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Sample records for antigen psa failure

  1. 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 ...

  2. 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.

  3. 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] ...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

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

    DTIC Science & Technology

    2007-05-01

    stage 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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  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. 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.

  4. 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, Taimur; Peters, Max; Kanthabalan, Abi; McCartan, Neil; Fatola, Yomi; van der Voort van Zyp, Jochem; van Vulpen, Marco; Freeman, Alex; Moore, Caroline M.; Arya, Manit; Emberton, Mark; Ahmed, Hashim U.

    2016-01-01

    Background Treatment options for radio-recurrent prostate cancer are either androgen deprivation therapy or salvage prostatectomy. Whole-gland 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 localized disease following prior external beam radiotherapy (2005-2012). No upper threshold was applied for risk category, Prostate Specific Antigen (PSA), or Gleason grade either at presentation or at time of failure. Progression was defined as a composite with either biochemical failure (Phoenix criteria [PSA>nadir+2ng/mL]), start of systemic therapies or metastases. Results Median age (IQR), pre-treatment PSA (IQR), and Gleason score (range), were 68years (64-72), 5.9ng/mL (2.2-11.3), and 7 (6-9), respectively. Median follow-up was 64months (49-84). 24/50 (48%) avoided androgen deprivation therapies. 28/50 (56%) achieved a PSA-nadir <0.5ng/ml. 15/50 (30%) had a nadir ≥0.5ng/ml. 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year PFS was 72%, 40% and 31%, respectively. Actuarial 1, 3, and 5-year OS was 100%, 94% and 87%, respectively. When comparing patients with PSA nadir <0.5ng/ml, nadir ≥0.5 and non-responders a statistically significant difference in PFS was seen (p<0.0001). 3-year PFS in each group was 57%, 20% and 0%, respectively. 5-year overall survival was 96%, 100% and 38%, respectively. Early in the learning curve, between 2005-2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measures 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-metastases, disease control rates were promising in PSA-responders, however with significant morbidity. Additionally, post-HIFU PSA-nadir appears to be an

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. Diagnostic value of microRNAs in prostate cancer patients with prostate specific antigen (PSA) levels between 2, and 10 ng/mL

    PubMed Central

    Akbayır, Serin; Muşlu, Necati; Erden, Sema; Bozlu, Murat

    2016-01-01

    Objective Prostate specific antigen (PSA), used for the early diagnosis of prostate cancer (PCa), is one of the best tumour markers known so far. However, in situations when PSA is between 2–10 ng/mL, which is named as grey zone, PSA falls short of distinguishing benign prostate diseases from PCa. On the other hand, it was demonstrated in many previous studies that microRNA (miRNA) could be a marker for cancer. Therefore, in this study, it was aimed to enhance the diagnostic power of PSA, especially with grey zone patients, by the use of miRNA. Material and Methods Ninety-four patients included in the study were divided into three groups as “control group” (n=44, PSA=2–10 ng/mL and benign), “PCa 1 group” (n=37, PSA=2–10 ng/mL), and “PCa 2 group” (n=13, PSA >10 ng/mL), according to their pathological results and PSA levels. Free PSA (fPSA) and total PSA (T-PSA) levels were measured with chemiluminometric sandwich immunoassay method. Expressions of miRNAs were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) method. The most appropriate specificity, sensitivity and prediction values were found by drawing the receiver operating characteristic (ROC) curves of total PSA, free/total PSA (f/T PSA) ratio, and miRNAs, and the diagnostic powers were compared with each other. Results Diagnostic powers of the f/T PSA ratio and miRNA were compared in PCa 1 and the control groups to determine the marker with higher area under the curve (AUC). It was shown that the diagnostic power of the combination of miR-16-5p and f/T PSA was higher than that obtained when they were used separately. Conclusion As a result, while making the the discrimination between benign and malignant prostate in patients with grey zone, it was determined that the combination of miR-16-5p and f/T PSA was more valuable than T-PSA or f/T PSA alone. It was thought that diagnostic role of miRNAs in the early diagnosis of the different stages of PCa needed to

  10. 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

  11. 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

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

    DTIC Science & Technology

    2006-05-01

    14. ABSTRACT: Following surgery or radiation of primary early-stage prostate cancer ( PrCA ), one in three patients will experience an elevation in...androgen ablation. We hypothesize that the host- PrCA balance in asymptomatic men with biochemically recurrent PrCA , as reflected by the PSA rise, is...Registry letters Reminder Call Script 4 Introduction: Prostate cancer ( PrCA ) is the most commonly occurring cancer, excluding skin

  13. 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

  14. Lycopene Supplementation in the Complementary Management of PSA Failure: A Randomized Placebo-Controlled Trial for Prostate Cancer Survivors

    DTIC Science & Technology

    2007-01-01

    Curr Probl Surg. 1996 Nov;33(11):881-952. 18. Madan A, Beech DJ. Laparoscopic revision of bariatric surgery . (Video submitted to American College of...Years after successful treatment by surgery or radiation, some patients present with biochemical (PSA) relapse or failure for which the effects of...research assistant position in the department of surgery at Meharry Medical College, and he will be able to spend part of his time on this project

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  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

    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.

  1. 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

  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. 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

  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. 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.

  7. 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

  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. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. [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.

  15. 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

  16. 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. |

  17. 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

  18. 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…

  19. 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)

  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. [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.

  2. 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

  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. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  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. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  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. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. [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.

  6. 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

  7. 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.

  8. 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. |

  9. 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. |

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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 .

  19. 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

  20. 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

  1. 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.

  2. 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

  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. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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%.

  13. 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.

  14. 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

  15. 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.

  16. 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

  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. 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.

  19. 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.

  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. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. [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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. [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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. [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.

  19. 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.

  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. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. Prostate Cancer Screening: Should You Get a PSA Test?

    MedlinePlus

    ... Whether you're taking medications that affect PSA measurements, such as finasteride (Propecia, Proscar), dutasteride (Avodart) and ... in the United States, 2015: A review of current American Cancer Society guidelines and current issues in ...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. [Prostate-specific antigen. The role in the prostate cancer diagnosis].

    PubMed

    Sánchez-Martínez, Luis Carlos; Paredes-Solís, César Armando; Hernández-Ordóñez, Octavio Francisco; Sánchez-Ruvalcaba, Itzel Rigel

    2013-01-01

    Prostate cancer (PC) is a common malignant neoplasia in males over 50 years. The serum level of prostate specific antigen (PSA) is a tool in the diagnosis of PC and benign prostatic hyperplasia patients that improves the efficiency obtained with the digital rectal examination. The use of PSA increases the detection rates of organ-confined PC. The PSA must be requested by the primary care physician in male population over 45 years and if the result is above the normal levels, the patient must be send to an urologist.

  6. 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.

  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. 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.

  9. 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

  10. ‘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

  11. 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.

  12. 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

  13. 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

  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. 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.

  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. 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

  18. 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.

  19. Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects

    PubMed Central

    Dearnaley, D P; Hall, E; Lawrence, D; Huddart, R A; Eeles, R; Nutting, C M; Gadd, J; Warrington, A; Bidmead, M; Horwich, A

    2005-01-01

    Radical radiotherapy is a standard form of management of localised prostate cancer. Conformal treatment planning spares adjacent normal tissues reducing treatment-related side effects and may permit safe dose escalation. We have tested the effects on tumour control and side effects of escalating radiotherapy dose and investigated the appropriate target volume margin. After an initial 3–6 month period of androgen suppression, 126 men were randomised and treated with radiotherapy using a 2 by 2 factorial trial design. The initial radiotherapy tumour target volume included the prostate and base of seminal vesicles (SV) or complete SV depending on SV involvement risk. Treatments were randomised to deliver a dose of 64 Gy with either a 1.0 or 1.5 cm margin around the tumour volume (1.0 and 1.5 cm margin groups) and also to treat either with or without a 10 Gy boost to the prostate alone with no additional margin (64 and 74 Gy groups). Tumour control was monitored by prostate-specific antigen (PSA) testing and clinical examination with additional tests as appropriate. Acute and late side effects of treatment were measured using the Radiation Treatment and Oncology Groups (RTOG) and LENT SOM systems. The results showed that freedom from PSA failure was higher in the 74 Gy group compared to the 64 Gy group, but this did not reach conventional levels of statistical significance with 5-year actuarial control rates of 71% (95% CI 58–81%) in the 74 Gy group vs 59% (95% CI 45–70%) in the 64 Gy group. There were 23 failures in the 74Gy group and 33 in the 64 Gy group (Hazard ratio 0.64, 95% CI 0.38–1.10, P=0.10). No difference in disease control was seen between the 1.0 and 1.5 cm margin groups (5-year actuarial control rates 67%, 95% CI 53–77% vs 63%, 95% CI 50–74%) with 28 events in each group (Hazard ratio 0.97, 95% CI 0.50–1.86, P=0.94). Acute side effects were generally mild and 18 weeks after treatment, only four and five of the 126 men

  20. 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.

  1. 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

  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. 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.

  4. 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

  5. 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.

  6. 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 ...

  7. 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.

  8. 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

  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. 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

  11. 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.

  12. 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)

  13. 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.

  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. 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

  16. 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.

  17. 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.

  18. The effect of high level natural ionizing radiation on expression of PSA, CA19-9 and CEA tumor markers in blood serum of inhabitants of Ramsar, Iran.

    PubMed

    Heidari, Mohammad Hassan; Porghasem, Mohsen; Mirzaei, Nazanin; Mohseni, Jafar Hesam; Heidari, Matine; Azargashb, Eznollah; Movafagh, Abolfazl; Heidari, Reihane; Molouki, Aidin; Larijani, Leila

    2014-02-01

    Since several high level natural radiation areas (HLNRAs) exist on our planet, considerable attention has been drawn to health issues that may develop as the result of visiting or living in such places. City of Ramsar in Iran is an HNLRA, and is a tourist attraction mainly due to its hot spas. However, the growing awareness over its natural radiation sources has prompted widespread scientific investigation at national level. In this study, using an ELISA method, the level of expression of three tumor markers known as carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and carcino antigen 19-9 (CA19-9) in blood serum of 40 local men of Ramsar (subject group) was investigated and compared to 40 men from the city of Noshahr (control group). Noshahr was previously identified as a normal level natural radiation area (NLNRA) that is some 85 km far from Ramsar. According to statistical analysis, there was a significant difference in the levels of PSA and CA19-9 markers between the two groups (p < 0.001) with those of Ramsar being considerably higher. CEA level did not show any difference. Although some of the volunteers tested positive to the markers, they were in good health as confirmed by the physician. Moreover, the high number of positive markers in Noshahr was considerable. Therefore, future study is needed to further validate this result and to determine the level of positivity to tumor markers in both cities.

  19. 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.

  20. Inhibition of Pneumococcal Adherence to Human Nasopharyngeal Epithelial Cells by Anti-PsaA Antibodies

    PubMed Central

    Romero-Steiner, Sandra; Pilishvili, Tamar; Sampson, Jacquelyn S.; Johnson, Scott E.; Stinson, Annie; Carlone, George M.; Ades, Edwin W.

    2003-01-01

    The role of pneumococcal (Pnc) surface adhesin A (PsaA) in the adherence of Streptococcus pneumoniae (pneumococcus) to host cells is not well defined. We examined the effect of anti-PsaA antibodies in an inhibition of adherence assay using Detroit 562 nasopharyngeal human epithelial cells. Rabbit polyclonal (Pab) anti-recombinant PsaA (rPsaA) sera, a purified mouse monoclonal antibody (MAb) (MAb 6F62G8E12), and 22 healthy adult sera with known anti-PsaA IgG levels (obtained by enzyme-linked immunosorbent assay) were evaluated for their abilities to inhibit Pnc adherence to confluent monolayers (measured as percent reduction in CFU counts compared to those of uninhibited controls). Pnc adherence was dependent on capsular phenotype (no or low adherence for opaque strains). With an inoculum of 104 to 105 bacteria/well, the mean ± standard deviation count in controls was 163 ± 32 CFU/well for transparent strains. Low adherence was observed for a PsaA-minus mutant even at higher inoculum doses. Mean percent inhibitions of adherence with Pab and MAb were 54 and 50%, respectively. Adult sera showed inhibition in a dose-response fashion with a range of 98 to 8%, depending on the serum anti-PsaA antibody concentration. Absorption of Pab with rPsaA restored Pnc adherence to control levels. Absorption of sera with a PsaA-minus mutant did not result in a significant decrease (P >0.05) of inhibition of adherence activity. Additionally, nearly 100% of Pnc adherence was inhibited by lipidated rPsaA at 2.5 μg/ml. Our data support the argument that PsaA is an adhesin that mediates Pnc adherence to human nasopharyngeal cells. This functional assay may be useful in evaluating antibodies elicited in response to PsaA vaccination. PMID:12626450

  1. Ultrasensitive Detection of Prostate-Specific Antigen and Thrombin Based on Gold-Upconversion Nanoparticle Assembled Pyramids.

    PubMed

    Hao, Tiantian; Wu, Xiaoling; Xu, Liguang; Liu, Liqiang; Ma, Wei; Kuang, Hua; Xu, Chuanlai

    2017-03-29

    Self-assembled nanostructures have been used for the detection of numerous cancer biomarkers. In this study, a gold-upconversion-nanoparticle (Au-UCNP) pyramid based on aptamers is fabricated to simultaneously detect thrombin and prostate-specific antigen (PSA) using surface-enhanced Raman scattering (SERS) and fluorescence, respectively. The higher the concentration of thrombin, the lower the intensity of SERS. PSA connected with the PSA aptamer leads to an increase in fluorescence intensity. The limit of detection of thrombin and PSA reaches 57 × 10(-18) and 0.032 × 10(-18) m, respectively. In addition, the pyramid also exhibits great target specificity. The results of human serum target detection demonstrate that the Au-UCNP pyramid is an excellent choice for the quantitative determination of cancer biomarkers, and is feasible for the early diagnosis of cancer.

  2. Fifth-Generation Digital Immunoassay for Prostate Specific Antigen Using Single Molecule Arrays

    PubMed Central

    Wilson, D.H.; Hanlon, D.W.; Provuncher, G.K.; Chang, L.; Song, L.; Patel, P.P.; Ferrell, E.P.; Lepor, H; Partin, A.W.; Chan, D.W.; Sokoll, L.J.; Cheli, C.D.; Thiel, R.P.; Fournier, D.R.; Duffy, D.C.

    2012-01-01

    BACKGROUND Measurement of prostate specific antigen (PSA) in prostate cancer patients following radical prostatectomy (RP) has been limited by the sensitivity of available assays. Because radical prostatectomy removes the tissue responsible for PSA production, post-surgical PSA is typically undetectable with current assay methods. However, evidence suggests that more sensitive determination of PSA status following RP could improve assessment of patient prognosis, response to treatment, and better target secondary therapy to those who may benefit most. We report the development and validation of an investigational digital immunoassay with two logs greater sensitivity than today’s ultrasensitive third-generation PSA assays. METHODS Reagents were developed for a paramagnetic bead-based ELISA for use with high-density arrays of femtoliter-volume wells. Anti-PSA capture-beads with immunocomplexes and associated enzyme labels were singulated within the wells of the arrays and interrogated for the presence of enzymatic product. Analytical performance of the assay was characterized, its accuracy compared with a commercially available test, and longitudinal serum samples from a pilot study of 33 RP patients were analyzed. RESULTS The assay exhibited a functional sensitivity (20% inter-assay CV) of less than 0.00005 ng/mL (0.05 pg/mL), total imprecision of less than 10% from 1 to 50 pg/mL, and excellent agreement with the comparator method. All RP samples were well within the assay measurement capability. PSA values following surgery were examined in the context of five-year biochemical cancer recurrence. CONCLUSION The assay demonstrated a robust two-log advance in measurement sensitivity relative to current ultrasensitive assays, and the analytical performance for accurate assessment of PSA status after RP. PMID:21998342

  3. 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.

  4. 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.

  5. 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.

  6. Sensitive and selective detection of prostate-specific antigen using a photonic crystal nanolaser.

    PubMed

    Hachuda, Shoji; Watanabe, Takumi; Takahashi, Daichi; Baba, Toshihiko

    2016-06-13

    The detection of low-concentration biomarkers is expected to facilitate the early diagnosis of severe diseases, including malignant tumors. Using photonic crystal nanolaser sensors, we detected prostate-specific antigen (PSA) from a concentration of 1 fM, which is difficult to detect by conventional enzyme-linked immunosorbent assay. The signal intensity and stability were improved by using a surfactant (i.e., ethanolamine). Even when a contaminant such as bovine serum albumin was mixed into the PSA sample, thereby increasing the concentration of the contaminant ten billion times, it was still possible to maintain a high level of detection.

  7. A Summary of Taxonomies of Digital System Failure Modes Provided by the DigRel Task Group

    SciTech Connect

    Chu T. L.; Yue M.; Postma, W.

    2012-06-25

    Recently, the CSNI directed WGRisk to set up a task group called DIGREL to initiate a new task on developing a taxonomy of failure modes of digital components for the purposes of PSA. It is an important step towards standardized digital I&C reliability assessment techniques for PSA. The objective of this paper is to provide a comparison of the failure mode taxonomies provided by the participants. The failure modes are classified in terms of their levels of detail. Software and hardware failure modes are discussed separately.

  8. Identification of HLA-DRB1*1501-restricted T-cell epitopes from prostate-specific antigen.

    PubMed

    Klyushnenkova, Elena N; Link, Jason; Oberle, Warren T; Kodak, James; Rich, Cathleen; Vandenbark, Arthur A; Alexander, Richard B

    2005-04-15

    The development of immunotherapy for prostate cancer based on the induction of autoimmunity to prostate tissue is very attractive because prostate is not a vital organ beyond the reproductive years. CD4 T cells play an important role in the development of antitumor immune responses, yet the identification of naturally processed MHC Class II-restricted epitopes derived from prostate differentiation antigens has not been described. To facilitate the search for prostate-specific antigen (PSA)-derived MHC class II-restricted peptides, we immunized mice transgenic for HLA-DRB1*1501 with human PSA and showed a robust dose-dependent immune response to the antigen. Screening a library of overlapping 20-mer peptides that span the entire PSA sequence identified two 20-mer peptides, PSA(171-190) and PSA(221-240), which were responsible for this reactivity. Immunization of DR2b transgenic mice with these peptides induced specific responses to the peptide and whole PSA. Identified peptides were used to stimulate CD4 T cells from HLA-DRB1*1501+ patients with a rare condition, granulomatous prostatitis, and who seem to have a preexisting immune response directed against the prostate gland. We previously showed a linkage of granulomatous prostatitis to HLA-DRB1*1501, suggesting that this disease may have an autoimmune etiology. Peptide-specific CD4 T-cell lines were generated from the peripheral blood of these patients as well as one patient with prostate cancer. These lines also recognized whole, processed PSA in the context of HLA-DRB1*1501. This study will be instrumental in understanding the interaction between circulating self-reactive T cells, organ-specific autoimmunity, and antitumor immune response. The use of these peptides for the immunotherapy of prostate cancer is under investigation.

  9. A structural model for the prostate disease marker, human prostate-specific antigen.

    PubMed Central

    Villoutreix, B. O.; Getzoff, E. D.; Griffin, J. H.

    1994-01-01

    Prostate-specific antigen (PSA) provides an excellent serum marker for prostate cancer, the most frequent form of cancer in American males. PSA is a 237-residue protease based on sequence homology to kallikrein-like enzymes. To predict the 3-dimensional structure of PSA, homology modeling studies were performed based on sequence and structural alignments with tonin, pancreatic kallikrein, chymotrypsin, and trypsin. The structurally conserved regions of the 4 reference X-ray proteins provided the core structure of PSA, whereas the loop structures were modeled on the loops of tonin and kallikrein. The unique "kallikrein loop" insert, between Ser 95b and Pro 95k of kallikrein, was constructed using molecular mechanics, dynamics, and electrostatics calculations. In the resulting PSA structure, the catalytic triad, involving residues His 57, Asp 102, and Ser 195, and hydrophobic and electrostatic interactions typical of serine proteases were extremely well conserved. Similarly, the 5-disulfide bonds of kallikrein were also conserved in PSA. These results, together with the fact that no major steric clashes arose during the modeling process, provide strong evidence for the validity of the PSA model. Calculation of the electrostatic potential contours of kallikrein and PSA was carried out using the finite difference Poisson-Boltzmann method. The calculations revealed matching areas of negative potential near the catalytic triad, but differences in the positive potential surrounding the active site. The PSA glycosylation site, Asn 61, is fully accessible to the solvent and is enclosed in a positive region of the isopotential map. The bottom of the substrate specificity pocket, residue S1, is a serine (Ser 189) as in chymotrypsin, rather than aspartate (Asp 189) as in tonin, kallikrein, and trypsin. This fact, plus other features of the S1 binding-pocket region, suggest that PSA would prefer substrates with hydrophobic residues at the P1 position. The location of a

  10. Network commercials promote legal drugs: outnumber anti-drug PSA's 45-to-1.

    PubMed

    Fedler, F; Phillips, M; Raker, P; Schefsky, D; Soluri, J

    1994-01-01

    During the week of September 16 to 22, 1990, commercials promoting drugs and alcohol outnumbered the networks' news stories, documentaries, and PSA's about illegal drugs by a ratio of almost 39-to-1. If you consider the PSA's alone, the commercials promoting drugs and alcohol outnumbered them by a ratio of almost 45-to-1.

  11. Synthesis of PSA Inhibitors as SPECT- and PET-Based Imaging Agents for Prostate Cancer

    DTIC Science & Technology

    2011-06-01

    for their ability to inhibit PSA and chymotrypsin. 15. SUBJECT TERMS Prostate cancer , PSA inhibitors, boronic acids, peptidomimetics, serine protease...prostate cancer . First, all men undergoing androgen ablation, eventually relapse and no longer respond to hormone treatment . Therefore, there is an...Imaging Agents for Prostate Cancer PRINCIPAL INVESTIGATOR: Maya Kostova, Ph.D. CONTRACTING ORGANIZATION: Johns Hopkins University

  12. Distribution of PSA-NCAM in normal, Alzheimer's and Parkinson's disease human brain.

    PubMed

    Murray, Helen C; Low, Victoria F; Swanson, Molly E V; Dieriks, Birger V; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

    2016-08-25

    Polysialated neural cell adhesion molecule (PSA-NCAM) is a membrane bound glycoprotein widely expressed during nervous system development. While commonly described in the neurogenic niches of the adult human brain, there is limited evidence of its distribution in other brain regions. PSA-NCAM is an important regulator of cell-cell interactions and facilitates cell migration and plasticity. Recent evidence suggests these functions may be altered in neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD). This study provides a detailed description of the PSA-NCAM distribution throughout the human brain and quantitatively compares the staining load in cortical regions and sub-cortical structures between the control, AD and PD brain. Our results provide evidence of widespread, yet specific, PSA-NCAM expression throughout the human brain including regions devoid of PSA-NCAM in the rodent brain such as the caudate nucleus (CN) and cerebellum (CB). We also detected a significant reduction in PSA-NCAM load in the entorhinal cortex (EC) of cases that was inversely correlated with hyperphosphorylated tau load. These results demonstrate that PSA-NCAM-mediated structural plasticity may not be limited to neurogenic niches and is conserved in the aged brain. We also provide evidence that PSA-NCAM is reduced in the EC, a region severely affected by AD pathology.

  13. Activity-dependent PSA expression regulates inhibitory maturation and onset of critical period plasticity.

    PubMed

    Di Cristo, Graziella; Chattopadhyaya, Bidisha; Kuhlman, Sandra J; Fu, Yu; Bélanger, Marie-Claude; Wu, Cai Zhi; Rutishauser, Urs; Maffei, Lamberto; Huang, Z Josh

    2007-12-01

    Functional maturation of GABAergic innervation in the developing visual cortex is regulated by neural activity and sensory inputs and in turn influences the critical period of ocular dominance plasticity. Here we show that polysialic acid (PSA), presented by the neural cell adhesion molecule, has a role in the maturation of GABAergic innervation and ocular dominance plasticity. Concentrations of PSA significantly decline shortly after eye opening in the adolescent mouse visual cortex; this decline is hindered by visual deprivation. The developmental and activity-dependent regulation of PSA expression is inversely correlated with the maturation of GABAergic innervation. Premature removal of PSA in visual cortex results in precocious maturation of perisomatic innervation by basket interneurons, enhanced inhibitory synaptic transmission, and earlier onset of ocular dominance plasticity. The developmental and activity-dependent decline of PSA expression therefore regulates the timing of the maturation of GABAergic inhibition and the onset of ocular dominance plasticity.

  14. Hybrid membrane--PSA system for separating oxygen from air

    DOEpatents

    Staiger, Chad L [Albuquerque, NM; Vaughn, Mark R [Albuquerque, NM; Miller, A Keith [Albuquerque, NM; Cornelius, Christopher J [Blackburg, VA

    2011-01-25

    A portable, non-cryogenic, oxygen generation system capable of delivering oxygen gas at purities greater than 98% and flow rates of 15 L/min or more is described. The system consists of two major components. The first component is a high efficiency membrane capable of separating argon and a portion of the nitrogen content from air, yielding an oxygen-enriched permeate flow. This is then fed to the second component, a pressure swing adsorption (PSA) unit utilizing a commercially available, but specifically formulated zeolite compound to remove the remainder of the nitrogen from the flow. The system is a unique gas separation system that can operate at ambient temperatures, for producing high purity oxygen for various applications (medical, refining, chemical production, enhanced combustion, fuel cells, etc . . . ) and represents a significant advance compared to current technologies.

  15. Comparison of Digital Rectal Examination and Serum Prostate Specific Antigen in the Early Detection of Prostate Cancer: Results of a Multicenter Clinical Trial of 6,630 Men.

    PubMed

    Catalona, William J; Richie, Jerome P; Ahmann, Frederick R; Hudson, M'Liss A; Scardino, Peter T; Flanigan, Robert C; DeKernion, Jean B; Ratliff, Timothy L; Kavoussi, Louis R; Dalkin, Bruce L; Waters, W Bedford; MacFarlane, Michael T; Southwick, Paula C

    2017-02-01

    To compare the efficacy of digital rectal examination and serum prostate specific antigen (PSA) in the early detection of prostate cancer, we conducted a prospective clinical trial at 6 university centers of 6,630 male volunteers 50 years old or older who underwent PSA determination (Hybritech Tandom-E or Tandem-R assays) and digital rectal examination. Quadrant biopsies were performed if the PSA level was greater than 4 μg./l. or digital rectal examination was suspicious, even if transrectal ultrasonography revealed no areas suspicious for cancer. The results showed that 15% of the men had a PSA level of greater than 4 μg./l., 15% had a suspicious digital rectal examination and 26% had suspicious findings on either or both tests. Of 1,167 biopsies performed cancer was detected in 264. PSA detected significantly more tumors (82%, 216 of 264 cancers) than digital rectal examination (55%, 146 of 264, p = 0.001). The cancer detection rate was 3.2% for digital rectal examination, 4.6% for PSA and 5.8% for the 2 methods combined. Positive predictive value was 32% for PSA and 21% for digital rectal examination. Of 160 patients who underwent radical prostatectomy and pathological staging 114 (71%) had organ confined cancer: PSA detected 85 (75%) and digital rectal examination detected 64 (56%, p = 0.003). Use of the 2 methods in combination increased detection of organ confined disease by 78% (50 of 64 cases) over digital rectal examination alone. If the performance of a biopsy would have required suspicious transrectal ultrasonography findings, nearly 40% of the tumors would have been missed. We conclude that the use of PSA in conjunction with digital rectal examination enhances early prostate cancer detection. Prostatic biopsy should be considered if either the PSA level is greater than 4 μg./l. or digital rectal examination is suspicious for cancer, even in the absence of abnormal transrectal ultrasonography findings.

  16. An inexpensive, fast and sensitive quantitative lateral flow magneto-immunoassay for total prostate specific antigen.

    PubMed

    Barnett, Jacqueline M; Wraith, Patrick; Kiely, Janice; Persad, Raj; Hurley, Katrina; Hawkins, Peter; Luxton, Richard

    2014-09-01

    We describe the detection characteristics of a device the Resonant Coil Magnetometer (RCM) to quantify paramagnetic particles (PMPs) in immunochromatographic (lateral flow) assays. Lateral flow assays were developed using PMPs for the measurement of total prostate specific antigen (PSA) in serum samples. A detection limit of 0.8 ng/mL was achieved for total PSA using the RCM and is at clinically significant concentrations. Comparison of data obtained in a pilot study from the analysis of serum samples with commercially available immunoassays shows good agreement. The development of a quantitative magneto-immunoassay in lateral flow format for total PSA suggests the potential of the RCM to operate with many immunoassay formats. The RCM has the potential to be modified to quantify multiple analytes in this format. This research shows promise for the development of an inexpensive device capable of quantifying multiple analytes at the point-of-care using a magneto-immunoassay in lateral flow format.

  17. An Inexpensive, Fast and Sensitive Quantitative Lateral Flow Magneto-Immunoassay for Total Prostate Specific Antigen

    PubMed Central

    Barnett, Jacqueline M.; Wraith, Patrick; Kiely, Janice; Persad, Raj; Hurley, Katrina; Hawkins, Peter; Luxton, Richard

    2014-01-01

    We describe the detection characteristics of a device the Resonant Coil Magnetometer (RCM) to quantify paramagnetic particles (PMPs) in immunochromatographic (lateral flow) assays. Lateral flow assays were developed using PMPs for the measurement of total prostate specific antigen (PSA) in serum samples. A detection limit of 0.8 ng/mL was achieved for total PSA using the RCM and is at clinically significant concentrations. Comparison of data obtained in a pilot study from the analysis of serum samples with commercially available immunoassays shows good agreement. The development of a quantitative magneto-immunoassay in lateral flow format for total PSA suggests the potential of the RCM to operate with many immunoassay formats. The RCM has the potential to be modified to quantify multiple analytes in this format. This research shows promise for the development of an inexpensive device capable of quantifying multiple analytes at the point-of-care using a magneto-immunoassay in lateral flow format. PMID:25587419

  18. Treatment Outcomes in Non-Metastatic Prostate Cancer Patients With Ultra-High Prostate-Specific Antigen

    SciTech Connect

    Tai, Patricia; Tonita, Jon; Woitas, Carla; Zhu Tong; Joseph, Kurian; Skarsgard, David

    2012-07-15

    Purpose: It is commonly believed that prostate cancer patients with very high prostate-specific antigen (PSA) levels are unlikely to benefit from definitive local treatment, and patients with very high PSA are often underrepresented in, or excluded from, randomized clinical trials. Consequently, little is known about their optimal treatment or prognosis. We performed a registry-based analysis of management and outcome in this population of patients. Methods and Materials: Our provincial Cancer Registry was used to identify all men who were diagnosed with prostate cancer from 1990 to 2001. A retrospective chart review provided information on stage, Gleason score, PSA at diagnosis, and treatment. In this study, ultra-high PSA was defined as PSA of {>=}50 ng/ml. For a more complete perspective, treatment outcomes of patients with PSA of 20 to 49.9 ng/ml were also studied. Results: Of the 8378 men diagnosed with prostate cancer during this period, 6,449 had no known nodal or distant metastatic disease. The median follow-up of this group was 67.2 months (range, 0-192 months). A total of 1534 patients had PSA of {>=}20 ng/ml. Among the 995 patients with PSA 20 to 49.9 ng/ml, 85 had radical prostatectomy (RP), and their 5- and 10-year cause-specific survivals (CSS) were 95% and 84%, respectively. The 497 patients treated with radiotherapy (RT) had 5- and 10-year CSS of 92% and 71%. For the 332 patients with PSA 50-99.9 ng/ml, RT was associated with 5- and 10-year CSS of 81% and 55%. For the 207 patients with PSA of {>=}100 ng/ml, RT was associated with 5- and 10-year CSS of 80% and 54%. Conclusions: This is the largest series in the world on non metastatic cancer patients with ultra-high PSA at diagnosis. Even in the setting of a very high presenting PSA level, prostatectomy and radiotherapy are often associated with prolonged survival.

  19. Prostate-specific antigen-retargeted recombinant newcastle disease virus for prostate cancer virotherapy.

    PubMed

    Shobana, Raghunath; Samal, Siba K; Elankumaran, Subbiah

    2013-04-01

    Oncolytic virus (OV) therapies of cancer are based on the use of replication-competent, tumor-selective viruses with limited toxicity. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising OV and is inherently tumor selective and cytotoxic only to tumor cells. Replication is restricted in normal cells. Despite encouraging phase I/II clinical trials with NDV, further refinements for tumor-specific targeting are needed to enhance its therapeutic index. Systemically delivered NDV fails to reach solid tumors in therapeutic concentrations and also spreads poorly within the tumors due to barriers including complement, innate immunity, and the extracellular matrix. Overcoming these hurdles is paramount to realizing the exceptional oncolytic efficacy of NDV. We engineered the F protein of NDV and generated a recombinant NDV (rNDV) whose F protein is cleavable exclusively by prostate-specific antigen (PSA). The rNDV replicated efficiently and specifically in prostate cancer (CaP) cells and 3-dimensional prostaspheres but failed to replicate in the absence of PSA. Induction of intracellular PSA production by a synthetic androgen analog (R1881) enhanced fusogenicity in androgen-responsive CaP cells. Further, PSA-cleavable rNDV caused specific lysis of androgen-independent and androgen-responsive/nonresponsive CaP cells and prostaspheres, with a half-maximal effective concentration (EC50) ranging from a multiplicity of infection of 0.01 to 0.1. PSA-retargeted NDV efficiently lysed prostasphere tumor mimics, suggesting efficacy in vivo. Also, PSA-cleavable NDV failed to replicate in chicken embryos, indicating no pathogenicity for chickens. Prostate-specific antigen targeting is likely to enhance the therapeutic index of rNDV owing to tumor-restricted replication and enhanced fusogenicity.

  20. Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk.

    PubMed

    Bonn, Stephanie E; Sjölander, Arvid; Tillander, Annika; Wiklund, Fredrik; Grönberg, Henrik; Bälter, Katarina

    2016-07-01

    High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate-specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010-2012. During follow-up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high-grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log-PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer-free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: -2.1 to -1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI-categories of 25 < 30, 30 < 35 and ≥35 kg/m(2), respectively, compared to the reference (18.5 < 25 kg/m(2)). No statistically significant associations were seen between BMI and prostate cancer risk although results were indicative of a positive association to incidence rates of high-grade disease and an inverse association to incidence of low-grade disease. However, findings regarding risk are limited by the short follow-up time. In conclusion, BMI was inversely associated to PSA-levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA-levels.

  1. Distinctive PSA-NCAM and NCAM hallmarks in glutamate-induced dendritic atrophy and synaptic disassembly.

    PubMed

    Podestá, María Fernanda; Yam, Patricia; Codagnone, Martín Gabriel; Uccelli, Nonthué Alejandra; Colman, David; Reinés, Analía

    2014-01-01

    Dendritic and synapse remodeling are forms of structural plasticity that play a critical role in normal hippocampal function. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) participate in neurite outgrowth and synapse formation and plasticity. However, it remains unclear whether they contribute to dendritic retraction and synaptic disassembly. Cultured hippocampal neurons exposed to glutamate (5 µM) showed a reduced MAP-2 (+) area in the absence of neuronal death 24 h after the insult. Concomitantly, synapse loss, revealed by decreased synaptophysin and post-synaptic density-95 cluster number and area, together with changes in NCAM and PSA-NCAM levels were found. Dendritic atrophy and PSA-NCAM reduction proved NMDA-receptor dependent. Live-imaging experiments evidenced dendritic atrophy 4 h after the insult; this effect was preceded by smaller NCAM clusters (1 h) and decreased surface and total PSA-NCAM levels (3 h). Simultaneously, total NCAM cluster number and area remained unchanged. The subsequent synapse disassembly (6 h) was accompanied by reductions in total NCAM cluster number and area. A PSA mimetic peptide prevented both the dendritic atrophy and the subsequent synaptic changes (6 h) but had no effect on the earliest synaptic remodeling (3 h). Thus, NCAM-synaptic reorganization and PSA-NCAM level decrease precede glutamate-induced dendritic atrophy, whereas the NCAM level reduction is a delayed event related to synapse loss. Consequently, distinctive stages in PSA-NCAM/NCAM balance seem to accompany glutamate-induced dendritic atrophy and synapse loss.

  2. A nanoparticle label/immunochromatographic electrochemical biosensor for rapid and sensitive detection of prostate-specific antigen

    SciTech Connect

    Lin, Ying-Ying; Wang, Jun; Liu, Guodong; Wu, Hong; Wai, Chien M.; Lin, Yuehe

    2008-06-15

    We present a nanoparticle (NP) label/immunochromatographic electrochemical biosensor (IEB) for rapid and sensitive detection of prostate-specific antigen (PSA) in human serum. This IEB integrates the immunochromatographic strip with the electrochemical detector for transducing quantitative signals. The NP label, made of CdSe@ZnS, serves as a signal-amplifier vehicle. A sandwich immunoreaction was performed on the immunochromatographic strip. The captured NP labels in the test zone were determined by highly sensitive stripping voltammetric measurement of the dissolved metallic component (cadmium) with a disposable-screen-printed electrode, which is embedded underneath the membrane of the test zone. Experimental parameters (e.g., immunoreaction time, the amount of anti-PSA-NP conjugations applied) and electrochemical detection conditions (e.g., preconcentration potential and time) were optimized using this biosensor for PSA detection. The analytical performance of this biosensor was evaluated with serum PSA samples according to the “figure-of-merits” (e.g., dynamic range, reproducibility, and detection limit). The results were validated with enzyme-linked immunosorbent assay (ELISA) and show high consistency. It is found that this biosensor is very sensitive with the detection limit of 0.02 ng/mL PSA and is quite reproducible. This method is rapid, clinically accurate, and less expensive than other diagnosis tools for PSA; therefore, this IEB coupled with a portable electrochemical analyzer shows great promise for simple, sensitive, quantitative point-of-care testing of disease-related protein biomarkers.

  3. Prostate-specific antigen testing in inner London general practices: are those at higher risk most likely to get tested?

    PubMed Central

    Nderitu, Paul; Van Hemelrijck, Mieke; Ashworth, Mark; Mathur, Rohini; Hull, Sally; Dudek, Alexandra; Chowdhury, Simon

    2016-01-01

    Objectives To investigate the association between factors influencing prostate-specific antigen (PSA) testing prevalence including prostate cancer risk factors (age, ethnicity, obesity) and non-risk factors (social deprivation and comorbidity). Setting A cross-sectional database of 136 inner London general practices from 1 August 2009 to 31 July 2014. Participants Men aged ≥40 years without prostate cancer were included (n=150 481). Primary outcome Logistic regression analyses were used to estimate the association between PSA testing and age, ethnicity, social deprivation, body mass index (BMI) and comorbidity while adjusting for age, benign prostatic hypertrophy, prostatitis and tamsulosin or finasteride use. Results PSA testing prevalence was 8.2% (2013–2014), and the mean age was 54 years (SD 11). PSA testing was positively associated with age (OR 70–74 years compared to 40–44 years: 7.34 (95% CI 6.82 to 7.90)), ethnicity (black) (OR compared to white: 1.78 (95% CI 1.71 to 1.85)), increasing BMI and cardiovascular comorbidity. Testing was negatively associated with Chinese ethnicity and with increasing social deprivation. Conclusions PSA testing among black patients was higher compared to that among white patients, which differs from lower testing rates seen in previous studies. PSA testing was positively associated with prostate cancer risk factors and non-risk factors. Association with non-risk factors may increase the risk of unnecessary invasive diagnostic procedures. PMID:27406644

  4. Analysis of Urinary Prostate-Specific Antigen Glycoforms in Samples of Prostate Cancer and Benign Prostate Hyperplasia

    PubMed Central

    Hsiao, Chun-Jen; Tzai, Tzong-Shin; Chen, Chein-Hung; Yang, Wen-Horng; Chen, Chung-Hsuan

    2016-01-01

    Glycans of prostate-specific antigen (PSA) in prostate cancer were found to be different from that in benign disease. It is difficult to analyze heterogeneous PSA glycoforms in each individual specimen because of low protein abundance and the limitation of detection sensitivity. We developed a method for prostate cancer diagnosis based on PSA glycoforms. Specific glycoforms were screened in each clinical sample based on liquid chromatography-tandem mass spectrometry with ion accumulation. To look for potential biomarkers, normalized abundance of each glycoform in benign prostate hyperplasia (BPH) and in prostate cancer was evaluated. The PSA glycoform, Hex5HexNAc4NeuAc1dHex1, and monosialylated, sialylated, and unfucosylated glycoforms differed significantly between the prostate cancer and BPH samples. The detection sensitivity (87.5%) and specificity (60%) for prostate cancer identification are higher than those of the serum PSA marker. As low as 100 amol PSA could be detected with the ion accumulation method which has not been reported before. The improved detection specificity can help reduce unnecessary examinations. PMID:27065039

  5. Oral selenium supplementation has no effect on prostate-specific antigen velocity in men undergoing active surveillance for localized prostate cancer.

    PubMed

    Stratton, M Suzanne; Algotar, Amit M; Ranger-Moore, James; Stratton, Steven P; Slate, Elizabeth H; Hsu, Chiu-Hsieh; Thompson, Patricia A; Clark, Larry C; Ahmann, Frederick R

    2010-08-01

    The Nutritional Prevention of Cancer trial showed a 52% lower incidence of prostate cancer in men supplemented with selenium. As a result, our study was designed to assess whether selenium supplementation attenuates the progression of prostate cancer. A phase 2 randomized, double-blind, placebo-controlled clinical trial was conducted in men with localized nonmetastatic prostate cancer who had elected to forgo active treatment and be followed by active surveillance. A total of 140 men were randomized to placebo (n = 46), 200 microg/d (n = 47), or 800 microg/d (n = 47) selenium p.o. (as selenized yeast) and followed every 3 months for up to 5 years. Prostate-specific antigen (PSA) velocity was used as a marker of prostate cancer progression and was estimated using mixed-effects regression. Adjusting for age, body mass index, baseline selenium, smoking, baseline PSA, race, PSA method, and Gleason score, PSA velocities for the 200 microg/d and 800 microg/d treatment groups were not statistically significantly different from placebo (P = 0.32 and P = 0.61, respectively). In the highest quartile of baseline selenium, men supplemented with 800 microg selenium showed statistically significantly higher PSA velocity as compared with placebo (P = 0.018). Selenium supplementation did not show a protective effect on PSA velocity in subjects with localized prostate cancer. On the contrary, supplementation with high-dose selenium was observed to be a risk factor for increased PSA velocity in men with high baseline plasma selenium concentrations.

  6. [Prostate-specific antigen use among men without prostate cancer in France (2008-2010)].

    PubMed

    Tuppin, Philippe; Samson, Solène; Perrin, Paul; Ruffion, Alain; Millat, Bertrand; Weill, Alain; Ricordeau, Philippe; Allemand, Hubert

    2012-05-01

    This study evaluated the rate of prostate-specific antigen (PSA) dosage in men age 40 or older, affiliated to the general social security system in France between 2008 and 2010: 10.9 million men, excluding those with known prostate cancer. In 2010, 30.7% of this male population had at least one dosage of PSA, i.e. 12.3% of those between 40 and 54, 47.7% of those between 55 and 74, and 47.6% of those 75 years old or older. Percentages of men who had at least one dosage in the three-year period were 26.2%, 77.3% and 75.6% for the same age brackets, respectively. Overall, 13% of men age 40 or older, and in particular 21% of men 75 years old or older had more than three PSA dosages during the three-year time period. Eighty-eight percent of PSA dosages performed in 2010 were prescribed by a general practitioner and 3.2% by an urologist. Conflicting with French and internationally published recommendations regarding PSA dosage, the present results demonstrate a shift toward chaotic mass screening of prostate cancer particularly in men aged 75 or older.

  7. Determining the binding affinities of prostate-specific antigen to lectins: SPR and microarray approaches.

    PubMed

    Damborský, Pavel; Zámorová, Martina; Katrlík, Jaroslav

    2016-12-01

    Prostate cancer (PCa) is one of the most common newly diagnosed cancers among men and we focused on its traditional biomarker, prostate-specific antigen (PSA), using targeted glycomics-based strategies. The aberrant glycosylation pattern of PSA may serve as a valuable tool for improving PCa diagnosis including its early-stage. In this study, we evaluated the usability of two techniques, surface plasmon resonance and protein microarray assay, for the study and characterization of interactions of PSA (both free and complexed) with six lectins (SNA, ConA, RCA, AAL, WGA and MAA II). The information on the character of such interactions is important for the application of lectins as prospective bioreceptors for biomarker glycoprofiling in a follow-up biosensing assays. SPR as well as established bioanalytical techniques allowed determination of KD values of PSA-lectin interactions in a more reliable way than protein microarray. The protein microarray method did not allow accurate quantification of KD values. However, the features of a microarray approach, such as speed and costs, enabled the screening and estimation of the nature of lectin-glycan biomarker interaction in an effective and time-saving way. All of the tested lectins interacted with commercial PSA standard isolated from healthy persons, except MAA II which reacted only very weakly.

  8. Real-life experience of using conventional disease-modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA). Retrospective analysis of the efficacy of methotrexate, sulfasalazine, and leflunomide in PsA in comparison to spondyloarthritides other than PsA and literature review of the use of conventional DMARDs in PsA

    PubMed Central

    Roussou, Euthalia; Bouraoui, Aicha

    2017-01-01

    Objective With the aim of assessing the response to treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) used in patients with psoriatic arthritis (PsA), data on methotrexate, sulfasalazine (SSZ), and leflunomide were analyzed from baseline and subsequent follow-up (FU) questionnaires completed by patients with either PsA or other spondyloarthritides (SpAs). Material and Methods A single-center real-life retrospective analysis was performed by obtaining clinical data via questionnaires administered before and after treatment. The indices used were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Function Index (BASFI), wellbeing (WB), and treatment effect (TxE). The indices measured at baseline were compared with those measured on one occasion in a FU visit at least 1 year later. Results A total of 73 patients, 51 with PsA (mean age 49.8±12.8 years; male-to-female ratio [M:F]=18:33) and 22 with other SpAs (mean age 50.6±16 years; M:F=2:20), were studied. BASDAI, BASFI, and WB displayed consistent improvements during FU assessments in both PsA patients and controls in comparison to baseline values. SSZ exhibited better efficacy as confirmed by TxE in both PsA patients and controls. ESR and CRP displayed no differences in either the PsA or the SpA group between the cases before and after treatment. Conclusion Real-life retrospective analysis of three DMARDs used in PsA (and SpAs other than PsA) demonstrated that all three DMARDs that were used brought about improvements in BASDAI, BASFI, TxE, and WB. However, the greatest improvements at FU were seen with SSZ use in both PsA and control cohorts. PMID:28293446

  9. Systems Pharmacology Modeling of Prostate‐Specific Antigen in Patients With Prostate Cancer Treated With an Androgen Receptor Antagonist and Down‐Regulator

    PubMed Central

    Mistry, HB; Young, J; Clack, G; Dickinson, PA

    2016-01-01

    First‐in‐human (FIH) studies with AZD3514, a selective androgen receptor (AR) down‐regulator, showed decreases of >30% in the prostate‐specific antigen (PSA) in some patients. A modeling approach was adopted to understand these observations and define the optimum clinical use hypothesis for AZD3514 for clinical testing. Initial empirical modeling showed that only baseline PSA correlated significantly with this biological response, whereas drug concentration did not. To identify the mechanistic cause of this observation, a mechanism‐based model was first developed, which described the effects of AZD3514 on AR protein and PSA mRNA levels in LNCaP cells with and without dihydrotestosterone (DHT). Second, the mechanism‐based model was linked to a population pharmacokinetic (PK) model; PSA effects of clinical doses were subsequently simulated under different clinical conditions. This model was used to adjust the design of the ongoing clinical FIH study and direct the backup program. PMID:27299938

  10. Failure Engineering Study and Accelerated Stress Test Results for the Mars Global Surveyor Spacecraft's Power Shunt Assemblies

    NASA Technical Reports Server (NTRS)

    Gibbel, Mark; Larson, Tim

    1999-01-01

    Due to a post launch failure of a part a new plan for the Mars Global Surveyor was developed. This new plan involved the addition of many deep thermal cycles to the Power Shunt Assemblies (PSA's). This new plan exceeds the previous acceptance cold level, and fatigue life on packaging design. This presentation reviews the experiments that were used to test the capabilities of the PSA to function in the new situation. It also reviews the analyses preformed to verify the most likely failure mechanism, and the likelihood that these failures would impact the new mission requirements.

  11. Unification of a common biochemical failure definition for prostate cancer treated with brachytherapy or external beam radiotherapy with or without androgen deprivation

    SciTech Connect

    Fitch, Dwight L.; McGrath, Samuel; Martinez, Alvaro A.; Vicini, Frank A.; Kestin, Larry L. . E-mail: lkestin@beaumont.edu

    2006-12-01

    Purpose: Minimal data are available regarding selection of an optimal biochemical failure (BF) definition for patients treated with brachytherapy, external beam radiotherapy (EBRT), and combinations of these treatments with or without androgen deprivation (AD). We retrospectively analyzed our institution's experience treating localized prostate cancer in an attempt to determine a BF definition that could be applied for these various treatment modalities. Methods and Materials: A total of 2376 patients with clinical stage T1-T3 N0 M0 prostate cancer were treated with conventional dose (median, 66.6 Gy) EBRT (n = 1201), high-dose (median, 75.6 Gy) adaptive radiation therapy (n = 465), EBRT + high-dose-rate brachytherapy boost (n 416), or brachytherapy alone (n = 294) between 1987 and 2003. A total of 496 patients (21%) received neoadjuvant AD with radiation therapy. There were 21924 posttreatment prostate-specific antigen (PSA) measurements. Multiple BF definitions were tested for their sensitivity, specificity, positive predictive value (+PV), and negative PV (-PV) in predicting subsequent clinical failure (CF) (any local failure or distant metastasis), overall survival (OS), and cause-specific survival (CSS). Median follow-up was 4.5 years. The date of BF was the date BF criteria were met (e.g., date of third rise). Results: A total of 290 patients (12%) experienced CF at a median interval of 3.6 years (range, 0.2-15.2 years). The 5- and 10-year CF rates were 12% and 26%, respectively. Three consecutive rises yielded a 46% sensitivity and 84% specificity for predicting CF. The 10-year CF for those 475 patients who experienced three rises (BF) was 37% vs. 17% for those patients who did not meet these criteria (biochemically controlled [BC]). For all patients, the following definitions were superior to three rises for predicting CF for both +PV, and -PV: n + 1 ({>=}1 ng/mL above nadir), n + 2, n + 3, threshold 2 (any PSA {>=}2.0 ng/mL at or after nadir), threshold 3

  12. Prostate-specific antigen kinetics after primary stereotactic body radiation therapy using CyberKnife for localized prostate cancer

    PubMed Central

    Park, Yong Hyun; Choi, In Young; Yoon, Sei Chul; Jang, Hong Seok; Moon, Hyong Woo; Hong, Sung-Hoo; Kim, Sae Woong; Hwang, Tae-Kon; Lee, Ji Youl

    2015-01-01

    Purpose To assess prostate-specific antigen (PSA) kinetics and report on the oncologic outcomes for patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT) using CyberKnife. Methods We extracted the list and data of 39 patients with clinically localized prostate cancer who had undergone primary SBRT using CyberKnife between January 2008 and December 2012 from the Smart Prostate Cancer database system of Seoul St. Mary's Hospital. Changes in PSA over time, PSA velocity, and PSA nadir were evaluated from the completion of SBRT using CyberKnife. Biochemical recurrence (BCR)-free survival after primary SBRT using CyberKnife was determined using Kaplan–Meier analysis. Results The rate of PSA decrease was maximal in the first month (median −3.34 ng/mL/mo), which then fell gradually with median values of −1.51, −0.32, −0.28, −0.20, and −0.03 ng/mL/mo for durations of 3, 6, 9, 12, and 24 months after SBRT using CyberKnife, respectively. The median PSA nadir was 0.31 ng/mL after a median 23 months. Kaplan–Meier analysis calculates an actuarial 5-year BCR-free survival after SBRT using CyberKnife as 80.8%. Conclusions PSA decline occurred rapidly in the first month, and then the rate of PSA decline fell off steadily over time throughout 2 years after treatment. Also, SBRT using CyberKnife leads to long-term favorable BCR-free survival in localized prostate cancer. PMID:26157760

  13. Associations of aspirin, nonsteroidal anti-inflammatory drug and paracetamol use with PSA-detected prostate cancer: findings from a large, population-based, case-control study (the ProtecT study).

    PubMed

    Murad, Ali S; Down, Liz; Davey Smith, George; Donovan, Jenny L; Athene Lane, Janet; Hamdy, Freddie C; Neal, David E; Martin, Richard M

    2011-03-15

    Evidence from laboratory studies suggests that chronic inflammation plays an important role in prostate cancer aetiology. This has resulted in speculation that nonsteroidal anti-inflammatory drugs may protect against prostate cancer development. We analysed data from a cross-sectional case-control study (n(cases) = 1,016; n(controls) = 5,043), nested within a UK-wide population-based study that used prostate specific antigen (PSA) testing for identification of asymptomatic prostate cancers, to investigate the relationship of aspirin, nonsteroidal anti-inflammatory drug (NSAID) and paracetamol use with prostate cancer. In conditional logistic regression models accounting for stratum matching on age (5-year age bands) and recruitment centre, use of non-aspirin NSAIDs [odds ratio (OR) = 1.32; 95% confidence interval (CI): 1.04-1.67] or all NSAIDs (OR = 1.25; 95% CI = 1.07-1.47) were positively associated with prostate cancer. There were weaker, not conventionally statistically significant, positive associations of aspirin (OR = 1.13; 95% CI = 0.94-1.36) and paracetamol (OR = 1.20; 95% CI = 0.90-1.60) with prostate cancer. Mutual adjustment for aspirin, non-aspirin NSAIDs or paracetamol made little difference to these results. There was no evidence of confounding by age, family history of prostate cancer, body mass index or self-reported diabetes. Aspirin, NSAID and paracetamol use were associated with reduced serum PSA concentrations amongst controls. Our findings do not support the hypothesis that NSAIDs reduce the risk of PSA-detected prostate cancer. Our conclusions are unlikely to be influenced by PSA detection bias because the inverse associations of aspirin, NSAID and paracetamol use with serum PSA would have attenuated (not generated) the observed positive associations.

  14. Potentiometric stripping analysis (PSA) for monitoring of antimony in samples of vegetation from a mining area.

    PubMed

    Toro Gordillo, M C; Pinilla Gil, E; Rodríguez González, M A; Murciego Murciego, A; Ostapczuk, P

    2001-06-01

    A potentiometric stripping analysis (PSA) method has been developed and checked for the fast and reliable determination of antimony in vegetation samples of Cistus ladanifer from a mining area in Badajoz, Southwest Spain. The method, modified from previous PSA methods for Sb in environmental samples, is based on dry ashing of the homogenized leaves, dissolution in hydrochloric acid, and PSA analysis on a mercury film plated on to a glassy carbon disk electrode. The influence of experimental variables such as the deposition potential, the deposition time, the signal stability and the calibration parameters, has been investigated. The method has been compared with an independent technique (instrumental neutron activation analysis) by analysis of standards and reference materials and comparison of the results. As a result of automation of the PSA equipment, the proposed method enables unattended analysis of 20 digested samples in a total time of 2 h, thus providing a useful tool for Sb monitoring of a large number of samples.

  15. COS Imaging TA and Spectroscopic WCA-PSA/BOA offset verifications

    NASA Astrophysics Data System (ADS)

    Penton, Steven

    2013-10-01

    This program builds upon the monitoring and calibration of the FGSs (13616 - HST Cycle 21 Focal Plane Calibration (SI-FGS Alignment)). HST 13616 performs back-to-back PSA/MIRRORA & PSA/MIRRORB ACQ/IMAGES, from which all the results herein are bootstrapped.The list of proposals, cycles, and the order in which the alignment is checked is given below. 11878->12399->12781->13171->13616 C17->C18 ->C19->C20->C21 STIS->WFC3->ACS->COSThis program will be repeated every cycle and we will once again use it's COS exposures as the baseline for this program.This program performs a PSA/MIRRORA ACQ/IMAGE on a target that should already be centered in the aperture. This verifies the COS NUV PSA aperture position in the SIAF. After this PSA+MIRRORA ACQ/IMAGE, a PSA+MIRRORB ACQ/IMAGE is then performed. This exposure bootstraps the PSA+MIRRORB centering to the PSA+MIRROR SIAF verification. This allows us to monitor the properties of the PSA+MIRRORB image in a controlled way on a centered target. No spectra are taken in 13616 due to time constraints.This program extends the SIAF verification of 13616 to the other two ACQ/IMAGE combinations (BOA+MIRRORA & BOA+MIRRORB) by bootstraping from the PSA+MIRRORB verification of 13616.Visit 1 of this program begins with a PSA+MIRRORB NUV ACQ/IMAGE followed by a BOA+MIRRORA ACQ/IMAGE. Both observations are high S/N to get the most accurate centering information possible. The program then takes a PSA+MIRRORB IMAGE to ensure that we are still properly centered. We prefer that Visit 01 of this program executes within 45 days of Visit 02 of 13616, to ensure that no long term instrument or telescope focus changes impart our results.After the Imaging verification , Visit 1 of this program will obtain a S/N > 60 NUV spectrum using the most popular NUV grating (G230L, G185M, & G285M), and FUV Spectra using G130M/1309 and G140L/1280. This allows the direct verification of the NUV and FUV WCA-to-PSA cross-dispersion offsets used by ACQ/PEAKXD.Visit 02 of

  16. Prostate-specific Antigen as a Risk Factor for Skeletal Metastasis in Native Ethnic African Men with Prostate Cancer: A Case-control Study

    PubMed Central

    Qureshi, Ayman M.; Makhdomi, Khalid; Stones, William

    2017-01-01

    Prostate cancer is the most common noncutaneous cancer in males. Men of African origin are at a significantly higher risk as reflected in the higher incidence and mortality rates in this racial group. Metastases incidence increases parallel to serum levels of prostate-specific antigen (PSA), contributing significantly to morbidity and mortality. Staging of the disease involves bone scans, which are sensitive in detecting skeletal metastases. Suggestions that these scans may be omitted in some situations in patients with low prostate specific antigen levels have drawn attention to the matter. In this case-control study, using radiology and pathology records, a registry of prostate cancer patients recorded as being of dark-skinned ethnicity was obtained. Images were presented to image reviewers blinded to the PSA level, to determine the presence of skeletal metastases. The risk factor for the outcome of interest (skeletal metastases) was PSA level above 20 ng/mL. The reliability of image reporting was also assessed. Of the 122 patients, skeletal metastases were present in 50 (41%) while these were absent in 72 (59%). The prevalence of metastases among the high PSA group was 55.9% [95% confidence interval (CI) 44.1–67.7%] and among the normal/low PSA group was 22.2% (95% CI 11.1–33.3%). The odds ratio (OR) for skeletal metastases in the exposed (high PSA) group was 4.4 (95% CI, 2.01–9.78.) Intraobserver agreement on image interpretation was 88.5% with a Kappa statistic of 0.76. A relatively higher prevalence of skeletal metastasis is seen in regional dark-skinned African males with prostate cancer at both low and high prostate specific antigen levels. Bone scanning in this population should therefore, be considered even at PSA levels below 20 ng/mL. PMID:28217016

  17. A Comparison of the Biological Features of Prostate Cancer with (PSA+, PSMA+) Profile according to RKIP

    PubMed Central

    Ben Jemaa, Awatef; Bouraoui, Yosra; Sallami, Sataa; Nouira, Yassine; Oueslati, Ridha

    2013-01-01

    Purpose. To investigate differences in the biological features of the most immunoexpressed prostate cancer (PC) profiles (PSA+, PSMA+) according to the RKIP. Methods. 19 PC with dominant Gleason grade ≥8 were studied. Expression of PSA, PSMA, RKIP, Raf-1, MEK-1, ERK-1, ERK-2, p-Akt (T308), p-Akt (S473), NF-κB p50, and NF-κBp65 were detected immunohistochemically. Results. Loss of RKIP in the most immunoexpressed PC (PSA+, PSMA+) profile was associated with increased levels of PSA and PSMA expression. Intensities of immunoreactions to PSA and PSMA were higher in cancer cells negative for RKIP (12.51 ± 1.6 and 34.95 ± 1.92) compared to those positive for RKIP (4.68 ± 1.11 and 28.56 ± 0.91). In parallel, missing RKIP expression in PC patients with PSA+, PSMA+ profile was connected with increased components of both Raf-1/MEK/ERK and NF-κB (p65/p50), whereas Akt is activated independently of RKIP. Conclusions. Although characterized by the same (PSA+, PSMA+) profile, PC phenotype missing the RKIP related to invasive potential and greater biological aggressiveness reflected in overexpression of components of Raf-1/MEK/ERK and NF-κB (p65/p50) in which Akt is activated independently of RKIP. Taking into account the PC phenotypes according to RKIP among PSA-PSMA profiles may improve distinguishing them from cancers that will become more aggressive and therefore adapt the therapeutic strategies in those patients. PMID:23991415

  18. Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes

    PubMed Central

    Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M.; Aleixandre, Rosa N.; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

    2016-01-01

    New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic. PMID:27279911

  19. Motexafin lutetium-photodynamic therapy of prostate cancer: Short and long term effects on PSA

    PubMed Central

    Patel, Hiral; Mick, Rosemarie; Finlay, Jarod; Zhu, Timothy C.; Rickter, Elizabeth; Cengel, Keith A.; Malkowicz, S. Bruce; Hahn, Stephen M.; Busch, Theresa M.

    2009-01-01

    Purpose: The time course of serum PSA response to photodynamic therapy (PDT) of prostate cancer was measured. Experimental Design: Seventeen patients were treated in a Phase I trial of motexafin lutetium-PDT. PDT dose was calculated in each patient as the product of the ex vivo-measured pre-PDT photosensitizer level and the in situ-measured light dose. Serum PSA level was measured within two months prior to PDT (baseline), and at day 1; weeks 1-3; months 1, 2 and 3; months 4-6 and months 7-11 after PDT. Results: At 24h after PDT, serum PSA increased by 98±36% (mean ± SE) relative to baseline levels (p=0.007). When patients were dichotomized based on median PDT dose, those who received high PDT dose demonstrated a 119±52% increase in PSA compared to a 54±27% increase in patients treated at low PDT dose. Patients treated with high vs. low PDT dose demonstrated a median biochemical delay of 82 vs. 43 days (p=0.024), with biochemical delay defined as the length of time between PDT and a nonreversible increase in PSA to a value ≥baseline. Conclusions: Results show PDT to induce large, transient increases in serum PSA levels. Patients who experienced high PDT dose demonstrated greater short-term increase in PSA and a significantly more durable PSA response (biochemical delay). These data strongly promote the need for individualized delivery of PDT dose and assessment of treatment effect in PDT of prostate cancer. Information gained from such patient-specific measurements could facilitate the introduction of multiple PDT sessions in patients who would benefit. PMID:18676760

  20. High serum prostate-specific antigen concentrations in hirsute women do not decrease with treatment by the combination of spironolactone and the contraceptive pill.

    PubMed

    Guzelmeric, K; Seker, N; Unal, O; Turan, C

    2004-10-01

    Using an ultrasensitive assay, prostate-specific antigen (PSA) has been detected in female serum and has been proposed as a potential marker of androgen excess in hirsute women. Measurement of PSA levels in serum may play a role in monitoring hirsutism during antiandrogen therapy. We investigated the role of PSA as a marker of androgen activity in hirsute patients taking spironolactone together with oral contraceptive pills containing ethinyl estradiol and gestodene. Twenty-eight hirsute patients were included in the study. Clinical and biochemical variables including serum levels of PSA (using an ultrasensitive chemiluminscent immunoassay), dehydroepiandrosterone sulfate, total testosterone, free testosterone and 17-hydroxyprogesterone concentrations were recorded at baseline and after six cycles of treatment. Fifteen healthy women were included in the study as controls. Serum PSA levels in hirsute women were clearly higher than in the control group (0.023 +/- 0.004 vs. 0.006 +/- 0.003 ng/ml, p < 0.001) and correlated with baseline serum free testosterone concentrations (r = 0.518, p = 0.005). After 6 months, serum PSA concentrations as compared with baseline values did not change significantly in patients who were given spironolactone plus contraceptive pills (p = 0.4) despite a marked decrease in total testosterone, free testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate and hirsutism score (p < 0.05). Thus, serum PSA levels in hirsute women were higher than in non-hirsute healthy controls. A 6-month course of treatment with spironolactone combined with contraceptive pills containing ethinylestradiol and gestodene did not reduce high serum PSA levels in these subjects. In conclusion, the serum PSA level is not a convenient biochemical marker with the available assays for the management of hirsute women treated with the combination of spironolactone and oral contraceptives.

  1. Race, genetic West African ancestry, and prostate cancer prediction by prostate-specific antigen in prospectively screened high-risk men.

    PubMed

    Giri, Veda N; Egleston, Brian; Ruth, Karen; Uzzo, Robert G; Chen, David Y T; Buyyounouski, Mark; Raysor, Susan; Hooker, Stanley; Torres, Jada Benn; Ramike, Teniel; Mastalski, Kathleen; Kim, Taylor Y; Kittles, Rick

    2009-03-01

    "Race-specific" prostate-specific antigen (PSA) needs evaluation in men at high risk for prostate cancer for optimizing early detection. Baseline PSA and longitudinal prediction for prostate cancer were examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Eligibility criteria were age 35 to 69 years, family history of prostate cancer, African American race, or BRCA1/2 mutations. Biopsies were done at low PSA values (<4.0 ng/mL). WA ancestry was discerned by genotyping 100 ancestry informative markers. Cox proportional hazards models evaluated baseline PSA, self-reported race, and genetic WA ancestry. Cox models were used for 3-year predictions for prostate cancer. Six hundred forty-six men (63% African American) were analyzed. Individual WA ancestry estimates varied widely among self-reported African American men. Race-specific differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with > or =1 follow-up visit (405 total, 54% African American), 3-year prediction for prostate cancer with a PSA of 1.5 to 4.0 ng/mL was higher in African American men with age in the model (P = 0.025) compared with European American men. Hazard ratios of PSA for prostate cancer were also higher by self-reported race (1.59 for African American versus 1.32 for European American, P = 0.04). There was a trend for increasing prediction for prostate cancer with increasing genetic WA ancestry. "Race-specific" PSA may need to be redefined as higher prediction for prostate cancer at any given PSA in African American men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing prostate cancer early detection.

  2. Is there any association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer?

    PubMed Central

    Doluoglu, Omer Gokhan; Ceylan, Cavit; Kilinc, Fatih; Gazel, Eymen; Resorlu, Berkan; Odabas, Oner

    2016-01-01

    ABSTRACT Purpose We investigated the association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer. Materials and Methods The data of 440 patients who had undergone prostate biopsies due to high PSA levels and suspicious digital rectal examination findings were reviewed retrospectively. The patients were divided into two groups based on the presence of accompanying NIH IV prostatitis. The exclusion criteria were as follows: Gleason score>6, PSA level>20ng/mL, >2 positive cores, >50% cancerous tissue per biopsy, urinary tract infection, urological interventions at least 1 week previously (cystoscopy, urethral catheterization, or similar procedure), history of prostate biopsy, and history of androgen or 5-alpha reductase use. All patient's age, total PSA and free PSA levels, ratio of free to total PSA, PSA density and prostate volume were recorded. Results In total, 101 patients were included in the study. Histopathological examination revealed only PCa in 78 (77.2%) patients and PCa+NIH IV prostatitis in 23 (22.7%) patients. The median total PSA level was 7.4 (3.5–20.0) ng/mL in the PCa+NIH IV prostatitis group and 6.5 (0.6–20.0) ng/mL in the PCa group (p=0.67). The PSA level was≤10ng/mL in 60 (76.9%) patients in the PCa group and in 16 (69.6%) patients in the PCa+NIH IV prostatitis group (p=0.32). Conclusions Our study showed no statistically significant difference in PSA levels between patients with and without NIH IV prostatitis accompanying PCa. PMID:27256190

  3. Predicting Gleason score using the initial serum total prostate-specific antigen in Black men with symptomatic prostate adenocarcinoma in Nigeria

    PubMed Central

    Nnabugwu, Ikenna I; Udeh, Emeka I; Ugwumba, Fredrick O; Ozoemena, Francis O

    2016-01-01

    Background Men of Black African descent are known to have the highest incidence of prostate cancer. The disease is also more aggressive in this group possibly due to biologically more aggressive tumor or late presentation. Currently, serum prostate-specific antigen (PSA) assay plays a significant role in making the diagnosis of prostate cancer. However, the obtained value of serum PSA may not directly relate with the Gleason score (GS), a measure of tumor aggression in prostate cancer. This study explores the relationship between serum total PSA at presentation (iPSA) and GS. Patients and methods The iPSA of patients with histologically confirmed prostate cancer was compared with the obtained GS of the prostate biopsy specimens. The age of the patients at presentation and the prostate volumes were also analyzed with respect to the iPSA and GS. The data were analyzed retrospectively using IBM SPSS Version 20. Pearson correlation was used for numeric variables, whereas Fisher’s exact test was used for categorical variables. Significance was set at P≤0.05. Results There were 205 patients from January 2010 to November 2013 who satisfied the inclusion criteria. iPSA as well as age at presentation and prostate volume were not found to significantly correlate with the primary Gleason grade, the secondary Gleason grade, or the GS. However, the presence of distant metastasis was identified to significantly correlate positively with GS. Conclusion GS may not be confidently predicted by the iPSA. Higher iPSA does not correlate with higher GS and vice versa. PMID:27486316

  4. Role of androgen metabolism genes CYP1B1, PSA/KLK3, and CYP11alpha in prostate cancer risk and aggressiveness.

    PubMed

    Cicek, Mine S; Liu, Xin; Casey, Graham; Witte, John S

    2005-09-01

    Candidate genes involved with androgen metabolism have been hypothesized to affect the risk of prostate cancer. To further investigate this, we evaluated the relationship between prostate cancer and multiple potentially functional polymorphisms in three genes involved in androgen metabolism: CYP1B1 (two single nucleotide polymorphisms: 355G/T and 4326C/G), prostate-specific antigen (PSA/KLK3 (three single nucleotide polymorphisms: -158A/G, -4643G/A, and -5412C/T), and CYP11alpha [(tttta)(n) repeat], using a moderately large (n = 918) sibling-based case-control population. When looking at all subjects combined, no association was observed between any polymorphism-or their haplotypes-and prostate cancer risk. However, among men with more aggressive prostate cancer, the CYP1B1 355G/T variant was positively associated with disease: carrying one or two T alleles gave odds ratios (OR) of 1.90 [95% confidence interval (95% CI), 1.09-3.31; P = 0.02] and 3.73 (95% CI, 1.39-10.0; P = 0.009), respectively. Similarly, carrying the CYP1B1 355T-4326C haplotype was positively associated with prostate cancer among men with high aggressive disease (P = 0.01). In addition, the PSA -158G/-158G genotype was positively associated with prostate cancer among men with less aggressive disease (OR, 2.71; 95% CI, 1.06-6.94; P = 0.04). Our findings suggest that CYP1B1 and PSA variants may affect the risk of prostate cancer and tumor aggressiveness.

  5. Novel antigen delivery systems

    PubMed Central

    Trovato, Maria; Berardinis, Piergiuseppe De

    2015-01-01

    Vaccines represent the most relevant contribution of immunology to human health. However, despite the remarkable success achieved in the past years, many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases. For these pathogens the known strategies for making vaccines have been unsuccessful and thus, new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors, the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants. A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses. Recent advances in vector delivery technologies, immunology, vaccinology and system biology, have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses, offering new strategies of vaccinations. This review is an update of current strategies with respect to live attenuated and inactivated vaccines, DNA vaccines, viral vectors, lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles. In addition, this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a non-pathogenic prokaryotic organism: the “E2 scaffold” of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus. PMID:26279977

  6. COS Imaging TA and Spectroscopic WCA-PSA/BOA offset verifications

    NASA Astrophysics Data System (ADS)

    Penton, Steven

    2012-10-01

    This program builds upon the monitoring and calibration of the FGSs. The list of proposals, cycles, and the order in which the alignment is checked is given below.11878->12399->12781->13171C17->C18->C19->C20STIS->WFC3->ACS->COSVisit 01 of the C20 SIAF verification program, 13171, executed on Mar 2, 2012, and Visit 02 is scheduled for Sep 1, 2103. This program performs a PSA/MIRRORA ACQ/IMAGE on a target that should already be centered in the aperture. This verifies the COS NUV PSA aperture position in the SIAF. After this PSA+MIRRORA ACQ/IMAGE, a PSA+MIRRORB ACQ/IMAGE is then performed. This exposure bootstraps the PSA+MIRRORB centering to the PSA+MIRROR SIAF verification. This allows us to monitor the properties of the PSA+MIRRORB image in a controlled way on a centered target. No spectra are taken in 13171 due to time constrains.This program extends the SIAF verification of 13171 to the other two ACQ/IMAGE combinations {BOA+MIRRORA & BOA+MIRRORB} by bootstraping from the PSA+MIRRORB verification of 13171.Visit 1 of this program begins with a PSA+MIRRORB NUV ACQ/IMAGE followed by a BOA+MIRRORA ACQ/IMAGE. Both observations are high S/N to get the most accurate centering information possible. The program then takes a PSA+MIRRORB IMAGE to ensure that we are still properly centered. We prefer that Visit 01 of this program executes after Visit 02 of 13171, but more than 17, but less than 45 days after to ensure that no long term instrument or telescope focus changes impart our results.After the Imaging verification Visit 1 of this program will obtain a S/N > 60 NUV spectrum using the most popular NUV grating {G230L, G185M, & G285M}, and FUV Spectra using G130M/1309 and G140L/1280. This allows the direct verification of the NUV and FUV WCA-to-PSA cross-dispersion offsets used by ACQ/PEAKXD.Visit 02 of this program follows the style of Visit 01, but the initial ACQ/IMAGE is a BOA+MIRRORA and the second ACQ/IMAGE is BOA/MIRRORB. Visit 02 should occur after Visit 01 by

  7. Distribution of ESA's planetary mission data via the Planetary Science Archive (PSA)

    NASA Astrophysics Data System (ADS)

    Heather, David; Barthelemy, Maud; Arviset, Christophe; Osuna, Pedro; Ortiz, Inaki

    Scientific and engineering data from the European Space Agency'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. All data in the PSA are compatible with the Planetary Data System (PDS) Standard of NASA, and the PSA staff work in close collaboration with the PDS staff. One major part of the ongoing development of the IPDA (International Planetary Data Alliance) has been to draw upon the lessons learned on both sides of this working relationship in order to refine and streamline the Standards. This is driving towards ‘interoperability' of the data systems maintained at all Agencies archiving planetary data, and it is hoped that in the long-run any data can be obtained from any of the co-operating archives using the same protocol. Currently, the PSA contains data from the GIOTTO spacecraft, several ground-based cometary observations, and the Mars Express, Smart-1, and Huygens missions. Independent reviews for the first Venus Express data are schedule for Spring 2008 and the first Venus Express data should be released on the PSA in late spring 2008. The first data release from the ROSETTA mission is also expected to be released on the PSA by spring 2008. Preparation for the release of data from the SMART-1 spacecraft is ongoing. Future missions such as ExoMars and Bepi- Colombo will also aim to work with the PSA to distribute their data to the community. 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

  8. Distinctive PSA-NCAM and NCAM Hallmarks in Glutamate-Induced Dendritic Atrophy and Synaptic Disassembly

    PubMed Central

    Podestá, María Fernanda; Yam, Patricia; Codagnone, Martín Gabriel; Uccelli, Nonthué Alejandra; Colman, David; Reinés, Analía

    2014-01-01

    Dendritic and synapse remodeling are forms of structural plasticity that play a critical role in normal hippocampal function. Neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) participate in neurite outgrowth and synapse formation and plasticity. However, it remains unclear whether they contribute to dendritic retraction and synaptic disassembly. Cultured hippocampal neurons exposed to glutamate (5 µM) showed a reduced MAP-2 (+) area in the absence of neuronal death 24 h after the insult. Concomitantly, synapse loss, revealed by decreased synaptophysin and post-synaptic density-95 cluster number and area, together with changes in NCAM and PSA-NCAM levels were found. Dendritic atrophy and PSA-NCAM reduction proved NMDA-receptor dependent. Live-imaging experiments evidenced dendritic atrophy 4 h after the insult; this effect was preceded by smaller NCAM clusters (1 h) and decreased surface and total PSA-NCAM levels (3 h). Simultaneously, total NCAM cluster number and area remained unchanged. The subsequent synapse disassembly (6 h) was accompanied by reductions in total NCAM cluster number and area. A PSA mimetic peptide prevented both the dendritic atrophy and the subsequent synaptic changes (6 h) but had no effect on the earliest synaptic remodeling (3 h). Thus, NCAM-synaptic reorganization and PSA-NCAM level decrease precede glutamate-induced dendritic atrophy, whereas the NCAM level reduction is a delayed event related to synapse loss. Consequently, distinctive stages in PSA-NCAM/NCAM balance seem to accompany glutamate-induced dendritic atrophy and synapse loss. PMID:25279838

  9. The new Planetary Science Archive (PSA): Exploration and discovery of scientific datasets from ESA's planetary missions

    NASA Astrophysics Data System (ADS)

    Martinez, Santa; Besse, Sebastien; Heather, Dave; Barbarisi, Isa; Arviset, Christophe; De Marchi, Guido; Barthelemy, Maud; Docasal, Ruben; Fraga, Diego; Grotheer, Emmanuel; Lim, Tanya; Macfarlane, Alan; Rios, Carlos; Vallejo, Fran; Saiz, Jaime; ESDC (European Space Data Centre) Team

    2016-10-01

    The Planetary Science Archive (PSA) is the European Space Agency's (ESA) repository of science data from all planetary science and exploration missions. The PSA provides access to scientific datasets through various interfaces at http://archives.esac.esa.int/psa. All datasets are scientifically peer-reviewed by independent scientists, and are compliant with the Planetary Data System (PDS) standards. The PSA is currently implementing a number of significant improvements, mostly driven by the evolution of the PDS standard, and the growing need for better interfaces and advanced applications to support science exploitation. The newly designed PSA will enhance the user experience and will significantly reduce the complexity for users to find their data promoting one-click access to the scientific datasets with more specialised views when needed. This includes a better integration with Planetary GIS analysis tools and Planetary interoperability services (search and retrieve data, supporting e.g. PDAP, EPN-TAP). It will be also up-to-date with versions 3 and 4 of the PDS standards, as PDS4 will be used for ESA's ExoMars and upcoming BepiColombo missions. Users will have direct access to documentation, information and tools that are relevant to the scientific use of the dataset, including ancillary datasets, Software Interface Specification (SIS) documents, and any tools/help that the PSA team can provide. A login mechanism will provide additional functionalities to the users to aid / ease their searches (e.g. saving queries, managing default views). This contribution will introduce the new PSA, its key features and access interfaces.

  10. Validation of prostate‐specific antigen laboratory values recorded in Surveillance, Epidemiology, and End Results registries

    PubMed Central

    Adamo, Margaret (Peggy); Boten, Jessica A.; Coyle, Linda M.; Lam, Clara J. K.; Negoita, Serban; Penberthy, Lynne; Stevens, Jennifer L.; Ward, Kevin C.

    2016-01-01

    BACKGROUND Researchers have used prostate‐specific antigen (PSA) values collected by central cancer registries to evaluate tumors for potential aggressive clinical disease. An independent study collecting PSA values suggested a high error rate (18%) related to implied decimal points. To evaluate the error rate in the Surveillance, Epidemiology, and End Results (SEER) program, a comprehensive review of PSA values recorded across all SEER registries was performed. METHODS Consolidated PSA values for eligible prostate cancer cases in SEER registries were reviewed and compared with text documentation from abstracted records. Four types of classification errors were identified: implied decimal point errors, abstraction or coding implementation errors, nonsignificant errors, and changes related to “unknown” values. RESULTS A total of 50,277 prostate cancer cases diagnosed in 2012 were reviewed. Approximately 94.15% of cases did not have meaningful changes (85.85% correct, 5.58% with a nonsignificant change of <1 ng/mL, and 2.80% with no clinical change). Approximately 5.70% of cases had meaningful changes (1.93% due to implied decimal point errors, 1.54% due to abstract or coding errors, and 2.23% due to errors related to unknown categories). Only 419 of the original 50,277 cases (0.83%) resulted in a change in disease stage due to a corrected PSA value. CONCLUSIONS The implied decimal error rate was only 1.93% of all cases in the current validation study, with a meaningful error rate of 5.81%. The reasons for the lower error rate in SEER are likely due to ongoing and rigorous quality control and visual editing processes by the central registries. The SEER program currently is reviewing and correcting PSA values back to 2004 and will re‐release these data in the public use research file. Cancer 2017;123:697–703. © 2016 American Cancer Society. PMID:27783399

  11. Association of black race with follow-up of an abnormal prostate-specific antigen test.

    PubMed

    Turner, Barbara J; Mavandadi, Shahrzad; Weiner, Mark G

    2011-02-01

    Delayed evaluation after a clearly abnormal prostate-specific antigen (PSA) result may contribute to more advanced prostate cancer at diagnosis in black men. In 46 primary care practices over a period of 4.5 years, we studied men aged more than 50 years without known prostate cancer who had a PSA of at least 10.0 ng/mL for the first time. PSA follow-up included: a urology appointment, a new prostate diagnosis, or repeat PSA test. Cox proportional hazards models assessed time to follow-up, adjusting for demographic, clinical, and health care factors with censoring at a time that represents excessive delay (200 days). Among all 724 study men (27% black), delay until PSA follow-up averaged 115.2 days (+/- 79.7 d) and the unadjusted hazard ratio (HR) for follow-up was shorter for black men than nonblack men (HR, 1.23; 95% CI, 1.00-1.51). However, black men were more likely to have had prior urology care and had higher index PSA levels than other men; both factors were associated with shorter follow-up. After adjustment, delay did not differ for black vs nonblack race (HR, 1.05; 95% Cl, 0.78-1.43) but men aged at least 75 years had a longer delay than men aged 74 years or less (HR, 0.72; 95% CI, 0.59-0.89). Despite black men having greater risk of advanced prostate disease at diagnosis and better linkage to urologic care, follow-up was delayed, on average, by more than 3 months and did not differ by race. These results reveal a potentially important, remediable factor to improve prostate cancer prevention and care for black men.

  12. Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia

    PubMed Central

    Leidinger, Petra; Keller, Andreas; Milchram, Lisa; Harz, Christian; Hart, Martin; Werth, Angelika; Lenhof, Hans-Peter; Weinhäusel, Andreas; Keck, Bastian; Wullich, Bernd

    2015-01-01

    Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients’ sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia. PMID:26039628

  13. Ultrasensitive amperometric immunosensor for PSA detection based on Cu2O@CeO2-Au nanocomposites as integrated triple signal amplification strategy.

    PubMed

    Li, Faying; Li, Yueyun; Feng, Jinhui; Dong, Yunhui; Wang, Ping; Chen, Lei; Chen, Zhiwei; Liu, Hui; Wei, Qin

    2017-01-15

    In this work, a novel label-free electrochemical immunosensor was developed for the quantitative detection of prostate specific antigen (PSA). To this end, the amino functionalized cuprous oxide @ ceric dioxide (Cu2O@CeO2-NH2) core-shell nanocomposites were prepared to bond gold nanoparticles (Au NPs) by constructing stable Au-N bond between Au NPs and -NH2. Because the synergetic effect presents in Cu2O@CeO2 core-shell loaded with Au NPs (Cu2O@CeO2-Au), it shows better electrocatalytic activity towards the reduction of hydrogen peroxide (H2O2) than single Cu2O, Au NPs and Cu2O@CeO2. Featured by large specific surface area, good biocompatibility and good electrochemical properties which can greatly improve the electronic transmission rate, Cu2O@CeO2-Au was used as transducing materials to achieve efficiently capture antibodies and triple signal amplification of the proposed immunosensor. Under the optimal conditions, the proposed immunosensor exhibited a wide linear range from 0.1pg/mL to 100ng/mL with a low detection limit of 0.03pg/mL (S/N=3). Furthermore, the proposed label-free immunosensor has been used to determine PSA in human serum with satisfactory results. Meanwhile, it displayed good reproducibility, acceptable selectivity, and long-term stability, which had promising application in bioassay analysis.

  14. Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia.

    PubMed

    Leidinger, Petra; Keller, Andreas; Milchram, Lisa; Harz, Christian; Hart, Martin; Werth, Angelika; Lenhof, Hans-Peter; Weinhäusel, Andreas; Keck, Bastian; Wullich, Bernd; Ludwig, Nicole; Meese, Eckart

    2015-01-01

    Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients' sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia.

  15. In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

    PubMed Central

    Bahi-Jaber, Narges; Petitdidier, Elodie; Markikou-Ouni, Wafa; Aoun, Karim; Moreno, Javier; Carrillo, Eugenia; Salotra, Poonam; Kaushal, Himanshu; Negi, Narender Singh; Arevalo, Jorge; Falconi-Agapito, Francesca; Privat, Angela; Cruz, Maria; Pagniez, Julie; Papierok, Gérard-Marie; Rhouma, Faten Bel Haj; Torres, Pilar; Lemesre, Jean-Loup; Chenik, Mehdi; Meddeb-Garnaoui, Amel

    2014-01-01

    PSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in several Leishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice. We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in a L. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L. braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals were subdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantum infection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high or low levels of IFN-γ in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detected in sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-γ, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-α in more. No significant cytokine response was observed in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increase in CD4+ T cells producing IFN-γ after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between the percentage of IFN-γ-producing CD4+ T cells and the released IFN-γ. We showed that the LaPSA-38S protein was able to induce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infection indicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacity of Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infection. PMID:24786587

  16. Respiratory Failure

    MedlinePlus

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, ... brain, need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can' ...

  17. Nanogold-functionalized g-C3N4 nanohybrids for sensitive impedimetric immunoassay of prostate-specific antigen using enzymatic biocatalytic precipitation.

    PubMed

    Ding, Li-Li; Ge, Jing-Ping; Zhou, Wen-Quan; Gao, Jian-Ping; Zhang, Zheng-Yu; Xiong, Ya

    2016-11-15

    This work reports on a new impedimetric immunosensing strategy for sensitive detection of prostate-specific antigen (PSA) in biological fluids. The assay was carried out on monoclonal anti-PSA capture antibody-modified glassy carbon electrode with a sandwich-type detection format. Gold nanoparticles-decorated g-C3N4 nanosheets (AuNP/g-C3N4), synthesized by the wet-chemistry method, were utilized for the labeling of polyclonal anti-PSA detection antibody and horseradish peroxidase (HRP). Upon target PSA introduction, the sandwiched immunocomplex could be formed between capture antibody and detection antibody. Followed by the AuNP/g-C3N4, the labeled HRP could catalyze 4-choloro-1-naphthol into benzo-4-chlorohexadienone. The as-generated insoluble product was coated on the electrode surface, thus increasing the Faradaic impedance of Fe(CN)6(4-/3)(-) indicator between the solution and the base electrode. Under the optimal conditions, the impedance increased with the increasing target PSA in the sample, and exhibited a wide linear range from 10pgmL(-1) and 30ngmL(-1) with a detection limit of 5.2pgmL(-1). A repeatability and intermediate precision of <14% was accomplished. The specificity and method accuracy in comparison with commercial PSA ELISA kit for analysis of human serum specimens were relatively satisfactory.

  18. Solitary recurrence of castration-resistant prostate cancer with low or undetectable levels of prostate specific antigen salvaged with local ablative radiation therapy: A case report

    PubMed Central

    WANG, CHIACHIEN JAKE; YING, JAMES; KAPUR, PAYAL; WOHLFELD, BRYAN; ROEHRBORN, CLAUS; KIM, DONG W. NATHAN

    2016-01-01

    Prostate cancer recurrences are usually first detected by increased levels of prostate specific antigen (PSA), and systemic therapy is often initiated if distant metastasis is confirmed. However, low or nearly undetectable levels of PSA in the modern era of ultrasensitive PSA assay may be difficult to interpret in patients with a history of prostate cancer. Deciding whether to initiate additional systemic therapy in limited indolent metastatic disease while balancing the quality of life of the patient and ensuring the oncologic control of the disease may be challenging. In the present study, the case of a biopsy-confirmed solitary spine recurrence of prostate cancer with nearly undetectable but persistent levels of PSA (0.05 ng/ml) is reported. Treatment of the recurrence with local ablative radiotherapy improved the pain experienced by the patient, and reduced his levels of PSA to undetectable limits (<0.05 ng/ml). Repeated imaging analysis, PSA assay and clinical assessment demonstrated durable control of the disease without the requirement for additional systemic treatments. The present case highlighted the importance of initiating appropriate work-up according to the clinical scenario. Local treatment for solitary or oligometastatic recurrence of prostate cancer may enhance the effectiveness of current therapeutic strategies and benefit certain patients. PMID:26870272

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

    PubMed

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

    2017-01-01

    Guidelines regarding recommendations for PSA screening for early detection of prostate cancer are conflicting. In 2012, the United States Preventive Services Task Force (USPSTF) assigned a grade of D (recommending against screening) for men aged ≥75 years in 2008 and for men of all ages in 2012. Understanding temporal trends in rates of screening before and after the 2012 recommendation in terms of usage patterns in PSA screening, changes in prostate cancer incidence and biopsy patterns, and how the recommendation has influenced physician's and men's attitudes about PSA screening and subsequent ordering of other screening tests is essential within the scope of prostate cancer screening policy. Since the 2012 recommendation, rates of PSA screening decreased by 3-10% in all age groups and across most geographical regions of the USA. Rates of prostate biopsy and prostate cancer incidence have declined in unison, with a shift towards tumours being of higher grade and stage upon detection. Despite the recommendation, some physicians report ongoing willingness to screen appropriately selected men, and many men report intending to continue to ask for the PSA test from their physician. In the coming years, we expect to have an improved understanding of whether these decreased rates of screening will affect prostate cancer metastasis and mortality.

  20. Reviewing PSA-based analyses to modify technical specifications at nuclear power plants

    SciTech Connect

    Samanta, P.K.; Martinez-Guridi, G.; Vesely, W.E.

    1995-12-01

    Changes to Technical Specifications (TSs) at nuclear power plants (NPPs) require review and approval by the United States Nuclear Regulatory Commission (USNRC). Currently, many requests for changes to TSs use analyses that are based on a plant`s probabilistic safety assessment (PSA). This report presents an approach to reviewing such PSA-based submittals for changes to TSs. We discuss the basic objectives of reviewing a PSA-based submittal to modify NPP TSs; the methodology of reviewing a TS submittal, and the differing roles of a PSA review, a PSA Computer Code review, and a review of a TS submittal. To illustrate this approach, we discuss our review of changes to allowed outage time (AOT) and surveillance test interval (STI) in the TS for the South Texas Project Nuclear Generating Station. Based on this experience gained, a check-list of items is given for future reviewers; it can be used to verify that the submittal contains sufficient information, and also that the review has addressed the relevant issues. Finally, recommended steps in the review process and the expected findings of each step are discussed.

  1. Heart Failure

    MedlinePlus

    Heart failure is a condition in which the heart can't pump enough blood to meet the body's needs. Heart failure does not mean that your heart has stopped ... Tiredness and shortness of breath Common causes of heart failure are coronary artery disease, high blood pressure and ...

  2. Visually Estimated MRI Targeted Prostate Biopsy Could Improve the Detection of Significant Prostate Cancer in Patients with a PSA Level <10 ng/mL

    PubMed Central

    Lee, Dong Hoon; Nam, Jong Kil; Park, Sung Woo; Lee, Seung Soo; Han, Ji-Yeon; Lee, Sang Don; Lee, Joon Woo

    2016-01-01

    Purpose To compare prostate cancer detection rates between 12 cores transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and visually estimated multiparametric magnetic resonance imaging (mp-MRI)-targeted prostate biopsy (MRI-visual-Bx) for patients with prostate specific antigen (PSA) level less than 10 ng/mL. Materials and Methods In total, 76 patients with PSA levels below 10 ng/mL underwent 3.0 Tesla mp-MRI and TRUS-Bx prospectively in 2014. In patients with abnormal lesions on mp-MRI, we performed additional MRI-visual-Bx. We compared pathologic results, including the rate of clinically significant prostate cancer cores (cancer length greater than 5 mm and/or any Gleason grade greater than 3 in the biopsy core). Results The mean PSA was 6.43 ng/mL. In total, 48 of 76 (63.2%) patients had abnormal lesions on mp-MRI, and 116 targeted biopsy cores, an average of 2.42 per patient, were taken. The overall detection rates of prostate cancer using TRUS-Bx and MRI-visual-Bx were 26/76 (34.2%) and 23/48 (47.9%), respectively. In comparing the pathologic results of TRUS-Bx and MRI-visual-Bx cores, the positive rates were 8.4% (77 of 912 cores) and 46.6% (54 of 116 cores), respectively (p<0.001). Mean cancer core lengths and mean cancer core percentages were 3.2 mm and 24.5%, respectively, in TRUS-Bx and 6.3 mm and 45.4% in MRI-visual-Bx (p<0.001). In addition, Gleason score ≥7 was noted more frequently using MRI-visual-Bx (p=0.028). The detection rate of clinically significant prostate cancer was 27/77 (35.1%) and 40/54 (74.1%) for TRUS-Bx and MRI-visual-Bx, respectively (p<0.001). Conclusion MRI-visual-Bx showed better performance in the detection of clinically significant prostate cancer, compared to TRUS-Bx among patients with a PSA level less than 10 ng/mL. PMID:26996553

  3. Cytosolic aminopeptidases influence MHC class I-mediated antigen presentation in an allele-dependent manner.

    PubMed

    Kim, Eunkyung; Kwak, Heechun; Ahn, Kwangseog

    2009-12-01

    Antigenic peptides presented by MHC class I molecules are generated mainly by the proteasome in the cytosol. Several cytosolic aminopeptidases further trim proteasomal products to form mature epitopes or individual amino acids. However, the distinct function of cytosolic aminopeptidases in MHC class I Ag processing remains to be elucidated. In this study, we show that cytosolic aminopeptidases differentially affect the cell surface expression of MHC class I molecules in an allele-dependent manner in human cells. In HeLa cells, knockdown of puromycin-sensitive aminopeptidase (PSA) by RNA interference inhibited optimal peptide loading of MHC class I molecules, and their cell surface expression was correspondingly reduced. In contrast, depletion of bleomycin hydrolase (BH) enhanced optimal peptide loading and cell surface expression of MHC class I molecules. We did not find evidence on the effect of leucine aminopeptidase knockdown on the MHC class I Ag presentation. Moreover, we demonstrated that PSA and BH influence the peptide loading and surface expression of MHC class I in an allele-specific manner. In the absence of either PSA or BH, the surface expression and peptide-dependent stability of HLA-A68 were reduced, whereas those of HLA-B15 were enhanced. The surface expression and peptide-dependent stability of HLA-A3 were enhanced by BH knockdown, although those of HLA-B8 were increased in PSA-depleted conditions.

  4. National Evidence on the Use of Shared Decision Making in Prostate-Specific Antigen Screening

    PubMed Central

    Han, Paul K. J.; Kobrin, Sarah; Breen, Nancy; Joseph, Djenaba A.; Li, Jun; Frosch, Dominick L.; Klabunde, Carrie N.

    2013-01-01

    PURPOSE Recent clinical practice guidelines on prostate cancer screening using the prostate-specific antigen (PSA) test (PSA screening) have recommended that clinicians practice shared decision making—a process involving clinician-patient discussion of the pros, cons, and uncertainties of screening. We undertook a study to determine the prevalence of shared decision making in both PSA screening and nonscreening, as well as patient characteristics associated with shared decision making. METHODS A nationally representative sample of 3,427 men aged 50 to 74 years participating in the 2010 National Health Interview Survey responded to questions on the extent of shared decision making (past physician-patient discussion of advantages, disadvantages, and scientific uncertainty associated with PSA screening), PSA screening intensity (tests in past 5 years), and sociodemographic and health-related characteristics. RESULTS Nearly two-thirds (64.3%) of men reported no past physician-patient discussion of advantages, disadvantages, or scientific uncertainty (no shared decision making); 27.8% reported discussion of 1 to 2 elements only (partial shared decision making); 8.0% reported discussion of all 3 elements (full shared decision making). Nearly one-half (44.2%) reported no PSA screening, 27.8% reported low-intensity (less-than-annual) screening, and 25.1% reported high-intensity (nearly annual) screening. Absence of shared decision making was more prevalent in men who were not screened; 88% (95% CI, 86.2%–90.1%) of nonscreened men reported no shared decision making compared with 39% (95% CI, 35.0%–43.3%) of men undergoing high-intensity screening. Extent of shared decision making was associated with black race, Hispanic ethnicity, higher education, health insurance, and physician recommendation. Screening intensity was associated with older age, higher education, usual source of medical care, and physician recommendation, as well as with partial vs no or full shared

  5. The Relationship Between Metformin and Serum Prostate‐Specific Antigen Levels

    PubMed Central

    Jayalath, Viranda H.; Ireland, Christopher; Fleshner, Neil E.; Hamilton, Robert J.

    2016-01-01

    BACKGROUND Metformin is the first‐line oral antihyperglycemic of choice for individuals with type 2 diabetes. Recent evidence supports a role for metformin in prostate cancer chemoprotection. However, whether metformin indeed influences prostate biology is unknown. We aimed to study the association between metformin and serum prostate‐specific antigen (PSA) levels—the primary prostate cancer biomarker. METHODS We conducted a cross‐sectional study of 326 prostate cancer‐free men with type 2 diabetes were recruited between 2004 and 2013 at St. Michael's Hospital. Men were excluded if they had a PSA ≥10‐ng/ml, or used >2,550‐mg/d metformin or supplemental androgens. Multivariate linear regressions quantified the association between metformin dose and log‐PSA. Secondary analyses quantified the association between other antihyperglycemics (sulfonylureas, thiazolidinediones) and PSA; sensitivity analyses tested covariate interactions. RESULTS Median PSA was 0.9‐ng/ml (IQR: 0.5–1.6‐ng/ml). Metformin dose associated positively with BMI, HbA1c, diabetes duration, and number of statin, acetylsalicylic acid, diuretic users, and number of antihyperglycemics used, and negatively with LDL‐C. In multivariate models, PSA changed by −8% (95%CI: −13 to −2%, P = 0.011) per 500‐mg/d increase in metformin. Men with diabetes for ≥6 years (n = 163) saw a greater difference in PSA per 500‐mg/d metformin (−12% [95% CI: −19 to −4%, P = 0.002], P‐interaction = 0.018). Serum PSA did not relate with sulfonylureas, thiazolidinediones, or total number of antihyperglycemic agents used. Our findings are limited by the cross‐sectional design of this study. CONCLUSIONS Metformin dose‐dependently inversely associated with serum PSA, independent of other antihyperglycemic medications. Whether metformin confers a dose‐dependent benefit on prostate tumorigenesis and progression warrants investigation. Prostate 76:1445–1453, 2016.

  6. Low prefrontal PSA-NCAM confers risk for alcoholism-related behavior.

    PubMed

    Barker, Jacqueline M; Torregrossa, Mary M; Taylor, Jane R

    2012-10-01

    The factors underlying vulnerability to alcoholism are largely unknown. We identified in rodents an innate endophenotype predicting individual risk for alcohol-related behaviors that was associated with decreased expression of the neuroplasticity-related polysialylated neural cell adhesion molecule (PSA-NCAM). Depletion of PSA-NCAM in the ventromedial prefrontal cortex was sufficient to render mice unable to extinguish alcohol seeking, indicating a causal role of naturally occurring variation. These data suggest a mechanism of aberrant prefrontal neuroplasticity that underlies enhanced propensity for inflexible addiction-related behavior.

  7. A cluster-randomised, parallel group, controlled intervention study of genetic prostate cancer risk assessment and use of PSA tests in general practice—the ProCaRis study: study protocol

    PubMed Central

    Kirkegaard, Pia; Vedsted, Peter; Edwards, Adrian; Fenger-Grøn, Morten; Bro, Flemming

    2013-01-01

    Introduction Unsystematic screening for prostate cancer (PCa) is common, causing a high number of false-positive results. Valid instruments for assessment of individual risk of PCa have been called for. A DNA-based genetic test has been tested retrospectively. The clinical use of this test needs further investigation. The primary objective is to evaluate the impact on the use of prostate-specific antigen (PSA) tests of introducing genetic PCa risk assessment in general practice. The secondary objectives are to evaluate PCa-related patient experiences, and to explore sociocultural aspects of genetic risk assessment in patients at high PCa risk. Methods and analysis The study is a cluster-randomised, controlled intervention study with practice as the unit of randomisation. We expect 140 practices to accept participation and include a total of 1244 patients in 4 months. Patients requesting a PSA test in the intervention group practices will be offered a genetic PCa risk assessment. Patients requesting a PSA test in the control group practices will be handled according to current guidelines. Data will be collected from registers, patient questionnaires and interviews. Quantitative data will be analysed according to intention-to-treat principles. Baseline characteristics will be compared between groups. Longitudinal analyses will include time in risk, and multivariable analysis will be conducted to evaluate the influence of general practitioner and patient-specific variables on future PSA testing. Interview data will be transcribed verbatim and analysed from a social-constructivist perspective. Ethics and dissemination Consent will be obtained from patients who can withdraw from the study at any time. The study provides data to the ongoing conceptual and ethical discussions about genetic risk assessment and classification of low-risk and high-risk individuals. The intervention model might be applicable to other screening areas regarding risk of cancer with identified

  8. Salvage reirradiation for locoregional failure after radiation therapy for prostate cancer: who, when, where and how?

    PubMed

    Créhange, G; Roach, M; Martin, E; Cormier, L; Peiffert, D; Cochet, A; Chapet, O; Supiot, S; Cosset, J-M; Bolla, M; Chung, H T

    2014-10-01

    Even in the current era of dose-escalated radiotherapy for prostate cancer, biochemical recurrence is not uncommon. Furthermore, biochemical failure is not specific to the site of recurrence. One of the major challenges in the management of prostate cancer patients with biochemical failure after radiotherapy is the early discrimination between those with locoregional recurrence only and those with metastatic disease. While the latter are generally considered incurable, patients with locoregional disease may benefit from emerging treatment options. Ultimately, the objective of salvage therapy is to control disease while ensuring minimal collateral damage, thereby optimizing both cancer and toxicity outcomes. Advances in functional imaging, including multiparametric prostate MRI, abdominopelvic lymphangio-MRI, sentinel node SPECT-CT and/or whole-body PET/CT have paved the way for salvage radiotherapy in patients with local recurrence, microscopic nodal disease limited to the pelvis or oligometastatic disease. These patients may be considered for salvage reirradiation using different techniques: prostate low-dose or high-dose rate brachytherapy, pelvic and/or lomboaortic image-guided radiotherapy with elective nodal irradiation, focal nodal or bone stereotactic body radiation therapy (SBRT). An individualized approach is recommended. The decision about which treatment, if any, to use will be based on the initial characteristics of the disease, relapse patterns and the natural history of the rising prostate specific antigen (PSA). Preliminary results suggest that more than 50% of patients who have undergone salvage reirradiation are biochemically relapse-free with very low rates of severe toxicity. Large prospective studies with a longer follow-up are needed to confirm the promising benefit/risk ratio observed with salvage brachytherapy and or salvage nodal radiotherapy and/or bone oligometastatic SBRT when compared with life-long palliative hormones.

  9. Prostate-specific antigen kinetics after stereotactic body radiotherapy as monotherapy or boost after whole pelvic radiotherapy for localized prostate cancer

    PubMed Central

    Kim, Hun Jung; Phak, Jung Hoon; Kim, Woo Chul

    2015-01-01

    Purpose Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. However, prostate-specific antigen (PSA) kinetics after SBRT has not been well characterized. The purpose of the current study is to assess the kinetics of PSA for low- and intermediate-risk prostate cancer patients treated with SBRT using Cyberknife as both monotherapy and boost after whole pelvic radiotherapy (WPRT) in the absence of androgen deprivation therapy. Methods A total of 61 patients with low- and intermediated-risk prostate cancer treated with SBRT as monotherapy (36.25 Gy in 5 fractions in 32 patients) and SBRT (21 Gy in 3 fractions in 29 patients) boost combined with WPRT (45 Gy in 25 fractions). Patients were excluded if they failed therapy by the Phoenix definition or had androgen deprivation therapy. PSA nadir and rate of change in PSA over time (slope) were calculated and compared. Results With a median follow-up of 52.4 months (range, 14–74 months), for SBRT monotherapy, the median PSA nadir was 0.31 ng/mL (range, 0.04–1.15 ng/mL) and slopes were –0.41 ng/mL/mo, –0.17 ng/mL/mo, –0.12 ng/mL/mo, and –0.09 ng/mL/mo, respectively, for durations of 1 year, 2 years, 3 years, and 4 years postradiotherapy. Similarly, for SBRT boost after WPRT, the median PSA nadir was 0.34 ng/mL (range, 0.04–1.44 ng/mL) and slopes were –0.53 ng/mL/mo, –0.25 ng/mL/mo, –0.14 ng/mL/mo, and –0.09 ng/mL/mo, respectively. The median nadir and slopes of SBRT monotherapy did not differ significantly from those of SBRT boost after WPRT. Benign PSA bounces were common in 30.4% of all cohorts, and the median time to PSA bounce was 12 months (range, 6–25 months). Conclusions In this report of low- and intermediate-risk prostate cancer patients, an initial period of rapid PSA decline was followed by a slow decline, which resulted in a lower PSA nadir. The PSA kinetics of SBRT monotherapy appears to be comparable to those achieved

  10. PSA-NCAM is up-regulated during optic nerve regeneration in lizard but not in goldfish.

    PubMed

    Harman, A M; Rodger, J; Ahmat, A; Thomas, C; Bartlett, C; Chen, P; Dunlop, S A; Beazley, L D

    2003-07-01

    The addition of polysialic acid (PSA) to neural cell adhesion molecule (NCAM) facilitates axon growth. Here we use Western blots and immunohistochemistry to examine expression of PSA-NCAM during optic nerve regeneration. In lizard, retinal ganglion cell axons become transiently PSA-NCAM positive. By contrast, goldfish RGC axons are PSA-NCAM negative both in normal animals and throughout regeneration with the exception of a PSA-NCAM-positive fascicle arising from newly generated RGCs. Transient sialylation of NCAM in lizard may assist regeneration in the nonpermissive reptilian visual pathway and facilitate the reestablishment of a crude topographic map; down-regulation in the long term may contribute to the breakdown in topography. The lack of sialylation in goldfish presumably reflects the permissive nature of the substrate allowing axon regeneration and the successful reestablishment of a topographic map.

  11. Diagnostic ability of %p2PSA and prostate health index for aggressive prostate cancer: a meta-analysis

    PubMed Central

    Wang, Wenying; Wang, Meilin; Wang, Li; Adams, Tamara S.; Tian, Ye; Xu, Jianfeng

    2014-01-01

    The role of [-2]proPSA (p2PSA) based diagnostic tests for the detection of aggressive prostate cancer (PCa) has not been fully evaluated. We conducted a meta-analysis to evaluate the diagnostic performance of p2PSA/free PSA (%p2PSA) and prostate health index (Phi) tests for PCa and to evaluate their ability in discriminating between aggressive and non-aggressive PCa. A total of 16 articles were included in this meta-analysis. For the detection of PCa, the pooled sensitivity, specificity, and AUC were 0.86 (95% CI, 0.84–0.87), 0.40 (95% CI, 0.39–042) and 0.72 (95% CI, 0.67–0.77) for %p2PSA respectively, and were 0.85 (95% CI, 0.83–0.86), 0.45 (95% CI, 0.44–0.47) and 0.70 (95% CI = 0.65–0.74) for Phi, respectively. In addition, the sensitivity for discriminating PCa between higher Gleason score (≥7) and lower Gleason score (<7) was 0.96 (95% CI, 0.93–0.98) and 0.90 (95% CI, 0.87–0.92) for %p2PSA and Phi respectively, and the specificity was low, only 0.09 (95% CI, 0.06–0.12) and 0.17 (95% CI, 0.14–0.19) for %p2PSA and Phi, respectively. Phi and %p2PSA have a high diagnostic accuracy rates and can be used in PCa diagnosis. Phi and %p2PSA may be useful as tumor markers in predicating patients harboring more aggressive disease and guiding biopsy decisions. PMID:24852453

  12. Student-Designed Public Service Announcement (PSA) Videos to Enhance Motivation and Engagement

    ERIC Educational Resources Information Center

    Abrams, Kenneth

    2012-01-01

    Educators often focus on enhancing student motivation and engagement. This article describes an activity with these aims, in which undergraduates (a) learn about theories and research on means of persuasion and (b) in small groups design and record a public service announcement (PSA) video, write a brief paper that outlines the theories used to…

  13. Proteomics of Peripheral Leukocytes in Patients with Elevated Serum Levels of PSA

    DTIC Science & Technology

    2011-09-01

    3 INTRODUCTION: This research has the long-term goal of developing a test that will discriminate between prostate cancer ( PrCA ) and benign...observed to have an elevated serum level of PSA, in order to distinguish among CP, BPH and PrCA . To achieve these objectives, we proposed to employ mass

  14. The dendritic spines of interneurons are dynamic structures influenced by PSA-NCAM expression.

    PubMed

    Guirado, Ramon; Perez-Rando, Marta; Sanchez-Matarredona, David; Castillo-Gómez, Esther; Liberia, Teresa; Rovira-Esteban, Laura; Varea, Emilio; Crespo, Carlos; Blasco-Ibáñez, José Miguel; Nacher, Juan

    2014-11-01

    Excitatory neurons undergo dendritic spine remodeling in response to different stimuli. However, there is scarce information about this type of plasticity in interneurons. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is a good candidate to mediate this plasticity as it participates in neuronal remodeling and is expressed by some mature cortical interneurons, which have reduced dendritic arborization, spine density, and synaptic input. To study the connectivity of the dendritic spines of interneurons and the influence of PSA-NCAM on their dynamics, we have analyzed these structures in a subpopulation of fluorescent spiny interneurons in the hippocampus of glutamic acid decarboxylase-enhanced green fluorescent protein transgenic mice. Our results show that these spines receive excitatory synapses. The depletion of PSA in vivo using the enzyme Endo-Neuraminidase-N (Endo-N) increases spine density when analyzed 2 days after, but decreases it 7 days after. The dendritic spine turnover was also analyzed in real time using organotypic hippocampal cultures: 24 h after the addition of EndoN, we observed an increase in the apparition rate of spines. These results indicate that dendritic spines are important structures in the control of the synaptic input of hippocampal interneurons and suggest that PSA-NCAM is relevant in the regulation of their morphology and connectivity.

  15. Social ecological predictors of prostate-specific antigen blood test and digital rectal examination in black American men.

    PubMed Central

    Woods, V. Diane; Montgomery, Susanne B.; Herring, R. Patti; Gardner, Robert W.; Stokols, Daniel

    2006-01-01

    BACKGROUND: Black American men continue to suffer disproportionately from epidemically higher rates of prostate cancer. We hypothesize that complex reasons for persistently higher death rates of prostate cancer in this group are steeped in social factors associated with health access. METHODS: We utilized data from the It's All About U prostate cancer prevention study among black men to investigate: 1) what social ecological factors were predictive of prostate-specific antigen (PSA) testing and digital rectal examinations (DRE); 2) if black men were aware of prostate cancer screening and, if screening was available, would they take the PSA and DRE? Quantitative cross-sectional data from a cohort of 276 black men with no diagnosis of prostate cancer were analyzed to identify characteristics, beliefs, practices and attitudes of this group toward prostate cancer screening. We created a social ecological model to examine which social factors (i.e., environmental, personal, person/environment interplay, black culture and institutional policy) were predictive of PSA and DRE, PSA only and DRE only. To reduce data and identify data patterns, factor analyses (tested for reliability by calculating Cronbach alpha scores) were performed. Variables were standardized with Z scores and analyzed with predictive analytic software technology (SPSS, version 12). A multivariate binary logistic regression was conducted to identify predictors of PSA and DRE. RESULTS: A significant predictor of both PSA and DRE was the physician's direct prostate cancer communication message (P<0.010). Significant correlations exist in PSA and DRE outcomes with a physician's engaging communication style (P<0.012), encouragement to screen (P<0.001) and sharing prostate cancer information (P<0.001); as was men understanding the serious risk of prostate cancer (P<0.001), culture (P<0.004), positive interaction with healthcare staff, significant other(s) and providers (P<0.001), and environmental dimensions

  16. Usefulness of Total PSA Value in Prostate Diseases Diagnosis

    PubMed Central

    Prcic, Alden; Begic, Edin; Hiros, Mustafa

    2016-01-01

    Introduction: Analysis of total value of prostate specific antigen (PSAT), with the unavoidable digital rectal examination (DRE) is the basis of prostate cancer detection. Aim: The aim of this study was to determine the specificity and sensitivity of the total value of PSAT in the diagnosis of prostate cancer. The aim was also to determine the significance of PSAT in diagnosis of benign prostate hyperplasia, precancerous conditions and inflammatory and atrophic changes of the prostate. Material and methods: Data were collected from the “Register of PH biopsy” of Clinic of Urology, CCU Sarajevo. Results: Analysis of correlation between the diagnosis and the PSAT value shows statistically significant negative correlation (r =-0,186; p = 0.006) in the sense that the value of the PSAT is highest in cancer patients, and the lowest in patients with benign prostatic hyperplasia. PSAT increases with age (r = 0.152; p = 0.025). For prostate cancer optimal sensitivity and specificity for PSAT value occurs at cut off value of> 8.6 ng /mL. Values lower than 2 ng/mL and higher than 10 ng/mL are most specific, and PPV increases with increasing value of PSAT. PSAT at values of <2 ng/mL and > 10 ng/mL are at high levels of specificity, and value > 10 ng / mL is also of high sensitivity in the detection of prostate cancer, and in this moment these values represent the optimal mode for the subsequent treatment. Conclusion: PSAT has a relative significance in the detection of prostate cancer, and should not be used as a guideline without DRE. PMID:27482127

  17. Proteomic analysis of patient tissue reveals PSA protein in the stroma of benign prostatic hyperplasia

    PubMed Central

    O’Malley, Katherine J.; Eisermann, Kurtis; Pascal, Laura E.; Parwani, Anil V.; Majima, Tsuyoshi; Graham, Lara; Hrebinko, Katherine; Acquafondata, Marie; Stewart, Nicolas A.; Nelson, Joel B.; Yoshimura, Naoki; Wang, Zhou

    2014-01-01

    BACKGROUND Benign prostatic hyperplasia (BPH) is an age-related disease frequently associated with lower urinary tract symptoms (LUTS) that involves hyperplasia of both epithelial and stromal cells. Stromal fibrosis is a distinctive feature of BPH, but the exact mechanisms underlying this phenomenon are poorly understood. METHODS In the current study, proteomics analyses were utilized to identify proteins altered in the BPH stromal compartment from patients with symptomatic BPH. Stromal cells were isolated from histological nodules of BPH by laser capture microdissection (LCM) and subjected to liquid chromatography/mass spectrometry. RESULTS Proteins identified included several stromal-specific proteins involved in extracellular matrix remodeling, focal adhesion and cellular junctions. Additionally, the proteomics array identified the presence of luminal epithelial secretory protein PSA. Immunostaining, ELISA, and in situ hybridization analyses of BPH tissues verified the presence of PSA protein but absence of PSA mRNA in the stromal compartment. E-cadherin was down-regulated in BPH epithelial cells compared to normal adjacent tissues, suggesting that alteration of cellular junctions could contribute to the presence of luminal epithelial secreted proteins PSA and KLK2 in the stromal compartment. CONCLUSIONS The above findings suggest that the presence of secreted proteins PSA and KLK2 from prostate luminal epithelial cells in BPH stroma is a hallmark of BPH nodules which could in part be due to alterations in cellular junction proteins and/or increased epithelial barrier permeability. Elucidating the cause and consequence of these secreted proteins in the stromal compartment of BPH may lead to new understanding of BPH pathogenesis as well as approaches to prevent and/or treat this common disease. PMID:24711254

  18. Mass-tag enhanced immuno-laser desorption/ionization mass spectrometry for sensitive detection of intact protein antigens.

    PubMed

    Lorey, Martina; Adler, Belinda; Yan, Hong; Soliymani, Rabah; Ekström, Simon; Yli-Kauhaluoma, Jari; Laurell, Thomas; Baumann, Marc

    2015-05-19

    A new read-out method for antibody arrays using laser desorption/ionization-mass spectrometry (LDI-MS) is presented. Small, photocleavable reporter molecules with a defined mass called "mass-tags" are used for detection of immunocaptured proteins from human plasma. Using prostate specific antigen (PSA), a biomarker for prostate cancer, as a model antigen, a high sensitivity generic detection methodology based immunocapture with a primary antibody and with a biotin labeled secondary antibody coupled to mass-tagged avidin is demonstrated. As each secondary antibody can bind several avidin molecules, each having a large number of mass-tags, signal amplification can be achieved. The developed PSA sandwich mass-tag analysis method provided a limit of detection below 200 pg/mL (6 pM) for a 10 μL plasma sample, well below the clinically relevant cutoff value of 3-4 ng/mL. This brings the limit of detection (LOD) for detection of intact antigens with matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) down to levels comparable to capture by anti-peptide antibodies selected reaction monitoring (SISCAPA SRM) and enzyme linked immunosorbent assay (ELISA), as 6 pM corresponds to a maximal amount of 60 amol PSA captured on-spot. We propose the potential use of LDI (laser desorption/ionization) with mass-tag read-out implemented in a sandwich assay format for low abundant and/or early disease biomarker detection.

  19. Primary cryptococcal prostatitis and correlation with serum prostate specific antigen in a renal transplant recipient.

    PubMed

    Siddiqui, Tahseen J; Zamani, Tanveer; Parada, Jorge P

    2005-10-01

    The prostate gland is a rare site of primary infection due to Cryptococcus neoformans; however, it may serve as a site of its sequestration after an occult or treated disseminated infection. Serum prostate specific antigen may correlate with the severity of prostatic inflammation, but its role as a diagnostic and prognostic marker is unclear. We report the first case of primary cryptococcal prostatitis in a renal transplant recipient. The diagnosis was established based on asymmetrically enlarged prostate gland, markedly elevated serum PSA levels, cryptococcal fungemia, an ultrasound-guided prostatic biopsy that demonstrated cryptococcal fungal elements and growth of C. neoformans on culture. The patient was successfully treated with a prolonged course of fluconazole and remained disease-free for more than 28 months of follow-up. In addition, we present a review of the published literature since 1946 and discuss possible correlation with PSA levels.

  20. Gold Nanoparticle Based Activatable Probe for Sensing Ultra-Low Levels of Prostate Specific Antigen

    PubMed Central

    Liu, Dingbin; Huang, Xinglu; Wang, Zhantong; Jin, Albert; Sun, Xiaolian; Zhu, Lei; Wang, Fu; Ma, Ying; Niu, Gang; HightWalker, Angela R.; Chen, Xiaoyuan

    2013-01-01

    It is still in high demand to develop extremely sensitive and accurate clinical tools for biomarkers of interest for early diagnosis and monitoring of diseases. In this report, we present a highly sensitive and compatible gold nanoparticle (AuNP)-based fluorescence activatable probe for sensing ultra-low levels of prostate-specific antigen (PSA) in patient serum samples. The limit of detection of the newly-developed probe for PSA was pushed down to 0.032 pg/mL, which is more than two orders of magnitude lower than that of the conventional fluorescence probe. The ultrahigh sensitivity of this probe was attributed to the high loading efficiency of the dyes on AuNP surfaces and high fluorescence quenching unquenching abilities of the dye-AuNP pairs. The efficiency and robustness of this probe was investigated in patient serum samples, demonstrating the great potential of this probe in real-world applications. PMID:23683064

  1. Sweet characterisation of prostate specific antigen using electrochemical lectin-based immunosensor assay and MALDI TOF/TOF analysis: Focus on sialic acid.

    PubMed

    Pihikova, Dominika; Pakanova, Zuzana; Nemcovic, Marek; Barath, Peter; Belicky, Stefan; Bertok, Tomas; Kasak, Peter; Mucha, Jan; Tkac, Jan

    2016-12-01

    The construction of a sensitive electrochemical lectin-based immunosensor for detection of a prostate specific antigen (PSA) is shown here. Three lectins with different carbohydrate specificities were used in this study to glycoprofile PSA, which is the most common biomarker for prostate cancer (PCa) diagnosis. The biosensor showed presence of α-L-fucose and α-(2,6)-linked terminal sialic acid within PSA´s glycan with high abundance, while only traces of α-(2,3)-linked terminal sialic acid were found. MALDI TOF/TOF mass spectrometry was applied to validate results obtained by the biosensor with a focus on determination of a type of sialic acid linkage by two methods. The first direct comparison of electrochemical immunosensor assay employing lectins for PSA glycoprofiling with mass spectrometric techniques is provided here and both methods show significant agreement. Thus, electrochemical lectin-based immunosensor has potential to be applied for prostate cancer diagnosis.

  2. Comparison of quantum-dots- and fluorescein-isothiocyanate-based technology for detecting prostate-specific antigen expression in human prostate cancer.

    PubMed

    Ruan, Y; Yu, W; Cheng, F; Zhang, X; Rao, T; Xia, Y; Larré, S

    2011-06-01

    Quantum dots (QDs) are a new class of fluorescent labelling for biological and biomedical applications. In this study, the authors evaluated the sensitivity and stability of quantum-dots-based immunolabelling, in comparison with the conventional fluorescein-isothiocyanate-based immunolabelling (FITC), for detecting prostate-specific antigen (PSA) expression in human prostate cancer. The authors' data revealed that the two methods had similar sensitivity in differential display of the PSA expression correlated with tumour stage and grade (=0.88, p<0.001). Moreover, the intensity of QDs fluorescence remain stable for 10 days after conjugation to the PSA protein in 97% of the cases and more than 1 month in 92% of the cases, although the FITC fluorescence became undetectable after 6 min for all cases.

  3. Trends in prostate cancer incidence and mortality in Canada during the era of prostate-specific antigen screening

    PubMed Central

    Dickinson, James; Shane, Amanda; Tonelli, Marcello; Gorber, Sarah Connor; Joffres, Michel; Singh, Harminder; Bell, Neil

    2016-01-01

    Background: Widespread use of prostate-specific antigen (PSA) to screen for prostate cancer began in the early 1990s. Advocates for screening assert that this has caused a decrease in prostate cancer mortality. We sought to describe secular changes in prostate cancer incidence and mortality in Canada in relation to the onset of PSA screening. Methods: Age-standardized and age-specific prostate cancer incidence (1969-2007) and mortality (1969-2009) from Public Health Agency of Canada databases were analyzed by joinpoint regression. Changes in incidence and mortality were related to introduction of PSA screening. Results: Prior to PSA screening, prostate cancer incidence increased from 54.2 to 99.8 per 100 000 between 1969 and 1990. Thereafter, incidence increased sharply (12.8% per year) to peak at 140.8/100 000 in 1993. After decreasing in all age groups between 1993 and 1996, incidence continued to increase for men aged less than 70 years, but decreased for older men. Age-standardized mortality was stable from 1969 to 1977, increased 1.4% per year to peak in 1995 and subsequently decreased at 3.3% per year; the decline started from 1987 in younger men (age < 60 yr). Interpretation: Incidence was increasing before PSA screening occurred, but rose further after it was introduced. Reductions in prostate cancer mortality began before PSA screening was widely used and were larger than could be anticipated from screening alone. These findings suggest that screening caused artifactual increase in incidence, but no more than a part of reductions in prostate cancer mortality. The reduction may be due to changing treatment or certification of death. PMID:27280117

  4. Prostate-specific Antigen Density Variation Rate as a Potential Guideline Parameter for Second Prostate Cancer Detection Biopsy

    PubMed Central

    Xie, Gan-Sheng; Lyv, Jin-Xing; Li, Gang; Yan, Chun-Yin; Hou, Jian-Quan; Pu, Jin-Xian; Ding, Xiang; Huang, Yu-Hua

    2016-01-01

    Background: The diagnostic value of current prostate-specific antigen (PSA) tests is challenged by the poor detection rate of prostate cancer (PCa) in repeat prostate biopsy. In this study, we proposed a novel PSA-related parameter named PSA density variation rate (PSADVR) and designed a clinical trial to evaluate its potential diagnostic value for detecting PCa on a second prostate biopsy. Methods: Data from 184 males who underwent second ultrasound-guided prostate biopsy 6 months after the first biopsy were included in the study. The subjects were divided into PCa and non-PCa groups according to the second biopsy pathological results. Prostate volume, PSA density (PSAD), free-total PSA ratio, and PSADVR were calculated according to corresponding formulas at the second biopsy. These parameters were compared using t-test or Mann-Whitney U-test between PCa and non-PCa groups, and receiver operating characteristic analysis were used to evaluate their predictability on PCa detection. Results: PCa was detected in 24 patients on the second biopsy. Mean values of PSA, PSAD, and PSADVR were greater in the PCa group than in the non-PCa group (8.39 μg/L vs. 7.16 μg/L, 0.20 vs. 0.16, 14.15% vs. −1.36%, respectively). PSADVR had the largest area under the curve, with 0.667 sensitivity and 0.824 specificity when the cutoff was 10%. The PCa detection rate was significantly greater in subjects with PSADVR >10% than PSADVR ≤10% (28.6% vs. 6.5%, P < 0.001). In addition, PSADVR was the only parameter in this study that showed a significant correlation with mid-to-high-risk PCa (r = 0.63, P = 0.03). Conclusions: Our results demonstrated that PSADVR improved the PCa detection rate on second biopsies, especially for mid-to-high-risk cancers requiring prompt treatment. PMID:27453228

  5. Impact of capillary conditioning and background electrolyte composition on capillary electrophoresis analysis of prostate specific antigen isoforms.

    PubMed

    Farina-Gomez, Noemi; Puerta, Angel; Gonzalez, Monica; Diez-Masa, Jose Carlos; de Frutos, Mercedes

    2016-04-22

    Glycoproteins expressed in the human body can experience modifications as result of pathological situations. Detection of those changes can be useful as disease biomarkers. As a result of these modifications, size and/or electrical charge of the glycoprotein can be altered. Migration in capillary zone electrophoresis (CZE) is governed by the size to charge ratio of the analyte and therefore this separation technique can be used to monitor those modifications. At its turn, the alteration of the electrophoretical pattern of a given glycoprotein could be used as disease biomarker. To this aim, high repeatability for separation of a large number of peaks for a given glycoprotein is desirable. For prostate cancer, new markers are needed to decrease the high number of false positive results provided by the biomarkers currently used in clinics. In this sense, CZE methods for analysis of the several prostate specific antigen (PSA) peaks which this glycoprotein exhibit, called isoforms and containing one or more glycoforms, could be useful to study the PSA pattern as prostate cancer marker. In this study two complementary strategies to achieve both lot-to-lot capillary repeatability and high resolution of a large number of PSA isoforms are developed. Better performance and precision have been obtained for capillaries conditioned with HCl than for those conditioned with NaOH. Optimization of the background electrolyte (BGE) pH value to 8.0 and inclusion of 3M urea on its composition were the two factors of highest impact for enhancing resolution of the highest number of PSA peaks. Under the optimized conditions for capillary conditioning and BGE pH and composition, long-term resolution of 10 isoforms of PSA was achieved. Inter-day (n=3) %RSD was 0.55 for the ratio tm/tEOF, 1.15 for μeff, and 5.02 for % Acorr of the PSA peaks.

  6. Novel chemotactic-antigen DNA vaccine against cancer.

    PubMed

    Zhang, Shuren; Zhang, Youhui

    2008-04-01

    Dendritic cells play a pivotal role in immune induction. Dendritic cells perform antigen uptake, processing and presentation to T cells only when they are matured and in the functional state. In the development of a vaccine, it is of utmost importance to consider how to make dendritic cells' functions immunologically adequate. In this paper, we report the development of a series of antitumor DNA vaccines with similar structural framework, in which a gene encoding tumor-associated antigenic peptide is ligated upstream to the gene coding secondary lymphoid-tissue chemokine and downstream to the gene encoding the Fc portion of IgG (named chemotactic-antigen DNA vaccine [CADV]). CCR7(+) T, B, natural killer and dendritic cells can be attracted by secondary lymphoid-tissue chemokine, and Fc facilitates antigen uptake via Fc receptors expressed on dendritic cells. In a series of experiments in mice vaccinated by CADV with such tumor-associated antigenic specificities as HPV-16 E7, PSA-PSM-PAP, HER-2/neu, p53 and hTERT, CADV can attract immune cells to the vaccine inoculation site, remarkably inhibit tumor growth and extend survival time in tumor-bearing mice. The antitumor effect is more efficacious than that in mice treated with SLC-Ag or Ag-Fc hybrid gene. Tumor-associated antigenic-specific cytotoxic T lymphocytes can be induced by in vitro experiment in a human system. When combined with measures blocking the negative immune feedback circuits, the therapeutic effect of the vaccine can be further enhanced. Large-scale production of CADV is possible for clinical application.

  7. A protein related to prokaryotic UMP kinases is involved in psaA/B transcript accumulation in Arabidopsis.

    PubMed

    Hein, Paul; Stöckel, Jana; Bennewitz, Stefan; Oelmüller, Ralf

    2009-03-01

    Dpt1 (defect in p saA/B transcript accumulation 1) is a novel photosystem (PS) I mutant in Arabidopsis. dpt1 mutants fail to grow photoautotrophically, and are impaired in the accumulation of psaA/B transcripts while the transcript levels for the remaining PSI subunits, for subunits of the PSII, the cyt-b ( 6 )/f-complex, and the ribulose-1,5-bisphosphate carboxylase are comparable to the wild type. In-organello run-on transcription assays demonstrate that the lower psaA/B transcript abundance in dpt1-1 is not caused by the inability to transcribe the psaA/psaB/rps14 operon. psaA/B transcripts in the mutant are associated with polyribosomes and translated. Thus, the mutation affects post-transcriptional processes specific for psaA/B. The dpt1 gene was isolated by map-based cloning. The protein is localized in the stroma of the chloroplast and exhibits striking similarities to UMP kinases of prokaryotic origin. Our results show that the nuclear encoded protein Dpt1 is essential for retaining photosynthetic activity in higher plant chloroplasts and involved in post-transcriptional steps of psaA/B transcript accumulation. We discuss that Dpt1 may be a bifunctional protein that couples the pyrimidine metabolism to the photosynthetic electron transport.

  8. The Low Molecular Weight Protein PsaI Stabilizes the Light-Harvesting Complex II Docking Site of Photosystem I.

    PubMed

    Plöchinger, Magdalena; Torabi, Salar; Rantala, Marjaana; Tikkanen, Mikko; Suorsa, Marjaana; Jensen, Poul-Erik; Aro, Eva Mari; Meurer, Jörg

    2016-09-01

    PsaI represents one of three low molecular weight peptides of PSI. Targeted inactivation of the plastid PsaI gene in Nicotiana tabacum has no measurable effect on photosynthetic electron transport around PSI or on accumulation of proteins involved in photosynthesis. Instead, the lack of PsaI destabilizes the association of PsaL and PsaH to PSI, both forming the light-harvesting complex (LHC)II docking site of PSI. These alterations at the LHCII binding site surprisingly did not prevent state transition but led to an increased incidence of PSI-LHCII complexes, coinciding with an elevated phosphorylation level of the LHCII under normal growth light conditions. Remarkably, LHCII was rapidly phosphorylated in ΔpsaI in darkness even after illumination with far-red light. We found that this dark phosphorylation also occurs in previously described mutants impaired in PSI function or state transition. A prompt shift of the plastoquinone (PQ) pool into a more reduced redox state in the dark caused an enhanced LHCII phosphorylation in ΔpsaI Since the redox status of the PQ pool is functionally connected to a series of physiological, biochemical, and gene expression reactions, we propose that the shift of mutant plants into state 2 in darkness represents a compensatory and/or protective metabolic mechanism. This involves an increased reduction and/or reduced oxidation of the PQ pool, presumably to sustain a balanced excitation of both photosystems upon the onset of light.

  9. Kidney Failure

    MedlinePlus

    ... Dialysis or Transplant Paying for Kidney Failure Treatment Contact Us Health Information Center Phone: 1-800-860- ... to share this content freely. October 2, 2013 Contact Us Health Information Center Phone: 1-800-860- ...

  10. Heart Failure

    MedlinePlus

    ... for people who can't tolerate ACE inhibitors. Beta blockers. This class of drugs not only slows your ... rhythms and lessen your chance of dying unexpectedly. Beta blockers may reduce signs and symptoms of heart failure, ...

  11. Prostatic cancer surveillance following whole-gland high-intensity focused ultrasound: comparison of MRI and prostate-specific antigen for detection of residual or recurrent disease

    PubMed Central

    Punwani, S; Emberton, M; Walkden, M; Sohaib, A; Freeman, A; Ahmed, H; Allen, C; Kirkham, A

    2012-01-01

    Objective This retrospective study compares dynamic contrast-enhanced (DCE) MRI with the serial prostate-specific antigen (PSA) measurement for detection of residual disease following whole-gland high-intensity focused ultrasound (HIFU) therapy of prostate cancer. Methods Patients in whom post-HIFU DCE-MRI was followed within 3 months by ultrasound-guided transrectal biopsy were selected from a local database. 26 patients met the study inclusion criteria. Serial PSA levels following HIFU and post-HIFU follow-up MRI were retrieved for each patient. Three radiologists unaware of other investigative results independently assessed post-HIFU MRI studies for the presence of cancer, scoring on a four-point scale (1, no disease; 2, probably no disease; 3, probably residual disease; and 4, residual disease). Sensitivity, specificity and receiver operating characteristic (ROC) analysis were performed for each reader, post-HIFU PSA nadir and pre-biopsy PSA level thresholds of >0.2 and >0.5 ng ml−1. Results The sensitivity of DCE-MRI for detection of residual disease for the three readers ranged between 73% and 87%, and the specificity between 73% and 82%. There was good agreement between readers (κ=0.69–0.77). The sensitivity and specificity of PSA thresholds was 60–87% and 73–100%, respectively. The area under the ROC curve was greatest for pre-biopsy PSA (0.95). Conclusion DCE-MRI performed following whole-gland HIFU has similar sensitivity and specificity and ROC performance to serial PSA measurements for detection of residual or recurrent disease. PMID:22253342

  12. p,p'-Dichlorodiphenyltrichloroethane (p,p'-DDT) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) repress prostate specific antigen levels in human prostate cancer cell lines.

    PubMed

    Wong, Lilian I L; Labrecque, Mark P; Ibuki, Naokazu; Cox, Michael E; Elliott, John E; Beischlag, Timothy V

    2015-03-25

    Despite stringent restrictions on their use by many countries since the 1970s, the endocrine disrupting chemicals, DDT and DDE are still ubiquitous in the environment. However, little attention has been directed to p,p'-DDT and the anti-androgen, p,p'-DDE on androgen receptor (AR) target gene transcription in human cells. Inhibitors of androgenic activity may have a deleterious clinical outcome in prostate cancer screens and progression, therefore we determined whether environmentally relevant concentrations of p,p'-DDT and p,p'-DDE negatively impact AR-regulated expression of prostate-specific antigen (PSA), and other AR target genes in human LNCaP and VCaP prostate cancer cells. Quantitative real-time PCR and immuno-blotting techniques were used to measure intracellular PSA, PSMA and AR mRNA and protein levels. We have shown for the first time that p,p'-DDT and p,p'-DDE repressed R1881-inducible PSA mRNA and protein levels in a dose-dependent manner. Additionally, we used the fully automated COBAS PSA detection system to determine that extracellular PSA levels were also significantly repressed. These chemicals achieve this by blocking the recruitment of AR to the PSA promoter region at 10 μM, as demonstrated by the chromatin immunoprecipitation (ChIP) in LNCaP cells. Both p,p'-DDT and p,p'-DDE repressed R1881-inducible AR protein accumulation at 10 μM. Thus, we conclude that men who have been exposed to either DDT or DDE may produce a false-negative PSA test when screening for prostate cancer, resulting in an inaccurate clinical diagnosis. More importantly, prolonged exposure to these anti-androgens may mimic androgen ablation therapy in individuals with prostate cancer, thus exacerbating the condition by inadvertently forcing adaptation to this stress early in the disease.

  13. The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up

    PubMed Central

    Antonarakis, Emmanuel S.; Feng, Zhaoyong; Trock, Bruce J.; Humphreys, Elizabeth B.; Carducci, Michael A.; Partin, Alan W.; Walsh, Patrick C.; Eisenberger, Mario A.

    2011-01-01

    OBJECTIVE To describe metastasis-free survival (MFS) in men with prostate-specific antigen (PSA) recurrence following radical prostatectomy, and to define clinical prognostic factors modifying metastatic risk. PATIENTS AND METHODS We conducted a retrospective analysis of 450 men treated with prostatectomy at a tertiary hospital between July 1981 and July 2010 who developed PSA recurrence (≥0.2 ng/mL) and never received adjuvant or salvage therapy before the development of metastatic disease. We estimated MFS using the Kaplan–Meier method, and investigated factors influencing the risk of metastasis using Cox proportional hazards regression. RESULTS Median follow-up after prostatectomy was 8.0 years, and after biochemical recurrence was 4.0 years. At last follow-up, 134 of 450 patients (29.8%) had developed metastases, while median MFS was 10.0 years. Using multivariable regressions, two variables emerged as independently predictive of MFS: PSA doubling time (<3.0 vs 3.0–8.9 vs 9.0–14.9 vs ≥15.0 months) and Gleason score (≤6 vs 7 vs 8–10). Using these stratifications of Gleason score and PSA doubling time, tables were constructed to predict median, 5- and 10-year MFS after PSA recurrence. In different patient subsets, median MFS ranged from 1 to 15 years. CONCLUSIONS In men undergoing prostatectomy, MFS after PSA recurrence is variable and is most strongly influenced by PSA doubling time and Gleason score. These parameters serve to stratify men into different risk groups with respect to metastatic progression. Our findings may provide the background for appropriate selection of patients, treatments and endpoints for clinical trials. PMID:21777360

  14. First Prototype of a Web Map Interface for ESA's Planetary Science Archive (PSA)

    NASA Astrophysics Data System (ADS)

    Manaud, N.; Gonzalez, J.

    2014-04-01

    We present a first prototype of a Web Map Interface that will serve as a proof of concept and design for ESA's future fully web-based Planetary Science Archive (PSA) User Interface. The PSA is ESA's planetary science archiving authority and central repository for all scientific and engineering data returned by ESA's Solar System missions [1]. All data are compliant with NASA's Planetary Data System (PDS) Standards and are accessible through several interfaces [2]: in addition to serving all public data via FTP and the Planetary Data Access Protocol (PDAP), a Java-based User Interface provides advanced search, preview, download, notification and delivery-basket functionality. It allows the user to query and visualise instrument observations footprints using a map-based interface (currently only available for Mars Express HRSC and OMEGA instruments). During the last decade, the planetary mapping science community has increasingly been adopting Geographic Information System (GIS) tools and standards, originally developed for and used in Earth science. There is an ongoing effort to produce and share cartographic products through Open Geospatial Consortium (OGC) Web Services, or as standalone data sets, so that they can be readily used in existing GIS applications [3,4,5]. Previous studies conducted at ESAC [6,7] have helped identify the needs of Planetary GIS users, and define key areas of improvement for the future Web PSA User Interface. Its web map interface shall will provide access to the full geospatial content of the PSA, including (1) observation geometry footprints of all remote sensing instruments, and (2) all georeferenced cartographic products, such as HRSC map-projected data or OMEGA global maps from Mars Express. It shall aim to provide a rich user experience for search and visualisation of this content using modern and interactive web mapping technology. A comprehensive set of built-in context maps from external sources, such as MOLA topography, TES

  15. Simulation of Unique Pressure Changing Steps and Situations in Psa Processes

    NASA Technical Reports Server (NTRS)

    Ebner, Armin D.; Mehrotra, Amal; Knox, James C.; LeVan, Douglas; Ritter, James A.

    2007-01-01

    A more rigorous cyclic adsorption process simulator is being developed for use in the development and understanding of new and existing PSA processes. Unique features of this new version of the simulator that Ritter and co-workers have been developing for the past decade or so include: multiple absorbent layers in each bed, pressure drop in the column, valves for entering and exiting flows and predicting real-time pressurization and depressurization rates, ability to account for choked flow conditions, ability to pressurize and depressurize simultaneously from both ends of the columns, ability to equalize between multiple pairs of columns, ability to equalize simultaneously from both ends of pairs of columns, and ability to handle very large pressure ratios and hence velocities associated with deep vacuum systems. These changes to the simulator now provide for unique opportunities to study the effects of novel pressure changing steps and extreme process conditions on the performance of virtually any commercial or developmental PSA process. This presentation will provide an overview of the cyclic adsorption process simulator equations and algorithms used in the new adaptation. It will focus primarily on the novel pressure changing steps and their effects on the performance of a PSA system that epitomizes the extremes of PSA process design and operation. This PSA process is a sorbent-based atmosphere revitalization (SBAR) system that NASA is developing for new manned exploration vehicles. This SBAR system consists of a 2-bed 3-step 3-layer system that operates between atmospheric pressure and the vacuum of space, evacuates from both ends of the column simultaneously, experiences choked flow conditions during pressure changing steps, and experiences a continuously changing feed composition, as it removes metabolic CO2 and H20 from a closed and fixed volume, i.e., the spacecraft cabin. Important process performance indicators of this SBAR system are size, and the

  16. Doctors' perspectives on PSA testing illuminate established differences in prostate cancer screening rates between Australia and the UK: a qualitative study

    PubMed Central

    Pickles, Kristen; Carter, Stacy M; Rychetnik, Lucie; Entwistle, Vikki A

    2016-01-01

    Objectives To examine how general practitioners (GPs) in the UK and GPs in Australia explain their prostate-specific antigen (PSA) testing practices and to illuminate how these explanations are similar and how they are different. Design A grounded theory study. Setting Primary care practices in Australia and the UK. Participants 69 GPs in Australia (n=40) and the UK (n=29). We included GPs of varying ages, sex, clinical experience and patient populations. All GPs interested in participating in the study were included. Results GPs' accounts revealed fundamental differences in whether and how prostate cancer screening occurred in their practice and in the broader context within which they operate. The history of prostate screening policy, organisational structures and funding models appeared to drive more prostate screening in Australia and less in the UK. In Australia, screening processes and decisions were mostly at the discretion of individual clinicians, and varied considerably, whereas the accounts of UK GPs clearly reflected a consistent, organisationally embedded approach based on local evidence-based recommendations to discourage screening. Conclusions The GP accounts suggested that healthcare systems, including historical and current organisational and funding structures and rules, collectively contribute to how and why clinicians use the PSA test and play a significant role in creating the mindlines that GPs employ in their clinic. Australia's recently released consensus guidelines may support more streamlined and consistent care. However, if GP mindlines and thus routine practice in Australia are to shift, to ultimately reduce unnecessary or harmful prostate screening, it is likely that other important drivers at all levels of the screening process will need to be addressed. PMID:27920082

  17. Ferrocene-graphene sheets for high-efficiency quenching of electrochemiluminescence from Au nanoparticles functionalized cadmium sulfide flower-like three dimensional assemblies and sensitive detection of prostate specific antigen.

    PubMed

    Yang, Jiu-Jun; Cao, Jun-Tao; Wang, Hui; Liu, Yan-Ming; Ren, Shu-Wei

    2017-05-15

    A signal-switchable electrochemiluminescence (ECL) aptasensor was presented for sensitive prostate specific antigen (PSA) assay using ferrocene-graphene sheets (Fc-GNs) for high-efficiency quenching of ECL from Au nanoparticles functionalized cadmium sulfide flower-like three dimensional (3D) assemblies (Au-CdS flower-like 3D assemblies). Au-CdS flower-like 3D assemblies were synthesized and employed as luminophore, exhibiting strong and stable ECL intensity, and followed by assembling captured DNA (cDNA) and hybridizing it with half of base sequence of PSA aptamer on the Au-CdS flower-like 3D assemblies modified electrode. The remaining part of the non-complementary base of the aptamer could preferentially adsorb GN with the signal switched "off" state. While in the presence of the PSA, the binding of PSA with aptamer caused desorption of aptamer from the surface of Fc-GNs and was then released from electrode surface, thus allowing the ECL signal enhancement. With the transformation of luminescence signal from "off" to "on", the aptasensor displays high sensitivity for PSA detection with a linear range from 1pgmL(-1) to 25ngmL(-1) and a detection limit of 0.38pgmL(-1)S/N=3). Moreover, this developed method could be successfully applied to the determination of PSA in human serum samples with recoveries of 85.8-104.0%, suggesting great potential applications in biochemical analysis.

  18. Serum levels of prostate-specific antigen and androgens after nasal administration of a gonadotropin releasing hormone-agonist in hirsute women.

    PubMed

    Kocak, Muberra; Tarcan, Aytül; Beydilli, Gülay; Koç, Sevgi; Haberal, Ali

    2004-04-01

    We aimed to determine whether ovarian suppression affects the production rate of prostate-specific antigen (PSA) in hirsute women. A total of 34 hirsute women who had a modified Ferriman-Gallwey (FG) score of > or = 7 and 14, non-hirsute women as the control group were recruited for this prospective controlled study. Serum samples for evaluation of basal hormones and PSA concentration were collected and were analyzed by commercial kits and chemiluminescent enzyme immunoassay. The hirsute women were given 400 microg/day nafarelin acetate for 3 months. Basal hormones, PSA levels and FG scores were then assessed. ANOVA and Tukey test were used to compare differences in means between the hirsute and the non-hirsute group at the beginning of the study. Student's t test, Tukey test and repeated measures variance analysis were used to evaluate differences in the study group and between the women with polycystic ovary syndrome (PCOS) and idiopathic hirsutism after gonadotropin releasing hormone (GnRH)-agonist administration. Statistical significance was assumed with a value of p < 0.05. PCOS and idiopathic hirsutism were diagnosed in 58.8% and 41.2% of 34 hirsute women, respectively. Age and body mass index (BMI) were similar in the hirsute and the control group (p > 0.05). FG scores in the PCOS group (20.3 +/- 1.7) were statistically similar to those of the group with idiopathic hirsutism (17.6 +/- 1.7) (p > 0.05). The non-hirsute women had significantly lower serum PSA concentrations than the hirsute group (p < 0.001). The basal mean level of PSA was 0.095 +/- 0.001 in the PCOS, 0.0061 +/- 0.009 in the idiopathic hirsute and 0.0040 +/- 0.004 ng/ml in the control group. No significant difference in the mean PSA levels was noted between the PCOS and the idiopathic hirsute subgroups before and after GnRH agonist treatment (0.0096 +/- 0.01 and 0.0051 +/- 0.032 ng/ml, respectively) (p > 0.05). FG scores, testosterone, 17alpha-hydroxyprogesterone and dehydroepiandrosterone

  19. Twelve-Month Prostate-Specific Antigen Values and Perineural Invasion as Strong Independent Prognostic Variables of Long-Term Biochemical Outcome After Prostate Seed Brachytherapy

    SciTech Connect

    Ding, William; Lee, John; Chamberlain, David; Cunningham, James; Yang Lixi; Tay, Jonathan

    2012-11-15

    Purpose: To determine whether post-treatment prostate-specific antigen (ptPSA) values at 12 months and other clinical parameters predict long-term PSA relapse-free survival (PRFS) following prostate seed brachytherapy. Methods and Materials: Records of 204 hormone-naieve patients with localized adenocarcinoma of the prostate treated at St. Mary's Regional Medical Center in Reno, NV, and at Carson Tahoe Regional Medical Center in Carson City, NV, between 1998 and 2003, using I-125 or Pd-103 seed brachytherapy, were retrospectively analyzed. Treatment planning was done using a preplanned, modified peripheral loading technique. A total of 185 of 204 patients had PSA records at 12 months after implant. Variables included were age, initial pretreatment PSA, Gleason score, T stage, National Comprehensive Cancer Network (NCCN) risk group (RG), perineural invasion (PNI), external beam boost, dose, and ptPSA levels at 12 months with cutpoints at {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml. Results: Median follow-up was 80 months, and median age was 69 years. The numbers of patients stratified by NCCN low, intermediate, and high RG were 110:65:10, respectively. Monotherapy and boost prescription doses were 145 Gy and 110 Gy for I-125, and 125 Gy and 100 Gy for Pd-103 seeds, respectively. The median dose (D90) was 95.4% of the prescribed dose. The 5-year PRFS at the 12-months ptPSA levels of {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml were 98.5%, 85.7%, 61.5%, and 22.2%, respectively. The 10-year PRFS at the 12-months ptPSA levels of {<=}1 and 1.01 to 2.00 ng/ml were 90.5% and 85.7%, respectively. In multivariate analysis, both ptPSA and PNI were significant independent predictors of PRFS. Hazard ratios (HR) for ptPSA levels at {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml at 12 months were 1, 4.96, 27.57, and 65.10, respectively. PNI had an HR of 6.1 (p = 0.009). Conclusions: Presence of PNI and ptPSA values at 12 months are strong prognostic variables for

  20. Frequency of Propionibacterium acnes Infection in Prostate Glands with Negative Biopsy Results Is an Independent Risk Factor for Prostate Cancer in Patients with Increased Serum PSA Titers

    PubMed Central

    Ito, Takashi; Uchida, Keisuke; Sekine, Masaki; Nakajima, Yutaka; Furukawa, Asuka; Suzuki, Yoshimi; Kumagai, Jiro; Akashi, Takumi

    2017-01-01

    Background Propionibacterium acnes has recently been implicated as a cause of chronic prostatitis and this commensal bacterium may be linked to prostate carcinogenesis. The occurrence of intracellular P. acnes infection in prostate glands and the higher frequency of P. acnes-positive glands in radical prostatectomy specimens from patients with prostate cancer (PCa) than in those from patients without PCa led us to examine whether the P. acnes-positive gland frequency can be used to assess the risk for PCa in patients whose first prostate biopsy, performed due to an increased prostate-specific antigen (PSA) titer, was negative. Methods We retrospectively collected the first and last prostate biopsy samples from 44 patients that were diagnosed PCa within 4 years after the first negative biopsy and from 36 control patients with no PCa found in repeated biopsy for at least 3 years after the first biopsy. We evaluated P. acnes-positive gland frequency and P. acnes-positive macrophage number using enzyme-immunohistochemistry with a P. acnes-specific monoclonal antibody (PAL antibody). Results The frequency of P. acnes-positive glands was higher in PCa samples than in control samples in both first biopsy samples and in combined first and last biopsy samples (P < 0.001). A frequency greater than the threshold (18.5 and 17.7, respectively) obtained by each receiver operating characteristic curve was an independent risk factor for PCa (P = 0.003 and 0.001, respectively) with odds ratios (14.8 and 13.9, respectively) higher than those of serum PSA titers of patients just before each biopsy (4.6 and 2.3, respectively). The number of P. acnes-positive macrophages did not differ significantly between PCa and control samples. Conclusions These results suggested that the frequency of P. acnes-positive glands in the first negative prostate biopsy performed due to increased PSA titers can be supportive information for urologists in planning repeated biopsy or follow-up strategies

  1. Transcutaneous antigen delivery system

    PubMed Central

    Lee, Mi-Young; Shin, Meong-Cheol; Yang, Victor C.

    2013-01-01

    Transcutaneous immunization refers to the topical application of antigens onto the epidermis. Transcutaneous immunization targeting the Langerhans cells of the skin has received much attention due to its safe, needle-free, and noninvasive antigen delivery. The skin has important immunological functions with unique roles for antigen-presenting cells such as epidermal Langerhans cells and dermal dendritic cells. In recent years, novel vaccine delivery strategies have continually been developed; however, transcutaneous immunization has not yet been fully exploited due to the penetration barrier represented by the stratum corneum, which inhibits the transport of antigens and adjuvants. Herein we review recent achievements in transcutaneous immunization, focusing on the various strategies for the enhancement of antigen delivery and vaccination efficacy. [BMB Reports 2013; 46(1): 17-24] PMID:23351379

  2. A novel immobilization strategy for electrochemical detection of cancer biomarkers: DNA-directed immobilization of aptamer sensors for sensitive detection of prostate specific antigens.

    PubMed

    Yang, Zhugen; Kasprzyk-Hordern, Barbara; Goggins, Sean; Frost, Christopher G; Estrela, Pedro

    2015-04-21

    We report on a novel strategy for DNA aptamer immobilization to develop sensitive electrochemical detection of a protein biomarker, with prostate specific antigen (PSA) as a case biomarker. Thiolated single-stranded DNA (ssDNA) was co-immobilized with 3-mercapto-1-propanol on gold electrodes, and used as a scaffold for DNA aptamer attachment through hybridization of the aptamer overhang (so-called "DNA-directed immobilization aptamer sensors", DDIAS). In the approach, the complementary DNA aptamer against PSA was assembled by the probe ssDNA onto the electrode to detect PSA; or the probe ssDNA directly hybridized with a complementary DNA aptamer/PSA complex following their pre-incubation in solution, so-called 'on-chip' and 'in-solution' methods, respectively. A double stranded DNA intercalator with a ferrocenyl (Fc) redox marker was synthesized to evaluate the feasibility of the strategy. The results demonstrate that the 'in-solution' method offers a favourable medium (in a homogeneous solution) for the binding between the aptamer and PSA, which shows to be more efficient than the 'on-chip' approach. DDIAS shows promising analytical performance under optimized conditions, with a limit of detection in the range of fM and low non-specific adsorption.

  3. Heart failure

    PubMed Central

    2011-01-01

    Introduction Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of multidisciplinary interventions for heart failure? What are the effects of exercise in people with heart failure? What are the effects of drug treatments for heart failure? What are the effects of devices for treatment of heart failure? What are the effects of coronary revascularisation for treatment of heart failure? What are the effects of drug treatments in people at high risk of heart failure? What are the effects of treatments for diastolic heart failure? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 80 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: aldosterone receptor antagonists, amiodarone, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, anticoagulation, antiplatelet agents, beta-blockers, calcium

  4. [Relationship between PTH and PSA values in patients with pathological finding of benign prostatic hyperplasia].

    PubMed

    Romeo, Salvatore; Napoli, Giancarlo; Melloni, Guglielmo; Dispensa, Nino; Melloni, Darwin

    2012-01-01

    The functional relationship between parathyroid glands and prostatic gland is commonly very well known. The aim of our study was to investigate the relationship between serum levels of PTH and serum levels of PSA in patients with pathological finding of BPH. According to 261 transrectal ultrasound-guided prostatic biopsies performed from March 2009 to March 2010, 75 patients, responding to our inclusion criteria, were selected. 26 patients (34.6%) ended the study. All patients with high serum levels of PSA (>4 ng/mL), with histological diagnosis of benign prostatic hyperplasia, underwent the assay of serum levels of PTH. We observed high levels of PTH (> 66 pg/mL) in 9 patients (35.2%).

  5. Optimized design of PSA nitrogen-manufacturing system based on PLC

    NASA Astrophysics Data System (ADS)

    Nie, Zongyao; Ma, Xiushui; Jiang, Jun

    2010-12-01

    Firstly introducing principle and technological process of PSA nitrogen-manufacturing system, on condition of its high air consumption and weak in nitrogen-manufacturing system at present. We repeatedly studied the controlled object in this process, analyzed the PLC procedure based on the program rule of PLC of Siemens S7-200 series, then re-program PLC procedure without altering the nitrogen production technique of PSA nitrogen-manufacturing system. At the same time, in order to improve the operation efficiency of the response of action, we also did experiment and demonstration in the consistency of the I/O port and peripheral equipment. In this paper, through optimization of hardware and software design, the nitrogen producing cost was calculated at RMB 0.35 per m3, declined by 12% from the original RMB 0.4 per m3.

  6. Optimized design of PSA nitrogen-manufacturing system based on PLC

    NASA Astrophysics Data System (ADS)

    Nie, Zongyao; Ma, Xiushui; Jiang, Jun

    2011-05-01

    Firstly introducing principle and technological process of PSA nitrogen-manufacturing system, on condition of its high air consumption and weak in nitrogen-manufacturing system at present. We repeatedly studied the controlled object in this process, analyzed the PLC procedure based on the program rule of PLC of Siemens S7-200 series, then re-program PLC procedure without altering the nitrogen production technique of PSA nitrogen-manufacturing system. At the same time, in order to improve the operation efficiency of the response of action, we also did experiment and demonstration in the consistency of the I/O port and peripheral equipment. In this paper, through optimization of hardware and software design, the nitrogen producing cost was calculated at RMB 0.35 per m3, declined by 12% from the original RMB 0.4 per m3.

  7. Biosensor based on a silicon nanowire field-effect transistor functionalized by gold nanoparticles for the highly sensitive determination of prostate specific antigen.

    PubMed

    Presnova, Galina; Presnov, Denis; Krupenin, Vladimir; Grigorenko, Vitaly; Trifonov, Artem; Andreeva, Irina; Ignatenko, Olga; Egorov, Alexey; Rubtsova, Maya

    2017-02-15

    We have demonstrated label-free and real-time detection of prostate specific antigen (PSA) in human serum using silicon nanowire field effect transistors (NW FETs) with Schottky contacts (Si-Ti). The NW FETs were fabricated from SOI material using high-resolution e-beam lithography, thin film vacuum deposition and reactive-ion etching processes eliminating complicated processes of doping and thermal annealing. This allowed substantial simplifying the transistors manufacturing. A new method for covalent immobilization of half-fragments of antibodies on silicon modified by 3-glycidopropyltrimethoxysilane with thiol groups and 5nm gold nanoparticles (GNPs) was established. NW FETs functionalized by GNPs revealed extremely high pH sensitivity of 70mV/pH and enhanced electrical performance in the detection of antigen due to enhanced surface/volume ratio, favorable orientation of antibody active sites and approaching the source of the electric field close to the transistor surface. Si NWFETs were applied for quantitative detection of PSA in a buffer and human serum diluted 1/100. Response time was about 5-10s, and analysis time per sample was 1min. The limit of PSA detection was of 23fg/mL, concentration range of 23fg/mL-500ng/mL (7 orders of magnitude). The PSA concentrations determined by the NW FETs in serum were compared with well-established ELISA method. The results matched well with the correlation coefficient of 0.97.

  8. Target-triggered signal turn-on detection of prostate specific antigen based on metal-enhanced fluorescence of Ag@SiO2@SiO2-RuBpy composite nanoparticles

    NASA Astrophysics Data System (ADS)

    Deng, Yun-Liang; Xu, Dang-Dang; Pang, Dai-Wen; Tang, Hong-Wu

    2017-02-01

    A three-layer core-shell nanostructure consisting of a silver core, a silica spacer, and a fluorescent dye RuBpy-doped outer silica layer was fabricated, and the optimal metal-enhanced fluorescence (MEF) distance was explored through adjusting the thickness of the silica spacer. The results show that the optimal distance is ˜10.4 nm with the maximum fluorescence enhancement factor 2.12. Then a new target-triggered MEF ‘turn-on’ strategy based on the optimized composite nanoparticles was successfully constructed for quantitative detection of prostate specific antigen (PSA), by using RuBpy as the energy donor and BHQ-2 as the acceptor. The hybridization of the complementary DNA of PSA-aptamer immobilized on the surface of the MEF nanoparticles with PSA-aptamer modified with BHQ-2, brought BHQ-2 in close proximity to RuBpy-doped silica shell and resulted in the decrease of fluorescence. In the presence of target PSA molecules, the BHQ-PSA aptamer is dissociated from the surface of the nanoparticles with the fluorescence switched on. Therefore, the assay of PSA was achieved by measuring the varying fluorescence intensity. The results show that PSA can be detected in the range of 1-100 ng ml-1 with a detection limit of 0.20 ng ml-1 (6.1 pM), which is 6.7-fold increase of that using hollow RuBpy-doped silica nanoparticles. Moreover, satisfactory results were obtained when PSA was detected in 1% serum.

  9. Effect of lubricants and a vaginal spermicide gel on the detection of prostate specific antigen, a biomarker of semen exposure, using a quantitative (Abbott ARCHITECT) assay☆, ☆☆, ★

    PubMed Central

    Snead, Margaret C.; Melendez, Johan H.; Kourtis, Athena P.; Chaney, Dorothy M.; Brown, Teresa M.; Black, Carolyn M.; Mauck, Christine K.; Schwartz, Jill L.; Zenilman, Jonathan M.; Jamieson, Denise J.; Macaluso, Maurizio; Doncel, Gustavo F.

    2015-01-01

    Objectives Little is known about the effects of commonly used lubricants on detection of biomarkers of semen exposure. We investigated the in vitro effect of Gynol®, K-Y Jelly®, Replens®, Astroglide®, Carbopol, and Silicorel on quantitative detection of prostate specific antigen (PSA). Study Design A predetermined concentration of each of the gels was added to serially diluted semen samples. Additionally, serial dilutions of each of the gels were added to three different semen dilutions (high, medium, or low). The resulting samples were tested for PSA on the Abbott ARCHITECT System. Results When using the Abbott ARCHITECT system, the only products that inhibited PSA detection were Gynol® and Replens®. The inhibition caused by Gynol® was dose-dependent, but that of Replens was dose-independent. K-Y Jelly®-spiked samples had higher PSA values than controls. Conclusions Caution is warranted when using the Abbott quantitative assay for PSA detection as a biomarker of semen exposure in settings where Gynol®, Replens® or K-Y Jelly® might also have been used. Neither Astroglide® nor Silicorel inhibited PSA detection. Additional studies evaluating other vaginal products, including microbicides, and their effects on other assays, are needed. In vivo studies will be especially important to optimize PSA detection from clinical samples. Implications Researchers should consider the potential for specific lubricants or any vaginal products to affect the particular assay used for semen biomarker detection. The Abbott ARCHITECT’s total PSA assay should not be used with the product Replens. Caution is warranted when using the assay in settings where Gynol or K-Y jelly may have been used. PMID:24314911

  10. Non-granule PSA-NCAM immunoreactive neurons in the rat hippocampus.

    PubMed

    Nacher, Juan; Blasco-Ibáñez, José M; McEwen, Bruce S

    2002-03-15

    The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) continues to be expressed in the adult hippocampus, mainly in a subset of neurons located in the innermost portion of the granule cell layer. PSA-NCAM immunoreactive neurons have also been described outside this layer in humans, where they are severely reduced in schizophrenic brains. Given this important clinical implication, we were interested in finding whether similar neurons existed in the adult rat hippocampus and to characterize their distribution, morphology and phenotype. PSA-NCAM immunocytochemistry reveals labeled neurons in the subiculum, fimbria, alveus, hilus, and stratum oriens, lucidum and radiatum of CA3 and CA1. They are mainly distributed in the ventral hippocampus, and have polygonal or fusiform somata with multipolar or bipolar morphology. These neurons show long straight dendrites, which reach several strata and even enter the fimbria and the alveus. These dendrites are often varicose, appear devoid of excrescences and apparently do not show spines. Most of these neurons display GABA immunoreactivity and further analysis has shown that a subpopulation expresses calretinin, but not somatostatin, neuropeptide Y, parvalbumin, calbindin or NADPH diaphorase. Our study demonstrates that there is an important subpopulation of PSA-NCAM immunoreactive neurons, many of which can be considered interneurons, outside the rat granule cell layer, probably homologous to those described in the human hippocampus. The presence of the polysialylated form of NCAM in these neurons could indicate that they are undergoing continuous remodeling during adulthood and may have an important role in hippocampal structural plasticity.

  11. Prostate Cancer Survivors with Rising PSA and Their Spouses: Treatment Decision Making and Quality of Life

    DTIC Science & Technology

    2009-12-31

    Center, Philadelphia. Patients will have been diagnosed with rising PSA but have no clinical evidence of cancer . Eligible patients and their spouse...From a psychological point of view, patients and their spouses/partners are forced to deal with a disease they believed they have overcome. For a... patients and their spouse/partners have to deal with the uncertainty of a cancer recurrence and cancer spread, and the possibility of death. Very

  12. Influence of dioxin exposure upon levels of prostate-specific antigen and steroid hormones in Vietnamese men.

    PubMed

    Sun, Xian Liang; Kido, Teruhiko; Honma, Seijiro; Okamoto, Rie; Manh, Ho Dung; Maruzeni, Shoko; Nishijo, Muneko; Nakagawa, Hideaki; Nakano, Takeshi; Koh, Eitetsu; Takasuga, Takumi; Nhu, Dang Duc; Hung, Nguyen Ngoc; Son, Le Ke

    2016-04-01

    Most studies on the relationship between Agent Orange and prostate cancer have focused on US veterans of the Vietnam War. There have been few studies focusing on the relationship between levels of prostate-specific antigen (PSA) and dioxins or steroid hormones in Vietnamese men. In 2009-2011, we collected blood samples from 97 men who had resided in a "dioxin hotspot" and 85 men from a non-sprayed region in Vietnam. Then levels of PSA, dioxins, and steroid hormones were analyzed. Levels of most dioxins, furans, and non-ortho polychlorinated biphenyls were higher in the hotspot than those in the non-sprayed region. Levels of testosterone, dehydroepiandrosterone, and estradiol differed significantly between the hotspot and the non-sprayed region, but there were no correlations between levels of PSA and steroid hormones and dioxins in either of the two regions. Our findings suggest that PSA levels in Vietnamese men are not associated with levels of dioxin or steroid hormones in these two regions.

  13. Application of PSA to review and define technical specifications for advanced nuclear power plants

    SciTech Connect

    Kim, I.S.; Samanta, P.K.; Reinhart, F.M.; Wohl, M.L.

    1995-11-01

    As part of the design certification process, probabilistic safety assessments (PSAS) are performed at the design stage for each advanced nuclear power plant. Among other usages, these PSAs are important inputs in defining the Technical Specifications (TSs) for these plants. Knowledge gained from their use in improving the TSs for operating nuclear power plants is providing methods and insights for using PSAs at this early stage. Evaluating the safety or the risk significance of the TSs to be defined for an advanced plant encompasses diverse aspects: (a) determining the basic limiting condition for operation (LCO); (b) structuring conditions associated with the LCO; (c) defining completion times (equivalent to allowed outage times in the TS for conventional plants); and, (d) prescribing required actions to be taken within the specified completion times. In this paper, we consider the use of PSA in defining the TSs for an advanced nuclear plant, namely General Electric`s Advanced Boiling Water Reactor (ABWR). Similar approaches are being taken for ABB-CE`s System 80+ and Westinghouse`s AP-600. We discuss the general features of an advanced reactor`s TS, how PSA is being used in reviewing the TSs, and we give an example where the TS submittal was reviewed using a PSA-based analysis to arrive at the requirements for the plant.

  14. Multiple external hazards compound level 3 PSA methods research of nuclear power plant

    NASA Astrophysics Data System (ADS)

    Wang, Handing; Liang, Xiaoyu; Zhang, Xiaoming; Yang, Jianfeng; Liu, Weidong; Lei, Dina

    2017-01-01

    2011 Fukushima nuclear power plant severe accident was caused by both earthquake and tsunami, which results in large amount of radioactive nuclides release. That accident has caused the radioactive contamination on the surrounding environment. Although this accident probability is extremely small, once such an accident happens that is likely to release a lot of radioactive materials into the environment, and cause radiation contamination. Therefore, studying accidents consequences is important and essential to improve nuclear power plant design and management. Level 3 PSA methods of nuclear power plant can be used to analyze radiological consequences, and quantify risk to the public health effects around nuclear power plants. Based on multiple external hazards compound level 3 PSA methods studies of nuclear power plant, and the description of the multiple external hazards compound level 3 PSA technology roadmap and important technical elements, as well as taking a coastal nuclear power plant as the reference site, we analyzed the impact of off-site consequences of nuclear power plant severe accidents caused by multiple external hazards. At last we discussed the impact of off-site consequences probabilistic risk studies and its applications under multiple external hazards compound conditions, and explained feasibility and reasonableness of emergency plans implementation.

  15. Vaginal myofibroblastoma with glands expressing mammary and prostatic antigens.

    PubMed

    Wallenfels, I; Chlumská, A

    2012-01-01

    A case of unusual vaginal myofibroblastoma containing glands which expressed mammary and prostatic markers is described. The tumor occurred in 70-year-old woman in the proximal third of the vagina. It showed morphology and immunophenotype typical of so-called cervicovaginal myofibroblastoma. The peripheral zone of the lesion contained a few groups of glands suggesting vaginal adenosis or prostatic-type glands on initial examination. The glands showed a surprising simultaneous expression of mammary markers mammaglobin and GCDFP-15 and prostatic markers prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP). Immunostains for alpha-smooth muscle actin, p63 and CD10 highlighted the myoepithelial cell layer of the glands. The finding indicates that simultaneous use of both mammary and prostatic markers for examination of unusual glandular lesions in the vulvovaginal location can be helpful for an exact diagnosis, and can contribute to better understanding of prostatic and mammary differentiations in the female lower genital tract.

  16. Heart failure

    PubMed Central

    2010-01-01

    Introduction Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug treatments, and of drug and invasive treatments, for heart failure? What are the effects of angiotensin-converting enzyme inhibitors in people at high risk of heart failure? What are the effects of treatments for diastolic heart failure? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 85 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: aldosterone receptor antagonists, amiodarone, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, anticoagulation, antiplatelet agents, beta-blockers, calcium channel blockers, cardiac resynchronisation therapy, digoxin (in people already receiving diuretics and angiotensin-converting enzyme inhibitors), exercise, hydralazine plus isosorbide dinitrate, implantable cardiac

  17. Effects of PSA Removal from NCAM on the Critical Period Plasticity Triggered by the Antidepressant Fluoxetine in the Visual Cortex

    PubMed Central

    Guirado, Ramon; La Terra, Danilo; Bourguignon, Mathieu; Carceller, Hector; Umemori, Juzoh; Sipilä, Pia; Nacher, Juan; Castrén, Eero

    2016-01-01

    Neuronal plasticity peaks during critical periods of postnatal development and is reduced towards adulthood. Recent data suggests that windows of juvenile-like plasticity can be triggered in the adult brain by antidepressant drugs such as Fluoxetine. Although the exact mechanisms of how Fluoxetine promotes such plasticity remains unknown, several studies indicate that inhibitory circuits play an important role. The polysialylated form of the neural cell adhesion molecules (PSA-NCAM) has been suggested to mediate the effects of Fluoxetine and it is expressed in the adult brain by mature interneurons. Moreover, the enzymatic removal of PSA by neuroaminidase-N not only affects the structure of interneurons but also has been shown to play a role in the onset of critical periods during development. We have here used ocular dominance plasticity in the mouse visual cortex as a model to investigate whether removal of PSA might influence the Fluoxetine-induced plasticity. We demonstrate that PSA removal in the adult visual cortex alters neither the baseline ocular dominance, nor the fluoxetine-induced shift in the ocular dominance. We also show that both chronic Fluoxetine treatment and PSA removal independently increase the basal FosB expression in parvalbumin (PV) interneurons in the primary visual cortex. Therefore, our data suggest that although PSA-NCAM regulates inhibitory circuitry, it is not required for the reactivation of juvenile-like plasticity triggered by Fluoxetine. PMID:26903807

  18. Antigen injection (image)

    MedlinePlus

    Leprosy is caused by the organism Mycobacterium leprae . The leprosy test involves injection of an antigen just under ... if your body has a current or recent leprosy infection. The injection site is labeled and examined ...

  19. Kidney (Renal) Failure

    MedlinePlus

    ... News Physician Resources Professions Site Index A-Z Kidney Failure Kidney failure, also known as renal failure, ... evaluated? How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain ...

  20. Reduction of PSA values by combination pharmacological therapy in patients with chronic prostatitis: implications for prostate cancer detection.

    PubMed

    Magri, Vittorio; Trinchieri, Alberto; Montanari, Emanuele; Del Nero, Alberto; Mangiarotti, Barbara; Zirpoli, Pasquale; de Eguileor, Magda; Marras, Emanuela; Ceriani, Isabella; Vral, Anne; Perletti, Gianpaolo

    2007-06-01

    We identified from our clinical database a total of 471 patients affected by cat. II chronic bacterial prostatitis (CBP), cat. III (IIIa and IIIb) chronic pelvic pain syndrome (CP/CPPS), or cat. IV asymptomatic inflammatory prostatitis (AIP), according to NIH criteria. 132 intent-to-treat patients, showing levels of PSA > or =4 ng/mL, were subjected to a 6-week course of combination pharmacological therapy with 500 mg/day ciprofloxacin, 500 mg/day azithromycin (3 days/week), 10 mg/day alfuzosin and 320 mg b.i.d. Serenoa repens extract. At the end of treatment, 111 per-protocol patients belonging to all categories of prostatitis showed a total 32.5% reduction of PSA levels. In the same group, 66 patients (59.4%) showed "normalization" of PSA values under the 4 ng/mL limit. Patients affected by cat. IIIb CP/CPPS showed the highest PSA reduction and normalization rates (40% and 68.4%, respectively). Follow-up data show that, after a marked, significant reduction at completion of therapy, PSA levels, urine peak flow rates and NIH-CPSI symptom scores remained constant or decreased throughout a period of 18 months in patients showing normalization of PSA values. Prostatic biopsy was proposed to 45 patients showing persistently high PSA values (> or = 4 ng/mL) at the end of treatment. Fourteen patients rejected biopsy; of the remaining 31, 10 were diagnosed with prostate cancer. Four months after a first biopsy, a second biopsy was proposed to the 21 patients with a negative first diagnosis and persistently elevated PSA levels. Three patients rejected the procedure; of the remaining 18, four were diagnosed with prostatic carcinoma. In summary, combination pharmacological therapy decreased the number of patients undergoing prostatic biopsy from 111 to 45. Normalization of PSA values in 59.4% of patients--not subjected to biopsy--increased the prostate cancer detection rate from 12.6% (14/111) to 31.1% (14/45). The reduction of PSA after a 6-week course of therapy was

  1. The Effect of Increasing Doses of Saw Palmetto Fruit Extract on Serum PSA Levels: Analysis of the CAMUS Randomized Trial

    PubMed Central

    Andriole, Gerald L.; McCullum-Hill, Christie; Sandhu, Gurdarshan S.; Crawford, E. David; Barry, Michael J.; Cantor, Alan

    2014-01-01

    Purpose Saw palmetto extracts are used for treating lower urinary tract symptoms in men despite level I evidence concluding that saw palmetto was ineffective in reducing lower urinary symptoms. We sought to determine whether higher doses of saw palmetto as studied in CAMUS affect serum PSA levels. Materials and Methods The CAMUS trial was a randomized, placebo-controlled double blind multi-centered North American trial conducted between June 5, 2008 and October 10, 2012 in which 369 men >45 years of age with AUA symptom score ≥ 8 and ≤ 24 were randomly assigned to placebo or dose escalation saw palmetto, which consisted of 320mg for first 24 weeks to 640mg for next 24 weeks to 960mg for last 24 weeks of this 72 week trial. Serum PSA levels (Beckman-Coulter) were obtained at baseline and at weeks 24, 48 and 72 and were compared between treatment groups using the pooled t and Fisher's exact tests. Results Serum PSA levels were similar at baseline for the placebo (1.93 ± 1.59 ng/ml) and saw palmetto groups (2.20 ± 1.95, p = 0.16). Changes in PSA levels over the course of the study were similar: placebo group mean change 0.16 ± 1.08 ng/ml and saw palmetto group mean change 0.23 ± 0.83 ng/ml (p value 0.50). Additionally, no differential effect on serum PSA levels was observed between treatment arms when groups were stratified by baseline PSA values. Conclusions Saw palmetto extract does not affect serum PSA levels more than placebo even at relatively high doses. PMID:23253958

  2. A novel sandwich-type electrochemical immunosensor for PSA detection based on PtCu bimetallic hybrid (2D/2D) rGO/g-C3N4.

    PubMed

    Feng, Jinhui; Li, Yueyun; Li, Mingdang; Li, Faying; Han, Jian; Dong, Yunhui; Chen, Zhiwei; Wang, Ping; Liu, Hui; Wei, Qin

    2017-05-15

    In this work, a sensitive sandwich-type electrochemical immunosensor was designed for the quantitative detection of prostate-specific antigen (PSA) by amperometric i-t. The Au loaded on thionine functionalized graphene oxide (Au@Th/GO) was used as a platform to immobilize primary antibodies (Ab1) and accelerate the electron transfer on the electrode interface. PtCu bimetallic hybrid were loaded on 2D/2D reduced graphene oxide/graphitic carbon nitride (PtCu@rGO/g-C3N4) with large surface area and biocompatibility, which were employed as labels for combining secondary antibodies (Ab2) and amplifying signals to improve the sensitivity of the designed immunosensor which attributes to its good activity for the reduction of hydrogen peroxide (H2O2). Under optimal conditions, the designed immunosensor exhibited a linear concentration range from 50fg/mL to 40ng/mL, with a low detection limit of 16.6fg/mL (S/N=3) for PSA. Additionally, the designed immunosensor showed acceptable selectivity, reproducibility and stability. The satisfactory results in analyze human serum samples indicated potential application promising in clinical monitoring of tumor markers.

  3. Infectious mononucleosis, other infections and prostate-specific antigen concentration as a marker of prostate involvement during infection.

    PubMed

    Sutcliffe, Siobhan; Nevin, Remington L; Pakpahan, Ratna; Elliott, Debra J; Langston, Marvin E; De Marzo, Angelo M; Gaydos, Charlotte A; Isaacs, William B; Nelson, William G; Sokoll, Lori J; Walsh, Patrick C; Zenilman, Jonathan M; Cersovsky, Steven B; Platz, Elizabeth A

    2016-05-01

    Although Epstein-Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult-onset IM on the prostate by measuring prostate-specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n = 55) and controls as men without an IM diagnosis (n = 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n = 90) and controls (n = 220). We found that IM cases were more likely to have a large PSA rise than controls (≥ 20 ng/mL: 19.7% versus 8.8%, p = 0.027; ≥ 40% rise: 25.7% versus 9.4%, p = 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p = 0.020; 27.7% versus 18.0%, p = 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men.

  4. Triple sensitivity amplification for ultrasensitive electrochemical detection of prostate specific antigen.

    PubMed

    Tang, Zhongxue; Wang, Liyuan; Ma, Zhanfang

    2017-06-15

    In general, current difference (ΔI) due to immunoreactions is significant in determining biosensor sensitivity. In this work, a new strategy of triple sensitivity amplification for ultrasensitive electrochemical detection of prostate specific antigen (PSA) was developed. Au-poly(methylene blue) (Au-PMB) was implemented as a redox species with strong current signal at -0.144V and used to fabricate the substrate of the biosensor. Conductive reduced graphene oxide-Au nanocomposites (Au-rGO) were coated on the Au-PMB modified glassy carbon electrode (GCE) to amplify current signal. After peptides (CEHSSKLQLAK-NH2) were fixed on the Au-rGO/Au-PMB/GCE, the fixed peptides reacted with glutaraldehyde to immobilize polydopamine-Au-horse radish peroxidase nanocomposites (PDA-Au-HRP). The electrochemical sensing interface for PSA was realized. Due to smaller resistance compared to antibodies, the peptides which can be cleaved specifically by PSA were employed. After the incubation of PSA, a large ΔI was obtained and behaved as the decrease of current signal. Then the remaining PDA-Au-HRP accelerated an enzyme-catalyzed precipitation reaction between 4-chloro-1-naphthol and H2O2. A further decrease in current signal (namely the increase in ΔI) resulted from the poorly conductive precipitation adhering onto the biosensor. The designed biosensor presented a wide linear range from 1.0fgmL(-1) to 100ngmL(-1) with an ultralow detection limit of 0.11fgmL(-1).

  5. Exploring Functional β-Cell Heterogeneity In Vivo Using PSA-NCAM as a Specific Marker

    PubMed Central

    Karaca, Melis; Castel, Julien; Tourrel-Cuzin, Cécile; Brun, Manuel; Géant, Anne; Dubois, Mathilde; Catesson, Sandra; Rodriguez, Marianne; Luquet, Serge; Cattan, Pierre; Lockhart, Brian; Lang, Jochen; Ktorza, Alain

    2009-01-01

    Background The mass of pancreatic β-cells varies according to increases in insulin demand. It is hypothesized that functionally heterogeneous β-cell subpopulations take part in this process. Here we characterized two functionally distinct groups of β-cells and investigated their physiological relevance in increased insulin demand conditions in rats. Methods Two rat β-cell populations were sorted by FACS according to their PSA-NCAM surface expression, i.e. βhigh and βlow-cells. Insulin release, Ca2+ movements, ATP and cAMP contents in response to various secretagogues were analyzed. Gene expression profiles and exocytosis machinery were also investigated. In a second part, βhigh and βlow-cell distribution and functionality were investigated in animal models with decreased or increased β-cell function: the Zucker Diabetic Fatty rat and the 48 h glucose-infused rat. Results We show that β-cells are heterogeneous for PSA-NCAM in rat pancreas. Unlike βlow-cells, βhigh-cells express functional β-cell markers and are highly responsive to various insulin secretagogues. Whereas βlow-cells represent the main population in diabetic pancreas, an increase in βhigh-cells is associated with gain of function that follows sustained glucose overload. Conclusion Our data show that a functional heterogeneity of β-cells, assessed by PSA-NCAM surface expression, exists in vivo. These findings pinpoint new target populations involved in endocrine pancreas plasticity and in β-cell defects in type 2 diabetes. PMID:19440374

  6. Experimental set-up for three PHOEBUS type large-area heliostats at the PSA

    SciTech Connect

    Haeger, M.; Schiel, W.; Romero, M.; Schmitz-Goeb, M.

    1995-11-01

    Three large-area heliostat prototypes are being erected at the Plataforma Solar de Almeria by Spanish and German industry. The objective is to demonstrate their technical and economical suitability for a PHOEBUS power tower plant. The two different heliostat designs including two 100 ml glass/metal faceted heliostats and one 150 m{sup 2} stressed membrane heliostat are tested at a representative distance of 485 m to the PSA`s CESA tower. The paper introduces the heliostat designs and test set-up, such as location, targets, flux measurement, data acquisition and control.

  7. Anisotropic In Situ-Coated AuNPs on Screen-Printed Carbon Surface for Enhanced Prostate-Specific Antigen Impedimetric Aptasensor

    NASA Astrophysics Data System (ADS)

    Do, Tram T. N.; Van Phi, Toan; Nguy, Tin Phan; Wagner, Patrick; Eersels, Kasper; Vestergaard, Mun'delanji C.; Truong, Lien T. N.

    2016-12-01

    An impedimetric aptasensor has been used to study the effect of charge transfer on the binding of prostate-specific antigen (PSA) to its aptamer. Full understanding of this mechanism will be beneficial to further improve its sensitivity for PSA detection in human semen at physiologically relevant concentrations. Bare gold electrodes (SPAuEs) and gold nanoparticles (AuNPs)-coated screen-printed carbon ink electrodes (AuNPs/SPCEs) were coated with aptamer solution at various concentrations and the sensor response to increasing PSA concentration in buffer solution examined. AuNPs were deposited onto carbon electrodes in 10 cycles. AuNPs/SPCEs were then coated with a self-assembled monolayer (SAM) of 16-mercaptohexadecanoic acid prior to aptamer immobilization at dose of 5 μg mL-1. The results indicate that anisotropic AuNPs/SPCEs outperform bare gold electrodes in terms of decreased amount of aptamer bunches as well as the number of intermediate PSA-aptamer complexes formed on the electrode surface. The key finding is that the fabricated aptasensor is sensitive enough [limit of detection (LoD) 1.95 ng mL-1] for early diagnosis of prostate cancer and displays linear response in the physiologically relevant concentration range (0 ng mL-1 to 10 ng mL-1), as shown by the calibration curve of the relative change in electron transfer resistance (ΔR CT) versus PSA concentration when aptamer/SAM/AuNPs/SPCEs were exposed to buffer containing PSA at different concentrations.

  8. Age-Adjusted PSA Levels in Prostate Cancer Prediction: Updated Results of the Tyrol Prostate Cancer Early Detection Program

    PubMed Central

    Heidegger, Isabel; Fritz, Josef; Klocker, Helmut; Pichler, Renate

    2015-01-01

    Objective To reduce the number of unnecessary biopsies in patients with benign prostatic disease, however, without missing significant PCa the present study re-evaluates the age-dependent PSA cut-offs in the Tyrol Prostate Cancer (PCa) early detection program. Patients and Methods The study population included 2225 patients who underwent prostate biopsy due to elevated PSA levels at our department. We divided our patient collective into four age groups: ≤49 years (n = 178), 50-59 years (n = 597), 60-69 years (n = 962) and ≥70 years (n = 488). We simulated different scenarios for PSA cut-off values between 1.25 and 6 ng/mL and fPSA% between 15 and 21% for all four age groups and calculated sensitivity, specificity, confidence intervals and predictive values. Results PCa was detected in 1218 men (54.7%). We found that in combination with free PSA ≤21% the following PSA cut-offs had the best cancer specificity: 1.75 ng/ml for men ≤49 years and 50-59 years, 2.25 ng/ml for men aged 60-69 years and 3.25 ng/ml for men ≥70 years. Using these adjusted PSA cut-off values all significant tumors are recognized in all age groups, yet the number of biopsies is reduced. Overall, one biopsy is avoided in 13 to 14 men (number needed to screen = 13.3, reduction of biopsies = 7.5%) when decision regarding biopsy is done according to the “new” cut-off values instead of the “old” ones. For the different age groups the number needed to screen to avoid one biopsy varied between 9.2 (≤49 years) and 17.4 (50-59 years). Conclusion With “new”, fine-tuned PSA cut-offs we detect all relevant PCa with a significant reduction of biopsies compared to the “old” cut-off values. Optimization of age-specific PSA cut-offs is one step towards a smarter strategy in the Tyrol PCa Early Detection Program. PMID:26218594

  9. Diagnostic Antigens of Leishmania.

    DTIC Science & Technology

    1994-01-31

    braziliensis (MHOM/BR/75/M2903), L. chagasi (MJOM/BR/82/BA-2,C 1), L. donovani (MHOMiEt/67iHU3), Leishmania guyanensis (MIHOMJBR/75/M4147), L. infantum (IPT-1...comparative test to a variety of other recombinant Leishmania antigens including L. chagasi hsp70, L. braziliensis hsp83/90, L. braziliensis eIF4A, L...34 4. AD CONTRACT NO: DAMD17-92-C-2082 EC•£ 2 j 994 ’i, L TITLE: DIAGNOSTIC ANTIGENS OF LEISHMANIA L PRINCIPAL INVESTIGATOR: Steven G. Reed, Ph.D

  10. A claudin 3 and claudin 4-targeted Clostridium perfringens protoxin is selectively cytotoxic to PSA-producing prostate cancer cells.

    PubMed

    Romanov, Victor; Whyard, Terry C; Waltzer, Wayne C; Gabig, Theodore G

    2014-09-01

    Prostate cancer is the second leading cause of non-cutaneous cancer-related death in males, and effective strategies for treatment of metastatic disease are currently limited. The tight junction proteins, claudin 3 and claudin 4, serve as cell-surface receptors for the pore-forming Clostridium perfringens enterotoxin [CPE]. Most prostate cancer cells overexpress claudin 3 and claudin 4, and claudins are aberrantly distributed over the plasma membrane, making these cells particularly sensitive to cytolysis by CPE. Prostate cancer cells secrete PSA locally that is proteolytically active; however, circulating PSA is inactivated via binding to protease inhibitors. To overcome systemic toxicity of CPE, a modified protoxin was constructed with a tethered ligand attached to the C-terminus connected by a flexible linker containing a PSA-specific protease cleavage site. This engineered protoxin selectively and efficiently lyses PSA-producing prostate cancer cells whereas CLDN3 and CLDN4 positive cells that do not express PSA are resistant to cytolysis.

  11. Early Choline Levels From 3-Tesla MR Spectroscopy After Exclusive Radiation Therapy in Patients With Clinically Localized Prostate Cancer are Predictive of Plasmatic Levels of PSA at 1 Year

    SciTech Connect

    Crehange, Gilles; Maingon, Philippe; Gauthier, Melanie; Parfait, Sebastien; Cochet, Alexandre; Mirjolet, Celine; Bonnetain, Franck; Cormier, Luc; Brunotte, Francois; Walker, Paul

    2011-11-15

    Purpose: To investigate the time course response of prostate metabolism to irradiation using magnetic resonance spectroscopy (MRS) at 3-month intervals and its impact on biochemical control. Methods and Materials: Between January 2008 and April 2010, 24 patients with localized prostate cancer were prospectively enrolled in the Evaluation of the Response to Irradiation with MR Spectroscopy (ERIS) trial. All the patients had been treated with intensity-modulated radiation therapy with or without long-term adjuvant hormonal therapy (LTHT) and underwent 3-T MRS and prostate-specific antigen (PSA) assays at baseline and every 3 months thereafter up to 12 months. Results: After radiation, the mean normalized citrate level (citrate/water) decreased significantly over time, both in the peripheral zone (PZ) (p = 0.0034) and in the entire prostate (p = 0.0008), whereas no significant change was observed in mean normalized choline levels (choline/water) in the PZ (p = 0.84) and in the entire prostate (p = 0.95). At 6 months after radiation, the mean choline level was significantly lower in the PZ for patients with a PSA value of {<=}0.5 ng/mL at 12 months (4.9 {+-} 1.7 vs. 7.1 {+-} 1.5, p = 0.0378). Similar results were observed at 12 months in the PZ (6.2 {+-} 2.3 vs. 11.4 {+-} 4.1, p = 0.0117 for choline level and 3.4 {+-} 0.7 vs. 16.1 {+-} 6.1, p = 0.0054 for citrate level) and also in the entire prostate (6.2 {+-} 1.9 vs. 10.4 {+-} 3.2, p = 0.014 for choline level and 3.0 {+-} 0.8 vs. 13.3 {+-} 4.7, p = 0.0054 for citrate level). For patients receiving LTHT, there was no correlation between choline or citrate levels and PSA value, either at baseline or at follow-up. Conclusions: Low normalized choline in the PZ, 6 months after radiation, predicts which patients attained a PSA {<=}0.5 ng/mL at 1 year. Further analyses with longer follow-up times are warranted to determine whether or not these new biomarkers can conclusively predict the early radiation response and the

  12. Hetero-organic thymus antigens.

    PubMed

    Beletskaya, L V; Gnezditskaya, E V

    1985-01-01

    The use of sera containing antibodies to tissue-specific antigens of highly specialized organs (skeletal muscles, heart, skin, excretory glands) enabled us to detect, by immunofluorescence, cells capable of synthesizing analogous antigens (i.e. hetero-organic thymus antigens) in human and animal thymus. Detection of hetero-organic antigens in the thymus is the basis for the hypothesis that natural immunological tolerance to tissue self antigens is formed within the thymus in the course of T-lymphocyte maturation, with thymus antigens taking part in the process.

  13. Heart failure.

    PubMed

    Braunwald, Eugene

    2013-02-01

    Despite major improvements in the treatment of virtually all cardiac disorders, heart failure (HF) is an exception, in that its prevalence is rising, and only small prolongations in survival are occurring. An increasing fraction, especially older women with diabetes, obesity, and atrial fibrillation exhibit HF with preserved systolic function. Several pathogenetic mechanisms appear to be operative in HF. These include increased hemodynamic overload, ischemia-related dysfunction, ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, excessive or inadequate proliferation of the extracellular matrix, accelerated apoptosis, and genetic mutations. Biomarkers released as a consequence of myocardial stretch, imbalance between formation and breakdown of extracellular matrix, inflammation, and renal failure are useful in the identification of the pathogenetic mechanism and, when used in combination, may become helpful in estimating prognosis and selecting appropriate therapy. Promising new therapies that are now undergoing intensive investigation include an angiotensin receptor neprilysin inhibitor, a naturally-occurring vasodilator peptide, a myofilament sensitizer and several drugs that enhance Ca++ uptake by the sarcoplasmic reticulum. Cell therapy, using autologous bone marrow and cardiac progenitor cells, appears to be promising, as does gene therapy. Chronic left ventricular assistance with continuous flow pumps is being applied more frequently and successfully as destination therapy, as a bridge to transplantation, and even as a bridge to recovery and explantation. While many of these therapies will improve the care of patients with HF, significant reductions in prevalence will require vigorous, multifaceted, preventive approaches.

  14. A novel immunosensing platform for highly sensitive prostate specific antigen detection based on dual-quenching of photocurrent from CdSe sensitized TiO2 electrode by gold nanoparticles decorated polydopamine nanospheres.

    PubMed

    Dong, Yu-Xiang; Cao, Jun-Tao; Liu, Yan-Ming; Ma, Shu-Hui

    2017-05-15

    Herein, a novel photoelectrochemical (PEC) immunosensing platform for highly sensitive detection of prostate specific antigen (PSA) was constructed based on dual-quenching of photocurrent from CdSe sensitized TiO2 electrode by gold nanoparticles decorated dopamine-melanin nanospheres (AuNPs-Dpa-melanin CNSs). In this proposal, CdSe sensitized TiO2 was used as photoelectrochemical matrix and the functional AuNPs-Dpa-melanin CNSs were used as signal quenching element. The dual quenching of the gold nanoparticles decorated Dpa-melanin CNSs to the CdSe sensitized TiO2 was achieved as follows: (i) the strong energy transfer between the CdSe quantum dots (QDs) and Au NPs diminishes the photocurrent signal of CdSe QDs; (ii) the steric hindrance of AuNPs-Dpa-melanin CNSs partly obstructs the diffusion of the electron donor, i.e. ascorbic acid, to the surface of photoelectrode, which make the depleting efficiency of the photogenerated holes decrease, leading to a declined photocurrent intensity. On the basis of the dual quenching effect of AuNPs-Dpa-melanin CNSs, a competitive immunosensing platform for PSA was designed upon the specific binding of anti-PSA to PSA and PSA functionalized AuNPs-Dpa-melanin CNSs conjugates. This proposed immunosensor possesses wide linear range from 1.0×10(-11)gmL(-1) to 1.0×10(-7)gmL(-1) with the detection limit of 2.7pgmL(-1). Moreover, the applicability of the present method was demonstrated in the determination of PSA in human serum. The strategy creates new paradigms for PSA and other tumor markers detection and demonstrates high sensitivity, good specificity, and satisfied applicability in complex biological samples.

  15. Antigen detection systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infectious agents or their constituent parts (antigens or nucleic acids) can be detected in fresh, frozen, or fixed tissues or other specimens, using a variety of direct or indirect assays. The assays can be modified to yield the greatest sensitivity and specificity but in most cases a particular m...

  16. Human liver nucleolar antigens.

    PubMed

    Busch, R K; Busch, H

    1981-10-01

    In an extension of previous studies on the antigens in rat liver nucleoli (R. K. Busch, R. C. Reddy, D. H. Henning, and H. Busch, Proc. Soc. Exp. Biol. Med. 160, 185 (1979); R. K. Busch and H. Busch, Tumori 63, 347 (1977); F. M. Davis, R. K. Busch, L. C. Yeoman, and H. Busch, Cancer Res. 38, 1906 (1978), rabbit antibodies were elicited to human liver nucleoli isolated by the sucrose--Mg2+ method (10). Fluorescent nucleoli were found in liver cryostat sections treated with rabbit anti-human liver nucleolar antibodies followed by fluorescein-conjugated goat anti-rabbit antibodies. In HeLa cells, fluorescence was distributed throughout the nucleus and in a nuclear network but was not localized to the nucleolus. In placental cryostat sections, an overall nuclear fluorescence was observed with some localization to nucleoli. Immunodiffusion analysis revealed two immunoprecipitin bands which appeared to be liver specific. Other immunoprecipitin bands were common to liver, placenta, and HeLa nuclear extracts. Rocket immunoelectrophoresis revealed two liver-specific antigens, one migrating to the cathode and the other to the anode Other rockets exhibited identity to antigens of other nuclear extracts. These results demonstrate the presence of human liver nucleolar-specific antigens which were not found in the HeLa and placental cells.

  17. Antigen smuggling in tuberculosis.

    PubMed

    Hudrisier, Denis; Neyrolles, Olivier

    2014-06-11

    The importance of CD4 T lymphocytes in immunity to M. tuberculosis is well established; however, how dendritic cells activate T cells in vivo remains obscure. In this issue of Cell Host & Microbe, Srivastava and Ernst (2014) report a mechanism of antigen transfer for efficient activation of antimycobacterial T cells.

  18. Antigen detection systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infectious agents or their constituent parts (antigens or nucleic acids) can be detected in fresh, frozen, or fixed tissue using a variety of direct or indirect assays. The assays can be modified to yield the greatest sensitivity and specificity but in most cases a particular methodology is chosen ...

  19. A Common Model to Handle PDS3 and PDS4 Data in the New Planetary Science Archive (PSA)

    NASA Astrophysics Data System (ADS)

    Macfarlane, A. J.; Barbarisi, I.; Rios, C.; Docasal, R.; Martinez, S.; Arviset, C.; Besse, S.; De Marchi, G.; Grotheer, E.; Gonzalez, J.; Lim, T.; Fraga, D.; Barthelemy, M.

    2015-12-01

    The first of the European Space Agency's (ESA) planetary missions to make use of the latest release of the Planetary Data Standards (PDS4) are currently in advanced stages of development (ExoMars, BepiColombo). This occurs at a time when the Planetary Science Archive (PSA) has been undergoing a complete reengineering in order to increase the accessibility of ESA's planetary data holdings utilising the latest technologies and to significantly improve the user experience for both the specialist scientific community and general public alike. The PSA must also keep on handling PDS3 data arriving to the archive from active missions (Rosetta, Mars Express, Venus Express) as well as continuing to provide access to missions that have reached the legacy phase (Huygens, SMART1, Giotto). Therefore, as part of the reengineering of the PSA, an effort has been made to map the key metadata from PDS3 and PDS4 into a common data model with the intention of providing transparency to the services that make up the new PSA, and consequently to the end user. We present how this common mapping allows the PSA to support the data deliveries from the pipelines of existing missions without the need to reprocess the PDS3 data and in addition how it should simplify the data deliveries from PDS4 missions. We review how the implementation of this data model, involving a PostgreSQL database with the PostGIS extension, enables the new PSA to be able to provide multiple methods of interoperability used by the international community, such as PDAP (Planetary Data Access Protocol), EPN-TAP (EuroPlanet-Table Access Protocol), and GIS-enabled technologies without the user having to know in detail the underlying structure of the data format.

  20. Label-free Electrochemiluminescent Immunosensor for Detection of Prostate Specific Antigen based on Aminated Graphene Quantum Dots and Carboxyl Graphene Quantum Dots.

    PubMed

    Wu, Dan; Liu, Yixin; Wang, Yaoguang; Hu, Lihua; Ma, Hongmin; Wang, Guoqin; Wei, Qin

    2016-02-04

    Prostate-specific antigen (PSA) was used as the model, an ultrasensitive label-free electrochemiluminescent immunosensor was developed based on graphene quantum dots. Au/Ag-rGO was sythsized and used as electrode material to load a great deal of graphene quantum dots due to the large surface area and excellent electron conductivity. After aminated graphene quantum dots and acarboxyl graphene quantum dots were modified onto the electrode, the ECL intensity was much high using K2S2O8 as coreactant. Then, antibody of PSA was immobilized on the surface of modified electrode surface through the adsorption of Au/Ag toward proteins, leading to the decrease of the ECL intensity. As proven by ECL spectra test and electrochemical impedance spectroscopy (EIS) analysis, the fabrication process of the immunosensor is successful. Under the optimal conditions, the ECL intensity decreased linearly with the logarithm of PSA concentration in the range of 1 pg/mL ~ 10 ng/mL. The detection limit achieved is 0.29 pg/mL. The immunosensor results were validated through the detection of PSA in serum samples with satisfactory results. Due to excellent stability, high sensitivity, acceptable repeatability and selectivity, the immunosensor has promising applications in disease and drug analysis.

  1. Graphene oxide quantum dots@silver core-shell nanocrystals as turn-on fluorescent nanoprobe for ultrasensitive detection of prostate specific antigen.

    PubMed

    Pei, Haimeng; Zhu, Shuyun; Yang, Minghui; Kong, Rongmei; Zheng, Yiqun; Qu, Fengli

    2015-12-15

    We report a fluorescent turn-on nanoprobe for ultrasensitive detection of prostate specific antigen (PSA) based on graphene oxide quantum dots@silver (GQDs@Ag) core-shell nanocrystals. The success of this work relies on the assembly of quantities of GQDs in one GQDs@Ag probe, which makes the ratio of probe to target significantly increased and thus enables the fluorescent signal enhancement. When the silver shell was removed via oxidative etching using hydrogen peroxide (H2O2), the incorporated GQDs could be readily released and the whole process caused little change to their fluorescence performance. We tested the probe for the ultrasensitive detection of PSA based on the sandwich protocol of immunosensors. In particular, magnetic beads (MBs) were employed to immobilize anti-PSA antibody (Ab1) and acted as a separable capture probe, while GQDs@Ag was used as detection probe by linking antibody (Ab2). The developed immunosensor showed a good linear relationship between the fluorescence intensity and the concentration of PSA in the range from 1 pg/mL to 20 ng/mL with a detection limit of 0.3 pg/mL. The immunosensor used for the analysis of clinical serum samples exhibited satisfactory results, which demonstrated its potential for practical diagnostic applications. This method provides a possible solution to the application of GQDs in immunosensing and could be potentially extended to other similar systems.

  2. A label-free electrochemiluminescence immunosensor based on EuPO4 nanowire for the ultrasensitive detection of Prostate specific antigen.

    PubMed

    Ma, Hongmin; Zhou, Jing; Li, Yan; Han, Tongqian; Zhang, Yong; Hu, Lihua; Du, Bin; Wei, Qin

    2016-06-15

    EuPO4 nanowire, which exhibited strong and stable cathodic electrochemiluminescence (ECL) activity, was used for the first time to fabricate an immunosensor for the detection of prostate specific antigen (PSA). EuPO4 has some inherent excellent properties such as long luminescence lifetime, narrow emission band, high quantum yield and low toxicity. Based on these properties, a novel label-free ECL immunosensor was developed using EuPO4 as a sensing matrix. Chitosan solution was used to disperse EuPO4 nanowires and the amino groups on chitosan enabled the covalent attachment of capture antibodies. After the modification of the electrode surface with EuPO4 nanowires, anti-PSA was then immobilized on them, forming a label-free immunosensing interface. The specific binding of PSA on the electrode inhibited the ECL reaction of EuPO4 nanowires with the coreactant due to the steric hindrance effect (Deng et al., 2013). Under the optimum conditions, a good linear relationship between ECL intensity and the logarithm of PSA concentration was obtained in the range of 0.0005-80 ng/mL with a detection limit of 177.33 fg/mL. The proposed ECL immunosensor showed good stability, acceptable selectivity and reproducibility.

  3. Real-time and label-free detection of the prostate-specific antigen in human serum by a polycrystalline silicon nanowire field-effect transistor biosensor.

    PubMed

    Huang, Yu-Wen; Wu, Chung-Shu; Chuang, Cheng-Keng; Pang, See-Tong; Pan, Tung-Ming; Yang, Yuh-Shyong; Ko, Fu-Hsiang

    2013-08-20

    In this research, we used a polycrystalline silicon nanowire field-effect transistor (poly-Si NWFET) as a biosensor that employs the sidewall spacer technique instead of an expensive electron beam lithography method. When compared with commercial semiconductor processes, the sidewall spacer technique has the advantages of simplicity and low cost. In this study, we employed a novel poly-Si NWFET device for real-time, label-free, and ultrahigh-sensitivity detection of prostate-specific antigen (PSA) in human serum. Since serum proteome is very complex containing high levels of salts and other interfering compounds, we hereby developed a standard operating procedure for real-sample pretreatment to keep a proper pH value and ionic strength of the desalted serum and also utilized Tween 20 to serve as the passivation agent by surface modification on the NWFET to reduce nonspecific binding for medical diagnostic applications. We first modified 3-aminopropyltriethoxysilane on the surface of a poly-Si nanowire device followed by glutaraldehyde functionalization, and the PSA antibodies were immobilized on the aldehyde terminal. While PSA was prepared in the buffers to maintain an appropriate pH value and ionic strength, the results indicated that the sensor could detect trace PSA at less than 5 fg/mL in a microfluidic channel. The novel poly-Si NWFET is developed as a diagnostic platform for monitoring prostate cancer and predicting the risk of early biochemical relapse.

  4. A new pressure swing adsorption (PSA) process for recovery of tritium from the ITER solid ceramic breeder helium purge gas

    SciTech Connect

    Sood, S.K.; Fong, C.; Kalyanam, K.M. ); Kveton, O.K. ); Busigin, A. ); Ruthven, D.M. )

    1992-03-01

    This paper reports on Pressure Swing Adsorption (PSA), a well established industrial process for separating and purifying industrial gases, it is proposed for recovery of hydrogen isotopes from the ITER (International Thermonuclear Experimental Reactor) solid breeder He purge stream. The PSA process has an inherent advantage over a recently proposed Temperature Swing Adsorption (TSA) design because it allows much faster cycling (10 vs. 480 min.) and therefore has significantly (48 times) lower tritium inventory. The maximum tritium inventory for a 10 minute PSA cycle is less than 0.5 g of tritium, thus meeting an important safety goal of ITER. The PSA process is based on using molecular sieve 5A at 77 K, with pressure cycling from 1-2 MPa during the adsorption cycle, to a rough vacuum during regeneration. Experiments have been carried out to confirm the H{sub 2}/He adsorption isotherms on molecular sieve 5A, and to develop new data points at low H{sub 2} partial pressures and a temperature of 77 K. A dynamic simulation model has been developed to facilitate system design and optimization.

  5. An ultrasensitive electrochemical immunosensor for the detection of prostate-specific antigen based on conductivity nanocomposite with halloysite nanotubes.

    PubMed

    Li, Yueyuan; Khan, Malik Saddam; Tian, Lihui; Liu, Li; Hu, Lihua; Fan, Dawei; Cao, Wei; Wei, Qin

    2017-03-01

    A sensitive label-free amperometric electrochemical immunosensor for detection of prostate-specific antigen (PSA) was proposed in this work. The nanocomposite of halloysite nanotubes with polypyrrole shell and palladium nanoparticles (HNTs@PPy-Pd) was used as a novel signal label. The HNTs with adequate hydroxyl groups are economically available raw materials. PPy, as an electrically conducting polymer material, can be absorbed to the surface of HNTs by in situ oxidative polymerization of the pyrrole monomer and form a shell on the HNTs. The shell of PPy could not only improve the conductivity of the nanocomposite but also absorb large amounts of Pd nanoparticles (NPs). The Pd NPs with high electrocatalytic activity toward the reduction of H2O2 and the HNTs@PPy-Pd nanocomposite as the analytical signal label could improve the sensitivity of the immunosensor. Under optimal conditions, the immunosensor showed a low detection limit (0.03 pg/mL) and a wide linear range (0.0001 to 25 ng/mL) of PSA. Moreover, its merits such as good selectivity, acceptable reproducibility, and stability indicate that the fabricated immunosensor has a promising application potential in clinical diagnosis. Graphical Abstract A new label-free amperometric electrochemical immunosensor based on HNTs@PPy-Pd nanocomposite for quantitative detection of PSA.

  6. Electrochemiluminescent immunosensing of prostate-specific antigen based on silver nanoparticles-doped Pb (II) metal-organic framework.

    PubMed

    Ma, Hongmin; Li, Xiaojian; Yan, Tao; Li, Yan; Zhang, Yong; Wu, Dan; Wei, Qin; Du, Bin

    2016-05-15

    In this work, silver nanoparticles-doped Pb (II) metal-organic framework (Ag-MOF) was prepared and exploited as a luminescence probe for the development of label-free electrochemiluminescence (ECL) immunosensing scheme for prostate-specific antigen (PSA). The β-cyclodextrin based MOF, Pb-β-cyclodextrin (Pb(II)-β-CD) shows excellent ECL behavior and unexpected reducing capacity towards silver ions. Silver nanoparticles could massively form on the surface of Pb(II)-β-CD (Ag@Pb(II)-β-CD) without use any additional reducing agent, while the ECL behavior of Pb(II)-β-CD still was well retained. The Ag@Pb(II)-β-CD was used as a substrate material to modify glass carbon electrodes and formed a sensing platform for the fabricating ECL immunosensor. The presence of silver nanoparticles enables the facile immobilization of capturing antibody of PSA. The specific binding of PSA onto the electrode surface induces the decrease of ECL signals. A linear range of 0.001-50 ng mL(-1) with a detection limit of 0.34 pg mL(-1) (S/N=3) was obtained after the optimization of experimental conditions. This simply fabricated immunosensor exhibits good stability, accuracy and acceptable reproducibility, which suggesting its potential applications in clinical diagnostics.

  7. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer

    PubMed Central

    Paller, CJ; Ye, X; Wozniak, PJ; Gillespie, BK; Sieber, PR; Greengold, RH; Stockton, BR; Hertzman, BL; Efros, MD; Roper, RP; Liker, HR; Carducci, MA

    2012-01-01

    BACKGROUND Pomegranate juice has been associated with PSA doubling time (PSADT) elongation in a single-arm phase II trial. This study assesses biological activity of two doses of pomegranate extract (POMx) in men with recurrent prostate cancer, using changes in PSADT as the primary outcome. METHODS This randomized, multi-center, double-blind phase II, dose-exploring trial randomized men with a rising PSA and without metastases to receive 1 or 3 g of POMx, stratified by baseline PSADT and Gleason score. Patients (104) were enrolled and treated for up to 18 months. The intent-to-treat (ITT) population was 96% white, with median age 74.5 years and median Gleason score 7. This study was designed to detect a 6-month on-study increase in PSADT from baseline in each arm. RESULTS: Overall, median PSADT in the ITT population lengthened from 11.9 months at baseline to 18.5 months after treatment (P<0.001). PSADT lengthened in the low-dose group from 11.9 to 18.8 months and 12.2 to 17.5 months in the high-dose group, with no significant difference between dose groups (P =0.554). PSADT increases >100% of baseline were observed in 43% of patients. Declining PSA levels were observed in 13 patients (13%). In all, 42% of patients discontinued treatment before meeting the protocol-definition of PSA progression, or 18 months, primarily due to a rising PSA. No significant changes occurred in testosterone. Although no clinically significant toxicities were seen, diarrhea was seen in 1.9% and 13.5% of patients in the 1- and 3-g dose groups, respectively. CONCLUSIONS POMx treatment was associated with ≥6 month increases in PSADT in both treatment arms without adverse effects. The significance of this on-study slowing of PSADT remains unclear, reinforcing the need for placebo-controlled studies in this patient population. PMID:22689129

  8. Biochemical failure after radical prostatectomy in intermediate-risk group men increases with the number of risk factors

    PubMed Central

    Furubayashi, Nobuki; Negishi, Takahito; Iwai, Hidenori; Nagase, Kei; Taguchi, Kenichi; Shimokawa, Mototsugu; Nakamura, Motonobu

    2017-01-01

    Introduction: We aimed to determine whether the number and type of risk factors are associated with biochemical recurrence-free survival after radical prostatectomy in men with D’Amico intermediate-risk prostate cancer. Materials and Methods: Between August 1998 and May 2013, 481 Japanese patients underwent antegrade radical prostatectomy. The relationships between the rate of PSA failure after radical prostatectomy and the number and type of risk factors were examined in the intermediate-risk group. Results: According to the D’Amico criteria, the low-, intermediate-, and high-risk groups comprised 107, 222, and 152 patients, respectively. The median follow-up period after surgery was 54.1 months. The 5-year PSA failure-free rates in the low-, intermediate-, and high-risk groups were 96.5%, 88.9%, and 72.6%, respectively (P < 0.001). The 5-year PSA failure-free rate in the intermediate-risk group with one, two, and three intermediate risk factors was 94.9%, 88.4%, and 49.0%, respectively (P < 0.001). The difference between the high- and intermediate-risk group with three intermediate risk factors was statistically significant based on the log-rank test (P = 0.039). Conclusion: The number of intermediate risk factors is significantly associated with the PSA failure-free survival rate after radical prostatectomy in the intermediate-risk group. Patients classified into the intermediate-risk group based on all three intermediate risk factors are less likely to achieve a complete cure through surgery alone. PMID:28197033

  9. Acute kidney failure

    MedlinePlus

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  10. What Is Heart Failure?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Heart Failure? Heart failure is a condition in which the heart can' ... force. Some people have both problems. The term "heart failure" doesn't mean that your heart has stopped ...

  11. The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels.

    PubMed Central

    Cote, R. J.; Skinner, E. C.; Salem, C. E.; Mertes, S. J.; Stanczyk, F. Z.; Henderson, B. E.; Pike, M. C.; Ross, R. K.

    1998-01-01

    Prostate cancer is a disease associated with androgens. It has been hypothesized that reducing the conversion of testosterone (T) to dihydrotestosterone (DHT) in the prostate by the use of the drug finasteride, a 5alpha-reductase inhibitor, will reduce the incidence of prostate cancer. We investigated the chemopreventive potential of finasteride by evaluating its effect on the prostate gland of men with elevated serum prostate-specific antigen (PSA). Fifty-two men with elevated PSA and prostate sextant biopsies negative for cancer were randomized to receive finasteride 5 mg day(-1) (27 patients) or no medication (25 patients) for 12 months and were rebiopsied at 12 months. The biopsies were evaluated for the presence of cancer, the proportion of glandular and hyperplastic tissue, and the presence of high-grade prostatic intraepithelial neoplasia (PIN). Epithelial proliferation was assessed in the prestudy and 12-month biopsies by immunohistochemistry using antibody to proliferating cell nuclear antigen (PCNA). Serum blood samples were drawn at baseline and after 1, 3, 6 and 12 months of study. In the control group, serum levels of PSA and T were unchanged throughout the 12 months. In the finasteride group, PSA decreased 48% (P < 0.001), DHT decreased 67% (P < 0.001) and T increased 21% (P < 0.001). Histological evaluation of prestudy and 12-month biopsy specimens revealed that the finasteride group had a 30% reduction in the percentage of hyperplastic epithelial tissue (P = 0.002), although this decrease was not statistically significantly different between the finasteride and control groups (P = 0.11). In patients with PIN on prestudy biopsy, no change occurred in the PIN lesions with finasteride treatment. Finasteride also had no effect on the proliferation index of prostatic epithelial cells. Of the 27 patients treated with finasteride, eight (30%) had adenocarcinoma of the prostate detected on the 12-month biopsy, compared with one (4%) of the control patients

  12. Microchip device with 64-site electrode array for multiplexed immunoassay of cell surface antigens based on electrochemiluminescence resonance energy transfer.

    PubMed

    Wu, Mei-Sheng; Shi, Hai-Wei; He, Li-Jing; Xu, Jing-Juan; Chen, Hong-Yuan

    2012-05-01

    This paper describes a novel on-chip microarray platform based on an electrochemiluminescence resonance energy transfer (ECL-RET) strategy for rapid assay of cancer cell surface biomarkers. This platform consists of 64 antigen-decorated CdS nanorod spots with the diameter of 1.0 cm uniformly distributed on 16 indium tin oxide (ITO) strips, which is coated with a multichannel decorated polydimethylsiloxane (PDMS) slice to realize multiplexed determination of antigens. To shorten the immune reaction time in the microchannels and simplify the device, magnetic stirring and four-channel universal serial bus (USB) ports for plug-and-play were used. When Ru(bpy)(3)(2+) labeled antibodies were selectively captured by the corresponding antigens on the CdS nanorod spot array, ECL-RET from the CdS nanorod (donor) by cathodic emission in the presence of K(2)S(2)O(8) to Ru(bpy)(3)(2+) (acceptor) occurred. With signal amplification of Ru(bpy)(3)(2+) and competitive immunoassay, carcinoembryonic antigen (CEA), α-fetoprotein (AFP), and prostate specific antigen (PSA) as models were detected on this microfluidic device via recording the increased ECL-RET signals on electrode surfaces. Furthermore, this multiplexed competitive immunoassay was successfully used for detecting cancer cell surface antigens via the specific antibody-cell interactions and cell counting via cell surface receptors and antigens on the CdS nanorod surface. This platform provides a rapid and simple but sensitive approach with microliter-level sample volume and holds great promise for multiplexed detection of antigens and antigen-specific cells.

  13. Heart failure - medicines

    MedlinePlus

    CHF - medicines; Congestive heart failure - medicines; Cardiomyopathy - medicines; HF - medicines ... You will need to take most of your heart failure medicines every day. Some medicines are taken ...

  14. Immune recognition of protein antigens

    SciTech Connect

    Laver, W.G.; Air, G.M.

    1985-01-01

    This book contains 33 papers. Some of the titles are: Antigenic Structure of Influenze Virus Hemagglutinin; Germ-line and Somatic Diversity in the Antibody Response to the Influenza Virus A/PR/8/34 Hemagglutinin; Recognition of Cloned Influenza A Virus Gene Products by Cytotoxic T Lymphocytes; Antigenic Structure of the Influenza Virus N2 Neuraminidase; and The Molecular and Genetic Basis of Antigenic Variation in Gonococcal Pillin.

  15. Effect of low-dose testosterone treatment on androgen regulated proteins prostate specific antigen and sex hormone binding globulin in short prepubertal boys: lack of initiation of puberty.

    PubMed

    Gupta, M K; Brown, D C; Faiman, C; Kelnar, C J H; Wu, F C W

    2003-01-01

    The efficacy of testosterone undecanoate (TU) treatment in constitutional delay of growth (CHD) is well recognized. We investigated its role in initiating puberty. Sera taken prior to, just after 6 months on and after 6 months off treatment with TU (20 mg daily) were analyzed from eight boys and compared to results from eight boys receiving placebo. Prostate specific antigen (PSA) and sex hormone binding globulin (SHBG), sleep-entrained pulsatility and mean overnight luteinizing hormone (mLH), and morning testosterone (T) levels were measured. Free androgen index (FAI) was calculated. Testicular volume (TV) and growth parameters were assessed. During treatment, there was a significant increase in height velocity in boys taking TU vs placebo (mean +/- SD: 5.7 +/- 2.0 vs 3.2 +/- 0.9 cm/year, p = 0.008) but no significant differences were observed in regard to LH pulsatility, mLH, T, SHBG, FAI, PSA and TV values. PSA was detectable in four patients (two each in the TU and placebo groups) at 6 months off treatment indicating pubertal progression. Among the hormones measured, only pretreatment mLH levels were significantly higher in the PSA-positive patients compared to 12 PSA-negative patients (mean +/- SEM: 1.5 +/- 0.39 vs 0.37 +/- 0.06 IU/l, p < 0.001). In conclusion, TU treatment shows no significant effect on initiation or advancement of puberty despite its resultant growth acceleration. Among the hormonal changes studied, mLH levels were the earliest indicator of pubertal initiation.

  16. Prostate-specific antigen 10–20 ng/mL: A predictor of degree of upgrading to ≥8 among patients with biopsy Gleason score 6

    PubMed Central

    Santok, Glen Denmer R.; Abdel Raheem, Ali; Kim, Lawrence HC; Chang, Kidon; Lum, Trenton GH; Chung, Byung Ha; Choi, Young Deuk

    2017-01-01

    Purpose This study aimed to identify the predictors of upgrading and degree of upgrading among patients who have initial Gleason score (GS) 6 treated with robot-assisted radical prostatectomy (RARP). Materials and Methods A retrospective review of the data of 359 men with an initial biopsy GS 6, localized prostate cancer who underwent RARP between July 2005 to June 2010 was performed. They were grouped into group 1 (nonupgrade) and group 2 (upgraded) based on their prostatectomy specimen GS. Logistic regression analysis of studied cases identified significant predictors of upgrading and the degree of upgrading after RARP. Results The mean age and prostate-specific antigen (PSA) was 63±7.5 years, 8.9±8.77 ng/mL, respectively. Median follow-up was 59 months (interquartile range, 47–70 months). On multivariable analysis, age, PSA, PSA density and ≥2 cores positive were predictors of upgrading with (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01–1.06; p=0.003; OR, 1.006; 95% CI, 1.01–1.11; p=0.018; OR, 0.65; 95% CI, 0.43–0.98, p=0.04), respectively. On subanalysis, only PSA level of 10–20 ng/mL is associated with upgrading into GS ≥8. They also had lower biochemical recurrence free survival, cancer specific survival, and overall survival (p≤0.001, p=0.003, and p=0.01, respectively). Conclusions Gleason score 6 patients with PSA (10–20 ng/mL) have an increased risk of upgrading to pathologic GS (≥8), subsequently poorer oncological outcome thus require a stricter follow-up. These patients should be carefully counseled in making an optimal treatment decision. PMID:28261677

  17. DNA fusion-gene vaccination in patients with prostate cancer induces high-frequency CD8(+) T-cell responses and increases PSA doubling time.

    PubMed

    Chudley, Lindsey; McCann, Katy; Mander, Ann; Tjelle, Torunn; Campos-Perez, Juan; Godeseth, Rosemary; Creak, Antonia; Dobbyn, James; Johnson, Bernadette; Bass, Paul; Heath, Catherine; Kerr, Paul; Mathiesen, Iacob; Dearnaley, David; Stevenson, Freda; Ottensmeier, Christian

    2012-11-01

    We report on the immunogenicity and clinical effects in a phase I/II dose escalation trial of a DNA fusion vaccine in patients with prostate cancer. The vaccine encodes a domain (DOM) from fragment C of tetanus toxin linked to an HLA-A2-binding epitope from prostate-specific membrane antigen (PSMA), PSMA(27-35). We evaluated the effect of intramuscular vaccination without or with electroporation (EP) on vaccine potency. Thirty-two HLA-A2(+) patients were vaccinated and monitored for immune and clinical responses for a follow-up period of 72 weeks. At week 24, cross-over to the immunologically more effective delivery modality was permitted; this was shown to be with EP based on early antibody data, and subsequently, 13/15 patients crossed to the +EP arm. Thirty-two HLA-A2(-) control patients were assessed for time to next treatment and overall survival. Vaccination was safe and well tolerated. The vaccine induced DOM-specific CD4(+) and PSMA(27)-specific CD8(+) T cells, which were detectable at significant levels above baseline at the end of the study (p = 0.0223 and p = 0.00248, respectively). Of 30 patients, 29 had a measurable CD4(+) T-cell response and PSMA(27)-specific CD8(+) T cells were detected in 16/30 patients, with or without EP. At week 24, before cross-over, both delivery methods led to increased CD4(+) and CD8(+) vaccine-specific T cells with a trend to a greater effect with EP. PSA doubling time increased significantly from 11.97 months pre-treatment to 16.82 months over the 72-week follow-up (p = 0.0417), with no clear differential effect of EP. The high frequency of immunological responses to DOM-PSMA(27) vaccination and the clinical effects are sufficiently promising to warrant further, randomized testing.

  18. Validating the use of Hospital Episode Statistics data and comparison of costing methodologies for economic evaluation: an end-of-life case study from the Cluster randomised triAl of PSA testing for Prostate cancer (CAP)

    PubMed Central

    Thorn, Joanna C; Turner, Emma L; Hounsome, Luke; Walsh, Eleanor; Down, Liz; Verne, Julia; Donovan, Jenny L; Neal, David E; Hamdy, Freddie C; Martin, Richard M; Noble, Sian M

    2016-01-01

    Objectives To evaluate the accuracy of routine data for costing inpatient resource use in a large clinical trial and to investigate costing methodologies. Design Final-year inpatient cost profiles were derived using (1) data extracted from medical records mapped to the National Health Service (NHS) reference costs via service codes and (2) Hospital Episode Statistics (HES) data using NHS reference costs. Trust finance departments were consulted to obtain costs for comparison purposes. Setting 7 UK secondary care centres. Population A subsample of 292 men identified as having died at least a year after being diagnosed with prostate cancer in Cluster randomised triAl of PSA testing for Prostate cancer (CAP), a long-running trial to evaluate the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. Results Both inpatient cost profiles showed a rise in costs in the months leading up to death, and were broadly similar. The difference in mean inpatient costs was £899, with HES data yielding ∼8% lower costs than medical record data (differences compatible with chance, p=0.3). Events were missing from both data sets. 11 men (3.8%) had events identified in HES that were all missing from medical record review, while 7 men (2.4%) had events identified in medical record review that were all missing from HES. The response from finance departments to requests for cost data was poor: only 3 of 7 departments returned adequate data sets within 6 months. Conclusions Using HES routine data coupled with NHS reference costs resulted in mean annual inpatient costs that were very similar to those derived via medical record review; therefore, routinely available data can be used as the primary method of costing resource use in large clinical trials. Neither HES nor medical record review represent gold standards of data collection. Requesting cost data from finance departments is impractical for large clinical trials. Trial registration number ISRCTN92187251

  19. Advanced Heart Failure

    MedlinePlus

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Advanced Heart Failure Updated:Feb 9,2017 When heart failure (HF) ... content was last reviewed on 04/06/2015. Heart Failure • Home • About Heart Failure • Causes and Risks for ...

  20. Stool Test: H. Pylori Antigen

    MedlinePlus

    ... Your 1- to 2-Year-Old Stool Test: H. Pylori Antigen KidsHealth > For Parents > Stool Test: H. Pylori Antigen A A A What's in this article? ... en español Muestra de materia fecal: antígeno de H. pylori What It Is Helicobacter pylori ( H. pylori ) bacteria ...

  1. Use of serology and urine antigen detection to estimate the proportion of adult community-acquired pneumonia attributable to Streptococcus pneumoniae.

    PubMed

    Watt, J P; Moïsi, J C; Donaldson, R L A; Reid, R; Ferro, S; Whitney, C G; Santosham, M; O'Brien, K L

    2010-12-01

    Streptococcus pneumoniae is a common cause of community-acquired pneumonia (CAP) but existing diagnostic tools have limited sensitivity and specificity. We enrolled adults undergoing chest radiography at three Indian Health Service clinics in the Southwestern United States and collected acute and convalescent serum for measurement of PsaA and PspA titres and urine for pneumococcal antigen detection. Blood and sputum cultures were obtained at the discretion of treating physicians. We compared findings in clinical and radiographic CAP patients to those in controls without CAP. Urine antigen testing showed the largest differential between CAP patients and controls (clinical CAP 13%, radiographic CAP 17%, control groups 2%). Serological results were mixed, with significant differences between CAP patients and controls for some, but not all changes in titre. Based on urine antigen and blood culture results, we estimated that 11% of clinical and 15% of radiographic CAP cases were due to pneumococcus in this population.

  2. Radioimmunoassays of hidden viral antigens

    SciTech Connect

    Neurath, A.R.; Strick, N.; Baker, L.; Krugman, S.

    1982-07-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure.

  3. Radioimmunoassays of hidden viral antigens.

    PubMed Central

    Neurath, A R; Strick, N; Baker, L; Krugman, S

    1982-01-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bond adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure. Images PMID:6956871

  4. Synthesis of cadmium, lead and copper alginate nanobeads as immunosensing probes for the detection of AFP, CEA and PSA.

    PubMed

    Wang, Zifeng; Liu, Na; Feng, Feng; Ma, Zhanfang

    2015-08-15

    A double-water-in-oil-emulsion procedure was designed to synthesize cadmium, lead and copper alginate nanobeads less than 200n m diameter under mild conditions. The cadmium, lead and copper alginate nanobeads can be activated to immobilize biomacromolecules and can directly produce distinctive electrochemical signals. Using the novel alginate nanobeads labeled with antibodies as electrochemical probes, a sandwich-type immunosensor was constructed using AFP, CEA and PSA as model analytes. This proposed immunosensor shows wide linear range with detection limits of 0.01, 0.0086 and 0.0075 ng mL(-1) for AFP, CEA and PSA, respectively. Analysis of clinical serum samples using this immunosensor was well consistent with the data determined by the enzyme-linked immunosorbent assay (ELISA). It suggested that the alginate nanobeads electrochemical probes could be generally extended to other multiple analytes detection.

  5. Enzymatic Triggered Release of an HIV-1 Entry Inhibitor from Prostate Specific Antigen Degradable Microparticles

    PubMed Central

    Clark, Meredith R.; Aliyar, Hyder A.; Lee, Chang-won; Jay, Julie I.; Gupta, Kavita M.; Watson, Karen M.; Stewart, Russell J.; Buckheit, Robert W.; Kiser, Patrick F.

    2011-01-01

    This paper describes the design, construction and characterization of the first anti-HIV drug delivery system that is triggered to release its contents in the presence of human semen. Microgel particles were synthesized with a crosslinker containing a peptide substrate for the seminal serine protease prostate specific antigen (PSA) and were loaded with the HIV-1 entry inhibitor sodium poly(styrene-4-sulfonate) (pSS). The particles were composed of N-2-hydroxyproplymethacrylamide and bis-methacrylamide functionalized peptides based on the PSA substrates GISSFYSSK and GISSQYSSK. Exposure to human seminal plasma (HSP) degraded the microgel network and triggered the release of the entrapped antiviral polymer. Particles with the crosslinker composed of the substrate GISSFYSSK showed 17 times faster degradation in seminal plasma than that of the crosslinker composed of GISSQYSSK. The microgel particles containing 1 mol% GISSFYSSK peptide crosslinker showed complete degradation in 30 hours in the presence of HSP at 37 °C and pSS released from the microgels within 30 minutes reached a concentration of 10 µg/mL, equivalent to the published IC90 for pSS. The released pSS inactivated HIV-1 in the presence of HSP. The solid phase synthesis of the crosslinkers, preparation of the particles by inverse microemulsion polymerization, HSP-triggered release of pSS and inactivation of HIV-1 studies are described. PMID:21511017

  6. Oriented Immobilization of Fab Fragments by Site-Specific Biotinylation at the Conserved Nucleotide Binding Site for Enhanced Antigen Detection.

    PubMed

    Mustafaoglu, Nur; Alves, Nathan J; Bilgicer, Basar

    2015-09-08

    Oriented immobilization of antibodies and antibody fragments has become increasingly important as a result of the efforts to reduce the size of diagnostic and sensor devices to miniaturized dimensions for improved accessibility to the end-user. Reduced dimensions of sensor devices necessitate the immobilized antibodies to conserve their antigen binding activity for proper operation. Fab fragments are becoming more commonly used in small-scaled diagnostic devices due to their small size and ease of manufacture. In this study, we used the previously described UV-NBS(Biotin) method to functionalize Fab fragments with IBA-EG11-Biotin linker utilizing UV energy to initiate a photo-cross-linking reaction between the nucleotide binding site (NBS) on the Fab fragment and IBA-Biotin molecule. Our results demonstrate that immobilization of biotinylated Fab fragments via UV-NBS(Biotin) method generated the highest level of immobilized Fab on surfaces when compared to other typical immobilization methods while preserving antigen binding activity. UV-NBS(Biotin) method provided 432-fold, 114-fold, and 29-fold improved antigen detection sensitivity than physical adsorption, NHS-Biotin, and ε-NH3(+), methods, respectively. Additionally, the limit of detection (LOD) for PSA utilizing Fab fragments immobilized via UV-NBS(Biotin) method was significantly lower than that of the other immobilization methods, with an LOD of 0.4 pM PSA. In summary, site-specific biotinylation of Fab fragments without structural damage or loss in antigen binding activity provides a wide range of application potential for UV-NBS immobilization technique across numerous diagnostic devices and nanotechnologies.

  7. TARP vaccination is associated with slowing in PSA velocity and decreasing tumor growth rates in patients with Stage D0 prostate cancer.

    PubMed

    Wood, Lauren V; Fojo, Antonio; Roberson, Brenda D; Hughes, Meghan S B; Dahut, William; Gulley, James L; Madan, Ravi A; Arlen, Philip M; Sabatino, Marianna; Stroncek, David F; Castiello, Luciano; Trepel, Jane B; Lee, Min-Jung; Parnes, Howard L; Steinberg, Seth M; Terabe, Masaki; Wilkerson, Julia; Pastan, Ira; Berzofsky, Jay A

    2016-08-01

    T-cell receptor alternate reading frame protein (TARP) is a 58-residue protein over-expressed in prostate and breast cancer. We investigated TARP peptide vaccination's impact on the rise in PSA (expressed as Slope Log(PSA) or PSA Doubling Time (PSADT)), validated tumor growth measures, and tumor growth rate in men with Stage D0 prostate cancer. HLA-A*0201 positive men were randomized to receive epitope-enhanced (29-37-9V) and wild-type (27-35) TARP peptides administered as a Montanide/GM-CSF peptide emulsion or as an autologous peptide-pulsed dendritic cell vaccine every 3 weeks for a total of five vaccinations with an optional 6th dose of vaccine at 36 weeks based on immune response or PSADT criteria with a booster dose of vaccine for all patients at 48 and 96 weeks. 41 patients enrolled with median on-study duration of 75 weeks at the time of this analysis. Seventy-two percent of patients reaching 24 weeks and 74% reaching 48 weeks had a decreased Slope Log(PSA) compared to their pre-vaccination baseline (p = 0.0012 and p = 0.0004 for comparison of overall changes in Slope Log(PSA), respectively). TARP vaccination also resulted in a 50% decrease in median tumor growth rate (g): pre-vaccine g = 0.0042/day, post-vaccine g = 0.0021/day (p = 0.003). 80% of subjects exhibited new vaccine-induced TARP-specific IFNγ ELISPOT responses but they did not correlate with decreases in Slope Log(PSA). Thus, vaccination with TARP peptides resulted in significant slowing in PSA velocity and reduction in tumor growth rate in a majority of patients with PSA biochemical recurrence.

  8. Antigenic variation in Giardia lamblia.

    PubMed

    Prucca, Cesar G; Lujan, Hugo D

    2009-12-01

    Giardia lamblia undergoes antigenic variation, both in vitro and within the intestines of infected individuals. Variant-specific surface proteins (VSPs) cover the entire surface of the trophozoites and are the main antigens recognized by the host. Only 1 of about 200 VSP genes encoded by the Giardia genome is expressed on the surface of individual Giardia cells at any time; however, VSP antigen switching occurs spontaneously. In the recent year, significant advances in the knowledge of the antigen switching process have been achieved, which strongly suggests that antigenic variation in Giardia is regulated at the post-transcriptional level by a mechanism similar to RNA interference (RNAi). Several enzymes of the RNAi pathway are directly involved in VSP mRNA silencing and/or translational repression. Although several questions remain regarding how individual VSP antigens are selected for expression on the parasite surface, it is clear that an epigenetic mechanism is involved. In this review, we summarize the characteristics of this fascinating mechanism, analyse conflicting information regarding the structure of VSPs as it relates to the host's immune response, and highlight the major issues that need to be resolved to fully understand antigenic variation in this important pathogen.

  9. Serospecific antigens of Legionella pneumophila.

    PubMed Central

    Otten, S; Iyer, S; Johnson, W; Montgomery, R

    1986-01-01

    Serospecific antigens isolated by EDTA extraction from four serogroups of Legionella pneumophila were analyzed for their chemical composition, molecular heterogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunological properties. The antigens were shown to be lipopolysaccharides and to differ from the lipopolysaccharides of other gram-negative bacteria. The serospecific antigens contained rhamnose, mannose, glucosamine, and two unidentified sugars together with 2-keto-3-deoxyoctonate, phosphate, and fatty acids. The fatty acid composition was predominantly branched-chain acids with smaller amounts of 3-hydroxymyristic acid. The antigens contain periodate-sensitive groups; mannosyl residues were completely cleaved by periodate oxidation. Hydrolysis of the total lipopolysaccharide by acetic acid resulted in the separation of a lipid A-like material that cross-reacted with the antiserum to lipid A from Salmonella minnesota but did not comigrate with it on sodium dodecyl sulfate gels. None of the four antigens contained heptose. All of the antigen preparations showed endotoxicity when tested by the Limulus amebocyte lysate assay. The results of this study indicate that the serogroup-specific antigens of L. pneumophila are lipopolysaccharides containing an unusual lipid A and core structure and different from those of other gram-negative bacteria. Images PMID:3017918

  10. Amplified quenching of electrochemiluminescence from CdS sensitized TiO2 nanotubes by CdTe-carbon nanotube composite for detection of prostate protein antigen in serum.

    PubMed

    Tian, Chun-Yuan; Zhao, Wei-Wei; Wang, Jing; Xu, Jing-Juan; Chen, Hong-Yuan

    2012-07-07

    This work reports an ECL immunoassay method for ultrasensitive detection of prostate protein antigen (PSA), by remarkably efficient energy-transfer induced electrochemiluminescence (ECL) quenching from the CdS nanoparticles (NPs) sensitized TiO(2) nanotube array (CdS-TiO(2) NTs) to the activated CdTe NPs functionalized multi-wall carbon nanotubes (CdTe-MWNTs) composite. The coupling of TiO(2) and CdS NPs results in a cathodic ECL intensity 14.7 times stronger than that of the pure TiO(2) NTs electrode, which could be efficiently quenched by the CdTe-MWNTs. The enhanced mechanism of TiO(2) NTs ECL by CdS NPs was studied in detail by cyclic voltammetry and ECL spectroscopy. The strong absorption of the CdTe-MWNTs in the wavelength range of 400-800 nm renders them highly efficient for ECL quenching labeled on anti-PSA antibody. Based on a sandwich structure, we developed an ECL immunoassay method for the sensitive and selective detection of PSA. The ECL intensity decrement was logarithmically related to the concentration of the PSA in the range of 1.0 fg mL(-1) to 10 pg mL(-1) with a detection limit of 1 fg mL(-1). Human serum samples were then tested using the proposed immunoassay with excellent correlations, suggesting that the proposed immunoassay method is of great promise in clinical screening of cancer biomarkers.

  11. Recognition Failure: Another Case of Retrieval Failure

    ERIC Educational Resources Information Center

    Rabinowitz, Jan; And Others

    1977-01-01

    A theoretical explanation of the phenomenon of recognition failure and a presentation of seven experiments investigating performance. Recognition failure is reduced when a more stringent recognition criterion is used, essentially eliminated when the proper access test is used and significantly reduced when variability in recognition performance is…

  12. Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

    SciTech Connect

    Wiegel, Thomas; Bartkowiak, Detlef; Bottke, Dirk; Thamm, Reinhard; Hinke, Axel; Stöckle, Michael; Wirth, Manfred; Störkel, Stephan; Golz, Reinhard; Engenhart-Cabillic, Rita; Hofmann, Rainer; Feldmann, Horst-Jürgen; Kälble, Tilman; Siegmann, Alessandra; Hinkelbein, Wolfgang; Steiner, Ursula; Miller, Kurt

    2015-02-01

    Objective: The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C). Methods and Materials: For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6, range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method. Results: Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression. Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups

  13. Daily Pomegranate Intake Has No Impact on PSA Levels in Patients with Advanced Prostate Cancer - Results of a Phase IIb Randomized Controlled Trial

    PubMed Central

    Stenner-Liewen, Frank; Liewen, Heike; Cathomas, Richard; Renner, Christoph; Petrausch, Ulf; Sulser, Tullio; Spanaus, Katharina; Seifert, Hans Helge; Strebel, Räto Thomas; Knuth, Alexander; Samaras, Panagiotis; Müntener, Michael

    2013-01-01

    Pomegranate has been shown to prolong PSA doubling time in early prostate cancer, but no data from a placebo controlled trial has been published yet. The objective of this study was to prospectively evaluate the impact of pomegranate juice in patients with prostate cancer. We conducted a phase IIb, double blinded, randomized placebo controlled trial in patients with histologically confirmed prostate cancer. Only patients with a PSA value ≥ 5ng/ml were included. The subjects consumed 500 ml of pomegranate juice or 500 ml of placebo beverage every day for a 4 week period. Thereafter, all patients received 250 ml of the pomegranate juice daily for another 4 weeks. PSA values were taken at baseline, day 14, 28 and on day 56. The primary endpoint was the detection of a significant difference in PSA serum levels between the groups after one month of treatment. Pain scores and adherence to intervention were recorded using patient diaries. 102 patients were enrolled. The majority of patients had castration resistant prostate cancer (68%). 98 received either pomegranate juice or placebo between October 2008 and May 2011. Adherence to protocol was good, with 94 patients (96%) completing the first period and 87 patients (89%) completing both periods. No grade 3 or higher toxicities occurred within the study. No differences were detected between the two groups with regard to PSA kinetics and pain scores. Consumption of pomegranate juice as an adjunct intervention in men with advanced prostate cancer does not result in significant PSA declines compared to placebo. PMID:24069070

  14. Daily Pomegranate Intake Has No Impact on PSA Levels in Patients with Advanced Prostate Cancer - Results of a Phase IIb Randomized Controlled Trial.

    PubMed

    Stenner-Liewen, Frank; Liewen, Heike; Cathomas, Richard; Renner, Christoph; Petrausch, Ulf; Sulser, Tullio; Spanaus, Katharina; Seifert, Hans Helge; Strebel, Räto Thomas; Knuth, Alexander; Samaras, Panagiotis; Müntener, Michael

    2013-01-01

    Pomegranate has been shown to prolong PSA doubling time in early prostate cancer, but no data from a placebo controlled trial has been published yet. The objective of this study was to prospectively evaluate the impact of pomegranate juice in patients with prostate cancer. We conducted a phase IIb, double blinded, randomized placebo controlled trial in patients with histologically confirmed prostate cancer. Only patients with a PSA value ≥ 5ng/ml were included. The subjects consumed 500 ml of pomegranate juice or 500 ml of placebo beverage every day for a 4 week period. Thereafter, all patients received 250 ml of the pomegranate juice daily for another 4 weeks. PSA values were taken at baseline, day 14, 28 and on day 56. The primary endpoint was the detection of a significant difference in PSA serum levels between the groups after one month of treatment. Pain scores and adherence to intervention were recorded using patient diaries. 102 patients were enrolled. The majority of patients had castration resistant prostate cancer (68%). 98 received either pomegranate juice or placebo between October 2008 and May 2011. Adherence to protocol was good, with 94 patients (96%) completing the first period and 87 patients (89%) completing both periods. No grade 3 or higher toxicities occurred within the study. No differences were detected between the two groups with regard to PSA kinetics and pain scores. Consumption of pomegranate juice as an adjunct intervention in men with advanced prostate cancer does not result in significant PSA declines compared to placebo.

  15. PSA-NCAM in the posterodorsal medial amygdala is necessary for the pubertal emergence of attraction to female odors in male hamsters.

    PubMed

    Job, Martin O; Cooke, Bradley M

    2015-09-01

    During puberty, attention turns away from same-sex socialization to focus on the opposite sex. How the brain mediates this change in perception and motivation is unknown. Polysialylated neural cell adhesion molecule (PSA-NCAM) virtually disappears from most of the central nervous system after embryogenesis, but it remains elevated in discrete regions of the adult brain. One such brain area is the posterodorsal subnucleus of the medial amygdala (MePD). The MePD has been implicated in male sexual attraction, measured here as the preference to investigate female odors. We hypothesize that PSA-NCAM gates hormone-dependent plasticity necessary for the emergence of males' attraction to females. To evaluate this idea, we first measured PSA-NCAM levels across puberty in several brain regions, and identified when female odor preference normally emerges in male Syrian hamsters. We found that MePD PSA-NCAM staining peaks shortly before the surge of pubertal androgen and the emergence of preference. To test the necessity of PSA-NCAM for female odor preference, we infused endo-neuraminidase-N into the MePD to deplete it of PSAs before female odor preference normally appears. This blocked female odor preference, which suggests that PSA-NCAM facilitates behaviorally relevant, hormone-driven plasticity.

  16. Serenoa repens (Permixon) inhibits the 5alpha-reductase activity of human prostate cancer cell lines without interfering with PSA expression.

    PubMed

    Habib, Fouad K; Ross, Margaret; Ho, Clement K H; Lyons, Valerie; Chapman, Karen

    2005-03-20

    The phytotherapeutic agent Serenoa repens is an effective dual inhibitor of 5alpha-reductase isoenzyme activity in the prostate. Unlike other 5alpha-reductase inhibitors, Serenoa repens induces its effects without interfering with the cellular capacity to secrete PSA. Here, we focussed on the possible pathways that might differentiate the action of Permixon from that of synthetic 5alpha-reductase inhibitors. We demonstrate that Serenoa repens, unlike other 5alpha-reductase inhibitors, does not inhibit binding between activated AR and the steroid receptor-binding consensus in the promoter region of the PSA gene. This was shown by a combination of techniques: assessment of the effect of Permixon on androgen action in the LNCaP prostate cancer cell line revealed no suppression of AR and maintenance of PSA protein expression at control levels. This was consistent with reporter gene experiments showing that Permixon failed to interfere with AR-mediated transcriptional activation of PSA and that both testosterone and DHT were equally effective at maintaining this activity. Our results demonstrate that despite Serenoa repens effective inhibition of 5alpha-reductase activity in the prostate, it did not suppress PSA secretion. Therefore, we confirm the therapeutic advantage of Serenoa repens over other 5alpha-reductase inhibitors as treatment with the phytotherapeutic agent will permit the continuous use of PSA measurements as a useful biomarker for prostate cancer screening and for evaluating tumour progression.

  17. K99 surface antigen of Escherichia coli: antigenic characterization.

    PubMed Central

    Isaacson, R E

    1978-01-01

    K99 prepared by acid precipitation hemagglutinated guinea pig erythrocytes, whereas K99 prepared by chromatography on diethylaminoethyl-Sephadex did not. K99 purified by either procedure hemagglutinated horse erythrocytes. K99 prepared by acid precipitation contained a second antigen not presnet in the K99 prepared by chromatography on diethylaminoethyl-Sephadex. This antigen could be detected by immunoprecipitation with some, but not all, sera prepared against K99-positive Escherichia coli strains. It was assumed that this second antigen is not K99 and is responsible for the guinea pig erythrocyte hemagglutination reaction. Furthermore, the second antigen has an isoelectric point of 4.2, which has been reported by Morris and co-workers to be the isoelectric point of K99. Images PMID:83300

  18. Failure pattern implications following external beam irradiation of prostate cancer: long-term follow-up and indications of cure.

    PubMed

    Hanlon, A L; Hanks, G E

    2000-04-01

    The purpose of this study was to present patterns and risk of biochemical failure following external beam irradiation of prostate cancer and to make comparisons to a published modern radical prostatectomy series. Between January 1987 and December 1994, 328 men were treated definitively at Fox Chase Cancer Center for localized prostate cancer using conventional or three-dimensional conformal radiotherapy. The median biochemical follow-up was 6.4 years, with all patients having at least 5 years follow-up. Two prognostic patient groups were established on the basis of proportional hazards modeling that considered treatment and presenting tumor characteristics. For each of the two prognostic groups, biochemical failure and hazard functions were estimated using the ASTRO consensus definition of failure and life table methodology. Failure risk comparisons were made to modern published radical prostatectomy series. Multivariate analysis demonstrated the independent predictive power of pretreatment PSA level, palpation stage, Gleason score, and dose. Thus, the favorable prognosis group, Group I, consisted of 83 patients who were treated with a dose level > or = 74 Gy and who presented with PSA levels < 20 ng/ml, T1/T2A tumors, and Gleason score 2-6. Group II consisted of 245 patients with at least one of the following: pretreatment PSA level > or = 20 ng/ml, T2B/T3 tumor, Gleason score 7-10, dose < 74 Gy. The 5- and 8-year bNED estimates were 76% and 76% for Group I, and 51% and 49% for Group II. Only three failures occurred after 5 years, all from Group II, representing 2% of the total failures observed. Hazard function estimates indicate maximum risk of failure at 24 to 36 months, tapering to a low rate at 4 years with no failures observed after 6 years. Differences in patterns of failure by prognostic group show maximum risk of failure at 24 months (median, 31 months) for Group I, and 12 to 36 months (median, 22 months) for Group II. Group II reaches low levels of risk

  19. Failure in glass

    NASA Technical Reports Server (NTRS)

    Keeton, S. C.

    1972-01-01

    Review of state of the art concerning glass failure mechanisms and fatigue theories discusses brittle fracture in glass, fatigue mechanisms, fatigue behavior, environmental effects on failure rate, and aging.

  20. [Understanding heart failure].

    PubMed

    Boo, José Fernando Guadalajara

    2006-01-01

    Heart failure is a disease with several definitions. The term "heart failure" is used by has brougth about confusion in the terminology. For this reason, the value of the ejection fraction (< 0.40 or < 0.35) is used in most meganalyses on the treatment of heart failure, avoiding the term "heart failure" that is a confounding concept. In this paper we carefully analyze the meaning of contractility, ventricular function or performance, preload, afterload, heart failure, compensation mechanisms in heart failure, myocardial oxygen consumption, inadequate, adequate and inappropriate hypertrophy, systole, diastole, compliance, problems of relaxation, and diastolic dysfunction. Their definitions are supported by the original scientific descriptions in an attempt to clarify the concepts about ventricular function and heart failure and, in this way, use the same scientific language about the meaning of ventricular function, heart failure, and diastolic dysfunction.

  1. Natural selection promotes antigenic evolvability.

    PubMed

    Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

  2. Failures in psychodynamic psychotherapy.

    PubMed

    Gold, Jerry; Stricker, George

    2011-11-01

    This article addresses the issue of failures in psychodynamic psychotherapy. Drawing on the clinical and research literatures, and utilizing our clinical experiences, we first describe and define criteria for success and failure in treatment. We then review five factors that can lead to failure: client factors, therapist factors, technical factors, relationship factors, and environmental factors. We illustrate our presentation with a case example, and conclude by discussing ways in which the likelihood of failures in psychodynamic treatment can be lowered.

  3. Ammonia tank failure

    SciTech Connect

    Sweat, M.E.

    1983-04-01

    An ammonia tank failure at Hawkeye Chemical of Clinton, Iowa is discussed. The tank was a double-wall, 27,000 metric-ton tank built in 1968 and commissioned in December 1969. The paper presented covers the cause of the failure, repair, and procedural changes made to prevent recurrence of the failure. (JMT)

  4. Heart Failure: A Primer.

    PubMed

    Lee, Christopher S; Auld, Jonathan

    2015-12-01

    Heart failure is a complex and multisystem clinical syndrome that results from impaired ventricular contractility and/or relaxation. Hypertension, diabetes mellitus, and coronary artery disease are common antecedents to heart failure. The main pathogenic mechanisms involved in heart failure include sympathetic nervous and renin-angiotensin-aldosterone system activation, as well as inflammation. A detailed history and physical examination and additional diagnostic tests may be needed to diagnose heart failure. Most treatment strategies target neurohormonal systems. Nonpharmacologic interventions and effective engagement in self-care are also important in overall heart failure management. Therapeutic strategies are geared toward prolonging life and optimizing quality of life.

  5. The failure of earthquake failure models

    USGS Publications Warehouse

    Gomberg, J.

    2001-01-01

    In this study I show that simple heuristic models and numerical calculations suggest that an entire class of commonly invoked models of earthquake failure processes cannot explain triggering of seismicity by transient or "dynamic" stress changes, such as stress changes associated with passing seismic waves. The models of this class have the common feature that the physical property characterizing failure increases at an accelerating rate when a fault is loaded (stressed) at a constant rate. Examples include models that invoke rate state friction or subcritical crack growth, in which the properties characterizing failure are slip or crack length, respectively. Failure occurs when the rate at which these grow accelerates to values exceeding some critical threshold. These accelerating failure models do not predict the finite durations of dynamically triggered earthquake sequences (e.g., at aftershock or remote distances). Some of the failure models belonging to this class have been used to explain static stress triggering of aftershocks. This may imply that the physical processes underlying dynamic triggering differs or that currently applied models of static triggering require modification. If the former is the case, we might appeal to physical mechanisms relying on oscillatory deformations such as compaction of saturated fault gouge leading to pore pressure increase, or cyclic fatigue. However, if dynamic and static triggering mechanisms differ, one still needs to ask why static triggering models that neglect these dynamic mechanisms appear to explain many observations. If the static and dynamic triggering mechanisms are the same, perhaps assumptions about accelerating failure and/or that triggering advances the failure times of a population of inevitable earthquakes are incorrect.

  6. A new Kupffer cell receptor mediating plasma clearance of carcinoembryonic antigen by the rat.

    PubMed Central

    Toth, C A; Thomas, P; Broitman, S A; Zamcheck, N

    1982-01-01

    Native human carcinoembryonic antigen is rapidly removed from the circulation by the rat liver Kupffer cell after intravenous injection. The molecule is subsequently transferred to the hepatocyte in an immunologically identifiable form. Carcinoembryonic antigen has a circulatory half-life of 3.7 (+/- 0.8) min, and cellular entry is by receptor-mediated endocytosis. Non-specific fluid pinocytosis and phagocytosis can be excluded as possible mechanisms by the kinetics of clearance and failure of colloidal carbon to inhibit uptake. Substances with known affinity for the hepatic receptors for mannose, N-acetylglucosamine, fucose and galactose all fail to inhibit carcinoembryonic antigen clearance. After two cycles of the Smith degradation, carcinoembryonic antigen is still able to inhibit clearance of the native molecule. Receptor specificity is apparently not dependent on those non-reducing terminal sugars of the native molecule. Performic acid-oxidized carcinoembryonic antigen also inhibits clearance of carcinoembryonic antigen in vivo. Receptor binding is not dependent on tertiary protein conformation. Non-specific cross-reacting antigen, a glycoprotein structurally similar to carcinoembryonic antigen, is cleared by the same mechanism. PMID:6896821

  7. A new Kupffer cell receptor mediating plasma clearance of carcinoembryonic antigen by the rat.

    PubMed

    Toth, C A; Thomas, P; Broitman, S A; Zamcheck, N

    1982-05-15

    Native human carcinoembryonic antigen is rapidly removed from the circulation by the rat liver Kupffer cell after intravenous injection. The molecule is subsequently transferred to the hepatocyte in an immunologically identifiable form. Carcinoembryonic antigen has a circulatory half-life of 3.7 (+/- 0.8) min, and cellular entry is by receptor-mediated endocytosis. Non-specific fluid pinocytosis and phagocytosis can be excluded as possible mechanisms by the kinetics of clearance and failure of colloidal carbon to inhibit uptake. Substances with known affinity for the hepatic receptors for mannose, N-acetylglucosamine, fucose and galactose all fail to inhibit carcinoembryonic antigen clearance. After two cycles of the Smith degradation, carcinoembryonic antigen is still able to inhibit clearance of the native molecule. Receptor specificity is apparently not dependent on those non-reducing terminal sugars of the native molecule. Performic acid-oxidized carcinoembryonic antigen also inhibits clearance of carcinoembryonic antigen in vivo. Receptor binding is not dependent on tertiary protein conformation. Non-specific cross-reacting antigen, a glycoprotein structurally similar to carcinoembryonic antigen, is cleared by the same mechanism.

  8. Does Antigen Masking by Ubiquitin Chains Protect from the Development of Autoimmune Diseases?

    PubMed Central

    Weil, Robert

    2014-01-01

    Autoimmune diseases are characterized by the production of antibodies against self-antigens and generally arise from a failure of central or peripheral tolerance. However, these diseases may develop when newly appearing antigens are not recognized as self by the immune system. The mechanism by which some antigens are “invisible” to the immune system is not completely understood. Apoptotic and complement system defects or autophagy imbalance can generate this antigenic autoreactivity. Under particular circumstances, cellular debris containing autoreactive antigens can be recognized by innate immune receptors or other sensors and can eventually lead to autoimmunity. Ubiquitination may be one of the mechanisms protecting autoreactive antigens from the immune system that, if disrupted, can lead to autoimmunity. Ubiquitination is an essential post-translational modification used by cells to target proteins for degradation or to regulate other intracellular processes. The level of ubiquitination is regulated during T cell tolerance and apoptosis and E3 ligases have emerged as a crucial signaling pathway for the regulation of T cell tolerance toward self-antigens. I propose here that an unrecognized role of ubiquitin and ubiquitin-like proteins could be to render intracellular or foreign antigens (present in cellular debris resulting from apoptosis, complement system, or autophagy defects) invisible to the immune system in order to prevent the development of autoimmunity. PMID:24917867

  9. Relationship of spermatoscopy, prostatic acid phosphatase activity and prostate-specific antigen (p30) assays with further DNA typing in forensic samples from rape cases.

    PubMed

    Romero-Montoya, Lydia; Martínez-Rodríguez, Hugo; Pérez, Miguel Antonio; Argüello-García, Raúl

    2011-03-20

    In the forensic laboratory the biological analyses for rape investigation commonly include vaginal swabs as sample material combined to biochemical tests including sperm cytology (SC) and detection of acid phosphatase activity (AP) and prostate-specific antigen (PSA, p30) for the conclusive identification of semen components. Most reports comparing these tests relied on analysis of semen samples or donor swabs taken under controlled conditions; however their individual or combined efficacy under real live sampling conditions in different laboratories is largely unknown. We carried out SC, APA and PSA analyses in vaginal swabs collected from casework rapes submitted to Mexican Forensic Laboratories at Texcoco and Toluca. On the basis of positive and negative results from each assay and sample, data were classified into eight categories (I-VIII) and compared with those obtained in the two only similar studies reported in Toronto, Canada and Hong Kong, China. SC and APA assays had the higher overall positivity in Toluca and Texcoco samples respectively and otherwise PSA had a lower but very similar positivity between these two laboratories. When compared to the previous studies some similarities were found, namely similar frequencies (at a ratio of approximately 1 out of 3) of samples being positive or negative by all techniques (Categories I and VI respectively) and a comparable overall positivity of APA and SC but higher than that of PSA. Indeed the combined results of using SC, APA and PSA tests was considered as conclusive for semen detection from approximately 1 out of 3 cases (Category I) to approximately 1 out of 2 cases in a scenario where at least SC is positive, strongly presumptive in 2 out of 3 cases (with at least one test positive) and the remainder 1 out of 3 cases (Category VI) suggested absence of semen. By determining Y-STR polymorphisms (12-loci) in additional samples obtained at Toluca laboratory, complete DNA profiles were determined from all

  10. Common antigen structures of HL-A antigens

    PubMed Central

    Miyakawa, Y.; Tanigaki, N.; Yagi, Y.; Pressman, D.

    1973-01-01

    Antigenic determinants recognizable by rabbits were found to be present on the molecular fragments (48,000 Daltons) which were obtained by papain-solubilization of the membrane fractions of cultured human lymphoid cells and which carried the HL-A determinants. Results were obtained which suggest that these antigenic determinants are present in common on these molecular fragments carrying HL-A determinants regardless of their HL-A specificity and are restricted to the molecular fragments which carry HL-A determinants. The study was made by use of radioimmune methods involving the binding of radioiodine-labelled soluble HL-A antigen preparations by anti-HL-A alloantisera and by rabbit antisera raised against the membrane fractions of cultured human lymphoid cells. PMID:4119543

  11. Kidney Failure: What to Expect

    MedlinePlus

    ... Kidneys & How They Work Kidney Disease A-Z Kidney Failure What is kidney failure and how is it treated? Kidney failure ... Methods for Kidney Failure: Peritoneal Dialysis . Peritoneal dialysis Kidney Transplant A kidney transplant places a healthy kidney ...

  12. How does antigen retrieval work?

    PubMed

    Leong, Trishe Y-M; Leong, Anthony S-Y

    2007-03-01

    The introduction of antigen retrieval has enabled immunohistology to become an integral component of morphologic diagnosis, routinely employed in cancer diagnosis, and for the identification of therapeutic and prognostic markers. The mechanism of antigen retrieval, however, remains speculative with the key to our understanding embedded in the actions of formaldehyde on proteins. One commonly held concept is that heat primarily breaks down protein cross-linkages that occur with aldehyde fixation, thus "unmasking" protein epitopes of interest. Enzymatic pretreatment is also thought to have a similar action whereas such "breakages" are the result of extremely rapid molecular movement induced by microwaves and ultrasound. The formation of rigid cagelike calcium complexes during formaldehyde fixation is another suggested mechanism of antigen masking requiring chelating agents for reversal. A more recent suggestion for the antigen retrieval phenomenon has evoked the Mannich reaction, which occurs with the cross-linking of some proteins. Such cross-linkages can be hydrolyzed by heat or alkalis so that the process of antigen retrieval may be the simple removal of such cross-linked proteins that are sterically interfering with the binding of antibodies to linear protein epitopes in the tissue section. We are clearly not yet in possession of all the answers to the problem.

  13. DNA fragmentation, caspase 3 and prostate-specific antigen genes expression induced by arsenic, cadmium, and chromium on nontumorigenic human prostate cells.

    PubMed

    El-Atta, Hend M Abo; El-Bakary, Amal A; Attia, Afaf M; Lotfy, Ahmed; Khater, Shery S; Elsamanoudy, Ayman Z; Abdalla, Hussein Abdelaziz

    2014-12-01

    Prostate cancer is one of the most common cancers and the second cause of cancer-related deaths among men. Metals are recognized as chemical carcinogens where chronic exposures to such metals are implicated in the development of cancer, including prostate cancer. This in vitro study demonstrates the relative death sensitivity of prostatic (RWPE-1) cells to arsenic (As), cadmium (Cd), and chromium (Cr) as environmental pollutants through its apoptotic effects and the effect of these chemicals on prostate-specific antigen (PSA) gene expression as a marker for their carcinogecity. RWPE-1 cells were divided into three groups that were treated with As, Cd, and Cr in three replicates, at three different concentrations for each metal for 48 h. A control group consisted of untreated RWPE1 cells was used. Apoptosis was assessed using comet assay and caspase 3 gene expression; meanwhile, PSA gene expression was evaluated by semiqualitative real-time PCR (RT-PCR). One of the novel findings of this study is that arsenic and cadmium at low concentrations decreased apoptosis of RWPE-1 cells in a concentration-dependent manner while chromium induced significant concentration-dependent increase in apoptosis. Yet, at the highest concentrations, apoptosis was relatively more induced by all chemicals. Arsenic was the most chemical inhibiting apoptosis in RWPE-1 cells at low concentration. While at the moderate and highest concentrations, cadmium was the most inhibiting chemical of RWPE-1 cells' apoptosis. No distinct differences between treated and untreated cells for PSA gene expression were observed. It can be concluded that As and Cd, at low concentrations, can reduce apoptosis of prostatic cells in a concentration-dependent manner while chromium induced it; however, all metal salts used in this study did not induce PSA gene expression.

  14. Associations of Prostate-Specific Antigen, Prostate Carcinoma Tissue Gleason Score, and Androgen Receptor Expression with Bone Metastasis in Patients with Prostate Carcinoma.

    PubMed

    Chen, Yehui; Lin, Yun; Nie, Pin; Jiang, Wen; Liu, Yanqing; Yuan, Runqiang; Li, Miaoyuan; Zhao, Shijia; Lin, Huaxin; Li, Penghui; Zhang, Jinxiang; Hu, Zhiwen; Xu, Jin; Zhu, Xusheng

    2017-04-12

    BACKGROUND Prostate carcinoma (PCa) is often not diagnosed until advanced disease with bone metastasis. Predictive factors for bone metastasis are required to improve patient outcomes. The study aimed to analyze the factors associated with bone metastases in newly diagnosed patients with PCa. MATERIAL AND METHODS This was a retrospective study of 80 patients newly diagnosed with PCa by pathological examination between January 2012 and December 2014. Bone metastases were diagnosed by positron emission computed tomography. Clinical data, serological laboratory results, and pathological examination results were collected. RESULTS Among the 80 patients, 45 (56%) had bone metastases. Age, serum alkaline phosphatase, prostate-specific antigen (PSA), erythrocyte sedimentation rate, PCa tissue Gleason score, androgen receptor (AR) expression, and Ki-67 expression were higher in patients with bone metastasis compared with those without (all P<0.05). Multivariate logistic regression showed that PSA (OR: 1.005; 95%CI: 1.001-1.010; P=0.016), Gleason score (OR: 4.095; 95%CI: 1.592-10.529; P=0.003), and AR expression (OR: 14.023; 95%CI: 3.531-55.6981; P=0.005) were independently associated with bone metastases. Cut-off values for PSA, Gleason score, and AR expression were 67.1 ng/ml (sensitivity: 55.6%; specificity: 97.1%), 7.5 (sensitivity: 75.6%; specificity: 82.9%), and 2.5 (sensitivity: 84.0%; specificity: 91.4%), respectively. CONCLUSIONS PSA, Gleason score, and AR expression in PCa tissues were independently associated with PCa bone metastases. These results could help identifying patients with PCa at high risk of bone metastases.

  15. Early complications. Respiratory failure.

    PubMed

    Zwischenberger, J B; Alpard, S K; Bidani, A

    1999-08-01

    Pulmonary complications following thoracic surgery are common and associated with significant morbidity and mortality. Respiratory failure after pneumonectomy occurs in approximately 5% to 15% of cases and significantly increases patient mortality. Strategies for ventilator support are based on the nature of the underlying complication and the pathophysiology of respiratory failure. This article describes the cause and pathophysiology of respiratory failure and pulmonary embolus postpneumonectomy. Diagnosis, management, and innovative therapies are also reviewed.

  16. Failure to thrive.

    PubMed

    Krugman, Scott D; Dubowitz, Howard

    2003-09-01

    Failure to thrive is a condition commonly seen by primary care physicians. Prompt diagnosis and intervention are important for preventing malnutrition and developmental sequelae. Medical and social factors often contribute to failure to thrive. Either extreme of parental attention (neglect or hypervigilance) can lead to failure to thrive. About 25 percent of normal infants will shift to a lower growth percentile in the first two years of life and then follow that percentile; this should not be diagnosed as failure to thrive. Infants with Down syndrome, intrauterine growth retardation, or premature birth follow different growth patterns than normal infants. Many infants with failure to thrive are not identified unless careful attention is paid to plotting growth parameters at routine checkups. A thorough history is the best guide to establishing the etiology of the failure to thrive and directing further evaluation and management. All children with failure to thrive need additional calories for catch-up growth (typically 150 percent of the caloric requirement for their expected, not actual, weight). Few need laboratory evaluation. Hospitalization is rarely required and is indicated only for severe failure to thrive and for those whose safety is a concern. A multidisciplinary approach is recommended when failure to thrive persists despite intervention or when it is severe.

  17. Ectopic Expression of Transcription Factor AP-2δ in Developing Retina: Effect on PSA-NCAM and Axon Routing

    PubMed Central

    Li, Xiaodong; Monckton, Elizabeth A.; Godbout, Roseline

    2015-01-01

    Retinal ganglion cells transmit the visual signal from the retina to the brain. We have previously shown that the AP-2δ (TFAP2D) transcription factor is expressed in one-third of ganglion cells in developing retina suggesting a specialized role for these AP-2δ-expressing cells. Here, we address the role of AP-2δ in retina by in ovo electroporation of RCAS/AP-2δ retroviral constructs into the eyes of chick embryos at day 2 of gestation. Ectopic expression of AP-2δ does not affect lineage differentiation in the developing retina. However, immunostaining of retinal tissue with markers associated with axonal growth such as GAP43 and PSA-NCAM demonstrates axonal misrouting and abnormal axonal bundling. Treatment of AP-2δ-misexpressing retinal cell cultures with Endo-N, an enzyme that removes PSA from NCAM, decreases AP-2δ-induced axonal bundling. Our data suggest a role for AP-2δ in polysialylation of NCAM, with ectopic expression of AP-2δ resulting in premature bundling of emerging axons and misrouting of axons. We propose that expression of AP-2δ in a subset of ganglion cells contributes to the fine-tuning of axonal growth in the developing retina. PMID:24188130

  18. Structural plasticity of interneurons in the adult brain: role of PSA-NCAM and implications for psychiatric disorders.

    PubMed

    Nacher, Juan; Guirado, Ramon; Castillo-Gómez, Esther

    2013-06-01

    Neuronal structural plasticity is known to have a major role in cognitive processes and in the response of the CNS to aversive experiences. This type of plasticity involves processes ranging from neurite outgrowth/retraction or dendritic spine remodeling, to the incorporation of new neurons to the established circuitry. However, the study of how these structural changes take place has been focused mainly on excitatory neurons, while little attention has been paid to interneurons. The exploration of these plastic phenomena in interneurons is very important, not only for our knowledge of CNS physiology, but also for understanding better the etiology of different psychiatric and neurological disorders in which alterations in the structure and connectivity of inhibitory networks have been described. Here we review recent work on the structural remodeling of interneurons in the adult brain, both in basal conditions and after chronic stress or sensory deprivation. We also describe studies from our laboratory and others on the putative mediators of this interneuronal structural plasticity, focusing on the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). This molecule is expressed by some interneurons in the adult CNS and, through its anti-adhesive and insulating properties, may participate in the remodeling of their structure. Finally, we review recent findings on the possible implication of PSA-NCAM on the remodeling of inhibitory neurons in certain psychiatric disorders and their treatments.

  19. Ectopic expression of transcription factor AP-2δ in developing retina: effect on PSA-NCAM and axon routing.

    PubMed

    Li, Xiaodong; Monckton, Elizabeth A; Godbout, Roseline

    2014-04-01

    Retinal ganglion cells transmit the visual signal from the retina to the brain. We have previously shown that the activator protein 2 (AP-2)δ (TFAP2D) transcription factor is expressed in one third of ganglion cells in developing retina suggesting a specialized role for these AP-2δ-expressing cells. Here, we address the role of AP-2δ in retina by in ovo electroporation of RCAS/AP-2δ retroviral constructs into the eyes of chick embryos at day 2 of gestation. Ectopic expression of AP-2δ does not affect lineage differentiation in the developing retina. However, immunostaining of retinal tissue with markers associated with axonal growth such as growth-associated protein 43 and polysialic acid-neural cell adhesion molecule (PSA-NCAM) demonstrates axonal misrouting and abnormal axonal bundling. Treatment of AP-2δ-misexpressing retinal cell cultures with endoneuraminidase, an enzyme that removes PSA from NCAM, decreases AP-2δ-induced axonal bundling. Our data suggest a role for AP-2δ in polysialylation of NCAM, with ectopic expression of AP-2δ resulting in premature bundling of emerging axons and misrouting of axons. We propose that expression of AP-2δ in a subset of ganglion cells contributes to the fine-tuning of axonal growth in the developing retina.

  20. Equivalent Biochemical Control and Improved Prostate-Specific Antigen Nadir After Permanent Prostate Seed Implant Brachytherapy Versus High-Dose Three-Dimensional Conformal Radiotherapy and High-Dose Conformal Proton Beam Radiotherapy Boost

    SciTech Connect

    Jabbari, Siavash; Weinberg, Vivian K.; Shinohara, Katsuto; Speight, Joycelyn L.; Gottschalk, Alexander R.; Hsu, I.-C.; Pickett, Barby; McLaughlin, Patrick W.; Sandler, Howard M.; Roach, Mack

    2010-01-15

    Purpose: Permanent prostate implant brachytherapy (PPI), three-dimensional conformal radiotherapy (3D-CRT), and conformal proton beam radiotherapy (CPBRT) are used in the treatment of localized prostate cancer, although no head-to-head trials have compared these modalities. We studied the biochemical control (biochemical no evidence of disease [bNED]) and prostate-specific antigen (PSA) nadir achieved with contemporary PPI, and evaluated it against 3D-CRT and CPBRT. Patients and Methods: A total of 249 patients were treated with PPI at the University of California, San Francisco, and the outcomes were compared with those from a 3D-CRT cohort and the published results of a high-dose CPBRT boost (CPBRTB) trial. For each comparison, subsets of the PPI cohort were selected with patient and disease criteria similar to those of the reference group. Results: With a median follow-up of 5.3 years, the bNED rate at 5 and 7 years achieved with PPI was 92% and 86%, respectively, using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, and 93% using the PSA nadir plus 2 ng/mL definition. Using the ASTRO definition, a 5-year bNED rate of 78% was achieved for the 3D-CRT patients compared with 94% for a comparable PPI subset and 93% vs. 92%, respectively, using the PSA nadir plus 2 ng/mL definition. The median PSA nadir for patients treated with PPI and 3D-CRT was 0.10 and 0.40 ng/mL, respectively (p < .0001). For the CPBRT comparison, the 5-year bNED rate after a CPBRTB was 91% using the ASTRO definition vs. 93% for a similar group of PPI patients. A greater proportion of PPI patients achieved a lower PSA nadir compared with those achieved in the CPBRTB trial (PSA nadir <=0.5 ng/mL, 91% vs. 59%, respectively). Conclusion: We have demonstrated excellent outcomes in low- to intermediate-risk patients treated with PPI, suggesting at least equivalent 5-year bNED rates and a greater proportion of men achieving lower PSA nadirs compared with 3D-CRT or

  1. A comparison of two anesthesia methods for the surgical removal of maxillary third molars: PSA nerve block technique vs. local infiltration technique

    PubMed Central

    2014-01-01

    Objectives: The purpose of this study was to compare the effect of PSA block injection with infiltration technique regarding local anesthesia for surgical extraction of upper third molar. Material and Methods: A prospective, intra individual, single-blind randomized controlled trial was designed to study the severity of pain during injection and after surgical extraction of the bilaterally and symmetrically similar upper third molar in a total of 53 patients, in addition to evaluating the need to repeat the injection and requirement of post operative anti-inflammatory tablets. Result: Although the average pain score for all studied times in PSA side was lower than the average pain score in infiltration technique, repeated statistical measures demonstrated that no significant pain reduction occurred in the two techniques. Conclusion: The both tested methods have the same statistic equivalence for the surgical extraction of maxillary third molars. Key words:Surgical extraction, maxillary third molars, PSA block, infiltration. PMID:24596629

  2. Antigenic determinants and functional domains in core antigen and e antigen from hepatitis B virus.

    PubMed Central

    Salfeld, J; Pfaff, E; Noah, M; Schaller, H

    1989-01-01

    The precore/core gene of hepatitis B virus directs the synthesis of two polypeptides, the 21-kilodalton subunit (p21c) forming the viral nucleocapsid (serologically defined as core antigen [HBcAg]) and a secreted processed protein (p17e, serologically defined as HBe antigen [HBeAg]). Although most of their primary amino acid sequences are identical, HBcAg and HBeAg display different antigenic properties that are widely used in hepatitis B virus diagnosis. To locate and to characterize the corresponding determinants, segments of the core gene were expressed in Escherichia coli and probed with a panel of polyclonal or monoclonal antibodies in radioimmunoassays or enzyme-linked immunosorbent assays, Western blots, and competition assays. Three distinct major determinants were characterized. The single conformational determinant responsible for HBc antigenicity in the assembled core (HBc) and a linear HBe-related determinant (HBe1) were both mapped to an overlapping hydrophilic sequence around amino acid 80; a second HBe determinant (HBe2) was assigned to a location in the vicinity of amino acid 138 but found to require for its antigenicity the intramolecular participation of the extended sequence between amino acids 10 and 140. It is postulated that HBcAg and HBeAg share common basic three-dimensional structure exposing the common linear determinant HBe1 but that they differ in the presentation of two conformational determinants that are either introduced (HBc) or masked (HBe2) in the assembled core. The simultaneous presentation of HBe1 and HBc, two distinctly different antigenic determinants with overlapping amino acid sequences, is interpreted to indicate the presence of slightly differently folded, stable conformational states of p21c in the hepatitis B virus nucleocapsid. Images PMID:2463383

  3. Varying expression of major histocompatibility complex antigens on human renal endothelium and epithelium.

    PubMed Central

    Evans, P. R.; Trickett, L. P.; Smith, J. L.; MacIver, A. G.; Tate, D.; Slapak, M.

    1985-01-01

    Pre-anastomosis wedge biopsies from 14 cadaveric donor kidneys were examined for the expression of class I (HLA-ABC) and class II (HLA-DR) antigens in renal tissue. Two monoclonal antibodies to class I antigens and four to class II antigens were used in an indirect immunoperoxidase technique. Consistent expression of both antigens was demonstrated on the surface of glomerular, peritubular capillary and venous endothelial cells. Renal arteries contained only class I antigens. Proximal tubules contained varying amounts of each antigen in their cytoplasm. Sixteen human lymphocytotoxic allo-antisera showed marked variation in their ability to detect HLA antigens on the kidney. The selection of donors for recipients of renal allografts involves the complement-dependent cytotoxicity test and the failure of some lymphocytotoxic antisera to bind to the kidney indicates that some suitable patients may be incorrectly excluded. The use of a binding assay using an immunoperoxidase technique should be included in cross-match techniques particularly for patients who have high levels of circulating cytotoxic antibodies. Images Fig. 1 Fig. 2 Fig. 3 PMID:3855644

  4. Detection of antibodies against hepatitis B virus surface antigen and hepatitis C virus core antigen in plasma with a waveguide-mode sensor.

    PubMed

    Shimizu, Takenori; Tanaka, Torahiko; Uno, Shigeyuki; Ashiba, Hiroki; Fujimaki, Makoto; Tanaka, Mutsuo; Awazu, Koichi; Makishima, Makoto

    2017-02-09

    In large-scale disasters, such as huge significant earthquakes, on-site examination for blood typing and infectious disease screening will be very helpful to save lives of victims who need surgical treatment and/or blood transfusion. However, physical damage, such as building collapse, electric power failure and traffic blockage, disrupts the capacity of the medical system. Portable diagnostic devices are useful in such cases of emergency. In this study, we evaluated a waveguide-mode sensor for detection of anti-hepatitis virus antibodies. First, we examined whether we can detect antigen-antibody interaction on a sensor chip immobilized hepatitis B virus surface (HBs) antigen and hepatitis C virus (HCV) core antigen using monoclonal mouse antibodies for HBs antigen and HCV core antigen. We obtained significant changes in the reflectance spectra, which indicate specific antigen-antibody interaction for anti-HBs antibody and anti-HCV antibody. Next, we examined the effect of horseradish peroxidase-conjugated secondary antibody using aminoethyl carbazole as the peroxidase substrate and found that the colorimetric reaction increases detection sensitivity for anti-HBs antibody more than 300 times. Finally, we successfully detected anti-HBs antibody in human blood samples with an enhancing method using a peroxidase reaction. Thus, a portable device utilizing a waveguide-mode sensor may be applied to on-site blood testing in emergency settings.

  5. Metastasis in urothelial carcinoma mimicking prostate cancer metastasis in Ga-68 prostate-specific membrane antigen positron emission tomography-computed tomography in a case of synchronous malignancy.

    PubMed

    Gupta, Manoj; Choudhury, Partha Sarathi; Gupta, Gurudutt; Gandhi, Jatin

    2016-01-01

    Prostate cancer is the second most common cancer in man. It commonly presents with urinary symptoms, bone pain, or diagnosed with elevated prostate-specific antigen.(PSA) levels. Correct staging and early diagnosis of recurrence by a precise imaging tool are the keys for optimum management. Molecular imaging of prostate cancer with Ga-68 prostate-specific membrane antigen.(PSMA), positron emission tomography-computed tomography.(PET-CT) has recently received significant attention and frequently used with a signature to prostate cancer-specific remark. However, this case will highlight the more cautious use of it. A-72-year-old male treated earlier for synchronous double malignancy.(invasive papillary urothelial carcinoma right ureter and carcinoma prostate) presented with rising PSA.(0.51.ng/ml) and referred for Ga-68 PSMA PET-CT, which showed a positive enlarged left supraclavicular lymph node. Lymph node biopsy microscopic and immunohistochemistry examination revealed metastatic carcinoma favoring urothelial origin. Specificity of PSMA scan to prostate cancer has been seen to be compromised in a certain situation mostly due to neoangiogenesis, and false positives emerged in renal cell cancer, differentiated thyroid cancer, glioblastoma, breast cancer brain metastasis, and paravertebral schwannomas. Understanding the causes of false positive will further enhance the confidence of interpretating PSMA scans.

  6. Living with Respiratory Failure

    MedlinePlus

    ... smoking. Emotional Issues and Support Living with respiratory failure may cause fear, anxiety, depression, and stress. Talk about how you feel with your health care team. Talking to a professional counselor also can ... to living with respiratory failure. You can see how other people who have ...

  7. Ampoule Failure System

    NASA Technical Reports Server (NTRS)

    Watring, Dale A. (Inventor); Johnson, Martin L. (Inventor)

    1996-01-01

    An ampoule failure system for use in material processing furnaces comprising a containment cartridge and an ampoule failure sensor. The containment cartridge contains an ampoule of toxic material therein and is positioned within a furnace for processing. An ampoule failure probe is positioned in the containment cartridge adjacent the ampoule for detecting a potential harmful release of toxic material therefrom during processing. The failure probe is spaced a predetermined distance from the ampoule and is chemically chosen so as to undergo a timely chemical reaction with the toxic material upon the harmful release thereof. The ampoule failure system further comprises a data acquisition system which is positioned externally of the furnace and is electrically connected to the ampoule failure probe so as to form a communicating electrical circuit. The data acquisition system includes an automatic shutdown device for shutting down the furnace upon the harmful release of toxic material. It also includes a resistance measuring device for measuring the resistance of the failure probe during processing. The chemical reaction causes a step increase in resistance of the failure probe whereupon the automatic shutdown device will responsively shut down the furnace.

  8. Prostate specific antigen biosensor based on long range surface plasmon-enhanced fluorescence spectroscopy and dextran hydrogel binding matrix.

    PubMed

    Wang, Yi; Brunsen, Annette; Jonas, Ulrich; Dostálek, Jakub; Knoll, Wolfgang

    2009-12-01

    A new biosensor based on surface plasmon-enhanced fluorescence spectroscopy (SPFS), which employs long-range surface plasmons (LRSP) and a photo-cross-linkable carboxymethyl dextran (PCDM) hydrogel binding matrix, is reported. LRSPs are surface plasmon modes that propagate along a thin metallic film with orders of magnitude lower damping compared to regular surface plasmons. Therefore, their excitation provides strong enhancement of the intensity of the electromagnetic field and a greatly increased fluorescence signal measured upon binding of fluorophore-labeled molecules on the sensor surface. In addition, these modes exhibit highly extended evanescent fields penetrating up to micrometers in distance from the metallic sensor surface. Therefore, a PCDM hydrogel with approximately micrometer thickness was anchored on the sensor surface to serve as the binding matrix. We show that this approach provides large binding capacity and allows for the ultrasensitive detection. In a model experiment, the developed biosensor platform was applied for the detection of free prostate specific antigen (f-PSA) in buffer and human serum by using a sandwich immunoassay. The limit of detection at the low femtomolar range was achieved, which is approximately 4 orders of magnitude lower than that for direct detection of f-PSA based on the monitoring of binding-induced refractive index changes.

  9. A microfluidic immunoassay platform for the detection of free prostate specific antigen: a systematic and quantitative approach.

    PubMed

    Madaboosi, Narayanan; Soares, Ruben R G; Chu, Virginia; Conde, João Pedro

    2015-07-07

    As a leading cause of cancer-related deaths in men globally, prostate cancer (PCa) demands immense attention for theranostic purposes. There is an increasing need for the development of rapid, sensitive, economical, miniaturized and multiplexable assays. Towards this goal, we present a systematic approach for the optimisation of a microfluidic sandwich immunoassay, which can be applied as a generic biosensor platform for PCa detection. Prostate specific antigen (PSA) was used as the model biomarker, and its free form was captured using commercially available antibodies and detected using chemiluminescence, both in spiked buffer and matrix solutions. Along with the optimisation of surface chemistry and microfluidic parameters, we report a bio-affinity amplification strategy based on biotin-streptavidin chemistry to bring the limits of detection for free-PSA from 21.4 ng mL(-1) down to 2.7 ng mL(-1), within the clinically relevant range. An estimate of the surface coverage and simulations of the interactions taking place in the microfluidic biosensor during the assay are also presented. This novel platform using a simple passive adsorption-based bio-affinity strategy, when coupled with multiplexing and integrated detection, can serve as a promising point-of-care diagnostic tool for PCa.

  10. Grafting of a peptide probe for Prostate-Specific Antigen detection using diazonium electroreduction and click chemistry.

    PubMed

    Strzemińska, I; Sainte Rose Fanchine, S; Anquetin, G; Reisberg, S; Noël, V; Pham, M C; Piro, B

    2016-07-15

    The main objective of this work was to validate a label-free electrochemical method of protein detection using peptides as capture probes. As a proof-of-concept, we used a 7 amino acids sequence (HSSKLQL) specific for Prostate Specific Antigen. We investigated various electrografting conditions of two anilines (2-[(4-aminophenyl)sulfanyl]-8-hydroxy-1,4-naphthoquinone and 4-azidoaniline) further converted in situ into their corresponding diazonium salts on glassy carbon electrodes. It was demonstrated that the best method to obtain a mixed layer is the simultaneous electroreduction of the two diazonium salts. 4-azidoaniline was used to covalently immobilize the ethynyl-functionalized peptide probe by click coupling, and the hydroxynaphthoquinone derivative plays the role of electrochemical transducer of the peptide-protein recognition. The proteolytic activity of PSA towards a small peptide substrate carrying streptavidin at its distal end was also investigated to design an original sensing architecture leading to a reagentless, label free, and "signal-on" PSA sensor. Without optimization, the limit of quantification can be estimated in the nM to pM range.

  11. New frontiers in prostate cancer imaging: clinical utility of prostate-specific membrane antigen positron emission tomography.

    PubMed

    Afaq, Asim; Batura, Deepak; Bomanji, Jamshed

    2017-02-14

    Prostate-specific membrane antigen positron emission tomography (PSMA PET) is a relatively new method of imaging prostate cancer that increases diagnostic accuracy in detecting and guiding management in various stages of the disease pathway. Gallium-68-labelled PSMA PET has increased the sensitivity of detection of disease recurrence at low PSA levels, thus allowing an optimal window for salvage treatment. Apart from its use in disease recurrence, PSMA PET has the potential for increasing sensitivity and specificity for primary tumour localisation and in detecting lymph node disease, leading to a more accurate initial staging of the condition. In advanced disease, the use of PSMA PET may be able to assess response to treatment and also guide treatment with radionuclide therapy. Newer ligands under development might provide avenues for theranostic or personalised therapy applications with early data showing high PSA response rates. The rate of translation of PSMA PET into clinical practice has been remarkable. The use of this modality is likely to increase with future efforts to modify the radiotracer including (18)F labelling to improve availability.

  12. Spectrum-based and color-selective electrochemiluminescence immunoassay for determining human prostate specific antigen in near-infrared region.

    PubMed

    Zhou, Jie; He, Yupeng; Zhang, Bin; Sun, Qiaoling; Zou, Guizheng

    2017-04-01

    The conventional electrochemiluminescence (ECL) analyses were performed via detecting the time (or potential) dependent ECL intensity with the proceeding of ECL reaction. Herein, by spectrally recording all the photons generated in ECL process, a spectral ECL immunoassay was developed in near-infrared (NIR) region with human prostate specific antigen (PSA) as target and dual-stabilizers-capped CdTe nanocrystals (NCs) as tags. The CdTe NCs displayed efficient ECL around 780nm with the full width at half-maximum around 70nm in the immune-complexes, the maximum intensity on ECL spectrum profiles increased linearly with the logarithmic increased concentration of PSA from 20.0fg/mL to 100.0pg/mL, indicating a sensitive and color-selective ECL immunoassay in NIR region with improved anti-interference performance to biological autofluorescence and tissue absorption. The spectral ECL immunoassay in NIR region might provide an important technique support for developing color-selective ECL assay of different wavebands.

  13. Detection of antibody-antigen reaction by silicon nitride slot-ring biosensors using protein G

    NASA Astrophysics Data System (ADS)

    Taniguchi, Tomoya; Hirowatari, Anna; Ikeda, Takeshi; Fukuyama, Masataka; Amemiya, Yoshiteru; Kuroda, Akio; Yokoyama, Shin

    2016-04-01

    Biosensors using ring resonators with silicon nitride (SiN) slot waveguides have been fabricated. The temperature coefficient of the resonance wavelength of the SiN resonator is 0.006 nm/°C, which is one order of magnitude smaller than that of Si. The sensitivity of the biosensor has been improved by using slot waveguide together with Si-binding protein (designated as Si-tag), which bonds to SiN or SiO2 surface, as an anchoring molecule to immobilize bioreceptors on the SiN rings in an oriented manner. Furthermore, the protein G, which strongly bonds to many kinds of mammalian antibodies only by mixing the antibody solution, is used to efficiently immobilize the antigen on the sensor surface. By means of these devises the sensitivity of the biosensor has been improved by factor of 10-100 compared with that of normal Si ring resonator sensors without slot. Then the detection of prostate specific antigen (PSA) with the sensitivity of ~1×10-8 g/ml, which is the concentration of strongly suspicious for the prostate cancer, has been achieved.

  14. Generalized energy failure criterion.

    PubMed

    Qu, R T; Zhang, Z J; Zhang, P; Liu, Z Q; Zhang, Z F

    2016-03-21

    Discovering a generalized criterion that can predict the mechanical failure of various different structural materials is one of ultimate goals for scientists in both material and mechanics communities. Since the first study on the failure criterion of materials by Galileo, about three centuries have passed. Now we eventually find the "generalized energy criterion", as presented here, which appears to be one universal law for various different kinds of materials. The validity of the energy criterion for quantitatively predicting the failure is experimentally confirmed using a metallic glass. The generalized energy criterion reveals the competition and interaction between shear and cleavage, the two fundamental inherent failure mechanisms, and thus provides new physical insights into the failure prediction of materials and structural components.

  15. Acute Decompensated Heart Failure

    PubMed Central

    Joseph, Susan M.; Cedars, Ari M.; Ewald, Gregory A.; Geltman, Edward M.; Mann, Douglas L.

    2009-01-01

    Hospitalizations for acute decompensated heart failure are increasing in the United States. Moreover, the prevalence of heart failure is increasing consequent to an increased number of older individuals, as well as to improvement in therapies for coronary artery disease and sudden cardiac death that have enabled patients to live longer with cardiovascular disease. The main treatment goals in the hospitalized patient with heart failure are to restore euvolemia and to minimize adverse events. Common in-hospital treatments include intravenous diuretics, vasodilators, and inotropic agents. Novel pharmaceutical agents have shown promise in the treatment of acute decompensated heart failure and may simplify the treatment and reduce the morbidity associated with the disease. This review summarizes the contemporary management of patients with acute decompensated heart failure. PMID:20069075

  16. Generalized energy failure criterion

    PubMed Central

    Qu, R. T.; Zhang, Z. J.; Zhang, P.; Liu, Z. Q.; Zhang, Z. F.

    2016-01-01

    Discovering a generalized criterion that can predict the mechanical failure of various different structural materials is one of ultimate goals for scientists in both material and mechanics communities. Since the first study on the failure criterion of materials by Galileo, about three centuries have passed. Now we eventually find the “generalized energy criterion”, as presented here, which appears to be one universal law for various different kinds of materials. The validity of the energy criterion for quantitatively predicting the failure is experimentally confirmed using a metallic glass. The generalized energy criterion reveals the competition and interaction between shear and cleavage, the two fundamental inherent failure mechanisms, and thus provides new physical insights into the failure prediction of materials and structural components. PMID:26996781

  17. Urinary microRNA-based signature improves accuracy of detection of clinically relevant prostate cancer within the prostate-specific antigen grey zone

    PubMed Central

    SALIDO-GUADARRAMA, ALBERTO IVAN; MORALES-MONTOR, JORGE GUSTAVO; RANGEL-ESCAREÑO, CLAUDIA; LANGLEY, ELIZABETH; PERALTA-ZARAGOZA, OSCAR; COLIN, JOSE LUIS CRUZ; RODRIGUEZ-DORANTES, MAURICIO

    2016-01-01

    At present, prostate-specific antigen (PSA) is used as a clinical biomarker for prostate cancer (PCa) diagnosis; however, a large number of patients with benign prostate hyperplasia (BPH) with PSA levels in the ʻgray areaʼ (4–10 ng/ml) are currently subjected to unnecessary biopsy due to overdiagnosis. Certain microRNAs (miRs) have been proven to be useful biomarkers, several of which are detectable in bodily fluids. The present study identified and validated a urinary miR-based signature to enhance the specificity of PCa diagnosis and to reduce the number of patients with benign conditions undergoing biopsy. Seventy-three urine samples from Mexican patients with diagnosis of PCa with a Gleason score ≥7 and 70 patients diagnosed with BPH were collected after digital rectal examination (DRE) of the prostate. miR expression profiles were determined using TaqMan Low Density Array experiments, and normalized Ct values for the miRs were compared between PCa and BPH groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether miR detection in urine is suitable for distinguishing patients with PCa from those with BPH. The identified miR-100/200b signature was significantly correlated with PCa. Using a multivariable logistic regression approach, a base model including the clinical variables age, prostate-specific antigen (PSA), the percentage of free PSA and DRE was generated, and a second base model additionally contained the miR-100/200b signature. ROC analysis demonstrated that the combined model significantly outperformed the capacity of PSA (P<0.001) and the base model (P=0.01) to discriminate between PCa and BPH patients. In terms of evaluation of the sub-group of patients in the gray zone of PSA levels, the performance of the combined model for predicting PCa cases was significantly superior to PSA level determination (P<0.001) and the base model (P=0.009). In addition, decision curve analysis demonstrated that the use of

  18. [Heart failure and comorbidities].

    PubMed

    Boully, Clémence; Hanon, Olivier

    2015-03-01

    Heart failure is a frequent disease in the elderly. Its clinical presentation is less typical and the prognosis more severe than in younger subjects because heart failure occurs in patients with multiple comorbidities. A comprehensive geriatric assessment should therefore be performed to detect the vulnerabilities and manage the comorbidities. The main diseases associated with heart failure are dementia, depression, malnutrition, atrial fibrillation, coronary artery disease, orthostatic hypotension, renal failure, anemia and iron deficiency. Comorbidities worsen heart failure and makes its treatment more difficult. The identification and treatment of comorbidities improve the prognosis in terms of mortality but especially in terms of quality of life. Caution with drugs is necessary because of pharmacokinetic or pharmacodynamic changes related to aging and the comorbidities. In this context, clinical and laboratory monitoring should be increased, mostly during an acute event (acute heart failure, infection, dehydration, fall, new therapy…). Therefore, the follow-up of elderly patients with heart failure requires a multidisciplinary approach that involves close cooperation between cardiologists, geriatricians, general practitioners, nurses, and pharmacists.

  19. Antigen Export Reduces Antigen Presentation and Limits T Cell Control of M. tuberculosis.

    PubMed

    Srivastava, Smita; Grace, Patricia S; Ernst, Joel D

    2016-01-13

    Persistence of Mycobacterium tuberculosis results from bacterial strategies that manipulate host adaptive immune responses. Infected dendritic cells (DCs) transport M. tuberculosis to local lymph nodes but activate CD4 T cells poorly, suggesting bacterial manipulation of antigen presentation. However, M. tuberculosis antigens are also exported from infected DCs and taken up and presented by uninfected DCs, possibly overcoming this blockade of antigen presentation by infected cells. Here we show that the first stage of this antigen transfer, antigen export, benefits M. tuberculosis by diverting bacterial proteins from the antigen presentation pathway. Kinesin-2 is required for antigen export and depletion of this microtubule-based motor increases activation of antigen-specific CD4 T cells by infected cells and improves control of intracellular infection. Thus, although antigen transfer enables presentation by bystander cells, it does not compensate for reduced antigen presentation by infected cells and represents a bacterial strategy for CD4 T cell evasion.

  20. Liver Failure in Pregnancy.

    PubMed

    Bacak, Stephen J; Thornburg, Loralei L

    2016-01-01

    Acute liver failure is a rare but life-threatening medical emergency in pregnancy whose true incidence remains unknown. Many cases of acute liver failure are caused by pregnancy-related conditions such as acute fatty liver of pregnancy and HELLP syndrome. However, acute deterioration in liver function can also be caused by drug overdose, viral infections, and an exacerbation of underlying chronic liver disease. This article provides an overview of the normal liver changes that occur during pregnancy, and summarizes the most common conditions and general management strategies of liver failure during pregnancy.

  1. Damage mechanics - failure modes

    SciTech Connect

    Krajcinovic, D.; Vujosevic, M.

    1996-12-31

    The present study summarizes the results of the DOE sponsored research program focused on the brittle failure of solids with disordered microstructure. The failure is related to the stochastic processes on the microstructural scale; namely, the nucleation and growth of microcracks. The intrinsic failure modes, such as the percolation, localization and creep rupture, are studied by emphasizing the effect of the micro-structural disorder. A rich spectrum of physical phenomena and new concepts that emerges from this research demonstrates the reasons behind the limitations of traditional, deterministic, and local continuum models.

  2. 'PSA-SPN' - A Parameter Sensitivity Analysis Method Using Stochastic Petri Nets: Application to a Production Line System

    SciTech Connect

    Labadi, Karim; Saggadi, Samira; Amodeo, Lionel

    2009-03-05

    The dynamic behavior of a discrete event dynamic system can be significantly affected for some uncertain changes in its decision parameters. So, parameter sensitivity analysis would be a useful way in studying the effects of these changes on the system performance. In the past, the sensitivity analysis approaches are frequently based on simulation models. In recent years, formal methods based on stochastic process including Markov process are proposed in the literature. In this paper, we are interested in the parameter sensitivity analysis of discrete event dynamic systems by using stochastic Petri nets models as a tool for modelling and performance evaluation. A sensitivity analysis approach based on stochastic Petri nets, called PSA-SPN method, will be proposed with an application to a production line system.

  3. HIV Antigens for Disease Intervention.

    DTIC Science & Technology

    and the transmembrane protein gp41 . HIV-1 vaccine development efforts conducted in this contract include developing strategies of modifying the...antigenicity of HIV envelope protein. The approaches adopted involve analysis of the possible function for N-linked glycosylation sites of gp 120 and gp41 ... gp41 . The role of N-linked sugars. a leucine zipper structure motif and the long cytoplasmic domain of gp4l in virus assembly, virus infectivity and

  4. Allergy to cockroach antigens in asthmatic patients.

    PubMed

    Romański, B; Dziedziczko, A; Pawlik-Miskiewicz, K; Wilewska-Klubo, T; Zbikowska-Gotz, M

    1981-01-01

    Cockroach allergy was investigated in a group of 56 patients with atopic bronchial asthma (37 men and 19 women with ages ranging from 16 to 65) all allergic to house dust antigen. In all patients, both intracutaneous tests and bronchial provocation tests were performed with cockroach antigen prepared from the species most common in Poland, Blattella germanica and Blatta orientalis. Positive skin reactions to cockroach antigen were found in 17 patients while an immediate bronchoconstrictive response was noted in 11. In the authors opinion, cockroach antigens may be partly responsible for the antigenic properties of house dust and may play a causative role in some cases of atopic asthma.

  5. Pseudomonas syringae pv. actinidiae (PSA) isolates from recent bacterial canker of kiwifruit outbreaks belong to the same genetic lineage.

    PubMed

    Mazzaglia, Angelo; Studholme, David J; Taratufolo, Maria C; Cai, Rongman; Almeida, Nalvo F; Goodman, Tokia; Guttman, David S; Vinatzer, Boris A; Balestra, Giorgio M

    2012-01-01

    Intercontinental spread of emerging plant diseases is one of the most serious threats to world agriculture. One emerging disease is bacterial canker of kiwi fruit (Actinidia deliciosa and A. chinensis) caused by Pseudomonas syringae pv. actinidiae (PSA). The disease first occurred in China and Japan in the 1980s and in Korea and Italy in the 1990s. A more severe form of the disease broke out in Italy in 2008 and in additional countries in 2010 and 2011 threatening the viability of the global kiwi fruit industry. To start investigating the source and routes of international transmission of PSA, genomes of strains from China (the country of origin of the genus Actinidia), Japan, Korea, Italy and Portugal have been sequenced. Strains from China, Italy, and Portugal have been found to belong to the same clonal lineage with only 6 single nucleotide polymorphisms (SNPs) in 3,453,192 bp and one genomic island distinguishing the Chinese strains from the European strains. Not more than two SNPs distinguish each of the Italian and Portuguese strains from each other. The Japanese and Korean strains belong to a separate genetic lineage as previously reported. Analysis of additional European isolates and of New Zealand isolates exploiting genome-derived markers showed that these strains belong to the same lineage as the Italian and Chinese strains. Interestingly, the analyzed New Zealand strains are identical to European strains at the tested SNP loci but test positive for the genomic island present in the sequenced Chinese strains and negative for the genomic island present in the European strains. Results are interpreted in regard to the possible direction of movement of the pathogen between countries and suggest a possible Chinese origin of the European and New Zealand outbreaks.

  6. A novel HSP90 inhibitor delays castrate resistant prostate cancer without altering serum PSA levels and inhibits osteoclastogenesis

    PubMed Central

    Lamoureux, Francois; Thomas, Christian; Yin, Min-Jean; Kuruma, Hidetoshi; Fazli, Ladan; Gleave, Martin E; Zoubeidi, Amina

    2015-01-01

    Purpose Prostate cancer responds initially to anti-androgen therapies, however, progression to castration resistant disease frequently occurs. Therefore there is an urgent need for novel therapeutic agents that can prevent the emergence of castration resistant prostate cancer (CRPC). Hsp90 is a molecular chaperone involved in the stability of many client proteins including Akt and androgen receptor (AR). 17-AAG have been reported to inhibit tumor growth in various cancers, however induces tumor progression in the bone microenvironment. Methods Cell growth, apoptosis, and AR transactivation were examined by crystal violet assay, flow cytometry and luciferase assays respectively. The consequence of HSP90 therapy in vivo was evaluated in LNCaP xenograft model. The consequence of PF-04928473 therapy on bone metastasis was studied using an osteoclastogenesis in vitro assay. Results PF-04928473 inhibits cell growth in a panel of prostate cancer cells, induces cell cycle arrest at sub-G1 and leads to apoptosis and increased caspase-3 activity. These biologic events were accompanied by decreased activation of Akt and Erk as well as decreased expression of Her2, and decreased AR expression and activation in vitro. In contrast to 17-AAG, PF-04928473 abrogates RANKL-induced osteoclast differentiation by affecting NF-kB activation and Src phosphorylation. Finally, PF-04929113 inhibited tumor growth and prolonged survival compared to controls. Surprisingly, PF-04929113 did not reduce serum PSA levels in vivo in parallel these decreases in tumor volume. Conclusion These data identify significant anti-cancer activity of PF-04929113 in CRPC but suggest that serum PSA may not prove useful as pharmaco-dynamic tool for this drug. PMID:21349995

  7. Pseudomonas syringae pv. actinidiae (PSA) Isolates from Recent Bacterial Canker of Kiwifruit Outbreaks Belong to the Same Genetic Lineage

    PubMed Central

    Taratufolo, Maria C.; Cai, Rongman; Almeida, Nalvo F.; Goodman, Tokia; Guttman, David S.; Vinatzer, Boris A.; Balestra, Giorgio M.

    2012-01-01

    Intercontinental spread of emerging plant diseases is one of the most serious threats to world agriculture. One emerging disease is bacterial canker of kiwi fruit (Actinidia deliciosa and A. chinensis) caused by Pseudomonas syringae pv. actinidiae (PSA). The disease first occurred in China and Japan in the 1980s and in Korea and Italy in the 1990s. A more severe form of the disease broke out in Italy in 2008 and in additional countries in 2010 and 2011 threatening the viability of the global kiwi fruit industry. To start investigating the source and routes of international transmission of PSA, genomes of strains from China (the country of origin of the genus Actinidia), Japan, Korea, Italy and Portugal have been sequenced. Strains from China, Italy, and Portugal have been found to belong to the same clonal lineage with only 6 single nucleotide polymorphisms (SNPs) in 3,453,192 bp and one genomic island distinguishing the Chinese strains from the European strains. Not more than two SNPs distinguish each of the Italian and Portuguese strains from each other. The Japanese and Korean strains belong to a separate genetic lineage as previously reported. Analysis of additional European isolates and of New Zealand isolates exploiting genome-derived markers showed that these strains belong to the same lineage as the Italian and Chinese strains. Interestingly, the analyzed New Zealand strains are identical to European strains at the tested SNP loci but test positive for the genomic island present in the sequenced Chinese strains and negative for the genomic island present in the European strains. Results are interpreted in regard to the possible direction of movement of the pathogen between countries and suggest a possible Chinese origin of the European and New Zealand outbreaks. PMID:22590555

  8. D-PSA-K: A Model for Estimating the Accumulated Potential Damage on Kiwifruit Canes Caused by Bacterial Canker during the Growing and Overwintering Seasons

    PubMed Central

    Do, Ki Seok; Chung, Bong Nam; Joa, Jae Ho

    2016-01-01

    We developed a model, termed D-PSA-K, to estimate the accumulated potential damage on kiwifruit canes caused by bacterial canker during the growing and overwintering seasons. The model consisted of three parts including estimation of the amount of necrotic lesion in a non-frozen environment, the rate of necrosis increase in a freezing environment during the overwintering season, and the amount of necrotic lesion on kiwifruit canes caused by bacterial canker during the overwintering and growing seasons. We evaluated the model’s accuracy by comparing the observed maximum disease incidence on kiwifruit canes against the damage estimated using weather and disease data collected at Wando during 1994–1997 and at Seogwipo during 2014–2015. For the Hayward cultivar, D-PSA-K estimated the accumulated damage as approximately nine times the observed maximum disease incidence. For the Hort16A cultivar, the accumulated damage estimated by D-PSA-K was high when the observed disease incidence was high. D-PSA-K could assist kiwifruit growers in selecting optimal sites for kiwifruit cultivation and establishing improved production plans by predicting the loss in kiwifruit production due to bacterial canker, using past weather or future climate change data. PMID:27904460

  9. D-PSA-K: A Model for Estimating the Accumulated Potential Damage on Kiwifruit Canes Caused by Bacterial Canker during the Growing and Overwintering Seasons.

    PubMed

    Do, Ki Seok; Chung, Bong Nam; Joa, Jae Ho

    2016-12-01

    We developed a model, termed D-PSA-K, to estimate the accumulated potential damage on kiwifruit canes caused by bacterial canker during the growing and overwintering seasons. The model consisted of three parts including estimation of the amount of necrotic lesion in a non-frozen environment, the rate of necrosis increase in a freezing environment during the overwintering season, and the amount of necrotic lesion on kiwifruit canes caused by bacterial canker during the overwintering and growing seasons. We evaluated the model's accuracy by comparing the observed maximum disease incidence on kiwifruit canes against the damage estimated using weather and disease data collected at Wando during 1994-1997 and at Seogwipo during 2014-2015. For the Hayward cultivar, D-PSA-K estimated the accumulated damage as approximately nine times the observed maximum disease incidence. For the Hort16A cultivar, the accumulated damage estimated by D-PSA-K was high when the observed disease incidence was high. D-PSA-K could assist kiwifruit growers in selecting optimal sites for kiwifruit cultivation and establishing improved production plans by predicting the loss in kiwifruit production due to bacterial canker, using past weather or future climate change data.

  10. Lifestyle/dietary supplement partial androgen suppression and/or estrogen manipulation. A novel PSA reducer and preventive/treatment option for prostate cancer?

    PubMed

    Moyad, Mark A

    2002-02-01

    There is a large interest in prostate cancer prevention and/or slowing the progression of this disease via dietary/lifestyle/supplement interventions. Numerous mechanisms have been suggested as to how these interventions may lower PSA levels. However, it is possible that the primary mechanism of action is partial androgen suppression and/or estrogen manipulation.

  11. Final Report - Development of New Pressure Swing Adsorption (PSA) Technology to Recover High Valued Products from Chemical Plant and Refinery Waste Systems

    SciTech Connect

    Keith Ludwig

    2004-06-14

    Project Objective was to extend pressure swing adsorption (PSA) technology into previously under-exploited applications such as polyolefin production vent gas recovery and H2 recovery from refinery waste gases containing significant amounts of heavy hydrocarbons, aromatics, or H2S.

  12. Active photosynthesis in cyanobacterial mutants with directed modifications in the ligands for two iron-sulfur clusters on the PsaC protein of photosystem I.

    PubMed Central

    Mannan, R M; He, W Z; Metzger, S U; Whitmarsh, J; Malkin, R; Pakrasi, H B

    1996-01-01

    The PsaC protein of the Photosystem I (PSI) complex in thylakoid membranes coordinates two [4Fe-4S] clusters, FA and FB. Although it is known that PsaC participates in electron transfer to ferredoxin, the pathway of electrons through this protein is unknown. To elucidate the roles of FA and FB, we created two site-directed mutant strains of the cyanobacterium Anabaena variabilis ATCC 29413. In one mutant, cysteine 13, a ligand for FB was replaced by an aspartic acid (C13D); in the other mutant, cysteine 50, a ligand for FA was modified similarly (C50D). Low-temperature electron paramagnetic resonance studies demonstrated that the C50D mutant has a normal FB center and a modified FA center. In contrast, the C13D strain has normal FA, but failed to reveal any signal from FB. Room-temperature optical studies showed that C13D has only one functional electron acceptor in PsaC, whereas two such acceptors are functional in the C50D and wild-type strains. Although both mutants grow under photoautotrophic conditions, the rate of PSI-mediated electron transfer in C13D under low light levels is about half that of C50D or wild type. These data show that (i) FB is not essential for the assembly of the PsaC protein in PSI and (ii) FB is not absolutely required for electron transfer from the PSI reaction center to ferredoxin. PMID:8617228

  13. Heart failure - discharge

    MedlinePlus

    ... Heart failure - overview Heart pacemaker High blood pressure Implantable cardioverter-defibrillator Smoking - tips on how to quit ... ask your doctor How to read food labels Implantable cardioverter defibrillator - discharge Low-salt diet Mediterranean diet ...

  14. Heart failure overview

    MedlinePlus

    ... heart failure: Fast or difficult breathing Leg swelling (edema) Neck veins that stick out (are distended) Sounds ( ... pacemaker High blood pressure Implantable cardioverter-defibrillator Pulmonary edema Stable angina Ventricular assist device Patient Instructions ACE ...

  15. Failure to communicate.

    PubMed

    Fiesta, J

    1998-02-01

    When a medication error is coupled with a communication problem, a patient may experience significant injury. Cases involving communication breakdown, i.e, failure to communicate or listen, are discussed.

  16. Triac failure detector

    NASA Technical Reports Server (NTRS)

    Nola, F. J. (Inventor)

    1983-01-01

    A failure detector is provided for detecting unidirectional failures in triacs, particularly as used in power factor controllers for induction motors. In a first embodiment, the triac voltage waveform is sensed and upon detection of an unbalanced signal, corresponding to failure of the triac in either the positive or negative direction, the triac is turned full on in both directions. In a second embodiment, a pair of pulsed signals are derived, the pulse durations of which are proportional to the phase difference between the load current and voltage for each half cycle, and the triac is turned full on responsive to a difference in pulse duration between the half cycle signals. An unidirectional open circuit detector is adapted to use a signal from either of the first and second embodiment to turn the triac off in response to an open circuit failure in either direction.

  17. Inverter ratio failure detector

    NASA Technical Reports Server (NTRS)

    Wagner, A. P.; Ebersole, T. J.; Andrews, R. E. (Inventor)

    1974-01-01

    A failure detector which detects the failure of a dc to ac inverter is disclosed. The inverter under failureless conditions is characterized by a known linear relationship of its input and output voltages and by a known linear relationship of its input and output currents. The detector includes circuitry which is responsive to the detector's input and output voltages and which provides a failure-indicating signal only when the monitored output voltage is less by a selected factor, than the expected output voltage for the monitored input voltage, based on the known voltages' relationship. Similarly, the detector includes circuitry which is responsive to the input and output currents and provides a failure-indicating signal only when the input current exceeds by a selected factor the expected input current for the monitored output current based on the known currents' relationship.

  18. Heart failure - tests

    MedlinePlus

    CHF - tests; Congestive heart failure - tests; Cardiomyopathy - tests; HF - tests ... An echocardiogram (Echo) is a test that uses sound waves to create a moving picture of the heart. The picture is much more detailed than a plain ...

  19. Common Cause Failure Modeling

    NASA Technical Reports Server (NTRS)

    Hark, Frank; Britton, Paul; Ring, Robert; Novack, Steven

    2015-01-01

    Space Launch System (SLS) Agenda: Objective; Key Definitions; Calculating Common Cause; Examples; Defense against Common Cause; Impact of varied Common Cause Failure (CCF) and abortability; Response Surface for various CCF Beta; Takeaways.

  20. Evaluation of ultrafiltration failure.

    PubMed

    Korbet, S M

    1998-07-01

    The evaluation of ultrafiltration failure is embarked upon when a patient has persistent problems with symptoms and signs of fluid overload. Fluid overload is a common problem in peritoneal dialysis (PD) patients and the risk of its occurrence increases with time on dialysis. Although often attributed to changes in peritoneal membrane function (membrane failure), there are a number of potential, and frequently more common factors that can contribute to the failure of adequate fluid removal in patients on PD. Many of the causes of ultrafiltration failure may be apparent after an initial informal evaluation. However, if after this the etiology remains unexplained, a systematic approach to the differential diagnosis of this problem can be utilized with the use of the peritoneal equilibration test. Once a diagnosis is confirmed, a logical therapeutic plan can be formulated.

  1. Living with Heart Failure

    MedlinePlus

    ... help you in the future. Follow Your Treatment Plan Treatment can relieve your symptoms and make daily ... or nurse about getting flu and pneumonia vaccines. Plan Ahead If you have heart failure, it's important ...

  2. What Causes Respiratory Failure?

    MedlinePlus

    ... Conditions Causing Respiratory Failure Figure A shows the location of the lungs, airways, diaphragm, rib cage, pulmonary arteries, brain, and spinal cord ... STATEMENT FOIA NO FEAR ACT OIG CONTACT US ...

  3. Common antigens between hydatid cyst and cancers

    PubMed Central

    Daneshpour, Shima; Bahadoran, Mehran; Hejazi, Seyed Hossein; Eskandarian, Abas Ali; Mahmoudzadeh, Mehdi; Darani, Hossein Yousofi

    2016-01-01