Despite its prevalence, the natural history of this disease is remarkably heterogeneous. In many patients, the cancer progresses slowly, resulting in moderately or poorly differentiated tumors that remain localized to the prostate gland. Although potentially life-threatening, such cancers are often curable. In other patients, however, tumor growth is rapid and can spread beyond the confines of the prostate. In such cases, the cancer is not curable, and long-term survival is considerably diminished. Strategies for managing prostate cancer have therefore been aimed at early detection and local treatment of the cancer. Prostate-specific antigen (PSA) is a tumor marker currently used for early detection of prostate cancer. Measurement of serum PSA levels has significant clinical application in other areas of prostate disease management. The purpose of this report is to provide current information on the use of PSA testing for: (1) the evaluation of men at risk for prostate cancer, (2) assistance in pretreatment staging, and (3) the posttreatment monitoring and management of men with this disease. The following summary is based on a review of the literature and the expert opinions of a multispecialty panel convened by the American Urological Association (AUA). It is intended to serve as a resource for urologists and primary care physicians.

  10. Prostate-Specific Antigen Working Group’s Guidelines on PSA Doubling Time

    PubMed Central

    Arlen, Philip M.; Bianco, Fernando; Dahut, William L.; D’Amico, Anthony; Figg, William D.; Freedland, Stephen J.; Gulley, James L.; Kantoff, Philip W.; Kattan, Michael W.; Lee, Andrew; Regan, Meredith M.; Sartor, Oliver

    2009-01-01

    Purpose Prostate-specific antigen is a glycoprotein found almost exclusively in normal and neoplastic prostate cells. PSA doubling time, or the change in PSA level over time, has emerged as a useful predictive marker for assessing disease outcome in patients with prostate cancer. It is important to agree on definitions and values for the calculation of PSADT and to develop a common approach to outcome analysis and reporting. Methods In September 2006 a conference was held at the National Cancer Institute in Bethesda, Maryland to define these parameters and develop guidelines for their use. Results The PSA Working Group defined the following criteria regarding PSADT: (1) calculation of PSADT, (2) evidence to support PSADT as a predictive factor in the setting of biochemical recurrence, and (3) use of PSADT as a stratification factor in clinical trials. Conclusions We propose that investigators calculate PSADT prior to enrolling patients on clinical studies and calculate it as an additional measurement of therapeutic activity. We believe we have developed practical guidelines for the calculation of PSADT and its use as a measurement of prognosis and outcome. Furthermore, the use of common standards for PSADT in clinical trials is important as we determine which treatments should progress to randomized trials in which “hard” end points such as survival will be employed. PMID:18423743

  11. Power-free chip enzyme immunoassay for detection of prostate specific antigen (PSA) in serum.

    PubMed

    Adel Ahmed, Heba; Azzazy, Hassan M E

    2013-11-15

    A power-free, portable "Chip EIA" was designed to render the popular Enzyme Linked Immunosorbent Assay (ELISA) more suitable for point-of-care testing. A number of microfluidic platforms have enabled miniaturization of the conventional microtitre plate ELISA, however, they require external pumping systems, valves, and electric power supply. The Chip EIA platform has eliminated the need for pumps and valves through utilizing a simple permanent magnet and magnetic nanoparticles. The magnetic nanoparticles act as solid support to capture the target and are then moved through chambers harboring different reagents necessary to perform a sandwich ELISA. The use of magnetic nanoparticles increases the volume-to-surface ratio reducing the assay time to 30 min. Changing the color of horseradish peroxidase (HRP) substrate to green indicates a positive result. In addition, a quantitative read-out was obtained through the use of cellphone camera imaging and analyzing the images using Matlab®. Cell phones, including smart ones, are readily available almost everywhere. The Chip EIA device was used to assay total prostate specific antigen (tPSA) in 19 serum samples. The PSA Chip EIA was tested for accuracy, precision, repeatability, and the results were correlated to the commercial Beckman Colter, Hybritech immunoassay® for determination of tPSA in serum samples with a Pearson correlation coefficient (R(2)=0.96). The lower detection limit of the PSA Chip EIA was 3.2 ng/mL. The assay has 88.9% recovery and good reproducibility (% CV of 6.5). We conclude that the developed Chip EIA can be used for detection of protein biomarkers in biological specimens.

  12. Does obesity affect the accuracy of prostate-specific antigen (PSA) for predicting prostate cancer among men undergoing prostate biopsy.

    PubMed

    Oh, Jong J; Jeong, Seong J; Lee, Byung K; Jeong, Chang W; Byun, Seok-Soo; Hong, Sung K; Lee, Sang E

    2013-08-01

    What's known on the subject? and what does the study add?: As most urologist known, obesity significantly lowers serum PSA levels. So there is some concern about delayed diagnosis of prostate cancer in obese men. In the present study, we found that the accuracy level of PSA for detecting prostate cancer was not significantly different between different obesity levels. A well-designed study adjusting for several factors, e.g. diet, exercise, medication and comorbidity, which may possibly compensate for the associated effects on PSA levels, is needed for confirmation of the present findings. To investigate prostate-specific antigen (PSA) accuracy in detecting prostate cancer according to body mass index (BMI) in Asian men with a PSA level of <30 ng/mL using contemporary multicore (≥ 12) prostate biopsy. We reviewed the records of 3471 patients, whose initial PSA levels were <30 ng/mL, who underwent multicore (≥ 12) transrectal ultrasound-guided prostate biopsy between January 2004 and May 2011. BMI was categorised as performed previously for the Asian population: <23, 23-24.9, 25-29.9, and ≥ 30 kg/m(2) . PSA accuracy for detecting prostate cancer in each BMI group was assessed based on the receiver operating characteristics-derived area under the curve. The mean age and median PSA level were inversely associated with BMI; the median PSA level in each BMI category was 7.84, 7.75, 7.33 and 5.79 ng/mL, respectively (P < 0.001). In all, prostate cancer was detected from biopsy in 1102 (31.7%) patients. The PSA accuracy for predicting prostate cancer in all patients was estimated to be 0.607, and PSA accuracies in each BMI category were 0.638, 0.572, 0.613 and 0.544, respectively; there was no significant difference among the groups in terms of PSA accuracy. The accuracy of PSA in predicting prostate cancer did not change regardless of BMI category in Asian men. However, as patients with higher BMIs had lower PSA levels than those with lower BMIs, it can therefore

  13. Serum prostate-specific antigen (PSA) concentration is positively associated with rate of disease reclassification on subsequent active surveillance prostate biopsy in men with low PSA density

    PubMed Central

    Umbehr, Martin H.; Platz, Elizabeth A.; Peskoe, Sarah B.; Bhavsar, Nrupen A.; Epstein, Jonathan I.; Landis, Patricia; Partin, Alan W.; Carter, H. Ballentine

    2014-01-01

    Objective To investigate the association between serum prostate-specific antigen (PSA) concentration at active surveillance (AS) entry and disease reclassification on subsequent AS biopsy (‘biopsy reclassification’) in men with low PSA density (PSAD). To investigate whether a clinically meaningful PSA threshold for AS eligibility/ineligibility for men with low PSAD can be identified based on risk of subsequent biopsy reclassification. Patients and Methods We included men enrolled in the Johns Hopkins AS Study (JHAS) who had a PSAD of <0.15 ng/mL/g (640 men). We estimated the incidence rates (IRs; per 100 person years) and hazard ratios (HR) of biopsy reclassification (Gleason score ≥ 7, any Gleason pattern 4 or 5, ≥3 positive cores, or ≥50% cancer involvement/biopsy core) for categories of serum PSA concentration at the time of entry into AS. We generated predicted IRs using Poisson regression to adjust for age and prostate volume, mean percentage free PSA (ratio of free to total PSA) and maximum percentage biopsy core involvement with cancer. Results The unadjusted IRs (per 100 person years) of biopsy reclassification across serum PSA concentration at entry into JHAS showed, in general, an increase; however, the pattern was not linear with higher IRs in the group ≥ 4 to <6 ng/mL (14.2, 95% confidence interval [CI] 11.8–17.2%) when compared with ≥ 6 to <8 ng/mL (8.4, 95% CI 5.7–12.3%) but almost similar IRs when compared with the group ≥ 8 to <10 ng/mL (14.8, 95% CI 8.4–26.1%). The adjusted predicted IRs of reclassification showed a similar non-linear increase in IRs, whereby the rates around 4 ng/mL were similar to the rates around 10 ng/mL. Conclusion Risk for biopsy reclassification increased non-linearly across PSA concentration in men with low PSAD, whereby no obvious clinically meaningful threshold could be identified. This information could be incorporated into decision-making for AS. However, longer follow-up times are needed to

  14. Recombinant Forms of Leishmania amazonensis Excreted/Secreted Promastigote Surface Antigen (PSA) Induce Protective Immune Responses in Dogs

    PubMed Central

    Petitdidier, Elodie; Pagniez, Julie; Papierok, Gérard; Vincendeau, Philippe; Lemesre, Jean-Loup; Bras-Gonçalves, Rachel

    2016-01-01

    Preventive vaccination is a highly promising strategy for interrupting leishmaniasis transmission that can, additionally, contribute to elimination. A vaccine formulation based on naturally excreted secreted (ES) antigens was prepared from L. infantum promastigote culture supernatant. This vaccine achieved successful results in Phase III trials and was licensed and marketed as CaniLeish. We recently showed that newly identified ES promastigote surface antigen (PSA), from both viable promastigotes and axenically-grown amastigotes, represented the major constituent and the highly immunogenic antigen of L. infantum and L. amazonensis ES products. We report here that three immunizations with either the recombinant ES LaPSA-38S (rPSA) or its carboxy terminal part LaPSA-12S (Cter-rPSA), combined with QA-21 as adjuvant, confer high levels of protection in naive L. infantum-infected Beagle dogs, as checked by bone marrow parasite absence in respectively 78.8% and 80% of vaccinated dogs at 6 months post-challenge. The parasite burden in infected vaccinated dogs was significantly reduced compared to placebo group, as measured by q-PCR. Moreover, our results reveal humoral and cellular immune response clear-cut differences between vaccinated and control dogs. An early increase in specific IgG2 antibodies was observed in rPSA/QA-21- and Cter-rPSA/QA-21-immunized dogs only. They were found functionally active in vitro and were highly correlated with vaccine protection. In vaccinated protected dogs, IFN-γ and NO productions, as well as anti-leishmanial macrophage activity, were increased. These data strongly suggest that ES PSA or its carboxy-terminal part, in recombinant forms, induce protection in a canine model of zoonotic visceral leishmaniasis by inducing a Th1-dominant immune response and an appropriate specific antibody response. These data suggest that they could be considered as important active components in vaccine candidates. PMID:27223609

  15. Tyrosine-phosphorylated Galectin-3 Protein Is Resistant to Prostate-specific Antigen (PSA) Cleavage*

    PubMed Central

    Balan, Vitaly; Nangia-Makker, Pratima; Kho, Dhong Hyo; Wang, Yi; Raz, Avraham

    2012-01-01

    Galectin-3 is a chimeric carbohydrate-binding protein, which interacts with cell surface carbohydrate-containing molecules and extracellular matrix glycoproteins and has been implicated in various biological processes such as cell growth, angiogenesis, motility, and metastasis. It is expressed in a wide range of tumor cells and is associated with tumor progression. The functions of galectin-3 are dependent on its localization and post-translational modifications such as cleavage and phosphorylation. Recently, we showed that galectin-3 Tyr-107 is phosphorylated by c-Abl; concomitantly, it was also shown that galectin-3 can be cleaved at this site by prostate-specific antigen (PSA), a chymotrypsin-like serine protease, after Tyr-107, resulting in loss of galectin-3 multivalency while preserving its carbohydrate binding activity. Galectin-3 is largely a monomer in solution but may form a homodimer by self-association through its carbohydrate recognition domain, whereas, in the presence of a ligand, galectin-3 polymerizes up to pentamers utilizing its N-terminal domain. Oligomerization is a unique feature of secreted galectin-3, which allows its function by forming ordered galectin-glycan structures, i.e. lattices, on the cell surface or through direct engagement of specific cell surface glycoconjugates by traditional ligand-receptor binding. We questioned whether Tyr-107 phosphorylation by c-Abl affects galectin-3 cleavage by PSA. The data suggest a role for galectin-3 in prostate cells associated with increased activity of c-Abl kinase and loss of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) activity. In addition, the ratio of phosphorylated/dephosphorylated galectin-3 might be used as a complementary value to that of PSA for prognosis of prostate cancer and a novel therapeutic target for the treatment of prostate cancer. PMID:22232548

  16. Patterns of prostate-specific antigen (PSA) testing in Australian men: the influence of family history.

    PubMed

    McDowell, Michelle E; Occhipinti, Stefano; Gardiner, Robert A; Chambers, Suzanne K

    2012-04-01

    To describe how a family history of prostate cancer influences men's prostate cancer testing behaviours, information support preferences, and motives for testing. Men with a first-degree family history (239 men) and a comparison sample from the general population of Queensland, Australia (289) aged 40-65 years, and no prior history of cancer. Cross-sectional, retrospective survey assessing: prevalence of prostate-specific antigen (PSA) testing and digital rectal examination (DRE); discussion of prostate cancer risks and benefits with a physician; prostate cancer information needs and preferences; motivations for testing. Men with a family history were more likely to report: having ever had a PSA test (odds ratio [OR] 4.98; 95% confidence interval [CI] 3.16-7.85), more PSA tests in their lifetimes (b 1.04; se 0.40; 95% CI 0.26-1.82); to have had a DRE (OR 2.23; 95% CI 1.54-3.23); to have spoken to a doctor about prostate cancer (OR 3.72; 95% CI 2.30-6.02); and to have instigated these discussions (OR 1.74; 95%CI 1.13-2.70). Most men from both groups did not recall any discussion of the 'cons' of prostate cancer testing with a doctor. Men with a family history reported a greater desire for information about prostate cancer prevention than did men without a family history. Men with a family history are more concerned about getting prostate cancer and are tested more often; however, information needs, discussions about prostate cancer, and motivations for testing are similar to those of all men. There appears to be a disparity between public health approaches that promote informed decision-making and what is happening in practice. © 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.

  17. Sensitive detection and glycoprofiling of a prostate specific antigen (PSA) using impedimetric assays

    PubMed Central

    Pihíková, D; Belický, Š; Kasák, P; Bertok, T; Tkac, J

    2016-01-01

    The study presents proof-of-concept for development of an impedimetric biosensor for ultrasensitive glycoprofiling of PSA. The biosensor exhibits three unique characteristics: 1) analysis of PSA with LOD down to 4 aM; 2) analysis of a glycan part of PSA with LOD down to 4 aM level and 3) both assays (i.e. PSA quantification and PSA glycoprofiling) can be performed on the same interface due to label-free format of analysis. PMID:26647853

  18. Portable smartphone quantitation of prostate specific antigen (PSA) in a fluoropolymer microfluidic device.

    PubMed

    Barbosa, Ana I; Gehlot, Poonam; Sidapra, Kalpita; Edwards, Alexander D; Reis, Nuno M

    2015-08-15

    We present a new, power-free and flexible detection system named MCFphone for portable colorimetric and fluorescence quantitative sandwich immunoassay detection of prostate specific antigen (PSA). The MCFphone is composed by a smartphone integrated with a magnifying lens, a simple light source and a miniaturised immunoassay platform, the Microcapillary Film (MCF). The excellent transparency and flat geometry of fluoropolymer MCF allowed quantitation of PSA in the range 0.9 to 60 ng/ml with<7% precision in 13 min using enzymatic amplification and a chromogenic substrate. The lower limit of detection was further improved from 0.4 to 0.08 ng/ml in whole blood samples with the use of a fluorescence substrate. The MCFphone has shown capable of performing rapid (13 to 22 min total assay time) colorimetric quantitative and highly sensitive fluorescence tests with good %Recovery, which represents a major step in the integration of a new generation of inexpensive and portable microfluidic devices with commercial immunoassay reagents and off-the-shelf smartphone technology. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  19. The percentage of prostate-specific antigen (PSA) isoform [-2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged ≤65 years.

    PubMed

    Boegemann, Martin; Stephan, Carsten; Cammann, Henning; Vincendeau, Sébastien; Houlgatte, Alain; Jung, Klaus; Blanchet, Jean-Sebastien; Semjonow, Axel

    2016-01-01

    To prospectively test the diagnostic accuracy of the percentage of prostate specific antigen (PSA) isoform [-2]proPSA (%p2PSA) and the Prostate Health Index (PHI), and to determine their role for discrimination between significant and insignificant prostate cancer at initial and repeat prostate biopsy in men aged ≤65 years. The diagnostic performance of %p2PSA and PHI were evaluated in a multicentre study. In all, 769 men aged ≤65 years scheduled for initial or repeat prostate biopsy were recruited in four sites based on a total PSA (t-PSA) level of 1.6-8.0 ng/mL World Health Organization (WHO) calibrated (2-10 ng/mL Hybritech-calibrated). Serum samples were measured for the concentration of t-PSA, free PSA (f-PSA) and p2PSA with Beckman Coulter immunoassays on Access-2 or DxI800 instruments. PHI was calculated as (p2PSA/f-PSA × √t-PSA). Uni- and multivariable logistic regression models and an artificial neural network (ANN) were complemented by decision curve analysis (DCA). In univariate analysis %p2PSA and PHI were the best predictors of prostate cancer detection in all patients (area under the curve [AUC] 0.72 and 0.73, respectively), at initial (AUC 0.67 and 0.69) and repeat biopsy (AUC 0.74 and 0.74). t-PSA and %f-PSA performed less accurately for all patients (AUC 0.54 and 0.62). For detection of significant prostate cancer (based on Prostate Cancer Research International Active Surveillance [PRIAS] criteria) the %p2PSA and PHI equally demonstrated best performance (AUC 0.70 and 0.73) compared with t-PSA and %f-PSA (AUC 0.54 and 0.59). In multivariate analysis PHI we added to a base model of age, prostate volume, digital rectal examination, t-PSA and %f-PSA. PHI was strongest in predicting prostate cancer in all patients, at initial and repeat biopsy and for significant prostate cancer (AUC 0.73, 0.68, 0.78 and 0.72, respectively). In DCA for all patients the ANN showed the broadest threshold probability and best net benefit. PHI as single parameter

  20. Contribution of genetic variation rs266882 to prostate-specific antigen levels in healthy controls with serum PSA below 2.0 ng/ml.

    PubMed

    Song, Jaeman; Park, Heeyoon; Lee, Gilho

    2013-04-01

    We evaluated the impact of genetic variation in the prostate-specific antigen (PSA) gene (rs266882) on serum PSA levels in healthy men as well as risk factors for benign prostate hypertrophy (BPH) and prostate cancer. The study population comprised 91 men with PSA levels below 2.0 ng/ml as healthy controls, 78 men with PSA 2-10 ng/ml as a BPH group, and 128 prostate cancer patients, all in Korea. DNA was amplified by polymerase chain reaction and the product was sequenced. We found that PSA levels were associated with a G/A polymorphism only in healthy controls. The transition, however, was not associated with PSA levels of BPH and cancer patients, nor was it a risk factor. In conclusion, this genetic factor is important for determining serum PSA levels in the naive group, whereas the disruption of prostatic architecture in BPH or prostate cancer may be a major determining factor for PSA levels.

  1. pH6 antigen (PsaA protein) of Yersinia pestis, a novel bacterial Fc-receptor.

    PubMed

    Zav'yalov, V P; Abramov, V M; Cherepanov, P G; Spirina, G V; Chernovskaya, T V; Vasiliev, A M; Zav'yalova, G A

    1996-05-01

    It was found that recombinant pH6 antigen (rPsaA protein) forming virulence-associated fimbriae on the surface of Yersinia pestis at pH 6.7 in host macrophage phagolysosomes or extracellularly in abscesses such as buboes, is a novel bacterial Fc-receptor. rPsaA protein displays reactivity with human IgG1, IgG2 and IgG3 subclasses but does not react with rabbit, mouse and sheep IgG.

  2. Immunoassay for the discrimination of free prostate-specific antigen (fPSA) forms with internal cleavages at Lys145 or Lys146 from fPSA without internal cleavages at Lys145 or Lys146

    PubMed Central

    Peltola, Mari T.; Niemelä, Pauliina; Alanen, Kalle; Nurmi, Martti; Lilja, Hans; Pettersson, Kim

    2014-01-01

    Total levels of circulating prostate-specific antigen (tPSA) are strongly associated with prostate cancer (PCa) risk and outcome but benign prostate disease is the most frequent cause of a moderately elevated PSA level. Free PSA (fPSA) forms are independently associated with PCa risk and contribute modest diagnostic enhancements above and beyond tPSA alone. We developed an immunoassay for fPSA subfractions containing internal cleavages at Lys145 or Lys146 (fPSA-N). The assay was based on blocking intact single-chain fPSA (fPSA-I) with antibody 4D4 which does not detect PSA containing internal cleavages at Lys145 or Lys146. We also measured fPSA-N in blood from healthy volunteers and in anti-coagulated plasma from 76 men with or without evidence of PCa at biopsy. The analytical and functional detection limits of this assay were 0.016 ng/mL and 0.10 ng/mL, respectively. The median recovery of male fPSA-N from female plasma was 95.0 %. All 12 female samples (average age 28 years) had fPSA-N concentrations at or below the analytical detection limit. The median fPSA-N concentration (0.050 ng/mL) in 9 healthy male volunteers (age < 40 years) was below the functional detection limit, 0.420 ng/mL in 27 patients with benign prostate conditions and 0.239 ng/mL in 49 patients with PCa. Deming regression analysis of the patient samples showed that the measured fPSA-N concentrations were generally 23% lower than the previously calculated (fPSA minus fPSA-I) concentrations, likely due to differences in the antibody combinations used. In conclusion, we have developed a sensitive, specific and direct immunoassay for fPSA-N which can be used to study the clinical relevance of this PSA isoform. PMID:21554885

  3. Postoperative Prostate-Specific Antigen Velocity Independently Predicts for Failure of Salvage Radiotherapy After Prostatectomy

    SciTech Connect

    King, Christopher R. Presti, Joseph C.; Brooks, James D.; Gill, Harcharan; Spiotto, Michael T.

    2008-04-01

    Purpose: Identification of patients most likely to benefit from salvage radiotherapy (RT) using postoperative (postop) prostate-specific antigen (PSA) kinetics. Methods and Materials: From 1984 to 2004, 81 patients who fit the following criteria formed the study population: undetectable PSA after radical prostatectomy (RP); pathologically negative nodes; biochemical relapse defined as a persistently detectable PSA; salvage RT; and two or more postop PSAs available before salvage RT. Salvage RT included the whole pelvic nodes in 55 patients and 4 months of total androgen suppression in 56 patients. The median follow-up was >5 years. All relapses were defined as a persistently detectable PSA. Kaplan-Meier and Cox proportional hazards multivariable analysis were performed for all clinical, pathological, and treatment factors predicting for biochemical relapse-free survival (bRFS). Results: There were 37 biochemical relapses observed after salvage RT. The 5-year bRFS after salvage RT for patients with postop prostate-specific antigen velocity {<=}1 vs. >1 ng/ml/yr was 59% vs. 29%, p = 0.002. In multivariate analysis, only postop PSAV (p = 0.0036), pre-RT PSA level {<=}1 (p = 0.037) and interval-to-relapse >10 months (p = 0.012) remained significant, whereas pelvic RT, hormone therapy, and RT dose showed a trend (p = {approx}0.06). PSAV, but not prostate-specific antigen doubling time, predicted successful salvage RT, suggesting an association of zero-order kinetics with locally recurrent disease. Conclusions: Postoperative PSA velocity independently predicts for the failure of salvage RT and can be considered in addition to high-risk features when selecting patients in need of systemic therapy following biochemical failure after RP. For well-selected patients, salvage RT can achieve high cure rates.

  4. The Effect of Testosterone Replacement Therapy on Prostate-Specific Antigen (PSA) Levels in Men Being Treated for Hypogonadism

    PubMed Central

    Kang, De-Ying; Li, Hong-Jun

    2015-01-01

    Abstract Testosterone replacement therapy is used for the treatment of age-related male hypogonadism, and prostate-specific antigen (PSA) is a primary screening tool for prostate cancer. The systematic review and meta-analysis aimed to determine the effect of testosterone replacement therapy on PSA levels. Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until February 28, 2014, and inclusion criteria were as follows: randomized controlled trial; intervention group received testosterone/androgen replacement therapy; control group did not receive treatment; and no history of prostate cancer. The primary outcome was change of PSA level between before and after treatment. Secondary outcomes were elevated PSA level after treatment, and the number of patients who developed prostate cancer. After initially identifying 511 articles, 15 studies with a total of 739 patients that received testosterone replacement and 385 controls were included. The duration of treatment ranged from 3 to 12 months. Patients treated with testosterone tended to have higher PSA levels, and thus a greater change than those that received control treatments (difference in means of PSA levels = 0.154, 95% confidence interval [CI] 0.069 to 0.238, P < 0.001). The difference in means of PSA levels were significant higher for patients that received testosterone intramuscularly (IM) than controls (difference in means of PSA levels = 0.271, 95% CI 0.117–0.425, P = 0.001). Elevated PSA levels after treatment were similar between patients that received treatment and controls (odds ratio [OR] = 1.02, 95% CI 0.48–2.20, P = 0.953). Only 3 studies provided data with respect to the development of prostate cancer, and rates were similar between those that received treatment and controls. Testosterone replacement therapy does not increase PSA levels in men being treated for hypogonadism, except when it is given IM and even the increase with IM administration

  5. Molecular forms of serum prostate-specific antigen: the clinical usefulness of percent free PSA to discriminate prostate cancer from BPH.

    PubMed

    Abrahamsson, P A; Kuriyama, M

    1998-04-01

    The development of increasingly specific diagnostic assays has allowed the detection of various forms of prostate-specific antigen (PSA). It has been found that the proportion of free to total PSA (percent free PSA) is significantly lower in men with prostate cancer than in those with other benign diseases. In order to distinguish early, curable prostate cancer from benign prostatic hyperplasia (BPH), percent free PSA measurement is most useful when the total PSA value is 3-10 ng/ml. The measurement of the proportions of these different forms of PSA, i.e., percent free PSA, may constitute an important diagnostic tool, able to differentiate between benign and malignant prostatic disease with increased specificity, reducing false-positive results and, therefore, improve patient prognosis.

  6. Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers.

    PubMed

    Filella, Xavier; Foj, Laura

    2016-10-26

    Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis.

  7. Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers

    PubMed Central

    Filella, Xavier; Foj, Laura

    2016-01-01

    Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis. PMID:27792187

  8. Vaccination with agonist peptide PSA: 154-163 (155L) derived from prostate specific antigen induced CD8 T-cell response to the native peptide PSA: 154-163 but failed to induce the reactivity against tumor targets expressing PSA: a phase 2 study in patients with recurrent prostate cancer.

    PubMed

    Kouiavskaia, Diana V; Berard, Carla A; Datena, Ellen; Hussain, Arif; Dawson, Nancy; Klyushnenkova, Elena N; Alexander, Richard B

    2009-01-01

    We conducted a clinical trial of peptide prostate specific antigen (PSA): 154-163 (155L) vaccination in human leukocyte antigen (HLA)-A2 patients with detectable and rising serum PSA after radical prostatectomy for prostate cancer (Clinicaltrials.gov identifier NCT00109811). The trial was a single dose-level, phase 2 pilot trial of 1 mg of PSA: 154-163 (155L) emulsified with adjuvant (Montanide ISA-51). The primary endpoint was the determination of immunogenicity of the vaccine; secondary outcomes were determination of toxicity and effect on serum PSA. The vaccine was given subcutaneously 7 times on weeks 0, 2, 4, 6, 10, 14, and 18. Peptide-specific CD8 T-cell responses in the peripheral blood mononuclear cells (PBMC) of patients were measured by interferon (IFN)-gamma enzyme-linked immunosorbent spot assay. CD8 T-cell cultures were also established by in vitro stimulation with the peptide presented by autologous dendritic cells. Five patients were enrolled and completed all vaccinations. No IFN-gamma response to PSA: 154-163 (155L) was detected in unfractioned PBMC in any patient either before or after vaccination. Three of 5 patients demonstrated strong IFN-gamma responses to PSA: 154-163 (155L) and native PSA: 154-163 peptides in CD8 T-cell cultures derived from postvaccination PBMC. However, peptide-specific T cells failed to recognize HLA-A2 positive targets expressing endogenous PSA. There were no significant changes in serum PSA level in any subject. No serious adverse events were observed. PSA: 154-163 (155L) is not an effective immunogen when given with Montanide ISA-51. The PSA: 154-163 peptide is poorly processed from endogenous PSA and therefore represents a cryptic epitope of PSA in HLA-A2 antigen-presenting cells.

  9. The tumor control probability model for transperineal permanent prostate brachytherapy and prostate-specific antigen failure free survival

    NASA Astrophysics Data System (ADS)

    Prete, James John

    1999-12-01

    The studies proposed were designed to investigate the relationship between transperineal permanent prostate implant quality, as modeled by the radiobiologicalquantifier of implant quality, tumor control probability (TCP), and treatment efficacy, as measured by prostatespecific antigen (PSA) failure free survival. It was hypothesized that TCP could be useful in identifying which patients, or group of patients, might be at an increased risk for treatment failure among patients receiving 125I transperineal permanent prostate brachytherapy (TPPB) as the sole modality of treatment for early or intermediate stage prostatic carcinoma. The formal statement of hypothesis was that the linear- quadratic tumor control probability model for monotherapeutic 125I transperineal permanent prostate brahytherapy correlates with prostate- specific antigen failure free survival. The specific aims were: [i]to implement the TCP model in a computerized treatment planning system for TPPB, using the recently recommended dose calculation formalism and benchmark data presented in AAPM TG43 and validate it, [ii]to compute and examine the relationship between TCP and PSA failure free survival for patients receiving monotherapeutic 125I TPPB, [iii]to investigate the influence of the definition of PSA failure on the relationship between TCP and PSA failure free survival rates, and [iv]to develop a method for improving the TCP model. The conclusions were: [i]the model as implemented using AAPM TG43 formalism, produced results which were similar to that calculated by the original model. TCP was demonstrated to correlate strongly and similarly with underdosed prostate volume in comparison to data published from the original model, [ii]an analysis of 125I implants demonstrated that patients stratified into the high TCP group had PSA failure free survival rates which were superior to the rates for patients in the low TCP group, regardless of which of the five definitions of PSA failure was applied to

  10. Failure to Achieve a PSA Level {<=}1 ng/mL After Neoadjuvant LHRHA Therapy Predicts for Lower Biochemical Control Rate and Overall Survival in Localized Prostate Cancer Treated With Radiotherapy

    SciTech Connect

    Mitchell, Darren M. McAleese, Jonathan; Park, Richard M.; Stewart, David P.; Stranex, Stephen; Eakin, Ruth L.; Houston, Russell F.; O'Sullivan, Joe M.

    2007-12-01

    Purpose: To investigate whether failure to suppress the prostate-specific antigen (PSA) level to {<=}1 ng/mL after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy in patients scheduled to undergo external beam radiotherapy for localized prostate carcinoma is associated with reduced biochemical failure-free survival. Methods and Materials: A retrospective case note review of consecutive patients with intermediate- or high-risk localized prostate cancer treated between January 2001 and December 2002 with neoadjuvant hormonal deprivation therapy, followed by concurrent hormonal therapy and radiotherapy was performed. Patient data were divided for analysis according to whether the PSA level in Week 1 of radiotherapy was {<=}1.0 ng/mL. Biochemical failure was determined using the American Society for Therapeutic Radiology and Oncology (Phoenix) definition. Results: A total of 119 patients were identified. The PSA level after neoadjuvant hormonal deprivation therapy was {<=}1 ng/mL in 67 patients and >1 ng/mL in 52. At a median follow-up of 49 months, the 4-year actuarial biochemical failure-free survival rate was 84% vs. 60% (p = 0.0016) in favor of the patients with a PSA level after neoadjuvant hormonal deprivation therapy of {<=}1 ng/mL. The overall survival rate was 94% vs. 77.5% (p = 0.0045), and the disease-specific survival rate at 4 years was 98.5% vs. 82.5%. Conclusions: The results of our study have shown that patients with a PSA level >1 ng/mL at the beginning of external beam radiotherapy after {>=}2 months of neoadjuvant luteinizing hormone-releasing hormone agonist therapy have a significantly greater rate of biochemical failure and lower survival rate compared with those with a PSA level of {<=}1 ng/mL. Patients without adequate PSA suppression should be considered a higher risk group and considered for dose escalation or the use of novel treatments.

  11. Clinical performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project.

    PubMed

    Lazzeri, Massimo; Haese, Alexander; Abrate, Alberto; de la Taille, Alexandre; Redorta, Joan Palou; McNicholas, Thomas; Lughezzani, Giovanni; Lista, Giuliana; Larcher, Alessandro; Bini, Vittorio; Cestari, Andrea; Buffi, Nicolòmaria; Graefen, Markus; Bosset, Olivier; Le Corvoisier, Philippe; Breda, Alberto; de la Torre, Pablo; Fowler, Linda; Roux, Jacques; Guazzoni, Giorgio

    2013-08-01

    To test the sensitivity, specificity and accuracy of serum prostate-specific antigen isoform [-2]proPSA (p2PSA), %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer (PCa) undergoing prostate biopsy for suspected PCa. To evaluate the potential reduction in unnecessary biopsies and the characteristics of potentially missed cases of PCa that would result from using serum p2PSA, %p2PSA and PHI. The analysis consisted of a nested case-control study from the PRO-PSA Multicentric European Study, the PROMEtheuS project. All patients had a first-degree relative (father, brother, son) with PCa. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. Of the 1026 patients included in the PROMEtheuS cohort, 158 (15.4%) had a first-degree relative with PCa. p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001), and free/total PSA (%fPSA) values significantly lower (P < 0.001) in the 71 patients with PCa (44.9%) than in patients without PCa. Univariable accuracy analysis showed %p2PSA (area under the receiver-operating characteristic curve [AUC]: 0.733) and PHI (AUC: 0.733) to be the most accurate predictors of PCa at biopsy, significantly outperforming total PSA ([tPSA] AUC: 0.549), free PSA ([fPSA] AUC: 0.489) and %fPSA (AUC: 0.600) (P ≤ 0.001). For %p2PSA a threshold of 1.66 was found to have the best balance between sensitivity and specificity (70.4 and 70.1%; 95% confidence interval [CI]: 58.4-80.7 and 59.4-79.5 respectively). A PHI threshold of 40 was found to have the best balance between sensitivity and specificity (64.8 and 71.3%, respectively; 95% CI 52.5-75.8 and 60.6-80.5). At 90% sensitivity, the thresholds for %p2PSA and PHI were 1.20 and 25.5, with a specificity of 37.9 and 25.5%, respectively. At a %p2PSA threshold of 1.20, a total of 39 (24.8%) biopsies could have been avoided, but two cancers with a Gleason score (GS) of 7 would have been missed

  12. Exposure to Agent Orange is a significant predictor of prostate-specific antigen (PSA)-based recurrence and a rapid PSA doubling time after radical prostatectomy

    PubMed Central

    Shah, Sagar R.; Freedland, Stephen J.; Aronson, William J.; Kane, Christopher J.; Presti, Joseph C.; Amling, Christopher L.; Terris, Martha K.

    2011-01-01

    OBJECTIVE To investigate and report the clinicopathological characteristics and outcomes after radical prostatectomy (RP) in patients with prostate cancer and previous exposure to Agent Orange (AO), particularly in relationship to race. PATIENTS AND METHODS In 1495 veterans who had undergone RP the clinicopathological characteristics, biochemical progression rates, and prostate-specific antigen (PSA) doubling time (DT) after recurrence between AO-exposed and unexposed men were compared using logistic and linear regression and Cox proportional hazards analyses, and stratified by race. RESULTS The 206 (14%) men with AO exposure were more likely to be black (P = 0.001), younger (P < 0.001), treated more recently (P < 0.001), have a higher body mass index (P = 0.001), have clinical stage T1 disease (P < 0.001), and have lower preoperative PSA levels (P = 0.001). After adjusting for several clinical characteristics, AO exposure was not significantly related to adverse pathological features but was significantly associated with biochemical progression risk (relative risk 1.55, 95% confidence interval 1.15–2.09, P = 0.004) and shorter PSADT (P < 0.001) after recurrence (8.2 vs 18.6 months). When stratified by race, these associations were present and similar in both races, with no significant interaction between race and AO exposure for predicting biochemical recurrence or mean adjusted PSADT (P interaction >0.20). CONCLUSIONS Patients with AO exposure and treated with RP were more likely to be black, present with lower risk features, have an increased risk of biochemical progression, and shorter PSADT after recurrence. When stratified by race, the association between AO exposure and poor outcomes was present in both races. These findings suggest that among selected men who choose RP, AO exposure might be associated with more aggressive prostate cancer. PMID:19298411

  13. Prostate-Specific Antigen (PSA)-Based Population Screening for Prostate Cancer: An Evidence-Based Analysis.

    PubMed

    Pron, G

    2015-01-01

    Prostate cancer (PC) is the most commonly diagnosed non-cutaneous cancer in men and their second or third leading cause of cancer death. Prostate-specific antigen (PSA) testing for PC has been in common practice for more than 20 years. A systematic review of the scientific literature was conducted to determine the effectiveness of PSA-based population screening programs for PC to inform policy decisions in a publicly funded health care system. A systematic review of bibliographic databases was performed for systematic reviews or randomized controlled trials (RCT) of PSA-based population screening programs for PC. A broad search strategy was employed to identify studies reporting on key outcomes of PC mortality and all-cause mortality. The search identified 5 systematic reviews and 6 RCTs. None of the systematic reviews found a statistically significant reduction in relative risk (RR) of PC mortality or overall mortality with PSA-based screening. PC mortality reductions were found to vary by country, by screening program, and by age of men at study entry. The European Randomized Study of Screening for Prostate Cancer found a statistically significant reduction in RR in PC mortality at 11-year follow-up (0.79; 95% CI, 0.67-0.92), although the absolute risk reduction was small (1.0/10,000 person-years). However, the primary treatment for PCs differed significantly between countries and between trial arms. The American Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) found a statistically non-significant increase in RR for PC mortality with 13-year follow-up (1.09; 95% CI, 0.87-1.36). The degree of opportunistic screening in the control arm of the PLCO trial, however, was high. None of the RCTs found a reduction in all-cause mortality and all found a statistically significant increase in the detection of mainly low-risk, organ-confined PCs in the screening arm. There was no evidence of a PC mortality reduction in the American PLCO trial, which

  14. Prostate-Specific Antigen (PSA)–Based Population Screening for Prostate Cancer: An Evidence-Based Analysis

    PubMed Central

    Pron, G

    2015-01-01

    Background Prostate cancer (PC) is the most commonly diagnosed non-cutaneous cancer in men and their second or third leading cause of cancer death. Prostate-specific antigen (PSA) testing for PC has been in common practice for more than 20 years. Objectives A systematic review of the scientific literature was conducted to determine the effectiveness of PSA-based population screening programs for PC to inform policy decisions in a publicly funded health care system. Data Sources A systematic review of bibliographic databases was performed for systematic reviews or randomized controlled trials (RCT) of PSA-based population screening programs for PC. Review Methods A broad search strategy was employed to identify studies reporting on key outcomes of PC mortality and all-cause mortality. Results The search identified 5 systematic reviews and 6 RCTs. None of the systematic reviews found a statistically significant reduction in relative risk (RR) of PC mortality or overall mortality with PSA-based screening. PC mortality reductions were found to vary by country, by screening program, and by age of men at study entry. The European Randomized Study of Screening for Prostate Cancer found a statistically significant reduction in RR in PC mortality at 11-year follow-up (0.79; 95% CI, 0.67–0.92), although the absolute risk reduction was small (1.0/10,000 person-years). However, the primary treatment for PCs differed significantly between countries and between trial arms. The American Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) found a statistically non-significant increase in RR for PC mortality with 13-year follow-up (1.09; 95% CI, 0.87–1.36). The degree of opportunistic screening in the control arm of the PLCO trial, however, was high. None of the RCTs found a reduction in all-cause mortality and all found a statistically significant increase in the detection of mainly low-risk, organ-confined PCs in the screening arm. Conclusions There was no

  15. 5-Year Downstream Outcomes Following Prostate-Specific Antigen (PSA) Screening in Older Men

    PubMed Central

    Walter, Louise C.; Fung, Kathy Z.; Kirby, Katharine A.; Shi, Ying; Espaldon, Roxanne; O'Brien, Sarah; Freedland, Stephen J.; Powell, Adam A.; Hoffman, Richard M.

    2013-01-01

    Background Despite ongoing controversies surrounding PSA screening, large numbers of men age 65+ undergo screening. However, there are few data quantifying the chain of events following screening in clinical practice to better inform decisions. The objective of this study is to quantify 5-year downstream outcomes following a PSA screening result > 4 ng/ml in older men. Methods Longitudinal cohort study of 295,645 men age 65+ who underwent PSA screening in the VA healthcare system in 2003 and were followed for 5 years using national VA and Medicare data. Among men whose index screening PSA was > 4 ng/ml we determined the number who underwent biopsy, were diagnosed with prostate cancer, were treated and survived 5-years, according to baseline characteristics. Biopsy and treatment complications were also assessed. Results 25,208 (8.5%) men had an index PSA > 4 ng/ml. During 5-year follow-up, 8,313 (33%) men underwent at least one biopsy, 5,220 (63%) of men biopsied were diagnosed with prostate cancer of whom 4,284 (82%) were treated. Receipt of biopsy decreased with advancing age and worsening comorbidity (P<0.001), whereas the percentage treated for biopsy-detected cancer exceeded 75% even among men age 85+, those with Charlson score 3+, and those with low-risk cancer. Among men with biopsy-detected cancer, the risk of dying of non-prostate cancer causes increased with advancing age and comorbidity (P<0.001). 468 (6%) of men had 7-day biopsy complications. Treatment complications included 584 (14%) men with new incontinence and 588 (14%) men with new erectile dysfunction. Conclusions Receipt of biopsy is low in older men with abnormal screening PSA and decreases with advancing age and comorbidity. However, once biopsy detects cancer most men undergo immediate treatment regardless of advancing age, comorbidity, or low-risk cancer. Understanding downstream outcomes in clinical practice should better inform individualized decisions among older men considering PSA

  16. Prostate-Specific Antigen (PSA) Screening and New Biomarkers for Prostate Cancer (PCa)

    PubMed Central

    Rittenhouse, Harry; Hu, Xinhai; Cammann, Henning; Jung, Klaus

    2014-01-01

    Abstract PSA screening reduces PCa-mortality but the disadvantages overdiagnosis and overtreatment require multivariable risk-prediction tools to select appropriate treatment or active surveillance. This review explains the differences between the two largest screening trials and discusses the drawbacks of screening and its meta-analysisxs. The current American and European screening strategies are described. Nonetheless, PSA is one of the most widely used tumor markers and strongly correlates with the risk of harboring PCa. However, while PSA has limitations for PCa detection with its low specificity there are several potential biomarkers presented in this review with utility for PCa currently being studied. There is an urgent need for new biomarkers especially to detect clinically significant and aggressive PCa. From all PSA-based markers, the FDA-approved prostate health index (phi) shows improved specificity over percent free and total PSA. Another kallikrein panel, 4K, which includes KLK2 has recently shown promise in clinical research studies but has not yet undergone formal validation studies. In urine, prostate cancer gene 3 (PCA3) has also been validated and approved by the FDA for its utility to detect PCa. The potential correlation of PCA3 with cancer aggressiveness requires more clinical studies. The detection of the fusion of androgen-regulated genes with genes of the regulatory transcription factors in tissue of ~50% of all PCa-patients is a milestone in PCa research. A combination of the urinary assays for TMPRSS2:ERG gene fusion and PCA3 shows an improved accuracy for PCa detection. Overall, the field of PCa biomarker discovery is very exciting and prospective. PMID:27683457

  17. Diagnostic value of biparametric magnetic resonance imaging (MRI) as an adjunct to prostate-specific antigen (PSA)-based detection of prostate cancer in men without prior biopsies.

    PubMed

    Rais-Bahrami, Soroush; Siddiqui, M Minhaj; Vourganti, Srinivas; Turkbey, Baris; Rastinehad, Ardeshir R; Stamatakis, Lambros; Truong, Hong; Walton-Diaz, Annerleim; Hoang, Anthony N; Nix, Jeffrey W; Merino, Maria J; Wood, Bradford J; Simon, Richard M; Choyke, Peter L; Pinto, Peter A

    2015-03-01

    To determine the diagnostic yield of analysing biparametric (T2- and diffusion-weighted) magnetic resonance imaging (B-MRI) for prostate cancer detection compared with standard digital rectal examination (DRE) and prostate-specific antigen (PSA)-based screening. Review of patients who were enrolled in a trial to undergo multiparametric-prostate (MP)-MRI and MR/ultrasound fusion-guided prostate biopsy at our institution identified 143 men who underwent MP-MRI in addition to standard DRE and PSA-based prostate cancer screening before any prostate biopsy. Patient demographics, DRE staging, PSA level, PSA density (PSAD), and B-MRI findings were assessed for association with prostate cancer detection on biopsy. Men with detected prostate cancer tended to be older, with a higher PSA level, higher PSAD, and more screen-positive lesions (SPL) on B-MRI. B-MRI performed well for the detection of prostate cancer with an area under the curve (AUC) of 0.80 (compared with 0.66 and 0.74 for PSA level and PSAD, respectively). We derived combined PSA and MRI-based formulas for detection of prostate cancer with optimised thresholds. (i) for PSA and B-MRI: PSA level + 6 x (the number of SPL) > 14 and (ii) for PSAD and B-MRI: 14 × (PSAD) + (the number of SPL) >4.25. AUC for equations 1 and 2 were 0.83 and 0.87 and overall accuracy of prostate cancer detection was 79% in both models. The number of lesions positive on B-MRI outperforms PSA alone in detection of prostate cancer. Furthermore, this imaging criteria coupled as an adjunct with PSA level and PSAD, provides even more accuracy in detecting clinically significant prostate cancer. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  18. Expression of prostate-specific antigen (PSA) and human glandular kallikrein 2 (hK2) in ileum and other extraprostatic tissues.

    PubMed

    Olsson, A Yvonne; Bjartell, Anders; Lilja, Hans; Lundwall, Ake

    2005-01-10

    Prostate-specific antigen (PSA) is a widely used marker for prostate cancer. In the literature, there are reports of nonprostatic expression of PSA that potentially can affect early diagnosis. However, the results are scattered and inconclusive, which motivated us to conduct a more comprehensive study of the tissue distribution of PSA and the closely related protein human glandular kallikrein 2 (hK2). RT-PCR, in situ hybridization and immunohistochemistry were used to detect expression of both PSA and hK2 in secretory epithelial cells of trachea, thyroid gland, mammary gland, salivary gland, jejunum, ileum, epididymis, seminal vesicle and urethra, as well as in Leydig cells, pancreatic exocrine glands and epidermis. Immunometric measurements revealed that the concentration of PSA in nonprostatic tissues represents less than 1% of the amount in normal prostate. Pronounced expression of PSA was detected in the Paneth cells in ileum, which prompted us to compare functional parameters of PSA in ileum and prostate. We found that in homogenates from these 2 tissues, PSA manifested equivalent amidolytic activity and capacity to form complexes with protease inhibitors in blood in vitro. Thus, PSA released from sources other than the prostate may add to the plasma pool of this protein, but given the lower levels detected from those sites, it is unlikely that nonprostatic PSA normally can interfere with the diagnosis of prostate cancer. Nevertheless, this risk should not be neglected as it may be of clinical significance under certain circumstances. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.

  19. Plasma Carotenoids and Tocopherols in Relation to Prostate-specific Antigen (PSA) Levels Among Men with Biochemical Recurrence of Prostate Cancer

    PubMed Central

    Antwi, Samuel; Steck, Susan E.; Zhang, Hongmei; Stumm, Lareissa; Zhang, Jiajia; Hurley, Thomas G.; Hebert, James R.

    2015-01-01

    Background Although men presenting with clinically localized prostate cancer (PrCA) often are treated with radical prostatectomy or radiation therapy with curative intent, about 25–40% develop biochemically recurrent PrCA within 5 years of treatment, which has no known cure. Studies suggest that carotenoid and tocopherol intake may be associated with PrCA risk and progression. We examined plasma carotenoid and tocopherol levels in relation to prostate-specific antigen (PSA) levels among men with PSA-defined biochemical recurrence of PrCA. Methods Data analyzed were from a 6-month diet, physical activity and stress-reduction intervention trial conducted in South Carolina among biochemically recurrent PrCA patients (n=39). Plasma carotenoids and tocopherol levels were measured using high-performance liquid chromatography (HPLC). Linear regression was used to estimate least-square means comparing PSA levels of men with high versus low carotenoid/tocopherol levels, adjusting for covariates. Results After adjusting for baseline PSA level, plasma cis-lutein/zeaxanthin level at 3 months was related inversely to PSA level at 3 months (P=0.0008), while α-tocopherol (P=0.01), β-cryptoxanthin (P=0.01), and all-trans-lycopene (P=0.004) levels at 3 months were related inversely to PSA levels at 6-months. Percent increase in α-tocopherol and trans-β-carotene levels from baseline to month 3 were associated with lower PSA levels at 3 and 6 months. Percent increase in β−cryptoxanthin, cislutein/zeaxanthin and all-trans-lycopene were associated with lower PSA levels at 6 months only. Conclusions Certain plasma carotenoids and tocopherols were related inversely to PSA levels at various timepoints, suggesting that greater intake of foods containing these micronutrients might be beneficial to men with PSA-defined PrCA recurrence. PMID:26165176

  20. Plasma carotenoids and tocopherols in relation to prostate-specific antigen (PSA) levels among men with biochemical recurrence of prostate cancer.

    PubMed

    Antwi, Samuel O; Steck, Susan E; Zhang, Hongmei; Stumm, Lareissa; Zhang, Jiajia; Hurley, Thomas G; Hebert, James R

    2015-10-01

    Although men presenting with clinically localized prostate cancer (PrCA) often are treated with radical prostatectomy or radiation therapy with curative intent, about 25-40% develop biochemically recurrent PrCA within 5 years of treatment, which has no known cure. Studies suggest that carotenoid and tocopherol intake may be associated with PrCA risk and progression. We examined plasma carotenoid and tocopherol levels in relation to prostate-specific antigen (PSA) levels among men with PSA-defined biochemical recurrence of PrCA. Data analyzed were from a 6-month diet, physical activity and stress-reduction intervention trial conducted in South Carolina among biochemically recurrent PrCA patients (n=39). Plasma carotenoids and tocopherol levels were measured using high-performance liquid chromatography (HPLC). Linear regression was used to estimate least-square means comparing PSA levels of men with high versus low carotenoid/tocopherol levels, adjusting for covariates. After adjusting for baseline PSA level, plasma cis-lutein/zeaxanthin level at 3 months was related inversely to PSA level at 3 months (P=0.0008), while α-tocopherol (P=0.01), β-cryptoxanthin (P=0.01), and all-trans-lycopene (P=0.004) levels at 3 months were related inversely to PSA levels at 6-months. Percent increase in α-tocopherol and trans-β-carotene levels from baseline to month 3 were associated with lower PSA levels at 3 and 6 months. Percent increase in β-cryptoxanthin, cis-lutein/zeaxanthin and all-trans-lycopene were associated with lower PSA levels at 6 months only. Certain plasma carotenoids and tocopherols were related inversely to PSA levels at various timepoints, suggesting that greater intake of foods containing these micronutrients might be beneficial to men with PSA-defined PrCA recurrence. Copyright © 2015. Published by Elsevier Ltd.

  1. Investigating the prostate specific antigen, body mass index and age relationship: is an age-BMI-adjusted PSA model clinically useful?

    PubMed

    Harrison, Sean; Tilling, Kate; Turner, Emma L; Lane, J Athene; Simpkin, Andrew; Davis, Michael; Donovan, Jenny; Hamdy, Freddie C; Neal, David E; Martin, Richard M

    2016-12-01

    Previous studies indicate a possible inverse relationship between prostate-specific antigen (PSA) and body mass index (BMI), and a positive relationship between PSA and age. We investigated the associations between age, BMI, PSA, and screen-detected prostate cancer to determine whether an age-BMI-adjusted PSA model would be clinically useful for detecting prostate cancer. Cross-sectional analysis nested within the UK ProtecT trial of treatments for localized cancer. Of 18,238 men aged 50-69 years, 9,457 men without screen-detected prostate cancer (controls) and 1,836 men with prostate cancer (cases) met inclusion criteria: no history of prostate cancer or diabetes; PSA < 10 ng/ml; BMI between 15 and 50 kg/m(2). Multivariable linear regression models were used to investigate the relationship between log-PSA, age, and BMI in all men, controlling for prostate cancer status. In the 11,293 included men, the median PSA was 1.2 ng/ml (IQR: 0.7-2.6); mean age 61.7 years (SD 4.9); and mean BMI 26.8 kg/m(2) (SD 3.7). There were a 5.1% decrease in PSA per 5 kg/m(2) increase in BMI (95% CI 3.4-6.8) and a 13.6% increase in PSA per 5-year increase in age (95% CI 12.0-15.1). Interaction tests showed no evidence for different associations between age, BMI, and PSA in men above and below 3.0 ng/ml (all p for interaction >0.2). The age-BMI-adjusted PSA model performed as well as an age-adjusted model based on National Institute for Health and Care Excellence (NICE) guidelines at detecting prostate cancer. Age and BMI were associated with small changes in PSA. An age-BMI-adjusted PSA model is no more clinically useful for detecting prostate cancer than current NICE guidelines. Future studies looking at the effect of different variables on PSA, independent of their effect on prostate cancer, may improve the discrimination of PSA for prostate cancer.

  2. Comparison of biochemical failure rates between permanent prostate brachytherapy and radical retropubic prostatectomy as a function of posttherapy PSA nadir plus 'X'.

    PubMed

    Ahmed, Kamran A; Davis, Brian J; Mynderse, Lance A; Slezak, Jeffrey M; Bergstralh, Eric J; Wilson, Torrence M; Choo, C Richard

    2014-07-29

    Prostate-specific antigen (PSA) nadir + 2 ng/mL, also known as the Phoenix definition, is the definition most commonly used to establish biochemical failure (BF) after external beam radiotherapy for prostate cancer management. The purpose of this study is to compare BF rates between permanent prostate brachytherapy (PPB) and radical retropubic prostatectomy (RRP) as a function of PSA nadir plus varying values of X and examine the associated implications. We retrospectively searched for patients who underwent PPB or RRP at our institution between 1998 and 2004. Only primary patients not receiving androgen-deprivation therapy were included in the study. Three RRP patients were matched to each PPB patient on the basis of prognostic factors. BF rates were estimated for PSA nadirs + different values of X. A total of 1,164 patients were used for analysis: 873 in the RRP group and 291 in the PPB group. Patients were equally matched by clinical stage, biopsy Gleason sum, primary Gleason grade, and pretherapy PSA value. Median follow-up was 3.1 years for RRP patients and 3.6 years in the PPB group (P = .01). Using PSA nadir + 0.1 ng/mL for the definition of BF, the 5-year BF rate was 16.3% for PPB patients and 13.5% for RRP patients (P = .007), whereas at nadir + 2 ng/mL or greater, the BF rates were less than 3% and were indistinguishable between PPB and RRP patients. In a cohort of well-matched patients who had prostatectomy or brachytherapy, we examined BF as a function of nadir + X, where X was treated as a continuous variable. As X increases from 0.1 to 2.0 ng/mL, the BF curves converge, and above 2.0 ng/mL they are essentially indistinguishable. The data presented are of interest as BF definitions continue to evolve.

  3. Prostate-specific antigen as a biomarker of condom failure: comparison of three laboratory assays and self-reported condom use problems in a randomized trial of female condom performance.

    PubMed

    Walsh, Terri; Warner, Lee; Macaluso, Maurizio; Frezieres, Ron; Snead, Margaret; Wraxall, Brian

    2012-07-01

    Prostate-specific antigen (PSA), a biomarker for semen exposure, may provide a more objective measure of condom failure than subject self-reports. Methods for measuring PSA vary and their comparability with respect to assessing condom performance has not been adequately evaluated. This study compared results from three different PSA assays of vaginal samples collected by subjects in a randomized clinical trial which compared the performance of female condoms. We selected 30 pairs of pre- and post-coital vaginal samples from subjects who reported condom functionality problems or whose original PSA assay was positive. Samples were retested using three different PSA assays [quantitative enzyme-linked immunoassay (EIA), rocket immune-electrophoresis (RIE) and chromatographic immunoassay (CIA)]. We compared the proportion of condom uses where the post-coital PSA result indicated semen exposure for each of the three assays. Despite varying levels of sensitivity, the results from all three assays were remarkably consistent. Self-reported condom failures did not correlate well with positive PSA results, suggesting that exclusive reliance on either PSA or user self-report may be inadequate for assessing condom functionality. In combination with user self-report of condom failure, PSA testing provides a reliable, objective marker of condom functionality. Studies based on PSA testing may improve on conventional contraceptive clinical trials by offering a more direct assessment of a condom product's ability to prevent semen exposure. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Utility of RhoC and ZAG protein expression as biomarkers for prediction of PSA failure following radical prostatectomy for high grade prostate cancer.

    PubMed

    Mills, John; Oliver, Alice; Sherwin, Justin C; Frydenberg, Mark; Peters, Justin S; Costello, Anthony; Harewood, Laurence; Love, Christopher; Redgrave, Nicholas; van Golen, Kenneth L; Bailey, Michael; Pedersen, John

    2012-10-01

    To assess the prognostic utility of semi-quantiative expression of RhoC protein in whole prostates from patients who had radical prostatectomies for high grade prostate cancer (PCa). Subjects who had surgery >55 months previously with primary Gleason pattern 4 PCa were identified from practice records, archival tissues were retrieved for review and RhoC immunohistochemistry, and ZAG expression was also assessed as a control. Eighty-nine subjects were included in the study; 57 had a rising prostate specific antigen (PSA) post-operatively ('cases') and 32 did not ('controls'). By univariate analysis, expression of both RhoC and ZAG proteins was greater in controls than cases, but this was significant only for ZAG. By multivariate analysis, Gleason variables (patterns and score), extraprostatic extension and decreased RhoC staining all contributed to predicting PSA failure (p < 0.05). ZAG expression was inversely correlated with Gleason pattern and hence was not independently predictive in our multivariate model. Increased RhoC expression predicted a good outcome after radical prostatectomy. ZAG staining also correlated with a favourable outcome but was not independently predictive due to its relationship with Gleason pattern.

  5. Prostatic specific antigen and bone scan in the diagnosis and follow-up of prostate cancer. Can diagnostic significance of PSA be increased?

    PubMed

    Bantis, Athanasios; Grammaticos, Philip

    2012-01-01

    Prostate cancer (PC) is currently the most frequently diagnosed cancer in males and constitutes a major health issue in developed countries. On the other hand, the majority of PC cases are considered clinically not significant and certainly not lethal. These discrepancies highlight the need for the early detection of especially those cases that have aggressive features and call for early and radical intervention. The clinical use of prostatic specific antigen (PSA) towards this end is recognized as inadequate since PSA is prostate specific, but not a PC specific marker, as it is known to increase in other prostate diseases such as benign hyperplasia, inflammations, transrectal ultrasound examination, biopsy and after transurethral prostatectomy. However due to lack of other more specific markers, digital rectal examination combined with serum PSA are suggested for PC screening and diagnosis. With regard to advanced disease where bone involvement is the rule, nuclear medicine bone scan using radioactive bisphosphonates such as technetium-99m methylene-diphosphonate is quite common and reliable technique for detecting and monitoring bone metastases. The major advantage of nuclear scintigraphy is its ability to reveal bone metastases significantly earlier than the conventional X-ray imaging techniques. PSA density, velocity, doubling time and free to total PSA ratio increase the significance of serum PSA in diagnosing PC. The combination of an increased PSA (>20ng/mL) and a high biopsy Gleason score (>8) enhances the possibility of bone metastases (P<0001) and mandates a bone scan. In conclusion, serum PSA testing is currently recommended in symptomatic PC patients for disease staging and treatment monitoring and in asymptomatic selected population groups aged more than 50 years. It is reasonable to suggest that PSA density, velocity, doubling time and free to total PSA ratio or combining PSA with Gleason score shall greatly increase PSA specificity in detecting PC

  6. The effect of testosterone replacement therapy on prostate-specific antigen (PSA) levels in men being treated for hypogonadism: a systematic review and meta-analysis.

    PubMed

    Kang, De-Ying; Li, Hong-Jun

    2015-01-01

    Testosterone replacement therapy is used for the treatment of age-related male hypogonadism, and prostate-specific antigen (PSA) is a primary screening tool for prostate cancer. The systematic review and meta-analysis aimed to determine the effect of testosterone replacement therapy on PSA levels.Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until February 28, 2014, and inclusion criteria were as follows: randomized controlled trial; intervention group received testosterone/androgen replacement therapy; control group did not receive treatment; and no history of prostate cancer. The primary outcome was change of PSA level between before and after treatment. Secondary outcomes were elevated PSA level after treatment, and the number of patients who developed prostate cancer.After initially identifying 511 articles, 15 studies with a total of 739 patients that received testosterone replacement and 385 controls were included. The duration of treatment ranged from 3 to 12 months. Patients treated with testosterone tended to have higher PSA levels, and thus a greater change than those that received control treatments (difference in means of PSA levels = 0.154, 95% confidence interval [CI] 0.069 to 0.238, P < 0.001). The difference in means of PSA levels were significant higher for patients that received testosterone intramuscularly (IM) than controls (difference in means of PSA levels = 0.271, 95% CI 0.117-0.425, P = 0.001). Elevated PSA levels after treatment were similar between patients that received treatment and controls (odds ratio [OR] = 1.02, 95% CI 0.48-2.20, P = 0.953). Only 3 studies provided data with respect to the development of prostate cancer, and rates were similar between those that received treatment and controls.Testosterone replacement therapy does not increase PSA levels in men being treated for hypogonadism, except when it is given IM and even the increase with IM administration is minimal.

  7. Improved porous silicon (P-Si) microarray based PSA (prostate specific antigen) immunoassay by optimized surface density of the capture antibody

    PubMed Central

    Lee, SangWook; Kim, Soyoun; Malm, Johan; Jeong, Ok Chan; Lilja, Hans; Laurell, Thomas

    2014-01-01

    Enriching the surface density of immobilized capture antibodies enhances the detection signal of antibody sandwich microarrays. In this study, we improved the detection sensitivity of our previously developed P-Si (porous silicon) antibody microarray by optimizing concentrations of the capturing antibody. We investigated immunoassays using a P-Si microarray at three different capture antibody (PSA - prostate specific antigen) concentrations, analyzing the influence of the antibody density on the assay detection sensitivity. The LOD (limit of detection) for PSA was 2.5ngmL−1, 80pgmL−1, and 800fgmL−1 when arraying the PSA antibody, H117 at the concentration 15µgmL−1, 35µgmL−1 and 154µgmL−1, respectively. We further investigated PSA spiked into human female serum in the range of 800fgmL−1 to 500ngmL−1. The microarray showed a LOD of 800fgmL−1 and a dynamic range of 800 fgmL−1 to 80ngmL−1 in serum spiked samples. PMID:24016590

  8. Correlation of prostate-specific antigen nadir and biochemical failure after high-intensity focused ultrasound of localized prostate cancer based on the Stuttgart failure criteria - analysis from the @-Registry.

    PubMed

    Ganzer, Roman; Robertson, Cary N; Ward, John F; Brown, Stephen C W; Conti, Giario N; Murat, Francois J; Pasticier, Gilles; Rebillard, Xavier; Thuroff, Stefan; Wieland, Wolf F; Blana, Andreas

    2011-10-01

    •To determine if the prostate-specific antigen (PSA) nadir after high-intensity focused ultrasound (HIFU) can be used as a predictor of the biochemical disease-free survival rate (DFSR). •Patient data were derived from the multicentre-based @-Registry, the largest registry to report outcomes in patients with localized prostate cancer after Ablatherm® HIFU. •PSA level was measured at 3-month intervals. Patients were stratified into four PSA nadir groups: group 1, ≤0.2 ng/mL; group 2, 0.21-0.5 ng/mL; group 3, 0.51-1 ng/mL; and group 4, >1 ng/mL. •Biochemical treatment failure was defined according to the Stuttgart definition (PSA nadir + 1.2 ng/mL) and the Phoenix definition (PSA nadir + 2 ng/mL). •Biopsy was performed at 3-6 months post-HIFU or if a PSA level was recorded that was considered clinically relevant. •The present study included 804 patients. Biochemical treatment success rates at 5 years according to the Stuttgart definition for the four PSA nadir sub-groups were as follows: 84, 64, 40 and 30% for groups 1-4, respectively. •The equivalent 5-year biochemical success rates using the Phoenix definition were 94, 74, 66 and 47%, respectively. •Significantly more patients had a negative biopsy in the lowest PSA nadir group than in the other sub-groups (91.6 vs 73.1%; P < 0.001). •The present study is limited by its retrospective nature and variations in clinical practice across participating centres. •This multicentre analysis confirms that PSA nadir after HIFU predicts biochemical DFSR in a statistically significant manner. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  9. Impact of Neoadjuvant Prostate-Specific Antigen Kinetics on Biochemical Failure and Prostate Cancer Mortality: Results From a Prospective Patient Database

    SciTech Connect

    Foo, Marcus; Lavieri, Mariel; Pickles, Tom

    2013-02-01

    Purpose: To confirm findings from an earlier report showing that neoadjuvant (NA) prostate-specific antigen (PSA) halving time (PSAHT) impacts biochemical failure (BF) rates, and to examine its association with prostate cancer-specific survival (PCSS), in a large prospective cohort of patients. Methods and Materials: A total of 502 patients were selected from a prospective database, who had localized prostate adenocarcinoma treated with 2-12 months of neoadjuvant androgen deprivation therapy (N-ADT) followed by external beam radiation therapy (EBRT) between 1994 and 2000, and had at least 2 NA PSA values. Seventy-four percent of patients had high-risk prostate cancer. Median initial PSA value, N-ADT duration, total ADT duration, and radiation therapy dose were 14 ng/mL, 6.9 months, 10.8 months, and 68 Gy, respectively. Results: At a median follow-up of 9.9 years, 210 patients have had a BF. Median PSAHT was 18 days. On univariate analysis, PSAHT was not shown to predict for BF (P=.69) or PCSS (P=.28). However, NA nadir PSA (nanPSA) and post-therapy nadir PSA (ptnPSA), when analyzed as continuous or categoric variables, predicted for BF (P<.001) and PCSS (P<.001). On multivariate analysis, nanPSA (P=.037) and ptnPSA (P<.001) continued to be significantly associated with BF. However, N-ADT duration lost significance (P=.67), and PSAHT remained a nonsignificant predictor (P=.97). For PCSS, multivariate analysis showed nanPSA (P=.049) and ptnPSA (P<.001) to be significant. Again PSAHT (P=.49) remained nonsignificant. Conclusions: In this large, prospective cohort of patients, NA PSA kinetics, expressed as PSAHT, did not predict BF or PCSS. However, nadir PSAs, in both the NA and post-therapy settings, were significant predictors of BF and PCSS. Optimization of therapy could potentially be based on early PSA response, with shorter durations of ADT for those predicted to do favorably, and intensification of therapy for those likely to have poorer outcomes.

  10. Prostate-specific antigen (PSA) screening and follow-up investigations in Māori and non-Māori men in New Zealand.

    PubMed

    Obertová, Zuzana; Scott, Nina; Brown, Charis; Hodgson, Fraser; Stewart, Alistair; Holmes, Michael; Lawrenson, Ross

    2014-08-26

    Māori men in New Zealand have higher mortality from prostate cancer, despite having lower incidence rates. The objective of this study was to examine patterns of screening for prostate cancer in primary care and follow-up investigations after an elevated prostate-specific antigen (PSA) result in Māori and non-Māori men in order to help explain the observed differences in incidence and mortality. Men aged 40+ years were identified from 31 general practices across the Midland Cancer Network region. Computerised practice records were cross-referenced with laboratory data to determine the number and value of PSA tests undertaken between January 2007 and December 2010. Screening rates were calculated for the year 2010 by age, ethnicity, and practice. For men with an elevated PSA result information on specialist referrals and biopsy was extracted from practice records. Practice characteristics were assessed with respect to screening rates for Māori and non-Māori men. The final study population included 34,960 men aged 40+ years; 14% were Māori. Māori men were less likely to be screened in 2010 compared with non-Māori men (Mantel Haenszel (M-H) age-adjusted risk ratio (RR), 0.52 [95% CI, 0.48, 0.56]). When screened, Māori men were more than twice as likely to have an elevated PSA result compared with non-Māori men (M-H age-adjusted RR, 2.16 [95% CI, 1.42, 3.31]). There were no significant differences between Māori and non-Māori men in the rate of follow-up investigations and cancer detection. Māori provider practices showed equal screening rates for Māori and non-Māori men, but they were also the practices with the lowest overall screening rates. Māori men were half as likely to be screened compared to non-Māori men. This probably explains the lower reported incidence of prostate cancer for Māori men. Practice characteristics had a major influence on screening rates. Large variation in screening behaviour among practices and differences in follow

  11. Endogenous and exogenous testosterone and the risk of prostate cancer and increased prostate-specific antigen (PSA) level: a meta-analysis.

    PubMed

    Boyle, Peter; Koechlin, Alice; Bota, Maria; d'Onofrio, Alberto; Zaridze, David G; Perrin, Paul; Fitzpatrick, John; Burnett, Arthur L; Boniol, Mathieu

    2016-11-01

    To review and quantify the association between endogenous and exogenous testosterone and prostate-specific antigen (PSA) and prostate cancer. Literature searches were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Prospective cohort studies that reported data on the associations between endogenous testosterone and prostate cancer, and placebo-controlled randomized trials of testosterone replacement therapy (TRT) that reported data on PSA and/or prostate cancer cases were retained. Meta-analyses were performed using random-effects models, with tests for publication bias and heterogeneity. Twenty estimates were included in a meta-analysis, which produced a summary relative risk (SRR) of prostate cancer for an increase of 5 nmol/L of testosterone of 0.99 (95% confidence interval [CI] 0.96, 1.02) without heterogeneity (I² = 0%). Based on 26 trials, the overall difference in PSA levels after onset of use of TRT was 0.10 ng/mL (-0.28, 0.48). Results were similar when conducting heterogeneity analyses by mode of administration, region, age at baseline, baseline testosterone, trial duration, type of patients and type of TRT. The SRR of prostate cancer as an adverse effect from 11 TRT trials was 0.87 (95% CI 0.30; 2.50). Results were consistent across studies. Prostate cancer appears to be unrelated to endogenous testosterone levels. TRT for symptomatic hypogonadism does not appear to increase PSA levels nor the risk of prostate cancer development. The current data are reassuring, although some caution is essential until multiple studies with longer follow-up are available. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  12. PSA nadir as a predictive factor for biochemical disease-free survival and overall survival following whole-gland salvage HIFU following radiotherapy failure

    PubMed Central

    Shah, T T; Peters, M; Kanthabalan, A; McCartan, N; Fatola, Y; van der Voort van Zyp, J; van Vulpen, M; Freeman, A; Moore, C M; Arya, M; Emberton, M; Ahmed, H U

    2016-01-01

    Background: Treatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound (HIFU) might have a role in this setting. Methods: An independent HIFU registry collated consecutive cases of HIFU. Between 2005 and 2012, we identified 50 men who underwent whole-gland HIFU following histological confirmation of localised disease following prior external beam radiotherapy (2005–2012). No upper threshold was applied for risk category, PSA or Gleason grade either at presentation or at the time of failure. Progression was defined as a composite with biochemical failure (Phoenix criteria (PSA>nadir+2 ng ml−1)), start of systemic therapies or metastases. Results: Median age (interquartile range (IQR)), pretreatment PSA (IQR) and Gleason score (range) were 68 years (64–72), 5.9 ng ml−1 (2.2–11.3) and 7 (6–9), respectively. Median follow-up was 64 months (49–84). In all, 24/50 (48%) avoided androgen-deprivation therapies. Also, a total of 28/50 (56%) achieved a PSA nadir <0.5 ng ml−1, 15/50 (30%) had a nadir ⩾0.5 ng ml−1 and 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year progression-free survival (PFS) was 72, 40 and 31%, respectively. Actuarial 1, 3 and 5-year overall survival (OS) was 100, 94 and 87%, respectively. When comparing patients with PSA nadir <0.5 ng ml−1, nadir ⩾0.5 and non-responders, a statistically significant difference in PFS was seen (P<0.0001). Three-year PFS in each group was 57, 20 and 0%, respectively. Five-year OS was 96, 100 and 38%, respectively. Early in the learning curve, between 2005 and 2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measure questionnaires showed incontinence (any pad-use) as 8/26 (31%). Conclusions: In our series of high-risk patients, in whom 30–50% may have micro

  13. PSA nadir as a predictive factor for biochemical disease-free survival and overall survival following whole-gland salvage HIFU following radiotherapy failure.

    PubMed

    Shah, T T; Peters, M; Kanthabalan, A; McCartan, N; Fatola, Y; van der Voort van Zyp, J; van Vulpen, M; Freeman, A; Moore, C M; Arya, M; Emberton, M; Ahmed, H U

    2016-09-01

    Treatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound (HIFU) might have a role in this setting. An independent HIFU registry collated consecutive cases of HIFU. Between 2005 and 2012, we identified 50 men who underwent whole-gland HIFU following histological confirmation of localised disease following prior external beam radiotherapy (2005-2012). No upper threshold was applied for risk category, PSA or Gleason grade either at presentation or at the time of failure. Progression was defined as a composite with biochemical failure (Phoenix criteria (PSA>nadir+2 ng ml(-1))), start of systemic therapies or metastases. Median age (interquartile range (IQR)), pretreatment PSA (IQR) and Gleason score (range) were 68 years (64-72), 5.9 ng ml(-1) (2.2-11.3) and 7 (6-9), respectively. Median follow-up was 64 months (49-84). In all, 24/50 (48%) avoided androgen-deprivation therapies. Also, a total of 28/50 (56%) achieved a PSA nadir <0.5 ng ml(-1), 15/50 (30%) had a nadir ⩾0.5 ng ml(-1) and 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year progression-free survival (PFS) was 72, 40 and 31%, respectively. Actuarial 1, 3 and 5-year overall survival (OS) was 100, 94 and 87%, respectively. When comparing patients with PSA nadir <0.5 ng ml(-1), nadir ⩾0.5 and non-responders, a statistically significant difference in PFS was seen (P<0.0001). Three-year PFS in each group was 57, 20 and 0%, respectively. Five-year OS was 96, 100 and 38%, respectively. Early in the learning curve, between 2005 and 2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measure questionnaires showed incontinence (any pad-use) as 8/26 (31%). In our series of high-risk patients, in whom 30-50% may have micro-metastases, disease control rates were promising in PSA

  14. Production of milligram concentrations of free prostate specific antigen (fPSA) from LNCaP cell culture: difference between fPSA from LNCaP cell and seminal plasma.

    PubMed

    Wu, J T; Lyons, B W; Liu, G H; Wu, L L

    1998-01-01

    We have established a procedure for the production of milligrams of free PSA (fPSA) from LNCaP cells derived from a human carcinoma of the prostate. By growing LNCaP cells in a serum-free medium in the presence of a synthetic androgen (R1881) and taking advantage of the special design of the Micro-mouse Hollow Fiber Bioreactor, relatively pure fPSA could be obtained. We found that columns containing either Sephacryl S-100 or S-200 could be used to remove the small amount of bovine serum albumin (BSA) and PSA-alpha 1-antichymotrypsin complex (PSA-ACT) from the preparation. More than 90% of the PSA from LNCaP cell cultures are fPSA. Like fPSA from seminal plasma, two fractions of fPSA differing in protease activity can be separated by DEAE-Sepharose chromatography. Based on the band pattern exhibited on the Western blot following sodium dodecyl sulfate-polyacrylamide electrophoresis separation, fPSA from LNCaP contains more inactive PSA isoforms. This was confirmed by chromatofocusing: the isoelectric point (pl) of the major PSA isoforms from the LNCaP cell culture were higher (6.8 and 6.6) than that (6.4 and 6.1) of fPSA from seminal fluid. We conclude that the LNCaP cell culture is a reliable source for obtaining large quantities of pure fPSA both for the preparation of assay calibrators and controls and for studying the difference in fPSA between benign prostate disease and prostate cancer.

  15. Outcomes of men with an elevated prostate-specific antigen (PSA) level as their sole preoperative intermediate- or high-risk feature

    PubMed Central

    Faisal, Farzana A.; Sundi, Debasish; Pierorazio, Phillip M.; Ball, Mark W.; Humphreys, Elizabeth B.; Han, Misop; Epstein, Jonathan I.; Partin, Alan W.; Carter, H. Ballentine; Bivalacqua, Trinity J.; Schaeffer, Edward M.; Ross, Ashley E.

    2015-01-01

    Objective To investigate the post-prostatectomy and long-term outcomes of men presenting with an elevated pretreatment prostate-specific antigen (PSA) level (>10 ng/mL), but otherwise low-risk features (biopsy Gleason score ≤6 and clinical stage ≤T2a). Patients and Methods PSA-incongruent intermediate-risk (PII) cases were defined as those patients with preoperative PSA >10 and ≤20 ng/mL but otherwise low-risk features, and PSA-incongruent high-risk (PIH) cases were defined as men with PSA >20 ng/mL but otherwise low-risk features. Our institutional radical prostatectomy database (1992–2012) was queried and the results were stratified into D’Amico low-, intermediate- and high risk, PSA-incongruent intermediate-risk and PSA-incongruent high-risk cases. Prostate cancer (PCa) features and outcomes were evaluated using appropriate comparative tests. Multivariable analyses were adjusted for age, race and year of surgery. Results Of the total cohort of 17 608 men, 1132 (6.4%) had PII-risk disease and 183 (1.0%) had PIH-risk disease. Compared with the low-risk group, the odds of upgrading at radical prostatectomy (RP) were 2.20 (95% CI 1.93–2.52; P < 0.001) for the PII group and 3.58 (95% CI 2.64–4.85; P < 0.001) for the PIH group, the odds of extraprostatic disease at RP were 2.35 (95% CI 2.05–2.68; P < 0.001) for the PII group and 6.68 (95% CI 4.89–9.15; P < 0.001) for the PIH group, and the odds of positive surgical margins were 1.97 (95% CI 1.67–2.33; P < 0.001) for the PII group and 3.54 (95% CI 2.50–4.95, P < 0.001) for the PIH group. Compared with low-risk disease, PII-risk disease was associated with a 2.85-, 2.99- and 3.32-fold greater risk of biochemical recurrence (BCR), metastasis and PCa-specific mortality, respectively, and PIH-risk disease was associated with a 5.32-, 6.14- and 7.07-fold greater risk of BCR, metastasis and PCa-specific mortality, respectively (P ≤ 0.001 for all comparisons). For the PII group, the higher risks of

  16. Reliability of prostate-specific antigen-marker in determining biochemical failure during the first 2 years after external beam radiation therapy and hormone therapy in patients with non-operated prostate cancer.

    PubMed

    Vigna-Taglianti, Riccardo; Russi, Elvio G; Boriano, Alberto; Gianello, Luca; Denaro, Nerina; Lucio, Francesco; Arena, Giuseppe; Buglione, Michela; Pergolizzi, Stefano; Ricardi, Umberto; Magrini, Stefano

    2014-01-01

    The presence of prostate-specific antigen (PSA)-bounce after external beam radiation therapy (EBRT) and hormone therapy (HT) makes PSA an unreliable marker in determining PSA biochemical failure (PSA-BF) during the first 2 years after EBRT + HT in patients with non-operated prostate cancer (CaP). To determine the reliability of PSA-BF in predicting clinical outcomes, the Kamat definition, which does not consider PSA-BF during the first 24 months after EBRT, was tested against three other more frequently used methods (American Society of Radiation Oncology, Vancouver, and American Society of Radiation Oncology-Phoenix), which do. Secondly, their relative accuracies in predicting the clinical outcomes were also calculated. In January 2011, 193 consecutive CaPs, treated with radical EBRT + HT in our institution from 1999 to 2002, were retrospectively investigated. BF was calculated according to the Kamat definition against the other three above-mentioned methods. Each BF-free survival was analyzed in function of every clinical endpoint (clinical-failure-free survival, cause specific survival, and overall survival) using univariate and multivariate Cox regression analyses. The accuracy of each definition in predicting clinical relapse was also calculated and compared. Only the Kamat BF definition had both a significant Cox hazard ratio, regarding clinical events or cancer deaths, and the best accuracy values in predicting clinical outcomes. Retrospective study design was the major limitation of the study. Only the Kamat definition, which does not consider PSA-BF during the first 24 months after EBRT + HT, was shown to be a reliable predictor of clinical events. Thus, our results suggest that solely PSA-based BF should not be considered as a reliable surrogate endpoint during the first 24 months after EBRT + HT. Consequently, caution should be used in adopting rescue treatment without further work-up on an individual basis. Copyright © 2014 Elsevier Inc. All rights

  17. Transperineal prostate biopsy detects significant cancer in patients with elevated prostate-specific antigen (PSA) levels and previous negative transrectal biopsies.

    PubMed

    Dimmen, Magne; Vlatkovic, Ljiljana; Hole, Knut-Håkon; Nesland, Jahn M; Brennhovd, Bjørn; Axcrona, Karol

    2012-07-01

    Several authors have previously reported that transrectal prostate biopsy has a false-negative rate of 20-30%, and that a number of prostate cancers missed on transrectal biopsy can be detected by transperineal biopsy. It has also been shown that most of these tumours are located anteriorly in the prostate gland. The present study showed a high rate of prostate cancer in patients with previous negative transrectal biopsies but elevated PSA levels, and that the cancers were located anteriorly in the prostate gland. Also, most of these cancers were clinically significant in patients that underwent RP, i.e. a high proportion of cancers were high-grade/high-stage tumours. We also showed that the transperineal biopsy technique can be applied successfully to patients with a closed anal orifice after previous surgery for rectal cancer. Transperineal biopsy can be done safely without routine antibiotic prophylaxis. To investigate the outcomes of transperineal prostate biopsies in patients with elevated prostate-specific antigen (PSA) levels and negative transrectal biopsies. The aim of this retrospective study was to evaluate the diagnostic yield of the transperineal biopsy approach in these patients, and to evaluate the pathology findings in subsequent radical prostatectomy (RP) specimens in patients undergoing RP. In all, 69 consecutive patients with previous negative transrectal biopsies but elevated PSA levels investigated at urological units in Norway who had been referred to The Norwegian Radium Hospital were included. The patients had undergone a mean (median; range) of 2.42 (2; 0-7) transrectal biopsies. The mean (range) age was 63.1 (42-78) years. The median (range) PSA level was 12 (4.3-229) ng/mL. The patients were examined with transperineal biopsy of the prostate between July 2007 and February 2009. The results of the transperineal biopsies were reviewed for Gleason biopsy score, and these were compared with the histopathology results of the RP specimens, i

  18. Comparison of biochemical failure definitions for permanent prostate brachytherapy

    SciTech Connect

    Kuban, Deborah A. . E-mail: dakuban@mdanderson.org; Levy, Larry B.; Potters, Louis; Beyer, David C.; Blasko, John C.; Moran, Brian J.; Ciezki, Jay P.; Zietman, Anthony L.; Zelefsky, Michael J.; Pisansky, Thomas M.; Elshaikh, Mohamed; Horwitz, Eric M.

    2006-08-01

    Purpose: To assess prostate-specific antigen (PSA) failure definitions for patients with Stage T1-T2 prostate cancer treated by permanent prostate brachytherapy. Methods and Materials: A total of 2,693 patients treated with radioisotopic implant as solitary treatment for T1-T2 prostatic adenocarcinoma were studied. All patients had a pretreatment PSA, were treated at least 5 years before analysis, 1988 to 1998, and did not receive hormonal therapy before recurrence. Multiple PSA failure definitions were tested for their ability to predict clinical failure. Results: Definitions which determined failure by a certain increment of PSA rise above the lowest PSA level to date (nadir + x ng/mL) were more sensitive and specific than failure definitions based on PSA doubling time or a certain number of PSA rises. The sensitivity and specificity for the nadir + 2 definition were 72% and 83%, vs. 51% and 81% for 3 PSA rises. The surgical type definitions (PSA exceeding an absolute value) could match this sensitivity and specificity but only when failure was defined as exceeding a PSA level in the 1-3 ng/mL range and only when patients were allowed adequate time to nadir. When failure definitions were compared by time varying covariate regression analysis, nadir + 2 ng/mL retained the best fit. Conclusions: For patients treated by permanent radioisotopic implant for prostate cancer, the definition nadir + 2 ng/mL provides the best surrogate for failure throughout the entire follow-up period, similar to patients treated by external beam radiotherapy. Therefore, the same PSA failure definition could be used for both modalities. For brachytherapy patients with long-term follow-up, at least 6 years, defining failure as exceeding an absolute PSA level in the 0.5 ng/mL range may be reasonable.

  19. Long-term follow-up of HLA-A2+ patients with high-risk, hormone-sensitive prostate cancer vaccinated with the prostate specific antigen peptide homologue (PSA146-154).

    PubMed

    Perambakam, Supriya; Xie, Hui; Edassery, Seby; Peace, David J

    2010-01-01

    Twenty-eight HLA-A2+ patients with high-risk, locally advanced or metastatic, hormone-sensitive prostate cancer were immunized with a peptide homologue of prostate-specific antigen, PSA146-154, between July 2002 and September 2004 and monitored for clinical and immune responses. Fifty percent of the patients developed strong PSA146-154-peptide-specific delayed-type hypersensitivity skin responses, tetramer and/or IFN-γ responses within one year. Thirteen patients had stable or declining serum levels of PSA one year post-vaccination. A decreased risk of biochemical progression was observed in patients who developed augmented tetramer responses at six months compared to pre-vaccination levels (P = .02). Thirteen patients have died while 15 patients remain alive with a mean overall survival of 60 months (95% CI, 51 to 68 months) per Kaplan-Meier analysis. A trend towards greater overall survival was detected in men with high-risk, hormone-sensitive CaP who developed specific T-cell immunity following vaccination with PSA146-154 peptide.

  20. Long-Term Follow-Up of HLA-A2+ Patients with High-Risk, Hormone-Sensitive Prostate Cancer Vaccinated with the Prostate Specific Antigen Peptide Homologue (PSA146-154)

    PubMed Central

    Perambakam, Supriya; Xie, Hui; Edassery, Seby; Peace, David J.

    2010-01-01

    Twenty-eight HLA-A2+ patients with high-risk, locally advanced or metastatic, hormone-sensitive prostate cancer were immunized with a peptide homologue of prostate-specific antigen, PSA146-154, between July 2002 and September 2004 and monitored for clinical and immune responses. Fifty percent of the patients developed strong PSA146-154-peptide-specific delayed-type hypersensitivity skin responses, tetramer and/or IFN-γ responses within one year. Thirteen patients had stable or declining serum levels of PSA one year post-vaccination. A decreased risk of biochemical progression was observed in patients who developed augmented tetramer responses at six months compared to pre-vaccination levels (P = .02). Thirteen patients have died while 15 patients remain alive with a mean overall survival of 60 months (95% CI, 51 to 68 months) per Kaplan-Meier analysis. A trend towards greater overall survival was detected in men with high-risk, hormone-sensitive CaP who developed specific T-cell immunity following vaccination with PSA146-154 peptide. PMID:21253471

  1. Prostate Specific Antigen (PSA) as Predicting Marker for Clinical Outcome and Evaluation of Early Toxicity Rate after High-Dose Rate Brachytherapy (HDR-BT) in Combination with Additional External Beam Radiation Therapy (EBRT) for High Risk Prostate Cancer

    PubMed Central

    Ecke, Thorsten H.; Huang-Tiel, Hui-Juan; Golka, Klaus; Selinski, Silvia; Geis, Berit Christine; Koswig, Stephan; Bathe, Katrin; Hallmann, Steffen; Gerullis, Holger

    2016-01-01

    High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer (PCa). Seventy-nine male patients (median age 71 years, range 50 to 79) with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval) with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA) value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index), Gleason score, D’Amico risk classification for PCa, digital rectal examination (DRE), PSA value after one/three/five year(s) follow-up (FU), time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis (p = 0.009), PSA on date of first HDR-BT (p = 0.033), and PSA on date of first follow-up after one year (p = 0.025) have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities. PMID:27834929

  2. Prostate Specific Antigen (PSA) as Predicting Marker for Clinical Outcome and Evaluation of Early Toxicity Rate after High-Dose Rate Brachytherapy (HDR-BT) in Combination with Additional External Beam Radiation Therapy (EBRT) for High Risk Prostate Cancer.

    PubMed

    Ecke, Thorsten H; Huang-Tiel, Hui-Juan; Golka, Klaus; Selinski, Silvia; Geis, Berit Christine; Koswig, Stephan; Bathe, Katrin; Hallmann, Steffen; Gerullis, Holger

    2016-11-10

    High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer (PCa). Seventy-nine male patients (median age 71 years, range 50 to 79) with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval) with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA) value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index), Gleason score, D'Amico risk classification for PCa, digital rectal examination (DRE), PSA value after one/three/five year(s) follow-up (FU), time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis (p = 0.009), PSA on date of first HDR-BT (p = 0.033), and PSA on date of first follow-up after one year (p = 0.025) have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities.

  3. Combination of prostate imaging reporting and data system (PI-RADS) score and prostate-specific antigen (PSA) density predicts biopsy outcome in prostate biopsy naïve patients.

    PubMed

    Washino, Satoshi; Okochi, Tomohisa; Saito, Kimitoshi; Konishi, Tsuzumi; Hirai, Masaru; Kobayashi, Yutaka; Miyagawa, Tomoaki

    2017-02-01

    To assess the value of the Prostate Imaging Reporting and Data System (PI-RADS) scoring system, for prostate multi-parametric magnetic resonance imaging (mpMRI) to detect prostate cancer, and classical parameters, such as prostate-specific antigen (PSA) level, prostate volume and PSA density, for predicting biopsy outcome in biopsy naïve patients who have suspected prostate cancer. Patients who underwent mpMRI at our hospital, and who had their first prostate biopsy between July 2010 and April 2014, were analysed retrospectively. The prostate biopsies were taken transperineally under transrectal ultrasonography guidance. In all, 14 cores were biopsied as a systematic biopsy in all patients. Two cognitive fusion-targeted biopsy cores were added for each lesion in patients who had suspicious or equivocal lesions on mpMRI. The PI-RADS scoring system version 2.0 (PI-RADS v2) was used to describe the MRI findings. Univariate and multivariate analyses were performed to determine significant predictors of prostate cancer and clinically significant prostate cancer. In all, 288 patients were analysed. The median patient age, PSA level, prostate volume and PSA density were 69 years, 7.5 ng/mL, 28.7 mL, and 0.26 ng/mL/mL, respectively. The biopsy results were benign, clinically insignificant, and clinically significant prostate cancer in 129 (45%), 18 (6%) and 141 (49%) patients, respectively. The multivariate analysis revealed that PI-RADS v2 score and PSA density were independent predictors for prostate cancer and clinically significant prostate cancer. When PI-RADS v2 score and PSA density were combined, a PI-RADS v2 score of ≥4 and PSA density ≥0.15 ng/mL/mL, or PI-RADS v2 score of 3 and PSA density of ≥0.30 ng/mL/mL, was associated with the highest clinically significant prostate cancer detection rates (76-97%) on the first biopsy. Of the patients in this group with negative biopsy results, 22% were subsequently diagnosed as prostate cancer. In contrast, a PI

  4. [5ARI and PSA: open questions.

    PubMed

    Tubaro, Andrea; Puccini, Federica; De Nunzio, Cosimo

    2014-09-23

    No consensus has ever been reached on the predictive value of serum prostate specific antigen(PSA) for the diagnosis of prostate cancer. Limitations of PSA testing in clinical practice have beenoften discussed in the peer-reviewed literature following data derived from clinical trials such as theProstate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events(REDUCE) study that showed a linear rise in the risk of prostate cancer with increasing PSA levels.Benign prostatic hyperplasia is a known confounding factor for the use of PSA as a marker of prostatecancer. Increased prostate volume observed with ageing, urinary retention, acute and chronicinflammatory conditions of the prostate, sexual activity and digital rectal examination may all cause anincrease of PSA values. Both finasteride and dutasteride, 5-alpha reductase inhibitors (5ARI) used inthe treatment of BPH, are known to induce a significant decrease of serum PSA levels close to 50%.The observed change in PSA values following 5ARI treatment has raised questions about the accuracyof PSA testing for the early diagnosis of prostate cancer in patients on finasteride/dutasteride treatment.Careful analysis of data from various clinical trials on pharmacological treatment of LUTS due toBPH suggested that the accuracy of PSA testing is not just maintained but rather increased following5ARI use. Then, the question of PSA accuracy during 5ARI treatment can be considered closed.

  5. PSA — EDRN Public Portal

    Cancer.gov

    KLK3, also known as PSA, or prostate specific antigen, a member of the kallikrein subgroup of serine proteases, is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Kallikreins are increasingly thought to be involved in carcinogenesis, and many act as cancer biomarkers. The product of the KLK3 gene is a protease present in seminal plasma. It is thought to function normally in the liquefaction of seminal coagulum. KLK3, or PSA, is well known for its role in diagnosing and monitoring prostate cancer. There are several isoforms of KLK3, generated by alternate splicing and transcript variants.

  6. A Diet, Physical Activity, and Stress Reduction Intervention in Men with Rising Prostate-Specific Antigen (PSA) after Treatment for Prostate Cancer

    PubMed Central

    Hébert, James R.; Hurley, Thomas G.; Harmon, Brook E.; Heiney, Sue; Hebert, Christine J.; Steck, Susan E.

    2011-01-01

    Background Nearly 35% of men treated for prostate cancer (PrCA) will experience biochemically defined recurrence, noted by a rise in PSA, within ten years of definitive therapy. Diet, physical activity, and stress reduction may affect tumor promotion and disease progression. Methods A randomized trial of an intensive diet, physical activity, and meditation intervention was conducted in men with rising post-treatment PSA after definitive treatment for PrCA. Intention-to-treat methods were used to compare usual care to the intervention in 47 men with complete data. Signal detection methods were used to identify dietary factors associated with PSA change. Results The intervention and control groups did not differ statistically on any demographic or disease-related factor. Although the intervention group experienced decreases of 39% in intakes of saturated fatty acid (SFA as percent of total calories) (p<0.0001) and 12% in total energy intake (218 kcal/day p<0.05)], no difference in PSA change was observed by intervention status. Signal detection methods indicated that in men increasing their consumption of fruit, 56% experienced no rise in PSA (vs. 29% in men who did not increase their fruit intake). Among men who increased fruit and fiber intakes, PSA increased in 83% of participants who also increased saturated fatty acid intake (vs. 44% in participants who decreased or maintained saturated fatty acid intake). Conclusion Results are discussed in the context of conventional treatment strategies that were more aggressive when this study was being conducted in the mid-2000s. Positive health changes in a number of lifestyle parameters were observed with the intervention, and both increased fruit and reduced saturated fat intakes were associated with maintaining PSA levels in men with biochemically recurrent disease. PMID:22018935

  7. PSA Isoforms' Velocities for Early Diagnosis of Prostate Cancer.

    PubMed

    Heidegger, Isabel; Klocker, Helmut; Pichler, Renate; Horninger, Wolfgang; Bektic, Jasmin

    2015-06-01

    Free prostate-specific antigen (fPSA) and its molecular isoforms are suggested for enhancement of PSA testing in prostate cancer (PCa). In the present study we evaluated whether PSA isoforms' velocities might serve as a tool to improve early PCa diagnosis. Our study population included 381 men who had undergone at least one ultrasound-guided prostate biopsy whose pathologic examination yielded PCa or showed no evidence of prostatic malignancy. Serial PSA, fPSA, and proPSA measurements were performed on serum samples covering 7 years prior to biopsy using Beckmann Coulter Access immunoassays. Afterwards, velocities of PSA (PSAV), fPSA% (fPSA%V), proPSA% (proPSA%V) and the ratio proPSA/PSA/V were calculated and their ability to discriminate cancer from benign disease was evaluated. Among 381 men included in the study, 202 (53%) were diagnosed with PCa and underwent radical prostatectomy at our Department. PSAV, fPSA%V, proPSA%V as well as proPSA/PSA/V were able to differentiate significantly between PCa and non-cancerous prostate. The highest discriminatory power between cancer and benign disease has been observed two and one year prior to diagnosis with all measured parameters. Among all measured parameters, fPSA%V showed the best cancer specificity of 45.3% with 90% of sensitivity. In summary, our results highlight the value of PSA isoforms' velocity for early detection of PCa. Especially fPSA%V should be used in the clinical setting to increase cancer detection specificity.

  8. Crystallization and preliminary X-ray diffraction analysis of PsaA, the adhesive pilin subunit that forms the pH 6 antigen on the surface of Yersinia pestis.

    PubMed

    Bao, Rui; Esser, Lothar; Sadhukhan, Annapurna; Nair, Manoj K M; Schifferli, Dieter M; Xia, Di

    2012-10-01

    Yersinia pestis has been responsible for a number of high-mortality epidemics throughout human history. Like all other bacterial infections, the pathogenesis of Y. pestis begins with the attachment of bacteria to the surface of host cells. At least five surface proteins from Y. pestis have been shown to interact with host cells. Psa, the pH 6 antigen, is one of them and is deployed on the surface of bacteria as thin flexible fibrils that are the result of the polymerization of a single PsaA pilin subunit. Here, the crystallization of recombinant donor-strand complemented PsaA by the hanging-drop vapor-diffusion method is reported. X-ray diffraction data sets were collected to 1.9 Å resolution from a native crystal and to 1.5 Å resolution from a bromide-derivatized crystal. These crystals displayed the symmetry of the orthorhombic space group P222(1), with unit-cell parameters a = 26.3, b = 54.6, c = 102.1 Å. Initial phases were derived from single isomorphous replacement with anomalous scattering experiments, resulting in an electron-density map that showed a single molecule in the crystallographic asymmetric unit. Sequence assignment was aided by residues binding to bromide ions of the heavy-atom derivative.

  9. [Reference values of prostate specific antigen (PSA) in 63926 workers without prostatic symptoms who participated in prostate screening cancer developed by the Ibermutuamur Prevention Society in 2006].

    PubMed

    Gelpi-Méndez, J A; Gómez-Fernández, E; Martín-Barallat, J; Cortés-Arcas, M V; Monsonis-Artero, J V; Calvo-Mora, A

    2010-09-01

    To determine the values of PSA in Spanish workers without history of prostate problems and compare them with other geographical latitudes. Observational, retrospective, multicenter and population-based study, conducted between January 1 and December 31, 2006. A total of 65303 workers participated in the Programme of prostate cancer screening conducted by the Ibermutuamur Prevention Society in different Spanish regions. Of these, were selected for this report, 63926: 149 were excluded by personal history of prostate problems and 1328 for being over 64 years. PSA determinations were performed using the Abbott test. Were specified PSA values for each age and for the following age ranges: younger than 40 years, 40-49 years, 50-59 years and 60-64 years. Also calculated the mean PSA values by Autonomous Communities. The data were expressed as mean (+/-SD), confidence intervals 95%, standard error of the mean (SEM) and in the percentiles 5, 25, 50, 75 and 95. The results obtained were compared with those in other areas of the world. All data were analysed using the statistical software GraphPad Quick Calcs. Mean PSA value: for all cases was 1.06 ng/ml (95% CI: +/-1,18) and age groups: under 40 years, 0.67 ng/ml (95% CI: +/-0.49), 40-49 years, 0, 77 ng/ml (95% CI: +/-0.66), 50-59 years, 1.11 ng/ml (95% CI: +/-1.22) and 60-64 years, 1.57 ng/ml (95% CI: +/-1.72). Depending on the age ranged between 0.67 ng/ml under age 40 and 1.70 in the 64 years. According to region, the lowest value was recorded in the País Vasco with 0.98 ng/ml (95% CI: 1.02) and higher in Asturias with 1.28 ng/ml (95% CI: 1.32). Percentile value PSA: the upper normal limit (95th percentile) was 1.40 ng/ml in those younger than 40 years, 1.70 ng/ml in 40-49 years, 3.30 ng/ml in 50-59 years and 5.18 ng/ml in the group 60-64 years. PSA values collected in this study may serve as a reference for the Spanish working population, using the range described for decades, or even better, those relating to each age.

  10. Detection of antibodies to ovarian antigens in women with premature ovarian failure.

    PubMed Central

    Wheatcroft, N J; Toogood, A A; Li, T C; Cooke, I D; Weetman, A P

    1994-01-01

    Premature ovarian failure is a common condition of uncertain aetiology in most cases, although autoimmunity is thought to play a role in a proportion of cases. The frequency of ovarian antibodies, which may be markers for an autoimmune aetiology in this condition, remains unclear. To define this further, we have examined the sera of 45 women with premature ovarian failure (five with iatrogenic ovarian failure, nine with an associated autoimmune disease, and 27 with idiopathic ovarian failure), as well as four women with infertility due to Turner's syndrome and 41 pre- and post-menopausal controls. Using two human ovarian antigen preparations, 24% and 60% of the ovarian failure patients reacted in an ELISA (P < 0.05 and P < 0.001 compared with controls), but frequent cross-reactivity was found with fallopian tube antigens. The apparent aetiology of ovarian failure did not correlate with the presence of ovarian antibodies. Using bovine ovary as an antigen, there was a significant overall increase in binding by the ovarian failure patients, but this was almost identical to binding in an ELISA with bovine fallopian tube. In contrast to a previous report, there was no significant increase of binding to soluble or Triton-extracted membrane fractions of bovine corpora lutea containing the LH/hCG receptor by the patients with ovarian failure. These results suggest that ovarian antibodies are common in premature ovarian failure, but their specificity and pathogenic role are questionable. PMID:8149656

  11. Cancer Antigen 125 is Associated with Length of Stay in Patients with Acute Heart Failure

    PubMed Central

    Kurt, Recep; Beton, Osman; Zorlu, Ali; Yucel, Hasan; Gunes, Hakan; Oguz, Didem; Yilmaz, Mehmet Birhan

    2017-01-01

    Length of stay is the primary driver of heart-failure hospitalization costs. Because cancer antigen 125 has been associated with poor morbidity and mortality rates in heart failure, we investigated the relationship between admission cancer antigen 125 levels and lengths of stay in heart-failure patients. A total of 267 consecutive patients (184 men, 83 women) with acute decompensated heart failure were evaluated prospectively. The median length of stay was 4 days, and the patients were classified into 2 groups: those with lengths of stay ≤4 days and those with lengths of stay >4 days. Patients with longer lengths of stay had a significantly higher cancer antigen 125 level of 114 U/mL (range, 9–298 U/mL) than did those with a shorter length of stay (19 U/mL; range; 3–68) (P <0.001). The optimal cutoff level of cancer antigen 125 in the prediction of length of stay was >48 U/mL, with a specificity of 95.8% and a sensitivity of 96% (area under the curve, 0.979; 95% confidence interval [CI], 0.953–0.992). In the multivariate logistic regression model, cancer antigen 125 >48 U/mL on admission (odds ratio=4.562; 95% CI, 1.826–11.398; P=0.001), sodium level (P<0.001), creatinine level (P=0.009), and atrial fibrillation (P=0.015) were also associated with a longer length of stay after adjustment for variables found to be statistically significant in univariate analysis and correlated with cancer antigen 125 level. In addition, it appears that in a cohort of patients with acute decompensated heart failure, cancer antigen 125 is independently associated with prolonged length of stay. PMID:28265209

  12. Clarifying the PSA grey zone: The management of patients with a borderline PSA.

    PubMed

    Ross, Talisa; Ahmed, Kamran; Raison, Nicholas; Challacombe, Ben; Dasgupta, Prokar

    2016-11-01

    Prostate specific antigen is a marker for prostate cancer and a key diagnostic tool, yet when to refer patients with a borderline PSA is currently unclear. This review describes how to assess a patient with borderline PSA and provides an algorithm for management. Current literature on reference values, factors affecting PSA, indications for referral, non-invasive investigations and the role of MRI were reviewed. Medline and EMBASE were searched using MeSH terms. The literature suggests that a PSA of over 1.5 ng/mL should be used as a cut-off to consider further testing for all age groups. There is strong evidence to show that adjuncts are useful when interpreting PSA results, most notably percentage free PSA and proPSA. Considerable weighting should also be given to the ERSPC risk calculator when deciding when to refer. Multi-parametric MRI is valuable in closely examining suspicious lesions to reduce the number of negative biopsies. MRI fusion biopsy (TRUS, transrectal ultrasonography or transperineal) should be considered over standard TRUS biopsy to detect more clinically significant disease. Management of borderline PSA is not straightforward. A cut-off of 1.5 ng/mL should be used in conjunction with digital rectal exam, risk calculation and PSA adjuncts. Imaging and biopsy should utilise mpMRI to achieve improved diagnosis of clinically significant prostate cancer, with fewer unnecessary investigations. © 2016 John Wiley & Sons Ltd.

  13. The optimal timing to perform 18F/11C-choline PET/CT in patients with suspicion of relapse of prostate cancer: trigger PSA versus PSA velocity and PSA doubling time.

    PubMed

    Calabria, Ferdinando; Rubello, Domenico; Schillaci, Orazio

    2014-12-09

    In the present short communication we considered the main publications focused on trigger prostate-specific antigen (PSA) and PSA kinetics that systematically compared 18F to 11C-choline PET/CT in order to establish the optimal time to perform choline PET/CT in relation to the trigger values and velocity, as well as doubling time of PSA serum levels.

  14. Decision-Making Processes among Prostate Cancer Survivors with Rising PSA Levels: Results from a Qualitative Analysis1

    PubMed Central

    Shen, Megan Johnson; Nelson, Christian J.; Peters, Ellen; Slovin, Susan F.; Hall, Simon J.; Hall, Matt; Herrera, Phapichaya Chaoprang; Leventhal, Elaine A.; Leventhal, Howard; Diefenbach, Michael A.

    2014-01-01

    Background Prostate cancer survivors with a rising prostate specific antigen (PSA) level have few treatment options, experience a heightened state of uncertainty about their disease trajectory that might include the possibility of cancer metastasis and death, and often experience elevated levels of distress as they have to deal with a disease they thought they had conquered. Guided by self-regulation theory, the present study examined the cognitive and affective processes involved in shared decision making between physician and patients who experience a rising PSA after definitive treatment for prostate cancer. Methods In-depth interviews were conducted with 34 prostate cancer survivors who had been diagnosed with a rising PSA (i.e., biochemical failure) within the past 12 months. Survivors were asked about their experiences and affective responses after being diagnosed with a rising PSA and while weighing potential treatment options. In addition, patients were asked about their decision-making process for the initial prostate cancer treatment. Results Compared to the initial diagnosis, survivors with a rising PSA reported increased negative affect following their diagnosis, concern about the treatability of their disease, increased planning and health behavior change, heightened levels of worry preceding doctor’s appointments (especially prior to the discussion of PSA testing results), and a strong reliance on physicians’ treatment recommendations. Conclusions Prostate cancer survivors’ decision-making processes for the treatment of a rising PSA are markedly different from those of the initial diagnosis of prostate cancer. Because patients experience heightened distress and rely more heavily on their physicians’ recommendations with a rising PSA, interactions with the health care provider provide an excellent opportunity to address and assist patients with managing the uncertainty and distress inherent with rising PSA levels. PMID:25385751

  15. Decision-making Processes among Prostate Cancer Survivors with Rising PSA Levels: Results from a Qualitative Analysis.

    PubMed

    Shen, Megan Johnson; Nelson, Christian J; Peters, Ellen; Slovin, Susan F; Hall, Simon J; Hall, Matt; Herrera, Phapichaya Chaoprang; Leventhal, Elaine A; Leventhal, Howard; Diefenbach, Michael A

    2015-05-01

    Prostate cancer survivors with a rising prostate-specific antigen (PSA) level have few treatment options, experience a heightened state of uncertainty about their disease trajectory that might include the possibility of cancer metastasis and death, and often experience elevated levels of distress as they have to deal with a disease they thought they had conquered. Guided by self-regulation theory, the present study examined the cognitive and affective processes involved in shared decision making between physicians and patients who experience a rising PSA after definitive treatment for prostate cancer. In-depth interviews were conducted with 34 prostate cancer survivors who had been diagnosed with a rising PSA (i.e., biochemical failure) within the past 12 months. Survivors were asked about their experiences and affective responses after being diagnosed with a rising PSA and while weighing potential treatment options. In addition, patients were asked about their decision-making process for the initial prostate cancer treatment. Compared with the initial diagnosis, survivors with a rising PSA reported increased negative affect following their diagnosis, concern about the treatability of their disease, increased planning and health behavior change, heightened levels of worry preceding doctor appointments (especially prior to the discussion of PSA testing results), and a strong reliance on physicians' treatment recommendations. Prostate cancer survivors' decision-making processes for the treatment of a rising PSA are markedly different from those of the initial diagnosis of prostate cancer. Because patients experience heightened distress and rely more heavily on their physicians' recommendations with a rising PSA, interactions with the health care provider provide an excellent opportunity to address and assist patients with managing the uncertainty and distress inherent with rising PSA levels. © The Author(s) 2014.

  16. PSA Velocity Does Not Improve Prostate Cancer Detection

    Cancer.gov

    A rapid increase in prostate-specific antigen (PSA) levels is not grounds for automatically recommending a prostate biopsy, according to a study published online February 24, 2011, in the Journal of the National Cancer Institute.

  17. Prostate-Specific Antigen Bounce After High-Dose-Rate Monotherapy for Prostate Cancer

    SciTech Connect

    Mehta, Niraj H.; Kamrava, Mitchell; Wang, Pin-Chieh; Steinberg, Michael; Demanes, Jeffrey

    2013-07-15

    Purpose: To characterize the magnitude and kinetics of prostate-specific antigen (PSA) bounces after high-dose-rate (HDR) monotherapy and determine relationships between certain clinical factors and PSA bounce. Methods and Materials: Longitudinal PSA data and various clinical parameters were examined in 157 consecutive patients treated with HDR monotherapy between 1996 and 2005. We used the following definition for PSA bounce: rise in PSA ≥threshold, after which it returns to the prior level or lower. Prostate-specific antigen failure was defined per the Phoenix definition (nadir +2 ng/mL). Results: A PSA bounce was noted in 67 patients (43%). The number of bounces per patient was 1 in 45 cases (67%), 2 in 19 (28%), 3 in 2 (3%), 4 in 0, and 5 in 1 (1%). The median time to maximum PSA bounce was 1.3 years, its median magnitude was 0.7, and its median duration was 0.75 years. Three patients (2%) were noted to have PSA failure. None of the 3 patients who experienced biochemical failure exhibited PSA bounce. In the fully adjusted model for predicting each bounce, patients aged <55 years had a statistically significant higher likelihood of experiencing a bounce (odds ratio 2.22, 95% confidence interval 1.38-3.57, P=.001). There was also a statistically significant higher probability of experiencing a bounce for every unit decrease in Gleason score (odds ratio 1.52, 95% confidence interval 1.01-2.04, P=.045). Conclusions: A PSA bounce occurs in a significant percentage of patients treated with HDR monotherapy, with magnitudes varying from <1 in 28% of cases to ≥1 in 15%. The median duration of bounce is <1 year. More bounces were identified in patients with lower Gleason score and age <55 years. Further investigation using a model to correlate magnitude and frequency of bounces with clinical variables are under way.

  18. The total influenza vaccine failure of 1947 revisited: major intrasubtypic antigenic change can explain failure of vaccine in a post-World War II epidemic.

    PubMed

    Kilbourne, Edwin D; Smith, Catherine; Brett, Ian; Pokorny, Barbara A; Johansson, Bert; Cox, Nancy

    2002-08-06

    Although vaccine-induced immunity to influenza A virus is continually challenged by progressively selected mutations in the virus's major antigens (antigenic drift), virus strains within a subtype (e.g., H1N1) are antigenically cross-reactive. Although cross-immunity diminishes as further mutations accumulate, necessitating frequent changes in vaccine strains, older vaccines are usually partially protective. The post-World War II epidemic of 1947 is notable for the total failure of a vaccine previously effective in the 1943-44 and 1944-45 seasons. We have combined extensive antigenic characterization of the hemagglutinin and neuraminidase antigens of the 1943 and 1947 viruses with analysis of their nucleotide and amino acid sequences and have found marked antigenic and amino acid differences in viruses of the two years. Furthermore, in a mouse model, vaccination with the 1943 vaccine had no effect on infection with the 1947 strain. These findings are important, because complete lack of cross-immunogenicity has been found previously only with antigenic shift, in which antigenically novel antigens have been captured by reassortment of human and animal strains, sometimes leading to pandemics. Although the 1947 epidemic lacked the usual hallmarks of pandemic disease, including an extensive increase in mortality, it warns of the possibility that extreme intrasubtypic antigenic variation (if coupled with an increase in disease severity) could produce pandemic disease without the introduction of animal virus antigens.

  19. [PSA doubling time and method of calculation].

    PubMed

    Ruffion, Alain; Rebillard, Xavier; Grima, François

    2005-12-01

    Prostate Specific Antigen (PSA) is currently the best marker for prostate cancer, although it is not very specific for this disease. The use of the PSA kinetic, in addition to its absolute value, is theoretically very attractive in a large number of clinical situations. Based on a review of the literature, the authors report the various methods used to study this kinetic, with particular emphasis on the most reliable method: the PSA doubling time. After describing the definitions and the methods used to calculate this parameter, the authors discuss the various clinical situations in which it could be useful: surveillance of prostatic tumours after the initial diagnosis in high-risk patients or patients refusing treatment, prognostic factor before curative treatment, evaluation of the efficacy of curative treatment, prognostic factor of tumour aggressiveness at the time of biochemical recurrence after curative treatment or during endocrine therapy.

  20. Increasing Fractional Doses Increases the Probability of Benign PSA Bounce in Patients Undergoing Definitive HDR Brachytherapy for Prostate Cancer.

    PubMed

    Hauck, Carlin R; Ye, Hong; Chen, Peter Y; Gustafson, Gary S; Limbacher, Amy; Krauss, Daniel J

    2017-05-01

    Prostate-specific antigen (PSA) bounce is a temporary elevation of the PSA level above a prior nadir. The purpose of this study was to determine whether the frequency of a PSA bounce following high-dose-rate (HDR) interstitial brachytherapy for the treatment of prostate cancer is associated with individual treatment fraction size. Between 1999 and 2014, 554 patients underwent treatment of low- or intermediate-risk prostate cancer with definitive HDR brachytherapy as monotherapy and had ≥3 subsequent PSA measurements. Four different fraction sizes were used: 950 cGy × 4 fractions, 1200 cGy × 2 fractions, 1350 cGy × 2 fractions, 1900 cGy × 1 fraction. Four definitions of PSA bounce were applied: ≥0.2, ≥0.5, ≥1.0, and ≥2.0 ng/mL above the prior nadir with a subsequent return to the nadir. The median follow-up period was 3.7 years. The actuarial 3-year rate of PSA bounce for the entire cohort was 41.3%, 28.4%, 17.4%, and 6.8% for nadir +0.2, +0.5, +1.0, and +2.0 ng/mL, respectively. The 3-year rate of PSA bounce >0.2 ng/mL was 42.2%, 32.1%, 41.0%, and 59.1% for the 950-, 1200-, 1350-, and 1900-cGy/fraction levels, respectively (P=.002). The hazard ratio for bounce >0.2 ng/mL for patients receiving a single fraction of 1900 cGy compared with those receiving treatment in multiple fractions was 1.786 (P=.024). For patients treated with a single 1900-cGy fraction, the 1-, 2-, and 3-year rates of PSA bounce exceeding the Phoenix biochemical failure definition (nadir +2 ng/mL) were 4.5%, 18.7%, and 18.7%, respectively, higher than the rates for all other administered dose levels (P=.025). The incidence of PSA bounce increases with single-fraction HDR treatment. Knowledge of posttreatment PSA kinetics may aid in decision making regarding management of potential biochemical failures. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Prognostic significance of 5-year PSA value for predicting prostate cancer recurrence after brachytherapy alone and combined with hormonal therapy and/or external beam radiotherapy.

    PubMed

    Stock, Richard G; Klein, Thomas J; Cesaretti, Jamie A; Stone, Nelson N

    2009-07-01

    To analyze the prognosis and outcomes of patients who remain free of biochemical failure during the first 5 years after treatment. Between 1991 and 2002, 742 patients with prostate cancer were treated with brachytherapy alone (n = 306), brachytherapy and hormonal therapy (n = 212), or combined implantation and external beam radiotherapy (with or without hormonal therapy; n = 224). These patients were free of biochemical failure (American Society for Therapeutic Radiology and Oncology [ASTRO] definition) during the first 5 post-treatment years and had a documented 5-year prostate-specific antigen (PSA) value. The median follow-up was 6.93 years. The actuarial 10-year freedom from PSA failure rate was 97% using the ASTRO definition and 95% using the Phoenix definition. The median 5-year PSA level was 0.03 ng/mL (range, 0-3.6). The 5-year PSA value was 0.01-0.10 in 31.1%, >0.10-0.2 in 10.2%, >0.2-0.5 in 7.82%, and >0.5 in 3.10%. The 5-year PSA value had prognostic significance, with a PSA value of PSA failure rate of 99% with the ASTRO definition and 98% with the Phoenix definition vs. 86% (ASTRO definition) and 81% (Phoenix definition) for a PSA value >or=0.2 ng/mL (n = 81; p < .0001). The treatment regimen had no effect on biochemical failure. None of the 742 patients in this study developed metastatic disease or died of prostate cancer. The results of this study have shown that the prognosis for patients treated with brachytherapy and who remain biochemically free of disease for >or=5 years is excellent and none developed metastatic disease during the first 10 years after treatment. The 5-year PSA value is prognostic, and patients with a PSA value <0.2 ng/mL are unlikely to develop subsequent biochemical relapse.

  2. PSA Response to Neoadjuvant Androgen Deprivation Therapy Is a Strong Independent Predictor of Survival in High-Risk Prostate Cancer in the Dose-Escalated Radiation Therapy Era

    SciTech Connect

    McGuire, Sean E.; Lee, Andrew K.; Cerne, Jasmina Z.; Munsell, Mark F.; Levy, Lawrence B.; Kudchadker, Rajat J.; Choi, Seungtaek L.; Nguyen, Quynh N.; Hoffman, Karen E.; Pugh, Thomas J.; Frank, Steven J.; Corn, Paul G.; Logothetis, Christopher J.; Kuban, Deborah A.

    2013-01-01

    Purpose: The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. Methods and Materials: We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specific mortality (PCSM) and overall survival (OS) were examined. Results: A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs {>=}0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. Conclusions: For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level {>=}0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level {>=}0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.

  3. Impact of Ultrahigh Baseline PSA Levels on Biochemical and Clinical Outcomes in Two Radiation Therapy Oncology Group Prostate Clinical Trials

    SciTech Connect

    Rodrigues, George; Bae, Kyounghwa; Roach, Mack; Lawton, Colleen; Donnelly, Bryan; Grignon, David; Hanks, Gerald; Porter, Arthur; Lepor, Herbert; Sandler, Howard

    2011-06-01

    Purpose: To assess ultrahigh (UH; prostate-specific antigen [PSA]levels {>=}50 ng/ml) patient outcomes by comparison to other high-risk patient outcomes and to identify outcome predictors. Methods and Materials: Prostate cancer patients (PCP) from two Phase III Radiation Therapy Oncology Group clinical trials (studies 9202 and 9413) were divided into two groups: high-risk patients with and without UH baseline PSA levels. Predictive variables included age, Gleason score, clinical T stage, Karnofsky performance score, and treatment arm. Outcomes included overall survival (OS), distant metastasis (DM), and biochemical failure (BF). Unadjusted and adjusted hazard ratios (HRs) were calculated using either the Cox or Fine and Gray's regression model with associated 95% confidence intervals (CI) and p values. Results: There were 401 patients in the UH PSA group and 1,792 patients in the non-UH PSA PCP group of a total of 2,193 high-risk PCP. PCP with UH PSA were found to have inferior OS (HR, 1.19; 95% CI, 1.02-1.39, p = 0.02), DM (HR, 1.51; 95% CI, 1.19-1.92; p = 0.0006), and BF (HR, 1.50; 95% CI, 1.29-1.73; p < 0.0001) compared to other high-risk PCP. In the UH cohort, PSA level was found to be a significant factor for the risk of DM (HR, 1.01; 95% CI, 1.001-1.02) but not OS and BF. Gleason grades of 8 to 10 were found to consistently predict for poor OS, DM, and BF outcomes (with HR estimates ranging from 1.41-2.36) in both the high-risk cohort and the UH cohort multivariable analyses. Conclusions: UH PSA levels at diagnosis are related to detrimental changes in OS, DM, and BF. All three outcomes can be modeled by various combinations of all predictive variables tested.

  4. Low-dose-rate prostate brachytherapy: 4-8 week postimplant prostate-specific antigen a novel predictor of biochemical failure-free survival.

    PubMed

    Callaghan, Cameron M; Wang, Lin; Alluri, Abhishek; Lauve, Andrew; Boyer, Cynthia; Russell, William

    2017-08-24

    The purpose of this study was to determine the relationship between patient, disease, and treatment variables and biochemical failure-free survival (bFFS) following low-dose-rate prostate brachytherapy (LDR-BT). Data from 624 consecutive patients who received LDR-BT for localized prostate cancer between 2002 and 2012 at a single institution were collected for various patient, disease, and treatment characteristics including a 4-8 week postimplant PSA (4-8wkPSA). Subgroup analysis was stratified by risk category and treatment regimen. Analysis was performed using Kaplan-Meier survival curves, Cox proportional hazard ratios (HRs), and receiver-operator characteristic curves. A total of 624 consecutive patients were included with followup time of 4.0 ± 3.1 years. Predictors of bFFS included PSA nadir and 4-8wkPSA (HR = 2.48, p = 0.000 and HR = 1.24, p = 0.000, respectively) for total population. Diabetes mellitus (p = 0.026), chronic obstructive pulmonary disease (p = 0.000), alcohol use (p = 0.024), and age (p = 0.002) were predictors for specific subgroups. Receiver-operator characteristic curves 4-8wkPSA were found to be significant (p = 0.036). 4-8wkPSA is a novel predictor of bFFS for patients receiving LDR-BT across several risk categories and treatment regimens with potential clinical utility as a prognostic indicator. Certain comorbidities and exposure histories also demonstrated significant relationships with bFFS including chronic obstructive pulmonary disease, diabetes mellitus, age, alcohol history, proton pump inhibitor use, PSA nadir, and PSA density. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  5. [Alternative tests to PSA for prostate cancer diagnosis].

    PubMed

    Defilippi, Elio; Zitella, Andrea; Tizzani, Alessandro

    2011-01-01

    Prostate specific antigen (PSA) is still the most useful tool to select the population requiring prostatebiopsy. The main downsides of PSA are an inadequate sensitivity to be used in screening and a low specificity for cancer detection. So far, a limited value for PSA derivates (velocity, density, free, proisoforms and doubling time) has been recognised. We present a short review of the literature describing a selection of the most promising alternatives to PSA being studied currently: PCA3, serum kallikreins, serum detectable prostate specific membrane antigen, the nuclear matrix protein EPCA, EPCA-2, prostatic acid phosphatase, urine detectable GSTP1, anti-AMACR antibodies, sarcosine, plasminogen activating urokinase, IGFBP, TGF beta 1,PSP94, IL6, plasmatic DNA, serum autoantibodies, neuroendocrine markers, proteomic analysis.

  6. [PSA bounce phenomenon after local treatment with radiation for prostate cancer].

    PubMed

    Rodríguez, M A Cabeza; Escutia, M A Pérez; Antolín, A Rodríguez; Costoso, N Gascón; García, A Cascales; González, E Lanzós

    2012-01-01

    Radiotherapy is a curative treatment for localized prostate cancer in its modalities of brachytherapy (BT) and external beam radiotherapy (EBRT). A temporary increase in prostate-specific antigen (PSA) values following a radiotherapy treatment coupled with a decrease without therapeutic intervention may happen in 30% of the patients. This phenomenon is known as PSA bounce and lacks prognostic effect in relation to tumor control. Additionally, it produces anxiety in the patient because of the fear of failure, and in the physicists due to the uncertainty about the state of the tumor. The etiology and pathogenesis are still unknown. Several factors associated with the tumor and the treatments have been evaluated in the studies which analyze this phenomenon, the age is the only observed factor with the highest consistency as a bounce predictor. The definition of biologic failure (BF)after EBRT or BT with or without androgenic deprivation (ADT) according to Phoenix criteria, which considers an increase of at least 2 ng/ml over PSA nadir, enables better taking the bounce phenomenon into account, although is not free from false BF that may affect to the relapse-free survival in patients with follow-up shorter than 3 years.

  7. Prognostic Value of the Interaction between Galectin-3 and Antigen Carbohydrate 125 in Acute Heart Failure

    PubMed Central

    Núñez, Julio; Rabinovich, Gabriel A.; Sandino, Justo; Mainar, Luis; Palau, Patricia; Santas, Enrique; Villanueva, Maria Pilar; Núñez, Eduardo; Bodí, Vicent; Chorro, Francisco J.; Miñana, Gema; Sanchis, Juan

    2015-01-01

    Aims Galectin-3 (Gal-3) and carbohydrate antigen 125 (CA125) have emerged as robust prognostic biomarkers in heart failure. Experimental data have also suggested a potential molecular interaction between CA125 and Gal-3; however, the biological and clinical relevance of this interaction is still uncertain. We sought to evaluate, in patients admitted for acute heart failure, the association between plasma Gal-3 with all-cause mortality and the risk for rehospitalizations among high and low levels of CA125. Methods and Results We included 264 consecutive patients admitted for acute heart failure to the Cardiology Department in a third-level center. Both biomarkers were measured on admission. Negative binomial and Cox regression models were used to evaluate the prognostic effect of the interaction between Gal-3 and CA125 (dichotomized by its median) with hospital readmission and all-cause mortality, respectively. During a median follow-up of 2 years (IQR = 1-2.8), 108 (40.9%) patients deaths and 365 rehospitalizations in 171 (69.5%) patients were registered. In a multivariable setting, the effect of Gal-3 on mortality and rehospitalization was differentially mediated by CA125 (p = 0.007 and p<0.001, respectively). Indeed, in patients with CA125 above median (>67 U/ml), values across the continuum of Gal-3 showed a positive and almost linear relationship with either the risk of death or rehospitalization. Conversely, when CA125 was below median (≤67 U/ml), Gal-3 lacked any prognostic effect on both endpoints. Conclusion In patients with acute heart failure, Gal-3 was strongly associated with higher risk of long-term mortality and repeated rehospitalizations, but only in those patients exhibiting higher values of CA125 (above 67 U/ml). PMID:25875367

  8. High-intensity focused ultrasound for prostate cancer: comparative definitions of biochemical failure.

    PubMed

    Blana, Andreas; Brown, Stephen C W; Chaussy, Christian; Conti, Giario N; Eastham, James A; Ganzer, Roman; Murat, Francois J; Pasticier, Gilles; Rebillard, Xavier; Rewcastle, John C; Robertson, Cary N; Thuroff, Stefan; Ward, John F

    2009-10-01

    To compare the specificity and sensitivity of different definitions of biochemical failure in patients treated with high-intensity focused ultrasound (HIFU) for prostate cancer, to identify the most accurate predictor of clinical failure after HIFU. Consecutively treated patients who underwent HIFU between October 1997 and July 2006 at two centres (Lyon, France; and Regensburg, Germany) were prospectively maintained within a central database and retrospectively reviewed for this study. Clinical failure was defined as a positive prostate biopsy after treatment, radiographic evidence of lymphatic or bony metastatic disease, or salvage treatment for prostate cancer (surgery, radiation, hormonal therapy or second HIFU). The serum prostate-specific antigen (PSA) values after HIFU were assessed as a biochemical surrogate of a therapeutic success or failure. PSA threshold values, 'PSA nadir plus', PSA velocity, PSA doubling time and the American Society or Therapeutic Radiotherapy and Oncology and Phoenix definition of biochemical failure were all considered. The sensitivity, specificity, positive predictive value and negative predictive value of each biochemical definition for predicting clinical failure were determined. The data from 285 patients (stage PSA <15 ng/mL, Gleason score PSA nadir was 0.13 ng/mL, which occurred at a median of 12.9 weeks after HIFU, and the median PSA at the last follow-up was 0.76 (1.6-2.7) ng/mL. Clinical failure occurred in 71 patients (25%); 24 due to a positive biopsy and 47 through the use of an additional therapy. Biochemical events that best predicted clinical failure were 'PSA nadir plus' values of 1.1-1.3 ng/mL, PSA velocities of <0.3 ng/mL/year and PSA doubling times of 1.25-1.75 years. A new definition of biochemical failure that is specific to patients treated with HIFU therapy is established, i.e. the 'Stuttgart definition', the 'PSA

  9. Total and free PSA serum concentrations are not influenced by extensive physical exercise and bicycle riding.

    PubMed

    Lippi, G; Corgnati, A; Salvagno, G; Schena, F; Franchini, M; Guidi, G

    2005-01-01

    Vigorous and prolonged physical exercise and mechanical involvement of the perineal region might influence prostatic function and measurement of both total (PSA) and free prostate specific antigen (fPSA), decreasing the diagnostic efficiency of the laboratory screening for either benign or neoplastic prostate disorders in athletes. To investigate the effects of regular and strenuous physical exercise with or without bicycle riding on integrity and biochemical function of prostatic tissue, we measured serum PSA and fPSA in 69 elite and professional cyclists, 31 members of the Italian national cross-country ski team, and in 43 sedentary healthy controls. The concentration of both PSA and fPSA did not differ significantly between sedentary individuals and physically active cross-country skiers (PSA 0.43 +/- 0.30 vs. 0.36+/-0.25, ns; fPSA 0.16+/-0.12 vs. 0.12+/-0.12, ns) or cyclists (PSA 0.43 +/- 0.30 vs. 0.36 +/- 0.23, ns; fPSA 0.16 +/- 0.12 vs. 0.13 +/- 0.08, ns), and the relative distribution of values appeared almost overlapping. We hypothesize that neither a heavy and regular physical exercise nor the extensive and prolonged mechanical involvement of the prostate region by the bicycle riding have significant influence on release of both PSA and fPSA.

  10. Study of Serum Total PSA and Free PSA as an Oncological Marker in Breast Tumour.

    PubMed

    Jahir, Elteza Tahjiba; Devi, Runi; Borthakur, Bibhuti Bhushan

    2017-03-01

    Breast Cancer (BC) cases are rising alarmingly all over the world and India is not an exception. This rising trend is due to an increased age at first child birth, decreased breast feeding, and the changing lifestyle mostly in urban India. With the advent of more sensitive methodologies and research works in this field, it has been suggested that Prostate Specific Antigen (PSA) plays an important role in the pathogenesis of breast cancer besides other established tumour markers. To study the molecular forms of PSA-total and free PSA in benign and malignant tumours and to analyse their association with the tumour burden. The present study was conducted in collaboration with Gauhati Medical College and Hospital and Dr B Borooah Cancer Institute, Guwahati, Assam, India. Women in the age group of 18-65 years with recently diagnosed tumour (benign/malignant) in the breast were included in the study. Women taking Oral Contraceptive Pill (OCP), hormone replacement therapy, with past/present history of gynaecological/other malignancy and chronic endocrine disease like diabetes, thyroid disorders were excluded. The case group comprised of 50 female subjects with newly diagnosed Benign Breast Disease (BBD) and 50 subjects with BC, while 50 age matched healthy females without any signs and symptoms of breast discomfort were included in the control group. Laboratory tests done were Serum Total PSA (TPSA), Free PSA (FPSA), Fasting Blood Glucose (FBS), serum urea, serum creatinine and fasting lipid profile. TPSA and FPSA was measured again in both the test groups after 10-14 days of surgery/therapy. A fall in postoperative value of total and free PSA in BC case group was noticed. In Grade I tumours the mean value of total PSA (1.813 ng/ml) and free PSA (1.149 ng/ml) were higher than those with Grade III tumours (TPSA-1.07 ng/ml and FPSA-1.002 ng/ml). Mean value of Fasting Blood Sugar (FBG), total cholesterol and Low Density Lipoprotein (LDL) in BC case group was higher than the

  11. Prostate-Specific Antigen at 4 to 5 Years After Low-Dose-Rate Prostate Brachytherapy Is a Strong Predictor of Disease-Free Survival

    SciTech Connect

    Lo, Andrea C.; Morris, W. James; Lapointe, Vincent; Hamm, Jeremy; Keyes, Mira; Pickles, Tom; McKenzie, Michael; Spadinger, Ingrid

    2014-01-01

    Purpose: To determine (1) the prognostic utility of prostate-specific antigen (PSA) concentration at 45 to 60 months (48mPSA) after low-dose-rate prostate brachytherapy (LDR-PB); (2) the predictors of 48mPSA; and (3) the prognostic utility of directional trends between PSA levels at 24, 36, and 48 months after LDR-PB. Methods and Materials: Between 1998 and 2008, 2223 patients with low- and intermediate-risk prostate cancer received LDR-PB monotherapy. A cohort of 1434 of these patients was identified with a documented 48mPSA and no evidence of disease relapse prior to the 48mPSA. In addition, a subset of this cohort (n=585) was identified with ≥72 months of follow-up and documented PSA values at both 24 and 36 months after implantation. Results: Median follow-up time was 76 months. Eight-year Kaplan-Meier disease-free survival (DFS) rates were 100% vs 73.4% for patients with 48mPSA ≤0.2 vs those with >0.2 ng/mL; 99.1% versus 53.8% for a 48mPSA threshold of ≤0.4 versus >0.4 ng/mL, respectively; and 97.3% versus 0% for a threshold of ≤1.0 versus >1.0 ng/mL, respectively. On multivariate analysis, the only factor predictive of DFS was 48mPSA (P<.0001). On subset analysis (n=585), 29 patients had a PSA rise (defined as >0.2 ng/mL) between 24 and 36 months, 24 patients had a rise between 36 and 48 months, and 11 patients had rises over both intervals. Failure rates in these patients were 52%, 79%, and 100%, respectively. On multivariate analysis, initial PSA, androgen deprivation therapy, and dose to 90% of the prostate significantly correlated with 48mPSA but together accounted for only ∼5% of its total variance. Conclusions: The 48mPSA after LDR-PB is highly predictive of long-term DFS. Patients with 48mPSA ≤0.4 ng/mL had a <1% risk of disease relapse at 8 years, whereas all patients with 48mPSA >1.0 ng/mL relapsed. Consecutive PSA rises of >0.2 ng/mL from 24 to 36 months and from 36 to 48 months were also highly predictive of subsequent failure.

  12. Evaluation of extraprostatic disease in the staging of prostate cancer by F-18 choline PET/CT: can PSA and PSA density help in patient selection?

    PubMed

    Calabria, Ferdinando; Chiaravalloti, Agostino; Tavolozza, Mario; Ragano-Caracciolo, Cristiana; Schillaci, Orazio

    2013-08-01

    The aim of our study was to evaluate the accuracy of F-18 choline positron emission tomography/computed tomography (PET/CT) in assessing the presence of extraprostatic disease during staging of prostate cancer, in relation to prostate-specific antigen (PSA) and PSA density, a PSA derivative that is useful for improving risk stratification in prostate cancer patients. F-18 choline PET/CT was performed in 45 patients for early staging of biopsy-proven prostate cancer. None of the examined patients had received therapy before the examination. In all of them a transrectal ultrasonography had been performed earlier to calculate the prostate volume and PSA density. The mean PSA value was 25.5 (±38.1) ng/ml, whereas the mean PSA density was 0.70 (±0.88). Results of F-18 choline PET/CT were related to PSA and PSA density. PET/CT was positive for extraprostatic disease in 18/45 patients (40%) (mean PSA and PSA density were, respectively, 44.08 ng/ml and 1.08); PET/CT was negative for extraprostatic disease in 27/45 patients (60%) (mean PSA and PSA density were, respectively, 13.12 ng/ml and 0.4). PET/CT was positive in 13/18 patients (72%) with a PSA cutoff value greater than or equal to 18 ng/ml and in 5/21 (24%) with a PSA value less than 18 ng/ml (P=0.0017). PET/CT was positive in 16/18 patients (89%) with PSA density greater than or equal to 0.31 and in 2/18 (11%) with PSA density lower than 0.31 (P=0.0234). The possibility of detecting extraprostatic disease of prostate cancer with F-18 choline PET/CT is related to PSA and PSA density. In particular, F-18 choline PET/CT should be recommended only in patients with a PSA value of at least 18 ng/ml, whereas a PSA density of at least 0.31 ng/ml is more probably associated with distant metastases.

  13. FDA Approves Test to Aid Post-PSA Biopsy Decisions | Division of Cancer Prevention

    Cancer.gov

    The Food and Drug Administration (FDA) has approved a test to help men with elevated prostate-specific antigen (PSA) test scores decide whether to have a biopsy to test for prostate cancer. The Access Hybritech p2PSA test is approved for use in men aged 50 or older who have a PSA test score between 4 and 10 ng/ml but who show no signs of cancer during a digital rectal exam. |

  14. Carbohydrate Antigen-125-Guided Therapy in Acute Heart Failure: CHANCE-HF: A Randomized Study.

    PubMed

    Núñez, Julio; Llàcer, Pau; Bertomeu-González, Vicente; Bosch, Maria José; Merlos, Pilar; García-Blas, Sergio; Montagud, Vicente; Bodí, Vicent; Bertomeu-Martínez, Vicente; Pedrosa, Valle; Mendizábal, Andrea; Cordero, Alberto; Gallego, Jorge; Palau, Patricia; Miñana, Gema; Santas, Enrique; Morell, Salvador; Llàcer, Angel; Chorro, Francisco J; Sanchis, Juan; Fácila, Lorenzo

    2016-11-01

    This study sought to evaluate the prognostic effect of carbohydrate antigen-125 (CA125)-guided therapy (CA125 strategy) versus standard of care (SOC) after a hospitalization for acute heart failure (AHF). CA125 has emerged as a surrogate of fluid overload and inflammatory status in AHF. After an episode of AHF admission, elevated values of this marker at baseline as well as its longitudinal profile relate to adverse outcomes, making it a potential tool for treatment guiding. In a prospective multicenter randomized trial, 380 patients discharged for AHF and high CA125 were randomly assigned to the CA125 strategy (n = 187) or SOC (n = 193). The aim in the CA125 strategy was to reduce CA125 to ≤35 U/ml by up or down diuretic dose, enforcing the use of statins, and tightening patient monitoring. The primary endpoint was 1-year composite of death or AHF readmission. Treatment strategies were compared as a time to first event and longitudinally. Patients allocated to the CA125 strategy were more frequently visited, and treated with ambulatory intravenous loop diuretics and statins. Likewise, doses of oral loop diuretics and aldosterone receptor blockers were more frequently modified. The CA125 strategy resulted in a significant reduction of the primary endpoint, whether evaluated as time to first event (66 events vs. 84 events; p = 0.017) or as recurrent events (85 events vs. 165 events; incidence rate ratio: 0.49; 95% confidence interval: 0.28 to 0.82; p = 0.008). The effect was driven by significantly reducing rehospitalizations but not mortality. The CA125 strategy was superior to the SOC in terms of reducing the risk of the composite of 1-year death or AHF readmission. This effect was mainly driven by significantly reducing the rate of rehospitalizations. (Carbohydrate Antigen-125-guided Therapy in Heart Failure [CHANCE-HF]; NCT02008110). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  15. Lack of an Association between Neutrophil-to-Lymphocyte Ratio and PSA Failure of Prostate Cancer Patients Who Underwent Radical Prostatectomy

    PubMed Central

    Maeda, Yoko; Kawahara, Takashi; Koizumi, Mitsuyuki; Ito, Hiroki; Kumano, Yohei; Ohtaka, Mari; Kondo, Takuya; Mochizuki, Taku; Hattori, Yusuke; Teranishi, Jun-ichi; Yumura, Yasushi; Miyoshi, Yasuhide; Yao, Masahiro; Miyamoto, Hiroshi; Uemura, Hiroji

    2016-01-01

    Introduction. The neutrophil-to-lymphocyte ratio (NLR), which can be easily calculated from routine complete blood counts of the peripheral blood, has been suggested to serve as a prognostic factor for some solid malignancies. In the present study, we aimed to determine the relationship between NLR in prostate cancer patients undergoing radical prostatectomy (RP) and their prognosis. Materials and Methods. We assessed NLR in 73 men (patients) who received RP for their prostate cancer. We also performed immunohistochemistry for CD8 and CD66b in a separate set of RP specimens. Results. The median NLR in the 73 patients was 1.85. There were no significant correlations of NLR with tumor grade (p = 0.834), pathological T stage (p = 0.082), lymph node metastasis (p = 0.062), or resection margin status (p = 0.772). Based on the area under the receiver operator characteristic curve (AUROC) to predict biochemical recurrence after RP, potential NLR cut-off point was determined to be 2.88 or 3.88. However, both of these cut-off points did not precisely predict the prognosis. There were no statistically significant differences in the number of CD66b-positive neutrophils or CD8-positive lymphocytes between stromal tissues adjacent to cancer glands and stromal tissues away from cancer glands and between different grades or stages of tumors. Conclusions. There was no association between NLR and biochemical failure after prostatectomy. PMID:27200375

  16. Lifestyle and Clinical Health Behaviors and PSA Tests

    ERIC Educational Resources Information Center

    Norris, Cynthia; McFall, Stephanie

    2006-01-01

    This study assessed the association of lifestyle and clinical health behaviors with prostate specific antigen (PSA) tests. The study used cross-sectional data from the 2002 Behavioral Risk Factor Surveillance System (BRFSS). We used Stata 8.0 to take into account the complex sample design in analyses. Both lifestyle and clinical health behaviors…

  17. PSA Screening Has Led to Overtreatment of Many Prostate Cancers

    Cancer.gov

    Screening for prostate cancer with the prostate-specific antigen (PSA) test has led to overtreatment of many prostate cancers, including aggressive treatments in older men considered to be at low risk for progression of the disease according to a study published in the July 26, 2010 Archives of Internal Medicine.

  18. Development of the IPRO-zone for fire PSA and its applications

    SciTech Connect

    Kang, D. I.; Han, S. H.

    2012-07-01

    A PSA analyst has been manually determining fire-induced component failure modes and modeling them into the PSA logics. These can be difficult and time-consuming tasks as they need much information and many events are to be modeled. KAERI has been developing the IPRO-ZONE (interface program for constructing zone effect table) to facilitate fire PSA works for identifying and modeling fire-induced component failure modes, and to construct a one top fire event PSA model. With the output of the IPRO-ZONE, the AIMS-PSA, and internal event one top PSA model, one top fire events PSA model is automatically constructed. The outputs of the IPRO-ZONE include information on fire zones/fire scenarios, fire propagation areas, equipment failure modes affected by a fire, internal PSA basic events corresponding to fire-induced equipment failure modes, and fire events to be modeled. This paper introduces the IPRO-ZONE, and its application results to fire PSA of Ulchin Unit 3 and SMART(System-integrated Modular Advanced Reactor). (authors)

  19. [Measurement of serum PSA by DELFIA PSA kit and its application for mass screening. The Gunma Urological Oncology Study Group].

    PubMed

    Imai, K; Watanabe, K; Higashi, H; Shinya, H; Okamura, K; Matsuo, Y; Yazima, H; Takezawa, Y; Yamanaka, H

    1993-09-01

    The significance of prostate specific antigen (PSA) measured by DELFIA PSA kit in the 1,177 serum samples examined by mass screening for prostate cancer was evaluated. All subjects were examined by questionnaire, digital rectal examination (DRE) and prostatic acid phosphatase (PAP) and the subjects in whom prostate cancer was suspected from abnormal DRE and/or elevated PAP were recommended to receive the secondary screening for the presence of prostate cancer. All serum specimens used for this study were kept in our serum bank. The cut-off value was investigated between non-cancer subjects (diagnosed as normal, voiding disturbance or BPH) and prostate cancer patients. When the cut-off value was 2.89 ng/ml, the sensitivity, specificity and accuracy as prostate marker was 80.6%, 90.0% and 89.4%, respectively. Therefore, the cut-off value was determined as 3.0 ng/ml. The significance of PSA was retrospectively evaluated compared to PAP in the subjects examined by our mass screening. Twenty eight of the 39 palpable prostate cancers which could not be detected from the PAP level were detected from the PSA level, namely the sensitivity of the detection using the PSA level is more excellent than that using PAP. However, the false negative rate obtained using PSA was high (30.3%) in the patients with stage B disease. The relationship among serum PSA concentration, prostate size estimated by DRE and age was investigated. PSA was increased with age and prostate size. This estimation should be confirmed by using an ultrasonography because the prostate size obtained by DRE is inaccurate as compared with that obtained by ultrasonography.

  20. External Beam Radiotherapy for Clinically Localized Hormone-Refractory Prostate Cancer: Clinical Significance of Nadir Prostate-Specific Antigen Value Within 12 Months

    SciTech Connect

    Ogawa, Kazuhiko Nakamura, Katsumasa; Sasaki, Tomonari; Onishi, Hiroshi; Koizumi, Masahiko; Shioyama, Yoshiyuki; Araya, Masayuki; Mukumoto, Nobutaka M.S.; Mitsumori, Michihide; Teshima, Teruki

    2009-07-01

    Purpose: To analyze retrospectively the results of external beam radiotherapy for clinically localized hormone-refractory prostate cancer and investigate the clinical significance of nadir prostate-specific antigen (PSA) value within 12 months (nPSA12) as an early estimate of clinical outcomes after radiotherapy. Methods and Materials: Eighty-four patients with localized hormone-refractory prostate cancer treated with external beam radiotherapy were retrospectively reviewed. The total radiation doses ranged from 30 to 76 Gy (median, 66 Gy), and the median follow-up period for all 84 patients was 26.9 months (range, 2.7-77.3 months). Results: The 3-year actuarial overall survival, progression-free survival (PFS), and local control rates in all 84 patients after radiotherapy were 67%, 61%, and 93%, respectively. Although distant metastases and/or regional lymph node metastases developed in 34 patients (40%) after radiotherapy, local progression was observed in only 5 patients (6%). Of all 84 patients, the median nPSA12 in patients with clinical failure and in patients without clinical failure was 3.1 ng/mL and 0.5 ng/mL, respectively. When dividing patients according to low (<0.5 ng/mL) and high ({>=}0.5 ng/mL) nPSA12 levels, the 3-year PFS rate in patients with low nPSA12 and in those with high nPSA12 was 96% and 44%, respectively (p < 0.0001). In univariate analysis, nPSA12 and pretreatment PSA value had a significant impact on PFS, and in multivariate analysis nPSA12 alone was an independent prognostic factor for PFS after radiotherapy. Conclusions: External beam radiotherapy had an excellent local control rate for clinically localized hormone-refractory prostate cancer, and nPSA12 was predictive of clinical outcomes after radiotherapy.

  1. Age, lifestyle, health risk indicators, and prostate-specific antigen scores in men participating in the world senior games.

    PubMed

    Merrill, Ray M; Perego, Ugo A M; Heiner, Stephen W

    2002-01-01

    A number of risk factors have been implicated for prostate cancer, with dietary fat intake the most commonly accepted modifiable risk. To assess the relationship between health risk indicators (e.g., cholesterol, blood pressure, blood sugar, and percent body fat), which are related to dietary fat intake, and prostate-specific antigen (PSA) scores. Relationships between demographics and select behaviors (e.g., cigarette smoking and physical activity) with PSA scores are also considered. The setting was the 1999 Huntsman World Senior Games in St. George, Utah. Subjects' analysis is based on 536 men aged 50 years and older completing a questionnaire and receiving free screening, including a PSA. Frequency distributions, multiple regression techniques, and the Spearman correlation coefficients. A positive relationship was observed between increasing age groups and mean PSA scores (Cochran-Mantel-Haenszel Chi-Square: 53.8, p < 0.0001). After adjusting for age, none of the personal risk factor indicators (i.e., cholesterol, blood pressure, blood sugar, and percent body fat) were related to PSA scores. Other factors not related to PSA scores after adjusting for age were race, marital status, education, history of chronic disease, cigarette smoking, alcohol use, and physical activity. Because risk indicators such as cholesterol, blood pressure, blood sugar, and percent body fat are associated with dietary fat intake, their failure to be related with PSA scores makes it further unclear how this commonly accepted modifiable risk factor for prostate cancer may influence the disease.

  2. Obesity and screening PSA levels among men undergoing an annual physical exam.

    PubMed

    Rundle, Andrew; Neugut, Alfred I

    2008-03-01

    Prior reports suggest that obesity is inversely associated with screening prostate-specific antigen (PSA) levels and may reduce screening sensitivity. We evaluated data on 10,623 men screened for prostate cancer during an annual physical examination program administered by EHE International, Inc., between 1/1/2004 and 6/30/2006. Of these, 3,623 men returned for additional physical exams during this period. We used multivariate linear regression analyses to determine whether higher BMI was inversely associated with PSA, and whether BMI, or change in BMI, was associated with change in PSA levels over time. We also developed a theoretical model for the effect of obesity on PSA levels in which increased plasma volume in the obese dilutes PSA levels. After control for age and race/ethnicity, higher BMI was associated with lower PSA levels; men with a BMI > or =40 had a geometric mean PSA level 0.14 ng/ml lower than men with a BMI <25 (P < 0.001). Prospectively, BMI at initial screening and change in BMI over 2 years were not associated with change in PSA or PSA velocity. Our theoretical model accurately predicted observed PSA levels and suggests that a screening PSA of 4.0 ng/ml in normal weight and overweight men corresponds to 3.5 ng/ml in obese men and 3.1 ng/ml in morbidly obese men. Across the study population, increased BMI was significantly inversely associated with lower PSA. Based on a theoretical model in which increased plasma volume in the obese dilutes PSA levels we propose new cut-points for a positive screening test. Copyright 2008 Wiley-Liss, Inc.

  3. [PSA variations in persons with latent prostate cancer].

    PubMed

    Stamatiou, K; Danciu, M; Karakos, C; Sofras, F

    2008-01-01

    The introduction and common use of serum PSA (Prostate Specific Antigen) has been demonstrated a useful index on latent prostate cancer diagnostic but in the same time has increased surgical intervention on histological forms with no eventual future evolution. Benign comportment of latent carcinomas being well known in advance, we correlated in vitro serum PSA from latent tumors, with the samples from a control group (prostates without signs of malignization). Levels of PSA were slightly elevated compared to age norms, mainly in cases with a large coexistent hypertrophy. Our reduced sample does not stand any statistic analysis, but this observation could eventually explain increased diagnostic and hyper-treatment of non-important carcinomas from a clinical point of view.

  4. PROSTATE CANCER SCREENING: PSA TEST AWARENESS AMONG ADULT MALES.

    PubMed

    Obana, Michael; O'Lawrence, Henry

    2015-01-01

    The overall purpose of this study was to determine whether visits to the doctor in the last 12 months, education level, and annual household income for adult males increased the awareness of prostate-specific antigen (PSA) tests. The effect of these factors for the knowledge of PSA exams was performed using statistical analysis. A retrospective secondary database was utilized for this study using the questionnaire in the California Health Interview Survey from 2009. Based on this survey, annual visits to the doctor, higher educational levels attained, and greater take-home pay were statistically significant and the results of the study were equivalent to those hypothesized. This also reflects the consideration of marketing PSA blood test screenings to those adult males who are poor, uneducated, and do not see the doctor on a consistent basis.

  5. Effect of Body mass index on the performance characteristics of PSA-related markers to detect prostate cancer

    PubMed Central

    Zhu, Yao; Han, Cheng-Tao; Zhang, Gui-Ming; Liu, Fang; Ding, Qiang; Xu, Jian-Feng; Vidal, Adriana C.; Freedland, Stephen J.; Ng, Chi-Fai; Ye, Ding-Wei

    2016-01-01

    To examine whether the predictive performance of prostate-specific antigen (PSA) and PSA-related markers for prostate cancer (PCa) is modified by body mass index (BMI). Patients with a PSA 2–10 ng/mL who underwent multicore prostate biopsies were recruited from three tertiary centers. Serum markers measured included total PSA (tPSA), free-to-total PSA (f/tPSA), p2PSA, percentage of p2PSA (%p2PSA), and prostate health index (PHI). The association between serum markers and PCa risk was assessed by logistic regression. Predictive performance for each marker was quantified using the area under the receiver operator curves (AUC). Among 516 men, 18.2% had PCa at biopsy. For all tested markers, their predictive value on PCa risk was lower in obese patients compared to normal weight patients. We found statistically significant interactions between BMI and tPSA (P = 0.0026) and p2PSA (P = 0.038). PHI achieved an AUC of 0.872 in normal weight patients and 0.745 in obese patients, which outperformed the other predictors regardless of BMI category. In conclusion, PHI achieved the best predictive performance for detecting PCa and was not influenced by BMI. PMID:26754552

  6. Early Prediction of Therapy Response to Abiraterone Acetate Using PSA Subforms in Patients with Castration Resistant Prostate Cancer

    PubMed Central

    Schlack, Katrin; Krabbe, Laura-Maria; Fobker, Manfred; Schrader, Andres Jan; Semjonow, Axel; Boegemann, Martin

    2016-01-01

    The purpose of this study was to evaluate the prognostic ability of early changes of total prostate specific antigen (tPSA), free PSA (fPSA), [−2]proPSA and the Prostate Health Index (PHI) following initiation of Abiraterone-therapy in men with castration resistant prostate cancer (mCRPC). In 25 patients, PSA-subforms were analyzed before and at 8–12 weeks under therapy as prognosticators of progression-free-survival (PFS) and overall survival (OS). Comparing patients with a PFS < vs. ≥12 months by using Mann–Whitney–Wilcoxon Tests, the relative-median-change of tPSA (−0.1% vs. −86.8%; p = 0.02), fPSA (12.1% vs. −55.3%; p = 0.03) and [−2]proPSA (8.1% vs. −59.3%; p = 0.05) differed significantly. For men with ≤ vs. >15 months of OS there was a non-significant trend for a difference in the relative-median-change of fPSA (17.0% vs. −46.3%; p = 0.06). In Kaplan–Meier analyses, declining fPSA and [−2]proPSA were associated with a longer median PFS (13 months, 95% confidence interval (CI): 9.6–16.4 vs. 10 months, 95% CI: 3.5–16.5; p = 0.11), respectively. Correspondingly, decreasing fPSA and [−2]proPSA values indicated an OS of 32 months (95% CI: not reached (NR)) compared to 21 months in men with rising values (95% CI: 7.7–34.3; p = 0.14), respectively. We concluded that the addition of fPSA- and [−2]proPSA-changes to tPSA-information might be further studied as potential markers of early Abiraterone response in mCRPC patients. PMID:27618028

  7. Early Prediction of Therapy Response to Abiraterone Acetate Using PSA Subforms in Patients with Castration Resistant Prostate Cancer.

    PubMed

    Schlack, Katrin; Krabbe, Laura-Maria; Fobker, Manfred; Schrader, Andres Jan; Semjonow, Axel; Boegemann, Martin

    2016-09-09

    The purpose of this study was to evaluate the prognostic ability of early changes of total prostate specific antigen (tPSA), free PSA (fPSA), [-2]proPSA and the Prostate Health Index (PHI) following initiation of Abiraterone-therapy in men with castration resistant prostate cancer (mCRPC). In 25 patients, PSA-subforms were analyzed before and at 8-12 weeks under therapy as prognosticators of progression-free-survival (PFS) and overall survival (OS). Comparing patients with a PFS < vs. ≥12 months by using Mann-Whitney-Wilcoxon Tests, the relative-median-change of tPSA (-0.1% vs. -86.8%; p = 0.02), fPSA (12.1% vs. -55.3%; p = 0.03) and [-2]proPSA (8.1% vs. -59.3%; p = 0.05) differed significantly. For men with ≤ vs. >15 months of OS there was a non-significant trend for a difference in the relative-median-change of fPSA (17.0% vs. -46.3%; p = 0.06). In Kaplan-Meier analyses, declining fPSA and [-2]proPSA were associated with a longer median PFS (13 months, 95% confidence interval (CI): 9.6-16.4 vs. 10 months, 95% CI: 3.5-16.5; p = 0.11), respectively. Correspondingly, decreasing fPSA and [-2]proPSA values indicated an OS of 32 months (95% CI: not reached (NR)) compared to 21 months in men with rising values (95% CI: 7.7-34.3; p = 0.14), respectively. We concluded that the addition of fPSA- and [-2]proPSA-changes to tPSA-information might be further studied as potential markers of early Abiraterone response in mCRPC patients.

  8. Patients treated with radical prostatectomy with positive digital rectal examination findings in the intermediate-risk group are prone to PSA recurrence

    PubMed Central

    FURUBAYASHI, NOBUKI; NEGISHI, TAKAHITO; URA, SHINTARO; MUTAGUCHI, JUN; TAGUCHI, KENICHI; SHIMOKAWA, MOTOTSUGU; NAKAMURA, MOTONOBU

    2016-01-01

    The present study aimed to evaluate the possibility of performing radical prostatectomy (RP) alone to achieve a radical cure for prostate cancer in the intermediate-risk group. Samples were collected from 638 Japanese patients who underwent antegrade RP between August 1998 and May 2013; subsequently, 157 patients were excluded. According to the D'Amico criteria, the low-, intermediate- and high-risk groups comprised 107, 222 and 152 patients, respectively. The 5-year prostate-specific antigen (PSA) failure-free survival rates in the low-, intermediate-, and high-risk groups were 96.5, 88.9 and 72.6%, respectively (P<0.001; degrees of freedom=2). In the intermediate-risk group, the difference in PSA failure-free survival between the 0PSA failure-free survival between the clinical tumor stage (cT)1c and cT2a/b groups was statistically significant based on the log-rank test (P<0.0001). The results of the multivariate analysis revealed that, of the preoperative characteristics, only the cT was a significant predictor in patients with and without PSA failure (P<0.001). Therefore, patients classified into the intermediate-risk group with cT2a/b stage, according to positive digital rectal examination findings, and are not considered to be likely to achieve a complete cure with RP surgery alone. In summary, for patients meeting these criteria in the intermediate-risk group, RP surgery alone is likely to be insufficient, and other additional treatments may be considered subsequent to RP. PMID:27313711

  9. PSA and beyond: alternative prostate cancer biomarkers.

    PubMed

    Saini, Sharanjot

    2016-04-01

    The use of biomarkers for prostate cancer screening, diagnosis and prognosis has the potential to improve the clinical management of the patients. Owing to inherent limitations of the biomarker prostate-specific antigen (PSA), intensive efforts are currently directed towards a search for alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and drive better treatment decisions. A literature search of Medline articles focused on recent and emerging advances in prostate cancer biomarkers was performed. The most promising biomarkers that have the potential to meet the unmet clinical needs in prostate cancer patient management and/or that are clinically implemented were selected. With the advent of advanced genomic and proteomic technologies, we have in recent years seen an enormous spurt in prostate cancer biomarker research with several promising alternative biomarkers being discovered that show an improved sensitivity and specificity over PSA. The new generation of biomarkers can be tested via serum, urine, or tissue-based assays that have either received regulatory approval by the US Food and Drug Administration or are available as Clinical Laboratory Improvement Amendments-based laboratory developed tests. Additional emerging novel biomarkers for prostate cancer, including circulating tumor cells, microRNAs and exosomes, are still in their infancy. Together, these biomarkers provide actionable guidance for prostate cancer risk assessment, and are expected to lead to an era of personalized medicine.

  10. PSA and beyond: alternative prostate cancer biomarkers

    PubMed Central

    2016-01-01

    Background The use of biomarkers for prostate cancer screening, diagnosis and prognosis has the potential to improve the clinical management of the patients. Owing to inherent limitations of the biomarker prostate-specific antigen (PSA), intensive efforts are currently directed towards a search for alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and drive better treatment decisions. Methods A literature search of Medline articles focused on recent and emerging advances in prostate cancer biomarkers was performed. The most promising biomarkers that have the potential to meet the unmet clinical needs in prostate cancer patient management and/or that are clinically implemented were selected. Conclusions With the advent of advanced genomic and proteomic technologies, we have in recent years seen an enormous spurt in prostate cancer biomarker research with several promising alternative biomarkers being discovered that show an improved sensitivity and specificity over PSA. The new generation of biomarkers can be tested via serum, urine, or tissue-based assays that have either received regulatory approval by the US Food and Drug Administration or are available as Clinical Laboratory Improvement Amendments-based laboratory developed tests. Additional emerging novel biomarkers for prostate cancer, including circulating tumor cells, microRNAs and exosomes, are still in their infancy. Together, these biomarkers provide actionable guidance for prostate cancer risk assessment, and are expected to lead to an era of personalized medicine. PMID:26790878

  11. Factors associated with blood loss during radical prostatectomy for localized prostate cancer in the prostate-specific antigen (PSA)-era: an overview of the Department of Defense (DOD) Center for Prostate Disease Research (CPDR) national database.

    PubMed

    Moul, Judd W; Sun, Leon; Wu, Hongyu; McLeod, David G; Amling, Christopher; Lance, Raymond; Foley, John; Sexton, Wade; Kusuda, Leo; Chung, Andrew; Soderdahl, Douglas; Donahue, Timothy

    2003-01-01

    Radical Prostatectomy (RP) has been traditionally associated with significant operative blood loss and high risk of transfusion. However, over the last few years, centers of excellence have reported less bleeding and transfusion. To verify and document changes in the epidemiology of bleeding and transfusion of men electing RP, we undertook an analysis of such cases in the Department of Defense (DoD) Center for Prostate Disease Research (CPDR) Multicenter Research Database. Using the Department of Defense Center for Prostate Disease Research (CPDR) Multicenter National Research Database, a query of all RPs performed between January 1, 1985 and December 31, 2000 was conducted revealing 2918 cases with blood-loss data available for analysis from nine hospital sites. These cases were analyzed over time (calendar year) and changes in the characteristics of the patients, disease severity, and surgical results were compared with estimated blood loss (EBL) and transfusion data. Among the 2918 evaluable men, 2399 (82%) underwent a retropubic RP, 97% had clinical T1-2 disease, and 77% had a PSA level > or =10.0 ng/mL. Overall median operation time was 3.8 h, and EBL was 1000 cc. Examining trends over time, there was a dramatic decline in median operative time, EBL, and transfusion rate. In multiple linear regression analysis, operative time, operative approach, surgery year, lymphadenectomy status, and neoadjuvant hormonal therapy were significant predictor of EBL. Blood loss difference between retropubic and perineal RP became insignificant in the latter years. Radical prostatectomy is being performed more commonly on men with earlier stage disease in the PSA-Era. The operation is now performed more rapidly with less blood loss and fewer transfusion requirements. In a broad practice experience represented here, autologous blood donation would appear to be unnecessary for the majority of men and the blood loss advantage traditionally associated with perineal RP is no longer

  12. Primary virus-induced lymphomas evade T cell immunity by failure to express viral antigens

    PubMed Central

    1989-01-01

    T lymphoma induction by the mink cell focus-inducing murine leukemia virus MCF 1233 in C57BL/10 and C57BL/6 mice is influenced by a strongly Th-dependent, H-2I-A-restricted antiviral immune response (25). We compared the MHC class I as well as viral env and gag antigenic cell surface profiles of frequent T lymphomas of H-2I-A nonresponder-type mice to that of rare T lymphomas of H-2I-A responder-type mice. Membrane immunofluorescence studies, with a panel of anti-env mAbs (reactive with the highly conserved gp70f epitope, the p15Ec epitope, and the gp70-p15E complex), a polyclonal anti-p30 serum, and anti-H-2 class I mAbs, showed that all 17 nonresponder tumors tested expressed high levels of both env and gag viral proteins, and 15 of these 17 nonresponder tumors expressed high levels of H-2 class I K and D antigens. In contrast, 10 of 11 responder lymphomas lacked env and/or gag determinants. The only responder lymphoma with both strong env and gag expression failed to express H-2K and -D antigens. Preferential loss of env or gag expression did not correlate with H-2 class I allelic specificities. Both responder and nonresponder T lymphoma DNA contained multiple, predominantly MCF-like, newly acquired proviral integrations. Differences in viral antigen cell surface expression were confirmed at cytoplasmic and RNA levels. The amounts of 8.2- and 3.2-kb viral RNA were greatly reduced in two responder lymphomas when compared with four nonresponder lymphomas. In both responder lymphomas, aberrantly sized viral RNA species were found. Upon in vivo passage of these responder lymphomas in either immunocompetent or T cell-deficient nu/nu mice, it was found that various molecular mechanisms may underlie the lack of viral antigen expression at the cell surface of these lymphomas. One lymphoma re-expressed viral antigens when transplanted with nu/nu mice, whereas the other remained stably gag negative. The combined findings indicate that an H-2I-A-regulated antiviral immune

  13. Impact of Biochemical Failure Classification on Clinical Outcome: A Secondary Analysis of Radiation Therapy Oncology Group 9202 and 9413

    PubMed Central

    Hamstra, Daniel A.; Bae, Kyounghwa; Hanks, Gerald; Hu, Chen; Shipley, William U.; Pan, Charlie C.; Roach, Mack; Lawton, Colleen A.; Sandler, Howard M.

    2015-01-01

    BACKGROUND Biochemical failure (BF) after radiation therapy is defined on the basis of a rising prostate-specific antigen (PSA) level (A1 failure) or any event that prompts the initiation of salvage androgen-deprivation therapy without PSA failure (A2). It was hypothesized that A2 failure may have a different prognosis. METHODS Data for 2799 eligible patients from Radiation Therapy Oncology Group (RTOG) 9202 and RTOG 9413 were analyzed. BF was defined according to the 1997 American Society for Therapeutic Radiology and Oncology consensus definition as A1 for PSA failure or as A2 for the start of salvage hormone therapy before 3 consecutive PSA rises. RESULTS Rates of all-cause mortality (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.5-2.0; P <.0001) and distant metastasis (DM; HR, 1.6; 95% CI, 1.3-2.0; P <.0001) were greater with A2 failure. The 5-year overall survival (OS) rates were 88.2% and 74.6% for A1 and A2, respectively (P <.0001), and the DM rates were 15.7% and 29.0%, respectively (P <.0001). The DM rate was greater at 5 years for A2 patients with DM as the first sign of failure versus patients with other A2 failures (87.3% vs 11.7%, P <.001), and this also correlated with worse OS at 5 years: 81.1% for A2 failure without DM and 52.8% with DM (P <.001). After the removal of patients with DM, the difference between A1 and A2 BF persisted for OS (P =.002) but not for DM (P =.16) CONCLUSIONS These results suggest that patients with rising PSA levels alone have less risk than those with A2 failures; although DM was the largest contributor of adverse risk to A2 failure, it did not account for all excess risk in A2 failure. PMID:25410885

  14. proPSA — EDRN Public Portal

    Cancer.gov

    ProPSA (-2), or [-2]proPSA, is a PSA isoform which has a leader peptide (-2) amino acids at its N terminal region and does not interact with ACT or alpha-2-macroglobulin or spermidine and therefore is detected as a separate isoform. ProPSA is produced primarily in the peripheral zone of the prostate gland and therefore is very useful in distinguishing between prostate cancer patients with PSA range of 2-10, from those who have BPH. Percent proPSA is the ratio of proPSA to free PSA. In July 2012 the FDA approved an assay measuring levels of [-2]proPSA for monitoring and diagnostic purposes.

  15. Accuracy of PSA Self-Reports among Low-Income Men with Prostate Cancer after a Public Health Nursing Intervention.

    PubMed

    Zavala, Mary Wassel; Yule, Arthur; Kwan, Lorna; Lambrechts, Sylvia; Maliski, Sally L; Litwin, Mark S

    2016-11-01

    To examine accuracy of patient-reported prostate-specific antigen (PSA) levels among indigent, uninsured men in a state-funded prostate cancer treatment program that provides case management, care coordination, and health education. Program evaluation. About 114 men with matched self- and lab-reported PSA levels at program enrollment and another time point within 18 months. Abstraction of self- and lab-reported PSA levels to determine self-report as "accurate" or "inaccurate," and evaluate accuracy change over time, before and after nursing interventions. Chi-square tests compared patients with accurate versus inaccurate PSA values. Nonlinear multivariate analyses explored trends in self-reported accuracy over time. Program enrollees receive prostate cancer education from a Nurse Case Manager (NCM), including significance of PSA levels. Men self-report PSA results to their NCM following lab draws and appointments. The NCM provides ongoing education about PSA levels. Of the sample, 46% (n = 53) accurately reported PSA levels. Accuracy of PSA self-reports improved with increasing time since program enrollment. Compared with men at public facilities, those treated at private facilities showed increasing accuracy in self-reported PSA (p = .038). A targeted nursing intervention may increase specific knowledge of PSA levels. Additionally, the provider/treatment setting significantly impacts a patient's disease education and knowledge. © 2016 Wiley Periodicals, Inc.

  16. Determining Interactions in PSA models: Application to a Space PSA

    SciTech Connect

    C. Smith; E. Borgonovo

    2010-06-01

    This paper addresses use of an importance measure interaction study of a probabilistic risk analysis (PSA) performed for a hypothetical aerospace lunar mission. The PSA methods used in this study follow the general guidance provided in the NASA Probabilistic Risk Assessment Procedures Guide for NASA Managers and Practitioners. For the PSA portion, we used phased-based event tree and fault tree logic structures are used to model a lunar mission, including multiple phases (from launch to return to the Earth surface) and multiple critical systems. Details of the analysis results are not provided in this paper – instead specific basic events are denoted by number (e.g., the first event is 1, the second is 2, and so on). However, in the model, we used approximately 150 fault trees and over 800 basic events. Following analysis and truncation of cut sets, we were left with about 400 basic events to evaluate. We used this model to explore interactions between different basic events and systems. These sensitivity studies provide high-level insights into features of the PSA for the hypothetical lunar mission.

  17. The PSA: Planetary Science Archive

    NASA Astrophysics Data System (ADS)

    Barthelemy, M.; Metselaar, H.; Martinez, S.; Heather, D.; Vazquez, J. L.; Wirth, K.; Manaud, N.; Ortiz, I.; Arviset, C.; Fernandez, M.

    2009-04-01

    Scientific and engineering data from ESA's planetary missions are made accessible to the world-wide scientific community via the Planetary Science Archive (PSA). The PSA consists of online services incorporating search, preview, download, notification and delivery basket functionality. Besides data from the GIOTTO spacecraft and several ground-based cometary observations, the PSA contains data from the Mars Express, Venus Express, Rosetta, and Huygens missions. Preparation for the release of data from the SMART-1 spacecraft is ongoing. The focus of the PSA activities is on the long-term preservation of data and knowledge from ESA's planetary missions. Scientific users can access the data online using several interfaces: The Classical Interface allows complex parameter based queries, providing the end user with a facility to complete very specific searches on meta-data and geometrical parameters. By nature, this interface requires careful use and heavy interaction with the end-user to input and control the relevant search parameters. The Map-based Interface is currently operational only for Mars Express HRCS and OMEGA data. This interface allows an end-user to specify a region-of-interest by dragging a box onto a base map of Mars. From this interface, it is possible to directly visualize query results. The Map-based and Classical interfaces are linked and cross-compatible. If a user defines a region-of-interest in the Map-based interface, the results can be refined by entering more detailed search parameters in the Classical interface. The Dataset Browser Interface is designed for more experienced users, and allows for direct browsing and access of the data set content through ftp-tree search. Each dataset contains documentation and calibration information in addition to the scientific or engineering data. All data are prepared by the corresponding instrument teams, mostly located in Europe. PSA staff supports the instrument teams in the full archiving process

  18. The PSA: Planetary Science Archive

    NASA Astrophysics Data System (ADS)

    Barthelemy, Maud; Metselaar, Harold; Martinez, Santa; Heather, David; Vazquez, Jose Luis; Manaud, Nicolas; Ortiz, Iñaki; Arviset, Christophe; Osuna, Pedro

    2010-05-01

    Scientific and engineering data from ESA's planetary missions are made accessible to the world-wide scientific community via the Planetary Science Archive (PSA). The PSA consists of online services incorporating search, preview, download, notification and delivery basket functionality. Besides data from the GIOTTO spacecraft and several ground-based cometary observations, the PSA contains data from the Mars Express, Venus Express, Rosetta, and Huygens missions. Preparation for the release of data from the SMART-1 spacecraft is ongoing. The focus of the PSA activities is on the long-term preservation of data and knowledge from ESA's planetary missions. Scientific users can access the data online using several interfaces: - The Classical Interface allows complex parameter based queries, providing the end user with a facility to complete very specific searches on meta-data and geometrical parameters. By nature, this interface requires careful use and heavy interaction with the end-user to input and control the relevant search parameters. - The Map-based Interface is currently operational only for Mars Express HRCS and OMEGA data. This interface allows an end-user to specify a region-of-interest by dragging a box onto a base map of Mars. From this interface, it is possible to directly visualize query results. The Map-based and Classical interfaces are linked and cross-compatible. If a user defines a region-of-interest in the Map-based interface, the results can be refined by entering more detailed search parameters in the Classical interface. - The Dataset Browser Interface is designed for more experienced users, and allows for direct browsing and access of the data set content through ftp-tree search. Each dataset contains documentation and calibration information in addition to the scientific or engineering data. All data are prepared by the corresponding instrument teams, mostly located in Europe. PSA staff supports the instrument teams in the full archiving process

  19. Prognostic effect of carbohydrate antigen 125-guided therapy in patients recently discharged for acute heart failure (CHANCE-HF). Study design.

    PubMed

    Núñez, Julio; Merlos, Pilar; Fácila, Lorenzo; Llàcer, Pau; Bosch, Maria José; Bertomeu-Martínez, Vicente; García-Blas, Sergio; Montagud, Vicente; Pedrosa, Valle; Mendizábal, Andrea; Cordero, Alberto; Miñana, Gema; Sanchis, Juan; Bertomeu-González, Vicente

    2015-02-01

    Morbidity and mortality after admission for acute heart failure remain prohibitively high. In that setting, plasma levels of antigen carbohydrate 125 have shown to correlate with the severity of fluid overload and the risk of mortality and readmission. Preliminary data suggests a potential role of antigen carbohydrate 125 to guide therapy. The objective of this study is to evaluate the prognostic effect of an antigen carbohydrate 125-guided management strategy vs standard therapy in patients recently discharged for acute heart failure. This is a multicenter, randomized, single-blind, efficacy trial study of patients recently discharged from acute heart failure (< 180 days), New York Heart Association functional class II-IV and antigen carbohydrate 125 > 35 U/ml. A randomization scheme was used to allocate participants (in a 1:1 ratio) to receive therapy guided by antigen carbohydrate 125 (aiming to keep normal values) or standard treatment. Mainly, antigen carbohydrate 125-guided therapy is focused on the frequency of monitoring and titration of decongestive therapies and statins. As of December 10, 2013, there were 383 patients enrolled. The primary outcome was the composite of 1-year all-cause mortality or rehospitalization for acute heart failure. Analysis was planned to be intention-to-treat. Discovering novel therapeutic strategies or finding better ways of optimizing established treatments have become a health care priority in heart failure. This study will add important knowledge about the potential of antigen carbohydrate 125 as a management tool for monitoring and titration of therapies where optimal utilization has not been well defined, such as diuretics and statins. ClinicalTrials.gov number: NCT02008110. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Prostate-specific antigen doubling time predicts clinical outcome and survival in prostate cancer patients treated with combined radiation and hormone therapy

    SciTech Connect

    Lee, Andrew K. . E-mail: aklee@mdanderson.org; Levy, Larry B.; Cheung, Rex; Kuban, Deborah

    2005-10-01

    Purpose: To determine whether prostate-specific antigen (PSA) doubling time predicts clinical outcomes in patients with prostate cancer that has been treated with combined radiation and hormone therapy. Methods and Materials: We reviewed the medical records of 621 men with nonmetastatic prostate cancer treated with radiation therapy and hormone therapy between 1989 and 2003. 'Any' clinical failure was defined as any distant, nodal, or local failure, or the use of salvage therapy. 'True' clinical failure was defined as any distant, nodal, or local failure. PSA doubling time was calculated by using the log PSA values from patients with a PSA failure as defined by the American Society of Therapeutic Radiology Oncology consensus statement. One hundred thirty-seven men were at intermediate risk for PSA failure (as determined by T2b, Gleason score of 7, or PSA 10.1-0 ng/mL) and 484 men were at high risk for failure (T2c-4; Gleason 8-10; or PSA >20 ng/mL). Pretreatment PSA value, Gleason score, tumor stage, timing and duration of hormone therapy, radiation therapy dose, and PSA doubling time were analyzed for any associations with time to clinical failure by using Cox regression analysis. Estimates of survival were calculated by using the Kaplan-Meier method. Pairwise comparisons were made by using the log-rank test. Results: Sixty-two men experienced any clinical failure, and 22 men experienced true clinical failure. Multivariate analysis revealed that pretreatment PSA (p = 0.013), Gleason score (p = 0.0019), and a PSA doubling time (PSADT) {<=}8 months (p < 0.001) were independently associated with time to any clinical failure. Tumor stage, hormone therapy timing, hormone therapy duration, and radiation therapy dose were not statistically significant on multivariate or univariate analysis. Only hormone therapy duration (p 0.008) and PSADT {<=}8 months (<0.001) were significantly associated with time to true clinical failure. The estimated 5-year rate of any clinical

  1. Statin Medications are Associated with a Lower Probability of Having an Abnormal Screening PSA Result

    PubMed Central

    Shi, Ying; Fung, Kathy Z.; Freedland, Stephen J.; Hoffman, Richard M.; Tang, Victoria L.; Walter, Louise C.

    2014-01-01

    Objective To investigate how statin use is associated with the probability of having an abnormal screening prostate-specific antigen (PSA) result according to common PSA thresholds for biopsy (>2.5, >4.0, and >6.5 ng/mL). Methods We conducted a cross-sectional study of 323,426 men aged 65+ who had a screening PSA test in 2003 at a VA facility. The primary predictor was the use of statin medications at the time of index screening PSA test. The main outcome was the screening PSA value. Poisson regressions were performed to calculate adjusted relative risks for having an abnormal screening PSA result according to statin usage. Results Percentages of men with PSA results exceeding commonly used thresholds >2.5, >4.0, and >6.5 ng/mL were 21.0%, 7.6%, and 1.6% respectively. These percentages decreased with statin use, increasing statin dose, duration of statin use, and potency of statin. For example, after adjusting for age, the percentage of men having a PSA exceeding 4.0 ng/mL ranged from 8.2% in non-statin users to 6.2% in men prescribed >40mg simvastatin dose. Adjusted relative risks of having a PSA >4.0 ng/mL were 0.89 (95% CI=0.86–0.93), 0.87 (95% CI=0.84–0.91), and 0.83 (95% CI=0.80–0.87) respectively for men on simvastatin dose of 5–20mg, >20–40mg, and >40mg versus non-statin users. Conclusion Statin use is associated with a reduction in the probability an older man will have an abnormal screening PSA result, regardless of PSA threshold. This reduction is more pronounced with higher statin dose, longer statin duration, and higher statin potency. PMID:25443902

  2. Baseline PSA measurements and subsequent prostate cancer risk in the Danish Diet, Cancer and Health cohort

    PubMed Central

    Larsen, Signe Benzon; Brasso, Klaus; Iversen, Peter; Christensen, Jane; Christiansen, Michael; Carlsson, Sigrid; Lilja, Hans; Friis, Søren; Tjønneland, Anne; Dalton, Susanne Oksbjerg

    2014-01-01

    Aim Although prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer. Methods and material Case-control study nested within the Danish ‘Diet, Cancer and Health’ cohort of 27,179 men aged 50–64 at enrolment. PSA measured in serum collected at cohort entry in 1993–1997 was used to evaluate prostate cancer risk diagnosed up to 14 years after. We identified 911 prostate cancer cases in the Danish Cancer Registry through 31 December 2007 1:1 age-matched with cancer-free controls. Aggressive cancer was defined as ≥T3 or Gleason score ≥7 or N1 or M1. Statistical analyses were based on conditional logistic regression with age as underlying time axis. Results Total PSA and free-to-total PSA ratio at baseline were strongly associated with prostate cancer risk up to 14 years later. PSA was grouped in quintiles and free-to-total PSA ratio divided in three risk groups. The incidence rate ratio for prostate cancer was 150 (95% confidence interval, 72–310) among men with a total PSA in the highest quartile (>5.1 ng/ml) compared to the lowest (<0.80 ng/ml). The risk of aggressive cancer was highly elevated in men with a PSA level in the highest quintile. The results indicate that one-time measurement of PSA could be used in an individualized screening strategy, sparing a large proportion of men from further PSA-based screening. PMID:23684783

  3. Incorporating Known Genetic Variants Does Not Improve the Accuracy of PSA Testing to Identify High Risk Prostate Cancer on Biopsy

    PubMed Central

    Gilbert, Rebecca; Martin, Richard M.; Evans, David M.; Tilling, Kate; Davey Smith, George; Kemp, John P.; Lane, J. Athene; Hamdy, Freddie C.; Neal, David E.; Donovan, Jenny L.; Metcalfe, Chris

    2015-01-01

    Introduction Prostate-specific antigen (PSA) testing is a widely accepted screening method for prostate cancer, but with low specificity at thresholds giving good sensitivity. Previous research identified four single nucleotide polymorphisms (SNPs) principally associated with circulating PSA levels rather than with prostate cancer risk (TERT rs2736098, FGFR2 rs10788160, TBX3 rs11067228, KLK3 rs17632542). Removing the genetic contribution to PSA levels may improve the ability of the remaining biologically-determined variation in PSA to discriminate between high and low risk of progression within men with identified prostate cancer. We investigate whether incorporating information on the PSA-SNPs improves the discrimination achieved by a single PSA threshold in men with raised PSA levels. Materials and Methods Men with PSA between 3-10ng/mL and histologically-confirmed prostate cancer were categorised as high or low risk of progression (Low risk: Gleason score≤6 and stage T1-T2a; High risk: Gleason score 7–10 or stage T2C). We used the combined genetic effect of the four PSA-SNPs to calculate a genetically corrected PSA risk score. We calculated the Area under the Curve (AUC) to determine how well genetically corrected PSA risk scores distinguished men at high risk of progression from low risk men. Results The analysis includes 868 men with prostate cancer (Low risk: 684 (78.8%); High risk: 184 (21.2%)). Receiver operating characteristic (ROC) curves indicate that including the 4 PSA-SNPs does not improve the performance of measured PSA as a screening tool for high/low risk prostate cancer (measured PSA level AU C = 59.5% (95% CI: 54.7,64.2) vs additionally including information from the 4 PSA-SNPs AUC = 59.8% (95% CI: 55.2,64.5) (p-value = 0.40)). Conclusion We demonstrate that genetically correcting PSA for the combined genetic effect of four PSA-SNPs, did not improve discrimination between high and low risk prostate cancer in men with raised PSA levels (3-10ng

  4. The PSA: Planetary Science Archive

    NASA Astrophysics Data System (ADS)

    Barthelemy, M.; Martinez, S.; Heather, D.; Vazquez, J. L.; Arviset, C.; Osuna, P.; PSA development Team

    2012-04-01

    Scientific and engineering data from ESA's planetary missions are made accessible to the world-wide scientific community via the Planetary Science Archive (PSA). The PSA consists of online services incorporating search, preview, download, notification and delivery basket functionality. Besides data from the GIOTTO spacecraft and several ground-based cometary observations, the PSA contains data from the Mars Express, Venus Express, Rosetta, SMART-1 and Huygens missions. The focus of the PSA activities is on the long-term preservation of data and knowledge from ESA's planetary missions. Scientific users can access the data online using several interfaces: - The Advanced Search Interface allows complex parameter based queries, providing the end user with a facility to complete very specific searches on meta-data and geometrical parameters. By nature, this interface requires careful use and heavy interaction with the end-user to input and control the relevant search parameters. - The Map-based Interface is currently operational only for Mars Express HRCS and OMEGA data. This interface allows an end-user to specify a region-of-interest by dragging a box onto a base map of Mars. From this interface, it is possible to directly visualize query results. The Map-based and Advanced interfaces are linked and cross-compatible. If a user defines a region-of-interest in the Map-based interface, the results can be refined by entering more detailed search parameters in the Advanced interface. - The FTP Browser Interface is designed for more experienced users, and allows for direct browsing and access of the data set content through ftp-tree search. Each dataset contains documentation and calibration information in addition to the scientific or engineering data. All data are prepared by the corresponding instrument teams, mostly located in Europe. PSA supports the instrument teams in the full archiving process, from the definition of the data products, meta-data and product labels

  5. The new insight of prostate-specific antigen reduction during finasteride therapy in aging men.

    PubMed

    Xu, Ding; Ding, Jie; Zhu, Yunkai; Qian, Xiaoqiang; Duan, Liujian; Qi, Jun

    2016-12-01

    To evaluate the effect of finasteride on prostate-specific antigen (PSA) in Chinese population. From Feb 2011 to Jan 2012, 83 benign prostatic hyperplasia (BPH) patients with prostate volume (PV) >30 mL were enrolled in our study. All the patients were older than 50 years and all of them received combined therapy (finasteride + doxazosin). All the patients were required for 1-year follow-up. PSA level and PV was measured at the start, 6 and 12 months, respectively. 79 patients completed the follow up. PSA level reduced by approximately 40 % during finasteride therapy. We defined baseline PSA as PSA1, PSA at 6 months as PSA2, PSA at 12 months as PSA3. PSA1 was significantly correlated with PSA2/PSA1 and PSA3/PSA1. However, prostate volume was not correlated with PSA1. We divided the patients into three groups according to PSA level. Groups 1, 2, 3 represented the patients with PSA less than 2 ng/mL, between 2 and 4 ng/mL and greater than 4 ng/mL, respectively. Both the PSA2/PSA1 and the PSA3/PSA1 had significant difference among three groups. Furthermore, group 1 and group 2 both showed the fairly large data variance. When baseline PSA level was greater than 4 ng/mL, the doubling rule could be used for screening. When baseline PSA level was less than 4 ng/Ml, the doubling rule might not be an accurate predictor. We can use the PSA rise from nadir or proPSA to predict prostate cancer.

  6. Establishment of a mammalian expression system for recombinant [-2]proPSA and a specific antibody against the truncated leader peptide.

    PubMed

    Hwang, Dobeen; Yoon, Aerin; Kim, Soohyun; Kim, Hyori; Chung, Junho

    2017-05-01

    A truncated precursor form of prostate-specific antigen (PSA), [-2]proPSA, is a well-known biomarker for prostate cancer. To develop a biomarker assay, highly purified [-2]proPSA is required as a standard reference and for generation of a specific antibody. In this study, we generated an efficient mammalian expression system for producing a recombinant [-2]proPSA-human kappa constant domain (Cκ ) fusion protein. N-terminal amino acid sequencing using Edman degradation demonstrated that over 95% of the recombinant protein produced is [-2]proPSA, thereby showing for the first time that recombinant [-2]proPSA can be produced as a major fraction. We also generated a recombinant chicken antibody specific to [-2]proPSA but not cross-reactive to recombinant [-7]proPSA-Cκ , [-5]proPSA-Cκ , and PSA purified from human seminal fluid in enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. Also, the recombinant chicken antibody reacted to recombinant [-2]proPSA protein bound to an anti-PSA antibody coated on the micrometer plate in a sandwich ELISA. All of these results suggest that the N-terminus of the [-2]proPSA-Cκ fusion protein resides on the exterior of the protein, thus allowing exposure to the antibody. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  7. Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD.

    PubMed

    Leveque-El Mouttie, Lucie; Koyama, Motoko; Le Texier, Laetitia; Markey, Kate A; Cheong, Melody; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; Alexander, Kylie A; Clouston, Andrew D; Blazar, Bruce R; Hill, Geoffrey R; MacDonald, Kelli P A

    2016-08-11

    Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD.

  8. Beyond PSA: The next generation of prostate cancer biomarkers

    PubMed Central

    Prensner, John R.; Rubin, Mark A.; Wei, John T.; Chinnaiyan, Arul M.

    2013-01-01

    Since the introduction of serum prostate specific antigen (PSA) screening twenty-five years ago, prostate cancer diagnosis and management have been guided by this biomarker. Yet, PSA has proven controversial as a diagnostic assay due to its limitations. The next wave of prostate cancer biomarkers has emerged, introducing new assays in serum and urine that may supplement or, in time, replace PSA due to higher cancer specificity. This expanding universe of biomarkers has been facilitated, in large part, by new genomic technologies that have enabled an unbiased look at cancer biology. Such efforts have produced several notable success stories, moving biomarkers from the bench to the clinic rapidly. However, biomarker research has centered on disease diagnostics, rather than prognosis and prediction, which could work toward disease prevention—an important focus moving forward. We review the current state of prostate cancer biomarker research, including the PSA revolution, its impact on early prostate cancer detection, the recent advances in biomarker discovery, and the future efforts that promise to improve clinical management of this disease. PMID:22461644

  9. Ultrasensitive Electrochemical Sensors for PSA Detection: Related Surface Functionalization Strategies.

    PubMed

    Blel, Nesrine; Fourati, Najla; Souiri, Mina; Zerrouki, Chouki; Omezzine, Asma; Bouslama, Ali; Othmane, Ali

    2017-08-21

    Prostate cancer is the most common male cancer in the world. The diagnosis, staging, prognosis and monitoring are usually done with Prostate Specific Antigen (PSA). Biosensors have emerging as a novel analytical technology for PSA detection. They provide several advantages for clinical applications and will benefit clinicians, patients and forensic workers in the future. Among them, electrochemical immunosensors have gained growing interests. Hence, their sensitivity is often improved by modifying them with nanoparticles especially iron oxide (IONP). Functionalized IONP attracted much attention in the fabrication of biosensing systems, due to their multiple properties, such as biocompatibility and signal amplification, and their ability to bind covalently to antibodies via their functional groups. In the present study, two electrochemical immunosensors were investigated for PSA detection. The first one was functionalized with 3- glycidoxypropyltrimethoxysilane self-assembled monolayer, while the second one was based on iron oxide nanoparticles functionalized with 3-aminopropyltriethoxysilane. Square wave voltammetry (SWV) has been investigated to follow-up the PSA detection in a phosphate buffer solution, in an artificial serum and in a human serum. The limit of detection (LOD) of both immunosensors was found of order of 10 fg/ml. When estimated in human serum this value increases up to 50 pg/ml. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Clinical significance of the prostate-specific antigen doubling time prior to and following radical prostatectomy to predict the outcome of prostate cancer

    PubMed Central

    Takeuchi, Hisashi; Ohori, Makoto; Tachibana, Masaaki

    2017-01-01

    With the advent of serum prostate-specific antigen (PSA), a larger number of prostate cancers in the early phase have been successfully detected. Although decisions to perform prostate biopsies are routinely based on PSA levels, the PSA level is easily influenced by benign prostatic hyperplasia, with poor specificity. Therefore, the aim of the present study was to assess the clinical significance of prostate-specific antigen doubling time (PSADT) prior to and following radical prostatectomy. In total, 488 patients with T1c-3N0M0 prostate cancer who underwent radical prostatectomy were included. Preoperative and postoperative PSADT were retrospectively correlated with pathological and clinical outcomes. Preoperative PSADT was measured in 204 of the 488 patients. In total, 16 out of 20 patients with a preoperative PSADT of >24 months had a cancer confined to the prostate compared with 105 of 184 patients with a PSADT of <24 months. The PSA non-recurrence rate at 5 years for patients with a preoperative PSADT of >24 months was significantly better compared with those with a preoperative PSADT of <24 months (P=0.011). Patients with a PSADT of >24 months and stable PSADT were associated with PSA recurrence following surgery, based on multivariate analysis. Postoperative PSADT was measured in 51 of 111 patients with PSA failure following surgery. Pathologically, 7 of 8 patients with a post-PSADT of >24 months had a cancer confined to the prostate compared with 14 of 43 patients with a post-PSADT of <24 months. These results suggest that patients with longer preoperative PSADTs appeared to have a favorable pathological result and a higher PSA non-recurrence rate compared with those with shorter preoperative PSADTs. A longer postoperative PSADT may facilitate the observation of patients with PSA recurrence without immediate secondary treatments. PMID:28357104

  11. Predictive value of [-2]propsa (p2psa) and its derivatives for the prostate cancer detection in the 2.0 to 10.0ng/mL PSA range

    PubMed Central

    Vukovic, I.; Djordjevic, D.; Bojanic, N.; Babic, U.; Soldatovic, I.

    2017-01-01

    ABSTRACT Introduction To assess predictive value of new tumor markers, precursor of prostate specific antigen (p2PSA) and its derivates-%p2PSA and prostate health index (PHI) in detection of patients with indolent and aggressive prostate cancer (PC) in a subcohort of man whose total PSA ranged from 2 to 10ng/mL. Materials and Methods This cross-sectional study included 129 consecutive male patients aged over 50 years, with no previous history of PC and with normal digital rectal examination findings, but with serum PSA in interval between 2 and 10ng/mL. All patients underwent standard transrectal ultrasonography guided prostate biopsy for the first time. For all patients, serum PSA, free PSA (fPSA) and p2PSA were measured and PHI and %p2PSA were calculated. Results PHI and %p2PSA levels were significanlty higher in patients with PC compared to those without this malignancy. The same findings have been observed in group of patients with Gleason score ≥7 compared to those with Gleason score <7. ROC analysis reveled the highest area under the curve with these two markers. Multivariate logistic regression showed significant improvement in PC detection and its agressive form (assumed as Gleason score ≥7). Conclusions New markers, derivates of p2PSA (especially %p2PSA and PHI), represente potentially very important clinical tool for predicting presence of PC, and even more important, to discriminate patients with Gleason score <7 from those with Gleason score ≥7 with total PSA in range from 2 to 10ng/mL. PMID:28124526

  12. Urinary prostate specific antigen levels after radical prostatectomy.

    PubMed

    Takayama, T K; Vessella, R L; Brawer, M K; True, L D; Noteboom, J; Lange, P H

    1994-01-01

    It was recently demonstrated that urinary prostate specific antigen (PSA) is discordant with serum PSA in many patients after radical prostatectomy. This observation led to the speculation that elevated urinary PSA in the face of undetectable serum PSA may indicate early disease recurrence. We measured urinary PSA levels in 30 patients who had undergone radical prostatectomy for prostate carcinoma and 7 patients who had undergone cystoprostatectomy for bladder cancer. PSA levels of randomly collected urine samples ranged from 0.00 to 22.9 ng./ml. and 0.01 to 8.37 ng./ml., respectively. There was no correlation among urinary and serum PSA levels, pathological stage or type of operation. In 14 patients who had undergone radical prostatectomy and who had measurable levels of urinary PSA voided specimens were divided into initial stream and end stream voided samples. The PSA levels in the end stream voided samples were significantly less than the initial stream sample in 12 of the 14 patients. In men who had undergone radical prostatectomy urethral swab samples were analyzed for PSA. Of 26 patients 24 had detectable levels of urethral swab PSA (range 0.01 to 39.04 ng./ml., median 0.93 ng./ml.). Urethral swab PSA levels did not correlate with serum PSA values or pathological stage of disease. Of 7 patients who had defunctionalized urethras after radical cystoprostatectomy 5 had significantly elevated PSA in the urethral wash or swab samples (range 4.3 to 24.5 ng./ml.). Immunohistochemical analysis of urethrectomy specimens demonstrated positive staining for PSA in 3 of 4 specimens. We conclude that the major source of urinary PSA following total prostatectomy is the urethra itself rather than residual prostate tissue. Measuring serial urinary PSA appears to have limited value in monitoring patients after radical prostatectomy. Whether this urethral PSA can ever contaminate the serum levels of PSA after radical prostatectomy is currently under investigation.

  13. Remaining Life Expectancy Measurement and PSA Screening of Older Men.

    PubMed

    Kotwal, Ashwin A; Mohile, Supriya G; Dale, William

    2012-07-01

    BACKGROUND: Guidelines recommend informed decision-making regarding prostate specific antigen (PSA) screening for men with at least 10 years of remaining life expectancy (RLE). Comorbidity measures have been used to judge RLE in previous studies, but assessments based on other common RLE measures are unknown. We assessed whether screening rates varied based on four clinically relevant RLE measures, including comorbidities, in a nationally-representative, community-based sample. METHODS: Using the National Social Life, Health and Aging Project (NSHAP), we selected men over 65 without prostate cancer (n=709). They were stratified into three RLE categories (0-7 years, 8-12 years, and 13+ years) based on validated measures of comorbidities, self-rated health status, functional status, and physical performance. The independent relationship of each RLE measure and a combined measure to screening was determined using multivariable logistic regressions. RESULTS: Self-rated health (OR = 6.82; p < 0.01) most closely correlated with RLE-based screening, while the comorbidity index correlated the least (OR = 1.50; p = 0.09). The relationship of RLE to PSA screening significantly strengthened when controlling for the number of doctor visits, particularly for comorbidities (OR= 43.6; p < 0.001). Men who had consistent estimates of less than 7 years RLE by all four measures had an adjusted PSA screening rate of 43.3%. CONCLUSIONS: Regardless of the RLE measure used, men who were estimated to have limited RLE had significant PSA screening rates. However, different RLE measures have different correlations with PSA screening. Specific estimates of over-screening should therefore carefully consider the RLE measure used.

  14. SBRT and HDR brachytherapy produce lower PSA nadirs and different PSA decay patterns than conventionally fractionated IMRT in patients with low- or intermediate-risk prostate cancer.

    PubMed

    Kishan, Amar U; Wang, Pin-Chieh; Upadhyaya, Shrinivasa K; Hauswald, Henrik; Demanes, D Jeffrey; Nickols, Nicholas G; Kamrava, Mitchell; Sadeghi, Ahmad; Kupelian, Patrick A; Steinberg, Michael L; Prionas, Nicolas D; Buyyounouski, Mark K; King, Christopher R

    2016-01-01

    To compare patterns of prostate-specific antigen (PSA) response following stereotactic body radiation therapy (SBRT), high-dose-rate (HDR) brachytherapy, and conventionally fractionated intensity modulated radiation therapy (IMRT) in patients with low- or intermediate-risk prostate cancer (CaP). Eligible study patients included 439 patients with low- or intermediate-risk prostate cancer who were treated with radiation therapy (RT) alone between 2003 and 2013, remained free of biochemical recurrence, and had at least 2 PSA values within the first year following RT. Of these, 130 were treated with SBRT, 220 with HDR brachytherapy, and 89 with IMRT. Multivariate regression analysis was used to compare PSA nadirs (nPSA), time to nPSA, and PSA bounce parameters among the 3 modalities. Indicator variable analysis was used to develop empirical models of PSA decay using the treatment modalities as indicator variables. Significantly more patients treated with SBRT or HDR brachytherapy achieved raw nPSAs of <0.5 ng/mL compared with patients treated with IMRT (76.2% and 75.9% vs 44.9%, respectively; P < .0001 for SBRT or HDR brachytherapy vs IMRT). On multivariate analysis, nPSA was significantly lower with SBRT and HDR compared with IMRT (P < .0001). Time to nPSA and bounce parameters was not significantly different among IMRT, SBRT, and HDR. Overall, SBRT and HDR brachytherapy caused significantly larger PSA decay rates (P < .001). When truncating follow-up at 1000 days, the corresponding decay rates were larger for all 3 modalities, with no significant differences between them. Stereotactic body radiation therapy and HDR brachytherapy produce lower nPSAs than IMRT. Within 1000 days of follow-up, the modalities produce similar rates of PSA decay; subsequently, decay continues (albeit at a slower pace) after SBRT and HDR brachytherapy but plateaus with IMRT. Because nPSA is a validated predictor of long-term outcome, these data not only suggest a distinct radiobiological

  15. High-sensitivity detection of PSA by time-resolved fluorometry with Europium chelate

    NASA Astrophysics Data System (ADS)

    Nahm, Kie B.; Jeong, Jin H.; Kim, Byoung C.; Kim, Jae H.; Kim, Young M.; Jeong, Dong S.; Oh, Sang W.; Choi, Eui Y.; Ko, Dong S.

    2006-01-01

    Prostate-specific antigen (PSA) is an androgen-dependent glycoprotein protease (M.W. 33 kDa) and a member of kallikrein super-family of serine protease, and has chymotrypsin-like enzymatic activity. It is synthesized by the prostate epithelial cells and found in the prostate gland and seminal plasma as a major protein. It is widely used as a clinical marker for diagnosis, screening, monitoring and prognosis of prostate cancer. In normal male adults, the concentration of PSA in the blood is below 4 ng/ml and this value increases in patients with the prostate cancer or the benign prostatic hyperplasia (BPH) due to its leakage into the circulatory system. As such, systematic monitoring of the PSA level in the blood can provide critical information about the progress of the prostatic disease. We have fabricated a bread-board time resolved fluorescence system that could detect a concentration of Prostate Specific Antigen t-PSA) at clinically meaningful level in plasma as well as in whole blood sample. We chose Europium chelates as the fluorescence markers to attach to the PSA for its long decay lifetime and relative photostability. We have simplified the electronic circuits considerably by employing a MCS. With this setup, we have successfully proved that PSA concentration of 4pg/mL can be detected with acceptable reliability.

  16. Galectin-3: a possible complementary marker to the PSA blood test

    PubMed Central

    Nangia-Makker, Pratima; Kho, Dhonghyo; Bajaj, Madhuri; Smith, Daryn; Heilbrun, Lance; Raz, Avraham; Heath, Elisabeth

    2013-01-01

    The prostate-specific antigen (PSA) test has served as a blood marker of prostate cancer (PCa), and for monitoring recurrence/metastasis in patients after therapeutic intervention. However, the applicability/reliability of the PSA test was recently questioned as it is not without challenges, in particular in men who have PCa without an elevated PSA (false negative), or in men who are disease-free with elevated levels of PSA (false positive). Galectin-3 is a tumor-associated protein; present in the seminal fluid and is a substrate for the PSA enzyme e.g., a chymotrypsin-like serine protease. We hypothesized that the cleavage status and level of galectin-3 in the prostate tissue and sera are associated with PCa. Thus, we compared galectin-3 levels obtained from sera of non-cancer urology patients to those of metastatic PCa patients. The data were confirmed by analyzing PCa tissue arrays. Here, we report that galectin-3 levels in the sera of patients with metastatic PCa were uniformly higher as compared to the non-cancer patient controls. The data suggest that galectin-3 serum level may be a useful serum complementary marker to the PSA blood test to be used for initial and follow-up PSA complimentary diagnostic/prognostic tool for recurrence in PCa patients. PMID:23625538

  17. ARE-I polymorphism on PSA gene in prostate cancer patients of a Turkish population.

    PubMed

    Kalay, Ebru; Ergen, Arzu; Narter, Fehmi; Agaçhan, Bedia; Görmüs, Uzay; Yigit, Nilüfer; Isbir, Turgay

    2009-04-01

    The gene for kallikrein-like serin protease, prostate-specific antigen (PSA), has been a candidate gene in several studies. It is known that androgens are important in the proliferation and development of prostate gland and they are the main regulators of PSA expression. The polymorphism of the ARE-I locus on the PSA gene was studied in prostate cancer patients to determine a possible relationship of that locus to prostate cancer risk. Forty-nine prostate cancer patients and forty-seven healthy control subjects were compared. Total and free PSA levels were measured by an enzymatic immunoassay method. PSA ARE-I polymorphism analyses were performed using a previously described PCR-restriction fragment length polymorphism (RFLP) method. There were no significant differences between the control and patient groups for any of the PSA-AREI genotypes, but the G allele carriers had a 2-fold higher risk of developing advanced prostate cancer. G allele carriers have a higher risk of developing advanced prostate cancer. With further research, such PSA-AREI polymorphism analyses may help in follow-up and in deciding the prognosis of prostate cancer patients.

  18. Predicting prostate biopsy results: The importance of PSA, age, and race.

    PubMed

    Grunkemeier, M Natalie; Vollmer, Robin T

    2006-07-01

    We studied whether age and race have a significant role in predicting the results of prostate biopsy after consideration of prostate-specific antigen (PSA) alone. We evaluated the results of 884 prostate biopsies performed on 695 men, including 188 black men. We used logistic regression analysis to evaluate relationships between presence of cancer in the biopsy specimen and the key predictor variables of PSA, age and black race. We also evaluated the importance of a Bayes-derived positive predictive value (PPV), which used age- and race-specific values of specificity and sensitivity of PSA and age- and race-specific Surveillance, Epidemiology, and End Results incidences of prostate cancer. In univariate analysis, the Bayes PPV was associated significantly with presence of cancer (chi2 = 216; P approximately .000); however, serum PSA provided more information (chi2 = 248; P approximately .000). With serum PSA in the logistic model, the Bayes PPV provided no further information (P > .08), and as additional variables, neither age nor black race contributed further information (P > .1). Serum PSA provides the most predictive information about the results of biopsy of the prostate, probably because it naturally correlates with age and race. Decisions about whether to biopsy should rest on values of serum PSA and need not consider age and race.

  19. [Parameters of PSA fractions in early diagnosis of prostatic cancer in healthy males over 50].

    PubMed

    Loran, O B; Krokhotina, L V; Pushkar', D Iu; Valiev, A Z; Rasner, P I

    1999-01-01

    292 symptomless males aged 50-85 years were examined for blood prostate-specific antigen (PSA) for early diagnosis of prostatic cancer. Males with total PSA (TPSA) higher than age-specific standard underwent free PSA (FPSA) assay to estimate FPSA/TPSA and transperineal biopsy of the prostate. TPSA ranged from 0.3 to 112.0 ng/ml and exceeded the age standard in 102 examinees (35%). Prognostically unfavorable FPSA/TPSA (under 15%) was registered in 17(5.8%) examinees. Biopsy of the prostate has revealed cancer in 7 of them. Among those whose TPSA was above the standard, but FPSA/TPSA > 15%, morphologically verified prostatic cancer was detected in 5 males. It is thought valid to include the method of PSA fractions estimation in the program of screening for males at risk to develop prostatic cancer as it is simple, cost effective and highly informative.

  20. Nanoparticle-based bio-barcode assay redefines “undetectable” PSA and biochemical recurrence after radical prostatectomy

    PubMed Central

    Thaxton, C. Shad; Elghanian, Robert; Thomas, Audrey D.; Stoeva, Savka I.; Lee, Jae-Seung; Smith, Norm D.; Schaeffer, Anthony J.; Klocker, Helmut; Horninger, Wolfgang; Bartsch, Georg; Mirkin, Chad A.

    2009-01-01

    We report the development of a previously undescribed gold nanoparticle bio-barcode assay probe for the detection of prostate specific antigen (PSA) at 330 fg/mL, automation of the assay, and the results of a clinical pilot study designed to assess the ability of the assay to detect PSA in the serum of 18 men who have undergone radical prostatectomy for prostate cancer. Due to a lack of sensitivity, available PSA immunoassays are often not capable of detecting PSA in the serum of men after radical prostatectomy. This new bio-barcode PSA assay is ≈300 times more sensitive than commercial immunoassays. Significantly, with the barcode assay, every patient in this cohort had a measurable serum PSA level after radical prostatectomy. Patients were separated into categories based on PSA levels as a function of time. One group of patients showed low levels of PSA with no significant increase with time and did not recur. Others showed, at some point postprostatectomy, rising PSA levels. The majority recurred. Therefore, this new ultrasensitive assay points to significant possible outcomes: (i) The ability to tell patients, who have undetectable PSA levels with conventional assays, but detectable and nonrising levels with the barcode assay, that their cancer will not recur. (ii) The ability to assign recurrence earlier because of the ability to measure increasing levels of PSA before conventional tools can make such assignments. (iii) The ability to use PSA levels that are not detectable with conventional assays to follow the response of patients to adjuvant or salvage therapies. PMID:19841273

  1. Predicting Post-External Beam Radiation Therapy PSA Relapse of Prostate Cancer Using Pretreatment MRI

    SciTech Connect

    Fuchsjaeger, Michael H.; Pucar, Darko; Zelefsky, Michael J.; Zhang Zhigang; Mo Qianxing; Ben-Porat, Leah S.; Shukla-Dave, Amita; Wang Liang; Reuter, Victor E.; Hricak, Hedvig

    2010-11-01

    Purpose: To investigate whether pretreatment endorectal magnetic resonance imaging (MRI) findings can predict biochemical relapse in patients with clinically localized prostate cancer treated with external beam radiation therapy (EBRT). Methods and Materials: Between January 2000 and January 2002, 224 patients (median age, 69 years; age range, 45-82 years) with biopsy-proven prostate cancer underwent endorectal MRI before high-dose ({>=}81Gy) EBRT. The value of multiple clinical and MRI variables in predicting prostate-specific antigen (PSA) relapse at 5 years was determined by use of univariate and multivariate stepwise Cox regression. Clinical variables included pretreatment PSA, clinical T stage, Gleason score, use of neoadjuvant hormonal therapy, and radiation dose. Magnetic resonance imaging variables, derived from retrospective consensus readings by two radiologists, were used to measure intraprostatic and extraprostatic tumor burden. Results: After a median follow-up of 67 months, PSA relapse developed in 37 patients (16.5%). The significant predictors of PSA relapse on univariate analysis were pretreatment PSA, clinical T stage, and multiple MRI variables, including MRI TN stage score; extracapsular extension (ECE) status; number of sextants involved by ECE, all lesions, or index (dominant) lesion; apical involvement; and diameter and volume of index lesion. Pretreatment PSA and ECE status were the only significant independent predictors on multivariate analysis (p < 0.05 for both). Extracapsular extension status was associated with the highest hazard ratio, 3.04; 5-year PSA relapse rates were 7% for no ECE, 20% for unilateral ECE, and 48% for bilateral ECE. Conclusions: Magnetic resonance imaging findings can be used to predict post-EBRT PSA relapse, with ECE status on MRI and pretreatment PSA being significant independent predictors of this endpoint.

  2. Practice Patterns of Korean Urologists for Screening and Managing Prostate Cancer according to PSA Level

    PubMed Central

    Chung, Mun Su; Lee, Seung Hwan; Lee, Dong Hoon; Kim, Se Joong; Kim, Choung Soo; Lee, Kyu Sung; Jung, Jae Il; Kim, Sae Woong; Lee, Yil Seob

    2012-01-01

    Purpose There are still debates on the benefit of mass screening for prostate cancer (PCA) by prostate specific antigen (PSA) testing, and on systemized surveillance protocols according to PSA level. Furthermore, there is a paucity of literature on current practice patterns according to PSA level in the Korean urologic field. Here, we report the results of a nationwide, multicenter, retrospective chart-review study. Materials and Methods Overall 2122 Korean men (>40 years old, PSA >2.5 ng/mL) were included in our study (from 122 centers, in 2008). The primary endpoint was to analyze the rate of prostate biopsy according to PSA level. Secondary aims were to analyze the detection rate of PCA, the clinical features of patients, and the status of surveillance for PCA according to PSA level. Results The rate of prostate biopsy was 7.1%, 26.3%, 54.2%, and 64.3% according to PSA levels of 2.5-3.0, 3.0-4.0, 4.0-10.0, and >10.0 ng/mL, respectively, and the PCA detection rate was 16.0%, 22.2%, 20.2%, and 59.6%, respectively. At a PSA level >4.0 ng/mL, we found a lower incidence of prostate biopsy in local clinics than in general hospitals (21.6% vs. 66.2%, respectively). A significant proportion (16.6%) of patients exhibited high Gleason scores (≥8) even in the group with low PSA values (2.5-4.0 ng/mL). Conclusion We believe that the results from this nationwide study might provide an important database for the establishment of practical guidelines for the screening and management of PCA in Korean populations. PMID:23074113

  3. The impact of HMG-CoA reductase therapy on serum PSA.

    PubMed

    Mener, David J; Cambio, Angelo; Stoddard, David G; Martin, Brad A; Palapattu, Ganesh S

    2010-05-01

    3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors, otherwise known as statins, inhibit the enzyme that controls the conversion of HMG-CoA to mevalonate, a precursor for cholesterol. Statins may be important to prostate cancer biology by inhibiting cell growth, inflammation, and oxidative stress. The purpose of this study was to assess the influence of statin therapy on serum prostate-specific antigen (PSA) levels. The computerized medical records at the University of Rochester Medical Center were used to identify men who filled statin prescriptions between May 31st, 2008 and September 30th, 2008. Men with at least one PSA assay performed within 2 years before and at least one PSA assay performed within 1 year after starting a statin medication were included. The primary endpoint was the change in PSA concentration computed as the difference between PSA levels before and after starting a statin medication. Paired t-tests were used to analyze the mean differences in PSA values. A total of 962 patients were identified. The mean difference in serum PSA level after statin administration was -0.29 ng/ml (-8.04%). Subgroup analyses for mean PSA concentration change before and after statin administration by age group revealed: 50-59 years old (-0.1609, 95% CI: -0.2444, -0.0775, P < 0.0002), 60-69 years old (-0.3393, 95% CI: -0.4641, -0.2145, P < 0.0001), and >70 years old (-0.351, 95% CI: -0.490, -0.212, P < 0.0001). These observations suggest a statistically significant reduction in serum PSA level that is associated with the onset of statin therapy.

  4. Correlation of High Body Mass Index With More Advanced Localized Prostate Cancer at Radical Prostatectomy Is Not Reflected in PSA Level and PSA Density but Is Seen in PSA Mass.

    PubMed

    Kryvenko, Oleksandr N; Epstein, Jonathan I; Meier, Frederick A; Gupta, Nilesh S; Menon, Mani; Diaz, Mireya

    2015-08-01

    Prostate cancer screening algorithms and preoperative nomograms do not include patients' body mass index (BMI). We evaluated outcomes at radical prostatectomy (RP) adjusted to BMI. Serum prostate-specific antigen (PSA) levels, PSA mass, PSA density (PSAD), and RP findings were analyzed with respect to BMI in 4,926 men who underwent RP between 2005 and 2014. In total, 1,001 (20.3%) men were normal weight, 2,547 (51.7%) were overweight, and 1,378 (28%) were obese. Median PSA levels (ng/mL) were normal weight, 5.0; overweight, 5.1; and obese, 5.2 (P = .094). Median PSA mass increased with increasing BMI: 15.9 vs 17.4 vs 19.4 μg (P < .001). Median PSAD was not significantly different: 0.11 vs 0.11 vs 0.11 ng/mL/g (P = .084). Median prostate weight increased with increasing BMI: 44 vs 45 vs 49 g (P < .001). Median prostatectomy tumor volume increased with increasing BMI: 3.9 vs 4.7 vs 5.9 cm(3) (P < .001). Overweight and obese patients had a higher Gleason score and more locally advanced cancer (P < .001). Frequency of positive surgical margins increased with higher BMIs (P < .001). Frequency of lymph node metastasis did not differ significantly (P = .088). While BMI correlates with tumor volume, Gleason score, and extent of disease at RP, there is no routinely measured clinical parameter reflecting this. Only PSA mass highlights this correlation. Thus, BMI and potentially PSA mass should be taken into account in predictive algorithms pertaining to prostate cancer and its surgical treatment. Copyright© by the American Society for Clinical Pathology.

  5. PSA Velocity Does Not Improve Prostate Cancer Detection | Division of Cancer Prevention

    Cancer.gov

    A rapid increase in prostate-specific antigen (PSA) levels is not grounds for automatically recommending a prostate biopsy, according to a study published online February 24 in the Journal of the National Cancer Institute. |

  6. Infographic: Benefits and Harms of PSA Screening for Prostate Cancer | Division of Cancer Prevention

    Cancer.gov

    As more has been learned about the benefits and harms of prostate-specific antigen (PSA) screening, organizations have begun to recommend against routine screening. Screening is a personal decision that, according to most experts, a man should make in consultation with his doctor, after he has been informed in detail about the potential benefits and harms. |

  7. Molecular heterogeneity of photosystem I. psaD, psaE, psaF, psaH, and psaL are all present in isoforms in Nicotiana spp.

    PubMed

    Obokata, J; Mikami, K; Hayashida, N; Nakamura, M; Sugiura, M

    1993-08-01

    The protein composition of photosystem I (PSI) was examined in Nicotiana spp. by high-resolution polyacrylamide gel electrophoresis, N-terminal amino acid sequencing, and immunoblot analysis. Five PSI proteins show polymorphism in an amphidiploid species, Nicotiana tabacum, but not in its ancestral diploid species, Nicotiana sylvestris and Nicotiana tomentosiformis. These Nicotiana spp. appear to have at least 18 PSI proteins per genome that range in molecular mass from 3 to 20 kD. They include the products of nuclear genes psaD, psaE, psaF, psaG, psaH, psaK, and psaL, the product of chloroplast gene psaC, N-terminally blocked proteins of 4.5 and 3.0 kD, and an unidentified protein of 12.5 kD. The psaD, psaF, psaH, and psaL products have two isoforms each that are distinguished by different mobilities in polyacrylamide gel electrophoresis, and the psaE product has four isoforms. The two isoforms of the psaD product have distinct amino acid sequences, indicating that they are encoded by different genes within the genome. Four isoforms of the psaE products can be classified into two groups by N-terminal amino acid sequence, indicating that at least two psaE genes are present in the genome. To examine whether the polymorphic nature of PSI is peculiar to Nicotiana spp., we carried out immunoblot analysis of the psaD and psaE products in isogenic lines of tomato (Lycopersicon esculentum), Arabidopsis thaliana, red bean (Vigna angularis), and corn (Zea mays). Two electrophoretically distinct isoforms were found for the psaD products of tomato, A. thaliana, and corn, and two isoforms of psaE products were detected in tomato, A. thaliana, and red bean. These results suggest that the nuclear-encoded subunits of PSI, except for the psaG and psaK products, generally have two isoforms.

  8. Diuretic Strategies in Acute Heart Failure and Renal Dysfunction: Conventional vs Carbohydrate Antigen 125-guided Strategy. Clinical Trial Design.

    PubMed

    García-Blas, Sergio; Bonanad, Clara; Llàcer, Pau; Ventura, Silvia; Núñez, José María; Sánchez, Ruth; Chamorro, Carlos; Fácila, Lorenzo; de la Espriella, Rafael; Vaquer, Juana María; Cordero, Alberto; Roqué, Mercè; Ortiz, Víctor; Racugno, Paolo; Bodí, Vicent; Valero, Ernesto; Santas, Enrique; Moreno, María Del Carmen; Miñana, Gema; Carratalá, Arturo; Bondanza, Lourdes; Payá, Ana; Cardells, Ingrid; Heredia, Raquel; Pellicer, Mauricio; Valls, Guillermo; Palau, Patricia; Bosch, María José; Raso, Rafael; Sánchez, Andrés; Bertomeu-González, Vicente; Bertomeu-Martínez, Vicente; Montagud-Balaguer, Vicente; Albiach-Montañana, Cristina; Pendás-Meneau, Jezabel; Marcaida, Goitzane; Cervantes-García, Sonia; San Antonio, Rodolfo; de Mingo, Elisabet; Chorro, Francisco J; Sanchis, Juan; Núñez, Julio

    2017-03-21

    The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days. The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Heart failure in patients with aortic stenosis: clinical and prognostic significance of carbohydrate antigen 125 and brain natriuretic peptide measurement.

    PubMed

    Antonini-Canterin, Francesco; Popescu, Bogdan A; Popescu, Andreea C; Beladan, Carmen C; Korcova, Renata; Piazza, Rita; Cappelletti, Piero; Rubin, Daniela; Cassin, Matteo; Faggiano, Pompilio; Nicolosi, Gian Luigi

    2008-08-29

    Brain natriuretic peptide (BNP) is related to symptomatic status and outcome in aortic stenosis (AS) patients. Carbohydrate antigen 125 (CA125) demonstrated recently a BNP-like behaviour in patients with congestive heart failure (CHF) but has never been studied in AS patients. We aimed to assess the role of CA125 and BNP in AS patients. CA125 and BNP blood levels, transthoracic echocardiography and independent evaluation of CHF symptoms were obtained in 64 consecutive patients (76+/-9 years; 35 males) with AS (valve area 0.9+/-0.3 cm(2)). A pre-specified combined end-point consisting of cardiac mortality, urgent aortic valve replacement and hospitalization for CHF was considered. The median follow-up was 8 months (interquartile range 4.5-10 months). Both CA125 and BNP have accurately identified patients with III-IV NYHA class: area under the ROC curve was 0.85 for CA125 and 0.78 for BNP (best cut-offs of 10.3 U/mL and 254.64 pg/mL respectively) and were independently correlated to left ventricular ejection fraction. Fifty-two percent of patients with CA125>or=10.3 U/mL vs. 13% with CA125<10.3 U/mL (p<0.01) and 65% patients with BNP>or=254 pg/mL vs. 7% with BNP<254 pg/mL (p<0.001) have reached the end-point. Both CA125 and BNP levels are significantly correlated with NYHA class and outcome in patients with AS. CA125 blood level assessment (less expensive) may improve the clinical management in this setting.

  10. Postradiotherapy PSA nadirs fail to support dose escalation study in patients with pretreatment PSA values < 10 ng/ml.

    PubMed

    Herold, D; Hanks, G; Movsas, B; Hanlon, A

    1997-01-01

    With three-dimensional conformal therapy, doses > 75 Gy have been delivered to the prostate with acceptable levels of morbidity; however, higher doses do appear to increase late gastrointestinal (GI) and genitourinary (GU) morbidity. Because patients with pretreatment prostate-specific antigen (PSA) values < 10 ng/ml can achieve 3-year actuarial bNED control rates of 90% after treatment with external beam radiotherapy to doses < 71 Gy, one might question the need for further dose escalation in this population. In this report, we examined the relationship between dose and PSA nadir for 90 patients with pretreatment PSA values < 10 ng/ml entered into a dose escalation study from March 1987 to October 1992. We wanted to see if nadir response data would predict a different outcome from our 3-year bNED control reports. All patients were treated with external beam radiotherapy to ICRU reporting point doses of 6,598 cGy to 7,895 cGy (median of 7,068 cGy). Minimum follow-up was 36 months (median, 47 months). Seven hundred thirty-nine posttreatment PSA nadir values were analyzed, yielding an average of 8.2 values per patient. Estimates of rates of bNED control and time to reach a posttreatment PSA of 1.0 ng/ml were calculated using the Kaplan-Meier product limit method. The log-rank test was used to evaluate differences in rates according to dose levels. Linear regression and Cox proportional hazard modeling were used to relate dose to bNED control on a continuum. Escalating doses from 66 to 79 Gy failed to increase the percentage of patients achieving nadir values < 1 ng/ml and similarly failed to increase the 3-year actuarial bNED control. Linear regression (P = .81) and the chi-square test of association (P = .23) supported the lack of a dose effect on nadir continuously and categorically, respectively, and the Cox regression model supported the conclusion that dose on a continuum has no effect on bNED control (P = .34). Furthermore, time to reach a posttreatment PSA

  11. Prostate-Specific Antigen Velocity Before and After Elimination of Factors That Can Confound the Prostate-Specific Antigen Level

    SciTech Connect

    Park, Jessica J.; Chen, Ming-Hui; Loffredo, Marian; D'Amico, Anthony V.

    2012-03-01

    Purpose: Prostate-specific antigen (PSA) velocity, like PSA level, can be confounded. In this study, we estimated the impact that confounding factors could have on correctly identifying a patient with a PSA velocity >2 ng/ml/y. Methods and Materials: Between 2006 and 2010, a total of 50 men with newly diagnosed PC comprised the study cohort. We calculated and compared the false-positive and false-negative PSA velocity >2 ng/ml/y rates for all men and those with low-risk disease using two approaches to calculate PSA velocity. First, we used PSA values obtained within 18 months of diagnosis; second, we used values within 18 months of diagnosis, substituting the prebiopsy PSA for a repeat, nonconfounded PSA that was obtained using the same assay and without confounders. Results: Using PSA levels pre-biopsy, 46% of all men had a PSA velocity >2 ng/ml/y; whereas this value declined to 32% when substituting the last prebiopsy PSA for a repeat, nonconfounded PSA using the same assay and without confounders. The false-positive rate for PSA velocity >2 ng/ml/y was 43% as compared with a false-negative rate of PSA velocity >2 ng/ml/y of 11% (p = 0.0008) in the overall cohort. These respective values in the low-risk subgroup were 60% and 16.7% (p = 0.09). Conclusion: This study provides evidence to explain the discordance in cancer-specific outcomes among groups investigating the prognostic significance of PSA velocity >2 ng/ml/y, and highlights the importance of patient education on potential confounders of the PSA test before obtaining PSA levels.

  12. Can the Free/Total PSA Ratio Predict the Gleason Score Before Prostate Biopsy?

    PubMed Central

    Ceylan, Cavit; Gazel, Eymen; Keleş, İbrahim; Doluoğlu, Ömer; Yığman, Metin

    2016-01-01

    Objectives To determine whether there is a correlation between high Gleason score and free/total (f/t) prostate specific antigen (PSA) in patients newly diagnosed with prostate carcinoma. Materials and Methods The study included 272 prostate biopsy patients whose total PSA value ranged from 4–10 ng/ml. The patients were divided into 2 groups according to the f/t PSA ratio: Group 1 ≤ 15% and Group 2 > 15%. Furthermore, the groups were also compared to each other in terms of mild (≤ 6), moderate (= 7), and high (≥ 8) Gleason score. Results Group 1 consisted of 135 (49.6%) patients and Group 2 consisted of 137 (50.4%) patients. While 27 (20%) patients had a high Gleason score in Group 1, only 10 (7.3%) patients had a high Gleason score in Group 2 (p = 0.008). Using Spearman's correlation test, we found that the f/t PSA ratios were observed to decrease significantly in all patients with increased Gleason scores (p = 0.002, r = −0.185). Conclusion According to our study, there is a relationship between higher Gleason score and decreased f/t PSA ratio. Therefore, f/t PSA can be an indicator for predicting the Gleason score. PMID:26989367

  13. Tumour and immune cell dynamics explain the PSA bounce after prostate cancer brachytherapy

    PubMed Central

    Yamamoto, Yoichiro; Offord, Chetan P; Kimura, Go; Kuribayashi, Shigehiko; Takeda, Hayato; Tsuchiya, Shinichi; Shimojo, Hisashi; Kanno, Hiroyuki; Bozic, Ivana; Nowak, Martin A; Bajzer, Željko; Dingli, David

    2016-01-01

    Background: Interstitial brachytherapy for localised prostate cancer may be followed by transient increases in prostate-specific antigen (PSA) that resolve without therapy. Such PSA bounces may be associated with an improved outcome but often cause alarm in the patient and physician, and have defied explanation. Methods: We developed a mathematical model to capture the interactions between the tumour, radiation and anti-tumour immune response. The model was fitted to data from a large cohort of patients treated exclusively with interstitial brachytherapy. Immunohistological analysis for T-cell infiltration within the same tumours was also performed. Results: Our minimal model captures well the dynamics of the tumour after therapy, and suggests that a strong anti-tumour immune response coupled with the therapeutic effect of radiation on the tumour is responsible for the PSA bounce. Patients who experience a PSA bounce had a higher density of CD3 and CD8 cells within the tumour that likely contribute to the PSA bounce and the overall better outcomes observed. Conclusions: Our observations provide a novel and unifying explanation for the PSA bounce in patients with early prostate cancer and also have implications for the use of immune-based therapies in such patients to improve outcomes. PMID:27404586

  14. PSA doubling time kinetics during prostate cancer biochemical relapse after external beam radiation therapy

    SciTech Connect

    Bates, Andrew Tom . E-mail: andrew.bates@doctors.org.uk; Pickles, Tom; Paltiel, Chuck

    2005-05-01

    Purpose: To investigate whether prostate-specific antigen PSA doubling time (PSADT) is constant in men with biochemical prostate cancer relapse after external beam radiotherapy (EBRT). Methods and Materials: A total of 513 men treated radically with EBRT, with or without androgen ablation (AA), between 1993 and 2000, developed biochemical relapse. The slope of the ln (PSA) vs. time graph is calculated for the first two values after PSA nadir (first slope), the last two recorded PSAs (last slope), and all values excluding the first and final PSA (mid slope). Differences in these slopes were compared statistically with subgroup analysis for AA and secondary intervention. Results: For men treated with EBRT and AA first slope was faster than either mid slope (p = 0.031) or last slope (p < 0.001). Men treated with EBRT alone had no change in PSADT over time unless they subsequently received secondary intervention. This group had a more rapid last slope compared with mid slope (p < 0.001). Conclusions: PSA initially rises more rapidly after AA cessation, probably because of testosterone recovery. A subgroup of patients, who received secondary intervention after treatment with radiotherapy alone, showed a change in PSADT, to a faster velocity. This greater than constant exponential PSA growth is presumably the catalyst for secondary intervention. Otherwise, PSADT did not change during prostate cancer biochemical relapse.

  15. Clinical outcomes after salvage radiotherapy without androgen deprivation therapy in patients with persistently detectable PSA after radical prostatectomy: results from a national multicentre study.

    PubMed

    Ploussard, Guillaume; Staerman, Frédéric; Pierrevelcin, Jean; Larue, Sébastien; Villers, Arnauld; Ouzzane, Adil; Bastide, Cyrille; Gaschignard, Nicolas; Buge, François; Pfister, Christian; Bonniol, Romain; Rebillard, Xavier; Fadli, Saad; Mottet, Nicolas; Saint, Fabien; Saad, Rodrigue; Beauval, Jean-Baptiste; Roupret, Morgan; Audenet, François; Peyromaure, Mickaël; Delongchamps, Nicolas Barry; Vincendeau, Sébastien; Fardoun, Tarek; Rigaud, Jérôme; Soulie, Michel; Salomon, Laurent

    2014-10-01

    To assess oncologic outcomes after salvage radiotherapy (SRT) without androgen deprivation therapy (ADT) in patients with persistently detectable PSA after radical prostatectomy (RT). Two hundred and one patients who failed to achieve an undetectable PSA received SRT without ADT. The primary endpoint was failure to SRT that was defined by clinical progression or use of second-line ADT. Clinicopathological parameters, 6-week PSA level, PSAV and pre-SRT PSA levels were assessed using time-dependent analyses. Median postoperative 6-week PSA and pre-SRT PSA levels were 0.25 and 0.48 ng/mL, respectively. Median time between surgery and SRT was 7 months. Failure to SRT was reported in 42.8 % of cases with the need for second-line ADT in 26.9 % of cases. Pre-SRT PSA was strongly correlated with postoperative 6-week PSA (p < 0.001) but not with PSAV. The risk of SRT failure was increased by threefold in case of Gleason score 8-10 (p = 0.036) or pT3b cancer (p = 0.006). Risk group classification based on these prognostic factors improved SRT failure prediction. Survival curves confirmed that 5-year ADT-free survival rates were significantly influenced by PSAV (p = 0.002) and pre-SRT PSA (p = 0.030). In patients with persistently detectable PSA after RP and selected for local salvage treatment, SRT offers good oncologic clinical outcomes. The most powerful pathologic predictive factors of SRT failure include a pT3b stage, a Gleason score 8 or more cancer and high PSAV and pre-SRT PSA levels. Patients having a high PSAV >0.04 ng/mL/mo would be potentially better candidates for a systemic therapy due to a high SRT failure rate.

  16. Structural basis for Myf and Psa fimbriae-mediated tropism of pathogenic strains of Yersinia for host tissues.

    PubMed

    Pakharukova, Natalia; Roy, Saumendra; Tuittila, Minna; Rahman, Mohammad M; Paavilainen, Sari; Ingars, Anna-Karin; Skaldin, Maksym; Lamminmäki, Urpo; Härd, Torleif; Teneberg, Susann; Zavialov, Anton V

    2016-11-01

    Three pathogenic species of the genus Yersinia assemble adhesive fimbriae via the FGL-chaperone/usher pathway. Closely related Y. pestis and Y. pseudotuberculosis elaborate the pH6 antigen (Psa), which mediates bacterial attachment to alveolar cells of the lung. Y. enterocolitica, instead, assembles the homologous fimbriae Myf of unknown function. Here, we discovered that Myf, like Psa, specifically recognizes β1-3- or β1-4-linked galactose in glycosphingolipids, but completely lacks affinity for phosphatidylcholine, the main receptor for Psa in alveolar cells. The crystal structure of a subunit of Psa (PsaA) complexed with choline together with mutagenesis experiments revealed that PsaA has four phosphatidylcholine binding pockets that enable super-high-avidity binding of Psa-fibres to cell membranes. The pockets are arranged as six tyrosine residues, which are all missing in the MyfA subunit of Myf. Conversely, the crystal structure of the MyfA-galactose complex revealed that the galactose-binding site is more extended in MyfA, enabling tighter binding to lactosyl moieties. Our results suggest that during evolution, Psa has acquired a tyrosine-rich surface that enables it to bind to phosphatidylcholine and mediate adhesion of Y. pestis/pseudotuberculosis to alveolar cells, whereas Myf has specialized as a carbohydrate-binding adhesin, facilitating the attachment of Y. enterocolitica to intestinal cells. © 2016 John Wiley & Sons Ltd.

  17. Presence of PSA auto-antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis).

    PubMed

    Lokant, M T; Naz, R K

    2015-04-01

    Prostate-specific antigen (PSA), produced by the prostate, liquefies post-ejaculate semen. PSA is detected in semen and blood. Increased circulating PSA levels indicate prostate abnormality [prostate cancer (PC), benign prostatic hyperplasia (BPH), prostatitis (PTIS)], with variance among individuals. As the prostate has been proposed as an immune organ, we hypothesise that variation in PSA levels among men may be due to presence of auto-antibodies against PSA. Sera from healthy men (n = 28) and men having prostatitis (n = 25), BPH (n = 30) or PC (n = 29) were tested for PSA antibody presence using enzyme-linked immunosorbent assay (ELISA) values converted to standard deviation (SD) units, and Western blotting. Taking ≥2 SD units as cut-off for positive immunoreactivity, 0% of normal men, 0% with prostatitis, 33% with BPH and 3.45% with PC demonstrated PSA antibodies. One-way analysis of variance (anova) performed on the mean absorbance values and SD units of each group showed BPH as significantly different (P < 0.01) compared with PC and prostatitis. All others were nonsignificant (P < 0.05). Men (33%) with BPH had PSA antibodies by ELISA and Western blot. These discoveries may find clinical application in differential diagnosis among prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis. © 2014 Blackwell Verlag GmbH.

  18. Characterizing the conformational dynamics of metal-free PsaA using molecular dynamics simulations and electron paramagnetic resonance spectroscopy.

    PubMed

    Deplazes, Evelyne; Begg, Stephanie L; van Wonderen, Jessica H; Campbell, Rebecca; Kobe, Bostjan; Paton, James C; MacMillan, Fraser; McDevitt, Christopher A; O'Mara, Megan L

    2015-12-01

    Prokaryotic metal-ion receptor proteins, or solute-binding proteins, facilitate the acquisition of metal ions from the extracellular environment. Pneumococcal surface antigen A (PsaA) is the primary Mn(2+)-recruiting protein of the human pathogen Streptococcus pneumoniae and is essential for its in vivo colonization and virulence. The recently reported high-resolution structures of metal-free and metal-bound PsaA have provided the first insights into the mechanism of PsaA-facilitated metal binding. However, the conformational dynamics of metal-free PsaA in solution remain unknown. Here, we use continuous wave electron paramagnetic resonance (EPR) spectroscopy and molecular dynamics (MD) simulations to study the relative flexibility of the structural domains in metal-free PsaA and its distribution of conformations in solution. The results show that the crystal structure of metal-free PsaA is a good representation of the dominant conformation in solution, but the protein also samples structurally distinct conformations that are not captured by the crystal structure. Further, these results suggest that the metal binding site is both larger and more solvent exposed than indicated by the metal-free crystal structure. Collectively, this study provides atomic-resolution insight into the conformational dynamics of PsaA prior to metal binding and lays the groundwork for future EPR and MD based studies of PsaA in solution. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Probability of an Abnormal Screening PSA Result Based on Age, Race, and PSA Threshold

    PubMed Central

    Espaldon, Roxanne; Kirby, Katharine A.; Fung, Kathy Z.; Hoffman, Richard M.; Powell, Adam A.; Freedland, Stephen J.; Walter, Louise C.

    2014-01-01

    Objective To determine the distribution of screening PSA values in older men and how different PSA thresholds affect the proportion of white, black, and Latino men who would have an abnormal screening result across advancing age groups. Methods We used linked national VA and Medicare data to determine the value of the first screening PSA test (ng/mL) of 327,284 men age 65+ who underwent PSA screening in the VA healthcare system in 2003. We calculated the proportion of men with an abnormal PSA result based on age, race, and common PSA thresholds. Results Among men age 65+, 8.4% had a PSA >4.0ng/mL. The percentage of men with a PSA >4.0ng/mL increased with age and was highest in black men (13.8%) versus white (8.0%) or Latino men (10.0%) (P<0.001). Combining age and race, the probability of having a PSA >4.0ng/mL ranged from 5.1% of Latino men age 65–69 to 27.4% of black men age 85+. Raising the PSA threshold from >4.0ng/mL to >10.0ng/mL, reclassified the greatest percentage of black men age 85+ (18.3% absolute change) and the lowest percentage of Latino men age 65–69 (4.8% absolute change) as being under the biopsy threshold (P<0.001). Conclusions Age, race, and PSA threshold together affect the pre-test probability of an abnormal screening PSA result. Based on screening PSA distributions, stopping screening among men whose PSA < 3ng/ml means over 80% of white and Latino men age 70+ would stop further screening, and increasing the biopsy threshold to >10ng/ml has the greatest effect on reducing the number of older black men who will face biopsy decisions after screening. PMID:24439009

  20. Clinically insignificant improvement of prostate cancer prediction by addition of sex steroid hormones and SHBG serum levels to serum PSA, fPSA%, and age in a screening setting.

    PubMed

    Heidegger, Isabel; Popovscaia, Marina; Ramoner, Reinhold; Schäfer, Georg; Stenzel, Birgit; Bektic, Jasmin; Horninger, Wolfgang; Klocker, Helmut

    2012-10-01

    Abstract Various findings implicate sex hormones in prostate growth and development and also in prostate carcinogenesis. We investigated if addition of sex steroid hormone and sex hormone binding globulin (SHBG) serum levels to standard risk assessment parameters [prostate-specific antigen (PSA), free PSA percentage (fPSA%), and age] improves prostate cancer prediction in a PSA screening setting. Steroid hormones testosterone (T), free testosterone (fT), and estradiol (E2), and binding protein SHBG levels were measured in 762 men undergoing prostate biopsy due to suspect PSA serum levels. Prostate cancer was diagnosed in 286 (37.5%) of these men. Our data confirmed that PSA (mean BE=5.09; mean CA=6.05; p=1.24×10-5), fPSA% (mean BE=22.08; mean CA=18.67; p=1.97×10-7), and age (mean BE=60.64; mean CA=64.5; p=7.05×10-10) differentiate men with cancer (CA) and men with benign disease (BE), such as benign prostate hyperplasia. In addition, SHBG (mean BE=50.3; mean CA=54.9; p=0.008) also differed statistically significantly between these two groups. All hormones except E2 and tumor markers correlated significantly with age (T: ρ=-0.09; fT: ρ=-0.27; SHBG: ρ=0.21; PSA: ρ=0.32; and fPSA%: ρ=0.22). Furthermore, we found that PSA correlates with E2 (ρ=0.08), and fPSA% with SHBG (ρ=0.1) and fT (ρ=-0.09). Addition of hormones and SHBG to a baseline marker model including PSA, fPSA%, and age improved cancer prediction in three multivariate classification methods; however, the improvement was minimal. The best improvement by 0.8% was obtained in the logistic regression model with the addition of T and SHBG or of E2 and SHBG, or in the support vector machine model with the addition of SHBG and all steroid hormones to the combination of standard markers PSA, fPSA%, and age; however, this additional gain of accuracy is too small to justify the additional efforts and costs.

  1. PSA enzymatic activity: a new biomarker for assessing prostate cancer aggressiveness.

    PubMed

    Ahrens, Michael J; Bertin, Paul A; Vonesh, Edward F; Meade, Thomas J; Catalona, William J; Georganopoulou, Dimitra

    2013-12-01

    With the advent of widespread prostate-specific antigen (PSA) testing in recent decades, prostate cancer (PCa) has emerged as the most frequently diagnosed non-skin cancer among men in the U.S. and Europe. Greater screening rates coupled with improved detection methods have caused a controversial upsurge in the number of men undergoing prostate biopsy and subsequent treatment. However, current diagnostic techniques generally suffer from limited ability to identify which seemingly indolent cancers are biologically aggressive. We collected prostatic fluid from 778 post-radical prostatectomy specimens and randomly selected samples from both the clinically confirmed aggressive (n = 50) and non-aggressive (n = 50) prostate cancer populations. We measured the level of proteolytic enzyme activity of PSA (aPSA) in each sample and used receiver operating characteristic (ROC) analysis to correlate aPSA levels with prostate cancer aggressiveness. We found aPSA in prostatic fluid to be inversely proportional to disease stage, such that patients with the most aggressive PCa have on average significantly reduced aPSA compared to those with less aggressive disease. Significantly, our results suggest that many (22% in our study population) of the diagnosed patients with non-aggressive PCa could have averted or delayed radical prostatectomy. Given the high level of debate surrounding PSA screening effectiveness [3-5] and the recent U.S. Preventative Services Task Force recommendation to discontinue PSA screening [6], our results provide renewed hope that a clinical monitoring tool may emerge that truly refines PCa treatment decision-making. © 2013 Wiley Periodicals, Inc.

  2. [Association between obesity-related plasma hemodilution and the concentration of prostate specific antigen].

    PubMed

    Li, Fanglong; Yin, Xiaotao; Li, Dewei; Yin, Zhaoyang; Qi, Siyong; Shi, Huaiyin; Gao, Jiangping; Zhang, Xu

    2015-12-01

    To determine the effect of obesity on prostate specific antigen (PSA) in men with benign prostatic hyperplasia (BPH) and develop a PSA-related parameter that can eliminate the effect of obesity. We reviewed the clinical data of 706 patients with BPH. Two PSA-related parameters, namely PSA mass (total circulating PSA protein) and PSA mass ratio (total circulation PSA protein per prostate volume), were calculated for all the patients and the association of BMI with PSA, PSA mass, and PSA mass ratio was assessed. A higher BMI was significantly associated with a greater plasma volume and prostate volume (P<0.05). Linear regression analysis revealed a greater adjusted R2 of BMI versus plasma volume than of BMI PSA (0.569 vs 0.027). PSA was positively associated with the prostate volume and negatively with BMI and plasma volume (P<0.05). PSA mass was positively associated with prostate volume (P<0.05) but was not associated with BMI or plasma volume (P>0.05). PSA mass ratio was not associated with prostate volume (P>0.05) but negatively associated with BMI and plasma volume. Plasma volume and prostate volume, PSA, and PSA mass ratio (P<0.05), but not PSA mass (P>0.05), differed significantly among normal-weight, overweight, and obese patients. A higher BMI is associated with a greater plasma volume in BPH patients. In obese patients with BPH, a lower PSA concentration may result from hemodilution caused by a greater plasma volume, and PSA mass can eliminate the effect of obesity on PSA.

  3. Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml(-1).

    PubMed

    Chen, Rui; Zhou, Li-Qun; Cai, Xiao-Bing; Xie, Li-Ping; Huang, Yi-Ran; He, Da-Lin; Gao, Xu; Xu, Chuan-Liang; Ding, Qiang; Wei, Qiang; Yin, Chang-Jun; Ren, Shan-Cheng; Wang, Fu-Bo; Tian, Ye; Sun, Zhong-Quan; Fu, Qiang; Ma, Lu-Lin; Zheng, Jun-Hua; Ye, Zhang-Qun; Ye, Ding-Wei; Xu, Dan-Feng; Hou, Jian-Quan; Xu, Ke-Xin; Yuan, Jian-Lin; Gao, Xin; Liu, Chun-Xiao; Pan, Tie-Jun; Sun, Ying-Hao

    2015-01-01

    Percent free prostatic-specific antigen (%fPSA) has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml-1 , however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer (PCa) and high-grade PCa (HGPCa) was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA>4.0 ng ml-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA (%fPSA + PSA) was determined by the area under the receivers operating characteristic curve (AUC). %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 , respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml-1 and 10.1-20.0 ng ml-1 .

  4. Role of PSA density in diagnosis of prostate cancer in obese men.

    PubMed

    Chiu, Peter Ka-Fung; Teoh, Jeremy Yuen-Chun; Chan, Samson Yun-Sang; Chu, Peggy Sau-Kwan; Man, Chi-Wai; Hou, See-Ming; Ng, Chi-Fai

    2014-12-01

    To compare the performance of prostate-specific antigen (PSA) density in the diagnosis of prostate cancer in obese and non-obese Chinese men. The results of transrectal ultrasound-guided (TRUS) prostate biopsies of Chinese men with PSA <20 ng/mL were reviewed. Parameters including age, body mass index (BMI), TRUS prostate volume, and TRUS biopsy results were recorded. The diagnostic yields of PSA density (>0.15 ng/mL as positive) in obese and non-obese men with PSA <20 ng/mL were compared. Obesity was defined as BMI ≥ 27 kg/m(2) according to WHO recommendation for Hong Kong Chinese. TRUS biopsy, BMI, and PSA density data were available for 854 men (mean age 65.9 ± 7.3). The mean PSA values for the obese and non-obese patients were 7.9 ± 3.7 and 8.2 ± 4.1 ng/mL, respectively (p = 0.416). TRUS volumes in obese and non-obese men were 63.2 ml and 51.6 ml, respectively (t test, p < 0.001), and PSA density was significantly lower in obese men (0.145 vs. 0.188, p < 0.001). For obese men, positive PSA density was associated with four times (41.1 vs. 9.5 %, p < 0.001) the risk of prostate cancer, compared to only twice the risk (18.8 vs. 9.7 %, p = 0.001) in non-obese men. The specificity and area under the curve of PSA density were 74.2 % and 0.731, respectively, for obese men, and 51.4 % and 0.653, respectively, for non-obese men. Among patients with a diagnosis of prostate cancer, the obese patient group had a significantly higher proportion of patients with Gleason 7-10 prostate cancer than the non-obese patient group (48.9 vs. 32.7 %, Chi-square test, p = 0.035), and a trend toward a higher proportion of bilateral lobe involvement. PSA density had better performance in obese men. Positive PSA density in obese men was associated with four times the risk of prostate cancer.

  5. Investigative clinical study on prostate cancer: on the role of the pretreatment total PSA to free testosterone ratio in selecting different biology groups of prostate cancer patients.

    PubMed

    Porcaro, Antonio B; Migliorini, Filippo; Romano, Mario; Petrozziello, Aldo; Antoniolli, Stefano Zecchini; Rubilotta, Emanuele; Lacola, Vincenzo; Sava, Teodoro; Ghimenton, Claudio; Caruso, Beatrice; Monaco, Carmelo; Comunale, Luigi

    2010-09-01

    To show that prostate cancer biology is related to serum levels of both free testosterone (FT) and prostate-specific antigen (PSA), that PSA level is linearly related to FT and that the PSA to FT ratio may be considered as the growth rate parameter expressing cancer phenotype biology. The study includes 135 consecutive patients diagnosed with prostate cancer. Pretreatment simultaneous serum samples for analyzing total testosterone (TT), FT and total PSA levels were obtained. The study was assessed according to a multidimensional approach of the five continuous variables including TT, FT, PSA, AGE and percentage of positive biopsies (=P+). The all sets of data were considered as one--sample with no groupings among the observations. Multivariate analysis included factor analysis (FA) and principal component analysis (PCA). Multivariate inferential statistics for comparing different groups of patients according to the PSA to free testosterone ratio (PSA/FT) included Hotteling's multivariate two-sample T²-Test for comparing two mean vectors as well as Box's M-Test with the chi-square approximation for comparing multiple covariance matrices when patients were sampled in more than two groups. Factor analysis showed the two natural grouping of variables, FT-TT and PSA-P+. PCA assessed FT and PSA as the two variables with large variances having a notable influence on the first two principal components. Multiple linear regression analysis showed that all the income variables, except age, significantly predicted the PSA/FT ratio. Patients were first sampled according to the PSA/FT ratio in group 1 (PSA/FT ≤ 0.20) and group 2 (PSA/FT > 0.20), and Hotteling's multivariate two sample T²-Test was significant (P < 0.01). Patients were then sampled according to the PSA/FT ratio in group 1 (PSA/FT ≤ 0.20), group 2 (PSA/FT > 0.20 and ≤ 0.40), and group 3 (PSA/FT > 0.40), and Box's M-Test comparing the covariance matrices of the 3 groups differed significantly (P < 0

  6. Free Prostate-Specific Antigen Provides More Precise Data on Benign Prostate Volume Than Total Prostate-Specific Antigen in Korean Population

    PubMed Central

    Choi, Hoon; Park, Jae Young; Shim, Ji Sung; Kim, Jae Heon

    2013-01-01

    Purpose To investigate the efficacy of total prostate-specific antigen (tPSA) and free prostate-specific antigen (fPSA) for the estimation of prostate volume (PV) in pathologically-proven benign prostatic hyperplasia (BPH) patients. Methods From January 2010 to March 2013, 165 Korean men with a PSA less than 10 ng/mL who were diagnosed without prostate cancer by prostate biopsy were enrolled. Patients were classified into three age groups: ≤60, 61-70, and >70 years old. The results were organized to estimate and compare the ability of serum tPSA and fPSA to assess the PV. Results Enrolled patients had a median age of 63.5 years (44 to 80), a median tPSA of 5.72 ng/mL, a median fPSA of 0.98 ng/mL and a median PV of 53.68 mL, respectively. Among the associations between tPSA, fPSA, age, and PV, the highest correlation was verified between fPSA and PV (r=0.377, P<0.0001); the correlation coefficient between tPSA and PV was much lower (r=0.262, P<0.001). All stratified age cohorts showed the same findings. The ROC curves (for PV greater than 30, 40, and 50 mL) showed that fPSA (area under the curve [AUC]=0.781, 0.718, and 0.700) outperformed tPSA (AUC=0.657, 0.583, and 0.67) in its ability to predict clinically significant PV enlargement. Conclusion Both tPSA and fPSA significantly correlated with PV in Korean men, while the correlation efficiency between fPSA and PV was more powerful. fPSA may be a useful tool in making therapeutic decisions and follow-up management in BPH patients. PMID:23869271

  7. PSA and Prostate Health Index based prostate cancer screening in a hereditary migration complicated population: implications in precision diagnosis

    PubMed Central

    Akizhanova, Mariyam; Iskakova, Elzira E.; Kim, Valdemir; Wang, Xiao; Kogay, Roman; Turebayeva, Aiym; Sun, Qinglei; Zheng, Ting; Wu, Shenghui; Miao, Lixia; Xie, Yingqiu

    2017-01-01

    Precision diagnosis requires specific markers for differential ethnic populations. Prostate-Specific Antigen (PSA) level (threshold of 4ng/ml) has been widely used to screen prostate cancer and as reference of pro-biopsy but false diagnosis frequently occurs. Prostate health Index (PHI) is a new diagnosis marker which combines PSA, free PSA and p2PSA4. Overall the PCa screening database is lacking in Kazakhstani patients. We analyzed the PSA levels and Gleason scores of 222 biopsies collected in 2015 in Almaty area, Kazakhstan approved by institutional ethics board. We found using PSA of 4ng/ml as threshold, only 25.68% of patients have cancer with Gleason score ranged 6-8 and 65.77% of patients have no character of cancer. Moreover, there is no significant correlation between PSA and cancerous (P=0.266) or Gleason grade (P=0.3046) based on pathological biopsy. In addition, PHI is not correlated to prostate cancer (P=0.4301). Our data suggest that false-positive rate is much higher than the correct-positive diagnosis when using PSA as the first screening. Thus in this cohort study, most patients can not get benefit from the PSA screening for precision PCa diagnosis. As Kazakhstani family trees are unique and complicated because of history and migration, the high rate of over diagnosis might be due to the hyperexpression of PSA via heterosis in Eurasian men. Therefore we should be cautious when using pro-biopsy in precision diagnosis for Eurasian prostate cancer patients. PMID:28607597

  8. Genome-wide Association Study Identifies Loci at ATF7IP and KLK2 Associated with Percentage of Circulating Free PSA1 2

    PubMed Central

    Jin, Guangfu; Zheng, Siqun Lilly; Lilja, Hans; Kim, Seong-Tae; Tao, Sha; Gao, Zhengrong; Young, Tracey; Wiklund, Fredrik; Feng, Junjie; Isaacs, William B; Rittmaster, Roger S; Gronberg, Henrik; Condreay, Lynn D; Sun, Jielin; Xu, Jianfeng

    2013-01-01

    Background Percentage of free-to-total prostate-specific antigen (%fPSA) is an independent predictor of risk for prostate cancer among men with modestly elevated level of total PSA (tPSA) in blood. Physiological and pathological factors have been shown to influence the %fPSA value and diagnostic accuracy. Materials/Methods To evaluate genetic determinants of %fPSA, we conducted a genome-wide association study of serum %fPSA by genotyping 642,584 single nucleotide polymorphisms (SNPs) in 3192 men of European ancestry, each with a tPSA level of 2.5 to 10 ng/ml, that were recruited in the REduction by DUtasteride of Prostate Cancer Events study. Single nucleotide polymorphisms (SNPs) with P < 10-5 were further evaluated among the controls of a population-based case-control study in Sweden (2899 prostate cancer cases and 1722 male controls), including 464 controls having tPSA levels of 2.5 to 10 ng/ml. Results We identified two loci that were associated with %fPSA at a genome-wide significance level (P <5 x 10-8). The first associated SNP was rs3213764 (P = 6.45 x 10-10), a nonsynonymous variant (K530R) in the ATF7IP gene at 12p13. This variant was also nominally associated with tPSA (P = .015). The second locus was rs1354774 (P = 1.25 x 10-12), near KLK2 at 19q13, which was not associated with tPSA levels, and is separate from the rs17632542 locus at KLK3 that was previously associated with tPSA levels and prostate cancer risk. Neither rs3213764 nor rs1354774 was associated with prostate cancer risk or aggressiveness. Conclusions These findings demonstrate that genetic variants at ATF7IP and KLK2 contribute to the variance of %fPSA. PMID:23359319

  9. Very late local recurrence after surgery for prostate cancer unaccompanied by detectable PSA levels.

    PubMed

    Roemeling, S; van Leenders, G J L H; Schröder, F H

    2006-01-01

    The possibility and possible aetiology of local prostate cancer (PC) recurrence despite undetectable prostate-specific antigen (PSA) levels are highlighted. A case of a local recurrence 8.5 years after radical prostatectomy for Gleason 3+4 PC is presented. It demonstrates that PC can recur, even after a prolonged period of time (8.5 years), despite undetectable levels (i.e. <0.02 ng/ml) of PSA. In conclusion, the decision to omit digital rectal examination from the follow-up regimens of men with undetectable PSA levels could be justified. In such exceptional cases, however, PC recurrence would be either missed or would only be diagnosed after a considerable delay.

  10. The ESA Planetary Science Archive User Group (PSA-UG)

    NASA Astrophysics Data System (ADS)

    Pio Rossi, Angelo; Cecconi, Baptiste; Fraenz, Markus; Hagermann, Axel; Heather, David; Rosenblatt, Pascal; Svedhem, Hakan; Widemann, Thomas

    2014-05-01

    ESA has established a Planetary Science Archive User Group (PSA-UG), with the task of offering independent advice to ESA's Planetary Science Archive (e.g. Heather et al., 2013). The PSA-UG is an official and independent body that continuously evaluates services and tools provided by the PSA to the community of planetary data scientific users. The group has been tasked with the following top level objectives: a) Advise ESA on future development of the PSA. b) Act as a focus for the interests of the scientific community. c) Act as an advocate for the PSA. d) Monitor the PSA activities. Based on this, the PSA-UG will report through the official ESA channels. Disciplines and subjects represented by PSA-UG members include: Remote Sensing of both Atmosphere and Solid Surfaces, Magnetospheres, Plasmas, Radio Science and Auxilliary data. The composition of the group covers ESA missions populating the PSA both now and in the near future. The first members of the PSA-UG were selected in 2013 and will serve for 3 years, until 2016. The PSA-UG will address the community through workshops, conferences and the internet. Written recommendations will be made to the PSA coordinator, and an annual report on PSA and the PSA-UG activities will be sent to the Solar System Exploration Working Group (SSEWG). Any member of the community and planetary data user can get in touch with individual members of the PSA-UG or with the group as a whole via the contacts provided on the official PSA-UG web-page: http://archives.esac.esa.int/psa/psa-ug. The PSA is accessible via: http://archives.esac.esa.int/psa References: Heather, D., Barthelemy, M., Manaud, N., Martinez, S., Szumlas, M., Vazquez, J. L., Osuna, P. and the PSA Development Team (2013) ESA's Planetary Science Archive: Status, Activities and Plans. EuroPlanet Sci. Congr. #EPSC2013-626

  11. The enhanced detection of persistent disease after prostatectomy with a new prostate specific antigen immunoassay.

    PubMed

    Takayama, T K; Vessella, R L; Brawer, M K; Noteboom, J; Lange, P H

    1993-08-01

    Prostate specific antigen (PSA) determinations after radical prostatectomy are valuable in detecting persistent disease. Previously, we determined that 0.4 ng./ml. PSA was a reliable clinical threshold using the Hybritech Tandem-R PSA assay. Recently, we reported that a new PSA immunoassay (Abbott IMx PSA) correlated well with results of the Tandem-R immunoradiometric PSA assay and had a lower threshold. Using a conservative threshold of 0.1 ng./ml. PSA for the IMx PSA assay, we analyzed IMx PSA values in serial postoperative serum from 72 radical prostatectomy patients whose initial Tandem-R levels were less than 0.4 ng./ml. PSA. The lower detection limits of the IMx PSA assay allowed approximately a third (15 of 42) more detection of persistent disease within 8 months of surgery. When the PSA level remained undetectable for more than 8 months but the disease eventually recurred the lead times averaged 9 to 12 months when 0.1 ng./ml. PSA was used to signify persistent disease. All patients whose PSA levels reached 0.1 ng./ml. PSA and were subsequently followed for more than 3 months continued to have increasing levels. Also, every man who eventually had recurrence also had a PSA serum level of at least 0.1 ng./ml. PSA within 28 months postoperatively, although the subsequent increase from 0.1 to 0.4 ng./ml. PSA sometimes took several years. Although the clinical impact of these findings is yet unknown, new or altered PSA assays with lower detection limits can provide unique information that may offer opportunities for improved clinical investigation and possibly patient management.

  12. Complex formation between human prostate-specific antigen and protease inhibitors in mouse plasma.

    PubMed

    Hekim, Can; Riipi, Tero; Zhu, Lei; Laakkonen, Pirjo; Stenman, Ulf-Håkan; Koistinen, Hannu

    2010-04-01

    When secreted from the prostate, most of prostate-specific antigen (PSA) is free and enzymatically active. Upon reaching circulation, active PSA is inactivated by complex formation with protease inhibitors. To justify the use of mouse models for evaluation of the function of PSA and for studies on therapeutic modalities based on modulation of PSA activity, it is important to know whether PSA complexation is similar in mouse and man. To characterize the circulating forms of PSA in mouse, we used subcutaneous LNCaP and 22RV1 human prostate cancer cell xenograft tumor models. We also added PSA directly to mouse serum. Free and total PSA were measured by immunoassay, and PSA complexes were extracted by immunopurification followed by SDS-PAGE, in-gel trypsin digestion and identification of signature peptides by mass spectrometry. In mice bearing xenograft tumors, 68% of the immunoreactive PSA occurred in complex, and when added to mouse serum, over 70% of PSA forms complexes that comprises alpha(2)-macroglobulin and members of the alpha(1)-antitrypsin (AAT) family. In mouse plasma, PSA forms complexes similar to those in man, but the major immunoreactive complex contains AAT rather than alpha(1)-antichymotrypsin, which is the main complex forming serpin in man. The complex formation of PSA produced by xenograft tumor models in mice is similar to that of human prostate tumors with respect to the complexation of PSA. (c) 2009 Wiley-Liss, Inc.

  13. HOXB13 overexpression is an independent predictor of early PSA recurrence in prostate cancer treated by radical prostatectomy

    PubMed Central

    Zabalza, Cristina Villares; Adam, Meike; Burdelski, Christoph; Wilczak, Waldemar; Wittmer, Corina; Kraft, Stefan; Krech, Till; Steurer, Stefan; Koop, Christina; Hube-Magg, Claudia; Graefen, Markus; Heinzer, Hans; Minner, Sarah; Simon, Ronald; Sauter, Guido; Schlomm, Thorsten; Tsourlakis, Maria Christina

    2015-01-01

    HOXB13 is a prostate cancer susceptibility gene which shows a cancer predisposing (G84E) mutation in 0.1–0.6% of males. We analyzed the prognostic impact of HOXB13 expression by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancers. Results were compared to tumor phenotype, biochemical recurrence, androgen receptor (AR) and prostate specific antigen (PSA) as well as molecular subtypes defined by ERG status and genomic deletions of 3p, 5q, 6q, and PTEN. HOXB13 immunostaining was detectable in 51.7% of 10,216 interpretable cancers and considered strong in 9.6%, moderate in 19.7% and weak in 22.3% of cases. HOXB13 expression was linked to advanced pT stage, high Gleason grade, positive lymph node status (p < 0.0001 each), high pre-operative PSA levels (p = 0.01), TMPRSS2:ERG fusion, PTEN deletions, AR expression, cell proliferation, reduced PSA expression and early PSA recurrence (p < 0.0001 each). The prognostic value of HOXB13 was independent from established parameters including Gleason, stage, nodal stage and PSA. Co-expression analysis identified a subset of tumors with high HOXB13 and AR but low PSA expression that had a particularly poor prognosis. HOXB13 appears to be a promising candidate for clinical routine tests either alone or in combination with other markers, including AR and PSA. PMID:25825985

  14. HOXB13 overexpression is an independent predictor of early PSA recurrence in prostate cancer treated by radical prostatectomy.

    PubMed

    Zabalza, Cristina Villares; Adam, Meike; Burdelski, Christoph; Wilczak, Waldemar; Wittmer, Corina; Kraft, Stefan; Krech, Till; Steurer, Stefan; Koop, Christina; Hube-Magg, Claudia; Graefen, Markus; Heinzer, Hans; Minner, Sarah; Simon, Ronald; Sauter, Guido; Schlomm, Thorsten; Tsourlakis, Maria Christina

    2015-05-20

    HOXB13 is a prostate cancer susceptibility gene which shows a cancer predisposing (G84E) mutation in 0.1-0.6% of males. We analyzed the prognostic impact of HOXB13 expression by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancers. Results were compared to tumor phenotype, biochemical recurrence, androgen receptor (AR) and prostate specific antigen (PSA) as well as molecular subtypes defined by ERG status and genomic deletions of 3p, 5q, 6q, and PTEN. HOXB13 immunostaining was detectable in 51.7% of 10,216 interpretable cancers and considered strong in 9.6%, moderate in 19.7% and weak in 22.3% of cases. HOXB13 expression was linked to advanced pT stage, high Gleason grade, positive lymph node status (p < 0.0001 each), high pre-operative PSA levels (p = 0.01), TMPRSS2:ERG fusion, PTEN deletions, AR expression, cell proliferation, reduced PSA expression and early PSA recurrence (p < 0.0001 each). The prognostic value of HOXB13 was independent from established parameters including Gleason, stage, nodal stage and PSA. Co-expression analysis identified a subset of tumors with high HOXB13 and AR but low PSA expression that had a particularly poor prognosis. HOXB13 appears to be a promising candidate for clinical routine tests either alone or in combination with other markers, including AR and PSA.

  15. Porous Silicon Antibody Microarrays for Quantitative Analysis: Measurement of Free and Total PSA in Clinical Plasma Samples

    PubMed Central

    Tojo, Axel; Malm, Johan; Marko-Varga, György; Lilja, Hans; Laurell, Thomas

    2014-01-01

    The antibody microarrays have become widespread, but their use for quantitative analyses in clinical samples has not yet been established. We investigated an immunoassay based on nanoporous silicon antibody microarrays for quantification of total prostate-specific-antigen (PSA) in 80 clinical plasma samples, and provide quantitative data from a duplex microarray assay that simultaneously quantifies free and total PSA in plasma. To further develop the assay the porous silicon chips was placed into a standard 96-well microtiter plate for higher throughput analysis. The samples analyzed by this quantitative microarray were 80 plasma samples obtained from men undergoing clinical PSA testing (dynamic range: 0.14-44ng/ml, LOD: 0.14ng/ml). The second dataset, measuring free PSA (dynamic range: 0.40-74.9ng/ml, LOD: 0.47ng/ml) and total PSA (dynamic range: 0.87-295ng/ml, LOD: 0.76ng/ml), was also obtained from the clinical routine. The reference for the quantification was a commercially available assay, the ProStatus PSA Free/Total DELFIA. In an analysis of 80 plasma samples the microarray platform performs well across the range of total PSA levels. This assay might have the potential to substitute for the large-scale microtiter plate format in diagnostic applications. The duplex assay paves the way for a future quantitative multiplex assay, which analyses several prostate cancer biomarkers simultaneously. PMID:22921878

  16. Comparative effectiveness of alternative PSA-based prostate cancer screening strategies

    PubMed Central

    Gulati, Roman; Gore, John L.; Etzioni, Ruth

    2013-01-01

    Background The US Preventive Services Task Force recently concluded that the harms of existing prostate-specific antigen (PSA) screening strategies outweigh benefits. Objective To evaluate comparative effectiveness of alternative PSA screening strategies. Design Microsimulation model of prostate cancer incidence and mortality quantifying harms and lives saved for alternative PSA screening strategies. Data Sources National and trial data on PSA growth, screening and biopsy patterns, incidence, treatment distributions, treatment efficacy, and mortality. Target Population A contemporary cohort of US men. Time Horizon Lifetime. Perspective Societal. Intervention 35 screening strategies that vary by start/stop ages, inter-screening intervals, and thresholds for biopsy referral. Outcome Measurements PSA tests, false positive tests, cancers detected, overdiagnoses, prostate cancer deaths, lives saved, and months of life saved. Results of Base-Case Analysis Without screening, the risk of prostate cancer death is 2.86%. A reference strategy that screens men aged 50–74 annually with a PSA threshold for biopsy referral of 4 μg/L reduces the risk of prostate cancer death to 2.15% with risk of overdiagnosis of 3.3%. A strategy that uses higher PSA thresholds for biopsy referral in older men achieves a similar risk of prostate cancer death (2.23%) but reduces the risk of overdiagnosis to 2.3%. A strategy that screens biennially with longer inter-screen intervals for men with low PSA levels achieves similar risks of prostate cancer death (2.27%) and overdiagnosis (2.4%) but reduces total tests by 59% and false positive tests by 50%. Results of Sensitivity Analysis Varying incidence inputs or reducing the survival improvement due to screening did not change conclusions. Limitations The model is a simplification of prostate cancer natural history, and the survival improvement due to screening is uncertain. Conclusions PSA screening strategies that use higher thresholds for

  17. Intermittent Androgen Suppression for Rising PSA Level after Radiotherapy

    PubMed Central

    Crook, Juanita M.; O’Callaghan, Christopher J.; Duncan, Graeme; Dearnaley, David P.; Higano, Celestia S.; Horwitz, Eric M.; Frymire, Eliot; Malone, Shawn; Chin, Joseph; Nabid, Abdenour; Warde, Padraig; Corbett, Thomas; Angyalfi, Steve; Goldenberg, S. Larry; Gospodarowicz, Mary K.; Saad, Fred; Logue, John P.; Hall, Emma; Schellhammer, Paul F.; Ding, Keyue; Klotz, Laurence

    2012-01-01

    BACKGROUND Intermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial. METHODS We enrolled patients with a PSA level greater than 3 ng per milliliter more than 1 year after primary or salvage radiotherapy for localized prostate cancer. Intermittent treatment was provided in 8-month cycles, with nontreatment periods determined according to the PSA level. The primary end point was overall survival. Secondary end points included quality of life, time to castration-resistant disease, and duration of nontreatment intervals. RESULTS Of 1386 enrolled patients, 690 were randomly assigned to intermittent therapy and 696 to continuous therapy. Median follow-up was 6.9 years. There were no significant between-group differences in adverse events. In the intermittent-therapy group, full testosterone recovery occurred in 35% of patients, and testosterone recovery to the trial-entry threshold occurred in 79%. Intermittent therapy provided potential benefits with respect to physical function, fatigue, urinary problems, hot flashes, libido, and erectile function. There were 268 deaths in the intermittent-therapy group and 256 in the continuous-therapy group. Median overall survival was 8.8 years in the intermittent-therapy group versus 9.1 years in the continuous-therapy group (hazard ratio for death, 1.02; 95% confidence interval, 0.86 to 1.21). The estimated 7-year cumulative rates of disease-related death were 18% and 15% in the two groups, respectively (P = 0.24). CONCLUSIONS Intermittent androgen deprivation was noninferior to continuous therapy with respect to overall survival. Some quality-of-life factors improved with intermittent therapy. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00003653.) PMID

  18. Wash-free magnetic immunoassay of the PSA cancer marker using SERS and droplet microfluidics.

    PubMed

    Gao, Rongke; Cheng, Ziyi; deMello, Andrew J; Choo, Jaebum

    2016-03-21

    We report a novel wash-free magnetic immunoassay technique for prostate-specific antigen (PSA) that uses a surface-enhanced Raman scattering (SERS)-based microdroplet sensor. The magnetic bar embedded in a droplet-based microfluidic system segregates the free and bound SERS tags by splitting the droplets into two smaller parts. The presence of PSA targets leads more SERS tags to immunocomplex in one droplet so that fewer SERS tags remain in another supernatant solution droplet. Thus, SERS signal measurement enables the quantitative evaluation of PSA markers. This approach can provide a rapid and sensitive assay that is applicable for PSA cancer markers in serum without any washing. Specifically, SERS signals were measured at 174 droplets per minute and averaged for quantitative evaluation of PSA. The limit of detection (LOD) determined by our SERS-based microdroplet sensor was estimated to be below 0.1 ng mL(-1), which is significantly below the clinical cut-off value for the diagnosis of prostate cancer. In addition, because the entire assay can be carried out automatically, only a minimal amount of sample is needed. Accordingly, the approach is expected to be useful as a potential clinical tool for the early diagnosis of prostate cancer.

  19. The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA

    PubMed Central

    Fleshner, Katherine; Carlsson, Sigrid V.; Roobol, Monique J.

    2017-01-01

    Guidelines conflict regarding recommendations for prostate-specific antigen (PSA) screening for early detection of prostate cancer. The United States Preventive Services Task Force (USPSTF) assigned a grade of D (recommending against screening) for men 75 and older in 2008 and for men of all ages in 2012. We reviewed temporal trends in rates of screening before and after the 2012 recommendation based on a literature search for studies published between 2011/01/01–2016/10/03 on PSA utilization patterns, changes in prostate cancer incidence and biopsy patterns, and how the recommendation has shaped physician and patient attitudes about PSA screening and subsequent ordering of other screening tests. Rates of PSA screening decreased by 3–10 percentage points among all age groups and within most U.S. geographic regions. Rates of prostate biopsy and prostate cancer incidence have declined in unison, with a notable shift towards higher grade, stage and risk upon detection. Despite the recommendation, some physicians reported ongoing willingness to screen appropriately selected men, and men largely reported intending to continue to ask for the PSA test. In the coming years, we expect to have a better picture of whether these decreased rates of screening will impact prostate cancer metastasis and mortality. PMID:27995937

  20. The ESA Planetary Science Archive User Group (PSA-UG)

    NASA Astrophysics Data System (ADS)

    Rossi, A. P.; Cecconi, B.; Fraenz, M.; Hagermann, A.; Heather, D.; Rosenblatt, P.; Svedhem, H.; Widemann, T.

    2014-04-01

    ESA has established a Planetary Science Archive User Group (PSA-UG), with the task of offering independent advice to ESA's Planetary Science Archive (e.g. Heather et al., 2013). The PSA-UG is an official and independent body that continuously evaluates services and tools provided by the PSA to the community of planetary data scientific users. The group has been tasked with the following top level objectives: a) Advise ESA on future development of the PSA. b) Act as a focus for the interests of the scientific community. c) Act as an advocate for the PSA. d) Monitor the PSA activities. Based on this, the PSA-UG will report through the official ESA channels. Disciplines and subjects represented by PSA-UG members include: Remote Sensing of both Atmosphere and Solid Surfaces, Magnetospheres, Plasmas, Radio Science and Auxilliary data. The composition of the group covers ESA missions populating the PSA both now and in the near future. The first members of the PSA-UG were selected in 2013 and will serve for 3 years, until 2016. The PSA-UG will address the community through workshops, conferences and the internet. Written recommendations will be made to the PSA coordinator, and an annual report on PSA and the PSA-UG activities will be sent to the Solar System Exploration Working Group (SSEWG). Any member of the community and planetary data user can get in touch with individual members of the PSA-UG or with the group as a whole via the contacts provided on the official PSA-UG web-page: http://archives.esac.esa.int/psa/psa-ug The PSA is accessible via: http://archives.esac.esa.int/psa

  1. Expression of PCA3 and PSA genes as a biomarker for differential diagnosis of nodular hyperplasia and prostate cancer.

    PubMed

    Coelho, F Fonseca; Guimarães, F Loli; Cabral, W L Ribeiro; Salles, P G Oliveira; Mateo, E Cueva; Nogueira e Nogueira, L Mendes; Fonseca, C E Corradi; Gomes, K Braga

    2015-10-28

    We evaluated the expression of the PCA3 gene in urine from patients with nodular hyperplasia/benign prostatic hyperplasia (PNH) or adenocarcinoma type prostate cancer (PCa).The study included 59 men: 22 with PCa, 26 with PNH, and 11 with no alterations (controls). Patients' urine was collected following prostatic massage and quantified by quantitative real-time PCR for prostate cancer antigen 3 gene (PCA3) and prostate-specific antigen gene (PSA) expression with the ACTB gene for normalization. PCA3 gene expression was detected in 16 patients with PCa and 4 with PNH; in the control group, there was no expression of the gene. No significant difference was observed in the mean levels of PCA3 and PSA expression, the PCA3/PSA ratio, and the total PSA levels when the groups of patients with PCa and PNH were compared. The area under the receiver operating characteristic (ROC) curve was 0.625, 0.596, 0.559, and 0.503 for PCA3 and PSA expression, the PCA3/PSA ratio, and total PSA levels, respectively. The sensitivity and specificity of the PCA3 test were 73 and 85%, respectively. Considering the estimated cutoff values (0.2219 and 0.5007 for PCA3 and PCA3/PSA, respectively), we observed a significant difference between the frequency of individuals with values above in the PCa group compared with the PNH group (P < 0.001). We conclude that the qualitative PCA3 test could be applied to initial screening for differentiation between individuals with PCa or PNH and those without prostate changes.

  2. African Americans’ Perceptions of PSA Prostate Cancer Screening

    PubMed Central

    Hunter, Jaimie C.; Vines, Anissa I.; Carlisle, Veronica

    2016-01-01

    Background In 2012, the US Preventive Services Task Force (USPSTF) released a hotly-debated recommendation against prostate-specific antigen (PSA) testing for all men. The present research examines African Americans’ beliefs about their susceptibility to prostate cancer (PCa) and the effectiveness of PSA testing in the context of the controversy surrounding this recommendation. Methods This study used a qualitative design to examine perceptions regarding susceptibility along with screening and facilitators of and barriers thereof. Data were collected at a community health center and three predominantly African American churches in North Carolina. Study participants were 46 African American men and women who attended one of four “listening sessions” for pretesting PCa educational materials (average age: 55 years). One-and-a-half-hour listening sessions were conducted to pretest materials; while presenting the materials, researchers probed beliefs and knowledge about PCa screening. The sessions were recorded and transcribed, and the transcripts were qualitatively analyzed using grounded theory. Results The four emergent themes indicated that participants: (1) cited behavioral, psychosocial, and biological reasons why African American men have higher PCa risk compared to others; (2) knew about the controversy and had varying responses and intentions; (3) believed screening could save lives, so it should be utilized regardless of the 2012 recommendation; and (4) felt that women can help men go to the doctor and make screening decisions. Conclusions Health education efforts to help community members understand health controversies, screening options, and how to make informed screening decisions are critical. PMID:25616411

  3. Genetic and antigenic characterization of a newly emerging porcine circovirus type 2b mutant first isolated in cases of vaccine failure in Korea.

    PubMed

    Seo, Hwi Won; Park, Changhoon; Kang, Ikjae; Choi, Kyuhyung; Jeong, Jiwoon; Park, Su-Jin; Chae, Chanhee

    2014-11-01

    This study describes the genetic and antigenic characterization of a newly emerging porcine circovirus type 2b (PCV2b) mutant first isolated in cases of vaccine failure in Korea. The full genome of the PCV2b isolates (SNUVR130689 and SNUVR140004) is 1,767 base pairs (bp) in length. The size of ORF1 is 945 bp, encoding a protein of 314 amino acids (aa), and the size of ORF2 is 705 bp, encoding a protein of 234 aa, which is 1 aa longer than that of the common PCV2 (233 aa). Korean PCV2b mutant strains had higher levels of nucleotide sequence identity to other PCV2b mutant strains (99.7-99.8 %) than to reference PCV2a (94.5-95.0 %) and PCV2b (95.5-96.1 %) strains. There was no difference in antigenic reactivity among PCV2a, PCV2b and PCV2b mutant strains to the polyclonal and monoclonal PCV2a antibodies. PCV2b mutant strains have distinct genetic characteristics but similar antigenic reactivity when compared to common PCV2a and 2b strains.

  4. Outcome After Conformal Salvage Radiotherapy in Patients With Rising Prostate-Specific Antigen Levels After Radical Prostatectomy

    SciTech Connect

    Geinitz, Hans; Riegel, Martina G.; Thamm, Reinhard; Astner, Sabrina T.; Lewerenz, Carolin; Zimmermann, Frank; Molls, Michael; Nieder, Carsten

    2012-04-01

    Purpose: This study attempts to improve our understanding of the role of salvage radiotherapy (SRT) in patients with prostate-specific antigen (PSA) relapse after radical prostatectomy with regard to biochemical control, rate of distant metastasis, and survival. Methods and Materials: We performed a retrospective analysis of 96 men treated with conformal prostate bed SRT (median, 64.8 Gy) at a single institution (median follow-up, 70 months). The majority had intermediate- or high-risk prostate cancer. Fifty-four percent underwent a resection with positive margins (R1 resection). The median time interval between surgery and SRT was 22 months. Results: After SRT, 66% of patients reached a PSA nadir of less than 0.2 ng/mL. However, the 5-year biochemical no evidence of disease rate was 35%. Seminal vesicle involvement was predictive for a significantly lower biochemical no evidence of disease rate. All patients with a preoperative PSA level greater than 50 ng/mL relapsed biochemically within 2 years. The 5-year distant metastasis rate was 18%, the 5-year prostate cancer-specific survival rate was 90%, and the 5-year overall survival rate was 88%. Significantly more distant metastases developed in patients with a PSA nadir greater than 0.05 ng/mL after SRT, and they had significantly inferior prostate cancer-specific and overall survival rates. Resection status (R1 vs. R0) was not predictive for any of the endpoints. Conclusions: Men with postoperative PSA relapse can undergo salvage treatment by prostate bed radiotherapy, but durable PSA control is maintained only in about one-third of the patients. Despite a high biochemical failure rate after SRT, prostate cancer-specific survival does not decrease rapidly.

  5. Prognostic value of PSA nadir {<=}4 ng/mL within 4 months of high-dose radiotherapy for locally advanced prostate cancer

    SciTech Connect

    Nickers, Philippe . E-mail: philippe.nickers@skynet.be; Albert, Adelin; Waltregny, David; Deneufbourg, Jean-Marie

    2006-05-01

    Purpose: To investigate early prostate-specific antigen (PSA) kinetics after high radiation doses of 85 Gy on locally advanced prostate cancer. Methods and Materials: A total of 201 patients were prospectively and consecutively treated with external beam radiotherapy and a brachytherapy boost. Of the 201 patients, 104 received concomitant hormonal therapy on the decision of the referring urologist and were excluded, yielding a study population of 97 patients. The first posttreatment PSA analysis was performed not earlier than 1 month after treatment completion but within the first 4 months, and then every 4 months. Analysis of PSA kinetics included the PSA nadir (nPSA) at values of {<=}4 ng/mL to {<=}0.5 ng/mL. The nPSA at {<=}4 ng/mL within 4 months (nPSA {<=}4/4m) was the variable of interest. Results: We established highly significant associations between an nPSA of {<=}1 and {<=}0.5 ng/mL and the nPSA {<=}4/4m (p <0.0001). A hazard ratio of 0.33 (95% Confidence Interval (CI), 0.12-0.91) underlined the lower risk of recurrence related to nPSA {<=}4/4m achievement (p = 0.033). Using time-dependent covariate models for patients who did not reach an nPSA {<=}4/4m, an nPSA of {<=}1 ng/mL remained without prognostic significance (p = 0.06). However, for patients who reached an nPSA {<=}4/4m, an nPSA of {<=}1 ng/mL did significantly improve the prognosis (p <0.001), but much later after treatment. The same analysis was repeated for nPSA {<=}0.5 ng/mL with similar conclusions as when nPSA {<=}4/4m was obtained (p <0.01). Conclusion: The nPSA {<=}4/4m has been demonstrated to be a significant predictor of biochemical no evidence of disease after high radiation doses of 85 Gy. Its major advantage is that it was available earlier than the other nadirs.

  6. Increased PSA expression on prostate cancer exosomes in in vitro condition and in cancer patients.

    PubMed

    Logozzi, Mariantonia; Angelini, Daniela F; Iessi, Elisabetta; Mizzoni, Davide; Di Raimo, Rossella; Federici, Cristina; Lugini, Luana; Borsellino, Giovanna; Gentilucci, Alessandro; Pierella, Federico; Marzio, Vittorio; Sciarra, Alessandro; Battistini, Luca; Fais, Stefano

    2017-09-10

    Prostate specific antigen (PSA) test is the most common, clinically validated test for the diagnosis of prostate cancer (PCa). While neoplastic lesions of the prostate may cause aberrant levels of PSA in the blood, the quantitation of free or complexed PSA poorly discriminates cancer patients from those developing benign lesions, often leading to invasive and unnecessary surgical procedures. Microenvironmental acidity increases exosome release by cancer cells. In this study we evaluated whether acidity, a critical phenotype of malignancy, could influence exosome release and increase the PSA expression in nanovesicles released by PCa cells. To this aim, we exploited Nanoparticle Tracking Analysis (NTA), an immunocapture-based ELISA, and nanoscale flow-cytometry. The results show that microenvironmental acidity induces an increased release of nanovesicles expressing both PSA and the exosome marker CD81. In order to verify whether the changes induced by the local selective pressure of extracellular acidity may correspond to a clinical pathway we used the same approach to evaluate the levels of PSA-expressing exosomes in the plasma of PCa patients and controls, including subjects with benign prostatic hypertrophy (BPH). The results show that only PCa patients have high levels of nanovesicles expressing both CD81 and PSA. This study shows that tumor acidity exerts a selective pressure leading to the release of extracellular vesicles that express both PSA and exosome markers. A comparable scenario was shown in the plasma of prostate cancer patients as compared to both BPH and healthy controls. These results suggest that microenvironmental acidity may represent a key factor which determines qualitatively and quantitatively the release of extracellular vesicles by malignant tumors, including prostate cancer. This condition leads to the spill-over of nanovesicles into the peripheral blood of prostate cancer patients, where the levels of tumor biomarkers expressed by

  7. Association of GPs’ risk attitudes, level of empathy, and burnout status with PSA testing in primary care

    PubMed Central

    Pedersen, Anette F; Carlsen, Anders H; Vedsted, Peter

    2015-01-01

    Background Rates of prostate specific antigen (PSA) test ordering vary among GPs. Aim To examine whether GPs’ risk attitude, level of empathy, and burnout status are associated with PSA testing. Design and setting Register and questionnaire study including 129 solo GPs (active in the Central Denmark Region) and 76 672 of their adult male patients with no history of or current prostate cancer diagnosis. Method PSA tests from 2012 were retrieved from a register and classified as incident (that is, the first PSA test within 24 months), repeated normal, or repeated raised tests. This was merged with information on GPs’ risk attitudes, empathy, and burnout status from a 2012 survey. Results Patients registered with a GP with a high score on anxiety caused by uncertainty (odds ratio [OR] 1.03, 95% confidence interval [CI] = 1.00 to 1.06, P = 0.025) or concern about bad outcomes (OR 1.04; 95% CI = 1.00 to 1.08, P = 0.034) were more likely to have an incident PSA test, whereas those registered with a GP with increased tolerance for ambiguity were less likely (OR 0.98, 95% CI = 0.96 to 1.00, P = 0.025). Patients registered with a GP reporting high tolerance for ambiguity (OR 0.96, 95% CI = 0.94 to 0.99, P = 0.009) or high propensity to risk-taking (OR 0.97, 95% CI = 0.93 to 1.00, P = 0.047) were less likely to have a repeated normal PSA test. Conclusion Various aspects of GPs’ risk-taking attitudes were associated with patients’ probability of having an incident and a repeated normal PSA test. The probability of having a repeated raised PSA test was not influenced by any of the psychological factors. Burnout and empathy were not associated with PSA testing. PMID:26541183

  8. Percent free prostate-specific antigen: entering a new era in the detection of prostate cancer.

    PubMed

    Vashi, A R; Oesterling, J E

    1997-04-01

    The introduction of prostate-specific antigen (PSA) testing into clinical medicine in 1986 revolutionized the management of patients with prostate cancer. The major limitation of this tumor marker stems from its inability to provide a clear distinction between benign prostate disease and prostate cancer, especially in patients with upper limit of normal or slightly increased PSA values. Recent research has established that PSA exists in the serum in several molecular forms. Patients with benign prostatic hyperplasia have more of the free form, whereas those with prostate cancer have more of a complexed form (PSA covalently bound to alpha 1-antichymotrypsin). Several investigations have now confirmed that determining percent free PSA (proportion of free PSA to total PSA) enhances the ability of PSA testing to distinguish between prostate cancer and benign prostatic hyperplasia. In addition, percent free PSA seems to have the greatest clinical significance in patients whose total PSA values range from 2.5 or 3.0 ng/mL (lower limit) to 10.0 ng/mL (upper limit). When the total PSA value is in the normal range (2.5 or 3.0 to 4.0 ng/mL), percent free PSA makes PSA a more sensitive test (increases cancer detection). When the total PSA level is minimally increased (4.1 to 10.0 ng/mL), percent free PSA makes PSA a more specific test (eliminates performance of unnecessary prostate biopsies). Although further work remains, it seems that percent free PSA can substantially improve the clinical utility of the PSA test for detecting early, curable prostate cancer.

  9. Integration of Passive System Reliability in PSA Studies

    SciTech Connect

    Burgazzi, Luciano; Marques, Michel

    2006-07-01

    The treatment of passive safety systems within the probabilistic safety assessment models is a difficult and challenging task. The main concern arises from the nature of the passive systems whose predominant operating principles are based on physical phenomena rather than on active components. The present study provides a consistent approach for the integration of passive safety systems into fault tree and event tree based Probabilistic Safety Assessment (PSA) model of accident sequences, in the fashion of and in combination with a front line system or a human action. With reference to the thermal-hydraulic passive systems (e.g. natural circulation systems), in addition to the component failures (i.e. mechanical and electrical faults), the impairment of the physical principle upon which the system relies, deserves special consideration. This makes the relative assessment process different as regards the system model commonly adopted in the fault tree approach (i.e. exponential failure model). For the thermal-hydraulic passive system, since the failure process is driven mainly by the occurrence of the phenomenological failure modes, each pertinent basic event will be characterized by defined critical parameters (e.g. non-condensable fraction) that are expected to drive the failure mechanisms. An application of this approach is presented, with reference to a system designed for decay heat removal of advanced Light Water Reactors, relying on natural circulation and provided with a heat exchanger immersed in a cooling pool, acting as heat sink, and connected to the pressure vessel via steam and condensate lines. (authors)

  10. Rosetta Planetary Science Archive (PSA) Status

    NASA Astrophysics Data System (ADS)

    Wirth, Kristin R.; Cardesin, A.; Barthelemy, M.; Diaz del Rio, J.; Zender, J.; Arviset, C.

    2006-09-01

    The Planetary Science Archive (PSA) is an online database (accessible via http://www.rssd.esa.int/PSA) implemented by ESA/RSSD. Currently the PSA contains the science data from the Giotto (Halley), Mars Express and SMART-1 (Moon) missions, and the Rosetta Supplementary Archive (Wirtanen). The PSA user is offered a broad range of search possibilities. Search queries can be combined without restrictions and are executed across the whole database. The PSA utilizes the Planetary Data System (PDS) standard. In spring 2007 the PSA will provide the first science and engineering data collected by Rosetta. In preparation for the initial Peer Review to be performed before publication of these data, an Internal Review was held in March 2006, executed by staff internal to the organizations responsible for the Rosetta archiving (ESA, PDS, CNES). The Internal Reviewers identified shortcomings in documentation, data structures, and completeness of the data delivery. They recommended the usage of unified conventions and formats across different instruments. Work is ongoing to include standardized geometry information in the datasets. Rosetta was launched in March 2004 to rendezvous with comet 67P/Churyumov-Gerasimenko (C-G) in May 2014. After having placed a lander on the comet's surface, the Rosetta orbiter will continue to orbit C-G and accompany the comet through perihelion. Rosetta makes use of three Earth swingbys and one Mars swingby in order to reach C-G. Rosetta will also perform close flybys at two asteroids, namely 2867 Steins in September 2008 and 21 Lutetia in July 2010. In addition, Rosetta makes scientific observations of targets of opportunity, e.g. lightcurves of the flyby asteroids to study the rotation, and plasma measurements when passing through cometary ion tails or meteoroid streams. Rosetta continuously monitored the encounter of the Deep Impact probe with comet 9P/Tempel 1 over an extended period of 16 days around the impact on 4 July 2005.

  11. Prostate-specific antigen and perfluoroalkyl acids in the C8 health study population.

    PubMed

    Ducatman, Alan; Zhang, Jianjun; Fan, Hongmin

    2015-01-01

    To inform questions raised by inconsistent findings regarding an association between perfluoroalkyl acids (PFAAs) and prostate cancer by assessing the relationship of PFAAs in human serum to prostate-specific antigen (PSA). Using 2005 to 2006 survey data from a large survey population, we compared serum PFAA concentrations in adult males with PSA concentrations adjusted for risk factors including age, body mass index, smoking status, and socioeconomic status. Perfluoroalkyl acids are not consistently associated with PSA concentration in general, or with PSA more than 4.0. These findings do not provide evidence that PFAA exposure is associated with PSA.

  12. Bayer Immuno 1 PSA Assay: an automated, ultrasensitive method to quantitate total PSA in serum.

    PubMed

    Morris, D L; Dillon, P W; Very, D L; Ng, P; Kish, L; Goldblatt, J L; Bruzek, D J; Chan, D W; Ahmed, M S; Witek, D; Fritsche, H A; Smith, C; Schwartz, D; Schwartz, M K; Noteboom, J L; Vessella, R L; Yeung, K K; Allard, W J

    1998-01-01

    The Bayer Immuno 1 PSA Assay measures total PSA in human serum and demonstrates excellent performance with an interassay CV < or = 3.4% and a biological detection limit of 0.03 microgram/L. No significant interference from common hormonal and chemotherapeutic drugs, kallikrein, prostatic acid phosphatase, and trypsin, or elevated levels of total bilirubin, hemoglobin, triglycerides, and IgG was observed. The 95th percentile values for healthy individuals increased with age from 3.0 micrograms/L for males 50-59 years and 3.3 micrograms/L for males 60-69 years, to 4.6 micrograms/L for males > or = 70 years. Clinical studies with retrospective samples demonstrated correspondence between serial measurements of PSA and clinical outcome for 98% of 159 prostate cancer patients. Clinical sensitivity for patients with clinical evidence of disease, untreated at the time of specimen draw, increased with increasing stage from 77.5-100%. Specificity of 60-70% for BPH and other benign urogenital diseases was consistent with previous findings. Bayer Immuno 1 PSA Assay values for 2131 specimens from healthy subjects and patients with prostate cancer, BPH, and other malignant and nonmalignant diseases correlated well with the Abbott IMx PSA Assay over the range 0.0-6,238 micrograms/L (Y = 1.10 x + 0.02). The Bayer Immuno 1 PSA Assay provides automated ultrasensitive, precise, and equimolar measurement of total PSA in human serum.

  13. Exosome targeting of tumor antigens expressed by cancer vaccines can improve antigen immunogenicity and therapeutic efficacy.

    PubMed

    Rountree, Ryan B; Mandl, Stefanie J; Nachtwey, James M; Dalpozzo, Katie; Do, Lisa; Lombardo, John R; Schoonmaker, Peter L; Brinkmann, Kay; Dirmeier, Ulrike; Laus, Reiner; Delcayre, Alain

    2011-08-01

    MVA-BN-PRO (BN ImmunoTherapeutics) is a candidate immunotherapy product for the treatment of prostate cancer. It encodes 2 tumor-associated antigens, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP), and is derived from the highly attenuated modified vaccinia Ankara (MVA) virus stock known as MVA-BN. Past work has shown that the immunogenicity of antigens can be improved by targeting their localization to exosomes, which are small, 50- to 100-nm diameter vesicles secreted by most cell types. Exosome targeting is achieved by fusing the antigen to the C1C2 domain of the lactadherin protein. To test whether exosome targeting would improve the immunogenicity of PSA and PAP, 2 additional versions of MVA-BN-PRO were produced, targeting either PSA (MVA-BN-PSA-C1C2) or PAP (MVA-BN-PAP-C1C2) to exosomes, while leaving the second transgene untargeted. Treatment of mice with MVA-BN-PAP-C1C2 led to a striking increase in the immune response against PAP. Anti-PAP antibody titers developed more rapidly and reached levels that were 10- to 100-fold higher than those for mice treated with MVA-BN-PRO. Furthermore, treatment with MVA-BN-PAP-C1C2 increased the frequency of PAP-specific T cells 5-fold compared with mice treated with MVA-BN-PRO. These improvements translated into a greater frequency of tumor rejection in a PAP-expressing solid tumor model. Likewise, treatment with MVA-BN-PSA-C1C2 increased the antigenicity of PSA compared with treatment with MVA-BN-PRO and resulted in a trend of improved antitumor efficacy in a PSA-expressing tumor model. These experiments confirm that targeting antigen localization to exosomes is a viable approach for improving the therapeutic potential of MVA-BN-PRO in humans.

  14. Repeat Prostate-Specific Antigen Tests Before Prostate Biopsy Decisions.

    PubMed

    Nordström, Tobias; Adolfsson, Jan; Grönberg, Henrik; Eklund, Martin

    2016-12-01

    Despite limited scientific support, a repeat prostate-specific antigen (PSA) test before prostate biopsy decisions is common. We analyzed biopsy outcomes in 1686 men from the STHLM3 study with PSA 3-10 ng/mL and two PSA tests taken within eight weeks and before prostate biopsy using percentages and multinomial logistic regression. We found that omitting prostate biopsy for men with PSA values decreasing to PSAs of 3 ng/mL or less would save 16.8% of biopsy procedures, while missing 5.4% of the cancers with Gleason scores (GSs) of 7 or higher. The proportion of cancers with GSs of 6 or lower was independent of the first PSA value, as well as of PSA change. Also, the risk of tumors with GSs of 7 or higher decreased with both decreasing and increasing PSA levels: It was 18.6% (95% confidence interval [CI] = 16.3% to 20.9%) for men with PSA changes of less than 20%, 12.1% (95% CI = 8.0% to 16.2%) for men with PSA levels increasing at least 20%, and 6.6% (95% CI = 3.8% to 9.3%) for men with PSA levels decreasing at least 20%. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA.

    PubMed

    Paur, Ingvild; Lilleby, Wolfgang; Bøhn, Siv Kjølsrud; Hulander, Erik; Klein, Willibrord; Vlatkovic, Ljiljana; Axcrona, Karol; Bolstad, Nils; Bjøro, Trine; Laake, Petter; Taskén, Kristin A; Svindland, Aud; Eri, Lars Magne; Brennhovd, Bjørn; Carlsen, Monica H; Fosså, Sophie D; Smeland, Sigbjørn S; Karlsen, Anette S; Blomhoff, Rune

    2017-06-01

    The effect of lycopene-containing foods in prostate cancer development remains undetermined. We tested whether a lycopene-rich tomato intervention could reduce the levels of prostate specific antigen (PSA) in prostate cancer patients. Prior to their curative treatment, 79 patients with prostate cancer were randomized to a nutritional intervention with either 1) tomato products containing 30 mg lycopene per day; 2) tomato products plus selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice, and green/black tea (tomato-plus); or 3) control diet for 3 weeks. The main analysis, which included patients in all risk categories, did not reveal differences in changes of PSA-values between the intervention and control groups. Post-hoc, exploratory analyses within intermediate risk (n = 41) patients based on tumor classification and Gleason score post-surgery, revealed that median PSA decreased significantly in the tomato group as compared to controls (-2.9% and +6.5% respectively, p = 0.016). In separate post-hoc analyses, we observed that median PSA-values decreased by 1% in patients with the highest increases in plasma lycopene, selenium and C20:5 n-3 fatty acid, compared to an 8.5% increase in the patients with the lowest increase in lycopene, selenium and C20:5 n-3 fatty acid (p = 0.003). Also, PSA decreased in patients with the highest increase in lycopene alone (p = 0.009). Three week nutritional interventions with tomato-products alone or in combination with selenium and n-3 fatty acids lower PSA in patients with non-metastatic prostate cancer. Our observation suggests that the effect may depend on both aggressiveness of the disease and the blood levels of lycopene, selenium and omega-3 fatty acids. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  16. Early dutasteride monotherapy in men with detectable serum prostate-specific antigen levels following radical prostatectomy: A prospective trial

    PubMed Central

    Shin, Yu Seob; Lee, Jea Whan; Kim, Myung Ki; Jeong, Young Beom

    2017-01-01

    Purpose To investigate the effects of early administration of dutasteride in patients with detectable serum prostate-specific antigen (PSA) levels after radical prostatectomy (RP). Materials and Methods A prospective open-label study, with a cumulative analysis of asymptomatic increase in PSA following RP, was conducted from January 2005 to December 2013. An early increase in PSA level was defined as detectable serum PSA level> 0.04 ng/mL. Patients with PSA level>0.04 ng/mL were treated with dutasteride 0.5 mg daily. Serum PSA level and biochemical recurrence (BCR) were monitored. We divided the patients into 2 groups based on the serum PSA response after dutasteride treatment. Results Eighty patients were included in the study. At the median follow-up of 51.8 months, 56 patients (70.0%) showed a decrease of greater than 10% in serum PSA level, and 24 showed increased PSA levels. Twelve of the 56 patients with PSA response showed subsequently increased PSA. Intergroup differences in preoperative PSA levels, PSA nadir levels, and Gleason score of 6 or less were significant (p=0.028, p=0.030, and p=0.035, respectively). A multivariate analysis revealed that Gleason score of 6 or less (p=0.018) and PSA nadir levels (p=0.011) were predictive factors for PSA response after early dutasteride treatment in men with increased PSA levels following RP. Conclusions Early monotherapy of dutasteride showed a decline in serum PSA levels in men with lower nadir PSA levels, and a Gleason score 6, when the serum PSA was detected after RP. PMID:28261678

  17. Imprinted gold 2D nanoarray for highly sensitive and convenient PSA detection via plasmon excited quantum dots.

    PubMed

    Song, Hong Yan; Wong, Ten It; Sadovoy, Anton; Wu, Lin; Bai, Ping; Deng, Jie; Guo, Shifeng; Wang, Yi; Knoll, Wolfgang; Zhou, Xiaodong

    2015-01-07

    We designed and fabricated two new nanostructured biosensing chips, with which the sensitive detection of prostate specific antigen (PSA) as low as 100 pg ml(-1) can be achieved, by measuring the plasmon enhanced fluorescence through a conventional dark field microscope. The gold nanostructure arrays, one with gold nanopillars of 140 nm, the other with gold nanoholes of 140 nm, were fabricated via nanoimprinting onto glass substrate, as localized surface plasmon resonance (LSPR) generators to enhance the fluorescent emission of fluorophore, e.g. quantum dot (QD). A sandwich bioassay of capture anti-PSA antibody (cAb)/PSA/detection anti-PSA (dAb) labeled by QD-655 was established on the nanostructures, and the perfect LSPR excitation distance (10-15 nm) between the nanostructure and QD-655 was simulated and controlled by a cleft cAb fragment and streptavidin modified QD. QD was chosen in this study due to its photo stability, broad Stokes shift, and long lifetime. As far as we know, this is the first time that QD is applied for PSA detection on the uniform nanostructured sensing chips based on the LSPR enhanced fluorescence. Due to the miniaturized nanoarray sensing chip (1.8 mm × 1.8 mm), the convenience and specificity for the detection of PSA via the sandwich assay, and the high optical detection sensitivity, the platform has great potential for the development of a portable point-of-care (POC) system for outpatient diagnosis and treatment monitoring.

  18. Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade.

    PubMed

    Momozono, Hiroyuki; Miyake, Hideaki; Tei, Hiromoto; Harada, Ken-Ichi; Fujisawa, Masato

    2016-05-01

    The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With the exception of 41 patients (15.1%) who did not undergo anti-androgen withdrawal due to the characteristics of PC suggesting aggressive diseases, prostate-specific antigen (PSA) declined from the baseline value in 83 patients (35.9%), including 18 (7.8%) with PSA decline >50%, but not in the remaining 148 (64.1%). No significant difference in the overall survival (OS) or cancer-specific survival (CSS) among the three groups was observed based on the response to anti-androgen withdrawal. Following the introduction of alternative anti-androgen therapy with flutamide, PSA decline was observed in 185 patients (68.0%), including 103 (37.9%) who achieved a PSA reduction of >50%; however, the PSA level continued to elevate in the remaining 87 (32.0%). Furthermore, of the numerous factors examined, only the duration of the initial MAB therapy was shown to be significantly correlated with the PSA decline following alternative anti-androgen therapy. Multivariate analysis of several factors identified revealed that only PSA decline following alternative anti-androgen therapy was an independent predictor of CSS and OS. If initial MAB is effective, the introduction of alternative anti-androgen therapy may be considered; however, anti-androgen withdrawal should be omitted, irrespective of the characteristics of advanced PC.

  19. Rapid Increase of the Serum PSA Level in Response to High-Intensity Focused Ultrasound Therapy may be a Potential Indicator of Biochemical Recurrence of Low- and Intermediate-Risk Prostate Cancer

    PubMed Central

    Inamoto, Teruo; Komura, Kazumasa; Watsuji, Toshikazu; Azuma, Haruhito

    2011-01-01

    Objectives: To determine the incidence and magnitude of the rapid increase in the serum PSA (riPSA) level after high-intensity focused ultrasound (HIFU) therapy for prostate cancer, and its correlation with clinical factors. Methods: A total of 176 patients with localized prostate cancer underwent HIFU therapy. Serum riPSA was determined on the basis of the same criteria as those for “PSA bounce”, ie, an increase of ≥0.2 ng/ml with a spontaneous return to the prebounce level or lower. Patients were stratified according to neoadjuvant PSA level, T stage, risk group, age, Gleason score, pretreatment PSA level, post-treatment PSA nadir, and number of HIFU sessions. Results: riPSA was seen in 53% of patients during a median follow-up period of 43 months. A PSA nadir was achieved within 3 months for 85.1% of the treatments. In all cases, onset of riPSA was seen two days after HIFU therapy, and the median magnitude was 23.69 ng/ml. A magnitude of >2 ng/ml was seen in 89.4% of cases. Univariate analysis revealed that patients with riPSA were associated with usage of hormonal therapy and the post-treatment PSA nadir level. Multivariate Cox regression analysis revealed that riPSA and the number of HIFU sessions were predictors of biochemical recurrence. A significant statistical association was found between the presence of riPSA and the risk of biochemical failure only in the low- and intermediate-risk group. Conclusion: Patients treated with HIFU who experience post-treatment riPSA may have an increased risk of biochemical recurrence, especially in non-high-risk patients. PMID:21603245

  20. The influence of stress, depression, and anxiety on PSA screening rates in a nationally-representative sample

    PubMed Central

    Kotwal, Ashwin A.; Schumm, Phil; Mohile, Supriya G.; Dale, William

    2012-01-01

    Background Prostate-specific antigen (PSA) testing for prostate cancer (PCa) is controversial, with concerning rates of both over- and under-screening. The reasons for the observed rates of screening are unknown, and few studies have examined the relationship of psychological health to PSA screening rates. Understanding this relationship can help guide interventions to improve informed-decision making (IDM) for screening. Methods A nationally-representative sample of men 57–85 years old without PCa (N=1,169) from the National Social life, Health and Aging Project (NSHAP) was analyzed. The independent relationship of validated psychological health scales measuring stress, anxiety, and depression to PSA testing rates was assessed using multvariable logistic regression analyses. Results PSA screening rates were significantly lower for men with higher perceived stress (OR=0.76, p=0.006), but not for higher depressive symptoms (OR=0.89, p=0.22) when accounting for stress. Anxiety influences PSA screening through an interaction with number of doctor visits (p=0.02). Among the men who visited the doctor 1 time, those with higher anxiety were less likely to be screened (OR=0.65, p=0.04). Conversely, among those who visited the doctor 10+ times with higher anxiety were more likely to be screened (OR=1.71, p=0.04). Conclusions Perceived stress significantly lowers PSA screening likelihood, and it appears to partly mediate the negative relationship of depression with screening likelihood. Anxiety affects PSA screening rates differently for men with different numbers of doctor visits. Interventions to influence PSA screening rates should recognize the role of the patients’ psychological state to improve their likelihood of making informed decisions and improve screening appropriateness. PMID:22955835

  1. Characterization of the Glycosylation Site of Human PSA Prompted by Missense Mutation using LC-MS/MS.

    PubMed

    Song, Ehwang; Hu, Yunli; Hussein, Ahmed; Yu, Chuan-Yih; Tang, Haixu; Mechref, Yehia

    2015-07-02

    Prostate specific antigen (PSA) is currently used as a diagnostic biomarker for prostate cancer. It is a glycoprotein possessing a single glycosylation site at N69. During our previous study of PSA N69 glycosylation, additional glycopeptides were observed in the PSA sample that were not previously reported and did not match glycopeptides of impure glycoproteins existing in the sample. This extra glycosylation site of PSA is associated with a mutation in KLK3 genes. Among single nucleotide polymorphisms (SNPs) of KLKs families, the rs61752561 in KLK3 genes is an unusual missense mutation resulting in the conversion of D102 to N in PSA amino acid sequence. Accordingly, a new N-linked glycosylation site is created with an N102MS motif. Here we report the first qualitative and quantitative glycoproteomic study of PSA N102 glycosylation site by LC-MS/MS. We successfully applied tandem MS to verify the amino acid sequence possessing N102 glycosylation site and associated glycoforms of PSA samples acquired from different suppliers. Among the three PSA samples, HexNAc2Hex5 was the predominant glycoform at N102, while HexNAc4Hex5Fuc1NeuAc1 or HexNAc4Hex5Fuc1NeuAc2 was the primary glycoforms at N69. D102 is the first amino acid of "kallikrein loop", which is close to a zinc-binding site and catalytic triad. The different glycosylation of N102 relative to N69 might be influenced by the close vicinity of N102 to these functional sites and steric hindrance.

  2. Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146-154 peptide.

    PubMed

    Perambakam, Supriya; Hallmeyer, Sigrun; Reddy, Samarth; Mahmud, Nadim; Bressler, Linda; DeChristopher, Phillip; Mahmud, Delores; Nunez, Rafael; Sosman, Jeffrey A; Peace, David J

    2006-09-01

    T cell immunotherapy of prostate cancer (CaP) offers the potential for less toxic, more effective outcomes. A clinical trial was conducted in 28 patients with locally advanced or metastatic CaP to determine whether an HLA-A2 binding epitope of prostate-specific antigen, PSA146-154 (PSA-peptide), can induce specific T cell immunity. Patients were vaccinated either by intradermal injection of PSA-peptide and GM-CSF or by intravenous administration of autologous dendritic cells pulsed with PSA-peptide at weeks 1, 4 and 10. Delayed-type hypersensitivity (DTH) skin testing was performed at weeks 4, 14, 26 and 52. Fifty percent of the patients developed positive DTH responses to PSA-peptide. The size of the DTH induration progressively increased over time in the majority of responding patients. Skin biopsies from seven DTH-positive patients were available and T cells that developed in situ were also characterized. The phenotype of recovered T cells demonstrated variable proportions of CD4+CD8-, CD4-CD8+ and CD4+CD8+ T cell populations. Cytokine analysis of PSA-peptide stimulated T cells per bead array assay exhibited specific IFN-gamma and TNF-alpha response in six of seven patients. Specific IL-4 response was observed in five patients, while IL-10 response was detected in one patient. Purified CD4-CD8+ T cells isolated from four patients demonstrated specific cytolytic activity per chromium release assay. In conclusion, immunization with PSA-peptide induced specific T cell immunity in one-half of the patients with locally advanced and hormone-sensitive, metastatic CaP. DTH-derived T cells exhibited PSA-peptide-specific cytolytic activity and predominantly expressed a type-1 cytokine profile.

  3. [Validity of PSA density of the transition zone in the diagnosis of prostate cancer].

    PubMed

    Anastasi, G; Magno, C; Carmignani, A; Inferrera, A; Petrelli, A; Broccio, G

    2000-12-01

    One hundred four patients (mean age 70.6 years) with prostatic specific antigen (PSA) values between 4 and 10 ng/ml (average 7.9 ng/ml), and with no suspects for neoplasia by digital rectal examination (DRE) and transrectal ultrasound (TRUS) were studied. In all patients PSA density for the entire prostate (PSAD) and PSA density for the transition zone (PSAT) were calculated. TRUS was performed using a 5 MHz probe. Prostate and transition zone volumes were obtained by ellipsoid formula. Aim of the study was to evaluate the PSAT predictivity for prostate cancer compared to the PSAD. Sixteen out of 104 patients (15.4%) had histologically confirmed prostate cancer, and 88 (84.6%) had benign prostatic hyperplasia. When cut-off for PSAD was 0.15 ng/ml/cc, specificity and sensitivity were respectively 75% and 68% with positive and negative predictive values of 54% and 17%; when cut-off for PSAT was 0.34% ng/ml/cc, sensitivity and specificity were respectively 100% and 68% with positive and negative predictive values of 60% and 18%. Our results, according to the literature data, suggest that PSAT seems to have a higher predictivity for prostate cancer than PSAD, providing an optimization for the employ of prostatic biopsy, especially for those patients with PSA values between 4 and 10 ng/ml.

  4. Flavonoids can block PSA production by breast and prostate cancer cell lines.

    PubMed

    Rosenberg Zand, Rachel S; Jenkins, David J A; Brown, Theodore J; Diamandis, Eleftherios P

    2002-03-01

    Prostatic carcinoma is the most commonly diagnosed cancer and the second leading cause of cancer death of North American men. Combined androgen blockade (CAB) is one treatment option for prostate cancer, using estrogen agonists, luteinizing hormone-releasing hormone (LHRH) agonists and non-steroidal anti-androgens such as nilutamide and cyproterone acetate. Since many of these drugs have serious side effects, many patients are searching for "natural" alternatives or complements to traditional therapy. These include phytoestrogens found in soy and other plant foods. Such compounds have only started to be evaluated for potential androgen-blocking activity. Inhibition of production of androgen-regulated proteins, including prostate-specific antigen (PSA), is one indicator of androgen blocking. The ability of 72 flavonoids and related compounds to inhibit PSA production in a breast cancer cell line, BT-474, and a prostate cancer cell line (PC-3), transfected with the human androgen receptor cDNA, PC-3(AR)(2) was examined. Twenty-two of the 72 flavonoids tested were found to significantly block PSA production by the BT-474 cell line at the highest tested concentration (10(-5) mol/l), with 17 of these compounds inhibiting production of PSA in the PC-3(AR)(2) cells as well. That several flavonoids may significantly block production of this androgen-regulated protein. It will be worthwhile to examine these compounds as possible candidates for prostate cancer prevention or management.

  5. A Microfluidic Love-Wave Biosensing Device for PSA Detection Based on an Aptamer Beacon Probe.

    PubMed

    Zhang, Feng; Li, Shuangming; Cao, Kang; Wang, Pengjuan; Su, Yan; Zhu, Xinhua; Wan, Ying

    2015-06-11

    A label-free and selective aptamer beacon-based Love-wave biosensing device was developed for prostate specific antigen (PSA) detection. The device consists of the following parts: LiTaO3 substrate with SiO2 film as wave guide layer, two set of inter-digital transducers (IDT), gold film for immobilization of the biorecongniton layer and a polydimethylsiloxane (PDMS) microfluidic channels. DNA aptamer, or "artificial antibody", was used as the specific biorecognition probe for PSA capture. Some nucleotides were added to the 3'-end of the aptamer to form a duplex with the 3'-end, turning the aptamer into an aptamer-beacon. Taking advantage of the selective target-induced assembly changes arising from the "aptamer beacon", highly selective and specific detection of PSA was achieved. Furthermore, PDMS microfluidic channels were designed and fabricated to realize automated quantitative sample injection. After optimization of the experimental conditions, the established device showed good performance for PSA detection between 10 ng/mL to 1 μg/mL, with a detection limit of 10 ng/mL. The proposed sensor might be a promising alternative for point of care diagnostics.

  6. Quantifying the role of PSA screening in the US prostate cancer mortality decline

    PubMed Central

    Tsodikov, Alex; Mariotto, Angela; Szabo, Aniko; Falcon, Seth; Wegelin, Jake; diTommaso, Dante; Karnofski, Kent; Gulati, Roman; Penson, David F.; Feuer, Eric

    2010-01-01

    Objective To quantify the plausible contribution of prostate-specific antigen (PSA) screening to the nearly 30% decline in the US prostate cancer mortality rate observed during the 1990s. Methods Two mathematical modeling teams of the US National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network independently projected disease mortality in the absence and presence of PSA screening. Both teams relied on Surveillance, Epidemiology, and End Results (SEER) registry data for disease incidence, used common estimates of PSA screening rates, and assumed that screening, by shifting disease from distant to local-regional clinical stage, confers a corresponding improvement in disease-specific survival. Results The teams projected similar mortality increases in the absence of screening and decreases in the presence of screening after 1985. By 2000, the models projected that 45% (Fred Hutchinson Cancer Research Center) to 70% (University of Michigan) of the observed decline in prostate cancer mortality could be plausibly attributed to the stage shift induced by screening. Conclusions PSA screening may account for much, but not all, of the observed drop in prostate cancer mortality. Other factors, such as changing treatment practices, may also have played a role in improving prostate cancer outcomes. PMID:18027095

  7. Isotope and Patient Age Predict for PSA Spikes After Permanent Prostate Brachytherapy

    SciTech Connect

    Bostancic, Chelsea; Merrick, Gregory S. . E-mail: gmerrick@urologicresearchinstitute.org; Butler, Wayne M.; Wallner, Kent E.; Allen, Zachariah; Galbreath, Robert; Lief, Jonathan; Gutman, Sarah E.

    2007-08-01

    Purpose: To evaluate prostate-specific antigen (PSA) spikes after permanent prostate brachytherapy in low-risk patients. Methods and Materials: The study population consisted of 164 prostate cancer patients who were part of a prospective randomized trial comparing {sup 103}Pd and {sup 125}I for low-risk disease. Of the 164 patients, 61 (37.2%) received short-course androgen deprivation therapy. The median follow-up was 5.4 years. On average, 11.1 post-treatment PSA measurements were obtained per patient. Biochemical disease-free survival was defined as a PSA level of {<=}0.40 ng/mL after nadir. A PSA spike was defined as an increase of {>=}0.2 ng/mL, followed by a durable decline to prespike levels. Multiple parameters were evaluated as predictors for a PSA spike. Results: Of the 164 patients, 44 (26.9%) developed a PSA spike. Of the 46 hormone-naive {sup 125}I patients and 57 hormone-naive {sup 103}Pd patients, 21 (45.7%) and 8 (14.0%) developed a PSA spike. In the hormone-naive patients, the mean time between implantation and the spike was 22.6 months and 18.7 months for {sup 125}I and {sup 103}Pd, respectively. In patients receiving neoadjuvant androgen deprivation therapy, the incidence of spikes was comparable between isotopes ({sup 125}I 28.1% and {sup 103}Pd 20.7%). The incidence of spikes was substantially different in patients <65 years vs. {>=}65 years old (38.5% vs. 16.3%). On multivariate Cox regression analysis, patient age (p < 0.001) and isotope (p = 0.002) were significant predictors for spike. Conclusion: In low-risk prostate cancer, PSA spikes are most common in patients implanted with {sup 125}I and/or <65 years of age. Differences in isotope-related spikes are most pronounced in hormone-naive patients.

  8. Long-term follow-up of {sup 111}In-capromab pendetide (ProstaScint) scan as pretreatment assessment in patients who undergo salvage radiotherapy for rising prostate-specific antigen after radical prostatectomy for prostate cancer

    SciTech Connect

    Nagda, Suneel N. . E-mail: snagda@gmail.com; Mohideen, Najeeb; Lo, Simon S.; Khan, Usman B.S.; Dillehay, Gary; Wagner, Robert; Campbell, Steven; Flanigan, Robert

    2007-03-01

    Purpose: To evaluate the long-term failure patterns in patients who underwent an {sup 111}In-capromab pendetide (ProstaScint) scan as part of their pretreatment assessment for a rising prostate-specific antigen (PSA) level after prostatectomy and subsequently received local radiotherapy (RT) to the prostate bed. Methods: Fifty-eight patients were referred for evaluation of a rising PSA level after radical prostatectomy. All patients had negative findings for metastatic disease after abdominal/pelvis imaging with CT and isotope bone scans. All patients underwent a capromab pendetide scan, and the sites of uptake were noted. All patients were treated with local prostate bed RT (median dose 66.6 Gy). Results: Of the 58 patients, 20 had biochemical failure (post-RT PSA level >0.2 ng/mL or a rise to greater than the nadir PSA), including 6 patients with positive uptake outside the bed (positive elsewhere). The 4-year biochemical relapse-free survival (bRFS) rates for patients with negative (53%), positive in the prostate bed alone (45%), or positive elsewhere (74%) scan findings did not differ significantly (p = 0.51). The positive predictive value of the capromab pendetide scan in detecting disease outside the bed was 27%. The capromab pendetide scan status had no effect on bRFS. Those with a pre-RT PSA level of <1 ng/mL had improved bRFS (p = 0.003). Conclusion: The capromab pendetide scan has a low positive predictive value in patients with positive elsewhere uptake and the 4-year bRFS was similar to that for those who did not exhibit positive elsewhere uptake. Therefore, patients with a postprostatectomy rising PSA level should considered for local RT on the basis of clinicopathologic factors.

  9. Prostate-specific antigen bounce after curative brachytherapy for early-stage prostate cancer: A study of 274 African-Caribbean patients.

    PubMed

    Leduc, N; Atallah, V; Creoff, M; Rabia, N; Taouil, T; Escarmant, P; Vinh-Hung, V

    2015-01-01

    Prostate cancer incidence in the African-Caribbean population ranks among the highest worldwide. We aim to evaluate the prostate-specific antigen (PSA) kinetics after brachytherapy, which so far remains unknown in this population. From 2005 to 2013, 371 patients received (125)I brachytherapy of 145 Gy for early-stage prostate cancer. Eligibility criteria were cTNM ≤T2c, Gleason score ≤7, and initial PSA ≤15 ng/mL. Pretreatment androgen deprivation therapy was allowed. PSA bounce was defined as an increase of ≥0.4 ng/mL, lasting ≥6 months, followed by a decrease without any anticancer therapy. We examined PSA kinetics during followup. For the 274 patients with at least 24 months followup, median age was 62 years old (range, 45-76). Initial PSA was <10 ng/mL in 244 and 10-15 ng/mL in 30 patients; 40 received androgen deprivation therapy. With a median followup of 50 months (range, 24-125), PSA declined continuously in 168 (61%) patients, bounced in 87 (31%), and initially declined and then rose in 22 (8%) patients. Among these latter patients, 18 presented clinical recurrence. Mean bounce intensity was 2.0 ng/mL (median, 1.2; range, 0.4-12.4). Bounces occurred in average 12 months after brachytherapy. Patients with bounce were significantly younger: mean age 59 vs. 63 years old in patients without bounce, p <0.001. Bounce was also significantly associated with the immediate post-brachytherapy PSA, mean 4.0 among bounce cases vs. 2.9 among non-bounce cases, p < 0.001. Bounce was not associated with recurrence. PSA bounce in our African-Caribbean population seemed earlier and was more intense than described in other populations. Early increase of PSA should not be ascribed to treatment failure. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  10. Serum concentrations of prostate-specific antigen after diagnostic procedures and transurethral microwave thermotherapy of benign prostatic hyperplasia.

    PubMed

    Daehlin, L; Frugård, J; Farstad, M

    1996-05-01

    The objective was to study the effects of diagnostic and therapeutic procedures on serum prostate-specific antigen (PSA) concentration. Urethrocystoscopy in combination with digital rectal examination was followed by a moderate increase of serum PSA for 7-10 days. At 1 day after transurethral microwave thermotherapy (TUMT), an acute and pronounced effect on PSA was observed, which returned to baseline level after 4 weeks. The initial rise in serum PSA corresponded to a PSA density of 1.11, compared to 0.07 at baseline. The present data should be taken into consideration in conjunction with endoscopic evaluation of the lower urinary tract. Additionally, the acute effect on PSA after TUMT strongly suggests the ability of thermotherapy to induce cellular injury and death. One-year follow-up, however, was associated with increased PSA levels, indicating that only a minor part of the PSA-producing compartment was lost in the acute phase.

  11. Stability of total and free prostate specific antigen in serum submitted to intermittent cold storage conditions.

    PubMed

    El Ezzi, Asmahan A; El-Saidi, Mohammed A

    2009-04-01

    The goal of this study was to determine the stability of Total Prostrate Specific antigen (PSA-T) and Free Prostrate Specific Antigen (PSA-F) in archival serum stored at 4°C and -20°C and subjected to temperature shift due to interruption in power supply. Our study showed that PSA-T was stable up to 285 days and PSA-F was stable for 158 days under these conditions. Since power supply interruption is an unavoidable problem in developing nations, our study has implication on the validity of measurement of PSA-T and PSA-F in serum that was not properly stored due to emergency situations and for certain types of retrospective studies.

  12. Ultrasensitive electrochemical immunosensor for PSA biomarker detection in prostate cancer cells using gold nanoparticles/PAMAM dendrimer loaded with enzyme linked aptamer as integrated triple signal amplification strategy.

    PubMed

    Kavosi, Begard; Salimi, Abdollah; Hallaj, Rahman; Moradi, Fathollah

    2015-12-15

    In the present study, a triple signal amplification strategy was developed for ultrasensitive immunosensing of prostate-specific antigen (PSA) tumor marker. The proposed system was achieved by modification of glassy carbon electrode with graphene oxide/chitosan film and covalently attached of monoclonal PSA antibody and thionine as redox probe onto the modified electrode surface. Then, immunosensing was completed using sandwich-type immunoreaction of the PSA-antigen between anti-PSA immobilized on the graphene/chitosan interface and PSA-aptamer. For improve the sensitivity, polyamidoamine dendrimer-encapsulated gold nanoparticles (AuNPs-PAMAM) was used for covalent attachment of PSA-aptamer and HRP linked aptamer (Au-PAMA/aptamer-HRP) as electrochemical label in the sandwich format and electrocatalytic reduction of H2O2 in the presence of enzymatically oxidized thionine was measured. Under optimized condition, the obtained detection limit and linear concentration range were 10 fg ml(-1)(S/N=3) and 0.1 pg ml(-1) to 90 ngml(-1) respectively, using differential pulse voltammetry as measuring technique. In addition, electrochemical impedance spectroscopy (EIS) was used as simple, rapid, low cost label free analytical technique for PSA measurement with detection limit of 5 pg ml(-1) at concentration range up to 35 ng ml(-1). Finally, the immunosensor is used to PSA detection in human serum and prostate tissue samples and the obtained result is well agreed with the values obtained by the standard ELISA method. The obtained results indicate the proposed immunosensor can be used for monitor the differences in PSA concentration in cancer tissue samples which holds great promise in clinical screening of cancer biomarkers. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Prospective Comparison of 18F-Fluoromethylcholine Versus 68Ga-PSMA PET/CT in Prostate Cancer Patients Who Have Rising PSA After Curative Treatment and Are Being Considered for Targeted Therapy.

    PubMed

    Morigi, Joshua J; Stricker, Phillip D; van Leeuwen, Pim J; Tang, Reuben; Ho, Bao; Nguyen, Quoc; Hruby, George; Fogarty, Gerald; Jagavkar, Raj; Kneebone, Andrew; Hickey, Adam; Fanti, Stefano; Tarlinton, Lisa; Emmett, Louise

    2015-08-01

    In prostate cancer with biochemical failure after therapy, current imaging techniques have a low detection rate at the prostate-specific antigen (PSA) levels at which targeted salvage therapy is effective. (11)C-choline and (18)F-fluoromethylcholine, though widely used, have poor sensitivity at low PSA levels. (68)Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga-N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid]) has shown promising results in retrospective trials. Our aim was to prospectively compare the detection rates of (68)Ga-PSMA versus (18)F-fluoromethylcholine PET/CT in men who were initially managed with radical prostatectomy, radiation treatment, or both and were being considered for targeted therapy. A sample of men with a rising PSA level after treatment, eligible for targeted treatment, was prospectively included. Patients on systemic treatment were excluded. (68)Ga-PSMA, (18)F-fluoromethylcholine PET/CT, and diagnostic CT were performed sequentially on all patients between January and April 2015, and the images were assessed by masked, experienced interpreters. The findings and their impact on management were documented, together with the results of histologic follow-up when feasible. In total, 38 patients were enrolled. Of these, 34 (89%) had undergone radical prostatectomy and 4 (11%) had undergone radiation treatment. Twelve (32%) had undergone salvage radiation treatment after primary radical prostatectomy. The mean PSA level was 1.74 ± 2.54 ng/mL. The scan results were positive in 26 patients (68%) and negative with both tracers in 12 patients (32%). Of the 26 positive scans, 14 (54%) were positive with (68)Ga-PSMA alone, 11 (42%) with both (18)F-fluoromethylcholine and (68)Ga-PSMA, and only 1 (4%) with (18)F-fluoromethylcholine alone. When PSA was below 0.5 ng/mL, the detection rate was 50% for (68)Ga-PSMA versus 12.5% for (18)F-fluoromethylcholine. When PSA was 0.5-2.0 ng/mL, the detection rate was 69% for (68)Ga-PSMA versus

  14. Potent and Selective Peptidyl Boronic Acid Inhibitors of the Serine Protease Prostate-Specific Antigen

    PubMed Central

    LeBeau, Aaron M.; Singh, Pratap; Isaacs, John T.; Denmeade, Samuel R.

    2012-01-01

    SUMMARY Prostate cancer cells produce high (microgram to milligram/milliliter) levels of the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active in the extracellular fluid surrounding prostate cancers but is found at 1,000- to 10,000-fold lower concentrations in the circulation, where it is inactivated due to binding to abundant serum protease inhibitors. The exclusive presence of high levels of active PSA within prostate cancer sites makes PSA an attractive candidate for targeted imaging and therapeutics. A synthetic approach based on a peptide substrate identified first peptide aldehyde and then boronic acid inhibitors of PSA. The best of these had the sequence Cbz-Ser-Ser-Lys-Leu-(boro)Leu, with a Ki for PSA of 65 nM. The inhibitor had a 60-fold higher Ki for chymotrypsin. A validated model of PSA’s catalytic site confirmed the critical interactions between the inhibitor and residues within the PSA enzyme. PMID:18635003

  15. Significance of preoperative PSA velocity in men with low serum PSA and normal DRE

    PubMed Central

    Makarov, Danil V.; Magheli, Ahmed; Zhao, Kevin; Humphreys, Elizabeth; Gonzalgo, Mark L.; Partin, Alan W.; Han, Misop

    2011-01-01

    Objectives A PSA velocity (PSAV) >0.35 ng/ml/year approximately 10–15 years prior to diagnosis is associated with a greater risk of lethal prostate cancer. Some have recommended that a PSAV >0.35 ng/ml/year should prompt a prostate biopsy in men with a low serum PSA (<4 ng/ml) and benign DRE. However, less is known about the utility of this PSAV cutpoint for the prediction of treatment outcomes among men undergoing radical prostatectomy (RP). Methods Between 1992 and 2007, 339 men underwent RP at our institution with a preoperative PSA <4 ng/ml, benign DRE, and multiple preoperative PSA measurements. PSAV was calculated by linear regression analysis using all PSA values within 18 months prior to diagnosis. Kaplan–Meier survival analysis was performed, and biochemical progression rates were compared between PSAV strata using the log-rank test. Results The preoperative PSAV was >0.35 ng/ml/year in 124 (36.6%) of 339 men. Although there were no significant differences in clinicopathological characteristics based upon PSAV, men with a PSAV >0.35 ng/ml/year were significantly more likely to experience biochemical progression after RP at a median follow-up of 4 years (P = 0.022). Conclusions In this low-risk population with a preoperative PSA <4 ng/ml and benign DRE, approximately 1/3 had a preoperative PSAV >0.35 ng/ml/year. Physicians should carefully monitor men with a preoperative PSA >0.35 ng/ml/year as they are at increased risk of biochemical progression following RP. PMID:21153643

  16. Anti-tumor effect of the alphavirus-based virus-like particle vector expressing prostate-specific antigen in a HLA-DR transgenic mouse model of prostate cancer.

    PubMed

    Riabov, V; Tretyakova, I; Alexander, R B; Pushko, P; Klyushnenkova, E N

    2015-10-05

    The goal of this study was to determine if an alphavirus-based vaccine encoding human Prostate-Specific Antigen (PSA) could generate an effective anti-tumor immune response in a stringent mouse model of prostate cancer. DR2bxPSA F1 male mice expressing human PSA and HLA-DRB1(*)1501 transgenes were vaccinated with virus-like particle vector encoding PSA (VLPV-PSA) followed by the challenge with Transgenic Adenocarcinoma of Mouse Prostate cells engineered to express PSA (TRAMP-PSA). PSA-specific cellular and humoral immune responses were measured before and after tumor challenge. PSA and CD8 reactivity in the tumors was detected by immunohistochemistry. Tumor growth was compared in vaccinated and control groups. We found that VLPV-PSA could infect mouse dendritic cells in vitro and induce a robust PSA-specific immune response in vivo. A substantial proportion of splenic CD8 T cells (19.6 ± 7.4%) produced IFNγ in response to the immunodominant peptide PSA(65-73). In the blood of vaccinated mice, 18.4 ± 4.1% of CD8 T cells were PSA-specific as determined by the staining with H-2D(b)/PSA(65-73) dextramers. VLPV-PSA vaccination also strongly stimulated production of IgG2a/b anti-PSA antibodies. Tumors in vaccinated mice showed low levels of PSA expression and significant CD8+ T cell infiltration. Tumor growth in VLPV-PSA vaccinated mice was significantly delayed at early time points (p=0.002, Gehan-Breslow test). Our data suggest that TC-83-based VLPV-PSA vaccine can efficiently overcome immune tolerance to PSA, mediate rapid clearance of PSA-expressing tumor cells and delay tumor growth. The VLPV-PSA vaccine will undergo further testing for the immunotherapy of prostate cancer.

  17. Intermittent androgen ablation in patients with biochemical failure after pelvic radiotherapy for localized prostate cancer

    SciTech Connect

    Cury, Fabio L.B.; Souhami, Luis . E-mail: luis.souhami@muhc.mcgill.ca; Rajan, Raghu; Tanguay, Simon; Gagnon, Bruno; Duclos, Marie; Shenouda, George; Faria, Sergio L.; David, Marc; Freeman, Carolyn R.

    2006-03-01

    Purpose: To assess the efficacy of intermittent androgen ablation (IAA) in patients with biochemical failure after radiotherapy for prostate cancer. Methods and Materials: Thirty-nine patients received a luteinizing hormone-releasing hormone analog every 2 months for a total of 4 doses. IAA was then discontinued if serum prostate-specific antigen (PSA) fell to a normal level with a castrate level of testosterone. Therapy was restarted when the serum PSA level reached {>=}10 ng/mL and was discontinued if hormone resistance or unacceptable toxicity occurred. Results: Median PSA was 9.1 ng/mL at the time of first IAA. The median time between the first and the second cycles was 20.1 months, decreasing to 15.5 months between the third and fourth cycles. Two patients discontinued the treatment because of severe hot flushes. Four patients developed hormone resistance. With a median follow-up of 56.4 months, 5-year survival is 92.3%. Three patients died of unrelated causes. The incidence of distant metastasis is 6.8%. Conclusions: The use of IAA seems to be a safe and effective treatment for patients with biochemical failure post radiotherapy and no evidence of metastatic disease. The use of IAA limits hormone-related side effects and health care costs without an apparent increase in the risk for the development of metastatic disease.

  18. Performance characteristics and relationship of PSA value/kinetics on carbon-11 acetate PET/CT imaging in biochemical relapse of prostate cancer

    PubMed Central

    Almeida, Fabio D; Yen, Chi-Kwan; Scholz, Mark C; Lam, Richard Y; Turner, Jeffrey; Bans, Larry L; Lipson, Robert

    2017-01-01

    An elevated serum prostate-specific antigen (PSA) level alone cannot distinguish between local-regional recurrences and distant metastases after treatment with curative intent. With available salvage treatments, it has become important to localize the site of recurrence. 11C-Acetate PET/CT was performed in patients with rising PSA, with statistical analysis of detection rates, sites/location of detection, PSA kinetics and comparison with other tracers (FDG and Choline). Correlation to biopsy, subsequent imaging and PSA response to focal treatment was also performed. 88% (637) of 721 11C-Acetate PET/CT scans performed were positive. There was a statistically significant difference in PSA values between the positive and negative scans (P < 0.001 for mean difference) with the percentage of positive scans and PSA having a positive correlation. A PSA of 1.09 ng/mL was found to be an optimal cutoff. PSAdT was significantly correlated with a positive scan only when the PSA was < 1.0 ng/mL. For this subgroup, a PSAdT of < 3.8 months appeared significant (P < 0.05) as an optimal cutoff point. 11C-Acetate PET/CT demonstrates a high detection rate for the site of recurrence/metastasis in biochemical relapsed prostate cancer (88% overall detection rate, PPV 90.8%). This analysis suggests an optimal PSA threshold of > 1.09 ng/mL or a PSAdT of < 3.8 months when the PSA is below 1.0 ng/mL as independent predictors of positive findings. PMID:28123863

  19. Expression System Based on an MTIIa Promoter to Produce hPSA in Mammalian Cell Cultures

    PubMed Central

    Santos, Anderson K.; Parreira, Ricardo C.; Resende, Rodrigo R.

    2016-01-01

    Because of the limitations of standard culture techniques, the development of new recombinant protein expression systems with biotechnological potential is a key challenge. Ideally, such systems should be able to effectively and accurately synthesize a protein of interest with intrinsic metabolic capacity. Here, we describe such a system that was designed based on a plasmid vector containing promoter elements derived from the metallothionein MTIIa promoter, as well as processing and purification elements. This promoter can be induced by heavy metals in a culture medium to induce the synthesis of human prostate-specific antigen (hPSA), which has been modified to insert elements for purification, proteolysis, and secretion. We optimized hPSA production in this system by comparing the effects and contributions of ZnCl2, CdCl2, and CuSO4 in HEK293FT, HeLa, BHK-21, and CHO-K1 cells. We also compared the effectiveness of three different transfection agents: multi-walled carbon nanotubes, Lipofectamine 2000, and X-tremeGENE HP Reagent. hPSA production was confirmed via the detection of enhanced green fluorescent protein fluorescence, and cell viability was determined. The expression of hPSA was compared with that of the native protein produced by LNCaP cells, using enzyme-linked immunosorbent assay and sodium dodecyl sulfate polyacrylamide gel electrophoresis. X-tremeGENE reagent, the BHK-21 cell line, and CuSO4 showed the highest hPSA production rates. Furthermore, BHK-21 cells were more resistant to the oxidative stress caused by 100 μM CuSO4. These results suggest that the proposed optimized inducible expression system can effectively produce recombinant proteins with desired characteristics for a wide range of applications in molecular biology. PMID:27582737

  20. Evaluation of a rapid quantitative determination method of PSA concentration with gold immunochromatographic strips.

    PubMed

    Wu, Cheng-Ching; Lin, Hung-Yu; Wang, Chao-Ping; Lu, Li-Fen; Yu, Teng-Hung; Hung, Wei-Chin; Houng, Jer-Yiing; Chung, Fu-Mei; Lee, Yau-Jiunn; Hu, Jin-Jia

    2015-11-03

    Prostate cancer remains the most common cancer in men. Qualitative or semi-quantitative immunochromatographic measurements of prostate specific antigen (PSA) have been shown to be simple, noninvasive and feasible. The aim of this study was to evaluate an optimized gold immunochromatographic strip device for the detection of PSA, in which the results can be analysed using a Chromogenic Rapid Test Reader to quantitatively assess the test results. This reader measures the reflectance of the signal line via a charge-coupled device camera. For quantitative analysis, PSA concentration was computed via a calibration equation. Capillary blood samples from 305 men were evaluated, and two independent observers interpreted the test results after 12 min. Blood samples were also collected and tested with a conventional quantitative assay. Sensitivity, specificity, positive and negative predictive values, and accuracy of the PSA rapid quantitative test system were 100, 96.6, 89.5, 100, and 97.4 %, respectively. Reproducibility of the test was 99.2, and interobserver variation was 8 % with a false positive rate of 3.4 %. The correlation coefficient between the ordinary quantitative assay and the rapid quantitative test was 0.960. The PSA rapid quantitative test system provided results quickly and was easy to use, so that tests using this system can be easily performed at outpatient clinics or elsewhere. This system may also be useful for initial cancer screening and for point-of-care testing, because results can be obtained within 12 min and at a cost lower than that of conventional quantitative assays.

  1. Primary care physician PSA screening practices before and after the final U.S. Preventive Services Task Force recommendation.

    PubMed

    Cohn, Joshua A; Wang, Chihsiung E; Lakeman, Justin C; Silverstein, Jonathan C; Brendler, Charles B; Novakovic, Kristian R; McGuire, Michael S; Helfand, Brian T

    2014-01-01

    In May 2012, United States Preventive Services Task Force (USPSTF) finalized its recommendation against prostate-specific antigen (PSA) screening in all men. We aimed to assess trends in PSA screening frequency amongst primary care physicians (PCPs) surrounding the May 2012 USPSTF recommendation. The electronic data warehouse was used to identify men aged between 40 and 79 years with no history of prostate cancer or urology visit who were evaluated by an internal medicine or family practice physician between 2007 and 2012. Analyses were directed toward PSA testing within 6-month time period from June to November, with particular focus on the 2011 (pre-USPSTF recommendation) and 2012 (post-USPSTF recommendation) cohorts. The primary outcome measure was proportion of men with at least 1 PSA test during the 6-month pre- and post-USPSTF recommendation periods. A total of 112,221 men met inclusion criteria. There was a significant decrease in screening frequency between the 2011 and 2012 cohorts (8.6% vs. 7.6%, P = 0.0001; adjusted odds ratio 0.89, 95% confidence interval 0.83-0.95). This decrease was most evident amongst patients aged 40 to 49 years (5.6% vs. 4.6%, P = 0.004) and 70 to 79 years (7.9% vs. 6.2%, P = 0.01). A significant decrease was also observed in patients with highest previous PSA value<1.0 (P<0.0001) and 1.0 to 2.49 ng/ml (P = 0.0074). Since the USPSTF recommendation was finalized, there is evidence of continuing decreases in PSA testing by PCPs. PCPs may be shifting toward more selective screening practices, as decreases in screening are most pronounced in the youngest and oldest patients and in those with history of PSA values<2.5 ng/ml. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Statins and Metformin Use Is Associated with Lower PSA Levels in Prostate Cancer Patients Presenting for Radiation Therapy

    PubMed Central

    Liu, Xiaonan; Li, Jing; Schild, Steven E.; Schild, Michael H.; Wong, William; Vora, Sujay; Herman, Michael G.; Fatyga, Mirek

    2017-01-01

    Background A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy. Methods Three hundred and eighty one patients treated between the years of 2000-2005 and 2009-2012 were included in this retrospective study. The information about statin, metformin and alpha-blockers use was recorded immediately prior to treatment. Differences in PSA levels prior to treatment by medication status were estimated using univa-riate and multivariate linear regression on log PSA values. Results Compared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004). We did not observe statistically significant associations between the use of statins or metformin and cancer stage, National Comprehensive Cancer Network (NCCN) risk score, or therapy outcome. A statistically significant association between the NCCN risk score and the use of alpha-blockers was observed (p = 0.002). Conclusions We found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions. We found no statistically significant associations between the use of these medications and treatment outcomes. PMID:28239505

  3. Limited PSA testing in indigent men in South Texas: An appropriate care or missing a prevention opportunity?

    PubMed Central

    Liang, Yuanyuan; Du, Fei; Thompson, Ian M; Turner, Barbara J.

    2012-01-01

    Background No previous study has examined racial-ethnic differences in prostate specific antigen (PSA) testing and follow-up in primary care practices serving an indigent population. Methods From electronic medical records of primary care practices affiliated with one health care system in San Antonio, we identified 9,267 men aged 50–74 with 2+ clinic visits from 2008 through 2010 and no prior prostate cancer diagnosis. Logistic regression was used to examine the association of race-ethnicity with the use of PSA testing and, if tested, with an abnormal result (≥4 ng/mL) adjusted for demographics, health care and clinical factors. Time to a follow-up activity after an abnormal PSA was assessed using Cox proportional models. Results The race-ethnicity of this cohort was 63% Hispanic, 27% non-Hispanic White, 7% African-American, and 3% other. In a 3-year period, 26.8% of men had at least one PSA test. Compared with African-Americans, non-Hispanic Whites were less likely to be tested (OR=0.68; 95% CI:0.55,0.83) but Hispanics did not differ (OR=0.95; 95% CI:0.79,1.15). African-Americans were more likely to have an abnormal PSA than others (12.4% versus 5.2%, p<0.001) and the shortest adjusted time to follow-up (p=0.004). Conclusions In this 3-year indigent cohort, about one quarter had a PSA test, approximately half of the national testing rate. Impact African-Americans were more likely to be tested than non-Hispanic Whites but had more abnormal results, raising concerns about missed prevention opportunities. African-Americans with high PSA results had the shortest time until follow-up, reflecting awareness of the threat of prostate cancer for African-Americans by physicians. PMID:22822113

  4. Analysis of Serum Total and Free PSA Using Immunoaffinity Depletion Coupled to SRM: Correlation with Clinical Immunoassay Tests

    SciTech Connect

    Liu, Tao; Hossain, Mahmud; Schepmoes, Athena A.; Fillmore, Thomas L.; Sokoll, Lori J.; Kronewitter, Scott R.; Izmirlian, Grant; Shi, Tujin; Qian, Weijun; Leach, Robin; Thompson, Ian M.; Chan, Daniel W.; Smith, Richard D.; Kagan, Jacob; Srinivastava, Sudhir; Rodland, Karin D.; Camp, David G.

    2012-08-03

    Sandwich immunoassay is the standard technique used in clinical labs for quantifying protein biomarkers for disease detection, monitoring and therapeutic intervention. Albeit highly sensitive, the development of a specific immunoassay is rather time-consuming and associated with extremely high cost due to the requirement for paired immunoaffinity reagents of high specificity. Recently, mass spectrometry-based methods, specifically selected reaction monitoring mass spectrometry (SRM-MS), have been increasingly applied to measure low abundance biomarker candidates in tissue and biofluids, owing to high sensitivity and specificity, simplicity of assay configuration, and great multiplexing capability. In this study, we report for the first time the development of immunoaffinity depletion-based workflows and SRM-MS assays that enable sensitive and accurate quantification of total and free prostate-specific antigen (PSA) in serum without the requirement for specific PSA antibodies. With stable isotope dilution and external calibration, low ng/mL level detection of both total and free PSA was consistently achieved in both PSA-spiked female serum samples and actual patient serum samples. Moreover, comparison of the results obtained when SRM PSA assays and conventional immunoassays were applied to the same samples showed very good correlation (R2 values ranging from 0.90 to 0.99) in several independent clinical serum sample sets, including a set of 33 samples assayed in a blinded test. These results demonstrate that the workflows and SRM assays developed here provide an attractive alternative for reliably measuring total and free PSA in human blood. Furthermore, simultaneous measurement of free and total PSA and many other biomarkers can be performed in a single analysis using high-resolution liquid chromatographic separation coupled with SRM-MS.

  5. A large, benign prostatic cyst presented with an extremely high serum prostate-specific antigen level.

    PubMed

    Chen, Han-Kuang; Pemberton, Richard

    2016-01-08

    We report a case of a patient who presented with an extremely high serum prostate specific antigen (PSA) level and underwent radical prostatectomy for presumed prostate cancer. Surprisingly, the whole mount prostatectomy specimen showed only small volume, organ-confined prostate adenocarcinoma and a large, benign intraprostatic cyst, which was thought to be responsible for the PSA elevation. 2016 BMJ Publishing Group Ltd.

  6. Early detection of prostate cancer. Role of prostate-specific antigen.

    PubMed Central

    Prabhakaran, V. M.

    1996-01-01

    Pressure to request prostate-specific antigen (PSA) tests for early detection of prostate cancer in middle-aged and older men is increasing. However, current scientific data suggest that such testing does more harm than good. Most professional groups do not advise routine screening for prostate cancer. This paper reviews the current status of PSA testing. PMID:8653039

  7. Insulin promotes cell migration by regulating PSA-NCAM.

    PubMed

    Monzo, Hector J; Coppieters, Natacha; Park, Thomas I H; Dieriks, Birger V; Faull, Richard L M; Dragunow, Mike; Curtis, Maurice A

    2017-06-01

    Cellular interactions with the extracellular environment are modulated by cell surface polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM). PSA-NCAM is involved in cellular processes such as differentiation, plasticity, and migration, and is elevated in Alzheimer's disease as well as in metastatic tumour cells. Our previous work demonstrated that insulin enhances the abundance of cell surface PSA by inhibiting PSA-NCAM endocytosis. In the present study we have identified a mechanism for insulin-dependent inhibition of PSA-NCAM turnover affecting cell migration. Insulin enhanced the phosphorylation of the focal adhesion kinase leading to dissociation of αv-integrin/PSA-NCAM clusters, and promoted cell migration. Our results show that αv-integrin plays a key role in the PSA-NCAM turnover process. αv-integrin knockdown stopped PSA-NCAM from being endocytosed, and αv-integrin/PSA-NCAM clusters co-labelled intracellularly with Rab5, altogether indicating a role for αv-integrin as a carrier for PSA-NCAM during internalisation. Furthermore, inhibition of p-FAK caused dissociation of αv-integrin/PSA-NCAM clusters and counteracted the insulin-induced accumulation of PSA at the cell surface and cell migration was impaired. Our data reveal a functional association between the insulin/p-FAK-dependent regulation of PSA-NCAM turnover and cell migration through the extracellular matrix. Most importantly, they identify a novel mechanism for insulin-stimulated cell migration. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Antibodies to variant surface antigens of Plasmodium falciparum-infected erythrocytes are associated with protection from treatment failure and the development of anemia in pregnancy.

    PubMed

    Feng, Gaoqian; Aitken, Elizabeth; Yosaatmadja, Francisca; Kalilani, Linda; Meshnick, Steven R; Jaworowski, Anthony; Simpson, Julie A; Rogerson, Stephen J

    2009-07-15

    In pregnancy-associated malaria (PAM), Plasmodium falciparum-infected erythrocytes (IEs) express variant surface antigens (VSA-PAM) that evade existing immunity and mediate placental sequestration. Antibodies to VSA-PAM develop with gravidity and block placental adhesion or opsonize IEs for phagocytic clearance, helping to prevent maternal anemia and low birth weight in infants. Using serum samples from 141 pregnant Malawian women with parasitemia enrolled in a randomized trial of antimalarials and VSA-PAM-expressing CS2 IEs, we quantified levels of immunoglobulin (Ig) G to VSA-PAM by flow cytometry and levels of opsonizing antibodies by measuring uptake of IEs by THP1 promonocytes. After controlling for gravidity and antimalarial treatment, higher levels of IgG to VSA-PAM were associated with decreased anemia at delivery (odds ratio [OR], 0.66 [95% confidence interval {CI}, 0.46-0.93]; P = .018) and were weakly associated with decreased parasitological failure (OR, 0.78 [95% CI, 0.60-1.03]; P = .075), especially reinfection (OR, 0.73 [95% CI, 0.53-1.01]; P = .057). Higher levels of opsonizing antibodies to CS2 IEs were associated with less maternal anemia (OR, 0.31 [95% CI, 0.13-0.74]; P = .008) and treatment failure (OR, 0.48 [95% CI, 0.25-0.90]; P = .023), primarily because of recrudescent infection (OR, 0.49 [95% CI, 0.21-1.12]; P = .089). Higher levels of both IgG antibodies to VSA-PAM and opsonizing antibodies, a functional measure of immunity, correlate with parasite clearance and less anemia in pregnancy malaria.

  9. An Analytical Study of Prostate-Specific Antigen Dynamics

    PubMed Central

    Deliz, Giovanni; Rivera-Rodriguez, Jaileen; Laureano, Stephanie M.

    2016-01-01

    The purpose of this research is to carry out a quantitative study of prostate-specific antigen dynamics for patients with prostatic diseases, such as benign prostatic hyperplasia (BPH) and localized prostate cancer (LPC). The proposed PSA mathematical model was implemented using clinical data of 218 Japanese patients with histological proven BPH and 147 Japanese patients with LPC (stages T2a and T2b). For prostatic diseases (BPH and LPC) a nonlinear equation was obtained and solved in a close form to predict PSA progression with patients' age. The general solution describes PSA dynamics for patients with both diseases LPC and BPH. Particular solutions allow studying PSA dynamics for patients with BPH or LPC. Analytical solutions have been obtained and solved in a close form to develop nomograms for a better understanding of PSA dynamics in patients with BPH and LPC. This study may be useful to improve the diagnostic and prognosis of prostatic diseases. PMID:27956935

  10. Analysis of postoperative PSA changes after ultrasound-guided permanent [125I] seed implantation for the treatment of prostate cancer.

    PubMed

    Bian, X L; Wang, C Z; Wang, Y; Li, Y N; Zhang, L Z; Liu, L

    2015-06-29

    The aim of this study was to explore postoperative changes in prostate-specific antigen (PSA) levels and risk factors that influence the clinical effects of ultrasound-guided permanent [(125)I] seed implantation in the treatment of prostate cancer. From July 2009 to December 2012, 41 prostate cancer patients who underwent transrectal ultrasound-guided [(125)I] seed implantation were followed up for 3-56 months. The patients were divided into 2 groups according to their results: group A, benign rebound group, 31 cases; and group B, biochemical relapse group, 10 cases. A blood analysis of group A showed that the initial PSA rise after a nadir occurred postoperatively at 16.8 ± 1.2 months, and in 65.8% (27/41) patients the rise occurred during 15-27 weeks. For group B, the initial PSA rise after a nadir occurred postoperatively at 30.2 ± 2.1 months, and the difference in the time parameter of the initial PSA rise after the nadir was statistically significant between the 2 groups (P < 0.01). During treatment, age was shown to be a risk factor for group A (P = 0.0027, P < 0.01). Postoperative changes in PSA levels after ultrasound-guided permanent [(125)I] seed implantation contributed to the assessment of the clinical treatment effects.

  11. Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP)

    PubMed Central

    Turner, E L; Metcalfe, C; Donovan, J L; Noble, S; Sterne, J A C; Lane, J A; Avery, K N; Down, L; Walsh, E; Davis, M; Ben-Shlomo, Y; Oliver, S E; Evans, S; Brindle, P; Williams, N J; Hughes, L J; Hill, E M; Davies, C; Ng, S Y; Neal, D E; Hamdy, F C; Martin, R M

    2014-01-01

    Background: Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. Methods: Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50–69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. Results: Among randomised practices, 271 (68%) in the intervention arm (198 114 men) and 302 (78%) in the control arm (221 929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). Conclusions: The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening. PMID:24867688

  12. [Evaluation of (-2)proPSA in combination with total PSA and free PSA for the early detection of prostate cancer].

    PubMed

    Lamy, Pierre-Jean; Montels, Frédéric; Tosi, Diego; Leizour, Benoit; Bascoul-Mollevi, Caroline; Castan, Florence; Roques, Sylvie; Nielloud, Fabien; Rebillard, Xavier

    2013-01-01

    The analytical and clinical validation of new biomarkers for the early detection of prostate is necessary. (-2)proPSA, total PSA and free PSA values are used to calculate a standardized PHI index linked to a higher probability of a positive biopsy in patients with PSA levels between 3-4 and 10 ng/L, the gray zone for prostate cancer diagnosis. The purpose of this study is to validate the analytical performance of the (-2)proPSA and to determine the predictive value of PHI for the early detection of prostate cancer. Analytical performances are correct. It is not necessary to dilute samples before analysis. The stability of (-2)proPSA is good until at least 3 hours at room temperature before centrifugation. The study of the PSAT, PSAL, (-2)proPSA and PHI values in a population of patients consulting for an early prostate cancer diagnosis shows that the index PHI is the most powerful predictive marker of cancer with an area under ROC curve of 0.70, whereas it is only 0.56 for total PSA.

  13. Immune Responses to Novel Pneumococcal Proteins Pneumolysin, PspA, PsaA, and CbpA in Adenoidal B Cells from Children

    PubMed Central

    Zhang, Qibo; Choo, Sharon; Finn, Adam

    2002-01-01

    Studies of mice suggest that pneumococcal proteins, including PspA, pneumolysin, PsaA, and CbpA, are promising vaccine candidates. To determine whether these proteins are good mucosal immunogens in humans, adenoidal lymphocytes from 20 children who had adenoidectomies were isolated and tested by ELISpot for antigen-specific antibody-secreting cells (ASCs). Cells were also cultured for 7 days in the presence of a concentrated culture supernatant (CCS) from a type 14 strain of pneumococcus which contained secreted pneumococcal proteins, including PspA, pneumolysin, PsaA, and CbpA, and then tested by ELISpot. ELISpot assays done on freshly isolated cells detected ASCs to all four antigens in most children studied. However, there were differences both between antigens and between isotypes. The densities of immunoglobulin G (IgG) ASCs against both PsaA and CbpA were significantly higher than those of ASCs for PspA and PdB (pneumolysin toxoid B) (P < 0.001). For all antigens, the numbers of IgA ASCs tended to be lower than those of both IgG and IgM ASCs. The numbers of anti-CbpA and -PsaA IgA ASCs were higher than those of anti-PdB IgA ASCs (P < 0.01). Concentrations of IgA antibodies to PspA and PsaA in saliva correlated with the numbers of IgA ASCs to PspA and PsaA in freshly isolated adenoidal cells, but no such correlation was found between salivary IgG antibody concentrations and IgG ASCs to the four antigens in adenoidal cells. In cultured cells, anti-PspA, -PsaA, and -CbpA IgG ASCs proliferated significantly, but only two of eight samples showed >2-fold increases in anti-CbpA and -PspA IgA ASCs after CCS stimulation. The results suggest that CbpA, PsaA, and PspA may be good upper respiratory mucosal antigens in children. Adenoids may be important inductive sites for memory IgG responses and important sources of salivary IgA. Some protein antigens may also prime for mucosal IgA memory. These data support the effort to explore mucosal immunization against

  14. Comparative analysis of prostate-specific antigen by two-dimensional gel electrophoresis and capillary electrophoresis.

    PubMed

    Barrabés, Sílvia; Farina-Gomez, Noemi; Llop, Esther; Puerta, Angel; Diez-Masa, Jose Carlos; Perry, Antoinette; de Llorens, Rafael; de Frutos, Mercedes; Peracaula, Rosa

    2017-02-01

    Serum levels of Prostate-Specific Antigen (PSA) are not fully specific for prostate cancer (PCa) diagnosis and several efforts are focused on searching to improve PCa markers through the study of PSA subforms that could be cancer associated. We have previously reported by 2DE a decrease in the sialic acid content of PSA from PCa compared to benign prostatic hyperplasia patients based on the different proportion of the PSA spots. However, faster and more quantitative techniques, easier to automate than 2DE, are desirable. In this study, we examined the potential of CE for resolving PSA subforms in different samples and compared the results with those obtained by 2DE. We first fractionated by OFFGEL the subforms of PSA from seminal plasma according to their pIs and analyzed each separated fraction by 2DE and CE. We also analyzed PSA and high pI PSA, both from seminal plasma, and PSA from urine of a PCa patient. These samples with different PSA spots proportions by 2DE, due to different posttranslational modifications, also presented different CE profiles. This study shows that CE is a useful and complementary technique to 2DE for analyzing samples with different PSA subforms, which is of high clinical interest.

  15. [Carcinoembryonic antigen as a marker of proliferative diseases of the lymphatic system in patients with chronic renal failure--case report].

    PubMed

    Janas, Marzena; Niemczyk, Stanisław; Mazur, Stanisław

    2014-10-01

    In patients with CKD, anaemia mainly develops due to a decreased renal synthesis of erythropoietin. The anaemia, both normochromic and normocytic, becomes more severe as the glomerular filtration rate progressively decreases. Tumor markers are used to detect or monitor proliferative diseases. Carcinoembryonic antigen (CEA) is usually produced in the gastrointestinal tract, but its production is terminated before birth. The main application of this indicator is to monitor the treatment and the presence of metastases of colorectal cancer. We present a case of 86-year-old woman who was diagnosed with renal anaemia in stage 4 of chronic kidney disease (CKD), treated by periodic blood transfusions. This paper presents the difficulties in diagnosis and treatment of anemia with complex and different than renal origin anemia in patients with CKD. Patients require the detailed haematological diagnosis. Pointed out the usefulness of CEA in the diagnosis of lymphoma with co-existing renal failure. The use of erythropoietin in doses of nephrology allowed to avoid further blood transfusion.

  16. Carcinoembryonic antigen: assay following heat compared with perchloric acid extraction in patients with colon cancer, non-neoplastic gastrointestinal diseases, or chronic renal failure.

    PubMed

    Witherspoon, L R; Shuler, S E; Alyea, K; Husserl, F E

    1983-10-01

    Heat inactivation has been proposed as an alternative to perchloric acid (PCA) precipitation for the extraction of carcinoembryonic antigen (CEA) from human plasma. We examined a commercial RIA kit using heat inactivation, and compared results with those obtained with PCA precipitation. Adequate sensitivity (1.5 micrograms CEA/l plasma), satisfactory analytical recovery of CEA added to plasma, and dilutional linearity of samples found to have elevated CEA concentrations, were demonstrated for the heat-inactivation assay. Between-assay precision was better with the heat inactivation than with the PCA assay. Although the absolute concentration of CEA estimated after heat inactivation was consistently lower than that estimated after PCA extraction of plasma specimens, there was excellent correlation between results obtained with the two methods in colon cancer patients free of disease, colon cancer patients with residual or recurrent disease, patients with benign gastrointestinal disease, and in patients with chronic renal failure. We conclude that the heat-inactivation assay is an excellent alternative to the PCA assay.

  17. Luminescence energy transfer detection of PSA in red region based on Mn2+-enhanced NaYF4:Yb, Er upconversion nanorods.

    PubMed

    Zhang, Jianguo; Wang, Shaozhen; Gao, Ni; Feng, Dexiang; Wang, Lun; Chen, Hongqi

    2015-10-15

    A new turn-on luminescence energy transfer (LET) system has been designed for the detection of prostate specific antigen (PSA, a cancer marker) that utilizes Mn(2+)-enhanced long wavelength luminescence NaYF4:Yb, Er upconversion nanorods as the donor and gold nanorods as the acceptor. The Mn(2+)-doped NaYF4:Yb,Er upconversion luminescence nanorods with an emission peak located in the red region were synthesized. The presence of Mn(2+) markedly increased the luminescence intensity over that of the NaYF4:Yb, Er upconversion nanomaterials (excited by a 980 nm continuous wavelength laser). The surfaces of Mn(2+)-doped NaYF4:Yb, Er upconversion nanorods were modified with poly(acrylic acid). Antibodies against prostate specific antigen were bound to the surface of the carboxyl-functionalized upconversion nanorods, which acted as the energy donor in this LET system. Gold nanorods with an absorption band at ~666 nm were synthesized by the seed growth method, acted as the energy acceptor. The emission band of the upconversion nanorods overlapped well with the absorption band of the gold nanorods. The luminescence was quenched because of the electrostatic interactions that shortened the distance between the donor (negatively charged) and the accepter (positively charged).When the PSA antigen was added into the system, the energy acceptor and the energy donors were separated because the binding affinity between PSA and anti-PSA was greater than the electrostatic interactions, and thereby the luminescence was recovered. The linear range of detecting PSA was from 0.1172 to 18.75 ng/mL (R=0.995), with a limit of detection for PSA as low as 0.1129 ng/mL. The method was successfully applied to the sensing of PSA in human serum samples.

  18. Long-Term Follow-Up and Risk of Cancer Death After Radiation for Post-Prostatectomy Rising Prostate-Specific Antigen

    SciTech Connect

    Swanson, Gregory P.; Du, Fei; Michalek, Joel E.; Hermans, Michael

    2011-05-01

    Purpose: The results of salvage radiation therapy for rising prostate-specific antigen (PSA) levels after radical prostatectomy appear favorable, but the ultimate outcome is uncertain, given the relatively short follow-up in most studies. We report on a group of patients at a median follow-up of 13.9 years after salvage radiation therapy. Methods and Materials: From 1990 to 1995, 92 patients were referred postoperatively for radiation for a rising PSA level. PSA level at the time of referral ranged from 0.1 to 30.5 ng/ml (median, 1.5 ng/ml). The median time from surgery to radiation was 2.1 years (range,, 0.3-7.4 years). Radiation was directed to the prostatic fossa only with a median dose of 6,500 cGy (range, 6,000-7,000 cGy). Results: Eighty-five patients experienced a PSA drop after radiation, as predicted by Gleason score and PSA level at the start of radiation. Five- and 10-year biochemical failure free survival (BFFS) was 35% and 26%, respectively, and overall survival was 86% and 67%, respectively. Median survival was 12.0 years, and median BFF was 2.3 years. The presurgery PSA level was not predictive, but the PSA level at the start of radiation predicted a response. Patients with Gleason 8 to 9 cancers had a significantly higher progression rate than those with lower Gleason scores. There were no significant differences in outcomes based on pathology findings (none vs. positive margins vs. positive seminal vesicles). Overall, 22 (24%) patients died directly from prostate cancer, resulting in a 10-year cancer-specific survival rate of 82%. Multivariate analysis risk factors for dying of cancer were Gleason's score (8 to 9) and PSA at the start of radiation therapy (>1.0 ng/ml). Conclusions: Patients have a good response to salvage radiation therapy. A small but durable subgroup appears to have permanent control. In those for whom therapy fails, radiation delays the need for other salvage therapy, indicating at least a transient benefit to most patients.

  19. Elevated prostate-specific antigen: a case report and analysis.

    PubMed

    Hicks, R J

    1993-09-01

    Prostate cancer is a frequent concern of the clinician caring for older male patients. The certainty of arriving at the correct diagnosis is related to the presenting patient's risk for prostate cancer, the results of the digital rectal examination, and the value of the serum prostate-specific antigen (PSA). A case report of a patient with acute urinary retention and an elevated PSA is presented. Possible explanations for the elevated PSA are discussed. The clinician's intuitive thought process is compared with an analytic approach using calculated probabilities. Several factors that complicate the estimation of the likelihood of prostate cancer are discussed.

  20. 3D MR-Spectroscopic Imaging Assessment of Metabolic Activity in the Prostate During the PSA 'Bounce' Following {sup 125}Iodine Brachytherapy

    SciTech Connect

    Kirilova, Anna; Damyanovich, Andrei; Crook, Juanita; Jezioranski, John; Wallace, Kris; Pintilie, Melania

    2011-02-01

    Purpose: A temporary increase in prostate-specific antigen (PSA) values is observed in 30%-40% of men following {sup 125} I brachytherapy (BT) for prostate cancer. We present the results of a study to characterize prostate metabolic activity during the PSA 'bounce' and to correlate metabolic changes with PSA levels using three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI). Methods and Materials: 3D-MRSI was performed in 24 patients during the PSA bounce. Eight of these had also had a baseline 3D-MRSI scan before BT for the purpose of tumor mapping. The 3D-MRSI was repeated at 6- and 12-month intervals, and PSA levels were monitored every 3 months. Twenty-one of the patients had favorable-risk prostate cancer, and 3 had intermediate risk. Results: The choline+creatine signal intensity, although markedly reduced, was observable following BT. Diffuse activity not corresponding to original biopsy-positive sites was observed in 22 cases, and 2 cases were documented to have local recurrence. No statistically significant correlation between metabolic activity and PSA levels at each interval was found. Conclusion: Post-BT prostate 3D-MRSI shows evidence of diffuse metabolic activity unrelated to residual malignancy. This supports the benign nature of the PSA bounce and suggests an inflammatory etiology. In the situation of a rising PSA, observation of focal activity on MRI/3D-MRSI could be a useful adjunct to suggest local recurrence at an earlier interval after brachytherapy when prostate biopsies would still be unhelpful. Longer follow-up is necessary to confirm the complex relationship between metabolic activity and PSA levels.

  1. Prostate-Specific Antigen Bounce After Permanent Iodine-125 Prostate Brachytherapy-An Australian Analysis

    SciTech Connect

    Zwahlen, Daniel R.; Smith, Ryan; Andrianopoulos, Nick; Matheson, Bronwyn; Royce, Peter; Millar, Jeremy L.

    2011-01-01

    Purpose: To report on prostate-specific antigen (PSA) 'bounces' after {sup 125}I prostate brachytherapy to review the relationship to biochemical control and correlate both clinical and dosimetric variables. Methods and Materials: We analyzed 194 hormone-naive patients with a follow-up of {>=}3 years. Four bounce definitions were applied: an increase of {>=}0.2 ng/mL (definition I), {>=}0.4 ng/mL (definition II), {>=}15% (definition III), and {>=}35% (definition IV) of a previous value with spontaneous return to the prebounce level or lower. Results: Using definition I, II, III, and IV, a bounce was detected in 50%, 34%, 11%, and 9% of patients, respectively. The median time to onset was 14-16 months, the duration was 12-21.5 months, and the magnitude of the increase was 0.5-2 ng/mL. A magnitude of >2 ng/mL, fulfilling the criteria for biochemical failure (BF) according to the American Society for Therapeutic Radiology and Oncology Phoenix definition, was detected in 11.3%, 16.9%, 47.6%, and 50% using definitions I, II, III, and IV, respectively; 11 patients (5.7%) had true BF. The PSA bounces occurred earlier than BF (p < 0.001). The prediction of BF remains controversial and is probably unrelated to biochemical control. The only statistically significant factor predictive of a PSA bounce was younger age (definitions I and II). Conclusion: PSA bounces are common after brachytherapy. All definitions resulted in a high number of false-positive calls for BF during the first 2 years. The definition of an increase of {>=}0.2 ng/mL should be preferred because of the lowest number of false-positive results for BF. Patients experiencing a PSA bounce during the first 2 years after brachytherapy should undergo surveillance every 3-6 months. Additional investigations are recommended for elevated postimplant PSA levels that have not corrected by 3 years of follow-up.

  2. Enhanced immunogenicity of pneumococcal surface adhesin A (PsaA) in mice via fusion to recombinant human B lymphocyte stimulator (BLyS)

    PubMed Central

    2011-01-01

    Background B lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor superfamily of ligands that mediates its action through three known receptors. BLyS has been shown to enhance the production of antibodies against heterologous antigens when present at elevated concentrations, supporting an immunostimulatory role for BLyS in vivo. Methods We constructed a fusion protein consisting of human BLyS and Pneumococcal Surface Adhesin A (PsaA) and used this molecule to immunize mice. The immunostimulatory attributes mediated by BLyS in vivo were evaluated by characterizing immune responses directed against PsaA. Results The PsaA-BLyS fusion protein was able to act as a co-stimulant for murine spleen cell proliferation induced with F(ab')2 fragments of anti-IgM in vitro in a fashion similar to recombinant BLyS, and immunization of mice with the PsaA-BLyS fusion protein resulted in dramatically elevated serum antibodies specific for PsaA. Mice immunized with PsaA admixed with recombinant BLyS exhibited only modest elevations in PsaA-specific responses following two immunizations, while mice immunized twice with PsaA alone exhibited undetectable PsaA-specific serum antibody responses. Sera obtained from PsaA-BLyS immunized mice exhibited high titers of IgG1, IgG2a, IgG2b, and IgG3, but no IgA, while mice immunized with PsaA admixed with BLyS exhibited only elevated titers of IgG1 following two immunizations. Splenocytes from PsaA-BLyS immunized mice exhibited elevated levels of secretion of IL-2, IL-4 and IL-5, and a very modest but consistent elevation of IFN-γ following in vitro stimulation with PsaA. In contrast, mice immunized with either PsaA admixed with BLyS or PsaA alone exhibited modestly elevated to absent PsaA-specific recall responses for the same cytokines. Mice deficient for one of the three receptors for BLyS designated Transmembrane activator, calcium modulator, and cyclophilin ligand [CAML] interactor (TACI) exhibited attenuated Psa

  3. Enhanced immunogenicity of pneumococcal surface adhesin A (PsaA) in mice via fusion to recombinant human B lymphocyte stimulator (BLyS).

    PubMed

    Gor, Dennis O; Ding, Xuedong; Li, Qing; Sultana, Dilara; Mambula, Salamatu S; Bram, Richard J; Greenspan, Neil S

    2011-02-09

    B lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor superfamily of ligands that mediates its action through three known receptors. BLyS has been shown to enhance the production of antibodies against heterologous antigens when present at elevated concentrations, supporting an immunostimulatory role for BLyS in vivo. We constructed a fusion protein consisting of human BLyS and Pneumococcal Surface Adhesin A (PsaA) and used this molecule to immunize mice. The immunostimulatory attributes mediated by BLyS in vivo were evaluated by characterizing immune responses directed against PsaA. The PsaA-BLyS fusion protein was able to act as a co-stimulant for murine spleen cell proliferation induced with F(ab')₂ fragments of anti-IgM in vitro in a fashion similar to recombinant BLyS, and immunization of mice with the PsaA-BLyS fusion protein resulted in dramatically elevated serum antibodies specific for PsaA. Mice immunized with PsaA admixed with recombinant BLyS exhibited only modest elevations in PsaA-specific responses following two immunizations, while mice immunized twice with PsaA alone exhibited undetectable PsaA-specific serum antibody responses. Sera obtained from PsaA-BLyS immunized mice exhibited high titers of IgG1, IgG2a, IgG2b, and IgG3, but no IgA, while mice immunized with PsaA admixed with BLyS exhibited only elevated titers of IgG1 following two immunizations. Splenocytes from PsaA-BLyS immunized mice exhibited elevated levels of secretion of IL-2, IL-4 and IL-5, and a very modest but consistent elevation of IFN-γ following in vitro stimulation with PsaA. In contrast, mice immunized with either PsaA admixed with BLyS or PsaA alone exhibited modestly elevated to absent PsaA-specific recall responses for the same cytokines. Mice deficient for one of the three receptors for BLyS designated Transmembrane activator, calcium modulator, and cyclophilin ligand [CAML] interactor (TACI) exhibited attenuated PsaA-specific serum antibody responses

  4. Long-Term Outcome and Toxicity of Salvage Brachytherapy for Local Failure After Initial Radiotherapy for Prostate Cancer

    SciTech Connect

    Burri, Ryan J.; Stone, Nelson N.; Unger, Pam; Stock, Richard G.

    2010-08-01

    Purpose: To describe long-term outcomes and toxicity after salvage brachytherapy (BT) for local failure after initial radiotherapy for prostate cancer. Methods and Materials: Between 1994 and 2008, 37 men with local failure after initial prostate radiotherapy (32 external-beam radiation therapy [EBRT] and 5 BT) underwent salvage BT with {sup 103}Pd or {sup 125}I. Estimates of freedom from biochemical failure (FFbF, Phoenix definition) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Toxicities were graded using CTCv3.0. Results: Median follow-up was 86 months (range, 2-156). The median dose to 90% of the prostate volume was 122 Gy (range, 67-166). The 10-year FFbF and CSS were 54% and 96%, respectively. On univariate analysis, prostate-specific antigen (PSA) >10 ng/mL at initial diagnosis was significantly associated with FFbF (p = 0.01), and there were trends for both age <70 years (p = 0.08) and PSA <6 ng/mL (p = 0.08) at the time of salvage BT. On multivariate analysis, only presalvage PSA <6 ng/mL (p = 0.046) was significantly associated with improved FFbF. There were three Grade 3 toxicities and one Grade 4 toxicity. Pelvic lymph node dissection before salvage BT was the only variable significantly associated with Grade {>=}2 toxicity (p = 0.03). Conclusion: With a median follow-up of 86 months, salvage prostate BT was associated with a 10-year FFbF of 54% and CSS of 96%. Improved FFbF was associated with a presalvage PSA <6 ng/mL. Toxicity was worse in patients who had undergone pelvic lymph node dissection before salvage BT. Careful patient selection for salvage BT may result in improved outcomes and reduced toxicity.

  5. Complete PSA Remission without Adjuvant Therapy after Secondary Lymph Node Surgery in Selected Patients with Biochemical Relapse after Radical Prostatectomy and Pelvic Lymph Node Dissection

    PubMed Central

    Winter, Alexander; Uphoff, Jens; Henke, Rolf-Peter; Wawroschek, Friedhelm

    2012-01-01

    Introduction. To evaluate whether secondary resection of lymph node (LN) metastases (LNMs) can result in PSA remission, we analysed the PSA outcome after resection of LNM detected on PET/CT in patients with biochemical failure. Materials and Methods. 11 patients with PSA relapse (mean 3.02 ng/mL, range 0.5–9.55 ng/mL) after radical prostatectomy without adjuvant therapy were included. Suspicious LN (1–3) detected on choline PET/CT and nearby LN were openly dissected (09/04–02/11). The PSA development was examined. Histological and PET/CT findings were compared. Results. 9 of 10 patients with histologically confirmed LNM showed a PSA response. 4 of 9 patients with single LNM had a complete permanent PSA remission (mean followup 31.8, range 1–48 months). Of metastasis-suspicious LNs (14) 12 could be histologically confirmed. The additionally removed 25 LNs were all correctly negative. Conclusions. The complete PSA remissions after secondary resection of single LNM argue for a feasible therapeutic benefit without adjuvant therapy. For this purpose the choline PET/CT is in spite of its limitations currently the most reliable routinely available diagnostic tool. PMID:21754926

  6. [Differences in Prostatic Specific Antigen request patterns in Primary Care setting: A Pilot study in Spain].

    PubMed

    Salinas, María; López-Garrigós, Maite; Flores, Emilio; Uris, Joaquin; Leiva-Salinas, Carlos

    2015-01-01

    Despite the controversies on its use, Prostatic Specific Antigen (PSA) screening is widely applied in clinical practice, and the variability these different recommendations could produce in daily clinical practice is not profoundly assessed. The objective was to compare the inter-practice and inter-regional variability in total and free PSA (tPSA and fPSA) requests by General Practitioners (GPs). 76 laboratories covering a population of 17,679,195 inhabitants filled out the number of tPSA and fPSA requested by GPs during the year 2012. Test requests per 1,000 inhabitants and fPSA/tPSA request ratio were calculated. These variables were compared for the different hospitals according to their setting (urban, urban-rural or rural, location), and type of management (public/private). The tPSA requests necessary to comply with the recent guidelines from the European Association of Urology were calculated according to Spanish demographic characteristics in two possible scenarios depending on tPSA request: 2-4 years and 8 years interval. tPSA/1,000 inhabitants ranged from 8.2 to 92.7. It was significantly higher in rural areas and varied significantly among the different geographical areas. fPSA/1,000 inhabitants was higher in hospitals with private management. A total of 1,755,712 additional tPSA tests would have been necessary to follow guidelines in the first scenario and 112,129 in the second. National and regional policies are necessary to optimize the use of tPSA to detect an early prostate cancer.

  7. Half-life determination of serum free prostate-specific antigen following radical retropubic prostatectomy.

    PubMed

    Richardson, T D; Wojno, K J; Liang, L W; Giacherio, D A; England, B G; Henricks, W H; Schork, A; Oesterling, J E

    1996-12-01

    Prostate-specific antigen (PSA) continues to be the the most clinically useful tumor marker for prostate cancer. Recently, several molecular forms of PSA have been detected and characterized. These specific forms, including free PSA and PSA complexed to alpha 1-antichymotrypsin, can be measured and their proportions determined. In doing so, the sensitivity of PSA as a tumor marker can be maintained while the specificity is improved. In order to maximize the clinical utility of free PSA, the half-life and elimination kinetics of free PSA from the serum were determined. Twenty-five patients, ages 43-74 years (mean 60 years) with biopsy proven, organ-confined adenocarcinoma of the prostate who underwent anatomic radical retropubic prostatectomy, were identified. For each patient, venous blood samples were obtained preoperatively, and at 60-minute intervals beginning 1 hour after the prostate was removed. The specimens were handled and stored in a consistent fashion. Using the AxSYM immunoassay analyzer (Abbott Diagnostics, Abbott Park, IL), the serum free PSA values were determined and plotted as a function of time for each patient. From the 25 individual elimination curves that were generated, the half-life of serum free PSA was determined. The mean half-life of serum free PSA was 110 minutes +/- 18.6 minutes (SD). Analysis of the individual and cumulative elimination curves indicates that the elimination of free PSA from the serum following radical prostatectomy follows a biphasic pattern. Unlike PSA, which has a half life of 2-3 days, the half-life of serum free PSA is 110 minutes (1.83 hours). This short half-life may have significant implications for the use of percentage of free PSA as a clinically useful tool in distinguishing patients with early, curable prostate cancer from men with benign prostatic hyperplasia (BPH) only.

  8. Medical center characteristics associated with PSA screening in elderly veterans with limited life expectancy.

    PubMed

    So, Cynthia; Kirby, Katharine A; Mehta, Kala; Hoffman, Richard M; Powell, Adam A; Freedland, Stephen J; Sirovich, Brenda; Yano, Elizabeth M; Walter, Louise C

    2012-06-01

    Although guidelines recommend against prostate-specific antigen (PSA) screening in elderly men with limited life expectancy, screening is common. We sought to identify medical center characteristics associated with screening in this population. We conducted a prospective study of 622,262 screen-eligible men aged 70+ seen at 104 VA medical centers in 2003. Primary outcome was the percentage of men at each center who received PSA screening in 2003, based on VA data and Medicare claims. Men were stratified into life expectancy groups ranging from favorable (age 70-79 with Charlson score = 0) to limited (age 85+ with Charlson score ≥1 or age 70+ with Charlson score ≥4). Medical center characteristics were obtained from the 1999-2000 VA Survey of Primary Care Practices and publicly available VA data sources. Among 123,223 (20%) men with limited life expectancy, 45% received PSA screening in 2003. Across 104 VAs, the PSA screening rate among men with limited life expectancy ranged from 25-79% (median 43%). Higher screening was associated with the following center characteristics: no academic affiliation (50% vs. 43%, adjusted RR = 1.14, 95% CI 1.04-1.25), a ratio of midlevel providers to physicians ≥3:4 (55% vs. 45%, adjusted RR = 1.20, 95% CI 1.09-1.32) and location in the South (49% vs. 39% in the West, adjusted RR = 1.25, 95% CI 1.12-1.40). Use of incentives and high scores on performance measures were not independently associated with screening. Within centers, the percentages of men screened with limited and favorable life expectancies were highly correlated (r = 0.90). Substantial practice variation exists for PSA screening in older men with limited life expectancy across VAs. The high center-specific correlation of screening among men with limited and favorable life expectancies indicates that PSA screening is poorly targeted according to life expectancy.

  9. A three-gene panel on urine increases PSA specificity in the detection of prostate cancer.

    PubMed

    Rigau, Marina; Ortega, Israel; Mir, Maria Carmen; Ballesteros, Carlos; Garcia, Marta; Llauradó, Marta; Colás, Eva; Pedrola, Núria; Montes, Melania; Sequeiros, Tamara; Ertekin, Tugce; Majem, Blanca; Planas, Jacques; Ruiz, Anna; Abal, Miguel; Sánchez, Alex; Morote, Juan; Reventós, Jaume; Doll, Andreas

    2011-12-01

    Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic "gray zone" (4-10 ng/ml) on a target subset of 82 men with no prior biopsy. By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver-operating characteristic curve was 0.74 versus 0.82 in the diagnostic "gray zone." Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone. Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Copyright © 2011 Wiley Periodicals, Inc.

  10. ProPSA and Diagnostic Biopsy Tissue DNA Content Combination Improves Accuracy to Predict Need for Prostate Cancer Treatment Among Men Enrolled in an Active Surveillance Program

    PubMed Central

    Isharwal, Sumit; Makarov, Danil V.; Sokoll, Lori J.; Landis, Patricia; Marlow, Cameron; Epstein, Jonathan I.; Partin, Alan W.; Carter, H. Ballentine; Veltri, Robert W.

    2015-01-01

    OBJECTIVES To assess a novel application of the Prostate Health Index (phi) and biopsy tissue DNA content in benign-adjacent and cancer areas to predict which patients would eventually require treatment of prostate cancer in the Proactive Surveillance cohort. METHODS We identified 71 men who had had serum and biopsy tissue from their diagnosis banked and available for the present study. Of the 71 patients, 39 had developed unfavorable biopsy findings and 32 had maintained favorable biopsy status during surveillance. The serum total prostate-specific antigen (tPSA), free PSA (fPSA) and [−2]proPSA were measured using the Beckman Coulter immunoassay. The DNA content measurements of Feulgen-stained biopsy sections were performed using the AutoCyte imaging system. RESULTS The ratio of phi was significantly greater (37.23 ± 15.76 vs 30.60 ± 12.28; P = .03) in men who ultimately had unfavorable biopsy findings. The serum phi ratio (P = .003), [−2]proPSA/%fPSA (P = .004), biopsy tissue DNA content (ie, benign-adjacent excess of optical density, P = .019; and cancer area standard deviation of optical density, P = .002) were significant predictors of unfavorable biopsy conversion on Cox regression analysis. However, phi and [−2]proPSA/%fPSA showed a highly significant correlation (rho = 0.927, P < .0001) and no difference in accuracy (c-index, 0.6247 vs 0.6158; P = .704) for unfavorable biopsy conversion prediction. Furthermore, phi and [−2]proPSA/%fPSA remained significant (P = .047 and P = .036, respectively) in the multivariate models and, combined with the biopsy tissue DNA content, showed improvement in the predictive accuracy (c-index, 0.6908 and 0.6884, respectively) for unfavorable biopsy conversion. CONCLUSIONS The Prostate Health Index to proPSA/%fPSA, combined with biopsy tissue DNA content, improved the accuracy to about 70% to predict unfavorable biopsy conversion at the annual surveillance biopsy examination among men enrolled in an Active

  11. The routine use of prostate-specific antigen for early detection of cancer prostate in India: Is it justified?

    PubMed

    Dubey, Deepak

    2009-04-01

    The use of prostate-specific antigen (PSA) for early detection of prostate cancer is a widely debated issue. The average Indian urologist is faced with the dilemma of whether PSA testing should be routinely offered to men over 50 years of age. The Urological Society of India is yet to issue any guidelines on PSA testing. This article attempts to explore scientific evidence dealing with this controversial subject. A MEDLINE search was performed using the words 'PSA screening', 'prostate cancer statistics', and 'PSA screening guidelines'. The relevant articles were then analysed for evidence regarding the utility of PSA screening. Prostate cancer does not qualify to be categorized as a major health problem in India. The natural history of screen-detected cancer is not known. Prostate-specific antigen testing for early detection of prostate cancer has questionable benefits and has a potential to cause harm to asymptomatic individuals. There is no consensus amongst learned medical societies as to what should be the best approach for PSA testing. Most organizations caution against widespread PSA screening and emphasize on informed consent and patient counseling with regard to PSA testing. Randomized prospective trials are ongoing to assess to the true impact of screening on prostate cancer mortality. There is no scientific rationale to advocate routine use of PSA for early detection of prostate cancer in Indian males. Results of randomized screening trials are awaited to clarify on this issue.

  12. C-reactive protein haplotype is associated with high PSA as a marker of metastatic prostate cancer but not with overall cancer risk

    PubMed Central

    Eklund, C M; Tammela, T L J; Schleutker, J; Hurme, M

    2009-01-01

    Growing evidence points to a role for inflammation in prostate carcinogenesis. The significance of C-reactive protein (CRP), an inflammatory and innate immunity molecule, has not been evaluated thoroughly in prostate cancer (PC). In this study of 739 Finnish patients with PC and 760 healthy men, we evaluated the associations of CRP genotypes and haplotypes with total PC risk and PC progression, using prostate-specific antigen (PSA) as a marker of metastatic disease. Although the haplotype frequencies were similar in patients and controls, an association between haplotype ACCCA and patients' PSA levels was found. The carriers more often had a high PSA than non-carriers (P=0.0002) and the SNP rs2794521 A-allele and rs1800947 C-allele carriers had a higher PSA than non-carriers (P=0.009 and P=0.0004, respectively). A trend for a younger age at diagnosis was found among the carriers of ACCCA (P=0.07) and the rs1800947 C-allele (P=0.06), as well as a trend for the latter to have more likely metastases (P=0.06), but not after Bonferroni correction (α=0.00208). This is the first study to suggest association between PSA and CRP variants in PC and, therefore, further studies are warranted. CRP alleles previously found to protect against increased CRP levels are now suggested to be associated with metastatic PC, indicated by elevated PSA. PMID:19436291

  13. Age of the magnetically active WW Psa and TX Psa members of the β Pictoris association

    NASA Astrophysics Data System (ADS)

    Messina, S.; Santallo, R.; Tan, T. G.; Elliott, P.; Feiden, G. A.; Buccino, A.; Mauas, P.; Petrucci, R.; Jofré, E.

    2017-05-01

    Context. There are a variety of different techniques available to estimate the ages of pre-main-sequence stars. Components of physical pairs, thanks to their strict coevality and the mass difference, such as the binary system analyzed in this paper, are best suited to test the effectiveness of these different techniques. Aims: We consider the system WW Psa + TX Psa whose membership of the 25-Myr β Pictoris association has been well established by earlier works. We aim to investigate which age-dating technique provides the best agreement between the age of the system and that of the association. Methods: We have photometrically monitored WW Psa and TX Psa and measured their rotation periods as P = 2.37 d and P = 1.086 d, respectively. We have retrieved their Li equivalent widths from the literature and measured their effective temperatures and luminosities. We investigated whether the ages of these stars derived using three independent techniques, that is based on rotation, Li equivalent widths, and the position in the HR diagram are consistent with the age of the β Pictoris association. Results: We find that the rotation periods and the Li contents of both stars are consistent with the distribution of other bona fide members of the cluster. On the contrary, the isochronal fitting provides similar ages for both stars, but a factor of about four younger than the quoted age of the association, or about 30% younger when the effects of magnetic fields are included. Conclusions: We explore the origin of the discrepant age inferred from isochronal fitting, including the possibilities that either the two components may be unresolved binaries or that the basic stellar parameters of both components are altered by enhanced magnetic activity. The latter is found to be the more reasonable cause, suggesting that age estimates based on Li content are more reliable than isochronal fitting for pre-main-sequence stars with pronounced magnetic activity.

  14. [-2]proPSA versus ultrasensitive PSA fluctuations over time in the first year from radical prostatectomy, in an high-risk prostate cancer population: A first report.

    PubMed

    De Luca, S; Passera, R; Sottile, A; Fiori, C; Scarpa, R M; Porpiglia, F

    2016-03-24

    [-2]proPSA and its derivatives have an higher diagnostic accuracy than PSA in predicting prostate cancer (PCa). In alternative to PSA, ultrasensitive PSA (uPSA) and [-2]proPSA could be potentially useful in recurrent disease detection. This research focused on [-2]proPSA and uPSA fluctuations over time and their possible clinical and pathological determinants, in the first year after RP. A cohort of 106 consecutive patients, undergoing RP for high-risk prostate cancer (pT3/pT4 and/or positive margins), was enrolled. No patient received either preoperative/postoperative androgen deprivation therapy or immediate adjuvant RT, this latter for patient choice. [-2]proPSA and uPSA were measured at 1, 3, 6, 9, 12 months after RP; their trends over time were estimated by the mixed-effects linear model. The uPSA relapse was defined either as 3 rising uPSA values after nadir or 2 consecutive uPSA >0.2 ng/ml after RP. The biochemical recurrence (BCR) rate at 1 year after RP was either 38.6 % (in case of 3 rising uPSA values) or 34.9 % (in case of PSA >0.2 ng/ml after nadir), respectively. The main risk factors for uPSA fluctuations over time were PSA at diagnosis >8 ng/ml (p = 0.014), pT (p = 0.038) and pN staging (p = 0.001). In turn, PSA at diagnosis >8 ng/ml (p = 0.012) and pN (p < 0.001) were the main determinants for [-2]proPSA trend over time. In a 39 patients subgroup, uPSA decreased from month 1 to 3, while [-2]proPSA increased in 90 % of them; subsequently, both uPSA and [-2]proPSA increased in almost all cases. The [-2]proPSA trend over time was independent from BCR status either in the whole cohort as well in the 39 men subgroup. Both uPSA and [-2]proPSA had independent significant fluctuations over time. PSA at diagnosis >8 ng/ml and pathological staging significantly modified both these trends over time. Since BCR was not confirmed as determinant of [-2]proPSA fluctuations, its use as marker of early biochemical relapse may not be

  15. Can Urinary PCA3 Supplement PSA in the Early Detection of Prostate Cancer?

    PubMed Central

    Wei, John T.; Feng, Ziding; Partin, Alan W.; Brown, Elissa; Thompson, Ian; Sokoll, Lori; Chan, Daniel W.; Lotan, Yair; Kibel, Adam S.; Busby, J. Erik; Bidair, Mohamed; Lin, Daniel W.; Taneja, Samir S.; Viterbo, Rosalia; Joon, Aron Y.; Dahlgren, Jackie; Kagan, Jacob; Srivastava, Sudhir; Sanda, Martin G.

    2014-01-01

    Purpose Given the limited sensitivity and specificity of prostate-specific antigen (PSA), its widespread use as a screening tool has raised concerns for the overdiagnosis of low-risk and the underdiagnosis of high-grade prostate cancer. To improve early-detection biopsy decisions, the National Cancer Institute conducted a prospective validation trial to assess the diagnostic performance of the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate cancer among men screened with PSA. Patients and Methods In all, 859 men (mean age, 62 years) from 11 centers scheduled for a diagnostic prostate biopsy between December 2009 and June 2011 were enrolled. The primary outcomes were to assess whether PCA3 could improve the positive predictive value (PPV) for an initial biopsy (at a score > 60) and the negative predictive value (NPV) for a repeat biopsy (at a score < 20). Results For the detection of any cancer, PPV was 80% (95% CI, 72% to 86%) in the initial biopsy group, and NPV was 88% (95% CI, 81% to 93%) in the repeat biopsy group. The addition of PCA3 to individual risk estimation models (which included age, race/ethnicity, prior biopsy, PSA, and digital rectal examination) improved the stratification of cancer and of high-grade cancer. Conclusion These data independently support the role of PCA3 in reducing the burden of prostate biopsies among men undergoing a repeat prostate biopsy. For biopsy-naive patients, a high PCA3 score (> 60) significantly increases the probability that an initial prostate biopsy will identify cancer. PMID:25385735

  16. Molecular forms of prostate-specific antigen in the serum of women with benign and malignant breast diseases.

    PubMed Central

    Borchert, G. H.; Melegos, D. N.; Tomlinson, G.; Giai, M.; Roagna, R.; Ponzone, R.; Sgro, L.; Diamandis, E. P.

    1997-01-01

    Using a highly sensitive immunofluorometric procedure, we measured the total prostate-specific antigen (PSA) concentration in 632 sera obtained from female blood donors and women with idiopathic hirsutism, breast cancer or benign breast diseases. A total of 50 sera with total PSA > 15 ng l(-1) were fractionated by high-performance liquid chromatography (HPLC) in order to resolve the two immunoreactive molecular forms, i.e. free PSA (approximately 30 kDa) and PSA bound to alpha1-antichymotrypsin (PSA-ACT, 100 kDa). We found that breast cancer patients have presurgical serum total PSA levels similar to those of blood donors. Total serum PSA concentration decreases with age in women with idiopathic hirsutism, in cancer patients and in patients with benign breast diseases. The major molecular form of PSA in the serum of all normal and hirsute women (n = 15) is PSA bound to the proteinase inhibitor alpha1-antichymotrypsin. The major molecular form in 44% of presurgical cancer patient sera is free PSA. A total of 58% of benign breast disease patients also have in their serum mainly free PSA. We conclude that about half the patients with breast cancer or benign breast diseases have free PSA as the major molecular form in their serum, whereas patients without breast pathologies (normal blood donors, idiopathic hirsutism) have PSA bound to alpha1-antichymotrypsin as the major molecular form. The ratio of PSA/PSA-ACT may have value as a simple biochemical test for diagnosis of breast pathologies including breast cancer. PMID:9376271

  17. Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival.

    PubMed

    Facchini, Gaetano; Caffo, Orazio; Ortega, Cinzia; D'Aniello, Carmine; Di Napoli, Marilena; Cecere, Sabrina C; Della Pepa, Chiara; Crispo, Anna; Maines, Francesca; Ruatta, Fiorella; Iovane, Gelsomina; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Pignata, Sandro; Cavaliere, Carla

    2016-01-01

    Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting. We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least 1 week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics. We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median PFS was 5.5 months (4.6-6.5) and the median OS was 17.1 months (8.8-25.2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12-0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06-0.72, p = 0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days. A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS.

  18. A Community Jury on PSA screening: what do well-informed men want the government to do about prostate cancer screening--a qualitative analysis.

    PubMed

    Rychetnik, Lucie; Doust, Jenny; Thomas, Rae; Gardiner, Robert; Mackenzie, Geraldine; Glasziou, Paul

    2014-04-30

    Cancer screening policies and programmes should take account of public values and concerns. This study sought to determine the priorities, values and concerns of men who were 'fully informed' about the benefits and harms of prostate-specific antigen (PSA) screening; and empirically examine the value of a community jury in eliciting public values on PSA screening. Community jury was convened on the Gold Coast, Queensland (Australia) to consider PSA screening benefits and harms, and whether government campaigns on PSA screening should be conducted. 27 men (volunteers) aged 50-70 with no personal history of prostate cancer and willing to attend jury 6-7 April 2013: 12 were randomly allocated to jury (11 attended). A qualitative analysis was conducted of the jury deliberations (audio-recorded and transcribed) to elicit the jury's views and recommendations. A survey determined the impact of the jury process on participants' individual testing decisions compared with control group. The jury concluded governments should not invest in programmes focused on PSA screening directed at the public because the PSA test did not offer sufficient reassurance or benefit and could raise unnecessary alarm. It recommended an alternative programme to support general practitioners to provide patients with better quality and more consistent information about PSA screening. After the jury, participants were less likely to be tested in the future compared with the controls, but around half said they would still consider doing so. The jury's unanimous verdict about government programmes was notable in the light of their divergent views on whether or not they would be screened themselves in the future. Community juries provide valuable insights into the priorities and concerns of men weighing up the benefits and harms of PSA screening. It will be important to assess the degree to which the findings are generalisable to other settings.

  19. Longitudinal modeling of ultrasensitive and traditional prostate-specific antigen and prediction of biochemical recurrence after radical prostatectomy

    PubMed Central

    Laajala, Teemu D.; Seikkula, Heikki; sadat, Fatemeh Seyednasrollah; Mirtti, Tuomas; Boström, Peter J.; Elo, Laura L.

    2016-01-01

    Ultrasensitive prostate-specific antigen (u-PSA) remains controversial for follow-up after radical prostatectomy (RP). The aim of this study was to model PSA doubling times (PSADT) for predicting biochemical recurrence (BCR) and to capture possible discrepancies between u-PSA and traditional PSA (t-PSA) by utilizing advanced statistical modeling. 555 RP patients without neoadjuvant/adjuvant androgen deprivation from the Turku University Hospital were included in the study. BCR was defined as two consecutive PSA values >0.2 ng/mL and the PSA measurements were log2-transformed. One third of the data was reserved for independent validation. Models were first fitted to the post-surgery PSA measurements using cross-validation. Major trends were then captured using linear mixed-effect models and a predictive generalized linear model effectively identified early trends connected to BCR. The model generalized for BCR prediction to the validation set with ROC-AUC of 83.6% and 95.1% for the 1 and 3 year follow-up censoring, respectively. A web-based tool was developed to facilitate its use. Longitudinal trends of u-PSA did not display major discrepancies from those of t-PSA. The results support that u-PSA provides useful information for predicting BCR after RP. This can be beneficial to avoid unnecessary adjuvant treatments or to start them earlier for selected patients. PMID:27805011

  20. Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor-Modified T Cells After Failure of Ibrutinib.

    PubMed

    Turtle, Cameron J; Hay, Kevin A; Hanafi, Laïla-Aïcha; Li, Daniel; Cherian, Sindhu; Chen, Xueyan; Wood, Brent; Lozanski, Arletta; Byrd, John C; Heimfeld, Shelly; Riddell, Stanley R; Maloney, David G

    2017-09-10

    Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib. Methods Twenty-four patients with CLL received lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2 × 10(5), 2 × 10(6), or 2 × 10(7) CAR-T cells/kg). Nineteen patients experienced disease progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not experience progression while receiving ibrutinib. Six patients were venetoclax refractory, and 23 had a complex karyotype and/or 17p deletion. Results Four weeks after CAR-T cell infusion, the overall response rate (complete response [CR] and/or partial response [PR]) by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria was 71% (17 of 24). Twenty patients (83%) developed cytokine release syndrome, and eight (33%) developed neurotoxicity, which was reversible in all but one patient with a fatal outcome. Twenty of 24 patients received cyclophosphamide and fludarabine lymphodepletion and CD19 CAR-T cells at or below the maximum tolerated dose (≤ 2 × 10(6) CAR-T cells/kg). In 19 of these patients who were restaged, the overall response rate by IWCLL imaging criteria 4 weeks after infusion was 74% (CR, 4/19, 21%; PR, 10/19, 53%), and 15/17 patients (88%) with marrow disease before CAR-T cells had no disease by flow cytometry after CAR-T cells. Twelve of these patients underwent deep IGH sequencing, and seven (58%) had no malignant IGH sequences detected in marrow. Absence of the malignant IGH clone in marrow of patients with CLL who responded by IWCLL criteria was associated with 100% progression-free survival and overall survival (median 6.6 months follow-up) after CAR-T cell immunotherapy. The progression-free survival was similar in patients with lymph node PR or CR by IWCLL criteria. Conclusion CD19 CAR-T cells are highly

  1. Racial differences in PSA screening interval and stage at diagnosis

    PubMed Central

    Carpenter, William R.; Howard, Daniel L.; Taylor, Yhenneko J.; Ross, Louie E.; Wobker, Sara E.; Godley, Paul A.

    2010-01-01

    Objectives This study examined PSA screening interval of black and white men aged 65 or older and its association with prostate cancer stage at diagnosis. Methods SEER-Medicare data were examined for 18,067 black and white men diagnosed with prostate cancer between 1994 and 2002. Logistic regression was used to assess the association between race, PSA screening interval, and stage at diagnosis. Analysis also controlled for age, marital status, comorbidity, diagnosis year, geographic region, income, and receipt of surgery. Results Compared to whites, blacks diagnosed with prostate cancer were more likely to have had a longer PSA screening interval prior to diagnosis, including a greater likelihood of no pre-diagnosis use of PSA screening. Controlling for PSA screening interval was associated with a reduction in blacks’ relative odds of being diagnosed with advanced (stage III or IV) prostate cancer, to a point that the stage at diagnosis was not statistically different from that of whites (OR=1.12, 95% CI=0.98–1.29). Longer intra-PSA intervals were systematically associated with greater odds of diagnosis with advanced disease. Conclusions More frequent or systematic PSA screening may be a pathway to reducing racial differences in prostate cancer stage at diagnosis, and, by extension, mortality. PMID:20333462

  2. Minimally Informative Prior Distributions for PSA

    SciTech Connect

    Dana L. Kelly; Robert W. Youngblood; Kurt G. Vedros

    2010-06-01

    A salient feature of Bayesian inference is its ability to incorporate information from a variety of sources into the inference model, via the prior distribution (hereafter simply “the prior”). However, over-reliance on old information can lead to priors that dominate new data. Some analysts seek to avoid this by trying to work with a minimally informative prior distribution. Another reason for choosing a minimally informative prior is to avoid the often-voiced criticism of subjectivity in the choice of prior. Minimally informative priors fall into two broad classes: 1) so-called noninformative priors, which attempt to be completely objective, in that the posterior distribution is determined as completely as possible by the observed data, the most well known example in this class being the Jeffreys prior, and 2) priors that are diffuse over the region where the likelihood function is nonnegligible, but that incorporate some information about the parameters being estimated, such as a mean value. In this paper, we compare four approaches in the second class, with respect to their practical implications for Bayesian inference in Probabilistic Safety Assessment (PSA). The most commonly used such prior, the so-called constrained noninformative prior, is a special case of the maximum entropy prior. This is formulated as a conjugate distribution for the most commonly encountered aleatory models in PSA, and is correspondingly mathematically convenient; however, it has a relatively light tail and this can cause the posterior mean to be overly influenced by the prior in updates with sparse data. A more informative prior that is capable, in principle, of dealing more effectively with sparse data is a mixture of conjugate priors. A particular diffuse nonconjugate prior, the logistic-normal, is shown to behave similarly for some purposes. Finally, we review the so-called robust prior. Rather than relying on the mathematical abstraction of entropy, as does the constrained

  3. Efficacy of degarelix in prostate cancer patients following failure on luteinizing hormone-releasing hormone agonist treatment: results from an open-label, multicentre, uncontrolled, phase II trial (CS27)

    PubMed Central

    Simson, Gabriele; Goble, Sandra; Persson, Bo-Eric

    2015-01-01

    Objective: To evaluate the efficacy of second-line degarelix in patients with prostate cancer (PCa) after treatment failure with a luteinizing hormone-releasing hormone (LHRH) agonist. Methods: This 1-year exploratory, multicentre, open-label phase II trial was performed in 2 patient cohorts (Cohort 1, n = 25; Cohort 2, n = 12) in Germany. Patients with castrate-resistant PCa after primary hormonal treatment received degarelix 240 mg, followed by 11 monthly maintenance doses of 80 mg. The primary endpoint was the proportion of patients with decreasing/stable prostate-specific antigen (PSA) (relative change ⩽+10% of baseline PSA) after 3 months. Results: At Month 3, the response rate (intention-to-treat, last observation carried forward analysis) was 16.7% [95% confidence interval (CI): 4.74–37.38] in Cohort 1 and 33.3% (95% CI: 9.92–65.11) in Cohort 2. The probability of completing 12 months without PSA progression was 8.8% (95% CI: 1.51–24.3) in Cohort 1 and 8.3% (95% CI: 0.5–31.1) in Cohort 2. Degarelix was well tolerated; the most frequently reported adverse events were local injection-site reactions. Conclusions: In PCa patients who failed LHRH therapy, degarelix was well tolerated and achieved a limited PSA response. Phase III trials show that disease control benefits with degarelix versus agonists are more clearly demonstrated as first-line therapy. PMID:26161141

  4. Mutational analysis of photosystem I polypeptides in the cyanobacterium Synechocystis sp. PCC 6803. Targeted inactivation of psaI reveals the function of psaI in the structural organization of psaL

    NASA Technical Reports Server (NTRS)

    Xu, Q.; Hoppe, D.; Chitnis, V. P.; Odom, W. R.; Guikema, J. A.; Chitnis, P. R.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    We cloned, characterized, and inactivated the psaI gene encoding a 4-kDa hydrophobic subunit of photosystem I from the cyanobacterium Synechocystis sp. PCC 6803. The psaI gene is located 90 base pairs downstream from psaL, and is transcribed on 0.94- and 0.32-kilobase transcripts. To identify the function of PsaI, we generated a cyanobacterial strain in which psaI has been interrupted by a gene for chloramphenicol resistance. The wild-type and the mutant cells showed comparable rates of photoautotrophic growth at 25 degrees C. However, the mutant cells grew slower and contained less chlorophyll than the wild-type cells, when grown at 40 degrees C. The PsaI-less membranes from cells grown at either temperature showed a small decrease in NADP+ photoreduction rate when compared to the wild-type membranes. Inactivation of psaI led to an 80% decrease in the PsaL level in the photosynthetic membranes and to a complete loss of PsaL in the purified photosystem I preparations, but had little effect on the accumulation of other photosystem I subunits. Upon solubilization with nonionic detergents, photosystem I trimers could be obtained from the wild-type, but not from the PsaI-less membranes. The PsaI-less photosystem I monomers did not contain detectable levels of PsaL. Therefore, a structural interaction between PsaL and PsaI may stabilize the association of PsaL with the photosystem I core. PsaL in the wild-type and PsaI-less membranes showed equal resistance to removal by chaotropic agents. However, PsaL in the PsaI-less strain exhibited an increased susceptibility to proteolysis. From these data, we conclude that PsaI has a crucial role in aiding normal structural organization of PsaL within the photosystem I complex and the absence of PsaI alters PsaL organization, leading to a small, but physiologically significant, defect in photosystem I function.

  5. Mutational analysis of photosystem I polypeptides in the cyanobacterium Synechocystis sp. PCC 6803. Targeted inactivation of psaI reveals the function of psaI in the structural organization of psaL

    NASA Technical Reports Server (NTRS)

    Xu, Q.; Hoppe, D.; Chitnis, V. P.; Odom, W. R.; Guikema, J. A.; Chitnis, P. R.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    We cloned, characterized, and inactivated the psaI gene encoding a 4-kDa hydrophobic subunit of photosystem I from the cyanobacterium Synechocystis sp. PCC 6803. The psaI gene is located 90 base pairs downstream from psaL, and is transcribed on 0.94- and 0.32-kilobase transcripts. To identify the function of PsaI, we generated a cyanobacterial strain in which psaI has been interrupted by a gene for chloramphenicol resistance. The wild-type and the mutant cells showed comparable rates of photoautotrophic growth at 25 degrees C. However, the mutant cells grew slower and contained less chlorophyll than the wild-type cells, when grown at 40 degrees C. The PsaI-less membranes from cells grown at either temperature showed a small decrease in NADP+ photoreduction rate when compared to the wild-type membranes. Inactivation of psaI led to an 80% decrease in the PsaL level in the photosynthetic membranes and to a complete loss of PsaL in the purified photosystem I preparations, but had little effect on the accumulation of other photosystem I subunits. Upon solubilization with nonionic detergents, photosystem I trimers could be obtained from the wild-type, but not from the PsaI-less membranes. The PsaI-less photosystem I monomers did not contain detectable levels of PsaL. Therefore, a structural interaction between PsaL and PsaI may stabilize the association of PsaL with the photosystem I core. PsaL in the wild-type and PsaI-less membranes showed equal resistance to removal by chaotropic agents. However, PsaL in the PsaI-less strain exhibited an increased susceptibility to proteolysis. From these data, we conclude that PsaI has a crucial role in aiding normal structural organization of PsaL within the photosystem I complex and the absence of PsaI alters PsaL organization, leading to a small, but physiologically significant, defect in photosystem I function.

  6. The impact of hypoxemia on serum total and free prostate-specific antigen levels in patients with chronic obstructive pulmonary disease.

    PubMed

    Ozge, Cengiz; Bozlu, Murat; Ozgur, Eylem Sercan; Tek, Mesut; Tunckiran, Ahmet; Muslu, Necati; Ilvan, Ahmet

    2015-05-01

    Prostate-specific antigen (PSA) is the most important biochemical marker in the diagnosis and follow-up of patients with prostate cancer. In recent years, a relationship between PSA levels and hypoxic conditions has been described. However, no study has investigated the PSA levels in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the impact of hypoxemia on serum total (tPSA) and free PSA (fPSA) levels in patients with COPD. Between January 2010 and January 2014, 95 male patients who hospitalized for acute exacerbations of COPD and 80 control subjects were enrolled in the study. Serum tPSA and fPSA levels and f/tPSA ratios were determined in all patients on the first day of hospitalization (exacerbation) and 7 days after the treatment (stable state). Statistical analysis included paired t test and Mann-Whitney U test. No statistically significant differences were found between COPD and control groups with regard to the baseline characteristics, except for smoking status. The levels of serum tPSA and fPSA during exacerbation of COPD were significantly higher than the levels of the stable period (p < 0.01), whereas f/tPSA ratio did not change (p > 0.05). Hypoxemia during acute exacerbation of COPD can cause a rise in serum tPSA and fPSA levels, but f/tPSA ratio is not affected. Acute exacerbation of COPD may be added to list of the events in which PSA measurements must be interpreted with caution.

  7. Age and total and free prostate-specific antigen levels for predicting prostate volume in patients with benign prostatic hyperplasia.

    PubMed

    Coban, Soner; Doluoglu, Omer Gokhan; Keles, Ibrahim; Demirci, Hakan; Turkoglu, Ali Riza; Guzelsoy, Muhammet; Karalar, Mustafa; Demirbas, Murat

    2016-06-01

    To investigate the predictive values of free prostate-specific antigen (fPSA), total PSA (tPSA) and age on the prostate volume. The data of 2148 patients with lower urinary tract symptoms were analyzed retrospectively. The patients who had transrectal ultrasonography guided 10 core biopsies owing to the findings obtained on digital rectal examination and presence of high PSA levels (PSA = 2.5-10 ng/dl), and proven to have BPH histopathologically were included in the study. Age, tPSA, fPSA and the prostate volumes (PV) of the patients were noted. One thousand patients that fulfilled the inclusion criteria were included in the study. The PV of the patients were significantly correlated with age, tPSA and fPSA (p < 0.001 and r = 0.307, p < 0.001 and r = 0.382, p < 0.001 and r = 0.296, respectively). On linear regression model, fPSA was found as a stronger predictive for PV (AUC = 0.75, p < 0.001) when compared to age (AUC = 0.64, p < 0.001), and tPSA (AUC = 0.69, p = 0.013). Although tPSA is an important prognostic factor for predicting PV, the predictive value of fPSA is higher. PV can easily be predicted by using age, and serum tPSA and fPSA levels.

  8. Review of APR+ Level 2 PSA. Revision 2

    SciTech Connect

    Lehner, John R.; Mubayi, Vinod; Pratt, W. Trevor; Kim, Do Sam; Cho, Yong Jin; Cho, Sang Jin; Kim, In Goo

    2012-02-17

    Brookhaven National Laboratory (BNL) assisted the Korea Institute of Nuclear Safety (KINS) in reviewing the Level 2 Probabilistic Safety Assessment (PSA) of the APR+ Advanced Pressurized Water Reactor (PWR) prepared by the Korea Hydro & Nuclear Power Co., Ltd (KHNP) and KEPCO Engineering & Construction Co., Inc. (KEPCO-E&C). The work described in this report involves a review of the APR+ Level 2 PSA submittal [Ref. 1]. The PSA and, therefore, the review is limited to consideration of accidents initiated by internal events. As part of the review process, the review team also developed three sets of Requests for Additional Information (RAIs). These RAIs were provided to KHNP and KEPCO-E&C for their evaluation and response. This final detailed report documents the review findings for each technical element of the PSA and includes consideration of all of the RAIs made by the reviewers as well as the associated responses. This final report was preceded by an interim report [Ref. 2] that focused on identifying important issues regarding the PSA. In addition, a final meeting on the project was held at BNL on November 21-22, 2011, where BNL and KINS reviewers discussed their preliminary review findings with KHNP and KEPCO-E&C staffs. Additional information obtained during this final meeting was also used to inform the review findings of this final report. The review focused not only on the robustness of the APR+ design to withstand severe accidents, but also on the capability and acceptability of the Level 2 PSA in terms of level of detail and completeness. The Korean nuclear regulatory authorities will decide whether the PSA is acceptable and the BNL review team is providing its comments for KINS consideration. Section 2.0 provides the basis for the BNL review. Section 3.0 presents the review of each technical element of the PSA. Conclusions and a summary are presented in Section 4.0. Section 5.0 contains the references.

  9. Highly elevated PSA and dietary PhIP intake in a prospective clinic-based study among African Americans.

    PubMed

    Bogen, K T; Keating, G A; Chan, J M; Paine, L J; Simms, E L; Nelson, D O; Holly, E A

    2007-01-01

    African-American men die from prostate cancer (PC) nearly twice as often as white US men and consume about twice as much of the predominant US dietary heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a genotoxic rat-prostate carcinogen found primarily in well-cooked chicken and beef. To investigate the hypothesis that PhIP exposure increases PC risk, an ongoing prospective clinic-based study compared PC screening outcomes with survey-based estimates of dietary PhIP intake among 40-70-year-old African-American men with no prior PC in Oakland, CA. They completed food-frequency and meat-cooking/consumption questionnaires and had a prostate-specific antigen (PSA) test and digital-rectal exam. Results for 392 men indicated a 17 (+/-17) ng/kg day mean (+/-1 s.d.) daily intake of PhIP, about twice that of white US men of similar age. PhIP intake was attributable mostly to chicken (61%) and positively associated (R(2)=0.32, P<0.0001) with saturated fat intake. An odds ratio (95% confidence interval) of 31 (3.1-690) for highly elevated PSA > or =20 ng/ml was observed in the highest 15% vs lowest 50% of estimated daily PhIP intake (> or =30 vs < or =10 ng/kg day) among men 50+ years old (P=0.0002 for trend) and remained significant after adjustment for self-reported family history of (brother or father) PC, saturated fat intake and total energy intake. PSA measures were higher in African-American men with positive family history (P=0.007 all men, P<0.0001 highest PSA quartile). These preliminary results are consistent with a positive association between PhIP intake and highly elevated PSA, supporting the hypothesis that dietary intervention may help reduce PC risk.

  10. Highly specific expression of luciferase gene in lungs of naive nude mice directed by prostate-specific antigen promoter

    SciTech Connect

    Li Hongwei; Li Jinzhong; Helm, Gregory A.; Pan Dongfeng . E-mail: Dongfeng_pan@yahoo.com

    2005-09-09

    PSA promoter has been demonstrated the utility for tissue-specific toxic gene therapy in prostate cancer models. Characterization of foreign gene overexpression in normal animals elicited by PSA promoter should help evaluate therapy safety. Here we constructed an adenovirus vector (AdPSA-Luc), containing firefly luciferase gene under the control of the 5837 bp long prostate-specific antigen promoter. A charge coupled device video camera was used to non-invasively image expression of firefly luciferase in nude mice on days 3, 7, 11 after injection of 2 x 10{sup 9} PFU of AdPSA-Luc virus via tail vein. The result showed highly specific expression of the luciferase gene in lungs of mice from day 7. The finding indicates the potential limitations of the suicide gene therapy of prostate cancer based on selectivity of PSA promoter. By contrary, it has encouraging implications for further development of vectors via PSA promoter to enable gene therapy for pulmonary diseases.

  11. Prostate-specific antigen levels as a predictor of lethal prostate cancer.

    PubMed

    Fall, Katja; Garmo, Hans; Andrén, Ove; Bill-Axelson, Anna; Adolfsson, Jan; Adami, Hans-Olov; Johansson, Jan-Erik; Holmberg, Lars

    2007-04-04

    Rates of long-term survival among patients with untreated localized prostate cancer are high. To avoid unnecessary treatment, tools are needed to identify the small proportion of patients who are destined to develop lethal prostate cancer. To evaluate the accuracy of early changes in prostate-specific antigen (PSA) levels as predictors of prostate cancer outcome, we assessed serial measurements of PSA level among 267 men with localized prostate cancer in a Scandinavian cohort of men who were diagnosed between 1989 and 1999 and who were managed by watchful waiting. We then 1) fitted individual regression lines to the PSA values assessed for each patient during the first 2 years of follow-up by using three different models, 2) evaluated early PSA curve characteristics as determinants of the cumulative incidence of lethal prostate cancer and calculated hazard ratios for baseline PSA value and rate of change in PSA level to prostate cancer outcome, and 3) plotted time-dependent receiver operating characteristic (ROC) curves. All P values are two-sided. During complete follow-up for a mean of 8.5 years, 34 patients (13%) died from prostate cancer, and 18 (7%) developed metastases but were still alive at end of follow-up. In a log-linear model, both PSA value at baseline (P = .05) and the rate of PSA change (P<.001) were associated with the development of lethal prostate cancer. In the ROC analysis, however, the accuracy of classifying the disease as either indolent or destined to progress was low, regardless of the cut point chosen for initial PSA level or rate of change in PSA level. Although baseline PSA value and rate of PSA change are prognostic factors for lethal prostate cancer, they are poor predictors of lethal prostate cancer among patients with localized prostate cancer who are managed by watchful waiting.

  12. An Eight-Year Experience of HDR Brachytherapy Boost for Localized Prostate Cancer: Biopsy and PSA Outcome

    SciTech Connect

    Bachand, Francois; Martin, Andre-Guy; Beaulieu, Luc; Harel, Francois M.Sc.; Vigneault, Eric

    2009-03-01

    Purpose: To evaluate the biochemical recurrence-free survival (bRFS), the 2-year biopsy outcome and the prostate-specific antigen (PSA) bounce in patients with localized prostate cancer treated with an inversely planned high-dose-rate (HDR) brachytherapy boost. Materials and methods: Data were collected from 153 patients treated between 1999 and 2006 with external beam pelvic radiation followed by an HDR Ir-192 prostate boost. These patients were given a boost of 18 to 20 Gy using inverse-planning with simulated annealing (IPSA).We reviewed and analyzed all prostate-specific antigen levels and control biopsies. Results: The median follow-up was 44 months (18-95 months). When categorized by risk of progression, 74.5% of patients presented an intermediate risk and 14.4% a high one. Prostate biopsies at 2 years posttreatment were negative in 86 of 94 patients (91.5%), whereas two biopsies were inconclusive. Biochemical control at 60 months was at 96% according to the American Society for Therapeutic Radiology and Oncology and the Phoenix consensus definitions. A PSA bounce (PSA values of 2 ng/mL or more above nadir) was observed in 15 patients of 123 (9.8%). The median time to bounce was 15.2 months (interquartile range, 11.0-17.7) and the median bounce duration 18.7 months (interquartile range, 12.1-29). The estimate of overall survival at 60 months was 97.1% (95% CI, 91.6-103%). Conclusions: Considering that inverse planned HDR brachytherapy prostate boosts led to an excellent biochemical response, with a 2-year negative biopsy rate, we recommend a conservative approach in face of a PSA bounce even though it was observed in 10% of patients.

  13. Free/Total Serum Prostate-Specific Antigen Ratio in Women with Colorectal Cancer Has Prognostic Significance.

    PubMed

    Duraker, Nüvit; Çaynak, Zeynep Civelek; Trabulus, Didem Can

    2017-03-01

    The presence of prostate-specific antigen (PSA) in colon cancer tissues has been shown, but its clinical significance has not been known yet in colorectal cancer patients. We investigated the prognostic significance of percent free PSA value (free PSA/total PSA × 100) in female patients with colorectal cancer. The serum concentrations of total and free PSA were measured by solid-phase two-site immunoradiometric assay in 184 patients. The cancer-specific survival (CSS) of patients with percent free PSA value ≥35 was significantly better compared to that of patients with percent free PSA value <35 (CSS rate was 82.9 and 55.5 %, respectively; log-rank x(2) = 8135, p = 0.004). In multivariate Cox analysis, this percent free PSA threshold value had independent prognostic significance (relative risk 0.27, 95 % confidence interval 0.11-0.64, p = 0.003). Percent free PSA value, calculated by serum total and free PSA levels, has prognostic significance in women with colorectal cancer. The studies with larger patient series, utilizing ultrasensitive PSA assays whose lowest detection limit is lower, are required for a clearer understanding of this issue.

  14. Is Serum Prostate-specific Antigen a Diagnostic Marker for Benign and Malignant Breast Tumors in Women?

    PubMed

    Razavi, Seyed Hasan Emami; Ghajarzadeh, Mahsa; Abdollahi, Alireza; Shoar, Saeed; Omranipour, Ramesh

    2015-01-01

    Breast cancer is the most common cancer in women. Prostate-specific antigen (PSA) is a marker of prostate gland malignancy, which has been considered in cases with breast cancer in recent years. The goal of this study was to determine total and free PSA levels in cases with malignant and benign breast lesions. In this case-control study, ninety women with histological proved malignant breast masses and 90 with benign breast masses were enrolled. Total and free PSA levels along with Histological grade and conditions of vascular and perinural invasion, status of hormonal tumor receptors, immune-histo-chemistry markers recorded for all cases. Total and free PSA levels were assessed after treatment in cases with malignant masses. Total and free PSA levels were significantly higher in cases with malignant masses. The best cut-off point for total PSA to differentiate benign and malignant masses was 0.31 with sensitivity and specificity of 100%, 100% (area under the curve [AUC] =1, P < 0.001) and the best cut-off point for free PSA to differentiate benign and malignant masses was 0.19 with sensitivity and specificity of 100% and 100% (AUC = 1, P < 0.001). After treatment, mean free PSA level was significantly lower than free PSA before treatment (0.23 ± 0.1 vs. 0.3 ± 0.08, P < 0.001). Serum PSA level could be applied for differentiating benign and malignant breast masses.

  15. Is Serum Prostate-specific Antigen a Diagnostic Marker for Benign and Malignant Breast Tumors in Women.

    PubMed

    Razavi, Seyed Hasan Emami; Ghajarzadeh, Mahsa; Abdollahi, Alireza; Taran, Ludmila; Shoar, Saeed; Omranipour, Ramesh

    2015-06-01

    Breast cancer is the most common cancer in women. Prostrate-specific antigen (PSA) is a marker of prostate gland malignancy which has been considered in cases with breast cancer in recent years. The goal of this study was to determine total and free PSA levels in cases with malignant and benign breast lesions. Ninety women with histological proved malignant breast masses and 90 with benign breast masses were enrolled. Total and free PSA levels along with histological grade and conditions of vascular and perinural invasion, status of hormonal tumor receptors, immune-histo-chemistry markers recorded for all cases. Total and free PSA levels were assessed after treatment in cases with malignant masses. Total and free PSA levels were significantly higher in cases with malignant masses. The best cut off point for total PSA to differentiate benign and malignant masses was 0.31 and the best cut off point for free PSA to differentiate benign and malignant masses was 0.19. After treatment, mean free PSA level was significantly lower than free PSA before treatment (0.23 vs 0.3, p<0.001). Serum PSA level could be applied for differentiating benign and malignant breast masses.

  16. Good Performance of Rapid Prostate-Specific Antigen Test for Detection of Semen Exposure in Women: Implications for Qualitative Research

    PubMed Central

    Hobbs, Marcia M.; Steiner, Markus J.; Rich, Kimberly D.; Gallo, Maria F.; Alam, Anadil; Rahman, Motiur; Menezes, Prema; Chipato, Tsungai; Warner, Lee; Macaluso, Maurizio

    2013-01-01

    Background Prostate-specific antigen (PSA) is a valid biomarker of semen exposure in women and has been used to assess reliability of self-reported sexual behavior as well as serve as a proxy measure for condom efficacy. Quantitative PSA tests are expensive and require specialized equipment. A simple, rapid, and inexpensive test for PSA would facilitate semen biomarker evaluation in a variety of research settings. This study evaluated the performance of a rapid PSA test compared with a quantitative assay to identify semen in vaginal swab specimens. Methods We tested 581 vaginal swabs collected from 492 women participating in 2 separate research studies in Bangladesh and Zimbabwe. PSA in vaginal secretions was detected using the quantitative IMx (Abbott Laboratories) assay and the ABAcard p30 (Abacus Diagnostics) rapid immunochromatographic strip test. Results The ABAcard test was 100% sensitive (95% confidence interval [CI], 98%–100%) and 96% specific (95% CI, 93%–97%) compared with the quantitative test in detecting >1.0 ng PSA/mL vaginal swab eluate. Rapid PSA results were semiquantitative and correlated well with PSA concentrations (κ = 0.88; 95% CI, 0.85–0.90). Conclusion Rapid PSA detection requires no instrumentation and can be performed easily and economically. Having rapid PSA results available immediately following interview provides opportunities to explore discrepancies between the objective marker of recent semen exposure and self-reported behaviors. PMID:19455082

  17. Good performance of rapid prostate-specific antigen test for detection of semen exposure in women: implications for qualitative research.

    PubMed

    Hobbs, Marcia M; Steiner, Markus J; Rich, Kimberly D; Gallo, Maria F; Alam, Anadil; Rahman, Motiur; Menezes, Prema; Chipato, Tsungai; Warner, Lee; Macaluso, Maurizio

    2009-08-01

    Prostate-specific antigen (PSA) is a valid biomarker of semen exposure in women and has been used to assess reliability of self-reported sexual behavior as well as serve as a proxy measure for condom efficacy. Quantitative PSA tests are expensive and require specialized equipment. A simple, rapid, and inexpensive test for PSA would facilitate semen biomarker evaluation in a variety of research settings. This study evaluated the performance of a rapid PSA test compared with a quantitative assay to identify semen in vaginal swab specimens. We tested 581 vaginal swabs collected from 492 women participating in 2 separate research studies in Bangladesh and Zimbabwe. PSA in vaginal secretions was detected using the quantitative IMx (Abbott Laboratories) assay and the ABAcard p30 (Abacus Diagnostics) rapid immunochromatographic strip test. The ABAcard test was 100% sensitive (95% confidence interval [CI], 98%-100%) and 96% specific (95% CI, 93%-97%) compared with the quantitative test in detecting >1.0 ng PSA/mL vaginal swab eluate. Rapid PSA results were semiquantitative and correlated well with PSA concentrations (kappa = 0.88; 95% CI, 0.85-0.90). Rapid PSA detection requires no instrumentation and can be performed easily and economically. Having rapid PSA results available immediately following interview provides opportunities to explore discrepancies between the objective marker of recent semen exposure and self-reported behaviors.

  18. Predictors of random sextant biopsy outcome in screened men with PSA > 4 ng/mL and a negative sextant biopsy at previous screening. Experience in a population-based screening program in Florence.

    PubMed

    Ciatto, S; Lombardi, C; Rubeca, T; Zappa, M

    2004-01-01

    The aim of this study was to evaluate possible pedictors of the outcome of repeat random sextant biopsy of the prostate prompted by a rise in prostate-specific antigen (PSA). Random biopsies performed for PSA elevation (>4 ng/mL) in the course of a randomized study of screening efficacy were reviewed, and 87 consecutive biopsies (carcinoma = 13, high-grade prostatic intraepithelial neoplasia = 6, negative = 68) performed in subjects with a negative random biopsy at the previous screening round were considered. Findings at digital rectal examination or transrectal ultrasonography and total PSA value were not useful predictors of repeat biopsy outcome, whereas PSA velocity was significantly associated with biopsy outcome. The positive predictive value for a cancer biopsy was 2.7% (1/36), 28.5% (2/7), and 22.7% (10/44) for PSA velocity values of <0.1, 0.1-0.19, and >0.19 ng/mL/yr, respectively. A cutoff of 0.1 ng/mL/yr for PSA velocity would have allowed to avoid approximately half (35/74 = 47.2%) of the benign biopsies while decreasing the sensitivity by 7.6% (1/13), and is thus suggested as a possible criterion for the indication of repeat random biopsy for persistent PSA elevation.

  19. Detection of Local, Regional, and Distant Recurrence in Patients With PSA Relapse After External-Beam Radiotherapy Using {sup 11}C-Choline Positron Emission Tomography

    SciTech Connect

    Breeuwsma, Anthonius J.; Pruim, Jan; Bergh, Alphons C.M. van den; Leliveld, Anna M.; Nijman, Rien J.M.; Dierckx, Rudi A.J.O.; Jong, Igle J. de

    2010-05-01

    Purpose: An elevated serum prostate-specific antigen (PSA) level cannot distinguish between local-regional recurrences and the presence of distant metastases after treatment with curative intent for prostate cancer. With the advent of salvage treatment such as cryotherapy, it has become important to localize the site of recurrence (local or distant). In this study, the potential of {sup 11}C-choline positron emission tomography (PET) to identify site of recurrence was investigated in patients with rising PSA after external-beam radiotherapy (EBRT). Methods and Materials: Seventy patients with histologically proven prostate cancer treated with EBRT and showing biochemical recurrence as defined by American Society for Therapeutic Radiology and Oncology consensus statement and 10 patients without recurrence underwent a PET scan using 400 MBq {sup 11}C-choline intravenously. Biopsy-proven histology from the site of suspicion, findings with other imaging modalities, clinical follow-up and/or response to adjuvant therapy were used as comparative references. Results: None of the 10 patients without biochemical recurrence had a positive PET scan. Fifty-seven of 70 patients with biochemical recurrence (median PSA 9.1 ng/mL; mean PSA 12.3 ng/mL) showed an abnormal uptake pattern (sensitivity 81%). The site of recurrence was only local in 41 of 57 patients (mean PSA 11.1 ng/mL at scan), locoregionally and/or distant in 16 of 57 patients (mean PSA 17.7 ng/mL). Overall the positive predictive value and negative predictive value for {sup 11}C-choline PET scan were 1.0 and 0.44 respectively. Accuracy was 84%. Conclusions: {sup 11}C-choline PET scan is a sensitive technique to identify the site of recurrence in patients with PSA relapse after EBRT for prostate cancer.

  20. High-Risk Prostate Cancer With Gleason Score 8-10 and PSA Level {<=}15 ng/ mL Treated With Permanent Interstitial Brachytherapy

    SciTech Connect

    Fang, L. Christine; Merrick, Gregory S.; Butler, Wayne M.; Galbreath, Robert W.; Murray, Brian C.; Reed, Joshua L.; Adamovich, Edward; Wallner, Kent E.

    2011-11-15

    Purpose: With widespread prostate-specific antigen (PSA) screening, there has been an increase in men diagnosed with high-risk prostate cancer defined by a Gleason score (GS) {>=}8 coupled with a relatively low PSA level. The optimal management of these patients has not been defined. Cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) were evaluated in brachytherapy patients with a GS {>=}8 and a PSA level {<=}15 ng/mL with or without androgen-deprivation therapy (ADT). Methods and Materials: From April 1995 to October 2005, 174 patients with GS {>=}8 and a PSA level {<=}15 ng/mL underwent permanent interstitial brachytherapy. Of the patients, 159 (91%) received supplemental external beam radiation, and 113 (64.9%) received ADT. The median follow-up was 6.6 years. The median postimplant Day 0 minimum percentage of the dose covering 90% of the target volume was 121.1% of prescription dose. Biochemical control was defined as a PSA level {<=}0.40 ng/mL after nadir. Multiple parameters were evaluated for impact on survival. Results: Ten-year outcomes for patients without and with ADT were 95.2% and 92.5%, respectively, for CSS (p = 0.562); 86.5% and 92.6%, respectively, for bPFS (p = 0.204); and 75.2% and 66.0%, respectively, for OS (p = 0.179). The median post-treatment PSA level for biochemically controlled patients was <0.02 ng/mL. Multivariate analysis failed to identify any predictors for CSS, whereas bPFS and OS were most closely related to patient age. Conclusions: Patients with GS {>=}8 and PSA level {<=}15 ng/mL have excellent bPFS and CSS after brachytherapy with supplemental external beam radiotherapy. The use of ADT did not significantly impact bPFS, CSS, or OS.

  1. Macrophage Inhibitory Cytokine 1 Biomarker Serum Immunoassay in Combination with PSA Is a More Specific Diagnostic Tool for Detection of Prostate Cancer

    PubMed Central

    Li, Ji; Veltri, Robert W.; Yuan, Zhen; Christudass, Christhunesa S.; Mandecki, Wlodek

    2015-01-01

    Background Prostate cancer (PCa) is the most common malignancy among men in the United States. Though highly sensitive, the often-used prostate-specific antigen (PSA) test has low specificity which leads to overdiagnosis and overtreatment of PCa. This paper presents results of a retrospective study that indicates that testing for macrophage inhibitory cytokine 1 (MIC-1) concentration along with the PSA assay could provide much improved specificity to the assay. Methods The MIC-1 serum level was determined by a novel p-Chip-based immunoassay run on 70 retrospective samples. The assay was configured on p-Chips, small integrated circuits (IC) capable of storing in their electronic memories a serial number to identify the molecular probe immobilized on its surface. The distribution of MIC-1 and pre-determined PSA concentrations were displayed in a 2D plot and the predictive power of the dual MIC-1/PSA assay was analyzed. Results MIC-1 concentration in serum was elevated in PCa patients (1.44 ng/ml) compared to normal and biopsy-negative individuals (0.93 ng/ml and 0.88 ng/ml, respectively). In addition, the MIC-1 level was correlated with the progression of PCa. The area under the receiver operator curve (AUC-ROC) was 0.81 providing an assay sensitivity of 83.3% and specificity of 60.7% by using a cutoff of 0.494 for the logistic regression value of MIC-1 and PSA. Another approach, by defining high-frequency PCa zones in a two-dimensional plot, resulted in assay sensitivity of 78.6% and specificity of 89.3%. Conclusions The analysis based on correlation of MIC-1 and PSA concentrations in serum with the patient PCa status improved the specificity of PCa diagnosis without compromising the high sensitivity of the PSA test alone and has potential for PCa prognosis for patient therapy strategies. PMID:25853582

  2. Risk of Pathologic Upgrading or Locally Advanced Disease in Early Prostate Cancer Patients Based on Biopsy Gleason Score and PSA: A Population-Based Study of Modern Patients

    SciTech Connect

    Caster, Joseph M.; Falchook, Aaron D.; Hendrix, Laura H.; Chen, Ronald C.

    2015-06-01

    Purpose: Radiation oncologists rely on available clinical information (biopsy Gleason score and prostate-specific antigen [PSA]) to determine the optimal treatment regimen for each prostate cancer patient. Existing published nomograms correlating clinical to pathologic extent of disease were based on patients treated in the 1980s and 1990s at select academic institutions. We used the Surveillance, Epidemiology, and End Results (SEER) database to examine pathologic outcomes (Gleason score and cancer stage) in early prostate cancer patients based on biopsy Gleason score and PSA concentration. Methods and Materials: This analysis included 25,858 patients whose cancer was diagnosed between 2010 and 2011, with biopsy Gleason scores of 6 to 7 and clinical stage T1 to T2 disease, who underwent radical prostatectomy. In subgroups based on biopsy Gleason score and PSA level, we report the proportion of patients with pathologically advanced disease (positive surgical margin or pT3-T4 disease) or whose Gleason score was upgraded. Logistic regression was used to examine factors associated with pathologic outcomes. Results: For patients with biopsy Gleason score 6 cancers, 84% of those with PSA <10 ng/mL had surgical T2 disease with negative margins; this decreased to 61% in patients with PSA of 20 to 29.9 ng/mL. Gleason score upgrading was seen in 43% (PSA: <10 ng/mL) to 61% (PSA: 20-29.9 ng/mL) of biopsy Gleason 6 patients. Patients with biopsy Gleason 7 cancers had a one-third (Gleason 3 + 4; PSA: <10 ng/mL) to two-thirds (Gleason 4 + 3; PSA: 20-29.9 ng/mL) probability of having pathologically advanced disease. Gleason score upgrading was seen in 11% to 19% of patients with biopsy Gleason 4 + 3 cancers. Multivariable analysis showed that higher PSA and older age were associated with Gleason score upgrading and pathologically advanced disease. Conclusions: This is the first population-based study to examine pathologic extent of disease and pathologic Gleason score

  3. Structural characterization of Dictyostelium discoideum prespore-specific gene D19 and of its product, cell surface glycoprotein PsA.

    PubMed Central

    Early, A E; Williams, J G; Meyer, H E; Por, S B; Smith, E; Williams, K L; Gooley, A A

    1988-01-01

    The Dictyostelium discoideum cell surface antigen PsA is a glycoprotein which first appears in the multicellular stage soon after tip formation and is selectively expressed on prespore cells. The D19 gene encodes an mRNA sequence which is highly enriched in prespore over prestalk cells in the slug stage. We have determined 81 amino acid residues of N-terminal sequence from immunoaffinity-purified PsA protein and shown this sequence to be identical to the predicted sequence of the D19 gene. There are several short repeat elements close to the C terminus, and unequal crossing-over within these is proposed to account for the size polymorphism observed in PsA protein isolated from different D. discoideum strains. The repeats are proline rich and show similarity to the C-terminal region of the D. discoideum cell adhesion molecule, contact sites A. The extreme C terminus, which is also homologous to contact sites A, is characteristic of proteins attached to the plasma membrane via a glycosyl-phosphatidylinositol link. We have marked the PsA gene by insertion of an oligonucleotide encoding an epitope of the human c-myc protein. A construct containing this gene and 990 base pairs of 5'-flanking region directed correct temporal and spatial mRNA accumulation. We found the marked PsA protein, detected with the human c-myc antibody, to be correctly localized on the surface of cells. Images PMID:2850494

  4. [Relationship between tumor volume and PSA recurrence after radical prostatectomy].

    PubMed

    Hashimoto, Yasuhiro; Momose, Akishi; Okamoto, Akiko; Yamamoto, Hayato; Hatakeyama, Shingo; Iwabuchi, Ikuya; Yoneyama, Takahiro; Koie, Takuya; Kamimura, Noritaka; Ohyama, Chikara

    2010-02-01

    We examined whether the tumor volume (TV) is a good predictor of PSA recurrence after radical prostatectomy. Data were collected for 158 patients with clinically localized prostate cancer undergoing radical prostatectomy without neoadjuvant hormonal therapy in our hospital since April 2005 to September 2007. Along with the routine pathological assessment, TV was assessed in all prostatectomy specimens. PSA recurrence was defined as PSA levels of greater than 0.2 ng/ml. The TVs were 1.81+/-1.66 ml (mean +/-SD) ranging from 0.02 to 8.20 ml. The TV in cT1c was 1.77+/-1.64, and 1.89+/-1.72 ml in cT2 (not significant). Significant differences were observed between TV and pT. The TVs in pT2a, pT2b and pT3/4 were 0.54+/-0.54, 1.63+/-1.47 and 2.67+/-1.80 ml, respectively. The median follow-up period was 32.3 months (range from 15 to 45) after radical prostatectomy, and PSA recurrence was observed in 32 cases. Patients with smaller TV (TV <1.3 ml) had a higher PSA-free survival rate (89.5%) than those with a larger TV (TV > or = 1.3 ml, 66.7%) with a significant difference atp <0.001 (log-rank test). A multivariate analysis was performed for PSA, TV, pT, Gleason Score (GS), and surgical margins. Significant differences were observed for GS, and surgical margins, but not for TV. Clinically organ-confined disease in Japanese patients with prostate cancer included various cancers from clinically insignificant to locally advanced ones. In our series, TV was not regarded as a predictor of PSA recurrence after radical prostatectomy.

  5. Cyber-Physical Security Assessment (CyPSA) Toolset

    SciTech Connect

    Garcia, Luis; Patapanchala, Panini; Zonouz, Saman; Davis, Kate; Davis, Matt; Berthier, Robin; Bamba, Mouna; Soubigou, Olivier; Rayala, Vishnu Priya; Weaver, Gabe; Rogers, Edmond; Bobba, Rakesh; Nicol, David; Sauer, Pete

    2016-08-31

    CyPSA seeks to organize and gain insight into the diverse sets of data that a critical infrastructure provider must manage. Specifically CyPSA inventories, manages, and analyzes assets and relations among those assets. A variety of interfaces are provided. CyPSA inventories assets (both cyber and physical). This may include the cataloging of assets through a common interface. Data sources used to generate a catalogue of assets include PowerWorld, NPView, NMap Scans, and device configurations. Depending upon the role of the person using the tool the types of assets accessed as well as the data sources through which asset information is accessed may vary. CyPSA allows practitioners to catalogue relations among assets and these may either be manually or programmatically generated. For example, some common relations among assets include the following: Topological Network Data: Which devices and assets are connected and how? Data sources for this kind of information include NMap scans, NPView topologies (via Firewall rule analysis). Security Metrics Outputs: The output of various security metrics such as overall exposure. Configure Assets:CyPSA may eventually include the ability to configure assets including relays and switches. For example, a system administrator would be able to configure and alter the state of a relay via the CyPSA interface. Annotate Assets: CyPSA also allows practitioners to manually and programmatically annotate assets. Sources of information with which to annotate assets include provenance metadata regarding the data source from which the asset was loaded, vulnerability information from vulnerability databases, configuration information, and the output of an analysis in general.

  6. Minimal percentage of dose received by 90% of the urethra (%UD90) is the most significant predictor of PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer

    PubMed Central

    2012-01-01

    Background To clarify the significant clinicopathological and postdosimetric parameters to predict PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer. Methods We studied 200 consecutive patients who received LDR-brachytherapy between July 2004 and November 2008. Of them, 137 patients did not receive neoadjuvant or adjuvant androgen deprivation therapy. One hundred and forty-two patients were treated with LDR-brachytherapy alone, and 58 were treated with LDR-brachytherapy in combination with external beam radiation therapy. The cut-off value of PSA bounce was 0.1 ng/mL. The incidence, time, height, and duration of PSA bounce were investigated. Clinicopathological and postdosimetric parameters were evaluated to elucidate independent factors to predict PSA bounce in hormone-naïve patients who underwent LDR-brachytherapy alone. Results Fifty patients (25%) showed PSA bounce and 10 patients (5%) showed PSA failure. The median time, height, and duration of PSA bounce were 17 months, 0.29 ng/mL, and 7.0 months, respectively. In 103 hormone-naïve patients treated with LDR-brachytherapy alone, and univariate Cox proportional regression hazard model indicated that age and minimal percentage of the dose received by 30% and 90% of the urethra were independent predictors of PSA bounce. With a multivariate Cox proportional regression hazard model, minimal percentage of the dose received by 90% of the urethra was the most significant parameter of PSA bounce. Conclusions Minimal percentage of the dose received by 90% of the urethra was the most significant predictor of PSA bounce in hormone-naïve patients treated with LDR-brachytherapy alone. PMID:22974428

  7. The helix-loop-helix Id-1 inhibits PSA expression in prostate cancer cells.

    PubMed

    Zielinski, Anne J; Fong, Sylvia; Allison, Juanita; Kawahara, Misako; Coppe, Jean-Philippe; Feiler, Heidi; Lee, Nancy M; Desprez, Pierre-Yves

    2010-05-15

    The inhibitor of basic helix-loop-helix transcription factors, Id-1, is an important gene whose expression increases during prostate cancer progression and that upregulates proliferation, migration and invasion. We used microarray analysis to identify the downstream genes whose transcriptional expression is modulated by Id-1 protein. We compared gene expression in control LNCaP cells and Id-1-transduced LNCaP cells, which become significantly more aggressive after Id-1 overexpression, thus mimicking the high levels of Id-1 detected in metastatic cell lines. We used the Affy HTA U133A Expression Arrays with 45,000 probe sets representing more than 39,000 transcripts. We found that one of the most significantly downregulated genes on Id-1 expression was kallikrein 3 [also called prostate specific antigen (PSA)], the most commonly used biomarker of prostate cancer. Here, we show that the reduction in PSA mRNA and protein expression associated with high-grade prostate cancers, which generally express high levels of Id-1, could be the consequence of Id-1 overexpression.

  8. Development of a New Method for Monitoring Prostate-Specific Antigen Changes in Men with Localised Prostate Cancer: A Comparison of Observational Cohorts

    PubMed Central

    Tilling, Kate; Garmo, Hans; Metcalfe, Chris; Holmberg, Lars; Hamdy, Freddie C; Neal, David E; Adolfsson, Jan; Martin, Richard M; Davis, Michael; Fall, Katja; Lane, J. Athene; Adami, Hans-Olaf; Bill-Axelson, Anna; Johansson, Jan-Eric; Donovan, Jenny L.

    2010-01-01

    Background Prostate-specific antigen (PSA) measurements are increasingly used to monitor men with localised prostate cancer (PCa), but there is little consensus about the method to use. Objective To apply age-specific predictions of PSA level (developed in men without cancer) to one cohort of men with clinically identified PCa and one cohort of men with PSA-detected PCa. We hypothesise that among men with clinically identified cancer, the annual increase in PSA level would be steeper than in men with PSA-detected cancer. Design, setting, and participants The Scandinavian Prostatic Cancer Group 4 (SPCG-4) cohort consisted of 321 men assigned to the watchful waiting arm of the SPCG-4 trial. The UK cohort consisted of 320 men with PSA-detected PCa in the Prostate Testing for Cancer and Treatment (ProtecT) study in nine UK centres between 1999 and 2007 who opted for monitoring rather than treatment. Multilevel models describing changes in PSA level were fitted to the two cohorts, and average PSA level at age 50, change in PSA level with age, and predicted PSA values were derived. Measurements PSA level. Results and limitations In the SPCG-4 cohort, mean PSA at age 50 was similar to the cancer-free cohort but with a steeper yearly increase in PSA level (16.4% vs 4.0%). In the UK cohort, mean PSA level was higher than that in the cancer-free cohort (due to a PSA biopsy threshold of 3.0 ng/ml) but with a similar yearly increase in PSA level (4.1%). Predictions were less accurate for the SPCG-4 cohort (median observed minus predicted PSA level: −2.0 ng/ml; interquartile range [IQR]: −7.6–0.7 ng/ml) than for the UK cohort (median observed minus predicted PSA level: −0.8 ng/ml; IQR: −2.1–0.1 ng/ml). Conclusions In PSA-detected men, yearly change in PSA was similar to that in cancer-free men, whereas in men with symptomatic PCa, the yearly change in PSA level was considerably higher. Our method needs further evaluation but has promise for refining active

  9. Biochemical failure as a determinant of distant metastasis and death in prostate cancer treated with radiotherapy.

    PubMed

    Pollack, Alan; Hanlon, Alexandra L; Movsas, Benjamin; Hanks, Gerald E; Uzzo, Robert; Horwitz, Eric M

    2003-09-01

    Biochemical failure (BF), defined by a rising prostate-specific antigen (PSA) profile, is an early surrogate of treatment failure. However, little evidence is available to show that BF is associated with death for patents with prostate cancer treated with radiotherapy. We examined the relationship between BF and death from prostate cancer. A total of 942 patients were treated between 1987 and 1998 with external beam radiotherapy who had sufficient PSA determinations in follow-up for the analyses described. The median radiation dose was 72 Gy, median PSA was 9.9 ng/mL, and median follow-up was 73 months. The American Society for Therapeutic Radiology and Oncology consensus definition was used to define BF. Kaplan-Meier calculations were from the start of radiotherapy. Cox proportional hazards regression multivariate analyses were used to investigate the association of BF (time-dependent variable) and other factors to distant metastasis (DM), cause-specific death (CSD), and overall death (OD). The year of treatment was included in some of the multivariate analyses to correct for potential unknown factors that may have occurred during the years of the study, such as stage migration. BF was observed in 316 patients (34%), and 66 (7%) experienced DM, 32 (3%) died of prostate cancer, and 230 (24%) died overall during the study period. The Kaplan-Meier 5-year rate estimates from the start of treatment for BF, DM, CSD, and OD were 38%, 6%, 3%, and 13%, respectively. All patients with DM had BF. In multivariate analyses, BF was associated with DM and CSD, but not OD. The inclusion of the year of treatment did not alter these relationships. BF, as a time-dependent covariate, was the strongest determinant of DM and was also very significantly related to CSD. The inclusion of the year of treatment had little effect on these associations. Longer follow-up is needed to determine conclusively the relationship of BF to OD.

  10. Reconnoitring the status of prostate specific antigen and its role in women.

    PubMed

    Dash, Prakruti

    2015-04-01

    Prostate specific antigen is considered to be a tumour marker having maximum utility and specificity for prostate cancer since decades. After the discovery of methods to quantify different molecular fractions of prostate specific antigen (PSA), its usefulness in diagnosing early prostate cancer cases has increased tremendously. The "specificity" of PSA, is now challenged by many studies which proved that PSA, once believed to be secreted exclusively by prostatic epithelium, is also present in females. The exact biological role of extraprostatic PSA is still debatable though many theories substantiated by in vitro evidence has been put forward. With the advent of ultrasensitive analytical techniques, PSA is now quantifiable in female serum in its various molecular forms and this has led to many assumptions of it being useful as a marker in female breast cancers. In a similar scenario to prostate cancer, the ratio of free to total PSA is shown to be useful in detecting early breast cancer cases. It is also shown to be a good prognostic indicator and a predictor of response to therapy and recurrence. Apart from its role in breast cancer, it has been advocated to be a marker of hyper androgenic states in women like hirsutism and polycystic ovarian syndrome. Conflicting reports regarding the role of extra prostatic PSA is accumulating but it has been proven beyond doubt that PSA is no longer specific and confined to prostate gland. Various studies have registered that PSA is an ubiquitous molecule, secreted by hormone responsive organs and its synthesis is stimulated by androgens and progesterone but not oestrogens. In this article, a review of various literatures is done about the presence of extra prostatic PSA, its probable role in those sites as well as its utility as a tumour marker in breast cancer.

  11. PSA block for maxillary molar's anesthesia - an obsolete technique?

    PubMed

    Padhye, Mukul; Gupta, Savina; Chandiramani, Girish; Bali, Rati

    2011-12-01

    Routine use of posterior superior alveolar (PSA) nerve block or maxillary infiltration for the removal of maxillary molars has been validated. The present study was undertaken to determine the relative contribution of posterior superior alveolar (PSA) block in cases of anesthesia required for maxillary molars. One hundred patients requiring removal of maxillary second and third molars were enrolled. These patients were divided into 2 groups. One group received infiltration for anesthesia and other group received PSA nerve block using lignocaine with vasoconstrictor. All extractions were performed using a consistent technique of intraalveolar extraction. Data relating to the pain during extraction obtained on a visual analog scale and a verbal response scale, requirement of repeated injection for anesthesia, efficacy of these injections in localized infections, and requirement of rescue analgesics 3 hours after extraction. Statistical data confirmed clinical equivalence between infiltration and PSA nerve block. Considering the difficulty in mastering the technique of PSA nerve block, and the possibility of more complications associated with it (compared with infiltration); it may not be necessary for anesthesia of maxillary molars. Copyright © 2011 Mosby, Inc. All rights reserved.

  12. Probability of an abnormal screening prostate-specific antigen result based on age, race, and prostate-specific antigen threshold.

    PubMed

    Espaldon, Roxanne; Kirby, Katharine A; Fung, Kathy Z; Hoffman, Richard M; Powell, Adam A; Freedland, Stephen J; Walter, Louise C

    2014-03-01

    To determine the distribution of screening prostate-specific antigen (PSA) values in older men, and how different PSA thresholds affect the proportion of white, black, and Latino men who would have an abnormal screening result across advancing age groups. We used linked national Veterans Affairs and Medicare data to determine the value of the first screening PSA test (ng/mL) of 327,284 men older than 65 years who underwent PSA screening in the Veterans Affairs health care system in 2003. We calculated the proportion of men with an abnormal PSA result based on age, race, and common PSA thresholds. Among men older than 65 years, 8.4% had a PSA >4.0 ng/mL. The percentage of men with a PSA >4.0 ng/mL increased with age and was highest in black men (13.8%) vs white (8.0%) or Latino men (10.0%) (P <.001). Combining age and race, the probability of having a PSA >4.0 ng/mL ranged from 5.1% of Latino men aged 65-69 years to 27.4% of black men older than 85 years. Raising the PSA threshold from >4.0 ng/mL to >10.0 ng/mL reclassified the greatest percentage of black men older than 85 years (18.3% absolute change) and the lowest percentage of Latino men aged 65-69 years (4.8% absolute change) as being under the biopsy threshold (P <.001). Age, race, and PSA threshold together affect the pretest probability of an abnormal screening PSA result. Based on screening PSA distributions, stopping screening among men whose PSA <3 ng/mL means more than 80% of white and Latino men older than 70 years would stop further screening, and increasing the biopsy threshold to >10 ng/mL has the greatest effect on reducing the number of older black men who will face biopsy decisions after screening. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. (68)Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour.

    PubMed

    Uprimny, Christian; Kroiss, Alexander Stephan; Decristoforo, Clemens; Fritz, Josef; von Guggenberg, Elisabeth; Kendler, Dorota; Scarpa, Lorenza; di Santo, Gianpaolo; Roig, Llanos Geraldo; Maffey-Steffan, Johanna; Horninger, Wolfgang; Virgolini, Irene Johanna

    2017-06-01

    Prostate cancer (PC) cells typically show increased expression of prostate-specific membrane antigen (PSMA), which can be visualized by (68)Ga-PSMA-11 PET/CT. The aim of this study was to assess the intensity of (68)Ga-PSMA-11 uptake in the primary tumour and metastases in patients with biopsy-proven PC prior to therapy, and to determine whether a correlation exists between the primary tumour-related (68)Ga-PSMA-11 accumulation and the Gleason score (GS) or prostate-specific antigen (PSA) level. Ninety patients with transrectal ultrasound biopsy-proven PC (GS 6-10; median PSA: 9.7 ng/ml) referred for (68)Ga-PSMA-11 PET/CT were retrospectively analysed. PET images were analysed visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax). The SUVmax of the primary tumour and pathologic lesions suspicious for lymphatic or distant metastases were then compared to the physiologic background activity of normal prostate tissue and gluteal muscle. The SUVmax of the primary tumour was assessed in relation to both PSA level and GS. Eighty-two patients (91.1%) demonstrated pathologic tracer accumulation in the primary tumour that exceeded physiologic tracer uptake in normal prostate tissue (median SUVmax: 12.5 vs. 3.9). Tumours with GS of 6, 7a (3+4) and 7b (4+3) showed significantly lower (68)Ga-PSMA-11 uptake, with median SUVmax of 5.9, 8.3 and 8.2, respectively, compared to patients with GS >7 (median SUVmax: 21.2; p < 0.001). PC patients with PSA ≥10.0 ng/ml exhibited significantly higher uptake than those with PSA levels <10.0 ng/ml (median SUVmax: 17.6 versus 7.7; p < 0.001). In 24 patients (26.7%), 82 lymph nodes with pathologic tracer accumulation consistent with metastases were detected (median SUVmax: 10.6). Eleven patients (12.2%) revealed 55 pathologic osseous lesions suspicious for bone metastases (median SUVmax: 11.6). The GS and PSA level correlated with the intensity of tracer accumulation in the primary tumours of

  14. Robotic Assisted Laparoscopic Prostatectomy after High Intensity Focused Ultrasound Failure

    PubMed Central

    Telis, Leon; Jazayeri, Seyed Behzad

    2017-01-01

    Background. Prostate cancer is the most common cancer diagnosed in men. As new focal therapies become more popular in treatment of prostate cancer, failure cases requiring salvage therapy with either surgical or other techniques are being reported. Objective. To report the options in treatment of prostate cancer after recurrence or failure of the primary treatment modality. Methods. We report a salvage robotic assisted laparoscopic radical prostatectomy (RALP) for prostate cancer recurrence following high intensity focused ultrasound treatment (HIFU) in the United States. Results. A 67-year-old man who underwent HIFU treatment for prostate adenocarcinoma 2 years prior was presented with a rising prostate specific antigen of 6.1 ng/mL to our clinic. A biopsy proven recurrent disease in the area of previous treatment documented the failure of treatment. The patient elected to undergo a salvage RALP. The operation time was 159 minutes. The patient was discharged from the hospital on postoperative day 1 with no complications. The catheter was removed on post-op day 10. The patient reserved sexual function and urinary continence. The PSA levels on 6 months' follow-up are undetectable. Conclusions. Salvage RALP is an effective and safe treatment choice for recurrent prostate adenocarcinoma following failed HIFU treatment if operated by an experienced surgeon. PMID:28243479

  15. Longitudinal changes of benign prostate-specific antigen and [-2]pro-prostate-specific antigen over 7 years in a community-based sample of men

    PubMed Central

    Rhodes, Thomas; Jacobson, Debra J.; McGree, Michaela E.; St. Sauver, Jennifer L.; Girman, Cynthia J.; Lieber, Michael M.; Klee, George G.; Demissie, Kitaw; Jacobsen, Steven J.

    2012-01-01

    Introduction and Objectives Benign prostate-specific antigen (BPSA) and [-2]pro-prostate-specific antigen ([-2]proPSA) have been shown to be predictive of prostate cancer and benign prostatic hyperplasia treatment, but little is known about longitudinal changes in these markers and how they relate to outcomes. Methods In 1990, a 25% subsample from a cohort of Caucasian men aged 40–79 years randomly selected from Olmsted County, MN residents completed a detailed clinical examination. BPSA and [-2]proPSA were measured from frozen sera. Subjects were evaluated biennially (median follow-up 7 years; range: 0–8.8 years). Mixed-effects regression models were used to estimate longitudinal changes in BPSA and [-2]proPSA levels overall and by outcomes. Spearman correlations were used to compare these changes with baseline levels and annualized changes in urologic measures. Results Median (25th, 75th percentiles) annualized percent change for [-2]proPSA and BPSA were 3.7% (2.5%, 5.2%) and 7.3% (6.8%, 7.7%), respectively. Annualized percent change for both markers were correlated with baseline and annualized changes in PSA and prostate volume. Annualized percent change increased with increasing age decade for [-2]proPSA, but not BPSA. The median (25th, 75th percentiles) rate of increase in [-2]proPSA was significantly greater for men who developed enlarged prostates (3.5% (2.6%, 4.4%)) or prostate cancer (8.1% (6.6%, 9.8%)) compared to those who did not develop enlarged prostates (1.9% (0.9%, 3.0%)) or prostate cancer (3.5% (2.3%, 4.8%)). Conclusions BPSA and [-2]proPSA levels increase over time. The annualized percent change in [-2]proPSA increases with age and may be a useful predictor of development of prostate cancer. PMID:22386420

  16. Long-Term Failure Patterns and Survival in a Randomized Dose-Escalation Trial for Prostate Cancer. Who Dies of Disease?

    SciTech Connect

    Kuban, Deborah A.; Levy, Lawrence B.; Cheung, M. Rex; Lee, Andrew K.; Choi, Seungtaek; Frank, Steven; Pollack, Alan

    2011-04-01

    Purpose: To report long-term failure patterns and survival in a randomized radiotherapy dose escalation trial for prostate cancer. Materials and Methods: A total of 301 patients with Stage T1b-T3 prostate cancer treated to 70 Gy versus 78 Gy now have a median follow-up of 9 years. Failure patterns and survival were compared between dose levels. The cumulative incidence of death from prostate cancer versus other causes was examined and regression analysis was used to establish predictive factors. Results: Patients with pretreatment prostate-specific antigen (PSA) >10 ng/mL or high-risk disease had higher biochemical and clinical failures rates when treated to 70 Gy. These patients also had a significantly higher risk of dying of prostate cancer. Patients <70 years old at treatment died of prostate cancer nearly three times more frequently than of other causes when they were radiated to 70 Gy, whereas those treated to 78 Gy died of other causes more frequently. Patients age 70 or older treated to 70 Gy died of prostate cancer as often as other causes, and those receiving 78 Gy never died of prostate cancer within 10 years of follow-up. In regression analysis, factors predicting for death from prostate cancer were pretreatment PSA >10.5 ng/mL, Gleason score 9 and 10, recurrence within 2.6 years of radiation, and doubling time of <3.6 months at the time of recurrence. Conclusions: Moderate dose escalation (78 Gy) decreases biochemical and clinical failure as well as prostate cancer death in patients with pretreatment PSA >10 ng/mL or high-risk disease.

  17. Urinary prostate-specific antigen: predictor of benign prostatic hyperplasia progression?

    PubMed

    Pejcic, Tomislav P; Tulic, Cane Dz; Lalic, Natasa V; Glisic, Biljana D; Ignjatovic, Svetlana D; Markovic, Biljana B; Hadzi-Djokic, Jovan B

    2013-04-01

    Urinary prostate-specific antigen (uPSA) can be used as additional parameter of benign prostatic hyperplasia (BPH) progression. From January 2001 to December 2011, uPSA was determined in 265 patients with benign prostate. Based on total prostate volume (TPV), the patients with benign prostate were divided in two groups: TPV < 31 mL and TPV ≥ 31 mL. Additional three groups were formed upon MTOPS study criteria: non- progressive BPH group (TPV < 31 mL, PSA < 1.6 ng/mL, age < 62 yrs), intermediate group (one, or two parameters {TPV, PSA, age} increased) and progressive BPH group (TPV ≥ 31 ml, PSA ≥ 1.6 ng/mL, age ≥ 62 yrs). Average uPSA values in the groups TPV < 31 mL and TPV ≥ 31 mL were 119.3 ± 124.5 and 255.5 ± 204.9 ng/mL, respectively and they were significantly different (p < 0.0001). Average uPSA values in the non- progressive BPH group, intermediate group and progressive BPH group were 86.8 ± 82.4 ng/mL, 166.6 ± 164.9 ng/mL and 274.9 ± 208.3 ng/mL, respectively and they were significantly different (p < 0.0001). The level of uPSA correlated significantly with TPV (r = 0.32, p < 0.0001). The cut off uPSA level of 150 ng/mL discriminates the patients with non-progressive BPH and progressive BPH with specificity of 0.83 and sensitivity of 0.67. The level of uPSA reflects prostatic hormonal activity and correlates with TPV, PSA and age. UPSA level ≥ 150 ng/mL can be used as additional predictive parameter of BPH progression.

  18. Association of Obesity-Related Hemodilution of Prostate-Specific Antigen, Dihydrotestosterone, and Testosterone.

    PubMed

    Klaassen, Zachary; Howard, Lauren E; Moreira, Daniel M; Andriole, Gerald L; Terris, Martha K; Freedland, Stephen J

    2017-04-01

    Prostate-specific antigen (PSA) hemodilution is the leading theory for lower PSA values in obese men. However, testosterone and dihydrotestosterone (DHT), which are necessary for PSA production, are reduced in obese men. We assessed the relationship of body mass index (BMI) and PSA, taking into consideration the effect of testosterone and DHT. Among 8,122 participants in Reduction by Dutasteride of Prostate Cancer Events (REDUCE), complete data were available for 7,275. BMI was categorized as normal (<25 kg/m(2) ), overweight (25-29.9 kg/m(2) ), obese (30-34.9 kg/m(2) ), or moderate + severely obese (≥35 kg/m(2) ). Associations between BMI, testosterone, and DHT and the outcome variable of PSA were examined using linear regression. There were 1,964 (27.0%) normal weight, 3,826 (52.6%) overweight, 1,200 (16.5%) obese, and 285 (3.9%) moderately + severely obese patients. With increasing BMI, there was a progressive decrease in PSA (P = 0.02), increase in prostate volume (P < 0.001), and decrease in both testosterone (P < 0.001) and DHT (P < 0.001). Using linear regression, increasing BMI was associated with decreasing serum PSA values. Furthermore, BMI remained inversely associated with PSA after individually adjusting for testosterone and DHT, as well as when adjusting for testosterone and DHT in the same model. Decreased androgen levels accounted for only 19% of the lower PSA in men with higher BMI. Only a fraction of lower PSA in obese men could be attributed to testosterone and DHT levels. The remaining factors explaining lower PSA are unaccounted for, presumably secondary to hemodilution associated with increased plasma volume in obese men. Prostate 77:466-470, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Changes in antigenicity of porcine serum albumin in gamma-irradiated sausage extract by treatment with pepsin and trypsin

    NASA Astrophysics Data System (ADS)

    Kim, Koth-Bong-Woo-Ri; Song, Eu-Jin; Lee, So-Young; Park, Jin-Gyu; Lee, Ju-Woon; Byun, Myung-Woo; Ahn, Dong-Hyun

    2011-11-01

    Pork is known as an allergenic food with porcine serum albumin (PSA, 66 kDa) representing the major allergen. This study was conducted to investigate the change in antigenicity of PSA in gamma-irradiated sausage extract treated with pepsin and trypsin. Sausage products (A and B) were irradiated at 1, 3, 10, and 20 kGy. After irradiation, sausage proteins were extracted and digested with pepsin (1:200, 30 min) and trypsin (1:300, 5, 30, 60, 90, and 120 min). The binding ability of PSA in extracts of the irradiated sausages (A and B) decreased by over 3 kGy relative to the binding ability of PSA in extracts of intact sausages and showed no notable differences when the dose of radiation ranged from 3 to 20 kGy. After treatment with pepsin and trypsin, the binding ability of PSA in extracts of the irradiated sausages was decreased more relative to that of intact sausages and showed no significant differences when the period of trypsin treatment is increased or when the dose of irradiation is increased. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results indicated that there was no visible change in the intensity of the PSA band in extracts of the irradiated sausages. After pepsin and trypsin treatment, the intensity of PSA band faded with increasing doses of irradiation. In conclusion, antigenicity of PSA in pork sausages could be reduced by gamma irradiation.

  20. Relationship between dietary factors and prostate-specific antigen in healthy men.

    PubMed

    Ohwaki, Kazuhiro; Endo, Fumiyasu; Kachi, Yuko; Hattori, Kazunori; Muraishi, Osamu; Nishikitani, Mariko; Yano, Eiji

    2012-01-01

    There is little evidence indicating whether dietary factors influence prostate-specific antigen (PSA) concentrations. We examined whether nutritional factors, including energy, protein, fat, and carbohydrate intake were associated with PSA in healthy men. We investigated 13,594 men aged 50 years and over who visited a hospital for a routine health checkup between 2003 and 2007. Dietary intake was assessed using a food frequency questionnaire. We performed a multiple linear regression to examine the association between PSA and dietary intake. After controlling for age, body mass index, and physical activity, PSA was significantly negatively associated with percent protein intake (p for trend < 0.001). Compared with the lowest quintile, PSA was 5.8% lower (95% CI: -8.9 to -2.5%) in the highest quintile. We also observed a significant positive association between percent fat intake and PSA concentration (p for trend 0.043). PSA was 3.4% greater (95% CI: 0-6.9%) among men in the highest quintile compared with those in the lowest quintile. Men who had a lower percent protein intake and higher percent fat intake had an elevated PSA level, although the magnitude of these associations was small. Copyright © 2012 S. Karger AG, Basel.

  1. PSA-Stratified Performance of (18)F- and (68)Ga-PSMA PET in Patients with Biochemical Recurrence of Prostate Cancer.

    PubMed

    Dietlein, Felix; Kobe, Carsten; Neubauer, Stephan; Schmidt, Matthias; Stockter, Simone; Fischer, Thomas; Schomäcker, Klaus; Heidenreich, Axel; Zlatopolskiy, Boris D; Neumaier, Bernd; Drzezga, Alexander; Dietlein, Markus

    2017-06-01

    Several studies outlined the sensitivity of (68)Ga-labeled PET tracers against the prostate-specific membrane antigen (PSMA) for localization of relapsed prostate cancer in patients with renewed increase in the prostate-specific antigen (PSA), commonly referred to as biochemical recurrence. Labeling of PSMA tracers with (18)F offers numerous advantages, including improved image resolution, longer half-life, and increased production yields. The aim of this study was to assess the PSA-stratified performance of the (18)F-labeled PSMA tracer (18)F-DCFPyL and the (68)Ga-labeled reference (68)Ga-PSMA-HBED-CC. Methods: We examined 191 consecutive patients with biochemical recurrence according to standard acquisition protocols using (18)F-DCFPyL (n = 62, 269.8 MBq, PET scan at 120 min after injection) or (68)Ga-PSMA-HBED-CC (n = 129, 158.9 MBq, 60 min after injection). We determined PSA-stratified sensitivity rates for both tracers and corrected our calculations for Gleason scores using iterative matched-pair analyses. As an orthogonal validation, we directly compared tracer distribution patterns in a separate cohort of 25 patients, sequentially examined with both tracers. Results: After prostatectomy (n = 106), the sensitivity of both tracers was significantly associated with absolute PSA levels (P = 4.3 × 10(-3)). Sensitivity increased abruptly, when PSA values exceeded 0.5 μg/L (P = 2.4 × 10(-5)). For a PSA less than 3.5 μg/L, most relapses were diagnosed at a still limited stage (P = 3.4 × 10(-6)). For a PSA of 0.5-3.5 μg/L, PSA-stratified sensitivity was 88% (15/17) for (18)F-DCFPyL and 66% (23/35) for (68)Ga-PSMA-HBED-CC. This significant difference was preserved in the Gleason-matched-pair analysis. Outside of this range, sensitivity was comparably low (PSA < 0.5 μg/L) or high (PSA > 3.5 μg/L). After radiotherapy (n = 85), tracer sensitivity was largely PSA-independent. In the 25 patients examined with both tracers, distribution patterns of (18)F-DCFPyL and

  2. Co-expression and impact of prostate specific membrane antigen and prostate specific antigen in prostatic pathologies

    PubMed Central

    2010-01-01

    Background The present study was undertaken to relate the co-expression of prostate-associated antigens, PSMA and PSA, with the degree of vascularization in normal and pathologic (hyperplasia and cancer) prostate tissues to elucidate their possible role in tumor progression. Methods The study was carried out in 6 normal, 44 benign prostatic hyperplastic and 39 cancerous human prostates. Immunohistochemical analysis were performed using the monoclonal antibody CD34 to determine the angiogenic activity, and the monoclonal antibodies 3E6 and ER-PR8 to assess PSMA and PSA expression, respectively. Results In our study we found that in normal prostate tissue, PSMA and PSA were equally expressed (3.7 ± 0.18 and 3.07 ± 0.11). A significant difference in their expression was see in hyperplastic and neoplastic prostates tissues (16.14 ± 0.17 and 30.72 ± 0.85, respectively) for PSMA and (34.39 ± 0.53 and 17.85 ± 1.21, respectively) for PSA. Study of prostate tumor profiles showed that the profile (PSA+, PSMA-) expression levels decreased between normal prostate, benign prostatic tissue and primary prostate cancer. In the other hand, the profile (PSA-, PSMA+) expression levels increased from normal to prostate tumor tissues. PSMA overexpression was associated with high intratumoral angiogenesis activity. By contrast, high PSA expression was associated with low angiogenesis activity. Conclusion These data suggest that these markers are regulated differentially and the difference in their expression showed a correlation with malignant transformation. With regard to the duality PSMA-PSA, this implies the significance of their investigation together in normal and pathologic prostate tissues. PMID:21189143

  3. Ejaculation increases the serum prostate-specific antigen concentration.

    PubMed

    Tchetgen, M B; Song, J T; Strawderman, M; Jacobsen, S J; Oesterling, J E

    1996-04-01

    To determine the effect of ejaculation on the serum prostate-specific antigen (PSA) concentration in men at risk for developing prostate cancer. A prospective, community-based study was conducted in which 64 men, aged 49 to 79 years, underwent a serum PSA determination immediately before ejaculation (baseline) and at 1 hour, 6 hours, and 24 hours following ejaculation. The serum PSA also was measured 48 hours and 1 week after ejaculation if the concentration had not returned to the baseline value by the previous time interval. All subjects abstained from ejaculation for a minimum of 7 days prior to the study and until the PSA concentration returned to the baseline level. Absolute and relative change in serum PSA concentration, as well as the time to return to baseline PSA concentration following ejaculation, were assessed. The serum PSA concentration increased following ejaculation in 87% of the subjects. The mean baseline PSA was 1.8 ng/mL (median, 0.7 ng/mL). The mean absolute PSA change +/- standard deviation 1 hour, 6 hours, 24 hours, and 48 hours after ejaculation was 0.8 +/- 1.32 ng/mL, 0.3 +/- 0.66 ng/mL, 0.2 +/- 0.33 ng/mL, and 0.4 +/- 0.40 ng/mL, respectively. The mean relative PSA change +/- standard error 1 hour, 6 hours, 24 hours, and 48 hours after ejaculation was 41 +/- 4%, 9 +/- 1.5%, 8 +/- 1.3%, and 10 +/- 2.3%, respectively. The absolute and relative changes in PSA concentration noted 1 hour, 6 hours, and 24 hours after ejaculation were statistically significant (P = 0.0001). A strong correlation was observed between absolute change in PSA and baseline serum PSA, at each time interval (1 hour: r = 0.68, 6 hours: r = 0.77, 24 hours: r = 0.70; P < 0.0001) after ejaculation. Similarly, a significant correlation was noted between absolute change in PSA and patient age at each time interval (1 hour: r = 0.37, 6 hours: r = 0.38; P = 0.002, 24 hours: r = 0.55; P < 0.0001). Ninety-two percent of subjects returned to baseline by 24 hours (95% confidence

  4. [Relationship between screening by stratifying cases into groups on prostate specific antigen level and the positive rate of transrectal ultrasound guided systematic sextant prostate biopsy].

    PubMed

    Cao, Xi-liang; Gao, Jiang-ping; Han, Gang; Tang, Jie; Hong, Bao-fa

    2006-03-15

    To evaluate the detection of prostate cancer in different prostate specific antigen (PSA) level and the predict value of PSA, digital rectal examination (DRE), transrectal ultrasound scan (TRUS) and PSA density (PSAD). The clinical data of 634 cases who had underwent transrectal ultrasound guided systematic sextant prostate biopsies between April 1996 to December 2002 due to being suspicious of prostate cancer were retrospectively analyzed. The detection of prostate cancer in different PSA groups, namely PSA < or = 4.0, 4.1-, 10.1-, > 20.0 microg/L, and the predict values of PSA, DRE, TRUS and PSAD were statistically analyzed using t test, chi2 test and logistic regression analysis. The rates of prostate cancer detection in different PSA groups were 11.6%, 26.8%, 39.8% and 68.6%, respectively. The higher the PSA, the higher the rate of prostate cancer detection, the same was the positive predictive value of DRE and TRUS. The sensitivity and specificity of PSA > 4.0 microg/L were 93.0% and 33.0%, and the efficiency of DRE and TRUS were very low. Logistic regression analysis indicated that PSAD was the most risk factor of prostate cancer in the group of PSA 4.1-20.0 microg/L (OR = 687.09 +/- 646.96, P = 0.000). The rates of prostate cancer detection in different PSA groups are different compared with other countries. The screening roles of DRE and TRUS are dependent on PSA level. Utilization of the screening protocol which to stratify cases into three PSA groups, namely PSA < or = 4.0, 4.1 - 20.0, > 20.0 microg/L, can elevate the positive rate of prostate biopsies without sacrificing cancers detected.

  5. Prostate-specific antigen and its derivatives in young adults occupationally exposed to quarry pollutants in southeastern Nigeria.

    PubMed

    Ewenighi, Chinwe O; Dimkpa, Uchechukwu; Onyeanusi, Joel C; Babtunde, Adejumo; Onoh, Linus U M; Onoh, Gladys O; Ezeugwu, Uchechukwu

    2017-09-03

    To evaluate the level of total prostate-specific antigen (PSA) and effect of duration of exposure to pollutants in quarry workers, 5 mls of blood sample was collected from participants: 72 male quarry workers exposed to quarry pollutants and 72 unexposed controls. PSA estimations were done using the principle of ELISA. Mean total PSA, free PSA, and free-total PSA ratio levels of quarry workers did not differ from those of controls and was below the cutoff for the risk of prostate diseases. Higher mean total PSA and free PSA were observed in workers exposed for > 3 years compared to the unexposed control and workers exposed for ≤ 3 years. Age-adjusted linear regression indicated significant association (R = 0.515; p < .001) between the duration of exposure and total PSA level in quarry workers. This study suggests that longer duration of exposure to the quarry pollutants may elevate PSA level if precautions are not taken to minimize dose of exposure.

  6. ‘Relationship between prostate-specific antigen, age and body mass index in a prostate cancer screening population

    PubMed Central

    Pater, Luke E.; Hart, Kimberly W.; Blonigen, Brian J.; Lindsell, Christopher J.; Barrett, William L.

    2011-01-01

    Background Recent studies questioning the benefit of prostate specific antigen (PSA) screening have increased the need for evaluating factors contributing to variance in levels and their clinical relevance. An inverse relationship between body mass index (BMI) and PSA has been illustrated, however the clinical implications have not been specified. We performed a retrospective review of patients screened through our free screening clinic to delineate any relationship between PSA and BMI in an attempt to understand its possible clinical significance. Methods The authors retrospectively reviewed data collected in relation to PSA values and patient characteristics from a community outreach program supplying information and screening for prostate cancer between June of 2003 and August of 2009. Results Mean BMI of our patient population was 28.7m/kg2 (SD 5.4) and our mean PSA value was 1.28 (SD 1.77). Our data indicates a small, but statistically significant decrease in PSA for an increasing BMI with a 0.026 decrease in PSA for every unit increase in BMI. Conclusions Our study confirms the previously reported inverse relationship between PSA value and BMI. The significance of this finding and its impact on the value do not appear to indicate a rationale to change the accepted abnormal value in obese patients and should be used in the context of the clinical scenario and other PSA altering factors. PMID:21577087

  7. Prostate Cancer in Patients With High Prostate-Specific Antigen Levels but Otherwise Very-Low-Risk Disease Behaves Like Prostate Cancer in High-Risk Patients.

    PubMed

    Gestaut, Matthew M; Pruszynski, Jessica E; Swanson, Gregory P

    2017-08-01

    Rarely, patients with prostate cancer present with prostate-specific antigen (PSA) scores > 20 ng/mL but with otherwise very-low-risk disease. Oncologists have debated whether the malignancies in these patients behave more comparably to low-risk or high-risk disease. Our objective was to elucidate the behavior of these malignancies. A retrospective review was conducted of prostate cancer patients treated with radiation from 2000 to 2013. The inclusion criteria for very-low-risk disease included stage T1a-T1c, Gleason score ≤ 6, ≤ 3 positive cores, ≤ 50% involvement of any core, and PSA level < 10 ng/mL. The divergent-risk group met all the same criteria but had a PSA score of 20 to 80 ng/mL. The high-grade, low-volume group consisted of patients with stage T1c-T2a, PSA level < 20 ng/mL, Gleason score of 4+4, and < 4 positive cores. Treatment failure was defined as a PSA nadir plus 2 ng/mL. A total of 18, 60, and 19 patients were in the divergent, low-risk, and high-grade groups, respectively. Biochemical progression-free survival at 5 years was 71.3% for the divergent group, 68.8% for the high-grade group, and 98.3% for the low-risk group. The biochemical failure rate for the divergent group differed significantly from the low-risk group (P = .021), and that for the low-risk group was significantly different from that of the high-grade group (P = .025). However, the divergent group did not appear different from the high-grade group (P = .53). The results of our study have shown that the disease prognosis for the divergent-risk group is worse than that for the very-low-risk disease group and does not appear to be different from that for the low-volume, high-grade disease group. Oncologists should be aware that the outcomes for divergent patients are similarly poor to their low-volume, classically high-risk counterparts. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Serum levels of PSA, ALP, ICTP, and BSP in prostate cancer patients and the significance of ROC curve in the diagnosis of prostate cancer bone metastases.

    PubMed

    Wei, R J; Li, T Y; Yang, X C; Jia, N; Yang, X L; Song, H B

    2016-06-03

    Bone metastasis is a common complication in prostate cancer patients that can cause bone pain and pathological fracture. This study tested serum levels of prostate specific antigen (PSA), alkaline phosphatase (ALP), bone sialoprotein (BSP), collagen type I pyridine crosslinking peptide (ICTP) in prostate cancer patients and the significance of the receiver operator characteristic (ROC) curve in the diagnosis of prostate cancer bone metastases. Eighty-three prostate cancer patients were enrolled including 42 in the bone metastases group and 41 in the non-bone metastases group. Serum levels of BSP, ALP, ICTP, and PSA were highest in the bone metastases group followed by the non-bone metastases group, hyperplasia group, and then the control group (P < 0.05). Based on Gleason score, serum levels were highest in the poorly differentiated group followed by moderately differentiated and well-differentiated groups (P < 0.05). ROC curve analysis revealed that the diagnostic efficiency of the biomarkers in turn was BSP, PSA, ICTP, and ALP. The sensitivity of BSP, ALP, ICTP, and PSA in the diagnosis of prostate cancer bone metastases were 80.95, 57.14, 69.05, 71.43%, respectively, and the specificity of the same markers were 72.80, 64.80, 76.80, and 88.80%, respectively. Combined detection of the four markers improved sensitivity to 97.62% and the negative-predictive value increased to 97.60%. PSA + BSP showed the best efficiency when combining two markers. In conclusion, serum levels of BSP, ALP, ICTP, and PSA increased in patients with bone metastases, and combined detection of all markers could improve the positive-predictive value.

  9. Association of [-2]proPSA with Biopsy Reclassification During Active Surveillance for Prostate Cancer

    PubMed Central

    Tosoian, Jeffrey J.; Loeb, Stacy; Feng, Zhaoyong; Isharwal, Sumit; Landis, Patricia; Elliot, Debra J.; Veltri, Robert; Epstein, Jonathan I.; Partin, Alan W.; Carter, H. Ballentine; Trock, Bruce; Sokoll, Lori J.

    2014-01-01

    Purpose Previous studies have suggested an association between [-2]proPSA expression and prostate cancer detection. Less is known about the utility of this marker in following prostate cancer patients on active surveillance. Thus, our objective was to examine the relationship between [-2]proPSA and biopsy results in men enrolled in an active surveillance program. Materials and Methods In 167 men from our institutional active surveillance program, we used Cox proportional hazards models to examine the relationship between [-2]proPSA and annual surveillance biopsy results. The outcome of interest was biopsy reclassification (Gleason score ≥7, or >2 positive biopsy cores, or >50% involvement of any core with cancer). We also examined the association of biopsy results with total PSA, %fPSA, [-2]proPSA/%fPSA, and the Beckman Coulter Prostate Health Index [phi=([-2]proPSA/fPSA) x (tPSA)½]. Results While on active surveillance (median time from diagnosis 4.3 years), 63 (37.7%) men demonstrated biopsy reclassification based on the above criteria, including 28 (16.7%) of whom had reclassification based on Gleason score upgrading (Gleason score≥7). Baseline and longitudinal %fPSA, %[-2]proPSA, [-2]proPSA/%fPSA, and phi measurements were significantly associated with biopsy reclassification, and %[-2]proPSA and phi provided the greatest predictive accuracy for high-grade cancer. Conclusions In men on active surveillance, measures based on [-2]proPSA such as phi, appear to provide improved prediction of biopsy reclassification during follow-up. Additional validation is warranted to determine whether clinically useful thresholds can be defined, and to better characterize the role of %[-2]proPSA and phi in conjunction with other markers in monitoring patients enrolled in active surveillance. PMID:22901577

  10. [PSA-screening for prostate cancer--yes or no?].

    PubMed

    Recker, F; Kwiatkowski, M

    2004-06-01

    Prostate cancer is a mayor health care problem, especially in the industrialised countries of the Western world. At this time it is the second most common cancer reason for death (CH: 1500 men/year) which will even get more importance in the future by demographic developments. While there is no doubt that in individuals early detection of organ confined disease with localised treatment the prostate cancer can be eradicated and individual men be cured there are uncertainties whether mass screening a population will contribute to reducing prostate cancer related mortality. Its value has not been proved definitively by prospective randomised controlled studies. Most of Medical Societies recommend a "well informed" decision by family physicians, where the men between 50-70 years know about the benefits and harms including: risk of cancer, diagnostic procedures, therapeutic consequences and possible side effects. After agreement of early detection a biopsy has to be done directly above a PSA level of 4.0 ng/ml or a suspicious digital rectal examination. A PSA "grey zone" 4-10 ng/ml can not further be postulated. The ratio of free/total PSA gives no support to prolong biopsy in this moment, because an elevated benign prostate with a higher production of free PSA can mask the tumor in the peripheral zone. Results of the ERSPC and the PLCO trials are expected to give information about the benefits and harms of mass screening in 2006/8.

  11. Prostate Cancer Screening: Should You Get a PSA Test?

    MedlinePlus

    ... results are in. These include: Worry about false-positive results caused by elevated PSA levels from something other than prostate cancer Invasive, stressful, expensive or time-consuming follow-up tests Stress or anxiety caused by knowing you have a ...

  12. GIS Technologies For The New Planetary Science Archive (PSA)

    NASA Astrophysics Data System (ADS)

    Docasal, R.; Barbarisi, I.; Rios, C.; Macfarlane, A. J.; Gonzalez, J.; Arviset, C.; De Marchi, G.; Martinez, S.; Grotheer, E.; Lim, T.; Besse, S.; Heather, D.; Fraga, D.; Barthelemy, M.

    2015-12-01

    Geographical information system (GIS) is becoming increasingly used for planetary science. GIS are computerised systems for the storage, retrieval, manipulation, analysis, and display of geographically referenced data. Some data stored in the Planetary Science Archive (PSA), for instance, a set of Mars Express/Venus Express data, have spatial metadata associated to them. To facilitate users in handling and visualising spatial data in GIS applications, the new PSA should support interoperability with interfaces implementing the standards approved by the Open Geospatial Consortium (OGC). These standards are followed in order to develop open interfaces and encodings that allow data to be exchanged with GIS Client Applications, well-known examples of which are Google Earth and NASA World Wind as well as open source tools such as Openlayers. The technology already exists within PostgreSQL databases to store searchable geometrical data in the form of the PostGIS extension. An existing open source maps server is GeoServer, an instance of which has been deployed for the new PSA, uses the OGC standards to allow, among others, the sharing, processing and editing of data and spatial data through the Web Feature Service (WFS) standard as well as serving georeferenced map images through the Web Map Service (WMS). The final goal of the new PSA, being developed by the European Space Astronomy Centre (ESAC) Science Data Centre (ESDC), is to create an archive which enables science exploitation of ESA's planetary missions datasets. This can be facilitated through the GIS framework, offering interfaces (both web GUI and scriptable APIs) that can be used more easily and scientifically by the community, and that will also enable the community to build added value services on top of the PSA.

  13. Prostate-specific antigen kinetics following hypofractionated stereotactic body radiotherapy boost as post-external beam radiotherapy versus conventionally fractionated external beam radiotherapy for localized prostate cancer

    PubMed Central

    Phak, Jeong Hoon; Kim, Hun Jung; Kim, Woo Chul

    2015-01-01

    Background Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. The purpose of this study was to compare the prostate-specific antigen (PSA) kinetics between conventionally fractionated external beam radiotherapy (CF-EBRT) and SBRT boost after whole pelvis EBRT (WP-EBRT) in localized prostate cancer. Methods A total of 77 patients with localized prostate cancer [T-stage, T1–T3; Gleason score (GS) 5–9; PSA < 20 ng/mL] were enrolled. A total of 35 patients were treated with SBRT boost (21 Gy in 3 fractions) after WP-EBRT and 42 patients were treated with CF-EBRT (45 Gy WP-EBRT and boost of 25.2–30.6 Gy in 1.8-Gy fractions). PSA nadir and rate of change in PSA (slope) were calculated and compared. Results With a median follow-up of 52.4 months (range, 14–74 months), the median PSA nadir and slope for SBRT boost were 0.29 ng/mL and −0.506, −0.235, −0.129, and −0.092 ng/mL/mo, respectively, for durations of 1 year, 2 years, 3 years, and 4 years postradiotherapy. Similarly, for CF-EBRT, the median PSA nadir and slopes were 0.39 ng/mL and −0.720 ng/mL/mo, −0.204 ng/mL/mo, −0.121 ng/mL/mo, and −0.067 ng/mL/mo, respectively. The slope of CF-EBRT was significantly different with a greater median rate of change for 1 year postradiotherapy than that of SBRT boost (P = 0.018). Contrastively, the slopes of SBRT boost for durations of 2 years, 3 years, and 4 years tended to be continuously greater than that of CF-EBRT. The significantly lower PSA nadir was observed in SBRT boost (median nadir 0.29 ng/mL) compared with CF-EBRT (median nadir 0.35 ng/mL, P = 0.025). Five-year biochemical failure (BCF) free survival was 94.3% for SBRT boost and 78.6% for CF-EBRT (P = 0.012). Conclusion Patients treated with SBRT boost after WP-EBRT experienced a lower PSA nadir and there tended to be a continuously greater rate of decline of PSA for durations of 2 years, 3 years, and

  14. Prostate-specific antigen test use and digital rectal examinations among African-American men, 2002-2006.

    PubMed

    Ross, Louie E; Meade, Shelly-Ann; Powe, Barbara D; Howard, Daniel L

    2009-07-01

    African-American men experience greater incidence and mortality from prostate cancer compared to White men as well as men from other groups. Few studies have examined prostate-specific antigen (PSA) test and digital rectal examination (DRE) use in African-American men. This study examined use of the PSA test and DRE among African-American men over time and identified correlates associated with the use of these procedures. Overall trends for years 2002-2006 showed a significant decrease in recent PSA test use and DRE among African-American men in 2004 and 2006 compared to year 2002. Recent PSA test use and DRE were associated with several factors including older ages, being married, higher levels of education and income, and overweight and obese body mass index (BMI). PSA test use and DRE among African-American men should be monitored over time to find out if this pattern continues.

  15. Bayesian Inference for Time Trends in Parameter Values: Case Study for the Ageing PSA Network of the European Commission

    SciTech Connect

    Dana L. Kelly; Albert Malkhasyan

    2010-06-01

    There is a nearly ubiquitous assumption in PSA that parameter values are at least piecewise-constant in time. As a result, Bayesian inference tends to incorporate many years of plant operation, over which there have been significant changes in plant operational and maintenance practices, plant management, etc. These changes can cause significant changes in parameter values over time; however, failure to perform Bayesian inference in the proper time-dependent framework can mask these changes. Failure to question the assumption of constant parameter values, and failure to perform Bayesian inference in the proper time-dependent framework were noted as important issues in NUREG/CR-6813, performed for the U. S. Nuclear Regulatory Commission’s Advisory Committee on Reactor Safeguards in 2003. That report noted that “industry lacks tools to perform time-trend analysis with Bayesian updating.” This paper describes an application of time-dependent Bayesian inference methods developed for the European Commission Ageing PSA Network. These methods utilize open-source software, implementing Markov chain Monte Carlo sampling. The paper also illustrates the development of a generic prior distribution, which incorporates multiple sources of generic data via weighting factors that address differences in key influences, such as vendor, component boundaries, conditions of the operating environment, etc.

  16. Association of Diet With Prostate Specific Antigen and Prostate Volume

    PubMed Central

    Shirazi, Mehdi; Ariafar, Ali; Zeyghami, Shahryar; Hosseini, Mohammad Mehdi; Khezri, Abdol Aziz

    2014-01-01

    Background: Prostate is an important male reproductive system gland and its disorders can affect men's quality of life and health. Prostatitis, benign prostatic hyperplasia (BPH), and prostate adenocarcinoma are major disorders that can be found in all men in different ages. Objectives: The aim of this study was to investigate the association of diet with serum prostate specific antigen (PSA) level as well as prostate volume. Patients and Methods: In this cross-sectional study, 950 men older than 40 years of age who had attended our clinic for a screening program for prostate cancer were enrolled. Data was extracted from the program database. The eligible cases included all noncancerous subjects with available data concerning serum PSA level and prostate volume; the patients had completed a 50-item self-administered food frequency questionnaire about their diet during the preceding two year. Results: No overall association was found between the consumption of foods and prostate volume as well as serum PSA level. There was a significant correlations between age and serum PSA level (r = 0.24) as well as with prostate volume (r = 0.22) (P < 0.001). In addition, there was a significant correlation between serum PSA level and prostate volume (r = 0.41 and P < 0.001). Conclusions: The results of this study confirmed the previous reports regarding the serum PSA level correlation with prostate volume. There was no evidence that dietary patterns might have any important effect on prostate volume and serum PSA in this Iranian population. PMID:25695023

  17. Prostate-Specific Antigen: Nonspecific in Deceased Organ Donors.

    PubMed

    Pabisiak, K; Ostrowski, M; Kram, A; Safranow, K; Myślak, M; Sieńko, J; Sulikowski, T; Ciechanowski, K

    2016-06-01

    Currently, there is no clear position regarding the donation of organs from donors with prostate carcinoma (CaP) in European countries, except Italy. The lengthening of life expectancy increases the probability of prostate cancer among potential organ donors. The concentration of prostate-specific antigen (PSA) >2 ng/mL at 60 years of age is related to the increasing possibility of identifying an advanced form of CaP. In recent years in Poland, the recommendation has been to determine tumor markers in potential donors. In the first year of the recommendation, 10% of potential male cadaveric donors were disqualified in West Pomerania, Poland, on the basis of elevated PSA levels (>10 ng/mL). To avoid reduction of the actual donor pool, each potential male donor reported to the center since January 2010 undergoes a routine histologic evaluation of the whole prostate, regardless of the PSA level, before organ implantation. In the study group (N = 52), histopathologic evaluation revealed 6 cases of CaP (12%). In CaP positive group Gleason score range from 2+2 to 3+4. In CaP donors PSA level have been noticed in range 1.79 ng/mL - 7.66 ng/mL. There was no correlation between histologically confirmed CaP and the PSA level. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. [Research on serum prostate-specific antigen measurement by characteristic spectral absorption method].

    PubMed

    Zhu, Jian-ming; Chen, Zhen-cheng

    2012-01-01

    A serum prostate-specific antigen (PSA) measurement method was studied using immunochromatography-based colloidal gold-marked test-strips and characteristic spectral absorption method. Some LEDs in the range from 520 to 535 nm irradiated the test-strips sampled by PSA, and then a photodiode in the range from 520 to 540 nm measured the reflex light at the specific area. Accordingly, the absorbency of the strip could be calculated, then the relationship between PSA level and strip absorbency could be ascertained by linear fit method. The experimental measurement system was calibrated by different PSA standard solutions in this research. As a result, in the range between 5 to 50 ng x mL(-1), the levels of PSA have a linear relationship with the absorbency of test-strips. Some experiments were completed by 21 different PSA standard solutions within that range, and then the correlation coefficient of the results is equal to 0.910, which proves that the proposed method for serum PSA level measurement is feasible.

  19. Semenogelins I and II bind zinc and regulate the activity of prostate-specific antigen.

    PubMed

    Jonsson, Magnus; Linse, Sara; Frohm, Birgitta; Lundwall, Ake; Malm, Johan

    2005-04-15

    In semen, the gel proteins SgI and SgII (semenogelins I and II) are digested by PSA (prostate-specific antigen), resulting in liquefaction and release of motile spermatozoa. Semen contains a high concentration of Zn2+, which is known to inhibit the protease activity of PSA. We characterized the binding of Zn2+ to SgI and SgII and found evidence that these proteins are involved in regulating the activity of PSA. Intact SgI and SgII and synthetic semenogelin peptides were used in the experiments. Binding of Zn2+ was studied by radioligand blotting, titration with a zinc (II) fluorophore chelator and NMR analysis. A chromogenic substrate was used to measure the enzymatic activity of PSA. SgI and SgII bound Zn2+ with a stoichiometry of at least 10 mol (mol of protein)(-1) and with an average dissociation constant of approx. 5 microM per site. Moreover, Zn2+-inhibited PSA was activated by exposure to SgI or SgII. Since both proteins have high affinity for Zn2+ and are the dominating proteins in semen, they probably represent the major Zn2+ binders in semen, one function of which may be to regulate the activity of PSA. The system is self-regulating, and PSA is maintained in an active state by its substrate.

  20. Extended use of Prostate Health Index and percentage of [-2]pro-prostate-specific antigen in Chinese men with prostate specific antigen 10–20 ng/mL and normal digital rectal examination

    PubMed Central

    Chiu, Peter Ka-Fung; Teoh, Jeremy Yuen-Chun; Lee, Wai-Man; Yee, Chi-Hang; Chan, Eddie Shu-Yin; Hou, See-Ming

    2016-01-01

    Purpose We investigated the extended use of Prostate Health Index (PHI) and percentage of [-2]pro-prostate-specific antigen (%p2PSA) in Chinese men with prostate-specific antigen (PSA) 10–20 ng/mL and normal digital rectal examination (DRE). Materials and Methods All consecutive Chinese men with PSA 10–20 ng/mL and normal DRE who agreed for transrectal ultrasound (TRUS)-guided 10-core prostate biopsy were recruited. Blood samples were taken immediately before TRUS-guided prostate biopsy. The performances of total PSA (tPSA), %free-to-total PSA (%fPSA), %p2PSA, and PHI were compared using logistic regression, receiver operating characteristic, and decision curve analyses (DCA). Results From 2008 to 2015, 312 consecutive Chinese men were included. Among them, 53 out of 312 (17.0%) men were diagnosed to have prostate cancer on biopsy. The proportions of men with positive biopsies were 6.7% in PHI<35, 22.8% in PHI 35–55, and 54.5% in PHI>55 (chi-square test, p<0.001). The area under curves (AUC) of the base model including age, tPSA and status of initial/repeated biopsy was 0.64. Adding %p2PSA and PHI to the base model improved the AUC to 0.79 (p<0.001) and 0.78 (p<0.001), respectively, and provided net clinical benefit in DCA. The positive biopsy rates of Gleason 7 or above prostate cancers were 2.2% for PHI<35, 7.9% for PHI 35–55, and 36.4% for PHI>55 (chi-square test, p<0.001). By utilizing the PHI cutoff of 35 to men with PSA 10–20 ng/mL and normal DRE, 57.1% (178 of 312) biopsies could be avoided. Conclusions Both PHI and %p2PSA performed well in predicting prostate cancer and high grade prostate cancer. The use of PHI and %p2PSA should be extended to Chinese men with PSA 10–20 ng/mL and normal DRE. PMID:27617315

  1. VVER 440 Reliability Data Used for PSA Studies

    SciTech Connect

    Cillik, Ivan; Prochaska, Jan; Halada, Peter

    2002-07-01

    The paper presents the methods used for the reliability parameter calculations. The method includes full procedure of a plant specific data gathering and processing for the purposes for full and low power conditions and shutdown states for V1 WWER 440/V230 and V2 WWER 440/V213 located in Jaslovske Bohunice, Slovakia. Presented calculations include unavailability due to maintenance and test as well as some special cases. More detail description of sources plant specific data used for final elaboration as well as software used for reliability parameters calculation is given. Different software output files present data formats required not only by PSA models including calculation background for defined component groups. Based on the quality of the presented VVER 440 data V E Trnava was contracted by U.S. DOE to support its PSA activities in Russia. (authors)

  2. Methyl selenium metabolites decrease prostate-specific antigen expression by inducing protein degradation and suppressing androgen-stimulated transcription.

    PubMed

    Cho, Sung Dae; Jiang, Cheng; Malewicz, Barbara; Dong, Yan; Young, Charles Y F; Kang, Kyung-Sun; Lee, Yong-Soon; Ip, Clement; Lü, Junxuan

    2004-05-01

    Prostate-specific antigen (PSA) is widely used clinically for prostate cancer diagnostics and as an indicator of therapeutic efficacy and recurrence. Several human chemoprevention trials are being conducted to validate the prostate cancer prevention efficacy of selenium and PSA is used in these trials as a biomarker of response. A better understanding of the effects of selenium metabolites on the kinetics of PSA turnover and secretion in prostate cancer cells treated with selenium at concentrations which are achievable physiologically will be important for interpreting the results of these trials. This study addresses whether the putative active anticancer selenium metabolite methylselenol or its precursor methylseleninic acid (MSeA) specifically inhibits PSA expression in the androgen-responsive LNCaP prostate cancer cell model. The results show that exposure to sub-apoptotic concentrations of MSeA and methylselenol inhibited PSA protein expression and secretion, whereas sodium selenite and selenomethionine lacked inhibitory effect. The inhibition was detectable at 3 h of exposure and required a threshold level of MSeA to sustain. Turnover experiments showed that MSeA caused rapid PSA degradation, which was partially blocked by lysosomal inhibitors, but not by a proteasomal inhibitor. Furthermore, MSeA treatment reduced PSA mRNA level, down-regulated androgen receptor protein expression, and inhibited androgen-stimulated PSA promoter transcription. In summary, methylselenol or MSeA specifically and rapidly inhibited PSA expression through two mechanisms of action: inducing PSA protein degradation and suppressing androgen-stimulated PSA transcription. These findings may have important mechanistic implications for the prostate specific cancer chemopreventive action of selenium.

  3. A genome-wide association study of serum levels of prostate-specific antigen in the Japanese population.

    PubMed

    Terao, Chikashi; Terada, Naoki; Matsuo, Keitaro; Kawaguchi, Takahisa; Yoshimura, Koji; Hayashi, Norio; Shimizu, Masakazu; Soga, Norihito; Takahashi, Meiko; Kotoura, Yoshihiko; Yamada, Ryo; Ogawa, Osamu; Matsuda, Fumihiko

    2014-08-01

    Prostate-specific antigen (PSA) is a useful marker for prostate cancer (PCa) and is widely used for screening of PCa. Previous studies have shown that genetic components influence the levels of PSA, and some of these genetic components would lead to better diagnostic sensitivity and specificity to PCa. However, genetic studies for PSA from Asian countries are limited. Our aim was to identify genetic components influencing PSA levels in the Japanese population using genome-wide association study (GWAS) and to analyse whether genetic components would lead to better screening abilities of PCa. We performed a GWAS comprising 1086 male subjects using 303 283 single nucleotide proteins, followed by a replication study of 1302 subjects. PSA levels were quantified by chemiluminescence immunoassay method. Quantitative linear regression analysis was performed to assess genetic components of PSA levels. A total of 413 subjects with prostate biopsies were analysed to examine whether genetic determinants would improve diagnostic ability. Rs16856139 in SLC45A3, the same region as the previous Chinese study, showed an overall significant association with PSA levels (p=2.4×10(-11)) along with rs1058205 in KLK3. In silico analysis revealed significant association between rs16856139 and expression of SLC45A3. Genetic scores of PSA showed a dose-dependent decrease of area under curve (AUC) of PCa and successfully subgrouped the individuals with significantly different AUC (p≤0.0097). Rs16856139, associated with the expression of SLC45A3, is significantly associated with the levels of PSA in the Japanese population. Classification of subjects based on PSA genetic determinants would improve screening ability of PSA to detect PCa. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. A Diet, Physical Activity, and Meditation Intervention in Men With Rising Prostate-Specific Antigen (PSA)

    DTIC Science & Technology

    2007-05-01

    mediators, and confounders of treatment effect. 15. SUBJECT TERMS Clinical Trial, Diet, Nutrition , Physical Activity, Meditation, Prevention ...Nurse, and other project staff. • A Project Coordinator trained in nutrition and exercise science was hired in August 2003. In the fall of 2004...Biostatistics. • Tom Hurley, biostatistian in the Statewide Cancer Prevention and Control Program and USC the Department of Epidemiology and Biostatistics

  5. Relationship of body mass index and prostate specific antigen in a population-based study.

    PubMed

    Thompson, Ian M; Leach, Robin; Troyer, Dean; Pollock, Brad; Naylor, Susan; Higgins, Betsy

    2004-01-01

    This study was designed to use a prospectively analyzed, population-based, multiethnic cohort of men to determine if there is a relationship between one measure of obesity/overweight (Body Mass Index) and Prostate Specific Antigen (PSA). A total of 1565 men without a prior diagnosis of prostate cancer were prospectively enrolled in the San Antonio study of Biomarkers Of Risk (SABOR) Clinical and Epidemiologic Center of the Early Detection Research Network of the National Cancer Institute. Body Mass Index (BMI) was compared with serum PSA levels, stratifying by ethnic group. No relationship was found between BMI and PSA in any ethnic group or in the cohort as a whole. This study suggests that there is no increased risk of overdetection of prostate cancer among obese men due to an elevation in PSA.

  6. Significance of serum total prostate specific antigen and digital rectal examination in the diagnosis of prostate cancer.

    PubMed

    Abdrabo, Abdelkarim A; Fadlalla, Adil I; Fadl-Elmula, Imad M

    2011-11-01

    To assess the significance of serum total prostate specific antigen (tPSA) and digital rectal examination (DRE) in the diagnosis of prostate cancer (PC). One hundred and eighteen patients with serum tPSA ranging between 2.5 and 10 ng/ml with lower urinary tract symptoms presented at the Urology Clinic of Soba University Hospital, Khartoum, Sudan from August 2008 and January 2010 were included in the study. Serum tPSA was measured using enzyme immunoassay method, and accordingly, the patients were classified into 2 groups: patients that had tPSA between 2.5-4.0 ng/ml; and patients that had tPSA between 4.1-10 ng/ml. The DRE was performed on all patients by a qualified urologist, and were recorded as a group with suspicion of PC, and a group with no suspicion of PC. All patients underwent transrectal sextant prostate biopsy. The DRE alone showed 63.8% sensitivity and 68% specificity with 46.9% positive predictive value (PPV) for the diagnosis of PC. The tPSA test revealed 91.6% sensitivity and 24% specificity with PPV of 34%. However, when combining DRE and tPSA, the sensitivity reached 100% and the specificity increased to 92% with PPV of 49%. Combining DRE and tPSA test increases the sensitivity, specificity, and PPV of PC detection.

  7. Opportunistic prostate-specific antigen screening in Italy: 6 years of monitoring from the Italian general practice database.

    PubMed

    D'Ambrosio, Gaetano Giorgio; Campo, Salvatore; Cancian, Maurizio; Pecchioli, Serena; Mazzaglia, Giampiero

    2010-11-01

    The practice of prostate-specific antigen (PSA) screening has been increasing in Italy despite uncertain scientific evidence and contrary recommendations from most scientific societies. In 2002, a survey of PSA screening diffusion among general practices was performed, looking for screening frequency and age pattern of screened individuals. The objective of this study was to assess whether the features of PSA screening did change after 6 years in the same considered setting. Using the data obtained from 500 Italian general practitioners providing information to the Health Search/CSD Patient database, we selected, for the study purpose 351,091 male individuals. We assumed PSA prescriptions performed during 2005-2008 in individuals without prostate cancer, or benign prostate disease, or urological symptoms history to have a screening purpose. Screening frequency was analyzed in the overall series, by year and by patient's age. Exposure to PSA screening (at least on PSA test in the considered period) of males aged over 50 years raised from 31.4% (confidence interval 95% 31.08-31.70%) during 2002 to 46.4% (confidence interval 95% 46.19-46.68%) during 2008. The highest yearly exposure to PSA screening (55%) and the highest frequency of repeat testing was observed in the 70-79 age range. PSA screening practice has continued to increase in Italy and is often performed in elderly people without any scientific rationale.

  8. Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer

    PubMed Central

    Hoffmann, Thomas J.; Passarelli, Michael N.; Graff, Rebecca E.; Emami, Nima C.; Sakoda, Lori C.; Jorgenson, Eric; Habel, Laurel A.; Shan, Jun; Ranatunga, Dilrini K.; Quesenberry, Charles P.; Chao, Chun R.; Ghai, Nirupa R.; Aaronson, David; Presti, Joseph; Nordström, Tobias; Wang, Zhaoming; Berndt, Sonja I.; Chanock, Stephen J.; Mosley, Jonathan D.; Klein, Robert J.; Middha, Mridu; Lilja, Hans; Melander, Olle; Kvale, Mark N.; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil; Van Den Eeden, Stephen K.; Witte, John S.

    2017-01-01

    Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa—such as genetics—can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant (P<5 × 10−8) single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified for PSA (14 of which were also PCa-associated), and 6 previously identified for PCa only. Further analysis incorporating PCa cases suggests that at least half of the 40 SNPs are PSA-associated independent of PCa. The 40 SNPs explain 9.5% of PSA variation in non-Hispanic whites, and the remaining GWAS SNPs explain an additional 31.7%; this percentage is higher in younger men, supporting the genetic basis of PSA levels. These findings provide important information about genetic markers for PSA that may improve PCa screening, thereby reducing over-diagnosis and over-treatment. PMID:28139693

  9. A highly sensitive prostate-specific antigen immunosensor based on gold nanoparticles/PAMAM dendrimer loaded on MWCNTS/chitosan/ionic liquid nanocomposite.

    PubMed

    Kavosi, Begard; Salimi, Abdollah; Hallaj, Rahman; Amani, Kamal

    2014-02-15

    We have developed a sensitive electrochemical immunosensor for the detection of prostate-specific antigen (PSA), based on covalently immobilizing of anti-PSA and redox mediator (thionine) onto gold nanoparticles-incorporated polyamidoamine dendrimer (AuNPs-PAMAM) and multiwalled carbon nanotubes/ionic liquid/chitosan nanocomposite (MWCNTs/IL/Chit) as the support platform. The MWCNTs/IL/Chit nanocomposite and synthesized AuNPs were characterized using SEM and TEM microscopy techniques. Greatly amplified immunoassay was established by sandwiching the antigen between anti-PSA immobilized on the MWCNTs/IL/Chit/AuNPs-PAMAM interface and anti-PSA labeled with horseradish peroxidase (HRP-labeled anti-PSA) as secondary antibody. Phtaloyl chloride (Ph) was used as linking agent for the subsequent immobilization of AuNPs-PAMAM onto platform and anti-PSA antibody and thionine onto AuNPs-PAMAM dendrimer. The increased electrocatalytic reduction of H2O2 by HRP was monitored by differential pulse voltammetry technique. Under optimized condition the calibration curve for PSA concentration was linear up to 80 ng ml(-1) with detection limit (signal-to-noise ratio of 3) of 1 pg ml(-1). AuNPs-PAMAM dendrimer as platform not only increased the amount of thionine and PSA antibody but also the electron transfer process accelerated by encapsulated AuNPs. Moreover, the proposed PSA immunosensor exhibited excellent stability and reproducibility. Accurate detection of PSA in human serum samples was demonstrated by comparison to standard ELISA assays. In addition, impedance technique was used as simple, rapid, low cost label free analytical method for PSA measurement with detection limit of 0.5 ng ml(-1) at concentration range up to 25 ng ml(-1). The results indicate that the present protocol is quite promising in developing other electrochemical immunosensors. © 2013 Elsevier B.V. All rights reserved.

  10. Is social support from family associated with PSA testing? An exploratory analysis using the Health Information National Trends Survey (HINTS) 2005.

    PubMed

    Thomas, Kamilah B; Simpson, Sean L; Tarver, Will L; Gwede, Clement K

    2010-03-01

    African American and White men have the highest rates of prostate cancer in the United States. Families represent important social contexts within which illness occurs.The purpose of this study is to explore whether prostate-specific antigen (PSA) testing is associated with instrumental and informational social support from family members among a sample of Black and White men aged 45 and older. Data from the 2005 Health Information National Trends Survey were analyzed using logistic regression. The dependent variable was having a PSA test within the past year or less. The independent variables consisted of selected demographic and family informational and instrumental social support variables. The statistically significant variables included age and having a family member with cancer. Additional studies to elucidate the mechanisms of social support from family for prostate cancer are needed.

  11. Trichosanthes kirilowii Exerts Androgenic Activity via Regulation of PSA and KLK2 in 22Rv1 Prostate Cancer Cells

    PubMed Central

    Jeong, Soo-Jin; Choi, Ji-Yoon; Dong, Mi-Sook; Seo, Chang-Seob; Shin, Hyeun-Kyoo

    2017-01-01

    Background: The androgen comprises a group of hormones that play roles in male reproductive activity as well as personal characteristics. Objective: We investigated the androgenic activity of various herbal medicines in human prostate cancer 22Rv1 cells. Materials and Methods: Herbal extracts of Trichosanthes kirilowii (TK), Asarum sieboldii (AS), Sanguisorba officinalis (SO), and Xanthium strumarium (XS) were selected to have androgenic effects based on a preliminary in vitro screening system. Results: TK, AS, SO, and XS enhanced the proliferation of 22Rv1 cells without having cytotoxic effects. All tested herbal extracts increased androgen receptor (AR)-induced transcriptional activity in the absence or presence of dihydrotestosterone (DHT). In an AR-binding assay, TK, but not AS, SO, or XS, produced a significant inhibition of AR binding activity, indicating it has androgenic activity. Additionally, TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen (PSA) and kallikrein 2 (KLK2) compared with untreated control. Conclusion: Taken together, TK-enhanced AR-mediated transcriptional activity might be an attractive candidate drug for treating androgen-related diseases. SUMMARY Trichosantheskirilowii (TK), Asarumsieboldii (AS), Sanguisorbaofficinalis (SO), and Xanthium strumarium (XS) enhanced the proliferation of 22Rv1 cells without having cytotoxic effects.TK, AS, SO, and XS increased androgen receptor (AR)-induced transcriptional activity.TK, but not AS, SO, or XS, produced a significant inhibition against AR-binding activity.TK treatment positively regulated mRNA expression of the AR-related molecular targets prostate-specific antigen and kallikrein 2. Abbreviations used: BPH: benign prostatic hyperplasia; AR: androgen receptor; DHT: dihydrotestosterone; PSA: prostate-specific antigen; TK: Trichosanthes kirilowii; AS: Asarum sieboldii; SO: Sanguisorba officinalis; XS: Xanthium strumarium; ATCC: American

  12. DEVELOPMENT AND VALIDATION OF A NOMOGRAM PREDICTING THE OUTCOME OF PROSTATE BIOPSY BASED ON PATIENT AGE, DIGITAL RECTAL EXAMINATION AND SERUM PROSTATE SPECIFIC ANTIGEN

    PubMed Central

    KARAKIEWICZ, PIERRE I.; BENAYOUN, SERGE; KATTAN, MICHAEL W.; PERROTTE, PAUL; VALIQUETTE, LUC; SCARDINO, PETER T.; CAGIANNOS, ILIAS; HEINZER, HANS; TANGUAY, SIMON; APRIKIAN, ARMEN G.; HULAND, HARTWIG; GRAEFEN, MARKUS

    2007-01-01

    Purpose We developed and validated a nomogram which predicts presence of prostate cancer (PCa) on needle biopsy. Materials and Methods We used 3 cohorts of men who were evaluated with sextant biopsy of the prostate and whose presenting prostate specific antigen (PSA) was not greater than 50 ng/ml. Data from 4,193 men from Montreal, Canada were used to develop a nomogram based on age, digital rectal examination (DRE) and serum PSA. External validation was performed on 1,762 men from Hamburg, Germany. Data from these men were subsequently used to develop a second nomogram in which percent free PSA (%fPSA) was added as a predictor. External validation was performed using 514 men from Montreal. Both nomograms were based on multivariate logistic regression models. Predictive accuracy was evaluated with areas under the receiver operating characteristic curve and graphically with loess smoothing plots. Results PCa was detected in 1,477 (35.2%) men from Montreal, 739 (41.9%) men from Hamburg and 189 (36.8%) men from Montreal. In all models all predictors were significant at 0.05. Using age, DRE and PSA external validation AUC was 0.69. Using age, DRE, PSA and %fPSA external validation AUC was 0.77. Conclusions A nomogram based on age, DRE, PSA and %fPSA can highly accurately predict the outcome of prostate biopsy in men at risk for PCa. PMID:15879784

  13. Prostate-Specific Antigen Modulates the Expression of Genes Involved in Prostate Tumor Growth1

    PubMed Central

    Bindukumar, B; Schwartz, Stanley A; Nair, Madhavan P N; Aalinkeel, Ravikumar; Kawinski, Elzbieta; Chadha, Kailash C

    2005-01-01

    Abstract Prostate-specific antigen (PSA) is a serine protease that is widely used as a surrogate marker in the early diagnosis and management of prostate cancer. The physiological relevance of tissue PSA levels and their role in prostate tumor growth and metastasis are not known. Free-PSA (f-PSA) was purified to homogeneity from human seminal plasma by column chromatography, eliminating hk2 and all known PSA complexes and retaining its protease activity. Confluent mono-layers of prostate cancer cell lines, PC-3M and LNCaP, were treated with f-PSA in a series of in vitro experiments to determine the changes in expression of various genes that are known to regulate tumor growth and metastasis. Gene array, quantitative polymerase chain reaction (QPCR), and enzyme-linked immunosorbent assay (ELISA) results show significant changes in the expression of various cancer-related genes in PC-3M and LNCaP cells treated with f-PSA. In a gene array analysis of PC-3M cells treated with 10 µM f-PSA, 136 genes were upregulated and 137 genes were downregulated. In LNCaP cells treated with an identical concentration of f-PSA, a total of 793 genes was regulated. QPCR analysis reveals that the genes for urokinase-type plasminogen activator (uPA), VEGF, and Pim-1 oncogene, known to promote tumor growth, were significantly downregulated, whereas IFN-γ, known to be a tumor-suppressor gene, was significantly upregulated in f-PSA-treated PC-3M cells. The effect of f-PSA on VEGF and IFN-γ gene expression and on protein release in PC-3M cells was distinctly dose-dependent. In vivo studies showed a significant reduction (P = .03) in tumor load when f-PSA was administered in the tumor vicinity of PC-3M tumor-bearing BALB/c nude mice. Our data support the hypothesis that f-PSA plays a significant role in prostate tumor growth by regulating various proangiogenic and antiangiogenic growth factors. PMID:15799824

  14. Comparison between prostate specific antigen and acid phosphatase for detection of semen in vaginal swabs from raped women.

    PubMed

    Peonim, Vichan; Worasuwannarak, Wisarn; Sujirachato, Kanchana; Teerakamchai, Somsri; Srisont, Smith; Udnoon, Jitta; Chudoung, Ubon

    2013-08-01

    To compare the effectiveness of the prostate specific antigen (PSA) test and the acid phosphatase (AP) test for semen detection in human vaginal samples. The source materials were vaginal swabs that were tested at Ramathibodi Hospital between 2008 and 2010 from 2450 cases of raped women. Each swab was tested for semen by three methods: sperm detection by light microscopy, the AP enzymatic reaction, and the presence of PSA by using an immuno-chromatographic rapid kit test. The efficiencies of the AP and PSA tests were compared using the light microscopy result for the presence of sperm as the gold standard. The specificities of the AP, the PSA and the combined AP-PSA tests were 96.4%, 92.3% and 91.9%, respectively, and the sensitivities were 65.5%, 80.4% and 84.5%, respectively. The receiver operating characteristic (ROC) area of the AP, PSA and combined AP-PSA tests were 0.8091, 0.8639 and 0.8823, respectively. The ROC area of the PSA test was significantly greater than that of the AP test (p < 0.0001), and the ROC area of the combined AP-PSA test was significantly greater than both the tests individually (p < 0.0001). Based on the ROC area, the PSA test was better than the AP test for semen detection in the vaginal swabs, and the combined results (AP + PSA) were better than the individual tests. The specificity of the AP test was higher than the PSA test in this study because a positive detection was made within only 15 s. While the PSA test was more convenient as it was available in a rapid test kit format, our recommendation is PSA detection should be done together with AP test and spermatozoa examination to identify evidence of rape. Using these three tests together (AP, PSA, and spermatozoa detection) was recommended as a forensic tool for investigations of vaginal swabs of the rape victims. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  15. Factors influencing use of the prostate-specific antigen screening test in primary care.

    PubMed

    Moran, W P; Cohen, S J; Preisser, J S; Wofford, J L; Shelton, B J; McClatchey, M W

    2000-03-01

    To evaluate the use of the prostate-specific antigen (PSA) test and digital rectal examination (DRE) in prostate cancer screening by primary care physicians. Physician survey and retrospective medical record review. We randomly selected and reviewed the medical records of 3 cross-sectional samples of male patients and surveyed their primary care physicians at 1-year intervals. All the physicians practiced in Colorado. The study spanned 3 years, including late 1992, when the American Cancer Society recommended the use of PSA in a prostate cancer screening guideline. We reviewed the medical records of 4772 male patients and surveyed 109 primary care physicians. We found that PSA testing for men aged 50 or older increased significantly from 1992 to 1994, from 24% in 1992 to 35% in 1993 and 40% in 1994 (overall odds ratio, 2.94; P < .05). Over the same time period, the DRE rate remained relatively unchanged (39% in 1992, 41% in 1993, and 36% in 1994). Overall PSA use was positively associated with patient age greater than 59 years, patient non-smoking status, physician "readiness to change cancer screening behavior," private insurance status, and nonsolo practice. Before the release of a prostate cancer screening guideline, participating physicians cited the American Cancer Society as the organization that most influenced their practice with respect to cancer screening. The magnitude of the reported influence of the American Cancer Society was correlated with the subsequent use of PSA in 1994 by primary care physicians after adjustment for change in DRE and baseline PSA rates, although the association did not reach statistical significance in multivariable regression models. Primary care physicians in Colorado significantly increased their use of the PSA test from 1992 to 1994, during which time the American Cancer Society issued a guideline recommending the use of PSA for prostate cancer screening. The reported influence of the American Cancer Society on cancer

  16. Prostate-specific antigen levels are associated with arterial stiffness in essential hypertensive patients.

    PubMed

    Vyssoulis, Gregory; Karpanou, Eva; Kyvelou, Stella-Maria; Vlachopoulos, Charalambos; Tzamou, Vanessa; Stefanadis, Christodoulos

    2012-12-01

    Prostate-specific antigen (PSA) has been recently related to cardiovascular system in a multifactorial way. Arterial stiffness is a independent predictor of cardiovascular events and is involved in the pathogenesis of hypertension. The aim of the present study was to investigate whether PSA values, are associated with arterial stiffness indices in patients with essential arterial hypertension. The study comprised 150 consecutive male patients (mean age 60 years) with uncomplicated never-treated essential hypertension. All patients underwent a complete clinical and laboratory evaluation, including measurement of PSA levels. Aortic stiffness and arterial wave reflection assessment was made by using carotid-femoral (PWVc-f) pulse wave velocity and aortic augmentation index corrected for heart rate (AIx75). Patients with prostate cancer or benign prostate hyperplasia (PSA > 4 ng/mL) were excluded from the study. PSA was positively associated with waist-to-hip ratio (r = 0.235, P = 0.04), PWVc-f (r = 0.426, P < 0.001), AIx75 (r = 0.264, P = 0.001), and high sensitivity C-reactive protein (hsCRP; r = 0.376, P < 0.001). In categorization to PSA quartiles, patients in the higher quartile presented with higher waist-to hip ratio (P = 0.009), PWVc-f (P < 0.00001), AIx75 (P < 0.001) and hsCRP (P < 0.001) values. In multivariate analysis after adjustment for various confounders PSA remained a significant determinant of PWVc-f values (beta [SE] = 0.477 [0.13], R(2) = 0.405, P < 0.001). The present study points towards an association between PSA levels and aortic stiffness in untreated essential hypertensive males. Potential causal relationships between PSA and arterial stiffness remain to be further explored. © 2010 International Society for Sexual Medicine.

  17. Role of (18)F-Choline PET/CT in guiding biopsy in patients with risen PSA levels and previous negative biopsy for prostate cancer.

    PubMed

    Jiménez Londoño, G A; García Vicente, A M; Amo-Salas, M; Fúnez Mayorga, F; López Guerrero, M A; Talavera Rubio, M P; Gutierrez Martin, P; González García, B; de la Torre Pérez, J A; Soriano Castrejón, Á M

    To study (18)F-Choline PET/CT in the diagnosis and biopsy guide of prostate cancer (pCa) in patients with persistently high prostate-specific antigen (PSA) and previous negative prostate biopsy. To compare the clinical risk factors and metabolic variables as predictors of malignancy. Patients with persistently elevated PSA in serum (total PSA >4ng/mL) and at least a previous negative or inconclusive biopsy were consecutively referred for a whole body (18)F-Choline PET/CT. Patient age, PSA level, PSA doubling time (PSAdt) and PSA velocity (PSAvel) were obtained. PET images were visually (positive or negative) and semiquantitatively (SUVmax) reviewed. (18)F-Choline uptake prostate patterns were defined as focal, multifocal, homogeneous or heterogeneous. Histology on biopsy using transrectal ultrasound-guided approach was the gold standard. Sensitivity (Se), specificity (Sp) and accuracy (Ac) of PET/CT for diagnosis of pCa were evaluated using per-patient and per-prostate lobe analysis. Receiver-operating-characteristic (ROC) curve analysis was used to assess the value of SUVmax to diagnose pCa. Correlation between PET/CT and biopsy results per-prostate lobe was assessed using the Chi-square test. Univariate and multivariate logistic regression analysis were applied to compare clinical risk factors and metabolic variables as predictors of malignancy. Thirty-six out of 43 patients with histologic confirmation were included. In 11 (30.5%) patients, pCa was diagnosed (Gleason score from 4 to 9). The mean values of patient age, PSA level, PSAdt and PSAvel were: 65.5 years, 15.6ng/ml, 28.1 months and 8.5ng/mL per year, respectively. Thirty-three patients had a positive PET/CT; 18 had a focal pattern, 7 multifocal, 4 homogeneous and 4 heterogeneous. Se, Sp and Ac of PET/CT were of 100%, 12% and 38% in the patient based analysis, and 87%, 29% and 14% in the prostate lobe based analysis, respectively. The ROC curve analysis of SUVmax showed an AUC of 0.568 (p=0.52). On a lobe

  18. High PSA anxiety and low health literacy skills: drivers of early use of salvage ADT among men with biochemically recurrent prostate cancer after radiotherapy?

    PubMed

    Mahal, B A; Chen, M-H; Bennett, C L; Kattan, M W; Sartor, O; Stein, K; D'Amico, A V; Nguyen, P L

    2015-07-01

    Although commonly used, early initiation of salvage androgen deprivation therapy (ADT) has not been proven to enhance survival. We evaluated whether prostate-specific antigen (PSA) anxiety or health literacy are associated with use of early salvage ADT among men with recurrent prostate cancer after radiotherapy. The prospective Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma Registry was used to study 375 men with biochemically recurrent prostate cancer after external beam radiation or brachytherapy. Multivariable logistic regression was used to determine whether PSA anxiety and health literacy are associated with salvage ADT as initial management after biochemical recurrence. Sixty-eight men (18.1%) received salvage ADT as initial management for PSA recurrence. Men with high PSA anxiety were twice as likely to receive salvage ADT compared with men who did not have high PSA anxiety on both univariable [28.8% versus 13.1%; odds ratio (OR) 2.15; 95% confidence interval (CI) 1.16-4.00; P = 0.015] and multivariable analysis [adjusted OR (AOR) 2.36; 95% CI 1.21-4.62; P = 0.012]. Furthermore, men who had higher levels of health literacy were nearly half as likely to undergo salvage ADT compared with men who had lower levels of health literacy on univariable analysis (15.2% versus 26.3%; OR 0.50; 95% CI 0.29-0.88; P = 0.016), with a trend toward this association on multivariable analysis (AOR 0.58; 95% CI 0.32-1.05; P = 0.07). Among men with PSA recurrence after radiotherapy, odds of use of salvage ADT were nearly twice as great among men with high PSA anxiety or low health literacy, suggesting that these men are receiving higher rates of unproven treatment. Given that early salvage ADT is costly, worsens quality of life, and has not been shown to improve survival, quality improvement strategies are needed for these individuals. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights

  19. Insights from the WGRISK workshop on the PSA of advanced and new reactors

    SciTech Connect

    Georgescu, G.; Ahn, K. I.; Amri, A.

    2012-07-01

    Probabilistic Safety Assessment /Probabilistic Risk Assessment for new and advanced reactors is recognized as an essential complement of the deterministic approaches to achieve improved safety and performances of new nuclear power plants, comparing to the operating plants. However, the development of PSA to these reactors is encountered to concurrent challenges, mainly due to the limited available design information, as well as due to potentially new initiating events, accident sequences and phenomena. The use of PSA in the decision making process is also challenging since the resulting PSA may not sufficiently reflect the future as-built, as-operated plant information. In order to address these aspects, the OECD/NEA/WGRISK initiated two coordinated tasks on 'PSA for Advanced Reactors' and 'PSA in the frame of Design and Commissioning of New NPPs'. In this context, a joint workshop was organized by OECD, during which related subjects were presented and discussed, including PSA for generation IV reactors, PSA for evolutionary reactors, PSA for small modular reactors, severe accidents and Level 2 PSA, Level 3 PSA and consequences analysis, digital I and C modeling, passive systems reliability, safety-security interface, as well as the results of the surveys performed in the frame of theses WGRISK tasks. (authors)

  20. High-sensitivity immunoassay with surface plasmon field-enhanced fluorescence spectroscopy using a plastic sensor chip: application to quantitative analysis of total prostate-specific antigen and GalNAcβ1-4GlcNAc-linked prostate-specific antigen for prostate cancer diagnosis.

    PubMed

    Kaya, Takatoshi; Kaneko, Tomonori; Kojima, Shun; Nakamura, Yukito; Ide, Youichi; Ishida, Kenji; Suda, Yoshihiko; Yamashita, Katsuko

    2015-02-03

    A high-sensitivity immunoassay system with surface plasmon field-enhanced fluorescence spectrometry (SPFS) was constructed using a plastic sensor chip and then applied to the detection of total prostate-specific antigen (total PSA) and GalNAcβ1-4GlcNAc-linked prostate-specific antigen (LacdiNAc-PSA) in serum, to discriminate between prostate cancer (PC) and benign prostate hyperplasia (BPH). By using this automated SPFS immunoassay, the detection limit for total PSA in serum was as low as 0.04 pg/mL, and the dynamic range was estimated to be at least five digits. A two-step sandwich SPFS immunoassay for LacdiNAc-PSA was constructed using both the anti-PSA IgG antibody to capture PSA and Wisteria floribunda agglutinin (WFA) for the detection of LacdiNAc. The results of the LacdiNAc-PSA immunoassay with SPFS showed that the assay had a sensitivity of 20.0 pg/mL and permitted the specific distinction between PC and BPH within the PSA gray zone. These results suggested that high-sensitivity automated SPFS immunoassay systems might become a powerful tool for the diagnosis of PC and other diseases.

  1. Evaluation of prostatic cancer prevalence in patients with prostatic-specific antigen between 4 and 10 and normal digital rectal examination

    PubMed Central

    Tadayon, Farhad; Arezegar, Hamid Reza; Khorrami, Mohammad Hatef; Hashemi Juzdani, Rasoul; Shahdoost, Amir Abbas; Mellat, Mehdi

    2016-01-01

    Background: Prostate cancer is one of the most common male cancers. The prevalence of prostate cancer is different due to genetic and environmental factors. Diagnosis of prostate cancer is by biopsy due to prostate-specific antigen (PSA) and Digital Rectal Examination (DRE). Controversy about decision making for prostate biopsy in PSA between 4 and 10 and normal DRE, is one of the problems in this time. In this study we evaluated the prevalence of prostate cancer in males with PSA between 4 and 10 and normal DRE. We also evaluated the PSA density and percent of free PSA in patients with prostate cancer. Materials and Methods: A total of 121 males with PSA between 4 and 10 and normal DRE, were evaluated. Then, transrectal ultrasonography (TRUS) andprostate biopsy from 12 points of peripheral zone, was done. These data were analyzed by Chi-square, t-test and ANOVA and Roc curve. Results: In this study, the prevalence of prostate cancer in PSA between 4 and 10 and normal DRE, was evaluated, 29.8%. With use of Roc curve, PSA density cutoff point was calculated 0.12 and percent of free PSA cutoff point, was calculated, 18%. Conclusion: In males with PSA between 4 and 10 and normal DRE, PSA density smaller than 0.12-0.15, and percent of free PSA greater than 18%, the prevalence of prostate cancer is very few and we can safely ignore the TRUS and prostate biopsy in these males and eliminate its costs and side effects. PMID:27403407

  2. Early Salvage Hormonal Therapy for Biochemical Failure Improved Survival in Prostate Cancer Patients After Neoadjuvant Hormonal Therapy Plus Radiation Therapy-A Secondary Analysis of Irish Clinical Oncology Research Group 97-01

    SciTech Connect

    Mydin, Aminudin R.; Dunne, Mary T.; Finn, Marie A.; Armstrong, John G.

    2013-01-01

    Purpose: To assess the survival benefit of early vs late salvage hormonal therapy (HT), we performed a secondary analysis on patients who developed recurrence from Irish Clinical Oncology Research Group 97-01, a randomized trial comparing 4 vs 8 months neoadjuvant HT plus radiation therapy (RT) in intermediate- and high-risk prostate adenocarcinoma. Methods and Materials: A total of 102 patients from the trial who recurred were analyzed at a median follow-up of 8.5 years. The patients were divided into 3 groups based on the timing of salvage HT: 57 patients had prostate-specific antigen (PSA) {<=}10 ng/mL and absent distant metastases (group 1, early), 21 patients had PSA >10 ng/mL and absent distant metastases (group 2, late), and 24 patients had distant metastases (group 3, late). The endpoint analyzed was overall survival (OS) calculated from 2 different time points: date of enrolment in the trial (OS1) and date of initiation of salvage HT (OS2). Survival was estimated using Kaplan-Meier curves and a Cox regression model. Results: The OS1 differed significantly between groups (P<.0005): OS1 at 10 years was 78% in group 1, 42% in group 2, and 29% in group 3. The OS2 also differed significantly between groups (P<.0005): OS2 at 6 years was 70% in group 1, 47% in group 2, and 22% in group 3. Group 1 had the longest median time from end of RT to biochemical failure compared with groups 2 and 3 (3.3, 0.9, and 1.7 years, respectively; P<.0005). Group 1 also had the longest median PSA doubling time compared with groups 2 and 3 (9.9, 3.6, and 2.4 months, respectively; P<.0005). On multivariate analysis, timing of salvage HT, time from end of RT to biochemical failure, and PSA nadir on salvage HT were significant predictors of survival. Conclusion: Early salvage HT based on PSA {<=}10 ng/mL and absent distant metastases improved survival in patients with prostate cancer after failure of initial treatment with neoadjuvant HT plus RT.

  3. Clinical outcomes and survival surrogacy studies of prostate‐specific antigen declines following enzalutamide in men with metastatic castration‐resistant prostate cancer previously treated with docetaxel

    PubMed Central

    Saad, Fred; Phung, De; Dmuchowski, Carl; Shore, Neal D.; Fizazi, Karim; Hirmand, Mohammad; Forer, David; Scher, Howard I.; Bono, Johann De

    2017-01-01

    BACKGROUND In the AFFIRM trial, enzalutamide significantly increased overall survival (OS) for men with metastatic castration‐resistant prostate cancer (mCRPC) after chemotherapy versus placebo and significantly decreased prostate‐specific antigen (PSA) levels. The goal of this post hoc analysis was to associate levels of PSA decline from baseline after enzalutamide with clinical outcomes in the postchemotherapy mCRPC setting. METHODS Men in the AFFIRM trial (n = 1199) were grouped by maximal PSA decline in the first 90 days of treatment. Kaplan‐Meier estimates evaluated the association of defined PSA changes from baseline with OS, progression‐free survival (PFS), radiographic PFS (rPFS), and pain response. Each PSA decline category was assessed for OS surrogacy using Prentice criteria, proportion of treatment effect explained (PTE), and proportion of variation explained. RESULTS Men treated with enzalutamide had improved OS (hazard ratio, 0.63; P < .001) and higher rates of PSA decline (odds ratio, >19.0; P < .001) versus placebo. PSA declines of any, ≥30%, ≥50%, and ≥90% with enzalutamide were strongly associated with greater OS, PSA PFS, rPFS (P < .001), and pain response (P < .026) versus PSA increase/no decline. Any, ≥30%, and ≥50% declines in PSA resulted in the PTE range of 1.07‐1.29, where treatment was no longer significant after adjustment for decline measures (P > .20). CONCLUSIONS PSA declines of any, ≥30%, and ≥50% following enzalutamide were associated with greater clinical and pain response and improvements in PFS and OS. Surrogacy of PSA decline for OS was not fully established, possibly due to lack of PSA declines with placebo, and discordant results between PSA and imaging responses over time, and because some declines were not durable due to rapid resistance development. However, a lack of PSA decline by 90 days following enzalutamide treatment was a poor prognosis indicator in this setting. Conclusions from sensitivity

  4. Clinical outcomes and survival surrogacy studies of prostate-specific antigen declines following enzalutamide in men with metastatic castration-resistant prostate cancer previously treated with docetaxel.

    PubMed

    Armstrong, Andrew J; Saad, Fred; Phung, De; Dmuchowski, Carl; Shore, Neal D; Fizazi, Karim; Hirmand, Mohammad; Forer, David; Scher, Howard I; Bono, Johann De

    2017-06-15

    In the AFFIRM trial, enzalutamide significantly increased overall survival (OS) for men with metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy versus placebo and significantly decreased prostate-specific antigen (PSA) levels. The goal of this post hoc analysis was to associate levels of PSA decline from baseline after enzalutamide with clinical outcomes in the postchemotherapy mCRPC setting. Men in the AFFIRM trial (n = 1199) were grouped by maximal PSA decline in the first 90 days of treatment. Kaplan-Meier estimates evaluated the association of defined PSA changes from baseline with OS, progression-free survival (PFS), radiographic PFS (rPFS), and pain response. Each PSA decline category was assessed for OS surrogacy using Prentice criteria, proportion of treatment effect explained (PTE), and proportion of variation explained. Men treated with enzalutamide had improved OS (hazard ratio, 0.63; P < .001) and higher rates of PSA decline (odds ratio, >19.0; P < .001) versus placebo. PSA declines of any, ≥30%, ≥50%, and ≥90% with enzalutamide were strongly associated with greater OS, PSA PFS, rPFS (P < .001), and pain response (P < .026) versus PSA increase/no decline. Any, ≥30%, and ≥50% declines in PSA resulted in the PTE range of 1.07-1.29, where treatment was no longer significant after adjustment for decline measures (P > .20). PSA declines of any, ≥30%, and ≥50% following enzalutamide were associated with greater clinical and pain response and improvements in PFS and OS. Surrogacy of PSA decline for OS was not fully established, possibly due to lack of PSA declines with placebo, and discordant results between PSA and imaging responses over time, and because some declines were not durable due to rapid resistance development. However, a lack of PSA decline by 90 days following enzalutamide treatment was a poor prognosis indicator in this setting. Conclusions from sensitivity analyses of maximal PSA decline from baseline over

  5. Intranasal immunization with the cholera toxin B subunit-pneumococcal surface antigen A fusion protein induces protection against colonization with Streptococcus pneumoniae and has negligible impact on the nasopharyngeal and oral microbiota of mice.

    PubMed

    Pimenta, F C; Miyaji, E N; Arêas, A P M; Oliveira, M L S; de Andrade, A L S S; Ho, P L; Hollingshead, S K; Leite, L C C

    2006-08-01

    One of the candidate proteins for a mucosal vaccine antigen against Streptococcus pneumoniae is PsaA (pneumococcal surface antigen A). Vaccines targeting mucosal immunity may raise concerns as to possible alterations in the normal microbiota, especially in the case of PsaA, which was shown to have homologs with elevated sequence identity in other viridans group streptococci. In this work, we demonstrate that intranasal immunization with a cholera toxin B subunit-PsaA fusion protein is able to protect mice against colonization with S. pneumoniae but does not significantly alter the natural oral or nasopharyngeal microbiota of mice.

  6. Impact of different variables on the outcome of patients with clinically confined prostate carcinoma: prediction of pathologic stage and biochemical failure using an artificial neural network.

    PubMed

    Ziada, A M; Lisle, T C; Snow, P B; Levine, R F; Miller, G; Crawford, E D

    2001-04-15

    The advent of advanced computing techniques has provided the opportunity to analyze clinical data using artificial intelligence techniques. This study was designed to determine whether a neural network could be developed using preoperative prognostic indicators to predict the pathologic stage and time of biochemical failure for patients who undergo radical prostatectomy. The preoperative information included TNM stage, prostate size, prostate specific antigen (PSA) level, biopsy results (Gleason score and percentage of positive biopsy), as well as patient age. All 309 patients underwent radical prostatectomy at the University of Colorado Health Sciences Center. The data from all patients were used to train a multilayer perceptron artificial neural network. The failure rate was defined as a rise in the PSA level > 0.2 ng/mL. The biochemical failure rate in the data base used was 14.2%. Univariate and multivariate analyses were performed to validate the results. The neural network statistics for the validation set showed a sensitivity and specificity of 79% and 81%, respectively, for the prediction of pathologic stage with an overall accuracy of 80% compared with an overall accuracy of 67% using the multivariate regression analysis. The sensitivity and specificity for the prediction of failure were 67% and 85%, respectively, demonstrating a high confidence in predicting failure. The overall accuracy rates for the artificial neural network and the multivariate analysis were similar. Neural networks can offer a convenient vehicle for clinicians to assess the preoperative risk of disease progression for patients who are about to undergo radical prostatectomy. Continued investigation of this approach with larger data sets seems warranted. Copyright 2001 American Cancer Society.

  7. Estimated blood loss as a predictor of PSA recurrence after radical prostatectomy: results from the SEARCH database.

    PubMed

    Lloyd, Jessica C; Bañez, Lionel L; Aronson, William J; Terris, Martha K; Presti, Joseph C; Amling, Christopher L; Kane, Christopher J; Freedland, Stephen J

    2010-02-01

    Diagnosis (exploratory cohort). 2b. To clarify the relationship between estimated blood loss (EBL) and biochemical recurrence, assessed by prostate-specific antigen (PSA) level, as blood loss is a long-standing concern associated with radical prostatectomy (RP), and no studies to date have examined the association between blood loss and cancer control. In all, 1077 patients were identified in the Shared Equal-Access Regional Cancer Hospital database who underwent retropubic RP (between 1998 and 2008) and had EBL and follow-up data available. We examined the relationship between EBL and recurrence using multivariate Cox regression analyses. Increased EBL was correlated with PSA recurrence in a multivariate-adjusted model (P = 0.01). When analysed by 500-mL EBL categories, those with an EBL of <1500 mL had a similar risk of recurrence. However, the risk of PSA recurrence tended to increase for an EBL of 1500-3499 mL, before decreasing again for patients with an EBL of > or =3500 mL. Men with an EBL of 2500-3499 mL had more than twice the risk of recurrence than men with an EBL of <1500 mL (P = 0.02). EBL was not associated with adverse tumour stage, grade or margin status. There was a significant correlation between EBL at the time of RP and biochemical recurrence. We hypothesized that this association might be due to transfusion-related immunosuppression, excessive blood obscuring the operative field, EBL being a marker of aggressive disease, or EBL being a marker of poor surgical technique. However, our data did not completely fit any one of these hypotheses, and thus the ultimate cause for the increased risk of recurrence remains unclear and requires further study.

  8. Cell viability and PSA secretion assays in LNCaP cells: a tiered in vitro approach to screen chemicals with a prostate-mediated effect on male reproduction within the ReProTect project.

    PubMed

    Lorenzetti, Stefano; Marcoccia, Daniele; Narciso, Laura; Mantovani, Alberto

    2010-08-01

    Prostate function is critical for male fertility; nevertheless, prostate was so far overlooked in reproductive toxicity assays. Within the EU project ReProTect, the human prostate cell line LNCaP was utilized to identify molecules targeting prostate function by the integrated assessment of cell viability (MTS assay) and prostate-specific antigen (PSA) secretion as specific marker; a training set - five (anti)androgenic chemicals - and a ReProTect feasibility set - ten chemicals - were used. Several compounds reduced PSA only at cytotoxic concentrations. Androgens (DHT, MT) markedly increased PSA as did the herbicide glufosinate ammonium, not known as androgen agonist. Anti-androgens (2OH-flutamide, linuron, vinclozolin, di-n-butyl phthalate) also increased PSA, but the effect of magnitude was much lower than for androgens. The ER-binder bisphenol A reduced PSA, while increasing cell viability. At this stage, the approach can identify chemicals able to interfere with prostate function: further refinements may allow to include prostate effects in reproductive toxicity in vitro testing.

  9. An Automated Micro-Total Immunoassay System for Measuring Cancer-Associated α2,3-linked Sialyl N-Glycan-Carrying Prostate-Specific Antigen May Improve the Accuracy of Prostate Cancer Diagnosis

    PubMed Central

    Ishikawa, Tomokazu; Yoneyama, Tohru; Tobisawa, Yuki; Hatakeyama, Shingo; Kurosawa, Tatsuo; Nakamura, Kenji; Narita, Shintaro; Mitsuzuka, Koji; Duivenvoorden, Wilhelmina; Pinthus, Jehonathan H.; Hashimoto, Yasuhiro; Koie, Takuya; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara

    2017-01-01

    The low specificity of the prostate-specific antigen (PSA) for early detection of prostate cancer (PCa) is a major issue worldwide. The aim of this study to examine whether the serum PCa-associated α2,3-linked sialyl N-glycan-carrying PSA (S2,3PSA) ratio measured by automated micro-total immunoassay systems (μTAS system) can be applied as a diagnostic marker of PCa. The μTAS system can utilize affinity-based separation involving noncovalent interaction between the immunocomplex of S2,3PSA and Maackia amurensis lectin to simultaneously determine concentrations of free PSA and S2,3PSA. To validate quantitative performance, both recombinant S2,3PSA and benign-associated α2,6-linked sialyl N-glycan-carrying PSA (S2,6PSA) purified from culture supernatant of PSA cDNA transiently-transfected Chinese hamster ovary (CHO)-K1 cells were used as standard protein. Between 2007 and 2016, fifty patients with biopsy-proven PCa were pair-matched for age and PSA levels, with the same number of benign prostatic hyperplasia (BPH) patients used to validate the diagnostic performance of serum S2,3PSA ratio. A recombinant S2,3PSA- and S2,6PSA-spiked sample was clearly discriminated by μTAS system. Limit of detection of S2,3PSA was 0.05 ng/mL and coefficient variation was less than 3.1%. The area under the curve (AUC) for detection of PCa for the S2,3PSA ratio (%S2,3PSA) with cutoff value 43.85% (AUC; 0.8340) was much superior to total PSA (AUC; 0.5062) using validation sample set. Although the present results are preliminary, the newly developed μTAS platform for measuring %S2,3PSA can achieve the required assay performance specifications for use in the practical and clinical setting and may improve the accuracy of PCa diagnosis. Additional validation studies are warranted. PMID:28241428

  10. HLA antigens and Berger's disease.

    PubMed

    Bignon, J D; Houssin, A; Soulillou, J P; Denis, J; Guimbretiere, J; Guenel, J

    1980-07-01

    We have studied the frequencies of HLA-A, -B antigens in 73 Berger's disease patients, plus HLA-DR antigens in 35 of them, and compared the percentages of antigens frequencies with those of a local and national panel. This study does not confirm the positive associations with HLA-Bw35 or HLA-B12 which have been previously reported. The HLA-DR typing only showed increased frequency of blanks in the patients (P smaller than 0.01, but no significant corr.P). Patients with Berger's disease and renal failure have a higher (but still not significant) HLA-Bw35 frequency than those without renal failure. The reasons for the discrepancy between our group and others are analysed.

  11. Heart Failure

    MedlinePlus

    ... version of this page please turn Javascript on. Heart Failure What is Heart Failure? In heart failure, the heart cannot pump enough ... failure often experience tiredness and shortness of breath. Heart Failure is Serious Heart failure is a serious and ...

  12. Prostate-specific Antigen Mass Density--A Measure Predicting Prostate Cancer Volume and Accounting for Overweight and Obesity-related Prostate-specific Antigen Hemodilution.

    PubMed

    Kryvenko, Oleksandr N; Diaz, Mireya; Matoso, Andres; Kates, Max; Cohen, Jason; Swanson, Gregory P; Epstein, Jonathan I

    2016-04-01

    To test prostate-specific antigen mass density (PSAMD) as a predictor of total tumor volume (TTV) at radical prostatectomy (RP). We conducted a detailed pathologic analysis of 469 RP from men with NCCN low-risk prostate cancer who had Gleason score of 3 + 3 = 6 (grade group 1) at RP. We then compared the ability of PSA, PSA density (PSAD), PSA mass (PSAM-absolute amount of PSA in patient's circulation), and PSAM density (PSAM divided by prostate weight without seminal vesicles) to predict TTV at RP. PSAM was calculated by multiplying plasma volume (estimated body surface [weight, kg(0.425) × height, m(0.72) × 0.007184] × 1.67) by PSA. Performance of the above measures in different BMI categories was assessed. Kruskal-Wallis test was used to compare the means and Spearman's rank correlation coefficient to assess the correlations. The 469 men were normal weight (n = 129), overweight (n = 253), and obese (n = 87). Mean age of the patients' was 57.4 years and PSA of 4.53 ng/ml. Increase of prostate weight with body mass index (BMI) was reflected in PSAM (both P <.001) but not in other measures. BMI did not correlate with TTV and PSA. Among PSA, PSAD, PSAM, and PSAMD, PSAMD had the highest correlation with TTV (r = 0.336; P <.001). Prostate weight had stronger (negative) association with PSAMD (r = -0.394; <.001) than TTV. PSAMD is the biochemical measure with the best correlation with TTV at RP. Unlike other measures, it is not affected by BMI-related hemodilution. Thresholds should be established to use this more objective measure clinically in surveillance algorithms and in planning radical prostatectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Association of healthcare barriers with prostate-specific antigen screening among African-American and Afro-Caribbean men.

    PubMed

    Lee, Daniel J; Consedine, Nathan S; Gonzalez, Joshua R; Spencer, Benjamin A

    2012-09-01

    To evaluate the association between the barriers to healthcare access and prostate-specific antigen (PSA) screening practices among African-American and Afro-Caribbean men. Stratified cluster sampling of census tracts in Brooklyn, New York yielded 533 men, aged 45-70 years. The men were classified into the following groups: U.S.-born white, U.S.-born African-American, Jamaican, and Trinidadian/Tobagonian. The subjects completed a written 6-item survey assessing the healthcare barriers. Overall, 27% of men reported never having had a PSA test and 28% reported that they had received annual PSA screening. On multivariate analysis, those who viewed the healthcare system as convenient were more likely to report an initial PSA test (odds ratio 1.8, P < .05). Those who perceived difficulty in accessing reliable care were less likely to ever have had a PSA test (odds ratio 0.6, P < .05). Subjects who had not had a comprehensive discussion with their physician about prostate cancer were less likely to have had an initial PSA test and more likely to have maintained annual PSA screening (odds ratio 0.3 and 1.7, respectively, P < .05). We identified 2 novel perceived barriers to prostate cancer screening: men who experience the healthcare system as inconvenient were less likely to initiate PSA testing, and those who found it difficult to obtain quality care were less likely to ever have had a PSA test. The perceived system barriers were more closely linked to PSA screening behavior than were the measures assessing perceptions of self-efficacy. Our results suggest that a broader discussion by physicians that addresses the perceptions regarding the healthcare system might enhance the understanding of, and increase the use of, prostate cancer screening among higher risk minority men. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. POOR GLYCEMIC CONTROL IS ASSOCIATED WITH REDUCED PROSTATE-SPECIFIC ANTIGEN CONCENTRATIONS IN MEN WITH TYPE 1 DIABETES

    PubMed Central

    Sarma, Aruna V.; Hotaling, James; Dunn, Rodney L.; Cleary, Patricia A.; Braffett, Barbara H.; Kim, Catherine; Martin, Catherine; Herman, William; Gatcomb, Patricia; Jacobson, Alan M.; Holt, Sarah K.; Wessells, Hunter

    2015-01-01

    PURPOSE Previous studies have demonstrated lower prostate-specific antigen (PSA) concentrations in men with type 2 diabetes (T2DM), paralleling the reported lower prevalence of prostate cancer among diabetic men. Data on PSA in men with type 1 diabetes (T1DM), in whom insulin and obesity profiles differ from those in T2DM, are lacking. The objective of this study was to examine the relationship between long-term glycemic control and PSA in men with T1DM. MATERIALS & METHODS Total PSA was measured at one time in 639 men in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow up of participants in the Diabetes Control and Complications Trial (DCCT). The relationship between DCCT/EDIC weighted mean HbA1c and log PSA was assessed using linear regression modeling after adjusting for age, body mass index (BMI), total testosterone, statin and thiazide medication use, diabetes duration, and DCCT randomization arm and cohort. RESULTS The subjects had a median age of 52 years, BMI of 28.4 kg/m2 and DCCT/EDIC time weighted HbA1c of 7.9%. Total median (interquartile range) for PSA levels was 0.64 (0.43, 1.05). PSA levels increased significantly with age (p<0.0001) and with lower time weighted HbA1c (p<0.0001). Each 10% increase in HbA1c was accompanied by an 11% reduction in PSA (p=0.0001). CONCLUSIONS PSA levels decrease as HbA1c increases in men with T1DM. This relationship is independent of age, BMI, androgen levels, medication use and measures of diabetes severity, which suggest that factors related to glycemia may be directly affecting PSA levels. PMID:25218922

  15. A prostate MRI atlas of biochemical failures following cancer treatment

    NASA Astrophysics Data System (ADS)

    Rusu, Mirabela; Kurhanewicz, John; Tewari, Ashutosh; Madabhushi, Anant

    2014-03-01

    Radical prostatectomy (RP) and radiation therapy (RT) are the most common treatment options for prostate cancer (PCa). Despite advancements in radiation delivery and surgical procedures, RP and RT can result in failure rates as high as 40% and >25%, respectively. Treatment failure is characterized by biochemical recurrence (BcR), which is defined in terms of prostate specific antigen (PSA) concentrations and its variation following treatment. PSA is expected to decrease following treatment, thereby its presence in even small concentrations (e.g 0.2 ng/ml for surgery or 2 ng/ml over the nadir PSA for radiation therapy) is indicative of treatment failure. Early identification of treatment failure may enable the use of more aggressive or neo-adjuvant therapies. Moreover, predicting failure prior to treatment may spare the patient from a procedure that is unlikely to be successful. Our goal is to identify differences on pre-treatment MRI between patients who have BcR and those who remain disease-free at 5 years post-treatment. Specifically, we focus on (1) identifying statistically significant differences in MRI intensities, (2) establishing morphological differences in prostatic anatomic structures, and (3) comparing these differences with the natural variability of prostatic structures. In order to attain these objectives, we use an anatomically constrained registration framework to construct BcR and non-BcR statistical atlases based on the pre-treatment magnetic resonance images (MRI) of the prostate. The patients included in the atlas either underwent RP or RT and were followed up for at least 5 years. The BcR atlas was constructed from a combined population of 12 pre-RT 1.5 Tesla (T) MRI and 33 pre-RP 3T MRI from patients with BcR within 5 years of treatment. Similarly, the non-BcR atlas was built based on a combined cohort of 20 pre-RT 1.5T MRI and 41 pre-RP 3T MRI from patients who remain disease-free 5 years post treatment. We chose the atlas framework as it

  16. Updating the Psoriatic Arthritis (PsA) Core Domain Set: A Report from the PsA Workshop at OMERACT 2016.

    PubMed

    Orbai, Ana-Maria; de Wit, Maarten; Mease, Philip J; Callis Duffin, Kristina; Elmamoun, Musaab; Tillett, William; Campbell, Willemina; FitzGerald, Oliver; Gladman, Dafna D; Goel, Niti; Gossec, Laure; Hoejgaard, Pil; Leung, Ying Ying; Lindsay, Chris; Strand, Vibeke; van der Heijde, Désirée M; Shea, Bev; Christensen, Robin; Coates, Laura; Eder, Lihi; McHugh, Neil; Kalyoncu, Umut; Steinkoenig, Ingrid; Ogdie, Alexis

    2017-10-01

    To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS). At OMERACT 2016, research conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants. We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted 24 focus groups with 130 patients from 7 countries representing 5 continents to identify patient domains. We achieved consensus through 2 rounds of separate surveys with 50 patients and 75 physicians, and a nominal group technique meeting with 12 patients and 12 physicians. We conducted a workshop and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient's global assessment, physical function, health-related quality of life, and systemic inflammation, which were recommended for all RCT and LOS. These were important, but not required in all RCT and LOS: economic cost, emotional well-being, participation, and structural damage. Independence, sleep, stiffness, and treatment burden were on the research agenda. The updated PsA Core Domain Set was endorsed at OMERACT 2016. Next steps for the PsA working group include evaluation of PsA outcome measures and development of a PsA Core Outcome Measurement Set.

  17. [Compound ciprofloxacin suppository combined with ningbitai and yunnan baiyao for histological prostatitis with PSA elevation].

    PubMed

    Huang, Bao-Xing; Su, Heng-Chuan; Sun, Fu-Kang

    2012-11-01

    To explore the efficacy of compound ciprofloxacin suppository (CCS) combined with Ningbitai (NBT) and Yunnan Baiyao (YB) capsules in the treatment of histological prostatitis with elevated levels of PSA. This study included 150 cases of type IIIA histological prostatitis, with PSA levels ranging from 4 to 50 microg/L. After 1 month's treatment with oral Levofloxacin tablets at 0.5 g qd, the PSA levels remained high in 86 patients. Prostate cancer was excluded by transrectal ultrasound-guided prostatic biopsy, and histological prostatitis was confirmed in 65 patients, who were assigned to an experimental group (n=45) and a control group (n=20) to receive CCS combined with NBT and YB capsules and CCS with NBT only, respectively, both for 4 weeks. We determined the PSA levels, obtained NIH-CPSI scores before and after medication, and compared them between the two groups. The two groups were well balanced in demographics and baseline characteristics. After treatment, both showed significant differences in the PSA level, PSA density (PSAD) and CPSI scores from the baseline (P<0.05), and there were also statistically significant differences between the two groups in the changes of the PSA level and CPSI scores after medication (P = 0.029 and 0.001). Compound ciprofloxacin suppository combined with Ningbitai and Yunnan Baiyao capsules can significantly decrease the level of serum PSA and relieve related symptoms in III A histological prostatitis with PSA elevation, and Yunnan Baiyao capsules can significantly enhance the therapeutic effect.

  18. Chronic hypoxia, physical exercise and PSA: correlation during high-altitude trekking (2004 K2 expedition).

    PubMed

    Verratti, Vittore; Di Giulio, Camillo; Di Francesco, Simona; Berardinelli, Francesco; Pellicciotta, Mario; Gidaro, Stefano; Zezza, Andrea; Tenaglia, Raffaele

    2007-01-01

    The aim of the present study was to identify the effects of physical exercise on PSA serum levels and the diagnostic validity of PSA in the screening of prostate cancer in subjects undergoing physical exercise during chronic hypoxia. The study was performed during trekking between 3,200 and 5,600 meters of altitude on K2 mountain for 26 days. Mean serum PSA values before and after exposure did not show significant difference due to physical exercise. These data indicate that physical exercise or mountain hypoxia do not affect the diagnostic validity of PSA.

  19. Clinician Factors Associated with Prostate-Specific Antigen Screening in Older Veterans with Limited Life Expectancy

    PubMed Central

    Tang, Victoria L.; Shi, Ying; Fung, Kathy; Tan, Jessica; Espaldon, Roxanne; Sudore, Rebecca; Wong, Melisa L.; Walter, Louise C.

    2017-01-01

    Importance Despite guidelines recommending against prostate-specific antigen (PSA) screening in elderly men with limited life expectancy, PSA screening remains common. Objectives Identify clinician characteristics associated with PSA screening in older veterans stratified by life expectancy. Design and Setting Cross-sectional study in the VA healthcare system. Participants 826,286 veterans aged ≥65 years eligible for PSA screening that had VA laboratory tests performed in 2011. Main Outcomes and Measures The primary outcome was the percentage of men with a screening PSA in 2011. Limited life expectancy was defined as age ≥85 with Charlson comorbidity score ≥1 or age ≥65 with Charlson comorbidity score ≥4. Primary predictors were clinician characteristics including degree-training level, specialty, age, and gender. We performed log-Poisson regression models for the association between each clinician characteristic and PSA screening stratified by patient life expectancy and adjusted for patient demographics and clinician clustering. Results In 2011, 56% of older veterans received PSA screening, including 39% of the 203,717 men with limited life expectancy. After adjusting for patient demographics, higher PSA screening in patients with limited life expectancy was associated with having a clinician who was an older male and was no longer in training. PSA screening ranged from 27% for men with a physician trainee to 42% for men with a physician attending (p <0.0001); 22% for men with a geriatrician to 82% for men with a urologist as their clinician (p <0.0001); 29% for men with a clinician ≤35 years old to 41% for those with a clinician ≥56 years old (p <0.0001); and 38% for men with a female clinician older than 55 years versus 43% for men with a male clinician older than 55 years (p=0.0008). Conclusion and Relevance Over a third of men with limited life expectancy received PSA screening. Men whose clinician was a physician trainee had substantially lower

  20. Clinician Factors Associated With Prostate-Specific Antigen Screening in Older Veterans With Limited Life Expectancy.

    PubMed

    Tang, Victoria L; Shi, Ying; Fung, Kathy; Tan, Jessica; Espaldon, Roxanne; Sudore, Rebecca; Wong, Melisa L; Walter, Louise C

    2016-05-01

    Despite guidelines recommending against prostate-specific antigen (PSA) screening in elderly men with limited life expectancy, PSA screening remains common. To identify clinician characteristics associated with PSA screening rates in older veterans stratified by life expectancy. Cross-sectional study of 826 286 veterans 65 years or older eligible for PSA screening who had VA laboratory tests performed in 2011 in the VA health care system. The primary outcome was the percentage of men with a screening PSA test in 2011. Limited life expectancy was defined as age of at least 85 years with Charlson comorbidity score of 1 or greater or age of at least 65 years with Charlson comorbidity score of 4 or greater. Primary predictors were clinician characteristics including degree-training level, specialty, age, and sex. We performed log-linear Poisson regression models for the association between each clinician characteristic and PSA screening stratified by patient life expectancy and adjusted for patient demographics and clinician clustering. In 2011, 466 017 (56%) of older veterans received PSA screening, including 39% of the 203 717 men with limited life expectancy. After adjusting for patient demographics, higher PSA screening rates in patients with limited life expectancy was associated with having a clinician who was an older man and was no longer in training. The PSA screening rates ranged from 27% for men with a physician trainee to 42% for men with an attending physician (P < .001); 22% for men with a geriatrician to 82% for men with a urologist as their clinician (P < .001); 29% for men with a clinician 35 years or younger to 41% for those with a clinician 56 years or older (P < .001); and 38% for men with a female clinician older than 55 years vs 43% for men with a male clinician older than 55 years (P < .001). More than one-third of men with limited life expectancy received PSA screening. Men whose clinician was a physician trainee had

  1. ANTIGENIC MODULATION

    PubMed Central

    Old, Lloyd J.; Stockert, Elisabeth; Boyse, Edward A.; Kim, Jae Ho

    1968-01-01

    Antigenic modulation (the loss of TL antigens from TL+ cells exposed to TL antibody in the absence of lytic complement) has been demonstrated in vitro. An ascites leukemia, phenotype TL.1,2,3, which modulates rapidly and completely when incubated with TL antiserum in vitro, was selected for further study of the phenomenon. Over a wide range of TL antibody concentrations modulation at 37°C was detectable within 10 min and was complete within approximately 1 hr. The cells were initially sensitized to C' by their contact with antibody, thereafter losing this sensitivity to C' lysis together with their sensitivity to TL antibody and C' in the cytotoxic test. The capacity of the cells to undergo modulation was abolished by actinomycin D and by iodoacetamide, and by reducing the temperature of incubation to 0°C. Thus modulation apparently is an active cellular process. Antigens TL. 1,2, and 3 are all modulated by anti-TL.1,3 serum and by anti-TL.3 serum. This modulation affects all three TL components together, even when antibody to one or two of them is lacking. aAnti-TL.2 serum does not induce modulation and in fact impairs modulation by the other TL antibodies. The influence of the TL phenotype of cells upon the demonstrable content of H-2 (D region) isoantigen, first shown in cells modulated in vivo, has been observed with cells modulated in vitro. Cells undergoing modulation show a progressive increase in H-2 (D region) antigen over a period of 4 hr, with no change in H-2 antigens of the K region. Restoration of the TL+ phenotype of modulated cells after removal of antibody is less rapid than TL+ → TL- modulation and may require several cell divisions. PMID:5636556

  2. Interoperability In The New Planetary Science Archive (PSA)

    NASA Astrophysics Data System (ADS)

    Rios, C.; Barbarisi, I.; Docasal, R.; Macfarlane, A. J.; Gonzalez, J.; Arviset, C.; Grotheer, E.; Besse, S.; Martinez, S.; Heather, D.; De Marchi, G.; Lim, T.; Fraga, D.; Barthelemy, M.

    2015-12-01

    As the world becomes increasingly interconnected, there is a greater need to provide interoperability with software and applications that are commonly being used globally. For this purpose, the development of the new Planetary Science Archive (PSA), by the European Space Astronomy Centre (ESAC) Science Data Centre (ESDC), is focused on building a modern science archive that takes into account internationally recognised standards in order to provide access to the archive through tools from third parties, for example by the NASA Planetary Data System (PDS), the VESPA project from the Virtual Observatory of Paris as well as other international institutions. The protocols and standards currently being supported by the new Planetary Science Archive at this time are the Planetary Data Access Protocol (PDAP), the EuroPlanet-Table Access Protocol (EPN-TAP) and Open Geospatial Consortium (OGC) standards. The architecture of the PSA consists of a Geoserver (an open-source map server), the goal of which is to support use cases such as the distribution of search results, sharing and processing data through a OGC Web Feature Service (WFS) and a Web Map Service (WMS). This server also allows the retrieval of requested information in several standard output formats like Keyhole Markup Language (KML), Geography Markup Language (GML), shapefile, JavaScript Object Notation (JSON) and Comma Separated Values (CSV), among others. The provision of these various output formats enables end-users to be able to transfer retrieved data into popular applications such as Google Mars and NASA World Wind.

  3. Improvements in progress for Russia`s new PSA law

    SciTech Connect

    Pugliaresi, L.; Hensel, A.C.

    1996-03-25

    Russian legislation making production sharing agreements (PSAs) fully legal under Russian law passed the upper house of the Russian Parliament (Federal Council) on December 19, 1995, was signed into law by President Boris Yeltsin on December 31, 1995, and took effect on January 11, 1996. While PSA legislation remains the central legal basis for large scale investment in the Russian petroleum sector, company views towards investment in this sector are tied to much more than the extent of legal guarantees. Investor attitudes are also shaped by expectations regarding political stability, behavior of Russian regulatory authorities, and prospects for the Russian economy. Furthermore, Western investors in the petroleum sector have some experience in dealing with the Russian government and existing frameworks for investment, particularly the joint venture (JV) deals with Russian entities and the often changing regulatory and tax treatment of these ventures. It is the view of the authors that attitudes among some Western companies in Russia on the political and economic environment may be too pessimistic and shaped more by press reports than actual conditions. News reports on violence, political instability, and a disastrous economy are not entirely borne out by the facts. Russian, of course, faces serious political and economic problems which must be carefully evaluated, but the overall outlook is much more complex, and some positive developments are underway. This paper reviews the economic, oil production and industry outlook as a result of the PSA law.

  4. Fluorescence of prostate-specific antigen as measured with a portable 1D scanner

    NASA Astrophysics Data System (ADS)

    Kim, Byeong C.; Jeong, Jin H.; Jeong, Dong S.; Kim, Young M.; Oh, Sang W.; Choi, Eui Y.; Kim, Jae H.; Nahm, Kie B.

    2005-01-01

    Prostate-specific antigen (PSA) is an androgen-dependent glycoprotein protease (M.W. 33 kDa) and a member of kallikrein super-family of serine protease, and has chymotrypsin-like enzymatic activity. It is synthesized by the prostate epithelial cells and found in the prostate gland and seminal plasma as a major protein. It is widely used as a clinical marker for diagnosis, screening, monitoring and prognosis of prostate cancer. In normal male adults, the concentration of PSA in the blood is below 4 ng/ml and this value increases in patients with the prostate cancer or the benign prostatic hyperplasia (BPH) due to its leakage into the circulatory system. As such, systematic monitoring of the PSA level in the blood can provide critical information about the progress of the prostatic disease. We have developed a compact integral system that can quantitatively measure the concentration of total PSA in human blood. This system utilizes the fluorescence emitted from the dye molecules attached to PSA molecules after appropriate immunoassay-based processing. Developed for the purpose of providing an affordable means of fast point-of-care testing of the prostate cancer, this system proved to be able to detect the presence of the PSA at the level of 0.18 ng/ml in less than 12 minutes, with the actual measurement taking less than 2 minutes. The design concept for this system is presented together with the result for a few representative samples.

  5. The Stability of Prostate-Specific Antigen in Semen Under Various Temperatures.

    PubMed

    Srettabunjong, Supawon; Betset, Parimol; Limawongpranee, Suvit; Ekpo, Pattama

    2015-11-01

    Prostate-specific antigen (PSA) is most commonly used for identifying semen, especially in the absence of sperm. However, PSA concentration varies according to storage temperature and duration, and little is known about its stability in semen. This study was therefore aimed to determine the stability under five different temperatures: -80, -20, 4, 25, and 37°C; and nine different durations: 1, 2, 3, 5, 7, 14, 30, 90, and 180 days. All samples were stored at -80°C after being secreted from the volunteers' body until analyzed. Results showed that the PSA concentration declined significantly over time under all temperatures studied except -80°C. At -20 and 4°C, PSA was still detectable on Day 180 with 50% and 70% decrease from its original concentration, respectively. At 25 and 37°C, PSA was detected up to Day 7 and 3, respectively. This information might assist forensic scientists understand more about PSA nature and integrate it into their works.

  6. Serum sialic acid and prostate-specific antigen in differential diagnosis of benign prostate hyperplasia and prostate cancer.

    PubMed

    Romppanen, Jarkko; Haapalainen, Terhi; Punnonen, Kari; Penttilä, Ilkka

    2002-01-01

    In order to improve the diagnostic accuracy of the serum total and free prostate-specific antigen (PSA) in differential diagnosis between benign prostate hyperplasia (BPH) and prostate cancer, the serum total sialic acid (TSA) was measured and logistic regression (LR) models were built. Significantly higher serum PSA (p<0.001) concentrations were observed in patients with prostate cancer compared to control subjects, but no statistically significant differences were found in serum TSA concentrations between these groups. Serum PSA reliably discriminated patients with prostate cancer from control subjects, the area under the ROC curve (AUC) being 0.991 (0.010). When serum PSA was in the gray zone, from 4 to 10 microg/l, the diagnostic accuracy of PSA in discriminating patients with prostate cancer from BPH patients was very poor, AUC being 0.563 (0.132). However, using the same set of patients the LR model combining serum PSA, free to total PSA ratio and TSA values, as well as digital rectal examination results, had good diagnostic accuracy in discriminating the prostate cancer patients from patients with BPH, the area under the ROC curve being 0.895 (0.054). The present data suggest that the logistic regression model combining laboratory measurements and results of the clinical examination may be a useful adjunct in the differential diagnosis of benign and malignant prostate disease.

  7. Antigen- and receptor-driven regulatory mechanisms. V. The failure of idiotype-coupled spleen cells to induce unresponsiveness in animals lacking the appropriate VH genes is caused by the lack of idiotype-matched targets.

    PubMed

    Sy, M S; Dietz, M H; Nisonoff, A; Germain, R N; Benacerraf, B; Greene, M I

    1980-11-01

    A/J anti-p-azobenzenearsonate (ABA) antibodies bearing cross-reactive idiotypic (CRI) determinants, when coupled to spleen cells and then injected intravenously into naive animals, stimulate suppressor T cell (Ts) responses. Moreover, previous studies have demonstrated that the ability of such idiotype-coupled spleen cells to induce immune unresponsiveness to subsequent immunization with ABA-coupled spleen cells is linked to Igh-1 genes. Thus, CRI bearing antibodies from A/J mice, when conjugated to normal BALB/c spleen cells in vitro and then injected intravenously to syngeneic BALB/c mice, failed to induce tolerance in these animals. However, spleen cells taken from these animals transferred significant degrees of suppression to Igh-1 congenic C.AL-20 but not to H-2 congenic, Igh-1 distinct B10.D2 mice. Therefore, the failure of CRI-coupled spleen cells to induce suppressor cell- mediated unresponsiveness in animals unable to express the appropriate VH genes (i.e. BALB/c and B10.D2) appears to be caused by the lack of idiotype- matched targets. The notion that the ability to express certain Vn genes in the recipient animal is a prerequisite for suppressor cell function was further supported by the observation that suppressor cells induced in C.AL-20 mice failed to transfer any degree of suppression to BALB/c mice. The ability to transfer suppression from BALB/c mice to C.AL-20 mice is a T cell- dependent phenomenon, since in vitro treatment with anti-Thy 1.2 antiserum and complement completely abrogated suppressor cell function. Furthermore, these suppressor T cells are antigen specific and can be enriched on idiotype-coated petri dishes, indicating they possess anti-idiotypic receptors. Therefore, appropriate anti-idiotype and idiotype interaction is essential for the manifestation of suppressor T cell function in ABA-specific suppressor pathways.

  8. Antigen- and receptor-driven regulatorymechanisms. The failure of idiotype- coupled spleen cells to induce unresponsiveness in animals lacking the appropriate VH genes is caused by the lack of idiotype-matehed targets

    PubMed Central

    Sy, M-S; Dietz, MH; Nisonoff, A; Germain, RN; Benacerraf, B; Greene, MI

    1980-01-01

    A/J anti-p-azobenzenearsonate (ABA) antibodies bearing cross-reactive idiotypic (CRI) determinants, when coupled to spleen cells and then injected intravenously into naive animals, stimulate suppressor T cell (Ts) responses. Moreover, previous studies have demonstrated that the ability of such idiotype-coupled spleen cells to induce immune unresponsiveness to subsequent immunization with ABA-coupled spleen cells is linked to Igh-1 genes. Thus, CRI bearing antibodies from A/J mice, when conjugated to normal BALB/c spleen cells in vitro and then injected intravenously to syngeneic BALB/c mice, failed to induce tolerance in these animals. However, spleen cells taken from these animals transferred significant degrees of suppression to Igh-1 congenic C.AL-20 but not to H-2 congenic, Igh-1 distinct B10.D2 mice. Therefore, the failure of CRI-coupled spleen cells to induce suppressor cell- mediated unresponsiveness in animals unable to express the appropriate VH genes (i.e. BALB/c and B10.D2) appears to be caused by the lack of idiotype- matched targets. The notion that the ability to express certain Vn genes in the recipient animal is a prerequisite for suppressor cell function was further supported by the observation that suppressor cells induced in C.AL-20 mice failed to transfer any degree of suppression to BALB/c mice. The ability to transfer suppression from BALB/c mice to C.AL-20 mice is a T cell- dependent phenomenon, since in vitro treatment with anti-Thy 1.2 antiserum and complement completely abrogated suppressor cell function. Furthermore, these suppressor T cells are antigen specific and can be enriched on idiotype-coated petri dishes, indicating they possess anti-idiotypic receptors. Therefore, appropriate anti-idiotype and idiotype interaction is essential for the manifestation of suppressor T cell function in ABA-specific suppressor pathways. PMID:6159446

  9. Differential blood-based diagnosis between benign prostatic hyperplasia and prostate cancer: miRNA as source for biomarkers independent of PSA level, Gleason score, or TNM status.

    PubMed

    Leidinger, Petra; Hart, Martin; Backes, Christina; Rheinheimer, Stefanie; Keck, Bastian; Wullich, Bernd; Keller, Andreas; Meese, Eckart

    2016-08-01

    Since the benefit of prostate-specific antigen (PSA) screening remains controversial, new non-invasive biomarkers for prostate carcinoma (PCa) are still required. There is evidence that microRNAs (miRNAs) in whole peripheral blood can separate patients with localized prostate cancer from healthy individuals. However, the potential of blood-based miRNAs for the differential diagnosis of PCa and benign prostatic hyperplasia (BPH) has not been tested. We compared the miRNome from blood of PCa and BPH patients and further investigated the influence of the tumor volume, tumor-node-metastasis (TNM) classification, Gleason score, pretreatment risk status, and the pretreatment PSA value on the miRNA pattern. By microarray approach, we identified seven miRNAs that were significantly deregulated in PCa patients compared to BPH patients. Using quantitative real time PCR (qRT-PCR), we confirmed downregulation of hsa-miR-221* (now hsa-miR-221-5p) and hsa-miR-708* (now hsa-miR-708-3p) in PCa compared to BPH. Clinical parameters like PSA level, Gleason score, or TNM status seem to have only limited impact on the overall abundance of miRNAs in patients' blood, suggesting a no influence of these factors on the expression of deregulated miRNAs.

  10. An electrochemical biosensor to simultaneously detect VEGF and PSA for early prostate cancer diagnosis based on graphene oxide/ssDNA/PLLA nanoparticles.

    PubMed

    Pan, Lung-Hsuan; Kuo, Shin-Hung; Lin, Tzu-Yang; Lin, Chih-Wen; Fang, Po-Yu; Yang, Hung-Wei

    2017-03-15

    Early diagnosis of prostate cancer (PCa) is critical for the prevention of metastasis and for early treatment; therefore, a simple and accurate device must be developed for this purpose. In this study, we reported a novel fabrication method for producing a dual-modality biosensor that can simultaneously detect vascular endothelial growth factor (VEGF) and prostate-specific antigen (PSA) in human serum for early diagnosis of PCa. This biosensor was constructed by coating graphene oxide/ssDNA (GO-ssDNA) on an Au-electrode for VEGF detection, and incorporated with poly-L-lactide nanoparticles (PLLA NPs) for signal amplification and PSA detection. The results showed that this biosensor has wide liner detection ranges (0.05-100ng/mL for VEGF and 1-100ng/mL for PSA), as well as high levels of sensitivity and selectivity (i.e., resisting interference from external factors, such as glucose, ascorbic acid human serum protein, immunoglobulin G, and immunoglobulin M), and demonstrated a high correlation with an enzyme-linked immunosorbent assay for sample detection in patients. Therefore, this biosensor could be utilized for early clinical diagnosis of PCa in the future.

  11. Improved cancer specificity in PSA assay using Aleuria aurantia lectin coated Eu-nanoparticles for detection.

    PubMed

    Kekki, Henna; Peltola, Mari; van Vliet, Sandra; Bangma, Chris; van Kooyk, Yvette; Pettersson, Kim

    2017-01-01

    The objective was to study the differences in PSA fucosylation obtained from LNCaP and PC-3 prostate cancer cell lines, seminal plasma PSA and recombinant precursor form of PSA expressed in baculovirus, using Aleuria aurantia lectin (AAL). The aim was to assess whether differences in fucosylation (Fucα1-6/3GlcNAc carbohydrates) of PSA either in urine, blood or tissue enable the discrimination of patients with prostate cancer (PCa) from benign prostatic hyperplasia (BPH) and young males. Two novel lectin-immunoassays were developed for the analysis of fucosylation of PSA by measuring the time-resolved fluorescence of europium chelate. The lectin-immunoassays utilize free PSA-specific Fab-fragments for capturing the analyte and either europium-labeled AAL or AAL coupled to Eu(III)-chelate-dyed nanoparticles for the detection of Fucα1-6/3GlcNAc carbohydrates on PSA. Using the novel lectin-immunoassays, we showed higher levels of Fucα1-6/3GlcNAc on PSA derived from LNCaP and PC-3 cells compared to seminal plasma PSA. With the more sensitive nanoparticle-based lectin-immunoassay we detected a statistically significant increase in the PSA fucosylation in PCa tissue compared to benign tissue (p=0.001) and in urine from PCa patients compared to BPH patients (p=0.030), and an even greater discrimination (p=0.010) when comparing BPH patients to PCa patients with Gleason score≥7. AAL coupled to Eu(III)-chelate-dyed nanoparticles improved the sensitivity of immunoassay for the detection of Fucα1-6/3GlcNAc structures on PSA. The preliminary findings show an increased fucosylation in PCa compared to benign conditions. Further validation is required to assess the true clinical utility of AAL in PCa diagnosis. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  12. Six Weeks of Fluoroquinolone Antibiotic Therapy for Patients With Elevated Serum Prostate-specific Antigen Is Not Clinically Beneficial: A Randomized Controlled Clinical Tri