Correlation of serum androgens and pituitary hormone levels with serum PSA less than 2.5 ng/ml.

PubMed

Sofikerim, Mustafa; Oruç, Ozgür; Eskicorapci, Sadettin; Guliyev, Fuat; Ozen, Haluk

2007-07-27

The aim of this clinical study was to determine whether there is a relationship between total serum testosterone, free testosterone, FSH (Follicle-Stimulating Hormone), LH (Luteinizing Hormone) and serum prostate specific antigen (PSA) levels. We postulated that such a correlation existed then the use of hormone specific reference ranges might enhance the usefullness of PSA concentrations <2.5 ng/mL as a marker for prostate cancer. Prior to digital rectal examination, serum was obtained from all patients between 8.30-10:00 AM for hormone and PSA concentrations. The study was performed on 210 male patients >40 years of age visiting our urology outpatient clinics. PSA was correlated to age (r = 0.23, p = 0.019), but there none between serum testosterone and age. No significant correlation was noted between testosterone or free testosterone and serum PSA levels, and none between serum FSH or LH and PSA. In age specific reference groups (41-49; 50-59; 60-69 years), we found no significant correlation between PSA and hormone concentrations. In this population of eugonadal men with serum PSA values less than 2.5 ng/ml, serum androgens and pituitary hormones do not appear to correlate with serum PSA.

[PSA testing, biopsy and cancer and benign prostate hyperplasia in France].

PubMed

Tuppin, P; Samson, S; Fagot-Campagna, A; Lukacs, B; Alla, F; Allemand, H; Paccaud, F; Thalabard, J-C; Vicaut, E; Vidaud, M; Millat, B

2014-07-01

Prostate-specific antigen (PSA) testing is high in France. The aim of this study was to estimate their frequency and those of biopsy and newly diagnosed cancer (PCa) according to the presence or absence of treated benign prostatic hyperplasia (BPH). This study concerned men 40 years and older covered by the main French national health insurance scheme (73 % of all men of this age). Data were collected from the national health insurance information system (SNIIRAM). This database comprehensively records all of the outpatient prescriptions and healthcare services reimbursed. This information are linked to data collected during hospitalisations. The frequency of men without diagnosed PCa (10.9 millions) with at least one PSA test was very high in 2011 (men aged 40 years and older: 30 %, 70-74 years: 56 %, 85 years and older: 33 % and without HBP: 25 %, 41 % and 19 %). Men with treated BPH totalized 9 % of the study population, but 18 % of the men with at least one PSA test, 44 % of those with at least one prostate biopsy and 40 % of those with newly managed PCa. Over a 3-year period, excluding men with PCa, 88 % of men with BPH had at least one PSA test and 52 % had three or more PSA tests versus 52 % and 15 % for men without BPH. One year after PSA testing, men of 55-69 years with BPH more frequently underwent prostate biopsy than those without BPH (5.4 % vs 1.8 %) and presented PCa (1.9 % vs 0.9 %). PSA testing frequencies in France are very high even after exclusion of men with BPH, who can be a group with more frequent managed PCa. 4. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Correlation between the complex PSA/total PSA ratio and the free PSA/total PSA ratio, sensitivity and specificity of both markers for the diagnosis of prostate cancer.

PubMed

Pérez-Lanzac-Lorca, A; Barco-Sánchez, A; Romero, E; Martinez-Peinado, A; López-Elorza, F; Sanchez-Sanchez, E; Alvarez-Ossorio-Fernandez, J L; Castiñeiras-Fernández, J

2013-09-01

To compare the behaviour of the PSAcomplex/PSAtotal percentage (PSAc%) against the PSA free/PSA total (PSAl%) and analyse both markers for their usefulness in diagnosing prostate cancer. We measured total PSA (PSAt), free PSA (PSAl), complex PSA (PSAc), PSAl% and PSAc% levels in 158 patients. Of these, 98 (62%) were biopsied for presenting PSAt≥3 ng/dl and PSAl%<20, PSAt>10, suspicious rectal examination or suspicious ultrasound node. We performed linear regression and Passing-Bablok regression analyses. The ROC curves were calculated to study the sensitivity and specificity of PSAl% and PSAc% and were compared to each other. The prostate cancer diagnoses were analysed by PSAl% and PSAc% by applying the χ(2) test. The correlation coefficient (r) was good (0.7447, P<.0001), and the index of determination (r(2)) was 0,5. The result of the Passing-Bablok analysis was a slope of 1.658 (1.452 to 1.897) and an intersection of 2.044 (-0,936 to 5.393). The optimal cutoff for PSAl% (≤14.7854) showed a sensitivity of 89.29% [95% CI, 0,642-0,823] and a specificity of 54.29% (95% CI, 0,642-0,823). The optimal cutoff for PSAc% (>89.7796) had a sensitivity of 71.43% (95% CI, 0,616-0,802) and a specificity of 71.43% (95% CI, 0,616-0,802). There were no significant differences when comparing the areas under the curve of both markers (P=.59). The PPV of PSAl% was less than that of PSAc% (45.7% vs. 71%). There was a good correlation between PSAl% and PSAc%. PSAc% has demonstrated greater specificity and efficacy than PSAl% in the diagnosis of prostate cancer. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis.

PubMed

Filella, Xavier; Giménez, Nuria

2013-04-01

The usefulness of %[-2] proPSA and Prostate Health Index (phi) in the detection of prostate cancer are currently unknown. It has been suggested that these tests can distinguish prostate cancer from benign prostatic diseases better than PSA or %fPSA. We performed a systematic review and meta-analysis of the available scientific evidence to evaluate the clinical usefulness of %[-2] proPSA and phi. Relevant published papers were identified by searching computerized bibliographic systems. Data on sensitivity and specificity were extracted from 12 studies: 10 studies about %[-2] proPSA (3928 patients in total, including 1762 with confirmed prostate cancer) and eight studies about phi (2919 patients in total, including 1515 with confirmed prostate cancer). The sensitivity for the detection of prostate cancer was 90% for %[-2] proPSA and phi, while the pooled specificity was 32.5% (95% CI 30.6-34.5) and 31.6% (95% CI 29.2-34.0) for %[-2] proPSA and phi, respectively. The measurement of %[-2] proPSA improves the accuracy of prostate cancer detection in comparison with PSA or %fPSA, particularly in the group of patients with PSA between 2 μg/L and 10 μg/L. Similar results were obtained measuring phi. Using these tests, it is possible to reduce the number of unnecessary biopsies, maintaining a high cancer detection rate. Published results also showed that %[-2] proPSA and phi are related to the aggressiveness of the tumor.

PSA-alpha-2-macroglobulin complex is enzymatically active in the serum of patients with advanced prostate cancer and can degrade circulating peptide hormones.

PubMed

Kostova, Maya B; Brennen, William Nathaniel; Lopez, David; Anthony, Lizamma; Wang, Hao; Platz, Elizabeth; Denmeade, Samuel R

2018-08-01

Prostate cancer cells produce high levels of the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active in the tumor microenvironment but is presumed to be enzymatically inactive in the blood due to complex formation with serum protease inhibitors α-1-antichymotrypsin and α-2-macroglobulin (A2M). PSA-A2M complexes cannot be measured by standard ELISA assays and are also rapidly cleared from the circulation. Thus the exact magnitude of PSA production by prostate cancer cells is not easily measured. The PSA complexed to A2M is unable to cleave proteins but maintains the ability to cleave small peptide substrates. Thus, in advanced prostate cancer, sufficient PSA-A2M may be in circulation to effect total A2M levels, levels of cytokines bound to A2M and hydrolyze small circulating peptide hormones. Total A2M levels in men with advanced prostate cancer and PSA levels above 1000 ng/mL were measured by ELISA and compared to controls. Additional ELISA assays were used to measure levels of IL-6 and TGF-beta which can bind to A2M. The ability of PSA-A2M complexes to hydrolyze protein and peptide substrates was analyzed ± PSA inhibitor. Enzymatic activity of PSA-A2M in serum of men with high PSA levels was also assayed. Serum A2M levels are inversely correlated with PSA levels in men with advanced prostate cancer. Il-6 Levels are significantly elevated in men with PSA >1000 ng/mL compared to controls with PSA <0.1 ng/mL. PSA-A2M complex in serum of men with PSA levels >1000 ng/mL can hydrolyze small fluorescently labeled peptide substrates but not large proteins that are PSA substrates. PSA can hydrolyze small peptide hormones like PTHrP and osteocalcin. PSA complexed to A2M retains the ability to degrade PTHrP. In advanced prostate cancer with PSA levels >1000 ng/mL, sufficient PSA-A2M is present in circulation to produce enzymatic activity against circulating small peptide hormones. Sufficient PSA is produced in advanced prostate

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

PubMed

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

2017-07-01

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

[Use of [-2] pro PSA and phi index for early detection of prostate cancer: a prospective of 452 patients].

PubMed

Houlgatte, A; Vincendeau, S; Desfemmes, F; Ramirez, J; Benoist, N; Bensalah, K; Durand, X

2012-05-01

Early detection of prostate cancer (Pca) is a real challenge to reduce morbidity and mortality while avoiding over-diagnosis and over-treatment. The prostate specific antigen (PSA) is characterized by its imperfections justifying the evaluation of new serum or urinary specific markers allowing a better selection of patients at risk of developing aggressive Pca. To compare the value of -2pro PSA and phi index to total and free PSA. Serum sampled from 452 patients from two university centers were used to determine levels of PSA before performing biopsies. The patients were included in this study based on the PSA serum concentration between 1.6 ng/mL and 8 ng/mL according to the WHO international standard. All biopsies were performed according to a standardized protocol consisting of 12 cores or more. Sera were analyzed centrally in one of the two institutions with on a single analyzer. Sera from 243 prostate cancer and 208 negative biopsies patients have been taken into account. Sera were analyzed blinded for total PSA, free PSA and [-2] proPSA using Access(®) immunoassay method from Beckman Coulter. The Prostate Health Index (phi) was calculated using the formula phi=([-2] proPSA/fPSA)×sqrt (PSA). The median value of the phi index is significantly (P>0.0001) higher for patients with cancer (phi=65.8) compared to patients with negative biopsies (phi=40.6). At a given sensitivity, the phi index significantly increases the specificity of detection of prostate cancer compared to other markers. The phi index currently appears as the best predictor of prostate cancer for patients with a total PSA between 1.6 and 8 ng/mL according to the WHO standard. The improvement in specificity of the phi index over tPSA could reduce significantly the numbers of unnecessary biopsies. Whether this new biomarker could be an indicator of aggressive prostate cancer remains to be confirmed. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

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

PubMed Central

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

2014-01-01

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

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

PubMed

McJimpsey, Erica L

2016-02-25

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.

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.

Impact of PSA density of transition zone as a potential parameter in reducing the number of unnecessary prostate biopsies in patients with psa levels between 2.6 and 10.0 ng/mL.

PubMed

Castro, Hugo A Socrates; Iared, Wagner; Santos, José Eduardo Mourão; Solha, Raphael Sandes; Shigueoka, David Carlos; Ajzen, Sergio Aron

2018-04-10

To assess the accuracy of prostate-specific antigen (PSA) adjusted for the transition zone volume (PSATZ) in predicting prostate cancer by comparing the ability of several PSA parameters in predicting prostate cancer in men with intermediate PSA levels of 2.6 - 10.0 ng/mL and its ability to reduce unnecessary biopsies. This study included 656 patients referred for prostate biopsy who had a serum PSA of 2.6 - 10.0 ng/mL. Total prostate and transition zone volumes were measured by transrectal ultrasound using the prolate ellipsoid method. The clinical values of PSA, free-to-total (F/T) ratio, PSA density (PSAD) and PSATZ for the detection of prostate cancer were calculated and statistical comparisons between biopsy-positive (cancer) and biopsy-negative (benign) were conducted. Cancer was detected in 172 patients (26.2%). Mean PSA, PSATZ, PSAD and F/T ratio were 7.5 ng/mL, 0.68 ng/mL/cc. 0.25 ng/mL/cc and 0.14 in patients with prostate cancer and 6.29 ng/mL, 0.30 ng/mL/cc, 0.16 ng/mL/cc and 0.22 in patients with benign biopsies, respectively. ROC curves analysis demonstrated that PSATZ had a higher area under curve (0,838) than F/T ratio (0,806) (P<0.001) and PSAD (0,806) (P<0.001). With a cut-off value of 0.22 ng/mL/cc, PSATZ had 100% of sensitivity and could have prevented 24% of unnecessary biopsies. PSATZ may be useful in enhancing the specificity of serum PSA. Compared to other PSA related parameters, it was better in differentiating between prostate cancer and benign prostatic enlargement. Also, PSATZ could reduce a significant number of unnecessary biopsies. Copyright® by the International Brazilian Journal of Urology.

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

PubMed Central

McJimpsey, Erica L.

2016-01-01

The prostate-specific antigen (PSA) assays currently employed for the detection of prostate cancer (PCa) lack the specificity needed to differentiate PCa from benign prostatic hyperplasia and have high false positive rates. The PSA calibrants used to create calibration curves in these assays are typically purified from seminal plasma and contain many molecular forms (intact PSA and cleaved subforms). The purpose of this study was to determine if the composition of the PSA molecular forms found in these PSA standards contribute to the lack of PSA test reliability. To this end, seminal plasma purified PSA standards from different commercial sources were investigated by western blot (WB) and in multiple research grade PSA ELISAs. The WB results revealed that all of the PSA standards contained different mass concentrations of intact and cleaved molecular forms. Increased mass concentrations of intact PSA yielded higher immunoassay absorbance values, even between lots from the same manufacturer. Standardization of seminal plasma derived PSA calibrant molecular form mass concentrations and purification methods will assist in closing the gaps in PCa testing measurements that require the use of PSA values, such as the % free PSA and Prostate Health Index by increasing the accuracy of the calibration curves. PMID:26911983

Updating the Psoriatic Arthritis (PsA) Core Domain Set: A Report from the PsA Workshop at OMERACT 2016.

PubMed

Orbai, Ana-Maria; de Wit, Maarten; Mease, Philip J; Callis Duffin, Kristina; Elmamoun, Musaab; Tillett, William; Campbell, Willemina; FitzGerald, Oliver; Gladman, Dafna D; Goel, Niti; Gossec, Laure; Hoejgaard, Pil; Leung, Ying Ying; Lindsay, Chris; Strand, Vibeke; van der Heijde, Désirée M; Shea, Bev; Christensen, Robin; Coates, Laura; Eder, Lihi; McHugh, Neil; Kalyoncu, Umut; Steinkoenig, Ingrid; Ogdie, Alexis

2017-10-01

To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS). At OMERACT 2016, research conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants. We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted 24 focus groups with 130 patients from 7 countries representing 5 continents to identify patient domains. We achieved consensus through 2 rounds of separate surveys with 50 patients and 75 physicians, and a nominal group technique meeting with 12 patients and 12 physicians. We conducted a workshop and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient's global assessment, physical function, health-related quality of life, and systemic inflammation, which were recommended for all RCT and LOS. These were important, but not required in all RCT and LOS: economic cost, emotional well-being, participation, and structural damage. Independence, sleep, stiffness, and treatment burden were on the research agenda. The updated PsA Core Domain Set was endorsed at OMERACT 2016. Next steps for the PsA working group include evaluation of PsA outcome measures and development of a PsA Core Outcome Measurement Set.

Repeat prostate-specific antigen (PSA) test before prostate biopsy: a 20% decrease in PSA values is associated with a reduced risk of cancer and particularly of high-grade cancer.

PubMed

De Nunzio, Cosimo; Lombardo, Riccardo; Nacchia, Antonio; Tema, Giorgia; Tubaro, Andrea

2018-07-01

To analyse the impact of repeating a prostate-specific antigen (PSA) level assessment on prostate biopsy decision in a cohort of men undergoing prostate biopsy. From 2015 onwards, we consecutively enrolled, at a single institution in Italy, men undergoing 12-core transrectal ultrasonography-guided prostate needle biopsy. Indication for prostate biopsy was a PSA level of ≥4 ng/mL. Demographic, clinical, and histopathological data were collected. The PSA level was tested at enrolment (PSA 1 ) and 4 weeks later on the day before biopsy (PSA 2 ). Variations in PSA level were defined as: stable PSA 2 within a 10% variation, stable PSA 2 within a 20% variation, PSA 2 decreased by ≥10%, PSA 2 decreased by ≥20%, PSA 2 increased by ≥10%, PSA 2 increased by ≥20%, and PSA 2 <4 ng/mL. Percentages and multinomial logistic regression were used to analyse biopsy outcomes. High-grade cancer was defined as Grade group ≥3. Overall, 331 patients were enrolled. Prostate cancer was diagnosed in 153/331 (46%) patients and of them 80/153 (52%) had high-grade disease. When compared to the rest of the population, patients with a stable PSA within 20% variation had a higher risk of prostate cancer (odds ratio [OR] 1.80, P < 0.05) and high grade disease (OR 2.56, P < 0.05), patients with a PSA2 decreased by ≥20% had a lower risk of prostate cancer (OR 0.37, P < 0.05) and high grade disease (OR 0.13, P < 0.05), whilst patients with a PSA2 increased by ≥10% had an increased risk of high-grade prostate cancer (OR 1.93, P < 0.05). When PSA returned to normal values (<4 ng/mL) both risks of prostate cancer and high-grade disease were reduced (OR 0.33 and 0.01, respectively, P = 0.001). In a cohort of Italian men undergoing prostate biopsy, a reduction of ≥20% in PSA levels significantly reduced the risk of high-grade prostate cancer. Further multicentre studies should validate our present results. © 2018 The Authors BJU International © 2018 BJU International Published by John

Post-treatment PSA < or = 0.2 ng/mL defines disease freedom after radiotherapy for prostate cancer using modern techniques.

PubMed

Critz, F A; Williams, W H; Holladay, C T; Levinson, A K; Benton, J B; Holladay, D A; Schnell, F J; Maxa, L S; Shrake, P D

1999-12-01

The prostate-specific antigen (PSA) definition of disease freedom after radiotherapy for prostate cancer is still in dispute. This report focuses on the PSA nadir achieved in men treated by modern radiotherapy techniques. From 1984 to 1994, 489 consecutive men with clinical Stage T1 -T2 prostate cancer were treated by simultaneous radiation: prostate iodine-125 implant followed by external beam radiation. A transperineal implant was performed on 143 men with Stage T1-T2NX, the focus of this study; 346 men with Stage T1-T2N0 had a retropubic implant. The median pretreatment PSA was 8.3 ng/mL (range 0.3 to 188). A rising PSA was defined as one that rose on three consecutive occasions above whatever nadir was achieved. A minimum 5-year follow-up (range 5 to 15) was reached by 453 men. After a minimum 5-year follow-up, 336 men had a nonrising PSA, and of this group, 107 had undergone simultaneous radiation by the transperineal implant technique. A PSA nadir of 0.2 ng/mL or less was achieved by 97% of the transperineally implanted men, and 3% had a nadir of 0.3 to 1.0 ng/mL. Of the 489 men, those who had a nadir of 0.2 ng/mL or less had a 92% nonrising PSA rate (P = 0.001) 10 years after treatment compared with a 41% rate for men who had a nadir of 0.3 to 1.0 ng/mL. All men whose nadir was greater than 1.0 ng/mL had recurrence. The median time to achieve the PSA nadir of 0.2 ng/mL was 27 months (range 3 to 102). Primarily on the basis of the results from men treated with simultaneous radiation using the transperineal technique, the definition of disease freedom for radiotherapy should be men who achieve and maintain a PSA nadir of 0.2 ng/mL or less.

Predictive criteria for prostate cancer detection in men with serum PSA concentration of 2.0 to 4.0 ng/mL.

PubMed

Kravchick, Sergey; Peled, Ronit; Dorfman, Dov; Agulansky, Leonid; Ben-Dor, David; Cytron, Shmuel

2005-09-01

To assess the usefulness of measuring testosterone, free testosterone, and the free/total (f/t) prostate-specific antigen (PSA) ratio with the intention of reducing the number of unnecessary biopsies in the patients with PSA values between 2.0 and 4.0 ng/mL. Cancer detection is not rare among patients with PSA values between 2.0 and 4.0 ng/mL. A total of 171 men with serum PSA levels of 2.0 to 4.0 ng/mL were enrolled in this study. The f/t PSA ratio and total and free testosterone levels were quantified. All patients underwent transrectal ultrasound-guided biopsy. The cancer detection rate, clinical and pathologic features of the cancers detected, and the probability of cancer detection in relation to the f/t PSA ratio and total and free testosterone levels were estimated. Two-step statistical analysis was used for descriptive purposes and in the detection of cancer predictors. Statistical significance was set at P < or = 0.05. The mean patient age was 63.3 years. Cancer was detected in 39 (22.8%) of the 171 patients. Only 15.4% of our patients had insignificant cancer. The f/t PSA ratio and total and free testosterone levels were significantly lower in the patients with prostate cancer (19.3%, 13.68 nmol/L, and 28.4 pmol/L, respectively; P < 0.001). The f/t PSA ratio and free testosterone were the strongest predictors of cancer detection (P < 0.001). The results of our study have shown that an important number of cancers could be detected in the PSA range of 2.0 to 4.0 ng/mL. The great majority of cancers detected have the features of medically significant tumors. The combination of the f/t PSA ratio and free testosterone measurements may reveal those patients who require biopsy.

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.

Prostate-specific Antigen (PSA) Density and Free to Total PSA Ratio in Diagnosing Prostate Cancer with Prostate-Specific Antigen Levels of 4.0 ng/ml or Less.

PubMed

Liu, Xin; Tang, Jie; Fei, Xiang; Li, Qiu-Yang

2015-11-01

We aimed to value the usefulness of free to total prostate-specific antigen and Prostate-specific antigen (PSA) density for prostate cancer in the patients with PSA levels of 4.0 ng/ml or less. A total of 343 subjects with PSA levels of 4.0 ng/ml or less were biopsied. All patients were divided into four groups according to the PSA levels: 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml. The reliability of cancer detection in relation to the f/t PSA ratio and PSAD were estimated. Overall, 65 people were diagnosed with prostate cancer. The detection rate was 16.28%、17.17%, 21.82%, 25.00% in subjects with PSA levels of 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml, respectively. The f/t PSA ratio was significantly lower in patients with prostate cancer and PSA levels of 2.1 to 4.0 ng/ml (P<0.05). The PSAD had no statistical significance between the two groups. Routine prostate biopsy should be undertaken if the f/t PSA ratio less than 15% with /without abnormal DRE/TRUS findings.

Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer.

PubMed

Nordström, Tobias; Akre, Olof; Aly, Markus; Grönberg, Henrik; Eklund, Martin

2018-04-01

Screening for prostate cancer using prostate-specific antigen (PSA) alone leads to un-necessary biopsying and overdiagnosis. PSA density is easily accessible, but early evidence on its use for biopsy decisions was conflicting and use of PSA density is not commonly recommended in guidelines. We analyzed biopsy outcomes in 5291 men in the population-based STHLM3 study with PSA ≥ 3 ng/ml and ultrasound-guided prostate volume measurements by using percentages and regression models. PSA density was calculated as total PSA (ng/ml) divided by prostate volume (ml). Main endpoint was clinically significant cancer (csPCa) defined as Gleason Score ≥ 7. The median PSA-density was 0.10 ng/ml 2 (IQR 0.075-0.14). PSA-density was associated with the risk of finding csPCa both with and without adjusting for the additional clinical information age, family history, previous biopsies, total PSA and free/total PSA (OR 1.06; 95% CI:1.05-1.07 and OR 1.07, 95% CI 1.06-1.08). Discrimination for csPCa was better when PSA density was added to a model with additional clinical information (AUC 0.75 vs. 0.73, P < 0.05). The proportion of men with Gleason Score 6 (ISUP 1) was similar across stratas of PSA-density. Omitting prostate biopsy for men with PSA-density ≤0.07 ng/ml 2 would save 19.7% of biopsy procedures, while missing 6.9% of csPCa. PSA-density cutoffs of 0.10 ng/ml 2 and 0.15 ng/ml 2 resulted in detection of 77% (729/947) and 49% (461/947) of Gleason Score ≥7 tumors. PSA-density might inform biopsy decisions, and spare some men from the morbidity associated with a prostate biopsy and diagnosis of low-grade prostate cancer.

The inverse relationship between prostate-specific antigen (PSA) and obesity.

PubMed

Aref, Adel; Vincent, Andrew D; O'Callaghan, Michael; Martin, Sean; Sutherland, Peter; Hoy, Andrew; Butler, Lisa M; Wittert, Gary

2018-06-25

Obese men have lower serum prostate-specific antigen (PSA) than comparably aged lean men, but the underlying mechanism remains unclear. The aim of this study was to determine the effect of obesity on PSA and the potential contributing mechanisms. A cohort of 1195 men aged 35 years and over at recruitment, with demographic, anthropometric (body mass index (BMI), waist circumference (WC)) and serum hormone (serum testosterone (T), estradiol (E2)), PSA and hematology assessments obtained over two waves was assessed. Men with a history of prostate cancer or missing PSA were excluded, leaving 970 men for the final analysis. Mixed-effects regressions and mediation analyses adjusting for hormonal and volumetric factors explore the potential mechanisms relating obesity to PSA. After adjusting for age, PSA levels were lower in men with greater WC (p=0.001). In a multivariable model including WC, age, E2/T and PlasV as predictors, no statistically significant associations were observed between with PSA and either WC (p=0.36) or PlasV (p=0.49), while strong associations were observed with both E2/T (p<0.001) and age (p<0.001). In the mediation analyses with PlasV as the mediator, the average causal mediation effect (ACME) explained roughly 0.2 of the total effect of WC on PSA (p=0.31), while when E2/T is a mediator; the ACME explained roughly 0.5 of the effect (p<0.001). Our findings indicate that lower PSA levels in obese men, as compared to normal weight men, can be explained both by hormonal changes (elevated E2/T ratio) and haemodilution. Hormonal factors therefore represent a substantial but underappreciated mediating pathway.

Measurement of serum isoform [-2]proPSA derivatives shows superior accuracy to magnetic resonance imaging in the diagnosis of prostate cancer in patients with a total prostate-specific antigen level of 2-10 ng/ml.

PubMed

Furuya, Kazuhiro; Kawahara, Takashi; Narahara, Masaki; Tokita, Takashi; Fukui, Sachi; Imano, Masashi; Mitome, Taku; Ito, Yusuke; Izumi, Koji; Osaka, Kimito; Yokomizo, Yumiko; Hayashi, Narihiko; Hasumi, Hisashi; Nawata, Shintaro; Kawano, Tsuyoshi; Yao, Masahiro; Uemura, Hiroji

2017-08-01

More accurate diagnostic procedures for prostate cancer are needed to avoid unnecessary biopsy due to the low specificity of prostate-specific antigen (PSA). Recent studies showed that the percentage of serum isoform [-2]proPSA (p2PSA) to free PSA (%p2PSA), the Prostate Health Index (PHI) and magnetic resonance imaging (MRI) were more accurate than PSA. The aim of this study was to test the accuracy of %p2PSA, PHI and MRI in discriminating patients with and without prostate cancer. The subjects were 50 consecutive men with a PSA level of 2.0-10.0 ng/ml, who underwent prostate biopsy from October 2012 to July 2014. These patients underwent multiparametric MRI before biopsy, and their serum samples were measured for PSA, free PSA and p2PSA. The sensitivity, specificity and accuracy of PHI, %p2PSA and MRI were compared with PSA in the diagnosis of biopsy-confirmed prostate cancer. In a univariate analysis, %p2PSA [area under the curve (AUC): 0.811] and PHI (AUC 0.795) were more accurate than MRI (AUC: 0.583) and PSA (AUC: 0.554) for prostate cancer detection. At 60% sensitivity, the specificity of PHI (76.5%) was higher than that of MRI (52.9%). For significant cancer detection, %p2PSA (AUC: 0.745), PHI (AUC: 0.791) and MRI (AUC: 0.739) were marginally more accurate than PSA (AUC: 0.696). At 85% sensitivity, the specificity of MRI (62.1%) was higher than that of PHI (34.5%). PHI and %p2PSA can be used for screening the general population and MRI can be used for detection of significant cancer in patients suspected, from screening tests, of having prostate cancer.

Prostate health index significantly reduced unnecessary prostate biopsies in patients with PSA 2-10 ng/mL and PSA >10 ng/mL: Results from a Multicenter Study in China.

PubMed

Na, Rong; Ye, Dingwei; Qi, Jun; Liu, Fang; Helfand, Brian T; Brendler, Charles B; Conran, Carly A; Packiam, Vignesh; Gong, Jian; Wu, Yishuo; Zheng, Siqun L; Mo, Zengnan; Ding, Qiang; Sun, Yinghao; Xu, Jianfeng

2017-08-01

The performance of prostate health index (phi) in predicting prostate biopsy outcomes has been well established for patients with prostate-specific antigen (PSA) values between 2 and 10 ng/mL. However, the performance of phi remains unknown in patients with PSA >10 ng/mL, the vast majority in Chinese biopsy patients. We aimed to assess the ability of phi to predict prostate cancer (PCa) and high-grade disease (Gleason Score ≥7) on biopsy in a Chinese population. This is a prospective, observational, multi-center study of consecutive patients who underwent a transrectal ultrasound guided prostate biopsy at four hospitals in Shanghai, China from August 2013 to December 2014. In the cohort of 1538 patients, the detection rate of PCa was 40.2%. phi had a significantly better predictive performance for PCa than total PSA (tPSA). The areas under the receiver operating characteristic curve (AUC) were 0.90 and 0.79 for phi and tPSA, respectively, P < 0.0001. A considerable proportion of patients in the cohort had PSAs >10 ng/mL (N = 838, 54.5%). The detection rates of PCa were 35.9% and 57.7% in patients with tPSA 10.1-20 and 20.1-50 ng/mL, respectively. The AUCs of phi (0.79 and 0.89, for these two groups, respectively) were also significantly higher than tPSA (0.57 and 0.63, respectively), both P < 0.0001. If a phi ≤35 was used as the cutoff, 599/1538 (39%) biopsies could have been avoided at a cost of missing small numbers of PCa patients: 49 (7.93%) PCa patients, including 18 (3.69%) high-grade tumors. Results from this study suggest that phi can be used to predict PCa and high-grade disease in Chinese men with high PSA levels (>10 ng/mL). © 2017 Wiley Periodicals, Inc.

What does postradiotherapy PSA nadir tell us about freedom from PSA failure and progression-free survival in patients with low and intermediate-risk localized prostate cancer?

PubMed

DeWitt, K D; Sandler, H M; Weinberg, V; McLaughlin, P W; Roach, M

2003-09-01

To determine whether the post-external beam radiotherapy (RT) prostate-specific antigen nadir (nPSA) improves our ability to predict freedom from PSA failure, progression-free survival (PFS), and overall survival. Controversy regarding the importance of nPSA after external beam RT as a prognostic indicator for patients with localized prostate cancer has continued. This analysis was based on the data from 748 patients with low and intermediate-risk localized prostate cancer treated with external beam RT alone. Patients were categorized by nPSA quartile groups with cutpoints of less than 0.3, 0.3 to less than 0.6, 0.6 to less than 1.2, and 1.2 ng/mL or greater. Both univariate and multivariate analyses were used to determine the significance of nPSA on PSA failure (American Society for Therapeutic Radiology Oncology consensus definition), PFS (death after PSA failure), and overall survival (death from any cause). Freedom from PSA failure was strongly associated with nadir quartile groups (P <0.0001). PFS was also significantly different statistically among nadir quartile groups (P = 0.02). No statistically significant difference was found in overall survival associated with nPSA at this point. nPSA is a strong independent predictor of freedom from PSA failure and PFS in patients with low and intermediate-risk localized prostate cancer treated with RT alone. Longer follow-up and larger patient numbers are required to confirm these observations.

Serum PSA levels in the Indian population: Is it different?

PubMed

Agrawal, Amit; Karan, Shailesh Chandra

2017-04-01

Serum prostate-specific antigen (PSA) is an important tumour, marker which is widely used to trigger trans-rectal ultrasound (TRUS)-guided prostate biopsy. However, the PSA levels vary with race and ethnicity. Therefore, there is a need to have an Indian reference range. All adult male patients meeting the inclusion and exclusion criteria were enrolled in this study. They were subjected to assessment of serum total PSA, digital rectal examination and trans-abdominal ultrasound. If any one or more of these were found abnormal, then a TRUS-guided 12-core prostate biopsy was done. Patients who were detected to have prostatic cancer were excluded from the final analysis. The data so obtained was grouped among the following three age groups: 40-49, 50-59 and 60-70 years, and the age-specific PSA values, prostatic volume and PSA density were found. A total of 1772 patients were analysed. The mean serum total PSA was 1.76 ng/ml with a standard deviation of 2.566 ng/ml. Group-wise age distribution of the mean serum total PSA was 1.22, 1.97 and 2.08 ng/ml in 40-49, 50-59 and 60-70 years age groups. The mean total PSA and the age-specific PSA range tend to be lower in the Indians than the Western population.

Ultra-sensitive PSA Following Prostatectomy Reliably Identifies Patients Requiring Post-Op Radiotherapy

PubMed Central

Kang, Jung Julie; Reiter, Robert; Steinberg, Michael; King, Christopher R.

2015-01-01

PURPOSE Integrating ultra-sensitive PSA (uPSA) into surveillance of high-risk patients following radical prostatectomy (RP) potentially optimizes management by correctly identifying actual recurrences, promoting an early salvage strategy and minimizing overtreatment. The power of uPSA following surgery to identify eventual biochemical failures is tested. PATIENTS AND METHODS From 1991–2013, 247 high-risk patients with a median follow-up was 44 months after RP were identified (extraprostatic extension and/or positive margin). Surgical technique, initial PSA (iPSA), pathology and post-op PSA were analyzed. The uPSA assay threshold was 0.01 ng/mL. Conventional biochemical relapse (cBCR) was defined as PSA ≥0.2 ng/mL. Kaplan Meier and Cox multivariate analyses (MVA) compared uPSA recurrence vs. cBCR rates. RESULTS Sensitivity analysis identified uPSA ≥0.03 as the optimal threshold identifying recurrence. First post-op uPSA ≥0.03, Gleason grade, T-stage, iPSA, and margin status predicted cBCR. On MVA, only first post-op uPSA ≥0.03, Gleason grade, and T-stage independently predicted cBCR. First post-op uPSA ≥0.03 conferred the highest risk (HR 8.5, p<0.0001) and discerned cBCR with greater sensitivity than undetectable first conventional PSA (70% vs. 46%). Any post-op PSA ≥0.03 captured all failures missed by first post-op value (100% sensitivity) with accuracy (96% specificity). Defining failure at uPSA ≥0.03 yielded a median lead-time advantage of 18 months (mean 24 months) over the conventional PSA ≥0.2 definition. CONCLUSION uPSA ≥0.03 is an independent factor, identifies BCR more accurately than any traditional risk factors, and confers a significant lead-time advantage. uPSA enables critical decisions regarding timing and indication for post-op RT among high-risk patients following RP. PMID:25463990

Prostate-Specific Antigen (PSA) Bounce After Dose-Escalated External Beam Radiation Therapy Is an Independent Predictor of PSA Recurrence, Metastasis, and Survival in Prostate Adenocarcinoma Patients.

PubMed

Romesser, Paul B; Pei, Xin; Shi, Weiji; Zhang, Zhigang; Kollmeier, Marisa; McBride, Sean M; Zelefsky, Michael J

2018-01-01

To evaluate the difference in prostate-specific antigen (PSA) recurrence-free, distant metastasis-free, overall, and cancer-specific survival between PSA bounce (PSA-B) and non-bounce patients treated with dose-escalated external beam radiation therapy (DE-EBRT). During 1990-2010, 1898 prostate adenocarcinoma patients were treated with DE-EBRT to ≥75 Gy with ≥5 years follow-up. Patients receiving neoadjuvant/concurrent androgen-deprivation therapy (n=1035) or with fewer than 4 PSA values obtained 6 months or more after post-EBRT completion (n=87) were excluded. The evaluable 776 patients were treated (median, 81.0 Gy). Prostate-specific antigen bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below. Prostate-specific antigen relapse was defined as post-radiation therapy PSA nadir + 2 ng/mL. Median follow-up was 9.2 years (interquartile range, 6.9-11.3 years). One hundred twenty-three patients (15.9%) experienced PSA-B after DE-EBRT at a median of 24.6 months (interquartile range, 16.1-38.5 months). On multivariate analysis, younger age (P=.001), lower Gleason score (P=.0003), and higher radiation therapy dose (P=.0002) independently predicted PSA-B. Prostate-specific antigen bounce was independently associated with decreased risk for PSA relapse (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.33-0.85; P=.008), distant metastatic disease (HR 0.34; 95% CI 0.12-0.94; P=.04), and all-cause mortality (HR 0.53; 95% CI 0.29-0.96; P=.04) on multivariate Cox analysis. Because all 50 prostate cancer-specific deaths in patients without PSA-B were in the non-bounce cohort, competing-risks analysis was not applicable. A nonparametric competing-risks test demonstrated that patients with PSA-B had superior cancer-specific survival compared with patients without PSA-B (P=.004). Patients treated with dose-escalated radiation therapy for prostate adenocarcinoma who experience posttreatment PSA-B have

Genetically-Adjusted PSA Values May Prevent Delayed Biopsies in African-American Men

PubMed Central

Donin, Nicholas; Loeb, Stacy; Cooper, Phillip R.; Roehl, Kimberly A.; Baumann, Nikola A.; J.Catalona, William; Helfand, Brian T.

2014-01-01

Purpose Genetic variants called PSA-single nucleotide polymorphisms (PSA-SNPs) have been associated with serum PSA levels. We previously demonstrated that genetic correction of serum PSA in Caucasian men could reduce both potentially unnecessary biopsies by 15% to 20% and potentially delayed biopsies by 3%. Our objective was to evaluate whether genetic correction with the PSA-SNPs could reduce potentially unnecessary and/or delayed biopsies in African-American (AA) men. Materials and Methods We compared the genotypes of 4 PSA-SNPs between 964 Caucasian and 363 AA men without known PC. We adjusted PSA values based upon an individual's PSA-SNP carrier status, and calculated the percentage of men that would meet commonly used PSA thresholds for biopsy (≥2.5 or ≥4.0ng/mL) before and after genetic correction. Potentially unnecessary and delayed biopsies were defined as those men who went below and above the biopsy threshold after genetic correction, respectively. Results Overall, 349 (96.1%) and 354 (97.5%) AA men had measured PSA levels <2.5 and <4.0 ng/mL. Genetic correction in AA men did not avoid any potentially unnecessary biopsies, but resulted in a significant (p<0.001) reduction in potentially delayed biopsies by 2.5% and 3.9% based upon the biopsy threshold cutoff. Conclusions There are significant differences in the influence of the PSA-SNPs between AA and Caucasian men without known PC, as genetic correction resulted in an increased proportion of AA men crossing the threshold for biopsy. These results raise the question whether genetic differences in PSA might contribute to delayed PC diagnosis in AA patients. PMID:24712975

Insulin promotes cell migration by regulating PSA-NCAM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monzo, Hector J.; Coppieters, Natacha; Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland

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

Investigative clinical study on prostate cancer part III: exploring total PSA and free testosterone distributions and linear correlations in groups and subgroups of operated prostate cancer patients according to the total PSA/FT ratio.

PubMed

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

2010-01-01

Prostate cancer is an interesting tumor for endocrine investigation. The prostate-specific antigen/free testosterone (PSA/FT) ratio has been shown to be effective in clustering patients in prognostic groups as follows: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40) and high risk (PSA/FT >0.40 and ≤1.5). In the present study we explored the total PSA and FT distributions, and linear regression of FT predicting PSA in the different groups (PSA/FT, pT and pG) and subgroups (pT and pG) of patients according to the prognostic PSA/FT ratio. The study included 128 operated prostate cancer patients. Pretreatment simultaneous serum samples were obtained for measuring free testosterone (FT) and total PSA levels. Patients were grouped according to the total PSA/FT ratio prognostic clusters (≤0.20, >0.20 and ≤0.40, >0.40), pT (2, 3a and 3b+4) and pathological Gleason score (pG) (≤6, = 7 >3 + 4, ≥7 >4 + 3). The pT and pG sets were subgrouped according to the prognostic PSA/FT ratio. Linear regression analysis of FT predicting total PSA was computed according to the different PSA/FT prognostic clusters for the: (1) total sample population, (2) pT and pG groups, (3) intraprostatic (pT2) and extraprostatic disease (pT3a/3b/4), and (4) low-intermediate grade (pG ≤6) and high-grade (pG ≥7) prostate cancer. Analysis of variance always showed highly significant different PSA distributions for (1) the different PSA/FT, pT and pG groups; and (2) the pT and pG prognostic subgroups. Significant FT distributions were detected for the (1) PSA/FT and pT groups; and (2) the pT2, pT3a and pG ≤6 prognostic PSA/FT subgroups. Correlation, variance and linear regression analysis of FT predicting total PSA was significant for (1) the PSA/FT prognostic clusters, (2) all the pT2 and pT3a subgroups, and (3) the pT3b/4 subgroup with PSA/FT >0.20 and ≤0.40, and (4) all the pG subsets. Linear regression analysis showed that the slopes of the predicting variable

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

Prevalence and causes of abnormal PSA recovery.

PubMed

Lautenbach, Noémie; Müntener, Michael; Zanoni, Paolo; Saleh, Lanja; Saba, Karim; Umbehr, Martin; Velagapudi, Srividya; Hof, Danielle; Sulser, Tullio; Wild, Peter J; von Eckardstein, Arnold; Poyet, Cédric

2018-01-26

Prostate-specific antigen (PSA) test is of paramount importance as a diagnostic tool for the detection and monitoring of patients with prostate cancer. In the presence of interfering factors such as heterophilic antibodies or anti-PSA antibodies the PSA test can yield significantly falsified results. The prevalence of these factors is unknown. We determined the recovery of PSA concentrations diluting patient samples with a standard serum of known PSA concentration. Based on the frequency distribution of recoveries in a pre-study on 268 samples, samples with recoveries <80% or >120% were defined as suspect, re-tested and further characterized to identify the cause of interference. A total of 1158 consecutive serum samples were analyzed. Four samples (0.3%) showed reproducibly disturbed recoveries of 10%, 68%, 166% and 4441%. In three samples heterophilic antibodies were identified as the probable cause, in the fourth anti-PSA-autoantibodies. The very low recovery caused by the latter interference was confirmed in serum, as well as heparin- and EDTA plasma of blood samples obtained 6 months later. Analysis by eight different immunoassays showed recoveries ranging between <10% and 80%. In a follow-up study of 212 random plasma samples we found seven samples with autoantibodies against PSA which however did not show any disturbed PSA recovery. About 0.3% of PSA determinations by the electrochemiluminescence assay (ECLIA) of Roche diagnostics are disturbed by heterophilic or anti-PSA autoantibodies. Although they are rare, these interferences can cause relevant misinterpretations of a PSA test result.

Comparative Study of Blood-Based Biomarkers, α2,3-Sialic Acid PSA and PHI, for High-Risk Prostate Cancer Detection.

PubMed

Ferrer-Batallé, Montserrat; Llop, Esther; Ramírez, Manel; Aleixandre, Rosa Núria; Saez, Marc; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

2017-04-17

Prostate Specific Antigen (PSA) is the most commonly used serum marker for prostate cancer (PCa), although it is not specific and sensitive enough to allow the differential diagnosis of the more aggressive tumors. For that, new diagnostic methods are being developed, such as PCA-3, PSA isoforms that have resulted in the 4K score or the Prostate Health Index (PHI), and PSA glycoforms. In the present study, we have compared the PHI with our recently developed PSA glycoform assay, based on the determination of the α2,3-sialic acid percentage of serum PSA (% α2,3-SA), in a cohort of 79 patients, which include 50 PCa of different grades and 29 benign prostate hyperplasia (BPH) patients. The % α2,3-SA could distinguish high-risk PCa patients from the rest of patients better than the PHI (area under the curve (AUC) of 0.971 vs. 0.840), although the PHI correlated better with the Gleason score than the % α2,3-SA. The combination of both markers increased the AUC up to 0.985 resulting in 100% sensitivity and 94.7% specificity to differentiate high-risk PCa from the other low and intermediate-risk PCa and BPH patients. These results suggest that both serum markers complement each other and offer an improved diagnostic tool to identify high-risk PCa, which is an important requirement for guiding treatment decisions.

Insulin promotes cell migration by regulating PSA-NCAM.

PubMed

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

2017-06-01

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

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

PubMed

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

2014-12-01

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

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

Murine Polyomavirus Virus-Like Particles Carrying Full-Length Human PSA Protect BALB/c Mice from Outgrowth of a PSA Expressing Tumor

PubMed Central

Eriksson, Mathilda; Andreasson, Kalle; Weidmann, Joachim; Lundberg, Kajsa; Tegerstedt, Karin

2011-01-01

Virus-like particles (VLPs) consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV) VLPs carrying the entire human Prostate Specific Antigen (PSA) (PSA-MPyVLPs) for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs). Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4+ and CD8+ cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4+ and CD8+ cells with a low induction of anti-VLP antibodies. PMID:21858228

PSA doubling time of prostate carcinoma managed with watchful observation alone.

PubMed

Choo, R; DeBoer, G; Klotz, L; Danjoux, C; Morton, G C; Rakovitch, E; Fleshner, N; Bunting, P; Kapusta, L; Hruby, G

2001-07-01

To study prostate-specific antigen (PSA) doubling time of untreated, favorable grade, prostate carcinoma. A prospective single-arm cohort study has been in progress to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication in untreated, localized, favorable grade prostate adenocarcinoma (T1b-T2bN0 M0, Gleason Score < or = 7, and PSA < or = 15 ng/mL). Patients are conservatively managed with watchful observation alone, as long as they do not meet the arbitrarily defined disease progression criteria. Patients are followed regularly and undergo blood tests including PSA at each visit. PSA doubling time (Td) is estimated from a linear regression of ln(PSA) on time, assuming a simple exponential growth model. As of March 2000, 134 patients have been on the study for a minimum of 12 months (median, 24; range, 12-52) and have a median frequency of PSA measurement of 7 times (range, 3-15). Median age is 70 years. Median PSA at enrollment is 6.3 (range, 0.5-14.6). The distribution of Td is as follows: <2 years, 19 patients; 2-5 years, 46; 5-10 years, 25; 10-20 years, 11; 20-50 years, 6; > 50 years, 27. The median Td is 5.1 years. In 44 patients (33%), Td is greater than 10 years. There was no correlation between Td and patient age, clinical T stage, Gleason score, or initial PSA level. Td of untreated prostate cancer varies widely. In our cohort, 33% have Td > 10 years. Td may be a useful tool to guide treatment intervention for patients managed conservatively with watchful observation alone.

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

PubMed

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

2017-03-01

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

Switches to English during French Service Encounters: Relationships with L2 French Speakers' Willingness to Communicate and Motivation

ERIC Educational Resources Information Center

McNaughton, Stephanie; McDonough, Kim

2015-01-01

This exploratory study investigated second language (L2) French speakers' service encounters in the multilingual setting of Montreal, specifically whether switches to English during French service encounters were related to L2 speakers' willingness to communicate or motivation. Over a two-week period, 17 French L2 speakers in Montreal submitted…

Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer.

PubMed

Parwani, Anil V; Marlow, Cameron; Demarzo, Angelo M; Mikolajczyk, Stephen D; Rittenhouse, Harry G; Veltri, Robert W; Chan, Theresa Y

2006-10-01

Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

Extent of disease in recurrent prostate cancer determined by [(68)Ga]PSMA-HBED-CC PET/CT in relation to PSA levels, PSA doubling time and Gleason score.

PubMed

Verburg, Frederik A; Pfister, David; Heidenreich, Axel; Vogg, Andreas; Drude, Natascha I; Vöö, Stefan; Mottaghy, Felix M; Behrendt, Florian F

2016-03-01

To examine the relationship between the extent of disease determined by [(68)Ga]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score. We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for [(68)Ga]PSMA-HBED-CC PET/CT. PET/CT was positive in 44%, 79% and 89% of patients with PSA levels of ≤1, 1-2 and ≥2 ng/ml, respectively. Patients with high PSA levels showed higher rates of local prostate tumours (p < 0.001), and extrapelvic lymph node (p = 0.037) and bone metastases (p = 0.013). A shorter PSAdt was significantly associated with pelvic lymph node (p = 0.026), extrapelvic lymph node (p = 0.001), bone (p < 0.001) and visceral (p = 0.041) metastases. A high Gleason score was associated with more frequent pelvic lymph node metastases (p = 0.039). In multivariate analysis, both PSA and PSAdt were independent determinants of scan positivity and of extrapelvic lymph node metastases. PSAdt was the only independent marker of bone metastases (p = 0.001). Of 20 patients with a PSAdt <6 months and a PSA ≥2 ng/ml, 19 (95%) had a positive scan and 12 (60%) had M1a disease. Of 14 patients with PSA <1 ng/ml and PSAdt >6 months, only 5 (36%) had a positive scan and 1 (7%) had M1a disease. [(68)Ga]PSMA-HBED-CC PET/CT will identify PCA lesions even in patients with very low PSA levels. Higher PSA levels and shorter PSAdt are independently associated with scan positivity and extrapelvic metastases, and can be used for patient selection for [(68)Ga]PSMA-HBED-CC PET/CT.

Percentage of free prostate-specific antigen (PSA) is a useful method in deciding to perform prostate biopsy with higher core numbers in patients with low PSA cut-off values.

PubMed

Yilmaz, Hasan; Ciftci, Seyfettin; Yavuz, Ufuk; Ustuner, Murat; Saribacak, Ali; Dillioglugil, Ozdal

2015-06-01

The aim of this study was to evaluate the predictive role of percentage of free prostate-specific antigen (%fPSA) cut-points in prostate cancer (PCa) detection in patients with total PSA (tPSA) levels between 2.5 ng/mL and 10.0 ng/mL. In total, 1321 consecutive initial transrectal ultrasound (TRUS)-guided 12-core biopsies performed between 2005 and 2011 were evaluated retrospectively. Benign pathologies, high-grade prostatic intraepithelial neoplasia, and atypical small acinary proliferations were categorized as noncancerous (benign), and prostate adenocarcinomas were categorized as cancerous (malignant). The patients were categorized according to: Catalona's published %fPSA categories (<10%, 10-15%, 15-20%, 20-25%, or > 25%); digital rectal examination (DRE) results [benign (negative) or suspicious of malignancy (positive)]. There was a significant relationship between the %fPSA cut-points and detection of PCa in DRE-negative patients. The presence of a 10% cut-point increased the probability of PCa threefold. The %fPSA was significantly more related to PCa than the tPSA value in receiver operating characteristic (ROC) curve analyses (p = 0.001). Based on our findings, a lower %fPSA, especially <10%, is an important parameter when deciding whether to perform a biopsy on patients with a tPSA between 2.5 ng/mL and 10 ng/mL. Copyright © 2015. Published by Elsevier Taiwan.

Variability of assay methods for total and free PSA after WHO standardization.

PubMed

Foj, L; Filella, X; Alcover, J; Augé, J M; Escudero, J M; Molina, R

2014-03-01

The variability of total PSA (tPSA) and free PSA (fPSA) results among commercial assays has been suggested to be decreased by calibration to World Health Organization (WHO) reference materials. To characterize the current situation, it is necessary to know its impact in the critical cutoffs used in clinical practice. In the present study, we tested 167 samples with tPSA concentrations of 0 to 20 μg/L using seven PSA and six fPSA commercial assays, including Access, ARCHITECT i2000, ADVIA Centaur XP, IMMULITE 2000, Elecsys, and Lumipulse G1200, in which we only measured tPSA. tPSA and fPSA were measured in Access using the Hybritech and WHO calibrators. Passing-Bablok analysis was performed for PSA, and percentage of fPSA with the Hybritech-calibrated access comparison assay. For tPSA, relative differences were more than 10 % at 0.2 μg/L for ARCHITECT i2000, and at a critical concentration of 3, 4, and 10 μg/L, the relative difference was exceeded by ADVIA Centaur XP and WHO-calibrated Access. For percent fPSA, at a critical concentration of 10 %, the 10 % relative difference limit was exceeded by IMMULITE 2000 assay. At a critical concentration of 20 and 25 %, ADVIA Centaur XP, ARCHITECT i2000, and IMMULITE 2000 assays exceeded the 10 % relative difference limit. We have shown significant discordances between assays included in this study despite advances in standardization conducted in the last years. Further harmonization efforts are required in order to obtain a complete clinical concordance.

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

Time from first detectable PSA following radical prostatectomy to biochemical recurrence: A competing risk analysis.

PubMed

de Boo, Leonora; Pintilie, Melania; Yip, Paul; Baniel, Jack; Fleshner, Neil; Margel, David

2015-01-01

In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8-91.5) and from detectable PSA was 18 months (IQR 11-32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery.

Analysis of urinary PSA glycosylation is not indicative of high-risk prostate cancer.

PubMed

Barrabés, Sílvia; Llop, Esther; Ferrer-Batallé, Montserrat; Ramírez, Manel; Aleixandre, Rosa N; Perry, Antoinette S; de Llorens, Rafael; Peracaula, Rosa

2017-07-01

The levels of core fucosylation and α2,3-linked sialic acid in serum Prostate Specific Antigen (PSA), using the lectins Pholiota squarrosa lectin (PhoSL) and Sambucus nigra agglutinin (SNA), can discriminate between Benign Prostatic Hyperplasia (BPH) and indolent prostate cancer (PCa) from aggressive PCa. In the present work we evaluated whether these glycosylation determinants could also be altered in urinary PSA obtained after digital rectal examination (DRE) and could also be useful for diagnosis determinations. For this purpose, α2,6-sialic acid and α1,6-fucose levels of urinary PSA from 53 patients, 18 biopsy-negative and 35 PCa patients of different aggressiveness degree, were analyzed by sandwich ELLA (Enzyme Linked Lectin Assay) using PhoSL and SNA. Changes in the levels of specific glycosylation determinants, that in serum PSA samples were indicative of PCa aggressiveness, were not found in PSA from DRE urine samples. Although urine is a simpler matrix for analyzing PSA glycosylation compared to serum, an immunopurification step was necessary to specifically detect the glycans on the PSA molecule. Those specific glycosylation determinants on urinary PSA were however not useful to improve PCa diagnosis. This could be probably due to the low proportion of PSA from the tumor in urine samples, which precludes the identification of aberrantly glycosylated PSA. Copyright © 2017 Elsevier B.V. All rights reserved.

Low percentage of free prostate-specific antigen (PSA) is a strong predictor of later detection of prostate cancer among Japanese men with serum levels of total PSA of 4.0 ng/mL or less.

PubMed

Sasaki, Mitsuharu; Ishidoya, Shigeto; Ito, Akihiro; Saito, Hideo; Yamada, Shigeyuki; Mitsuzuka, Koji; Kaiho, Yasuhiro; Shibuya, Daisuke; Yamaguchi, Takuhiro; Arai, Yoichi

2014-11-01

To investigate the effect of the percentage of free prostate-specific antigen (%fPSA) on future prostate cancer risk. We examined serum total PSA (tPSA) and %fPSA annually in a prostate cancer-screening cohort between July 2001 and June 2011. Men with tPSA >4.0 ng/mL or tPSA of 2.0-4.0 ng/mL with %fPSA ≤12% were screened as positive and were recommended to undergo a biopsy. The study population consisted of 6368 men, aged 40-79 years, who had tPSA ≤4.0 ng/mL at initial screening and who subsequently underwent 1 or more screenings. We calculated the cumulative risk and hazard ratio of prostate cancer stratified by the initial %fPSA groups as quartiles of prostate cancer patients. During a median follow-up of 36 months, 119 men were diagnosed with prostate cancer. The lowest quartile of %fPSA (<13.3%) was associated with a 21.2-fold higher risk of having prostate cancer compared with the highest quartile (>22.2%). For the subset with an initial tPSA ≤1.0 ng/mL, all men diagnosed with cancer had an initial %fPSA ≤33.3% (median). For the subset with tPSA >1.0 ng/mL, men with %fPSA ≤23.0% (median) had significantly higher risk for cancer than those with %fPSA >23.0% (P <.0001). Of the 114 men with prostate cancer in whom pathologic findings were available, 79 (69.3%) had a Gleason score ≥3 + 4 = 7. A low %fPSA is a strong predictor of a subsequent diagnosis of prostate cancer among men with tPSA levels ≤4.0 ng/mL. Measurement of %fPSA might enhance the detection of high-grade cancer that warrants aggressive treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

PSA kinetics following primary focal cryotherapy (hemiablation) in organ-confined prostate cancer patients.

PubMed

Kongnyuy, Michael; Islam, Shahidul; Mbah, Alfred K; Halpern, Daniel M; Werneburg, Glenn T; Kosinski, Kaitlin E; Chen, Connie; Habibian, David J; Schiff, Jeffrey T; Corcoran, Anthony T; Katz, Aaron E

2018-02-01

We aim to evaluate prostate-specific antigen (PSA) trends in post-primary focal cryotherapy (PFC) patients. This was an institutional review board-approved retrospective study of PFC patients from 2010 to 2015. Patients with at least one post-PFC PSA were included in the study. Biochemical recurrence (BCR) was determined using the Phoenix criteria. PSA bounce was also assessed. We analyzed rates of change of PSA over time of post-PFC between BCR and no BCR groups. PSA-derived variables were analyzed as potential predictors of BCR. A total of 104 PFC patients were included in our analysis. Median (range) age and follow-up time were 66 (48-82) years and 19 (6.3-38.6) months, respectively. Four (3.8%) patients experienced PSA bounce. The median percent drop in first post-PFC PSA of 80.0% was not associated with BCR (p = 0.256) and may indicate elimination of the index lesion. The rate of increase of PSA in BCR patients was significantly higher compared to patients who did not recur (median PSA velocity (PSAV): 0.15 vs 0.04 ng/ml/month, p = 0.001). Similar to PSAV (HR 9.570, 95% CI 3.725-24.592, p < 0.0001), PSA nadir ≥ 2 ng/ml [HR (hazard ratio) 1.251, 95% CI 1.100-1.422, p = 0.001] was independently associated with BCR. A significant drop in post-PFC PSA may indicate elimination of the index lesion. Patients who are likely to recur biochemically have a significantly higher PSAV compared to those who do not recur. Nadir PSA of less than 2 ng/ml may be considered the new normal PSA in focal cryotherapy (hemiablation) follow-up.

Stability and accuracy of total and free PSA values in samples stored at room temperature.

PubMed

Forde, J C; Blake, O; Crowley, V E; Lynch, T H

2016-11-01

In 2010, an estimated 476,076 total PSA tests were performed in Ireland, at a cost of €3.6 million with the majority ordered by general practitioners. We aimed to replicate storage conditions at room temperature and see if prolonged storage affected total and free PSA values. Blood samples were taken from 20 male patients in four VACUETTE ® Serum Separator tubes (Greiner-Bio-One, Austria) and stored at room temperature (22 °C) for different time intervals (4, 8, 24, 48 h) before being centrifuged and analyzed. Total PSA (tPSA) and free PSA (fPSA) values were determined using the Tosoh AIA 1800 assay (Tokyo, Japan). Mean tPSA values were measured at 4, 8, 24 and 48 h with values of 7.9, 8.1, 7.8 and 8.0 μg/L, respectively. Values ranged from -1.26 to +2.53 % compared to the initial 4 h interval reading, indicating tPSA remained consistent at room temperature. The tPSA showed no significance between groups (ANOVA, p = 0.283). Mean fPSA values at 4, 8, 24 and 48 h were 2.05, 2.04, 1.83, 1.82 μg/L, respectively. At 24 and 48 h there was 10.73 and 11.22 % reduction, respectively, in fPSA compared to the 4-h time interval, indicating prolonged storage resulted in reduced fPSA values. After 24 h, there was an 8.8 % reduction in the free/total PSA %. The fPSA showed significant differences between groups (ANOVA, p = 0.024). Our recommendation is that samples that have been stored for prolonged amounts of time (greater than 24 h) should not be used for free PSA testing.

Flood hazard assessment for french NPPs

NASA Astrophysics Data System (ADS)

Rebour, Vincent; Duluc, Claire-Marie; Guimier, Laurent

2015-04-01

This paper presents the approach for flood hazard assessment for NPP which is on-going in France in the framework of post-Fukushima activities. These activities were initially defined considering both European "stress tests" of NPPs pursuant to the request of the European Council, and the French safety audit of civilian nuclear facilities in the light of the Fukushima Daiichi accident. The main actors in that process are the utility (EDF is, up to date, the unique NPP's operator in France), the regulatory authority (ASN) and its technical support organization (IRSN). This paper was prepared by IRSN, considering official positions of the other main actors in the current review process, it was not officially endorsed by them. In France, flood hazard to be considered for design basis definition (for new NPPs and for existing NPPs in periodic safety reviews conducted every 10 years) was revised before Fukushima-Daichi accident, due to le Blayais NPP December 1999 experience (partial site flooding and loss of some safety classified systems). The paper presents in the first part an overview of the revised guidance for design basis flood. In order to address design extension conditions (conditions that could result from natural events exceeding the design basis events), a set of flooding scenarios have been defined by adding margins on the scenarios that are considered for the design. Due to the diversity of phenomena to be considered for flooding hazard, the margin assessment is specific to each flooding scenario in terms of parameter to be penalized and of degree of variation of this parameter. The general approach to address design extension conditions is presented in the second part of the paper. The next parts present the approach for five flooding scenarios including design basis scenario and additional margin to define design extension scenarios.

Use of integral experiments for the assessment of a new 235U IRSN-CEA evaluation

NASA Astrophysics Data System (ADS)

Ichou, Raphaëlle; Leclaire, Nicolas; Leal, Luiz; Haeck, Wim; Morillon, Benjamin; Romain, Pascal; Duarte, Helder

2017-09-01

The Working Party on International Nuclear Data Evaluation Co-operation (WPEC) subgroup 29 (SG 29) was established to investigate an issue with the 235U capture cross-section in the energy range from 0.1 to 2.25 keV, due to a possible overestimation of 10% or more. To improve the 235U capture crosssection, a new 235U evaluation has been proposed by the Institut de Radioprotection et de Sûreté Nucléaire (IRSN) and the CEA, mainly based on new time-of-flight 235U capture cross-section measurements and recent fission cross-section measurements performed at the n_TOF facility from CERN. IRSN and CEA Cadarache were in charge of the thermal to 2.25 keV energy range, whereas the CEA DIF was responsible of the high energy region. Integral experiments showing a strong 235U sensitivity are used to assess the new evaluation, using Monte-Carlo methods. The keff calculations were performed with the 5.D.1 beta version of the MORET 5 code, using the JEFF-3.2 library and the new 235U evaluation, as well as the JEFF-3.3T1 library in which the new 235U has been included. The benchmark selection allowed highlighting a significant improvement on keff due to the new 235U evaluation. The results of this data testing are presented here.

Metastatic prostate cancer in the modern era of PSA screening

PubMed Central

Fontenot, Philip A.; Nehra, Avinash; Parker, William; Wyre, Hadley; Mirza, Moben; Duchene, David A.; Holzbeierlein, Jeffrey; Thrasher, James Brantley; Veldhuizen, Peter Van; Lee, Eugene K.

2017-01-01

ABSTRACT Introduction To characterize initial presentation and PSA screening status in a contemporary cohort of men treated for metastatic prostate cancer at our institution. Materials and methods We reviewed records of 160 men treated for metastatic prostate cancer between 2008-2014 and assessed initial presentation, categorizing patients into four groups. Groups 1 and 2 presented with localized disease and received treatment. These men suffered biochemical recurrence late (>1 year) or earlier (<1 year), respectively, and developed metastases. Groups 3 and 4 had asymptomatic and symptomatic metastases at the outset of their diagnosis. Patients with a first PSA at age 55 or younger were considered to have guideline-directed screening. Results Complete records were available on 157 men for initial presentation and 155 men for PSA screening. Groups 1, 2, 3 and 4 included 27 (17%), 7 (5%), 69 (44%) and 54 (34%) patients, respectively. Twenty (13%) patients received guideline-directed PSA screening, 5/155 (3%) patients presented with metastases prior to age 55 with their first PSA, and 130/155 (84%) had their first PSA after age 55, of which 122/130 (94%) had metastasis at the time of diagnosis. Conclusion Despite widespread screening, most men treated for metastatic prostate cancer at our institution presented with metastases rather than progressed after definitive treatment. Furthermore, 25 (16%) patients received guideline-directed PSA screening at or before age 55. These data highlight that, despite mass screening efforts, patients treated for incurable disease at our institution may not have been a result of a failed screening test, but a failure to be screened. PMID:28338310

Cost implications of PSA screening differ by age.

PubMed

Rao, Karthik; Liang, Stella; Cardamone, Michael; Joshu, Corinne E; Marmen, Kyle; Bhavsar, Nrupen; Nelson, William G; Ballentine Carter, H; Albert, Michael C; Platz, Elizabeth A; Pollack, Craig E

2018-05-09

Multiple guidelines seek to alter rates of prostate-specific antigen (PSA)-based prostate cancer screening. The costs borne by payers associated with PSA-based screening for men of different age groups-including the costs of screening and subsequent diagnosis, treatment, and adverse events-remain uncertain. We sought to develop a model of PSA costs that could be used by payers and health care systems to inform cost considerations under a range of different scenarios. We determined the prevalence of PSA screening among men aged 50 and higher using 2013-2014 data from a large, multispecialty group, obtained reimbursed costs associated with screening, diagnosis, and treatment from a commercial health plan, and identified transition probabilities for biopsy, diagnosis, treatment, and complications from the literature to generate a cost model. We estimated annual total costs for groups of men ages 50-54, 55-69, and 70+ years, and varied annual prostate cancer screening prevalence in each group from 5 to 50% and tested hypothetical examples of different test characteristics (e.g., true/false positive rate). Under the baseline screening patterns, costs of the PSA screening represented 10.1% of the total costs; costs of biopsies and associated complications were 23.3% of total costs; and, although only 0.3% of all screen eligible patients were treated, they accounted for 66.7% of total costs. For each 5-percentage point decrease in PSA screening among men aged 70 and older for a single calendar year, total costs associated with prostate cancer screening decreased by 13.8%. For each 5-percentage point decrease in PSA screening among men 50-54 and 55-69 years old, costs were 2.3% and 7.3% lower respectively. With constrained financial resources and with national pressure to decrease use of clinically unnecessary PSA-based prostate cancer screening, there is an opportunity for cost savings, especially by focusing on the downstream costs disproportionately associated with

Time from first detectable PSA following radical prostatectomy to biochemical recurrence: A competing risk analysis

PubMed Central

de Boo, Leonora; Pintilie, Melania; Yip, Paul; Baniel, Jack; Fleshner, Neil; Margel, David

2015-01-01

Introduction: In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. Methods: We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. Results: The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8–91.5) and from detectable PSA was 18 months (IQR 11–32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. Conclusion: The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery. PMID:25624961

Immune Impact Induced by PROSTVAC (PSA-TRICOM), a Therapeutic Vaccine for Prostate Cancer

PubMed Central

Gulley, James L.; Madan, Ravi A.; Tsang, Kwong Y.; Jochems, Caroline; Marté, Jennifer L.; Farsaci, Benedetto; Tucker, Jo A.; Hodge, James W.; Liewehr, David J.; Steinberg, Seth M.; Heery, Christopher R.; Schlom, Jeffrey

2013-01-01

PSA-TRICOM (PROSTVAC) is a novel vector-based vaccine designed to generate a robust immune response against prostate-specific antigen (PSA)–expressing tumor cells. The purpose of this report is to present an overview of both published studies and new data in the evaluation of immune responses to the PSA-TRICOM vaccine platform, currently in phase III testing. Of 104 patients tested for T-cell responses, 57% (59/104) demonstrated a ≥ 2-fold increase in PSA-specific T cells 4 weeks after vaccine (median 5-fold increase) compared with pre-vaccine, and 68% (19/28) of patients tested mounted post-vaccine immune responses to tumor-associated antigens not present in the vaccine (antigen-spreading). The PSA-specific immune responses observed 28 days after vaccine (i.e., likely memory cells) are quantitatively similar to the levels of circulating T cells specific for influenza seen in the same patients. Measurements of systemic immune response to PSA may underestimate the true therapeutic immune response (as this does not account for cells that have trafficked to the tumor) and does not include antigen-spreading. Furthermore, while the entire PSA gene is the vaccine, only one epitope of PSA is evaluated in the T-cell responses. Since this therapeutic vaccine is directed at generating a cellular/Th1 immune response (T-cell costimulatory molecules and use of a viral vector), it is not surprising that < 0.6% of patients (2/349) tested have evidence of PSA antibody-induction following vaccine. This suggests that post-vaccine PSA kinetics were not affected by PSA antibodies. An ongoing phase III study will evaluate the systemic immune responses and correlation with clinical outcomes. PMID:24778277

Effectiveness of early adalimumab therapy in psoriatic arthritis patients from Reuma.pt - EARLY PsA.

PubMed

Santos, Helena; Eusébio, Mónica; Borges, Joana; Gonçalves, Diana; Ávila-Ribeiro, Pedro; Faria, Daniela Santos; Lopes, Carina; Rovisco, João; Águeda, Ana; Nero, Patrícia; Valente, Paula; Cravo, Ana Rita; Santos, Maria José

2017-01-01

Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating adalimumab (ADA), with short- and long-term disease duration and to evaluate the potential effect of concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) between June 2008-June 2016 who received ADA for ≥3 months. Psoriatic Arthritis Response Criteria (PsARC) response, tender and swollen joint count, inflammatory parameters, patient (PtGA) and physician global assessment (PhGA), Disease Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability Index (HAQ-DI) were compared between patients with <5 years of disease (early PsA) and those with ≥5 years of disease duration (late PsA). Time to achieving PsARC response was estimated using the Kaplan-Meier method. Results Of 135 PsA patients treated with ADA, 126 had information on disease duration (earlyPsA, n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs 62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs 1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and lower PhGA (6.3 vs 21.9; P<0.001), C-reactive protein (0.4 mg/dL vs 1.0 mg/dL; P=0.026), and DAS28 (2.2 vs 3.2; P=0.030). HAQ-DI decreased in both groups reaching a mean value at 24 months of 0.4 and 0.8 (P=ns) in early and late PsA, respectively. Early PsA patients obtained PsARC response more rapidly than late PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant glucocorticoids

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) significantly improve prostate cancer detection at initial biopsy in a total PSA range of 2-10 ng/ml.

PubMed

Ferro, Matteo; Bruzzese, Dario; Perdonà, Sisto; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; D'Esposito, Vittoria; Cosimato, Vincenzo; Buonerba, Carlo; Di Lorenzo, Giuseppe; Musi, Gennaro; De Cobelli, Ottavio; Chun, Felix K; Terracciano, Daniela

2013-01-01

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2-10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2-10 ng/ml at initial biopsy, outperforming currently used %fPSA.

The Efficacy of Buccal Infiltration of 4% Articaine and PSA Injection of 2% Lidocaine on Anesthesia of Maxillary Second Molars.

PubMed

Maljaei, Ensiyeh; Pourkazemi, Maryam; Ghanizadeh, Milad; Ranjbar, Rana

2017-01-01

During the early mixed dentition period, the location of the deciduous maxillary second molar results in ineffectiveness of the infiltration technique in this area. In such cases, administration of posterior superior alveolar (PSA) nerve block is recommended; however, such a technique has some complications. The present study was undertaken to compare the effects of buccal infiltration of 4% Articaine and PSA technique with 2% Lidocaine on the success of anesthesia of maxillary deciduous second molars in 6 to 9-year old children. In the present double-blind randomized clinical trial, 56 children aged 6-9 years requiring vital pulp therapy of deciduous maxillary second molar were included. In group 1, 4% Articaine was injected using a buccal infiltration technique. In group 2, 2% Lidocaine was injected using the PSA nerve block technique. After 10 min, the caries was removed and access cavity preparation was instituted. The patients were asked to report the presence or absence of pain during the procedure. Therefore, the existence of pain was measured by the patient's self-report. Data were analyzed with descriptive statistical methods and the chi -squared test. Pain was reported by 6 (21.4%) and 9 (32.1%) subjects in the Articaine and Lidocaine groups, respectively. Chi -squared test did not reveal any significant differences between the two groups ( P =0.54). Under the limitations of the present study, there was no significant differences between the results of Articaine buccal infiltration and Lidocaine PSA technique, so Articaine buccal infiltration can be used as a substitute for the PSA technique.

Activation of innate immunity by prostate specific antigen (PSA).

PubMed

Kodak, James A; Mann, Dean L; Klyushnenkova, Elena N; Alexander, Richard B

2006-11-01

Prostate specific antigen (PSA) is a serine protease secreted by the prostatic epithelium. The only known function of the protein is to cleave seminogelin. We wished to determine if PSA activated peripheral blood mononuclear cells (PBMC). PBMC and selected sub-populations were cultured with purified PSA. Secretion of IFNgamma was measured by cytokine capture flow cytometry and enzyme-linked immunosorbent assay. We observed secretion of IFNgamma and a proliferative response in PBMC cultured with PSA. We found that NK cells were the source of the IFNgamma but NK cells were not directly stimulated by PSA. Rather, a soluble factor secreted primarily by CD14 monocytes in response to PSA stimulated NK cells to secrete IFNgamma. PSA induces a pro-inflammatory response that results in the secretion of INFgamma by NK cells. The presence of large amounts of PSA could contribute to the common finding of inflammatory infiltrates in the prostate.

Can Prostate Imaging Reporting and Data System Version 2 reduce unnecessary prostate biopsies in men with PSA levels of 4-10 ng/ml?

PubMed

Xu, Ning; Wu, Yu-Peng; Chen, Dong-Ning; Ke, Zhi-Bin; Cai, Hai; Wei, Yong; Zheng, Qing-Shui; Huang, Jin-Bei; Li, Xiao-Dong; Xue, Xue-Yi

2018-05-01

To explore the value of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2) for predicting prostate biopsy results in patients with prostate specific antigen (PSA) levels of 4-10 ng/ml. We retrospectively reviewed multi-parameter magnetic resonance images from 528 patients with PSA levels of 4-10 ng/ml who underwent transrectal ultrasound-guided prostate biopsies between May 2015 and May 2017. Among them, 137 were diagnosed with prostate cancer (PCa), and we further subdivided them according to pathological results into the significant PCa (S-PCa) and insignificant significant PCa (Ins-PCa) groups (121 cases were defined by surgical pathological specimen and 16 by biopsy). Age, PSA, percent free PSA, PSA density (PSAD), prostate volume (PV), and PI-RADS score were collected. Logistic regression analysis was performed to determine predictors of pathological results. Receiver operating characteristic curves were constructed to analyze the diagnostic value of PI-RADS v2 in PCa. Multivariate analysis indicated that age, PV, percent free PSA, and PI-RADS score were independent predictors of biopsy findings, while only PI-RADS score was an independent predictor of S-PCa (P < 0.05). The areas under the receiver operating characteristic curve for diagnosing PCa with respect to age, PV, percent free PSA, and PI-RADS score were 0.570, 0.430, 0.589 and 0.836, respectively. The area under the curve for diagnosing S-PCa with respect to PI-RADS score was 0.732. A PI-RADS score of 3 was the best cutoff for predicting PCa, and 4 was the best cutoff for predicting S-PCa. Thus, 92.8% of patients with PI-RADS scores of 1-2 would have avoided biopsy, but at the cost of missing 2.2% of the potential PCa cases. Similarly, 83.82% of patients with a PI-RADS score ≤ 3 would have avoided biopsy, but at the cost of missing 3.3% of the potential S-PCa cases. PI-RADS v2 could be used to reduce unnecessary prostate biopsies in patients with PSA levels of 4-10 ng/ml.

PSA predicts development of incident lower urinary tract symptoms: results from the REDUCE study.

PubMed

Patel, Devin N; Feng, Tom; Simon, Ross M; Howard, Lauren E; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Roehrborn, Claus; Andriole, Gerald L; Freedland, Stephen J

2018-05-23

The relationship between baseline prostate-specific antigen (PSA) and development of lower urinary tract symptoms (LUTS) in asymptomatic and mildly symptomatic men is unclear. We sought to determine if PSA predicts incident LUTS in these men. A post-hoc analysis of the 4-year REDUCE study was performed to assess for incident LUTS in 1534 men with mild to no LUTS at baseline. The primary aim was to determine whether PSA independently predicted incident LUTS after adjusting for the key clinical variables of age, prostate size, and baseline International prostate symptom score (IPSS). Incident LUTS was defined as the first report of medical treatment, surgery, or sustained clinically significant symptoms (two IPSS >14). Cox proportional hazards, cumulative incidence curves, and the log-rank test were used to test our hypothesis. A total of 1534 men with baseline IPSS <8 were included in the study cohort. At baseline, there were 335 men with PSA 2.5-4 ng/mL, 589 with PSA 4.1-6 ng/mL, and 610 with PSA 6-10 ng/mL. During the 4-year study, 196 men progressed to incident LUTS (50.5% medical treatment, 9% surgery, and 40.5% new symptoms). As a continuous variable, higher PSA was associated with increased incident LUTS on univariable (HR 1.09, p = 0.019) and multivariable (HR 1.08, p = 0.040) analysis. Likewise, baseline PSA 6-10 ng/mL was associated with increased incident LUTS vs. PSA 2.5-4 ng/mL in adjusted models (HR 1.68, p = 0.016). This association was also observed in men with PSA 4.1-6 ng/mL vs. PSA 2.5-4 ng/mL (HR 1.60, p = 0.032). Men with mild to no LUTS but increased baseline PSA are at increased risk of developing incident LUTS presumed due to benign prostatic hyperplasia.

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

PubMed

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.

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

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) Significantly Improve Prostate Cancer Detection at Initial Biopsy in a Total PSA Range of 2–10 ng/ml

PubMed Central

Perdonà, Sisto; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; D’Esposito, Vittoria; Cosimato, Vincenzo; Buonerba, Carlo; Di Lorenzo, Giuseppe; Musi, Gennaro; De Cobelli, Ottavio; Chun, Felix K.; Terracciano, Daniela

2013-01-01

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2–10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2–10 ng/ml at initial biopsy, outperforming currently used %fPSA. PMID:23861782

The Efficacy of Buccal Infiltration of 4% Articaine and PSA Injection of 2% Lidocaine on Anesthesia of Maxillary Second Molars

PubMed Central

Maljaei, Ensiyeh; Pourkazemi, Maryam; Ghanizadeh, Milad; Ranjbar, Rana

2017-01-01

Introduction: During the early mixed dentition period, the location of the deciduous maxillary second molar results in ineffectiveness of the infiltration technique in this area. In such cases, administration of posterior superior alveolar (PSA) nerve block is recommended; however, such a technique has some complications. The present study was undertaken to compare the effects of buccal infiltration of 4% Articaine and PSA technique with 2% Lidocaine on the success of anesthesia of maxillary deciduous second molars in 6 to 9-year old children. Methods and Materials: In the present double-blind randomized clinical trial, 56 children aged 6-9 years requiring vital pulp therapy of deciduous maxillary second molar were included. In group 1, 4% Articaine was injected using a buccal infiltration technique. In group 2, 2% Lidocaine was injected using the PSA nerve block technique. After 10 min, the caries was removed and access cavity preparation was instituted. The patients were asked to report the presence or absence of pain during the procedure. Therefore, the existence of pain was measured by the patient's self-report. Data were analyzed with descriptive statistical methods and the chi-squared test. Results: Pain was reported by 6 (21.4%) and 9 (32.1%) subjects in the Articaine and Lidocaine groups, respectively. Chi-squared test did not reveal any significant differences between the two groups (P=0.54). Conclusion: Under the limitations of the present study, there was no significant differences between the results of Articaine buccal infiltration and Lidocaine PSA technique, so Articaine buccal infiltration can be used as a substitute for the PSA technique. PMID:28808450

Prostate-specific antigen (PSA) blood test

MedlinePlus

... very early. But there is debate over the value of the PSA test for detecting prostate cancer. No single answer fits all men. Before having the test, talk to your provider about the pros and cons of having a PSA test. Ask ...

Intensity Accents in French 2 Year Olds' Speech.

ERIC Educational Resources Information Center

Allen, George D.

The acoustic features and functions of accentuation in French are discussed, and features of accentuation in the speech of French 2-year-olds are explored. The four major acoustic features used to signal accentual distinctions are fundamental frequency of voicing, duration of segments and syllables, intensity of segments and syllables, and…

Evaluation of PSA-age volume score in predicting prostate cancer in Chinese populationArticle Subject.

PubMed

Wu, Yi-Shuo; Wu, Xiao-Bo; Zhang, Ning; Jiang, Guang-Liang; Yu, Yang; Tong, Shi-Jun; Jiang, Hao-Wen; Mao, Shan-Hua; Na, Rong; Ding, Qiang

2018-02-06

This study was performed to evaluate prostate-specific antigen-age volume (PSA-AV) scores in predicting prostate cancer (PCa) in a Chinese biopsy population. A total of 2355 men who underwent initial prostate biopsy from January 2006 to November 2015 in Huashan Hospital were recruited in the current study. The PSA-AV scores were calculated and assessed together with PSA and PSA density (PSAD) retrospectively. Among 2133 patients included in the analysis, 947 (44.4%) were diagnosed with PCa. The mean age, PSA, and positive rates of digital rectal examination result and transrectal ultrasound result were statistically higher in men diagnosed with PCa (all P < 0.05). The values of area under the receiver operating characteristic curves (AUCs) of PSAD and PSA-AV were 0.864 and 0.851, respectively, in predicting PCa in the entire population, both performed better than PSA (AUC = 0.805; P < 0.05). The superiority of PSAD and PSA-AV was more obvious in subgroup with PSA ranging from 2.0 ng ml-1 to 20.0 ng ml-1. A PSA-AV score of 400 had a sensitivity and specificity of 93.7% and 40.0%, respectively. In conclusion, the PSA-AV score performed equally with PSAD and was better than PSA in predicting PCa. This indicated that PSA-AV score could be a useful tool for predicting PCa in Chinese population.

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

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia

PubMed Central

Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

2017-01-01

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa. PMID:29100363

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia.

PubMed

Jia, Gaozhen; Dong, Zhenyang; Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

2017-09-29

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa.

FOXM1 promotes the progression of prostate cancer by regulating PSA gene transcription.

PubMed

Liu, Youhong; Liu, Yijun; Yuan, Bowen; Yin, Linglong; Peng, Yuchong; Yu, Xiaohui; Zhou, Weibing; Gong, Zhicheng; Liu, Jianye; He, Leye; Li, Xiong

2017-03-07

Androgen/AR is the primary contributor to prostate cancer (PCa) progression by regulating Prostate Specific Antigen (PSA) gene transcription. The disease inevitably evolves to androgen-independent (AI) status. Other mechanisms by which PSA is regulated and develops to AI have not yet been fully determined. FOXM1 is a cell proliferation-specific transcription factor highly expressed in PCa cells compared to non-malignant prostate epithelial cells, suggesting that the aberrant overexpression of FOXM1 contributes to PCa development. In addition to regulating AR gene transcription and cell cycle-regulatory genes, FOXM1 selectively regulates the gene transcription of KLK2 and PSA, typical androgen responsive genes. Screening the potential FOXM1-binding sites by ChIP-PCR, we found that FOXM1 directly binds to the FHK binding motifs in the PSA promoter/enhancer regions. AI C4-2 cells have more FOXM1 binding sites than androgen dependent LNCaP cells. The depletion of FOXM1 by small molecular inhibitors significantly improves the suppression of PSA gene transcription by the anti-AR agent Cadosax. This is the first report showing that FOXM1 promotes PCa progression by regulating PSA gene transcription, particularly in AI PCa cells. The combination of anti-AR agents and FOXM1 inhibitors has the potential to greatly improve therapy for late-stage PCa patients by suppressing PSA levels.

Neutron Fluence and Energy Reconstruction with the LNE-IRSN/MIMAC Recoil Detector MicroTPC at 27 keV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maire, D.; Lebreton, L.; Querre, Ph.

2015-07-01

The French Institute for Radiation protection and Nuclear Safety (IRSN), designated by the French Metrology Institute (LNE) for neutron metrology, is developing a time projection chamber using a Micromegas anode: microTPC. This work is carried out in collaboration with the Laboratory of Subatomic Physics and Cosmology (LPSC). The aim is to characterize the energy distribution of neutron fluence in the energy range 8 keV - 5 MeV with a primary procedure. The time projection chambers are gaseous detectors able to measure charged particles energy and to reconstruct their track if a pixelated anode is used. In our case, the gasmore » is used as a (n, p) converter in order to detect neutrons down to few keV. Coming from elastic collisions with neutrons, recoil protons lose a part of their kinetic energy by ionizing the gas. The ionization electrons are drifted toward a pixelated anode (2D projection), read at 50 MHz by a self-triggered electronic system to obtain the third track dimension. The neutron energy is reconstructed event by event thanks to proton scattering angle and proton energy measurements. The scattering angle is deduced from the 3D track. The proton energy is obtained by charge collection measurements, knowing the ionization quenching factor (i.e. the part of proton kinetic energy lost by ionizing the gas). The fluence is calculated thanks to the detected events number and the simulation of the detector response. The μTPC is a new reliable detector able to measure energy distribution of the neutron fluence without unfolding procedure or prior neutron calibration contrary to usual gaseous counters. The microTPC is still being developed and measurements have been carried out at the AMANDE facility, with neutrons energies going from 8 keV to 565 keV. After the context and the μ-TPC working principle presentation, measurements of the neutron energy and fluence at 27 keV and 144 keV are shown and compared to the complete detector response simulation. This

Two-year survival rates of anti-TNF-α therapy in psoriatic arthritis (PsA) patients with either polyarticular or oligoarticular PsA.

PubMed

Iannone, F; Lopriore, S; Bucci, R; Scioscia, C; Anelli, M G; Notarnicola, A; Lapadula, G

2015-05-01

To evaluate the 2-year drug survival rates of the tumour necrosis factor (TNF)-α blockers adalimumab, etanercept, and infliximab in psoriatic arthritis (PsA) patients with either oligoarticular (oligo-PsA) or polyarticular PsA (poly-PsA). We studied a prospective cohort of 328 PsA patients with peripheral arthritis (213 with poly-PsA and 115 with oligo-PsA), beginning their first ever anti-TNF-α treatment with adalimumab, etanercept, or infliximab. The aim of the study was to evaluate the drug survival rates and possible baseline predictors at 2 years. After 24 months, persistence in therapy with the first anti-TNF-α blocker was not statistically different in the oligo-PsA (70.4%) and poly-PsA (65.7%) subsets. Predictors of drug discontinuation were female sex [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.00-2.68, p = 0.04] and starting the therapy in years 2003-8 (HR 0.51, 95% CI 0.33-0.80, p = 0.003). In poly-PsA, the persistence of etanercept (68.3%) was significantly higher than that of adalimumab (51.9%, p = 0.01), whereas in oligo-PsA no significant difference was detected. In poly-PsA, the period 2003-8 was a negative predictor (HR 0.36, 95% CI 0.21-0.62, p = 0.0001) whereas in oligo-PsA female gender was a positive predictor of drug discontinuation (HR 2.08, 95% CI 1.02-4.24, p = 0.04). With regard to clinical outcomes, the best responses in terms of European League Against Rheumatism (EULAR) 'good' response or Disease Activity Score (DAS28) remission, crude or adjusted according to the LUND Efficacy indeX (LUNDEX), were seen in patients on etanercept or infliximab. Our study provides some evidence that anti-TNF-α drugs may perform differently in PsA, and that the analysis of clinical disease subsets may improve our knowledge and promote better management of PsA.

Men presenting with prostate-specific antigen (PSA) values of over 100 ng/mL.

PubMed

Ang, Mann; Rajcic, Branimir; Foreman, Darren; Moretti, Kim; O'Callaghan, Michael E

2016-04-01

To investigate overall survival and prostate cancer-specific mortality in men with prostate cancer presenting with a PSA level <100 ng/mL at the time of diagnosis. Five-thousand seven hundred and sixteen patients with prostate cancer and a recorded diagnostic PSA level extracted from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database. Men included were diagnosed between January 1998 and August 2013. Patients were divided into groups according to diagnostic PSA level: <20, 20-≤100, 100-≤200 ng/mL, 200-≤500 ng/mL, and >500 ng/mL. Outcomes measured include overall survival and prostate cancer-specific mortality. Clinical stage, Gleason score and the presence of bony metastasis was evaluated to determine if they were prognostic factors in patients with PSA over 100 at diagnosis. Cox proportional hazards and competing risks regression were used to model overall survival and prostate cancer-specific mortality outcomes respectively. Of this cohort, 241 patients (4.2%) had a diagnostic PSA level >100 ng/mL. Patients with PSA >100 ng/mL have a significant reduction in five (29.1% vs 62.5% vs 87%) and ten-year (18.2% vs 36.7% vs 70.7%) overall survival when compared to men with diagnostic PSA 20-100 and <20 ng/mL respectively. In this group, prostate cancer-specific mortality was associated with Gleason score and metastases, but not PSA level at diagnosis. Overall survival was associated with PSA level, Gleason score and age. There was a linear increase in risk (overall survival) as PSA increased until 200 and no association thereafter. Models of overall survival and prostate cancer-specific mortality incorporating a risk stratification developed by Izumi et al. predicted overall survival but not prostate cancer-specific mortality. The use of this stratification did not improve model accuracy. Only a small number of men (4.2%) with prostate cancer present with PSA >100 ng/mL at diagnosis. Overall survival at five and ten

Cyber-Physical Security Assessment (CyPSA) Toolset

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia, Luis; Patapanchala, Panini; Zonouz, Saman

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 accessedmore » 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.« less

Literacy, race, and PSA level among low-income men newly diagnosed with prostate cancer.

PubMed

Wolf, Michael S; Knight, Sara J; Lyons, E Allison; Durazo-Arvizu, Ramón; Pickard, Simon A; Arseven, Adnan; Arozullah, Ahsan; Colella, Kathleen; Ray, Paul; Bennett, Charles L

2006-07-01

Among men with newly diagnosed prostate cancer, prostate-specific antigen (PSA) levels are higher and the cancer stage more advanced for African Americans than for whites. An earlier study found that after adjustment for literacy, race was no longer a significant predictor of advanced stage at presentation. We investigated whether, after adjusting for literacy, race was a significant independent predictor of greater PSA levels among men with newly diagnosed prostate cancer. Consecutive patients with newly diagnosed prostate cancer from four outpatient care facilities in Chicago were interviewed and given a literacy assessment (n = 308). The PSA level at diagnosis was obtained from the medical charts. Logistic regression models were used to identify predictors of high PSA levels (greater than 20 ng/mL) at presentation. African-American men were three times more likely to have low literacy skills (sixth grade or less: 22.9% versus 7.1%; P <0.001) than were white men. In turn, men with low literacy skills were more than twice as likely to have a PSA level greater than 20 ng/mL at diagnosis (33.3% versus 13.5%; P = 0.009). On multivariate analyses, significant predictors of high PSA levels included low literacy (adjusted odds ratio 2.5, 95% confidence interval 1.5 to 4.2) and older age (age 65 to 74 years, adjusted odds ratio 2.6, 95% confidence interval 2.1 to 3.1 versus older than 74 years, adjusted odds ratio 3.4, 95% confidence interval 1.8 to 6.6), but not African-American race. In the current era in which PSA testing is common, low literacy may be an important and potentially overlooked factor associated with higher PSA levels at prostate cancer diagnosis among African-American and white men.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexander, Abraham S.; University of British Columbia, Vancouver, British Columbia; Mydin, Aminudin

2011-12-01

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

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

Safety Criticality Standards Using the French CRISTAL Code Package: Application to the AREVA NP UO{sub 2} Fuel Fabrication Plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doucet, M.; Durant Terrasson, L.; Mouton, J.

2006-07-01

Criticality safety evaluations implement requirements to proof of sufficient sub critical margins outside of the reactor environment for example in fuel fabrication plants. Basic criticality data (i.e., criticality standards) are used in the determination of sub critical margins for all processes involving plutonium or enriched uranium. There are several criticality international standards, e.g., ARH-600, which is one the US nuclear industry relies on. The French Nuclear Safety Authority (DGSNR and its advising body IRSN) has requested AREVA NP to review the criticality standards used for the evaluation of its Low Enriched Uranium fuel fabrication plants with CRISTAL V0, the recentlymore » updated French criticality evaluation package. Criticality safety is a concern for every phase of the fabrication process including UF{sub 6} cylinder storage, UF{sub 6}-UO{sub 2} conversion, powder storage, pelletizing, rod loading, assembly fabrication, and assembly transportation. Until 2003, the accepted criticality standards were based on the French CEA work performed in the late seventies with the APOLLO1 cell/assembly computer code. APOLLO1 is a spectral code, used for evaluating the basic characteristics of fuel assemblies for reactor physics applications, which has been enhanced to perform criticality safety calculations. Throughout the years, CRISTAL, starting with APOLLO1 and MORET 3 (a 3D Monte Carlo code), has been improved to account for the growth of its qualification database and for increasing user requirements. Today, CRISTAL V0 is an up-to-date computational tool incorporating a modern basic microscopic cross section set based on JEF2.2 and the comprehensive APOLLO2 and MORET 4 codes. APOLLO2 is well suited for criticality standards calculations as it includes a sophisticated self shielding approach, a P{sub ij} flux determination, and a 1D transport (S{sub n}) process. CRISTAL V0 is the result of more than five years of development work focusing on

Clinical outcomes and nadir prostate-specific antigen (PSA) according to initial PSA levels in primary androgen deprivation therapy for metastatic prostate cancer.

PubMed

Kitagawa, Yasuhide; Ueno, Satoru; Izumi, Kouji; Kadono, Yoshifumi; Mizokami, Atsushi; Hinotsu, Shiro; Akaza, Hideyuki; Namiki, Mikio

2016-03-01

To investigate the clinical outcomes of metastatic prostate cancer patients and the relationship between nadir prostate-specific antigen (PSA) levels and different types of primary androgen deprivation therapy (PADT). This study utilized data from the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. A total of 2982 patients treated with PADT were enrolled. Kaplan-Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) in patients treated using combined androgen blockade (CAB) and non-CAB therapies. The relationships between nadir PSA levels and PADT type according to initial serum PSA levels were also investigated. Among the 2982 enrolled patients, 2101 (70.5 %) were treated with CAB. Although CAB-treated patients had worse clinical characteristics, their probability of PFS and OS was higher compared with those treated with a non-CAB therapy. These results were due to a survival benefit with CAB in patients with an initial PSA level of 500-1000 ng/mL. Nadir PSA levels were significantly lower in CAB patients than in non-CAB patients with comparable initial serum PSA levels. A small survival benefit for CAB in metastatic prostate cancer was demonstrated in a Japanese large-scale prospective cohort study. The clinical significance of nadir PSA levels following PADT was evident, but the predictive impact of PSA nadir on OS was different between CAB and non-CAB therapy.

Association between PSA Levels and Biomarkers of Subclinical Systemic Inflammation in Middle-Aged Healthy Men from the General Population.

PubMed

Elzanaty, Saad; Rezanezhad, Babak; Borgquist, Rasmus

2016-10-01

This study was aimed to determine the association between PSA levels and biomarkers of subclinical systemic inflammation based on data from 119 middle-aged healthy men from the general population. Serum levels of PSA and biomarkers of systemic inflammation (CRP and fibrinogen) were measured. Demographic data were also collected. Subjects were divided into two groups according to PSA levels; < 2 ng/ml and ≥ 2 ng/ml. The mean (SD) age of men was 55 ± 4.0 years. We found a positive significant correlation between PSA and fibrinogen levels (r = 0.20, p = 0.04), and between CRP and fibrinogen levels (r = 0.60, p = 0.01). On the other hand, no significant correlation between PSA and CRP levels was found. Men with PSA values ≥ 2 ng/ml had significantly higher levels of fibrinogen as compared to those with PSA < 2 ng/ml (2.9 ng/ml vs. 2.4 ng/ml, p = 0.01). In a multivariate regression analysis model adjusted for the age of subjects, BMI, marital status, smoking, snuff, and alcohol intake with serum levels of PSA as a dependent variable, serum level of fibrinogen predicted higher PSA-values (odds ratio = 3.30, 95% CI = 1.05-10.20, p = 0.042). The present results indicate that serum fibrinogen is a biomarker of subclinical systemic inflammation associated with PSA elevation among middle-aged healthy men from the general population.

Long-term longitudinal changes in baseline PSA distribution and estimated prevalence of prostate cancer in male Japanese participants of population-based PSA screening.

PubMed

Oki, Ryo; Ito, Kazuto; Suzuki, Rie; Fujizuka, Yuji; Arai, Seiji; Miyazawa, Yoshiyuki; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro

2018-04-26

Japan has experienced a drastic increase in the incidence of prostate cancer (PC). To assess changes in the risk for PC, we investigated baseline prostate specific antigen (PSA) levels in first-time screened men, across a 25-year period. In total, 72,654 men, aged 50-79, underwent first-time PSA screening in Gunma prefecture between 1992 and 2016. Changes in the distribution of PSA levels were investigated, including the percentage of men with a PSA above cut-off values and linear regression analyses comparing log 10 PSA with age. The 'ultimate incidence' of PC and clinically significant PC (CSPC) were estimated using the PC risk calculator. Changes in the age-standardized incidence rate (AIR) during this period were analyzed. The calculated coefficients of linear regression for age versus log 10 PSA fluctuated during the 25-year period, but no trend was observed. In addition, the percentage of men with a PSA above cut-off values varied in each 5-year period, with no specific trend. The 'risk calculator (RC)-based AIR' of PC and CSPC were stable between 1992 and 2016. Therefore, the baseline risk for developing PC has remained unchanged in the past 25 years, in Japan. The drastic increase in the incidence of PC, beginning around 2000, may be primarily due to increased PSA screening in the country. © 2018 UICC.

Experiences of Uncertainty in Men With an Elevated PSA.

PubMed

Biddle, Caitlin; Brasel, Alicia; Underwood, Willie; Orom, Heather

2015-05-15

A significant proportion of men, ages 50 to 70 years, have, and continue to receive prostate specific antigen (PSA) tests to screen for prostate cancer (PCa). Approximately 70% of men with an elevated PSA level will not subsequently be diagnosed with PCa. Semistructured interviews were conducted with 13 men with an elevated PSA level who had not been diagnosed with PCa. Uncertainty was prominent in men's reactions to the PSA results, stemming from unanswered questions about the PSA test, PCa risk, and confusion about their management plan. Uncertainty was exacerbated or reduced depending on whether health care providers communicated in lay and empathetic ways, and provided opportunities for question asking. To manage uncertainty, men engaged in information and health care seeking, self-monitoring, and defensive cognition. Results inform strategies for meeting informational needs of men with an elevated PSA and confirm the primary importance of physician communication behavior for open information exchange and uncertainty reduction. © The Author(s) 2015.

Experiences of Uncertainty in Men With an Elevated PSA

PubMed Central

Biddle, Caitlin; Brasel, Alicia; Underwood, Willie; Orom, Heather

2016-01-01

A significant proportion of men, ages 50 to 70 years, have, and continue to receive prostate specific antigen (PSA) tests to screen for prostate cancer (PCa). Approximately 70% of men with an elevated PSA level will not subsequently be diagnosed with PCa. Semistructured interviews were conducted with 13 men with an elevated PSA level who had not been diagnosed with PCa. Uncertainty was prominent in men’s reactions to the PSA results, stemming from unanswered questions about the PSA test, PCa risk, and confusion about their management plan. Uncertainty was exacerbated or reduced depending on whether health care providers communicated in lay and empathetic ways, and provided opportunities for question asking. To manage uncertainty, men engaged in information and health care seeking, self-monitoring, and defensive cognition. Results inform strategies for meeting informational needs of men with an elevated PSA and confirm the primary importance of physician communication behavior for open information exchange and uncertainty reduction. PMID:25979635

Excess cases of prostate cancer and estimated overdiagnosis associated with PSA testing in East Anglia

PubMed Central

Pashayan, N; Powles, J; Brown, C; Duffy, S W

2006-01-01

This study aimed to estimate the extent of ‘overdiagnosis' of prostate cancer attributable to prostate-specific antigen (PSA) testing in the Cambridge area between 1996 and 2002. Overdiagnosis was defined conceptually as detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Records of PSA tests in Addenbrookes Hospital were linked to prostate cancer registrations by NHS number. Differences in prostate cancer registration rates between those receiving and not receiving prediagnosis PSA tests were calculated. The proportion of men aged 40 years or over with a prediagnosis PSA test increased from 1.4 to 5.2% from 1996 to 2002. The rate of diagnosis of prostate cancer was 45% higher (rate ratios (RR)=1.45, 95% confidence intervals (CI) 1.02–2.07) in men with a history of prediagnosis PSA testing. Assuming average lead times of 5 to 10 years, 40–64% of the PSA-detected cases were estimated to be overdiagnosed. In East Anglia, from 1996 to 2000, a 1.6% excess of cases was associated with PSA testing (around a quarter of the 5.3% excess incidence cases observed in East Anglia from 1996 to 2000). Further quantification of the overdiagnosis will result from continued surveillance and from linkage of incidence to testing in other hospitals. PMID:16832417

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

PubMed

Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J

2017-05-01

Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Understanding PSA and its derivatives in prediction of tumor volume: addressing health disparities in prostate cancer risk stratification

PubMed Central

Chinea, Felix M; Lyapichev, Kirill; Epstein, Jonathan I; Kwon, Deukwoo; Smith, Paul Taylor; Pollack, Alan; Cote, Richard J; Kryvenko, Oleksandr N

2017-01-01

Objectives To address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort. Results Using published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume <0.5 cm3. Variability across race/ethnicity was found in the univariable analysis for all PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014). Materials and Methods We retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3. Conclusions Increasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives’ ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer. PMID:28160549

Understanding PSA and its derivatives in prediction of tumor volume: Addressing health disparities in prostate cancer risk stratification.

PubMed

Chinea, Felix M; Lyapichev, Kirill; Epstein, Jonathan I; Kwon, Deukwoo; Smith, Paul Taylor; Pollack, Alan; Cote, Richard J; Kryvenko, Oleksandr N

2017-03-28

To address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort. Using published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume <0.5 cm3. Variability across race/ethnicity was found in the univariable analysis for all PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014). We retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3. Increasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives' ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer.

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

PubMed

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

2016-12-01

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

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer.

PubMed

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-08-30

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer

PubMed Central

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-01-01

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer. PMID:27494861

Age-Specific Cutoff Value for the Application of Percent Free Prostate-Specific Antigen (PSA) in Chinese Men with Serum PSA Levels of 4.0-10.0 ng/ml.

PubMed

Chen, Rui; Huang, Yiran; Cai, Xiaobing; Xie, Liping; He, Dalin; Zhou, Liqun; Xu, Chuanliang; Gao, Xu; Ren, Shancheng; Wang, Fubo; Ma, Lulin; Wei, Qiang; Yin, Changjun; Tian, Ye; Sun, Zhongquan; Fu, Qiang; Ding, Qiang; Zheng, Junhua; Ye, Zhangqun; Ye, Dingwei; Xu, Danfeng; Hou, Jianquan; Xu, Kexin; Yuan, Jianlin; Gao, Xin; Liu, Chunxiao; Pan, Tiejun; Sun, Yinghao

2015-01-01

The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies. Consecutive patients with a prostate-specific antigen (PSA) level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis. The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60-69, 70-79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0-10.0 ng/ml to detect 90% of all PCa. The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population.

Prostate-Specific Antigen (PSA) Test: MedlinePlus Lab Test Information

MedlinePlus

... gov/labtests/prostatespecificantigenpsatest.html Prostate-Specific Antigen (PSA) Test To use the sharing features on this page, ... JavaScript. What is a prostate-specific antigen (PSA) test? A prostate-specific antigen (PSA) test measures the ...

Correlation of pretreatment clinical parameters and PSA nadir after high-intensity focused ultrasound (HIFU) for localised prostate cancer.

PubMed

Ganzer, Roman; Bründl, Johannes; Koch, Daniel; Wieland, Wolf F; Burger, Maximilian; Blana, Andreas

2015-01-01

To determine which pretreatment clinical parameters were predictive of a low prostate-specific antigen (PSA) nadir following high-intensity focused ultrasound (HIFU) treatment. Retrospective study of patients with clinically localised prostate cancer undergoing HIFU at a single centre between December 1997 and September 2009. Whole-gland treatment was applied. Patients also included if they had previously undergone transurethral resection of the prostate (TURP). TURP was also conducted simultaneously to HIFU. Biochemical failure based on Phoenix definition (PSA nadir + 2). Univariate and multivariate analysis of pretreatment clinical parameters conducted to assess those factors predictive of a PSA nadir ≤0.2 and >0.2 ng/ml. Mean (SD) follow-up was 6.2 (2.8) years; median (range) was 6.3 (1.1-12.2) years. Kaplan-Meier estimate of biochemical disease-free survival rate at 8 years was 83 and 48 % for patients achieving a PSA nadir of ≤0.2 and >0.2 ng/ml, respectively. Prostate volume and incidental finding of cancer were significant predictors of low PSA nadir (≤0.2 ng/ml). Prostate volume and incidental finding of cancer could be predictors for oncologic success of HIFU based on post-treatment PSA nadir.

Rosetta Planetary Science Archive (PSA) Status

NASA Astrophysics Data System (ADS)

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

2006-09-01

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

The influence of PSA autoantibodies in prostate cancer patients: a prospective clinical study-II.

PubMed

Nakajima, Kosei; Heilbrun, Lance K; Smith, Daryn; Hogan, Victor; Raz, Avraham; Heath, Elisabeth

2017-03-14

The U.S. Preventive Services Task Force (USPSTF) has recommended against PSA-based screening for prostate cancer due to potential possibilities of false-results. Since no alternative test is available to replace it, we have initiated a trial with the purpose of establishing whether Galectin-3 (Gal-3) serum level and/or the patients' immune response to PSA and Gal-3 antigens could complement the PSA test as diagnostic tools for prostate cancer patients. A blind, prospective, single institution, pilot study was conducted. A total of 95 men were recruited and classified into 5 different groups: healthy controls (Group1), newly diagnosed patients (Group2), no recurrence after local therapy (Group3), rising PSA after local therapy (Group4), and metastatic patients (Group5). The primary endpoints were the levels of serum PSA, PSA autoantibodies (AAPSA), Gal-3, and Gal-3 autoantibodies (AAGal-3). Data were analyzed by Spearman's rank correlation (rho) and least squares linear regression modeling. The expression levels of PSA, AAPSA, Gal-3, and AAGal-3 were determined in both healthy controls and prostate cancer patients. Negative correlations were observed between PSA and AAPSA levels among all 95 men combined (rho = -0.321, P = 0.0021; fitted slope -0.288, P = 0.0048), and in metastatic patients (rho = -0.472, P = 0.0413; fitted slope -1.145, P = 0.0061). We suggest an association between PSA and AAPSA, whereby the AAPSA may alter PSA levels. It provides a novel outlook for prostate cancer diagnosis, and should serve as a basis for an all-inclusive diagnostic trial centering on patients with metastasis.

Long-term clinical impact of PSA surge in castration-resistant prostate cancer patients treated with abiraterone.

PubMed

Conteduca, Vincenza; Caffo, Orazio; Lolli, Cristian; Aieta, Michele; Scarpi, Emanuela; Bianchi, Emanuela; Maines, Francesca; Schepisi, Giuseppe; Salvi, Samanta; Massari, Francesco; Carrozza, Francesco; Veccia, Antonello; Chiuri, Vincenzo E; Campadelli, Enrico; Facchini, Gaetano; De Giorgi, Ugo

2017-06-01

Early changes in PSA have been evaluated in association to treatment outcome. The aim of this study was to assess PSA surge phenomenon in castration-resistant prostate cancer (CRPC) patients treated with abiraterone and to correlate those variations with long-term treatment outcome. We retrospectively evaluated 330 CRPC patients in 11 Italian hospitals, monitoring PSA levels at baseline and every 4 weeks. Other clinical, biochemical and molecular parameters were determined at baseline. We considered PSA surge as PSA increase within the first 8 weeks from starting abiraterone more than 1% from baseline followed by a PSA decline. The log-rank test was applied to compare survival between groups of patients according to PSA surge. The impact of PSA surge on survival was evaluated by Cox regression analyses. A total of 330 patients with CRPC, median age 74 years (range, 45-90), received abiraterone (281 chemotherapy-treated and 49 chemotherapy-naïve). PSA surge was observed in 20 (7%) post-chemotherapy and 2 (4%) chemotherapy-naïve patients. For overall patients presenting PSA surge, timing of PSA peak from baseline was 5 ± 1.8 weeks and PSA rise from baseline was 21 ± 18.4%. The overall median follow-up was 23 months (range 1-62). No significant differences in progression-free survival and overall survival were observed between patients with and without PSA surge (P = 0.16 and =0.86, respectively). In addition, uni- and multivariate analyses showed no baseline factors related to PSA surge. PSA surge occurs in both chemotherapy-treated and chemotherapy-naïve patients treated with abiraterone resulting, however, in no long-term impact on outcome. Physicians and patients should be aware of PSA surge challenge to prevent a premature discontinuation of potentially effective therapy with abiraterone. Further larger and prospective studies are warranted to investigate this not infrequent phenomenon. © 2017 Wiley Periodicals, Inc.

First postoperative PSA is associated with outcomes in patients with node positive prostate cancer: Results from the SEARCH database.

PubMed

McDonald, Michelle L; Howard, Lauren E; Aronson, William J; Terris, Martha K; Cooperberg, Matthew R; Amling, Christopher L; Freedland, Stephen J; Kane, Christopher J

2018-05-01

To analyze factors associated with metastases, prostate cancer-specific mortality, and all-cause mortality in pN1 patients. We analyzed 3,642 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Pathologic Gleason grade, number of lymph nodes (LN) removed, and first postoperative prostate-specific antigen (PSA) (<0.2 ng/ml or ≥0.2 ng/ml) were among covariates assessed. Cox regression was used to analyze the association between characteristics and survival outcomes. Kaplan-Meier was used to estimate survival in pN1 patients stratified by first postoperative PSA. Of 3,642 patients, 124 (3.4%) had pN1. There were 71 (60%) patients with 1 positive LN, 32 (27%) with 2 positive LNs, and 15 (13%) with ≥3. Among men with pN1, first postoperative PSA was<0.2ng/ml in 46 patients (51%) and ≥0.2ng/ml in 44 patients (49%). Univariable Cox regression determined pathological Gleason grade (P = 0.021), seminal vesicle invasion (P = 0.010), and first postoperative PSA ≥0.2 ng/ml (P = 0.005) were associated with metastases. First postoperative PSA ≥0.2ng/ml was associated with metastasis on multivariable analysis (P = 0.046). Log-rank analysis revealed a more favorable metastases-free survival in patients with a first postoperative PSA<0.2ng/ml (P = 0.001). Estimated 5-year metastases-free survival rate was 99% for patients with a first postoperative PSA<0.2ng/ml and 87% for ≥0.2ng/ml. pN1 patients with a first postoperative PSA ≥0.2ng/ml were more likely to develop metastases. First postoperative PSA may be useful in identifying pN1 patients who harbor distant disease and aid in secondary treatment decisions. Copyright © 2018 Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2017-05-01

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

Age-Specific Cutoff Value for the Application of Percent Free Prostate-Specific Antigen (PSA) in Chinese Men with Serum PSA Levels of 4.0–10.0 ng/ml

PubMed Central

Xie, Liping; He, Dalin; Zhou, Liqun; Xu, Chuanliang; Gao, Xu; Ren, Shancheng; Wang, Fubo; Ma, Lulin; Wei, Qiang; Yin, Changjun; Tian, Ye; Sun, Zhongquan; Fu, Qiang; Ding, Qiang; Zheng, Junhua; Ye, Zhangqun; Ye, Dingwei; Xu, Danfeng; Hou, Jianquan; Xu, Kexin; Yuan, Jianlin; Gao, Xin; Liu, Chunxiao; Pan, Tiejun; Sun, Yinghao

2015-01-01

Objective The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies. Methods Consecutive patients with a prostate-specific antigen (PSA) level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis. Results The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60–69, 70–79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0–10.0 ng/ml to detect 90% of all PCa. Conclusions The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population. PMID:26091007

PSA Response After Short-Term Hormonal Therapy Plus External Beam Radiotherapy and Outcome in Patients Treated on RTOG 9413

PubMed Central

Cury, Fabio L.; Hunt, Daniel; Roach, Mack; Shipley, William; Gore, Elizabeht; Hsu, I-Chow; Krisch, Robert E.; Seider, Michael J.; Sandler, Howard; Lawton, Colleen

2013-01-01

Purpose Assess the impact of PSA-complete response (PSA-CR), measured at the end of external beam radiotherapy (EBRT) and short-term hormonal therapy (STHT), on treatment outcomes. Design The Phase III RTOG-9413 trial had as part of its original protocol the assessment of PSA-CR, i.e. PSA≤0.3ng/ml, at the end of STHT as a secondary endpoint. STHT consisted of flutamide plus an LHRH-agonist for 4 months. Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). Cumulative incidence was used to estimate biochemical failure (BF), distant metastasis (DM), and disease-specific survival (DSS). Univariate and multivariate analyses were performed to correlate PSA-CR after STHT with all endpoints, and the following variables were considered for analysis: PSA at baseline, Gleason score, treatment arm, age, and baseline testosterone. Phoenix-consensus was used to define PSA failure. Results For 1070 evaluable patients, the median PSA at the end of STHT was 0.2ng/mL. A total of 744 patients (70%) had PSA-CR. With median follow-up of 7.2 years, failure to obtain PSA-CR was significantly associated with worse DSS (p=0.0003; hazard ratio, 2.03[95%CI, 1.38–2.97]) and DFS (p=0.003; 1.28[1.09–1.50]), as well as with a higher incidence of DM (p=0.0002; 1.92[1.37–2.69]) and BF (p<0.0001; 1.57[1.29–1.91]). The other factors associated with worse DSS were Gleason score 8–10 (p=0.0002; 3.06[1.71–5.47]) and PSA>20ng/mL (p=0.04; 1.55[1.02–2.30]). Conclusion Failure to obtain a post STHT and EBRT PSA-CR (≤0.3ng/mL) appears to be an independent predictor of unfavorable outcomes, and may help identify patients who could benefit from the addition of long-term androgen ablation. PMID:23504930

Effects of increasing the PSA cutoff to perform additional biomarker tests before prostate biopsy.

PubMed

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

2017-10-03

Multi-step testing might enhance performance of the prostate cancer diagnostic pipeline. Using PSA >1 ng/ml for first-line risk stratification and the Stockholm 3 Model (S3M) blood-test >10% risk of Gleason Score > 7 prostate cancer to inform biopsy decisions has been suggested. We aimed to determine the effects of changing the PSA cutoff to perform reflex testing with S3M and the subsequent S3M cutoff to recommend prostate biopsy while maintaining the sensitivity to detect Gleason Score ≥ 7 prostate cancer. We used data from the prospective, population-based, paired, diagnostic Stockholm 3 (STHLM3) study with participants invited by date of birth from the Swedish Population Register during 2012-2014. All participants underwent testing with PSA and S3M (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms, and clinical variables [age, family, history, previous prostate biopsy, prostate exam]). Of 47,688 men in the STHLM3 main study, we used data from 3133 men with S3M >10% and prostate biopsy data. Logistic regression models were used to calculate prostate cancer detection rates and proportion saved biopsies. 44.2%, 62.5% and 67.9% of the participants had PSA <1, <1.5 and <1.7 ng/ml, respectively. Increasing the PSA cut-off for additional work-up from 1 ng/ml to 1.5 ng/ml would thus save 18.3% of the performed tests, 4.9% of the biopsies and 1.3% (10/765) of Gleason Grade ≥ 7 cancers would be un-detected. By lowering the S3M cutoff to recommend biopsy, sensitivity to high-grade prostate cancer can be restored, to the cost of increasing the number of performed biopsies modestly. The sensitivity to detect prostate cancer can be maintained when using different PSA cutoffs to perform additional testing. Biomarker cut-offs have implications on number of tests and prostate biopsies performed. A PSA cutoff of 1.5 ng/ml to perform additional testing such as the S3M test might be considered. ISRCTN

Diversity of viral photosystem-I psaA genes

PubMed Central

Hevroni, Gur; Enav, Hagay; Rohwer, Forest; Béjà, Oded

2015-01-01

Marine photosynthesis is one of the major contributors to the global carbon cycle and the world's oxygen supply. This process is largely driven by cyanobacteria, namely Synechococcus and Prochlorococcus. Genes encoding photosystem-II (PSII) reaction center proteins are found in many cyanophage genomes, and are expressed during the infection of their hosts. On the basis of metagenomics, cyanophage photosystem-I (PSI) gene cassettes were recently discovered with two gene arrangements psaJF→C→A→B→K→E→D and psaD→C→A→B. It was suggested that the horizontal transfer of PSII and PSI genes is increasing phage fitness. To better understand their diversity, we designed degenerate primers to cover a wide diversity of organisms, and using PCR we targeted the psaC→A arrangement, which is unique to cyanophages cassettes. We examined viral concentrates from four islands in the Pacific Ocean and found samples containing the psaC→A arrangement. Analyses of the amplified viral psaA gene revealed six subgroups varying in their level of similarity and %G+C content, suggesting that the diversity of cyanophage PSI genes is greater than originally thought. PMID:25535938

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

PubMed

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

2017-04-01

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

Enhanced detection sensitivity of prostate-specific antigen via PSA-conjugated gold nanoparticles based on localized surface plasmon resonance: GNP-coated anti-PSA/LSPR as a novel approach for the identification of prostate anomalies.

PubMed

Jazayeri, M H; Amani, H; Pourfatollah, A A; Avan, A; Ferns, G A; Pazoki-Toroudi, H

2016-10-01

Prostate-specific antigen (PSA) is used to screen for prostate disease, although it has several limitations in its application as an organ-specific or cancer-specific marker. Furthermore, a highly specific/sensitive and/or label-free identification of PSA still remains a challenge in the diagnosis of prostate anomalies. We aimed to develop a gold nanoparticle (GNP)-conjugated anti-PSA antibody-based localized surface plasmon resonance (LSPR) as a novel approach to detect prostatic disease. A total of 25 nm colloidal gold particles were prepared followed by conjugation with anti-PSA pAb (GNPs-PSA pAb). LSPR was used to monitor the absorption changes of the aggregation of the particles. The size, shape and stability of the GNP-anti-PSA were evaluated by dynamic light scattering transmission electron microscopy (TEM) and zetasizer. The GNPs-conjugated PSA-pAb was successfully synthesized and subsequently characterized using ultraviolet absorption spectroscopy and TEM to determine the size distribution, crystallinity and stability of the particles (for example, stability of GNP: 443 mV). To increase the stability of the particles, we pegylated GNPs using an N-(3-dimethylaminopropyl)-N*-ethylcarbodiimide hydrochloride (EDC)/N-hydroxylsuccinimide (NHS) linker (for example, stability of GNP after pegylation: 272 mV). We found a significant increase in the absorbance and intensity of the particles with extinction peak at 545/2 nm, which was shifted by ~1 nm after conjugation. To illustrate the potential of the GNPs-PSA pAb to bind specifically to PSA, LSPR was used. We found that the extinction peak shifted 3 nm for a solution of 100 nM unlabeled antigen. In summary, we have established a novel approach for improving the efficacy/sensitivity of PSA in the assessment of prostate disease, supporting further investigation on the diagnostic value of GNP-conjugated anti-PSA/LSPR for the detection of prostate cancer.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hauck, Carlin R.; Ye, Hong; Chen, Peter Y.

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

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

PubMed

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

2017-05-01

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

Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL

PubMed Central

Bryce, A H; Alumkal, J J; Armstrong, A; Higano, C S; Iversen, P; Sternberg, C N; Rathkopf, D; Loriot, Y; de Bono, J; Tombal, B; Abhyankar, S; Lin, P; Krivoshik, A; Phung, D; Beer, T M

2017-01-01

Background: Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. Methods: Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. Results: Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26–2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. Conclusions: Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression. PMID:28117385

Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.

PubMed

Bryce, A H; Alumkal, J J; Armstrong, A; Higano, C S; Iversen, P; Sternberg, C N; Rathkopf, D; Loriot, Y; de Bono, J; Tombal, B; Abhyankar, S; Lin, P; Krivoshik, A; Phung, D; Beer, T M

2017-06-01

Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.

Circulating total testosterone and PSA concentrations in a nationally representative sample of men without a diagnosis of prostate cancer.

PubMed

Peskoe, Sarah B; Joshu, Corinne E; Rohrmann, Sabine; McGlynn, Katherine A; Nyante, Sarah J; Bradwin, Gary; Dobs, Adrian S; Kanarek, Norma; Nelson, William G; Platz, Elizabeth A

2015-08-01

The association between serum sex steroid hormones and PSA in a general population has not been described. Included were 378 men aged 40-85 years who participated in the National Health and Nutrition Examination Survey in 2001-2004, who did not have a prostate cancer diagnosis, and had not had a recent biopsy, rectal examination, cystoscopy, or prostate infection or inflammation. Serum total PSA, total testosterone, androstanediol glucuronide (3α-diol-G), estradiol, and sex hormone binding globulin (SHBG) concentrations were previously measured. Free testosterone was estimated by mass action. We applied sampling weights and calculated geometric mean PSA concentration by hormone quintiles adjusting for age and race/ethnicity, and also for body mass index, waist circumference, smoking, diabetes, and mutually for hormones. We estimated the OR of PSA ≥2.5 ng/ml per hormone quintile using logistic regression. Geometric mean PSA increased across testosterone quintiles after age and race/ethnicity (Q1: 0.80, Q5: 1.14 ng/ml; P-trend = 0.002) and multivariable (Q1: 0.79, Q5: 1.16 ng/ml; P-trend = 0.02) adjustment; patterns were similar for free testosterone and 3α-diol-G. SHBG was inversely associated with PSA only after multivariable adjustment (Q1: 1.32, Q5: 0.82 nmol/L; P-trend = 0.01). Estradiol and PSA were not associated. The OR of PSA ≥2.5 ng/ml was 1.54 (95% CI 1.18-2.01) per testosterone quintile after age and race/ethnicity adjustment, and 1.78 (95% CI 1.16-2.73) after multivariable adjustment. In this nationally representative sample, men with higher testosterone had higher PSA even after taking into account other hormones and modifiable factors. Men with higher SHBG had lower PSA, but only after multivariable adjustment. © 2015 Wiley Periodicals, Inc.

Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer's Disease Entorhinal Cortex.

PubMed

Murray, Helen C; Swanson, Molly E V; Dieriks, B Victor; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

2018-02-21

Polysialylated neural cell adhesion molecule (PSA-NCAM) is widely expressed in the adult human brain and facilitates structural remodeling of cells through steric inhibition of intercellular NCAM adhesion. We previously showed that PSA-NCAM immunoreactivity is decreased in the entorhinal cortex in Alzheimer's disease (AD). Based on available evidence, we hypothesized that a loss of PSA-NCAM + interneurons may underlie this reduction. PSA-NCAM expression by interneurons has previously been described in the human medial prefrontal cortex. Here we used postmortem human brain tissue to provide further evidence of PSA-NCAM + interneurons throughout the human hippocampal formation and additional cortical regions. Furthermore, PSA-NCAM + cell populations were assessed in the entorhinal cortex of normal and AD cases using fluorescent double labeling and manual cell counting. We found a significant decrease in the number of PSA-NCAM + cells per mm 2 in layer II and V of the entorhinal cortex, supporting our previous description of reduced PSA-NCAM immunoreactivity. Additionally, we found a significant decrease in the proportion of PSA-NCAM + cells that co-labeled with NeuN and parvalbumin, but no change in the proportion that co-labeled with calbindin or calretinin. These results demonstrate that PSA-NCAM is expressed by a variety of interneuron populations throughout the brain. Furthermore, that loss of PSA-NCAM expression by NeuN + cells predominantly contributes to the reduced PSA-NCAM immunoreactivity in the AD entorhinal cortex. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

A comparison of US and Australian men's values and preferences for PSA screening.

PubMed

Howard, Kirsten; Brenner, Alison T; Lewis, Carmen; Sheridan, Stacey; Crutchfield, Trisha; Hawley, Sarah; Nielsen, Matthew E; Pignone, Michael P

2013-10-05

Patient preferences derived from an assessment of values can help inform the design of screening programs, but how best to do so, and whether such preferences differ cross-nationally, has not been well-examined. The objective of this study was to compare the values and preferences of Australian and US men for PSA (prostate specific antigen) screening. We used an internet based survey of men aged 50-75 with no personal or family history of prostate cancer recruited from on-line panels of a survey research organization in the US and Australia. Participants viewed information on prostate cancer and prostate cancer screening with PSA testing then completed a values clarification task that included information on 4 key attributes: chance of 1) being diagnosed with prostate cancer, 2) dying from prostate cancer, 3) requiring a biopsy as a result of screening, and 4) developing impotence or incontinence as a result of screening. The outcome measures were self reported most important attribute, unlabelled screening test choice, and labelled screening intent, assessed on post-task questionnaires. We enrolled 911 participants (US:456; AU:455), mean age was 59.7; 88.0% were white; 36.4% had completed at least a Bachelors' degree; 42.0% reported a PSA test in the past 12 months. Australian men were more likely to be white and to have had recent screening. For both US and Australian men, the most important attribute was the chance of dying from prostate cancer. Unlabelled post-task preference for the PSA screening-like option was greater for Australian (39.1%) compared to US (26.3%) participants (adjusted OR 1.68 (1.28-2.22)). Labelled intent for screening was high for both countries: US:73.7%, AUS:78.0% (p = 0.308). There was high intent for PSA screening in both US and Australian men; fewer men in each country chose the PSA-like option on the unlabelled question. Australian men were somewhat more likely to prefer PSA screening. Men in both countries did not view the

Neutron fluence and energy reconstruction with the IRSN recoil detector μ-TPC at 27 keV, 144 keV and 565 keV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maire, D.; Lebreton, L.; Richer, J.P.

2015-07-01

The French Institute for Radioprotection and Nuclear Safety (IRSN), associated to the French Metrology Institute (LNE), is developing a time projection chamber using a Micromegas anode: μ-TPC. This work is carried out in collaboration with the Laboratory of Subatomic Physics and Cosmology (LPSC). The aim is to characterize with a primary procedure the energy distribution of neutron fluence in the energy range 8 keV - 1 MeV. The time projection chambers are gaseous detectors, which are able to measure charged particles energy and to reconstruct their track if a pixelated anode is used. In our case, the gas is usedmore » as a (n, p) converter in order to detect neutrons down to few keV. Coming from elastic collisions with neutrons, recoil protons lose a part of their kinetic energy by ionizing the gas. The ionization electrons are drifted toward a pixelated anode (2D projection), read at 50 MHz by a self-triggered electronic system to obtain the third track dimension. The neutron energy is reconstructed event by event thanks to proton scattering angle and proton energy measurements. The scattering angle is deduced from the 3D track. The proton energy is obtained by charge collection measurements, knowing the ionization quenching factor (i.e. the part of proton kinetic energy lost by ionizing the gas). The fluence is calculated thanks to the detected events number and the simulated detector response. The μ-TPC is a new reliable detector which enables to measure energy distribution of the neutron fluence without deconvolution or neutron calibration contrary to usual gaseous counters. The μ-TPC is still being developed and measurements have been carried out at the AMANDE facility, with neutrons energies going from 8 keV to 565 keV. After the context and the μ-TPC working principle presentation, measurements of the neutron energy and fluence at 27.2 keV, 144 keV and 565 keV are shown and compared to the complete detector simulation. This work shows the first direct

Enzymatic Activity of Free-Prostate-Specific Antigen (f-PSA) Is Not Required for Some of its Physiological Activities

PubMed Central

Chadha, Kailash C.; Nair, Bindukumar B.; Chakravarthi, Srikant; Zhou, Rita; Godoy, Alejandro; Mohler, James L.; Aalinkeel, Ravikumar; Schwartz, Stanley A.; Smith, Gary J.

2015-01-01

BACKGROUND Prostate specific antigen (PSA) is a well known biomarker for early diagnosis and management of prostate cancer. Furthermore, PSA has been documented to have anti-angiogenic and anti-tumorigenic activities in both in vitro and in vivo studies. However, little is known about the molecular mechanism(s) involved in regulation of these processes, in particular the role of the serine-protease enzymatic activity of PSA. METHODS Enzymatic activity of PSA isolated directly from seminal plasma was inhibited specifically (>95%) by incubation with zinc2+. Human umbilical vein endothelial cells (HUVEC) were utilized to compare/contrast the physiological effects of enzymatically active versus inactive PSA. RESULTS Equimolar concentrations of enzymatically active PSA and PSA enzymatically inactivated by incubation with Zn2+ had similar physiological effects on HUVEC, including inhibiting the gene expression of pro-angiogenic growth factors, like VEGF and bFGF, and up-regulation of expression of the anti-angiogenic growth factor IFN-γ; suppression of mRNA expression for markers of blood vessel development, like FAK, FLT, KDR, TWIST-1; P-38; inhibition of endothelial tube formation in the in vitro Matrigel Tube Formation Assay; and inhibition of endothelial cell invasion and migration properties. DISCUSSION Our data provides compelling evidence that the transcriptional regulatory and the anti-angiogenic activities of human PSA are independent of the innate enzymatic activity PMID:21446007

Long-term prognostic significance of rising PSA levels following radiotherapy for localized prostate cancer - focus on overall survival.

PubMed

Freiberger, Carla; Berneking, Vanessa; Vögeli, Thomas-Alexander; Kirschner-Hermanns, Ruth; Eble, Michael J; Pinkawa, Michael

2017-06-14

The aim of this study was to evaluate the long-term prognostic significance of rising PSA levels, particularly focussing on overall survival. Two hundred ninety-five patients with localized prostate cancer were either treated with low-dose-rate (LDR) brachytherapy with I-125 seeds as monotherapy (n = 94; 145Gy), high-dose-rate (HDR) brachytherapy with Ir-192 as a boost to external beam RT (n = 66; 50.4Gy in 1.8Gy fractions EBRT + 18Gy in 9Gy fractions HDR) or EBRT alone (70.2Gy in 1.8Gy fractions; n = 135). "PSA bounce" was defined as an increase of at least 0.2 ng/ml followed by spontaneous return to pre-bounce level or lower, biochemical failure was defined according to the Phoenix definition. Median follow-up after the end of radiotherapy was 108 months. A PSA bounce showed to be a significant factor for biochemical control (BC) and overall survival (OS) after ten years (BC10 of 83% with bounce vs. 34% without, p < 0.01; OS10 of 82% with bounce vs. 59% without bounce, p < 0.01). The occurrence of a bounce, a high nadir and the therapy modality (LDR-BT vs. EBRT and HDR-BT + EBRT vs. EBRT) proved to be independent factors for PSA recurrence in multivariate Cox regression analysis. A bounce was detected significantly earlier than a PSA recurrence (median 20 months vs. 32 months after RT; p < 0.01; median PSA doubling time 5.5 vs. 5.0 months, not significant). PSA doubling time was prognostically significant in case of PSA recurrence (OS10 of 72% vs. 36% with PSA doubling time ˃ 5 months vs. ≤ 5 months; p < 0.01). Rising PSA levels within the first two years can usually be classified as a benign PSA bounce, with favourable recurrence-free and overall survival rates. PSA doubling time is an important predictor for overall survival following the diagnosis of a recurrence.

Association of Reported Prostate Cancer Risk Alleles With PSA Levels Among Men Without a Diagnosis of Prostate Cancer

PubMed Central

Wiklund, Fredrik; Zheng, S. Lilly; Sun, Jielin; Adami, Hans-Olov; Lilja, Hans; Hsu, Fang-Chi; Stattin, Pär; Adolfsson, Jan; Cramer, Scott D.; Duggan, David; Carpten, John D.; Chang, Bao-Li; Isaacs, William B.; Grönberg, Henrik; Xu, Jianfeng

2012-01-01

BACKGROUND Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels. METHODS We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer. RESULTS Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P≤0.05) were found for six SNPs. These six SNPs had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P-trend=3.4×10−14. In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients. CONCLUSIONS Results from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic-specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk-associated SNPs may be confounded by the prevalent use of PSA screening. PMID:19116992

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

PubMed

Lokant, M T; Naz, R K

2015-04-01

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

Prostate Cancer Screening: Should You Get a PSA Test?

MedlinePlus

... Mayo Clinic Staff Cancer screening tests — including the prostate-specific antigen (PSA) test to look for signs of prostate ... of harm to the person undergoing the testing. Prostate-specific antigen (PSA) is a protein produced by both cancerous ( ...

French Teaching Aids.

ERIC Educational Resources Information Center

Miller, J. Dale

Supplementary teaching materials for French language programs are presented in this text. Primarily intended for secondary school students, the study contains seven units of material. They include: (1) French gestures, (2) teaching the interrogative pronouns, (3) French cuisine, (4) recreational learning games, (5) French-English cognates, (6)…

Planarian homolog of puromycin-sensitive aminopeptidase DjPsa is required for brain regeneration.

PubMed

Wu, Suge; Liu, Bin; Yuan, Zuoqing; Zhang, Xiufang; Liu, Hong; Pang, Qiuxiang; Zhao, Bosheng

2017-06-01

Puromycin-sensitive aminopeptidase (PSA) belongs to the M1 zinc metallopeptidase family. PSA is the most abundant aminopeptidase in the brain and plays a role in the metabolism of neuropeptides including those involved in neurodegeneration. A cDNA DjPsa was identified from the planarian Dugesia japonica cDNA library. It contains a 639-bp open reading frame corresponding to a deduced protein of 212 amino acids. Whole mount in situ hybridization revealed that DjPsa is expressed in the brain and ventral nerve cords of intact and regenerating animals and demonstrates a tissue and stage-specific expression pattern of DjPsa in developing embryos and larvae. Knocking down DjPsa gene expression with RNA interference during planarian regeneration inhibits the brain reformation completely. The results suggest that DjPsa is required for planarian brain regeneration.

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

PubMed Central

Tawfik, A

2015-01-01

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

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

PubMed Central

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

2014-01-01

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

Positive associations between galectin-3 and PSA levels in prostate cancer patients: a prospective clinical study-I.

PubMed

Nakajima, Kosei; Heilbrun, Lance K; Hogan, Victor; Smith, Daryn; Heath, Elisabeth; Raz, Avraham

2016-12-13

Galectin-3 (Gal-3), an oncogenic pro-inflammatory protein, has been suggested as a possible complementary diagnostic candidate to prostate specific antigen (PSA) blood test for prostate cancer patients. The presence of the proteins in the circulation (biomarkers) may elicit an intrinsic humoral immune reaction by generating autoantibodies, which consequently could alter the detection levels. Here, we report the associations of the two prostate cancer biomarkers, Gal-3 and PSA in patients at different clinical states of prostate cancer while taking into account the autoantibody levels. A blind, prospective, single institution, pilot study was conducted. A total of 95 men were classified into 5 groups: healthy controls (Group1), newly diagnosed patients (Group2), no recurrence after local therapy (Group3), rising PSA after local therapy (Group4), and metastatic patients (Group5). Gal-3 and PSA level were divided by their respective autoantibodies, which yielded relative PSA and relative Gal-3 levels. After the adjustments, Spearman's rank correlations and linear regression modeling revealed the positive associations between relative Gal-3 and relative PSA levels among all 95 men combined (rho = 0.446, P < 0.0001; fitted slope 0.448, P < 0.0001), in Group2 (rho = 0.616, P = 0.0050; fitted slope 0.438, P =0.0011), and Group3 (rho = 0.484, P = 0.0360; fitted slope 0.470, P = 0.0187). The data show positive associations of relative Gal-3 and relative PSA levels in prostate cancer patients, notably at early clinical time course. Allowing for the influence of autoantibodies, Gal-3 level might be considered as a potential biomarker since it is positively associated with PSA level.

Learning L2 Pronunciation with a Mobile Speech Recognizer: French /y/

ERIC Educational Resources Information Center

Liakin, Denis; Cardoso, Walcir; Liakina, Natallia

2015-01-01

This study investigates the acquisition of the L2 French vowel /y/ in a mobile-assisted learning environment, via the use of automatic speech recognition (ASR). Particularly, it addresses the question of whether ASR-based pronunciation instruction using a mobile device can improve the production and perception of French /y/. Forty-two elementary…

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer

PubMed Central

Narang, Amol K.; Trieu, Janson; Radwan, Noura; Ram, Ashwin; Robertson, Scott P.; He, Pei; Gergis, Carol; Griffith, Emily; Singh, Harleen; DeWeese, Tate A.; Honig, Stephanie; Annadanam, Anvesh; Greco, Stephen; DeVille, Curtiland; McNutt, Todd; DeWeese, Theodore L.; Song, Daniel Y.; Tran, Phuoc T.

2016-01-01

Background In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. Methods Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993–2006 and who had an EOR PSA (n=688, median follow-up 11.2 years). We analyzed the association of an end-of-radiation (EOR) prostate-specific antigen (PSA) level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ≥0.1 ng ml−1) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. Results At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% vs. 64.4%, p<0.001), 10-year MFS (84.8% vs. 92.0%, p=0.003), 10-year PCSS (94.3% vs. 98.2%, p=0.007), and 10-year OS (75.8% vs. 82.5%, p=0.01), as compared to men with an undetectable EOR PSA. Among NCCN intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37–14.65, p<0.001; NCCN risk level: HR 2.01, 95% CI 0.74–5.42, p=0.168). Main study limitations are retrospective study design and associated biases. Conclusions EOR PSA was significantly associated with survival endpoints in men who received treated with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation. PMID:28094250

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer.

PubMed

Narang, A K; Trieu, J; Radwan, N; Ram, A; Robertson, S P; He, P; Gergis, C; Griffith, E; Singh, H; DeWeese, T A; Honig, S; Annadanam, A; Greco, S; DeVille, C; McNutt, T; DeWeese, T L; Song, D Y; Tran, P T

2017-06-01

In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993 to 2006 and who had an end-of-radiation (EOR) PSA (n=688, median follow-up 11.2 years). We analyzed the association of an EOR PSA level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ⩾0.1 ng ml -1 ) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% versus 64.4%, P<0.001), 10-year MFS (84.8% versus 92.0%, P=0.003), 10-year PCSS (94.3% versus 98.2%, P=0.007) and 10-year OS (75.8% versus 82.5%, P=0.01), as compared to men with an undetectable EOR PSA. Among National Comprehensive Care Network (NCCN) intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37-14.65, P<0.001; NCCN risk level: HR 2.01, 95% CI 0.74-5.42, P=0.168). Main study limitations are retrospective study design and associated biases. EOR PSA was significantly associated with survival endpoints in men who received treatment with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation.

Mutations in the prostate specific antigen (PSA/KLK3) correlate with male infertility.

PubMed

Gupta, Nishi; Sudhakar, Digumarthi V S; Gangwar, Pravin Kumar; Sankhwar, Satya Narayan; Gupta, Nalini J; Chakraborty, Baidyanath; Thangaraj, Kumarasamy; Gupta, Gopal; Rajender, Singh

2017-09-11

Prostate specific antigen (PSA/KLK3) is known to be the chief executor of the fragmentation of semenogelins, dissolution of semen coagulum, thereby releasing sperm for active motility. Recent research has found that semenogelins also play significant roles in sperm fertility by affecting hyaluronidase activity, capacitation and motility, thereby making PSA important for sperm fertility beyond simple semen liquefaction. PSA level in semen has been shown to correlate with sperm motility, suggesting that PSA level/activity can affect fertility. However, no study investigating the genetic variations in the KLK3/PSA gene in male fertility has been undertaken. We analyzed the complete coding region of the KLK3 gene in ethnically matched 875 infertile and 290 fertile men to find if genetic variations in KLK3 correlate with infertility. Interestingly, this study identified 28 substitutions, of which 8 were novel (not available in public databases). Statistical comparison of the genotype frequencies showed that five SNPs, rs266881 (OR = 2.92, P < 0.0001), rs174776 (OR = 1.91, P < 0.0001), rs266875 (OR = 1.44, P = 0.016), rs35192866 (OR = 4.48, P = 0.025) and rs1810020 (OR = 2.08, P = 0.034) correlated with an increased risk of infertility. On the other hand, c.206 + 235 T > C, was more freuqent in the control group, showing protective association. Our findings suggest that polymorphisms in the KLK3 gene correlate with infertility risk.

Early diagnostic role of PSA combined miR-155 detection in prostate cancer.

PubMed

Guo, T; Wang, X-X; Fu, H; Tang, Y-C; Meng, B-Q; Chen, C-H

2018-03-01

As a kind of malignant tumor in the male genitourinary system, prostate cancer exhibits significantly increased occurrence. Prostate-specific antigen (PSA) expression can be seen in the prostate cancer, prostatitis, and other diseases, therefore, lack of diagnostic specificity. The miR-155 expression is abnormally increased in the tumors. Therefore, this study aims to explore the clinical significance of PSA combined miR-155 detection in the early diagnosis of prostate cancer. A total of 86 patients diagnosed with prostate cancer were enrolled in this study. PSA and miR-155 gene expression in tumor tissue were detected by using Real-time PCR. The serum levels of PSA were measured by using enzyme-linked immunosorbent assay (ELISA). The correlation of PSA and miR-155 expression with age, body mass index (BMI), tumor volume, tumor-node-metastasis (TNM) stage, lymph node metastasis (LNM), and other clinicopathological features were analyzed, respectively. Serum PSA expression and PSA gene in tumor tissue were significantly higher compared to that in adjacent tissues (p<0.05). PSA gene and protein increased significantly with the clinical stage of TNM and decreased following the increase of grade (p<0.05). The miR-155 level was significantly elevated in the tumor tissue compared with para-carcinoma tissue (p<0.05). PSA and miR-155 expressions were positively correlated with TNM stage, tumor volume, and LNM, and negatively correlated with grade (p<0.05). PSA and miR-155 were closely related to the clinicopathological features of prostate cancer. Combined detection is helpful for the early diagnosis of prostate cancer.

Optimization of PSA screening policies: a comparison of the patient and societal perspectives.

PubMed

Zhang, Jingyu; Denton, Brian T; Balasubramanian, Hari; Shah, Nilay D; Inman, Brant A

2012-01-01

To estimate the benefit of PSA-based screening for prostate cancer from the patient and societal perspectives. A partially observable Markov decision process model was used to optimize PSA screening decisions. Age-specific prostate cancer incidence rates and the mortality rates from prostate cancer and competing causes were considered. The model trades off the potential benefit of early detection with the cost of screening and loss of patient quality of life due to screening and treatment. PSA testing and biopsy decisions are made based on the patient's probability of having prostate cancer. Probabilities are inferred based on the patient's complete PSA history using Bayesian updating. The results of all PSA tests and biopsies done in Olmsted County, Minnesota, from 1993 to 2005 (11,872 men and 50,589 PSA test results). Patients' perspective: to maximize expected quality-adjusted life years (QALYs); societal perspective: to maximize the expected monetary value based on societal willingness to pay for QALYs and the cost of PSA testing, prostate biopsies, and treatment. From the patient perspective, the optimal policy recommends stopping PSA testing and biopsy at age 76. From the societal perspective, the stopping age is 71. The expected incremental benefit of optimal screening over the traditional guideline of annual PSA screening with threshold 4.0 ng/mL for biopsy is estimated to be 0.165 QALYs per person from the patient perspective and 0.161 QALYs per person from the societal perspective. PSA screening based on traditional guidelines is found to be worse than no screening at all. PSA testing done with traditional guidelines underperforms and therefore underestimates the potential benefit of screening. Optimal screening guidelines differ significantly depending on the perspective of the decision maker.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ko, Eric C.; Stone, Nelson N.; Department of Urology, Mount Sinai Medical Center, New York, NY

2012-06-01

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

PSA nadir of <0.5 ng/mL following brachytherapy for early-stage prostate adenocarcinoma is associated with freedom from prostate-specific antigen failure.

PubMed

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

2012-06-01

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

Do Men Receive Information Required for Shared Decision Making About PSA Testing? Results from a National Survey.

PubMed

Leyva, Bryan; Persoskie, Alexander; Ottenbacher, Allison; Hamilton, Jada G; Allen, Jennifer D; Kobrin, Sarah C; Taplin, Stephen H

2016-12-01

Most professional organizations, including the American College of Physicians and U.S. Preventive Services Task Force, emphasize that screening for prostate cancer with the prostate-specific antigen (PSA) test should only occur after a detailed discussion between the health-care provider and patient about the known risks and potential benefits of the test. In fact, guidelines strongly advise health-care providers to involve patients, particularly those at elevated risk of prostate cancer, in a "shared decision making" (SDM) process about PSA testing. We analyzed data from the National Cancer Institute's Health Information National Trends Survey 2011-2012-a nationally representative, cross-sectional survey-to examine the extent to which health professionals provided men with information critical to SDM prior to PSA testing, including (1) that patients had a choice about whether or not to undergo PSA testing, (2) that not all doctors recommend PSA testing, and (3) that no one is sure if PSA testing saves lives. Over half (55 %) of men between the ages of 50 and 74 reported ever having had a PSA test. However, only 10 % of men, regardless of screening status, reported receiving all three pieces of information: 55 % reported being informed that they could choose whether or not to undergo testing, 22 % reported being informed that some doctors recommend PSA testing and others do not, and 14 % reported being informed that no one is sure if PSA testing actually saves lives. Black men and men with lower levels of education were less likely to be provided this information. There is a need to improve patient-provider communication about the uncertainties associated with the PSA test. Interventions directed at patients, providers, and practice settings should be considered.

Serum complexed and free prostate-specific antigen (PSA) for the diagnosis of the polycystic ovarian syndrome (PCOS).

PubMed

Diamandis, Eleftherios P; Stanczyk, Frank Z; Wheeler, Sarah; Mathew, Anu; Stengelin, Martin; Nikolenko, Galina; Glezer, Eli N; Brown, Marshall D; Zheng, Yingye; Chen, Yen-Hao; Wu, Hsiao-Li; Azziz, Ricardo

2017-10-26

Polycystic ovarian syndrome (PCOS) is a common cause of reproductive and metabolic dysfunction. We hypothesized that serum prostate-specific antigen (PSA) may constitute a new biomarker for hyperandrogenism in PCOS. We conducted a cross-sectional study of 45 women with PCOS and 40 controls. Serum from these women was analyzed for androgenic steroids and for complexed PSA (cPSA) and free PSA (fPSA) with a novel fifth- generation assay with a sensitivity of ~10 fg/mL for cPSA and 140 fg/mL for fPSA. cPSA and fPSA levels were about three times higher in PCOS compared to controls. However, in PCOS, cPSA and fPSA did not differ according to waist-to-hip ratio, Ferriman-Gallwey score, or degree of hyperandrogenemia or oligo-ovulation. In PCOS and control women, serum cPSA and fPSA levels were highly correlated with each other, and with free and total testosterone levels, but not with other hormones. Adjusting for age, body mass index (BMI) and race, cPSA was significantly associated with PCOS, with an odds ratio (OR) of 5.67 (95% confidence interval [CI]: 1.86, 22.0). The OR of PCOS for fPSA was 7.04 (95% CI: 1.65, 40.4). A multivariate model that included age, BMI, race and cPSA yielded an area-under-the-receiver-operating-characteristic curve of 0.89. Serum cPSA and fPSA are novel biomarkers for hyperandrogenism in PCOS and may have value for disease diagnosis.

Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study.

PubMed

Thomsen, F B; Brasso, K; Berg, K D; Gerds, T A; Johansson, J-E; Angelsen, A; Tammela, T L J; Iversen, P

2016-03-01

The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting. Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method. Two hundred and sixty-three patients were included of which 116, 76 and 71 had a PSA at consent ≤10, 10.1-25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt ≤3 years: 62.0% versus PSAdt >3 years: 16.3% (Gray's test: P < 0.0001), PSAvel ≥2 ng/ml/year: 48.0% versus PSAvel <2 ng/ml/year: 11.0% (Gray's test: P = 0.0008), and PSAvRC 2: 45.0% versus 0-1: 3.8% (Gray's test: P = 0.001). In contrast, none of the PSA kinetics were significantly associated with changes of 13-year risks of PCa mortality in patients with PSA at consent ≤10 or >25 ng/ml. We found that magnitude changes in 13-year risks of PCa mortality that can be indicated by PSA kinetics depend on PSA level in patients with localised PCa who were managed observationally. Our results question PSA kinetics as surrogate marker for PCa mortality in patients with low and high PSA values. NCT00672282. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For

An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines.

PubMed

Paliouras, Miltiadis; Diamandis, Eleftherios P

2008-06-01

The androgen receptor (AR) plays an important role in early prostate cancer by activating transcription of a number of genes participating in cell proliferation and growth and cancer progression. However, as the cancer progresses, prostate cancer cells transform from an androgen-dependent to an androgen-independent state. Androgen-independent prostate cancer can manifest itself in several forms, including a percentage of cancers that show reduced levels of prostate-specific antigen (PSA) and can progress without the need for the ligand or active receptor. Therefore, our goal was to examine the role of intracellular signaling pathways in an androgen-independent prostate cancer in vitro model. Using the cell line PC3(AR)(2), we stimulated cells with 5-alpha-dihydrotestosterone (DHT) and epidermal growth factor (EGF) and then analyzed PSA expression. We observed lower PSA expression when cells were jointly stimulated with DHT and EGF, and this was associated with an increase in AKT activity. We examined the role of AKT in AR activity and PSA expression by creating stable PC3(AR)(2) cell lines transfected with a PI3K-Ras-effector loop mutant. These cell lines showed lower DHT-stimulated PSA expression that correlated to changes in the phosphorylated state of AR. Therefore, we propose an in vitro androgen-independent model in which a PI3K/AKT activity threshold and subsequent AR transactivation regulate PSA expression.

Deciding on PSA-screening - Quality of current consumer information on the Internet.

PubMed

Korfage, Ida J; van den Bergh, Roderick C N; Essink-Bot, Marie-Louise

2010-11-01

Given that screening for prostate cancer has the potential to reduce prostate cancer mortality at the expense of considerable overdiagnosis and overtreatment, the availability of core consumer information - correct, balanced and supportive of autonomous decision-making - is a must. We assessed the quality of consumer information available through the Internet per November 2009 and its possible contribution to informed decision-making by potential screenees. Consumer information on PSA-screening was sought through the Internet in November 2009. Materials had to be targeted at potential consumers, offered by not-for-profit organisations, released in 2005 or after, in English or Dutch. Per material 2 of the authors assessed independently from each other whether standardised pre-defined topics were addressed, whether the content was correct and which approach was taken towards the decision-making process about uptake. Twenty-three materials were included, of which 11 were released (shortly) after the results of 2 large randomized-controlled trials (RCTs) that evaluated the effectiveness of screening for prostate cancer had been published in March 2009. That a PSA-test result can be abnormal because of non-cancerous conditions (false positive) and that it may miss prostate cancer (false negative) was not addressed in 2/23 and 8/23 materials, respectively. The risk of overdiagnosis and overtreatment was not mentioned in 6 out of 23. PSA-screening was presented as a usual thing to do in some materials, whereas other materials emphasised the voluntary nature of PSA-screening ('it is your decision'). The content of 19/23 materials was considered sufficiently informative according to the pre-defined criteria, 12/23 materials were considered supportive of informed decision-making by men. Most materials of not-for-profit organizations supplied adequate information about PSA-screening, whilst the degree of persuasion towards uptake reflected variations in opinions on men

Prostate-Specific Antigen (PSA) Test

MedlinePlus

... incidence of prostate cancer than men in the control group but the same rate of deaths from the ... the PLCO trial who were assigned to the control group had nevertheless undergone PSA screening. This analysis suggested ...

Survival benefit of local versus no local treatment for metastatic prostate cancer-Impact of baseline PSA and metastatic substages.

PubMed

Pompe, Raisa S; Tilki, Derya; Preisser, Felix; Leyh-Bannurah, Sami-Ramzi; Bandini, Marco; Marchioni, Michele; Gild, Philipp; Tian, Zhe; Fossati, Nicola; Cindolo, Luca; Shariat, Shahrokh F; Huland, Hartwig; Graefen, Markus; Briganti, Alberto; Karakiewicz, Pierre I

2018-07-01

To test whether local treatment (LT), namely radical prostatectomy (RP) or brachytherapy (BT) still confers a survival benefit versus no local treatment (NLT), when adjusted for baseline PSA (bPSA). To further examine whether the effect of LT might be modulated according to bPSA and M1 substages. Of 13 906 mPCa patients within the SEER (2004-2014), 375 underwent RP, 175 BT, and 13 356 NLT. Multivariable competing risks regression (MVA CRR) analyses after 1:2 propensity score matching assessed the impact of LT versus NLT on cancer specific mortality (CSM). Interaction analyses tested the association between treatment type and bPSA within different M1 substages. MVA CRR analyses revealed lower CSM rates for LT (RP [HR: 0.55, CI: 0.44-0.70, P < 0.001] and BT [HR: 0.63, CI: 0.49-0.83, P < 0.001]) compared to NLT. A significant interaction existed between bPSA and treatment type, in M1b patients only. Here, LT conferred a survival benefit when bPSA was <60 ng/mL with maximum benefit when bPSA was <40 ng/mL. No survival benefit existed for M1b patients above the 60 ng/mL bPSA threshold and for M1c patients, regardless of bPSA. For M1a patients, LT conferred a survival benefit compared to NLT. However, dose-response according to bPSA could not be tested, due to insufficient sample size. Our observations provide new insight regarding the pivotal effect of bPSA and M1 substages on CSM, when LT is contemplated. While M1a patients benefited from LT, the survival benefit was modulated by bPSA in M1b patients and no survival benefit existed in M1c patients. © 2018 Wiley Periodicals, Inc.

Vocabulary Breadth in French L2 Learners

ERIC Educational Resources Information Center

David, Annabelle

2008-01-01

Vocabulary is one of the building blocks of language and is a necessary component of learners' development. This paper aims to describe the development of the L2 lexicon from the first year of learning French as a foreign language at school to the last year of undergraduate studies at university by setting out what learners know and how this…

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

PubMed

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

2017-01-01

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

PSA levels as a predictor of 68Ga PSMA PET/CT positivity in patients with prostate cancer?

PubMed

Soydal, Cigdem; Urun, Yuksel; Suer, Evren; Nak, Demet; Ozkan, Elgin; Kucuk, Ozlem N

2018-05-10

The aim of this study is to evaluate predictive factors of 68Gallium (68Ga) Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET)/Computed Tomography (CT) positivity. Relationships between serum Prostate Specific Antigen (PSA), Lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) levels, Gleason Score (GS) and positivity of 68Ga PSMA PET in patients who underwent 68Ga PSMA PET/CT for restaging for PCa were evaluated retrospectively. One hundred and four (median age: 67; range: 51-88) patients were included in this study. Of these patients, PSMA PET was positive in 75 (72%) patients. Mean serum PSA levels for PET negative and positive groups were 0.76±1.00 and 180.85±324.93 ng/ml (p<0.001). The sensitivity and specificity of 68Ga PSMA PET/CT for detection of disease recurrence were calculated as 92% and 80%, respectively, for the 1.4 ng/ml PSA cut-off and 92% and 90%, respectively, for the 2 ng/ml PSA cut-off values. The positivity rates for patients with PSA levels <1.4 ng/ml and ≥1.4 ng/ml were 21% and 90%, respectively (p<0.001). 68Ga PSMA PET/CT seems to be a highly sensitive in patients with early PSA recurrence. Patients with higher GS and early PSA recurrence could benefit from 68Ga PSMA PET/CT.

Insights for public education provided by French media on ideas about prostate cancer - A media analysis study.

PubMed

Zanchetta, Margareth S; Cognet, Marguerite; Lam-Kin-Teng, Mary Rachel; Dumitriu, Marie Elisabeth; Haag, Carlos; Kadio, Bernard; Desgrandchamps, François; Rénaud, Lise

2018-01-01

Background: This study explored the French media's presentation of ideas and medical information about prostate cancer (PC) that may influence men's understanding, attitudes and behavior. Methods: A qualitative media content analysis centered on PC information delivered by French professional media. The selected data were produced in the aftermath of the High Health Authority's decision in 2008 not to recommend systematic screening by prostate specific antigen(PSA) for men over 50. Source was the Media Archives of the French National Library. Content was analyzed from 15 television programs, 14 radio programs, and 55 articles from 35 popular French newspapers (online and printed, weekly and monthly) and 20 magazines. Audio content was narrated into textual form and submitted to manual coding along with the print content. Results: Television and radio content focused on the nature of PC, screening and treatment,and conveyed a gender-centric position linked to male sexuality and virility. Newspapers and magazines targeted the testing controversy, the lack of consensus among professionals, and scientific advances in screening and treatment. Conclusion: Media participation in the European testing debate is valuable for allowing patients to hear all opinions on PC risk factors. Debate on testing policy contributes to confusion and uncertainty regarding appropriate action.

Race, Genetic West African Ancestry, and Prostate Cancer Prediction by PSA in Prospectively Screened High-Risk Men

PubMed Central

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

2008-01-01

Introduction “Race-specific” PSA needs evaluation in men at high-risk for prostate cancer (PCA) for optimizing early detection. Baseline PSA and longitudinal prediction for PCA was examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Materials and Methods Eligibility criteria are age 35–69 years, FH of PCA, African American (AA) race, or BRCA1/2 mutations. Biopsies have been performed 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 PCA. Results 646 men (63% AA) were analyzed. Individual WA ancestry estimates varied widely among self-reported AA men. “Race-specific” differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with ≥ 1 follow-up visit (405 total, 54% AA), three-year prediction for PCA with a PSA of 1.5–4.0 ng/mL was higher in AA men with age in the model (p=0.025) compared to EA men. Hazard ratios of PSA for PCA were also higher by self-reported race (1.59 for AA vs. 1.32 for EA, p=0.04). There was a trend for increasing prediction for PCA with increasing genetic WA ancestry. Conclusions “Race-specific” PSA may need to be redefined as higher prediction for PCA at any given PSA in AA men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing PCA early detection. PMID:19240249

Ethnicity Is an Independent Determinant of Age-Specific PSA Level: Findings from a Multiethnic Asian Setting

PubMed Central

Sothilingam, Selvalingam; Malek, Rohan; Sundram, Murali; Hisham Bahadzor, Badrul; Ong, Teng Aik; Ng, Keng Lim; Sivalingam, Sivaprakasam; Razack, Azad Hassan Abdul

2014-01-01

Objectives To study the baseline PSA profile and determine the factors influencing the PSA levels within a multiethnic Asian setting. Materials and Methods We conducted a cross-sectional study of 1054 men with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The serum PSA concentration of each subject was assayed. Potential factors associated with PSA level including age, ethnicity, height, weight, family history of prostate cancer, lower urinary tract voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE) were evaluated using univariable and multivariable analysis. Results There were 38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a healthy PSA (≤4 ng/ml). The median PSA level of Malay, Chinese and Indian men was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively lower median PSA level and prostate volume than Malays and Chinese, who shared a comparable median PSA value across all 10-years age groups. The PSA density was fairly similar amongst all ethnicities. Further analysis showed that ethnicity, weight and prostate volume were independent factors associated with age specific PSA level in the multivariable analysis (p<0.05). Conclusion These findings support the concept that the baseline PSA level varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity may also need to be taken into account when investigating serum PSA concentrations in the multiethnic Asian population. PMID:25111507

Prostate specific antigen (PSA) kinetic as a prognostic factor in metastatic prostate cancer receiving androgen deprivation therapy: systematic review and meta-analysis.

PubMed

Afriansyah, Andika; Hamid, Agus Rizal Ardy Hariandy; Mochtar, Chaidir Arif; Umbas, Rainy

2018-01-01

Aim: Metastatic prostate cancer (mPCa) has a poor outcome with median survival of two to five years. The use of androgen deprivation therapy (ADT) is a gold standard in management of this stage.  Aim of this study is to analyze the prognostic value of PSA kinetics of patient treated with hormonal therapy related to survival from several published studies Method: Systematic review and meta-analysis was performed using literature searching in the electronic databases of MEDLINE, Science Direct, and Cochrane Library. Inclusion criteria were mPCa receiving ADT, a study analyzing Progression Free Survival (PFS), Overall Survival (OS), or Cancer Specific Survival (CSS) and prognostic factor of survival related to PSA kinetics (initial PSA, PSA nadir, and time to achieve nadir (TTN)). The exclusion criteria were metastatic castration resistant of prostate cancer (mCRPC) and non-metastatic disease. Generic inverse variance method was used to combine hazard ratio (HR) within the studies. Meta-analysis was performed using Review Manager 5.2 and a p-value <0.05 was considered statistically significant. Results: We found 873 citations throughout database searching with 17 studies were consistent with inclusion criteria. However, just 10 studies were analyzed in the quantitative analysis. Most of the studies had a good methodological quality based on Ottawa Scale. No significant association between initial PSA and PFS. In addition, there was no association between initial PSA and CSS/ OS. We found association of reduced PFS (HR 2.22; 95% CI 1.82 to 2.70) and OS/ CSS (HR 3.31; 95% CI 2.01-5.43) of patient with high PSA nadir. Shorter TTN was correlated with poor result of survival either PFS (HR 2.41; 95% CI 1.19 - 4.86) or CSS/ OS (HR 1.80; 95%CI  1.42 - 2.30) Conclusion: Initial PSA before starting ADT do not associated with survival in mPCa.  There is association of PSA nadir and TTN with survival.

Prostate specific antigen (PSA) kinetic as a prognostic factor in metastatic prostate cancer receiving androgen deprivation therapy: systematic review and meta-analysis

PubMed Central

Afriansyah, Andika; Hamid, Agus Rizal Ardy Hariandy; Mochtar, Chaidir Arif; Umbas, Rainy

2018-01-01

Aim: Metastatic prostate cancer (mPCa) has a poor outcome with median survival of two to five years. The use of androgen deprivation therapy (ADT) is a gold standard in management of this stage.  Aim of this study is to analyze the prognostic value of PSA kinetics of patient treated with hormonal therapy related to survival from several published studies Method: Systematic review and meta-analysis was performed using literature searching in the electronic databases of MEDLINE, Science Direct, and Cochrane Library. Inclusion criteria were mPCa receiving ADT, a study analyzing Progression Free Survival (PFS), Overall Survival (OS), or Cancer Specific Survival (CSS) and prognostic factor of survival related to PSA kinetics (initial PSA, PSA nadir, and time to achieve nadir (TTN)). The exclusion criteria were metastatic castration resistant of prostate cancer (mCRPC) and non-metastatic disease. Generic inverse variance method was used to combine hazard ratio (HR) within the studies. Meta-analysis was performed using Review Manager 5.2 and a p-value <0.05 was considered statistically significant. Results: We found 873 citations throughout database searching with 17 studies were consistent with inclusion criteria. However, just 10 studies were analyzed in the quantitative analysis. Most of the studies had a good methodological quality based on Ottawa Scale. No significant association between initial PSA and PFS. In addition, there was no association between initial PSA and CSS/ OS. We found association of reduced PFS (HR 2.22; 95% CI 1.82 to 2.70) and OS/ CSS (HR 3.31; 95% CI 2.01-5.43) of patient with high PSA nadir. Shorter TTN was correlated with poor result of survival either PFS (HR 2.41; 95% CI 1.19 – 4.86) or CSS/ OS (HR 1.80; 95%CI  1.42 – 2.30) Conclusion: Initial PSA before starting ADT do not associated with survival in mPCa.  There is association of PSA nadir and TTN with survival PMID:29904592

Predictive factors of 18F-choline PET/CT positivity in patients with prostate cancer recurrence after radiation therapy: is the impact of PSA nadir underestimated?

PubMed

Johnson, Alison C; Dugué, Audrey Emmanuelle; Silva, Marlon; Moise, Laura; Tillou, Xavier; Joly, Florence; Aide, Nicolas

2016-12-01

The objective of this study is to explore the impact of PSA nadirs on detection rates of prostate cancer (PCa) recurrence with 18 F-choline (CH) PET/CT after external beam radiation therapy (EBRT). In this retrospective study, data were collected from 54 patients with suspicion of PCa biochemical recurrence after EBRT (28 patients treated initially with EBRT and 26 as salvage therapy in the absence of PSA decrease after initial treatment), who underwent 18 F-CH PET/CT between 2010 and 2015. PSA nadir and trigger PSA were collected from patient files. Relative PSA was calculated by subtracting the nadir from the trigger PSA. Median PSA nadir was 0.31 (0.01-13.31) ng/mL, trigger PSA was 7.85 (0.47-111.60) ng/mL, and relative PSA was 6.05 (0.24-104.59) ng/mL. Overall, 40 (74%) PET/CT scans were positive: recurrence was local and/or regional in 29 patients, distant in 15 and combined both in four, with no association between PSA values and sites of recurrence. In univariate analysis, trigger (p = 0.015) and relative (p = 0.0005) PSA values and PSA velocity (p = 0.01) were significantly linked to positive PET/CT, but PSA nadir was not. In subgroup analysis, these significant differences were only found in the salvage EBRT group. Akaike Information Criterion multivariate model comparison found that relative PSA was a better predictor of positive PET/CT than trigger PSA (PSAt). 18 F-CH PET/CT detection rates increased with trigger and relative PSA: 0% (0/4 patients), 71% (5/7 patients), and 81% (35/43 patients) for PSAt <2 ng/mL, 2≤ PSAt ≤4 ng/mL, and PSAt >4 ng/mL, respectively, and 14% (1/7 patients), 50% (5/10 patients), and 92% (34/37 patients) when relative PSA was taken into account instead of trigger PSA, with seven (13%) patients changing subgroups. We found a high overall detection rate and an increase in detection rates proportional to trigger and relative PSAs. Although relative PSA, taking into account PSA nadir, was a better predictive

The impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or with androgen deprivation therapy for unfavorable-risk prostate cancer.

PubMed

Patel, S A; Chen, M-H; Loffredo, M; Renshaw, A; Kantoff, P W; D'Amico, A V

2017-06-01

The optimal management of men with PSA failure following initial prostate cancer (PC) therapy stratified by comorbidity is unknown. We investigated the impact that PSA doubling time (DT) and comorbidity had on the risk of all-cause mortality (ACM), prostate cancer-specific mortality (PCSM) and other-cause mortality (OCM) following PSA failure. Between 1995 and 2001, 206 men with unfavorable-risk PC were randomized to receive radiation therapy alone or in combination with 6 months of androgen deprivation therapy (ADT); 108 men experienced PSA failure and formed the study cohort. Cox and Fine-Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM, respectively, stratified by comorbidity status using a validated metric. After a median follow-up of 13.71 years following PSA failure, 81 of the 108 men (75%) died. Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal (adjusted hazard ratio (AHR) 0.33, 95% confidence interval (CI) 0.17-0.65, P=0.001) and moderate/severe comorbidity (AHR 0.014, 95% CI 0.002-0.129, P=0.0002). However, because of the different contributions of the risk of OCM to risk of ACM within comorbidity subgroups, increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal (AHR 0.69, 95% CI 0.50-0.96, P=0.03) but not moderate/severe comorbidity (AHR 0.95, 95% CI 0.51-1.78, P=0.87). Both the extent of comorbidity and the PSA DT should be taken into consideration when deciding on appropriate management and/or clinical trial eligibility at the time of PSA failure.

Prostate-specific antigen (PSA) testing of men in UK general practice: a 10-year longitudinal cohort study.

PubMed

Young, Grace J; Harrison, Sean; Turner, Emma L; Walsh, Eleanor I; Oliver, Steven E; Ben-Shlomo, Yoav; Evans, Simon; Lane, J Athene; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Martin, Richard M; Metcalfe, Chris

2017-10-30

Cross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa). Patient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man's age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study. The 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45-49 years to 53.0% for men aged 65-69 years (p for trend <0.001). For those with a PSA level ≥3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%, respectively). A high proportion of men aged 45-69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa. ISRCTN20141297,NCT02044172. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Prostate-specific antigen (PSA) testing of men in UK general practice: a 10-year longitudinal cohort study

PubMed Central

Young, Grace J; Harrison, Sean; Turner, Emma L; Walsh, Eleanor I; Oliver, Steven E; Ben-Shlomo, Yoav; Evans, Simon; Lane, J Athene; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Martin, Richard M; Metcalfe, Chris

2017-01-01

Objectives Cross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa). Setting, participants and outcome measures Patient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man’s age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study. Results The 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45–49 years to 53.0% for men aged 65–69 years (p for trend <0.001). For those with a PSA level ≥3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%, respectively). Conclusion A high proportion of men aged 45–69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa. Trial registration number ISRCTN20141297, NCT02044172. PMID:29084797

French MALE UAV Program

DTIC Science & Technology

2003-09-02

ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) MoD- France 8...1French Air Force MINISTÈRE DE LA DÉFENSE 1 SIDM CONOPS 2 FAF IMAGERY ARCHITECTURE 3 FUTURE FRENCH MALE UAV PROGRAM FRENCH MALE UAV PROGRAM Report...2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE French Male UAV Program 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

68Ga-PSMA PET/CT for the detection of bone metastasis in recurrent prostate cancer and a PSA level <2 ng/ml: Two case reports and a literature review

PubMed Central

Petersen, Lars J.; Nielsen, Julie B.; Dettmann, Katja; Fisker, Rune V.; Haberkorn, Uwe; Stenholt, Louise; Zacho, Helle D.

2017-01-01

Localization of prostate cancer recurrence, particularly in the bones, is a major challenge with standard of care imaging in patients with biochemical recurrence following curatively intended treatment. Gallium-68-labeled prostate specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) is a novel and promising method for imaging in prostate cancer. The present study reports two cases of patients with prostate cancer with biochemical recurrence, with evidence of bone metastases on 68Ga-PSMA PET/CT images and low prostate specific antigen PSA levels (<2 ng/ml) and PSA doubling time >6 months. The bone metastases were verified by supplementary imaging with 18F-sodium fluoride PET/CT and magnetic resonance imaging as well as biochemical responses to androgen deprivation therapy. Therefore, 68Ga-PSMA PET/CT is promising for the restaging of patients with prostate cancer with biochemical recurrence, including patients with low PSA levels and low PSA kinetics. PMID:28685078

[French translation and validation of a short version of the Suicide Intervention Response Inventory-2 (SIRI-2-VF)].

PubMed

Kopp-Bigault, C; Audouard-Marzin, Y; Scouarnec, P; Beauchamp, G; Séguin, M; Walter, M

2017-10-30

Training health professionals about suicidal crisis is one major line of suicide prevention worldwide. France has one of the highest suicide rates in Europe, and although crisis intervention training has been set up since 2001, there presently is no training assessment tool in the French language for health professionals trained in suicide prevention. In the four levels of Kirpatrick's education pyramid, training that takes place in France today solely assesses level one status, that is to say relative to the level of satisfaction of participants (self-report). This study proposes a validated short French version of the Suicide Intervention Response Inventory-2 (SIRI-2) of Neimeyer & Mc Innes. The SIRI-2 questionnaire assesses the ability of first line intervention in dealing with suicidal individuals. The translation methodology was inspired from Vallerand's model of cross-cultural back translation. This method is regularly used for translating from the English language to a French version. In order to translate the English version, we used an extensive 7-step methodology implicating several bilingual translators, expert reviewers (psychologists and psychiatrists) and a scientific committee. Participants were 107 students from different French universities and study programs: psychology, medicine and nursing (17 were men; average age was 26.6). Fifteen of these participants answered the SIRI-2-VF on two occasions (separated by a 15-day interval) in order to estimate the temporal stability of the instrument. The scores of the students were compared to six French experts in suicide prevention and with the original expert group who worked on the development of SIRI-2 (n=7). We used Student t Test for construct validity, Cronbach's Alpha for internal consistency and Pearson's correlation coefficient for temporal stability. Following a fidelity comparison of the results of the French experts with those of the American experts, ten items presenting the least good

A novel classification of prostate specific antigen (PSA) biosensors based on transducing elements.

PubMed

Najeeb, Mansoor Ani; Ahmad, Zubair; Shakoor, R A; Mohamed, A M A; Kahraman, Ramazan

2017-06-01

During the last few decades, there has been a tremendous rise in the number of research studies dedicated towards the development of diagnostic tools based on bio-sensing technology for the early detection of various diseases like cardiovascular diseases (CVD), many types of cancer, diabetes mellitus (DM) and many infectious diseases. Many breakthroughs have been developed in the areas of improving specificity, selectivity and repeatability of the biosensor devices. Innovations in the interdisciplinary areas like biotechnology, genetics, organic electronics and nanotechnology also had a great positive impact on the growth of bio-sensing technology. As a product of these improvements, fast and consistent sensing policies have been productively created for precise and ultrasensitive biomarker-based disease diagnostics. Prostate-specific antigen (PSA) is widely considered as an important biomarker used for diagnosing prostate cancer. There have been many publications based on various biosensors used for PSA detection, but a limited review was available for the classification of these biosensors used for the detection of PSA. This review highlights the various biosensors used for PSA detection and proposes a novel classification for PSA biosensors based on the transducer type used. We also highlight the advantages, disadvantages and limitations of each technique used for PSA biosensing which will make this article a complete reference tool for the future researches in PSA biosensing. Copyright © 2017 Elsevier B.V. All rights reserved.

Learning to Read in English and French: Emergent Readers in French Immersion

ERIC Educational Resources Information Center

Chung, Sheila Cira; Koh, Poh Wee; Deacon, S. Hélène; Chen, Xi

2017-01-01

This longitudinal study investigated the predictors of word reading in English and French for 69 children in early total French immersion from first through third grade. The influence of phonological awareness, orthographic processing, and vocabulary in English and French on the achievement and growth of word reading in the 2 languages were…

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.

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

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

PubMed

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

2016-05-01

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.

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

PubMed

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

2009-07-01

To analyze the prognosis and outcomes of patients who remain free of biochemical failure during the first 5 years after treatment. Between 1991 and 2002, 742 patients with prostate cancer were treated with brachytherapy alone (n = 306), brachytherapy and hormonal therapy (n = 212), or combined implantation and external beam radiotherapy (with or without hormonal therapy; n = 224). These patients were free of biochemical failure (American Society for Therapeutic Radiology and Oncology [ASTRO] definition) during the first 5 post-treatment years and had a documented 5-year prostate-specific antigen (PSA) value. The median follow-up was 6.93 years. The actuarial 10-year freedom from PSA failure rate was 97% using the ASTRO definition and 95% using the Phoenix definition. The median 5-year PSA level was 0.03 ng/mL (range, 0-3.6). The 5-year PSA value was 0.01-0.10 in 31.1%, >0.10-0.2 in 10.2%, >0.2-0.5 in 7.82%, and >0.5 in 3.10%. The 5-year PSA value had prognostic significance, with a PSA value of 2 ng/mL (n = 661) corresponding to a 10-year freedom from PSA failure rate of 99% with the ASTRO definition and 98% with the Phoenix definition vs. 86% (ASTRO definition) and 81% (Phoenix definition) for a PSA value >or=0.2 ng/mL (n = 81; p < .0001). The treatment regimen had no effect on biochemical failure. None of the 742 patients in this study developed metastatic disease or died of prostate cancer. The results of this study have shown that the prognosis for patients treated with brachytherapy and who remain biochemically free of disease for >or=5 years is excellent and none developed metastatic disease during the first 10 years after treatment. The 5-year PSA value is prognostic, and patients with a PSA value <0.2 ng/mL are unlikely to develop subsequent biochemical relapse.

Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results.

PubMed

Wenisch, Judith M; Mayr, Florian B; Spiel, Alexander O; Radicioni, Milko; Jilma, Bernd; Jilma-Stohlawetz, Petra

2014-03-01

Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease. We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively. After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%-39%) compared to baseline (p<0.0001). LHRH superagonists decrease PSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therapy.

The influence of PSA-RNA yield on the analysis of expressed prostatic secretions (EPS) for prostate cancer diagnosis.

PubMed

Whelan, Christopher; Crocitto, Laura; Kawachi, Mark; Chan, Kevin; Smith, David; Wilson, Timothy; Smith, Steven

2013-02-01

In patients with prostate cancer, luminal prostate-specific antigen (PSA) enters the circulation because the basement membrane and glandular epithelium are damaged. Given that excess mobilization of prostate cells during prostatic massage can influence normalization in diagnostic testing, we studied PSA mRNA levels in expressed prostatic secretions (EPS) from patients undergoing biopsy for prostate cancer to determine if prostate cells are preferentially mobilized from patients with prostate cancer during prostatic massage. Quantitative Reverse-Transcription PCR (qRT-PCR) was used to measure the RNA levels of GAPDH, PSA, TMPRSS2:ERG and PCA3 in EPS specimens obtained from patients undergoing biopsy for prostate cancer. The level of PSA mRNA is significantly elevated in EPS specimens obtained from patients with a subsequent diagnosis of prostate cancer. This correlation influenced diagnostic testing results from EPS in two ways. First, when used as an exclusion parameter it appears to improve the diagnostic performance of TMPRSS2:ERG in EPS. Second, when used as a normalization parameter it appears to decrease the performance of these same tests. When comparing the results of mRNA based prostate cancer diagnostics in EPS it will be essential to consider PSA mRNA as a prostate specific gene and not a housekeeping gene.

French Nuclear Forces,

DTIC Science & Technology

1984-05-05

integrated military structure of NATO. This paper briefly reviews French declaratory strategy, ex- plores France’s current and projected force structure, 2...major tendgn- cies in French foreign policy--independent, European, and Atlanticist--without forcing a choice between them. It per- mits France to... French politics, while they admit France m enjoys widespread agreement on defense issues, question the 0 C depth of the consensus. For example, Pierre

Attention, Awareness, and Accents in L2 French

ERIC Educational Resources Information Center

Sturm, Jessica L.

2013-01-01

The present research applies the concepts of attention, awareness, and noticing to a previously unresolved strand of inquiry: accent marks in L2 (second language) French. Previous research found that learners who typed accented words had better recall of the accent marks than those who wrote the same words by hand. Sturm suggested that it may have…

PSA-Stratified Performance of 18F- and 68Ga-PSMA PET in Patients with Biochemical Recurrence of Prostate Cancer.

PubMed

Dietlein, Felix; Kobe, Carsten; Neubauer, Stephan; Schmidt, Matthias; Stockter, Simone; Fischer, Thomas; Schomäcker, Klaus; Heidenreich, Axel; Zlatopolskiy, Boris D; Neumaier, Bernd; Drzezga, Alexander; Dietlein, Markus

2017-06-01

Several studies outlined the sensitivity of 68 Ga-labeled PET tracers against the prostate-specific membrane antigen (PSMA) for localization of relapsed prostate cancer in patients with renewed increase in the prostate-specific antigen (PSA), commonly referred to as biochemical recurrence. Labeling of PSMA tracers with 18 F offers numerous advantages, including improved image resolution, longer half-life, and increased production yields. The aim of this study was to assess the PSA-stratified performance of the 18 F-labeled PSMA tracer 18 F-DCFPyL and the 68 Ga-labeled reference 68 Ga-PSMA-HBED-CC. Methods: We examined 191 consecutive patients with biochemical recurrence according to standard acquisition protocols using 18 F-DCFPyL ( n = 62, 269.8 MBq, PET scan at 120 min after injection) or 68 Ga-PSMA-HBED-CC ( n = 129, 158.9 MBq, 60 min after injection). We determined PSA-stratified sensitivity rates for both tracers and corrected our calculations for Gleason scores using iterative matched-pair analyses. As an orthogonal validation, we directly compared tracer distribution patterns in a separate cohort of 25 patients, sequentially examined with both tracers. Results: After prostatectomy ( n = 106), the sensitivity of both tracers was significantly associated with absolute PSA levels ( P = 4.3 × 10 -3 ). Sensitivity increased abruptly, when PSA values exceeded 0.5 μg/L ( P = 2.4 × 10 -5 ). For a PSA less than 3.5 μg/L, most relapses were diagnosed at a still limited stage ( P = 3.4 × 10 -6 ). For a PSA of 0.5-3.5 μg/L, PSA-stratified sensitivity was 88% (15/17) for 18 F-DCFPyL and 66% (23/35) for 68 Ga-PSMA-HBED-CC. This significant difference was preserved in the Gleason-matched-pair analysis. Outside of this range, sensitivity was comparably low (PSA < 0.5 μg/L) or high (PSA > 3.5 μg/L). After radiotherapy ( n = 85), tracer sensitivity was largely PSA-independent. In the 25 patients examined with both tracers, distribution patterns of 18 F-DCFPyL and 68

Some Issues of Electrical Systems Modeling in Course of PSA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lankin, Michael

2002-07-01

Electrical power supply systems are one of the essential parts of nuclear power plants. The distinctive feature of these systems from the PSA analyst's point of view is significant amount of bi-directional dependencies present within electrical systems. This paper describes an approach that has been used for electrical systems modeling in course of Kola 4 NPP Level 1 PSA. (authors)

Cytokine profiling identifies an interaction of IL-6 and IL-1α to drive PSMA-PSA prostate clones.

PubMed

Jemaa, Awatef Ben; Bouraoui, Yosra; Rais, Nawfel Ben; Nouira, Yassine; Oueslati, Ridha

2016-12-01

Several PSMA-PSA prostate clones have been identified during prostate cancer progression; however, until now, their in situ inflammatory characteristics have remained unclear. We therefore investigated the interplay between proinflammatory cytokines and (PSMA,PSA) sub-groups. 27 benign prostate hyperplasia (BPH) and 18 prostate cancers (PC) were enrolled in this study. Immunohistochemical analysis was performed. Serum levels of PSA were assayed by Immulite autoanalyser. In BPH and PC patients with elevated serum PSA levels, IL-1α was the most proinflammatory cytokine expressed in (PSMA+,PSA-) subgroup. However, most samples of (PSMA+,PSA+) subgroup had positive immunoreaction to IL-6. In samples of PC with PSA serum levels of 4-20ng/mL or >20ng/mL, immunoreaction to TNF-α was seen only in (PSMA+,PSA+) subgroup. Interestingly, several combinations of proinflammatory cytokines (IL-6, IL-1α and TNF-α) showed that coexpression of tissue PSMA and PSA was concomitant with high immunoreactions to (IL-6+,TNF-α-), (IL-6+,IL-1α+) and (IL-1α+,TNFα-) in BPH and PC patients. (PSMA,PSA) subgroup lacking tissue PSA expression showed a high immunoexpression of the profile (IL-6+,TNF-α-). The combinations of (IL-6-, TNF-α-) and (IL-6-, IL-1α-) were absent in (PSMA+,PSA-) and (PSMA+,PSA+) BPH sub-groups. Collectively, these findings underscore the importance of TNF-α and highlight the interaction between IL-6 and IL-1α to generate an inflammatory microenvironment in driving (PSMA,PSA) prostate clones. Copyright © 2016 Elsevier GmbH. All rights reserved.

PDS4 Challenges in the PSA

NASA Astrophysics Data System (ADS)

Saiz, J.; Barbarisi, I.; Docasal, R.; Rios, C.; Montero, A.; Macfarlane, A.; Laantee, C.; Besse, S.; Vallat, C.; Marcos, J.; Arenas, J.; Osinde, J.; Arviset, C.

2018-04-01

The Planetary Science Archive (PSA) stores products from all planetary ESA missions. Adopting PDS4 as the standard for new missions, while being compatible with existing PDS3 products, has driven a design with several difficulties to overcome.

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.

The impact of the United States Preventive Services Task Force (USPTSTF) recommendations against prostate-specific antigen (PSA) testing on PSA testing in Australia.

PubMed

Zargar, Homayoun; van den Bergh, Roderick; Moon, Daniel; Lawrentschuk, Nathan; Costello, Anthony; Murphy, Declan

2017-01-01

To assess the impact of the United States Preventive Services Task Force (USPTSTF) recommendations on prostate-specific antigen (PSA) testing, prostate biopsy, and prostatectomy in Australian men based on the available Medicare data. Events were identified using Medicare item numbers for PSA testing (66655, 66659), prostate biopsy (37219), prostatectomy (37210), and prostatectomy with lymph node dissection (37211). The occurrences of each procedure was queried per 100 000 capita for consecutive financial years over the period 2000-2015. For each item number, reports were also generated for all Australian States. For PSA testing the data was stratified into three age groups of 45-54, 55-64, and 65-74 years. For assessing the rate of prostatectomy the capita rate values for two item numbers of prostatectomy (37210) and prostatectomy with lymph node dissection (37211) were combined. Steady declines in per capita incidences of all five item numbers assessed were seen for the three consecutive financial years (2013-2015) since the publication of the USPTSTF recommendation statement. These declines were seen across all Australian States. When examining the rate of PSA testing for the three age brackets 45-54, 55-64, and 65-74 years, similar trends were identified. Since the introduction of the USPTSTF recommendation statement there has been a steady nationwide decline in per capita incidences of PSA testing, prostate biopsy, and prostatectomy based on the Australian Medicare data. Whether these declines are in the right direction toward reduction in over-diagnosis and overtreatment of clinically insignificant prostate cancer or stage migration toward more locally advanced disease due to lost opportunity in diagnosing and treating early clinically significant prostate cancer will remain to be seen. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Vaginal Prostate Specific Antigen (PSA) Is a Useful Biomarker of Semen Exposure Among HIV-Infected Ugandan Women.

PubMed

Woolf-King, Sarah E; Muyindike, Winnie; Hobbs, Marcia M; Kusasira, Adrine; Fatch, Robin; Emenyonu, Nneka; Johnson, Mallory O; Hahn, Judith A

2017-07-01

The practical feasibility of using prostate specific antigen (PSA) as a biomarker of semen exposure was examined among HIV-infected Ugandan women. Vaginal fluids were obtained with self-collected swabs and a qualitative rapid test (ABAcard ® p30) was used to detect PSA. Trained laboratory technicians processed samples on-site and positive PSA tests were compared to self-reported unprotected vaginal sex (UVS) in the last 48 h. A total of 77 women submitted 126 samples for PSA testing at up to three study visits. Of these samples, 31 % (n = 39/126) were PSA positive, and 64 % (n = 25/39) of the positive PSA samples were accompanied by self-report of no UVS at the study visit the PSA was collected. There were no reported difficulties with specimen collection, storage, or processing. These findings provide preliminary data on high levels of misreported UVS among HIV-infected Ugandan women using practically feasible methods for PSA collection and processing.

Consequences of an Early PSA Response to Enzalutamide Treatment for Japanese Patients with Metastatic Castration-resistant Prostate Cancer.

PubMed

Kato, Haruo; Furuya, Yosuke; Miyazawa, Yoshiyuki; Miyao, Takeshi; Syuto, Takahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Suzuki, Kazuhiro

2016-11-01

Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor (AR)-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed early PSA response to enzalutamide and oncological outcomes to study their prognostic significance in the Japanese population. Fifty-one patients with mCRPC (26 of pre-docetaxel and 25 of post-docetaxel status) were treated with enzalutamide. The PSA progression-free survival (PFS), radiographic PFS (rPFS) and overall survival (OS) were assessed. The association of rPFS and OS in patients with an early PSA response at 4 weeks after commencement of enzalutamide was studied. Early PSA responses were significantly associated with a longer rPFS (median of 47.9 vs. 20.1 weeks, p<0.001, in patients exhibiting a 50% PSA response; median of 40.9 vs. 20.1 weeks, p=0.016, in patients exhibiting a 30% PSA response). OS was also significantly associated with an early PSA response (p=0.002 for patients exhibiting a 50% PSA response, p=0.003 for patients exhibiting a 30% PSA response). Multivariate analysis showed that the predictors of a 50% PSA response were an interval to mCRPC and a docetaxel treatment history, while the predictor of a 30% PSA response was a docetaxel treatment history. Furthermore, a 50% PSA response was independently prognostic of rPFS. An early PSA response to enzalutamide was significantly associated with a longer rPFS and OS. This information will aid in the management of patients treated with enzalutamide. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Impedimetric PSA aptasensor based on the use of a glassy carbon electrode modified with titanium oxide nanoparticles and silk fibroin nanofibers.

PubMed

Benvidi, Ali; Banaei, Maryam; Tezerjani, Marzieh Dehghan; Molahosseini, Hosein; Jahanbani, Shahriar

2017-12-14

This article describes an impedimetric aptasensor for the prostate specific antigen (PSA), a widely accepted prostate cancer biomarker. A glassy carbon electrode (GCE) was modified with titanium oxide nanoparticles (TiO 2 ) and silk fibroin nanofiber (SF) composite. The aptasensor was obtained by immobilizing a PSA-binding aptamer on the AuNP-modified with 6-mercapto-1-hexanol. The single fabrication steps were characterized by cyclic voltammetry and electrochemical impedance spectroscopy. The assay has two linear response ranges (from 2.5 fg.mL -1 to 25 pg.mL -1 , and from 25 pg.mL -1 to 25 ng.mL -1 ) and a 0.8 fg.mL -1 detection limit. After optimization of experimental conditions, the sensor is highly selective for PSA over bovine serum albumin and lysozyme. It was successfully applied to the detection of PSA in spiked serum samples. Graphical abstract Schematic of the fabrication of an aptasensor for the prostate specific antigen (PSA). It is based on the use of a glassy carbon electrode modified with gold nanoparticles and titanium oxide-silk fibroin. The immobilization process of aptamer and interaction with PSA were followed by electrochemical impedance spectroscopy technique.

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

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

PubMed

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

2015-11-03

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

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. © 2016 American Society of Plant Biologists. All rights reserved.

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.

Treatment strategy for metastatic prostate cancer with extremely high PSA level: reconsidering the value of vintage therapy.

PubMed

Yamada, Yasutaka; Sakamoto, Shinichi; Amiya, Yoshiyasu; Sasaki, Makoto; Shima, Takayuki; Komiya, Akira; Suzuki, Noriyuki; Akakura, Koichiro; Ichikawa, Tomohiko; Nakatsu, Hiroomi

2018-05-04

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml -1 ), intermediate (100-999 ng ml -1 ), and high (≥1000 ng ml -1 ). All patients received androgen deprivation therapy (ADT) immediately. We investigated PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P < 0.001, respectively). Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.

Prostate-specific antigen (PSA) as a possible biomarker in non-prostatic cancer: A review.

PubMed

Pérez-Ibave, Diana Cristina; Burciaga-Flores, Carlos Horacio; Elizondo-Riojas, Miguel-Ángel

2018-06-01

Prostate-specific antigen (PSA) is a serine protease produced by epithelial prostatic cells and its main function is to liquefy seminal coagulum. Currently, PSA is a biomarker for the diagnosis and screening of prostate cancer and it was the first cancer biomarker approved by the FDA. The quantity and serum isoforms of male PSA, allows distinguishing between carcinoma and benign inflammatory disease of the prostate. Initially, it was thought that PSA was produced only by the prostate, and thus, a protein that was expressed exclusively in men. However, several authors report that PSA is a protein that is expressed by multiple non-prostatic tissues not only in men but also in women. Some authors also report that in women, the expression of this protein is highly related to breast and colon cancer and therefore can act as a possible biomarker for early detection, diagnosis and prognosis of these cancers in women. In this review, we will focus on the characteristics of the PSA at a molecular level, its current clinical implications, the expression of this protein in non-prostatic tissues, and its relationship with cancer, especially in women. Copyright © 2018 Elsevier Ltd. All rights reserved.

27. BEDROOM #2 INTERIOR SHOWING DOUBLE FRENCH DOORS TO SCREENED ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

27. BEDROOM #2 INTERIOR SHOWING DOUBLE FRENCH DOORS TO SCREENED PORCH AND UNUSUAL WINDOWED CLOSET THROUGH OPEN FIVE-PANELED DOOR. VIEW TO WEST. - Big Creek Hydroelectric System, Powerhouse 8, Operator Cottage, Big Creek, Big Creek, Fresno County, CA

Co-delivery of PSA and PSMA DNA vaccines with electroporation induces potent immune responses.

PubMed

Ferraro, Bernadette; Cisper, Neil J; Talbott, Kendra T; Philipson-Weiner, Lindsey; Lucke, Colleen E; Khan, Amir S; Sardesai, Niranjan Y; Weiner, David B

2011-01-01

Prostate cancer (PCa) remains a significant public health problem. Current treatment modalities for PCa can be useful, but may be accompanied by deleterious side effects and often do not confer long-term control. Accordingly, additional modalities, such as immunotherapy, may represent an important approach for PCa treatment. The identification of tissue-specific antigens engenders PCa an attractive target for immunotherapeutic approaches. Delivery of DNA vaccines with electroporation has shown promising results for prophylactic and therapeutic targets in a variety of species including humans. Application of this technology for PCa immunotherapy strategies has been limited to single antigen and epitope targets. We sought to test the hypothesis that a broader collection of antigens would improve the breadth and effectiveness of a PCa immune therapy approach. We therefore developed highly optimized DNA vaccines encoding prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) as a dual antigen approach to immune therapy of PCa. PSA-and PSMA-specific cellular immunogenicity was evaluated in a mouse model for co-delivery and single antigen vaccination. Mice received 2 immunizations spaced 2 weeks apart and immunogenicity was evaluated 1 week after the second vaccination. Both the PSA and PSMA vaccines induced robust antigen-specific IFNγ responses by ELISpot. Further characterization of cellular immunogenicity by flow cytometry indicated strong antigen-specific TNFα production by CD4+ T cells and IFNγ and IL-2 secretion by both CD4+ and CD8+ T cells. There was also a strong humoral response as determined by PSA-specific seroconversion. These data support further study of this novel approach to immune therapy of PCa.

GPs views and understanding of PSA testing, screening and early detection; survey.

PubMed

Sutton, J; Melia, J; Kirby, M; Graffy, J; Moss, S

2016-05-01

There is currently no national prostate cancer screening programme in the UK. However, patients 50 years and older are entitled to a prostate specific antigen (PSA) test, if informed on the advantages and disadvantages of testing and their risk of cancer. The Prostate Cancer Risk Management Programme (PCRMP) provides this guidance. The aim of this study was to access GPs' views and understanding of PSA testing, prostate cancer screening and early detection. A total of 708 questionnaires were returned by GPs across two English regions in 2013 and the GP questionnaire responses were quantitatively analysed. In the 699 completed questionnaires, the majority of GPs were well informed about PSA testing, screening and early detection. Only 32% used guidelines for referral, 14% knew all age-specific PSA referral levels, 71% that Black men have a higher prostate cancer risk than White men (22% correctly answered threefold increase) and 82% that family history is a risk factor. A further 78% thought electronic prompts during consultation would encourage PCRMP guideline usage and 75% had never been offered a PSA test and prostate cancer educational course, of which 73% would like to attend a course. Only 23% were aware of the latest PSA screening evidence and 94% would like an update. Participating GPs seem to be well informed but need more information and tools to help follow recommended guidance. In particular, increased awareness of PCRMP guidelines especially by automated methods, further educational courses and evidence updates would be beneficial. © 2016 John Wiley & Sons Ltd.

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

PubMed

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

2016-11-01

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

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

PubMed

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

2016-01-01

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

Independent association between time to prostate-specific antigen (PSA) nadir and PSA progression-free survival in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer receiving abiraterone acetate, but not enzalutamide.

PubMed

Miyake, Hideaki; Hara, Takuto; Tamura, Keita; Sugiyama, Takayuki; Furuse, Hiroshi; Ozono, Seiichiro; Fujisawa, Masato

2017-06-01

The objective of this study was to compare the prognostic effect of time to prostate-specific antigen (PSA) nadir (TTPN) after treatment with abiraterone acetate (AA) and enzalutamide (Enz) in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer (mCRPC). This study included a total of 297 consecutive patients with mCRPC, of whom 125 and 172 received AA and Enz, respectively, without previous treatment with docetaxel and subsequently achieved any degree of PSA reduction after the administration of either agent. The mean values of TTPN in the AA and Enz groups were 19 and 14 weeks, respectively. Despite the lack of significant differences in several parameters according to the mean TTPN in the Enz group, patients with TTPN>19 weeks were characterized by longer duration of androgen deprivation therapy, better performance status, lower incidence of bone metastasis, lower value of nadir PSA, and higher incidence of PSA response than those with TTPN ≤19 weeks in the AA group. The PSA progression-free survival (PFS) in patients with TTPN >19 weeks was significantly superior when compared with TTPN ≤19 weeks in the AA group; however, there was no significant effect of the mean TTPN on the PSA-PFS in the Enz group. Furthermore, TTPN was identified as one of the independent predictors of PSA-PFS in the AA group but not in Enz group. A longer time to reach a PSA nadir after treatment with AA, but not Enz, appeared to be associated with favorable disease control in patients with docetaxel-naïve mCRPC. Copyright © 2017 Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Vallat, C.; Besse, S.; Barbarisi, I.; Arviset, C.; De Marchi, G.; Barthelemy, M.; Coia, D.; Costa, M.; Docasal, R.; Fraga, D.; Heather, D. J.; Lim, T.; Macfarlane, A.; Martinez, S.; Rios, C.; Vallejo, F.; Said, J.

2017-09-01

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://psa.esa.int. All datasets are scientifically peer-reviewed by independent scientists, and are compliant with the Planetary Data System (PDS) standards. The PSA has started to implement a number of significant improvements, mostly driven by the evolution of the PDS standards, and the growing need for better interfaces and advanced applications to support science exploitation.

Measurements of free and total PSA, tissue polypeptide-specific antigen (TPS), and CYFRA 21-1 in prostate cancer patients under intermittent androgen suppression therapy.

PubMed

Theyer, G; Dürer, A; Theyer, U; Haberl, I; Ulsperger, E; Baumgartner, G; Hamilton, G

1999-10-01

The present study evaluated monthly measurements of free and total prostate-specific antigen (PSA), and the tumor proliferation markers tissue polypeptide-specific antigen (TPS) and cytokeratin fragment 21-1 (CYFRA 21-1) in patients with advanced prostate cancer receiving intermittent androgen suppression therapy (IAS). Thirty-four men received alternating cycles of 8 month androgen suppression and treatment cessation (mean duration, 10.3 months) until PSA increased to >20 microg/l. Measurements of testosterone, percentage of free PSA, TPS, and CYFRA 21-1 were performed using ELISA and RIA assays. Periods of androgen suppression resulted in reversible reductions of testosterone (from 6 +/- 0.8 to <0.58 ng/ml), PSA (from 31.2 +/- 4.5 to <1.7 microg/l), and prostatic volume (mean reduction, 22.2 +/- 4.6%), indicating apoptotic regression of the tumors. Upon treatment cessation, testosterone increased to 6.1 +/- 0.56 ng/ml within 2 months, followed by an increase of PSA to 5.8 +/- 0.8 microg/l. The mean percentage of free PSA (15.1 +/- 2.6%) exhibited no significant change during the whole IAS cycle. TPS showed a decrease of 50% after 3 months, and CYFRA 21-1 a 25% decrease after 7 months of androgen suppression treatment. During treatment cessation, TPS exceeded the normal cutoff value of 90 U/l late in tumor regrowth (9-11 months), whereas CYFRA 21-1 remained below the normal cutoff value of 3.3 ng/ml. PSA is the best and most sensitive marker of prostate cancer regression and regrowth during IAS cycles of the markers tested in this study. Free PSA constitutes approximately 15% of total PSA (range, 5-32%), and its percentage showed no significant change during IAS cycles. The TPS and CYFRA 21-1 proliferation marker changes in IAS seem to be related mainly to effects on normal androgen-dependent tissues. Copyright 1999 Wiley-Liss, Inc.

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

PubMed

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

2014-12-01

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). 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. 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 positive surgical margins, upgrading, upstaging and

Manual of Tape Scripts: French, Level 2. Curriculum Bulletin, 1968-69 Series, Number 10.

ERIC Educational Resources Information Center

Lipton, Gladys; And Others

This second manual of tape scripts, together with a set of foreign language audio tapes for level 2 French, was prepared to support the curriculum bulletin, New York City Foreign Language Program for Secondary Schools: French, Levels 1-5. Vocabulary, repetition, transformation, and recombination drills on specific grammatical features allow…

Effects of Audiovisual Media on L2 Listening Comprehension: A Preliminary Study in French

ERIC Educational Resources Information Center

Becker, Shannon R.; Sturm, Jessica L.

2017-01-01

The purpose of the present study was to determine whether integrating online audiovisual materials into the listening instruction of L2 French learners would have a measurable impact on their listening comprehension development. Students from two intact sections of second-semester French were tested on their listening comprehension before and…

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Tao; Hossain, Mahmud; Schepmoes, Athena A.

2012-08-03

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

The Development of French Nuclear Forces

DTIC Science & Technology

1987-11-01

4.1 a rc I -MM RON -- .’-.U . . tn L) L- _*z T M - N EppCV :c 4:-ea THE DEVELOPMENT OF FRENCH NUCLEAR FORCES SMEEC TEV46 P 1 9 1988 Martin J. Wisda...TABLES 1. Transformation of the French Nuclear Force ..... . 100 2. Characteristics of French Nucleac Weapons . . .. 01 3. French Defense Expenditures...pap-er is to examine how and why the French undertook the development of their own nuclear force and through this examination, argue that the French

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirilova, Anna; Damyanovich, Andrei; Crook, Juanita, E-mail: jcrook@bccancer.bc.c

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 monitoredmore » 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.« less

Analysis of the criteria used by the International Commission on Radiological Protection to justify the setting of numerical protection level values.

PubMed

2006-01-01

This report compiles the various numerical protection level values published by the International Commission on Radiological Protection (ICRP) since its 1990 Recommendations (Publication 60). Several terms are used to denominate the protection levels: individual dose limit, 'maximum' individual dose, dose constraint, exemption level, exclusion level, action level, or intervention level. The reasons provided by the Commission for selecting the associated numerical values is quoted as far as available. In some cases the rationale is not totally explicit in the original ICRP report concerned; in such cases the Task Group that prepared the present report have proposed their own interpretation. Originally, this report was prepared by a Task Group at CEPN, a French research and development center, in behalf of IRSN, a French public expert body engaged in radiological protection and nuclear safety. It is published here with kind permission by CEPN and IRSN.

Applying strategies from libertarian paternalism to decision making for prostate specific antigen (PSA) screening

PubMed Central

2011-01-01

Background Despite the recent publication of results from two randomized clinical trials, prostate specific antigen (PSA) screening for prostate cancer remains a controversial issue. There is lack of agreement across studies that PSA screening significantly reduces prostate cancer mortality. In spite of these facts, the widespread use of PSA testing in the United States leads to overdetection and overtreatment of clinically indolent prostate cancer, and its associated harms of incontinence and impotence. Discussion Given the inconclusive results from clinical trials and incongruent PSA screening guidelines, the decision to screen for prostate cancer with PSA testing is an uncertain one for patients and health care providers. Screening guidelines from some health organizations recommend an informed decision making (IDM) or shared decision making (SDM) approach for deciding on PSA screening. These approaches aim to empower patients to choose among the available options by making them active participants in the decision making process. By increasing involvement of patients in the clinical decision-making process, IDM/SDM places more of the responsibility for a complex decision on the patient. Research suggests, however, that patients are not well-informed of the harms and benefits associated with prostate cancer screening and are also subject to an assortment of biases, emotion, fears, and irrational thought that interferes with making an informed decision. In response, the IDM/SDM approaches can be augmented with strategies from the philosophy of libertarian paternalism (LP) to improve decision making. LP uses the insights of behavioural economics to help people better make better choices. Some of the main strategies of LP applicable to PSA decision making are a default decision rule, framing of decision aids, and timing of the decision. In this paper, we propose that applying strategies from libertarian paternalism can help with PSA screening decision

Applying strategies from libertarian paternalism to decision making for prostate specific antigen (PSA) screening.

PubMed

Wheeler, David C; Szymanski, Konrad M; Black, Amanda; Nelson, David E

2011-04-21

Despite the recent publication of results from two randomized clinical trials, prostate specific antigen (PSA) screening for prostate cancer remains a controversial issue. There is lack of agreement across studies that PSA screening significantly reduces prostate cancer mortality. In spite of these facts, the widespread use of PSA testing in the United States leads to overdetection and overtreatment of clinically indolent prostate cancer, and its associated harms of incontinence and impotence. Given the inconclusive results from clinical trials and incongruent PSA screening guidelines, the decision to screen for prostate cancer with PSA testing is an uncertain one for patients and health care providers. Screening guidelines from some health organizations recommend an informed decision making (IDM) or shared decision making (SDM) approach for deciding on PSA screening. These approaches aim to empower patients to choose among the available options by making them active participants in the decision making process. By increasing involvement of patients in the clinical decision-making process, IDM/SDM places more of the responsibility for a complex decision on the patient. Research suggests, however, that patients are not well-informed of the harms and benefits associated with prostate cancer screening and are also subject to an assortment of biases, emotion, fears, and irrational thought that interferes with making an informed decision. In response, the IDM/SDM approaches can be augmented with strategies from the philosophy of libertarian paternalism (LP) to improve decision making. LP uses the insights of behavioural economics to help people better make better choices. Some of the main strategies of LP applicable to PSA decision making are a default decision rule, framing of decision aids, and timing of the decision. In this paper, we propose that applying strategies from libertarian paternalism can help with PSA screening decision-making. Our proposal to augment IDM

21 CFR 169.115 - French dressing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false French dressing. 169.115 Section 169.115 Food and... § 169.115 French dressing. (a) Description. French dressing is the separable liquid food or the..., lecithin, or polyglycerol esters of fatty acids. (d) Nomenclature. The name of the food is “French dressing...

Seven-month prostate-specific antigen (PSA) is prognostic in patients with prostate cancer initially diagnosed with distant metastases.

PubMed

Nieder, Carsten; Haukland, Ellinor; Pawinski, Adam; Norum, Jan

2018-03-05

Recent research suggests that prostate-specific antigen (PSA) ≤ 0.2 ng/dl at 7 months is prognostic for better survival with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer regardless of chemotherapy with docetaxel. These results were derived from a group of clinical trial participants. Therefore, we performed a confirmatory analysis in patients treated outside of trials. Furthermore, we limited inclusion to those who presented with metastases at the initial diagnosis of prostate cancer (synchronous metastases). A retrospective analysis of a comprehensive regional database was performed. The oncology care in this region (Nordland County, Northern Norway) was provided by one center. Patients who were diagnosed between January 01, 2004 and December 31, 2016 were included. Of 101 patients, 90 were alive at 7 months and had their PSA value measured. Their median age was 68.5 years. Only six patients (7%) achieved PSA ≤ 0.2 ng/dl at 7 months. The median value was 4.05 ng/dl. Median overall survival was shortest in patients with PSA > 4.0 ng/dl (22 months). For patients with PSA between 0.3 and 4.0 ng/dl, median survival was 54 months (p = 0.0001). No further increase was seen in the small group with lower PSA. Statistical significance was also found for a cutoff of ≤ 1.0 ng/dl (55 vs. 32 months). PSA at 7 months predicts overall survival. Given that only 7% of patients achieved PSA ≤ 0.2 ng/dl, confirmation of this particular cutoff requires additional studies in other populations.

The PSA testing dilemma: GPs' reports of consultations with asymptomatic men: a qualitative study.

PubMed

Clements, Alison; Watson, Eila; Rai, Tanvi; Bukach, Colleen; Shine, Brian; Austoker, Joan

2007-06-25

The National Health Service Prostate Cancer Risk Management Programme (PCRMP) has recommended that screening for prostate cancer is available for asymptomatic men, on the understanding that they have been provided with full and balanced information about the advantages and limitations of the prostate-specific antigen (PSA) test. Guidance has been distributed to all GPs in England and Wales to assist in the provision of information to men. This study aimed to elicit GPs' accounts of their discussions with asymptomatic men who consult with concerns about prostate cancer in order to identify the degree to which the PCRMP guidance was reflected in these consultations. Qualitative interview study. Semi-structured telephone interviews with 21 GPs from 18 GP practices in Oxfordshire. All GPs reported undertaking some discussion with asymptomatic men about the PSA test. They described focussing most of the discussion on the false-positive and false-negative rates of the test, and the risks associated with a prostate biopsy. They reported less discussion of the potential for diagnosing indolent cancers, the dilemmas regarding treatment options for localised prostate cancer and the potential benefits of testing. Considerable variation existed between GPs in their accounts of the degree of detail given, and GP's presentation of information appeared to be affected by their personal views of the PSA test. The GPs in this study appear to recognise the importance of discussions regarding PSA testing; however, a full and balanced picture of the associated advantages and limitations does not seem to be consistently conveyed. Factors specific to PSA testing which appeared to have an impact on the GPs' discussions were the GP's personal opinions of the PSA test, and the need to counter men's primarily positive views of the benefits of PSA testing. Awareness of the impact of their views on the consultations may help GPs give men a more balanced presentation of the benefits and

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

PubMed

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

2015-05-01

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

French Antilles and Guiana.

PubMed

1983-11-01

This discussion of French Antilles and Guiana cover the following: the people, geography, history, government, political conditions, economy, and relations with the US. In 1983 the population totaled 303,000 with an annual growth rate of 0.09%. The infant mortality rate (1981) was 12.6/1000 and life expectancy 68 years. About 98% of the people of Martinique are of Afro European or Afro European Indian descent. The remainder are the old planter families and a sizable number of metropolitan French. Most of the work force are employed in agriculture or food processing and associated industries. Most permanent residents of Guadeloupe are of mixed Afro European descent. A few thousand Metropolitan French reside there. Most French Guianese live along the coast, about 1/2 of them in the capital. Martinique is the northernmost of the Windward Islands, which are part of the Lesser Antilles chain in the Caribbean Sea southeast of Puerto Rico. Guadeloupe comprises 2 of the Leeward Islands, which are also part of the Lesser Antilles chain. French Guiana is located on the northern coast of South America, a few degrees north of the Equator. Indians were the 1st known indigenous inhabitants of French Guiana and the French Antilles. Columbus sighted Guadeloupe in 1493, Martinique in 1493 or 1502, and the Guiana coast probably during his 3rd voyage in 1498. French Guiana, Guadeloupe, and Martinique, as overseas departments of France since 1946, are integral parts of the French Republic. Their relationship to Metropolitan France is somewhat similar to that of Alaska and Hawaii to the counterminous US. Each department has a general council composed of 1 representative elected by each canton. Guadeloupe and Martinique each elect 2 senators to the French Senate and 3 deputies to the National Assembly. French Guiana elects 1 senator and 1 deputy. In each of the 3 departments exist individuals and small political parties that advocate immediate independence, but their adherents form only

High-Risk Prostate Cancer With Gleason Score 8-10 and PSA Level {<=}15 ng/ mL Treated With Permanent Interstitial Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, L. Christine; Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org; Butler, Wayne M.

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. Ofmore » 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.« less

Nuclear power and probabilistic safety assessment (PSA): past through future applications

NASA Astrophysics Data System (ADS)

Stamatelatos, M. G.; Moieni, P.; Everline, C. J.

1995-03-01

Nuclear power reactor safety in the United States is about to enter a new era -- an era of risk- based management and risk-based regulation. First, there was the age of `prescribed safety assessment,' during which a series of design-basis accidents in eight categories of severity, or classes, were postulated and analyzed. Toward the end of that era, it was recognized that `Class 9,' or `beyond design basis,' accidents would need special attention because of the potentially severe health and financial consequences of these accidents. The accident at Three Mile Island showed that sequences of low-consequence, high-frequency events and human errors can be much more risk dominant than the Class 9 accidents. A different form of safety assessment, PSA, emerged and began to gain ground against the deterministic safety establishment. Eventually, this led to the current regulatory requirements for individual plant examinations (IPEs). The IPEs can serve as a basis for risk-based regulation and management, a concept that may ultimately transform the U.S. regulatory process from its traditional deterministic foundations to a process predicated upon PSA. Beyond the possibility of a regulatory environment predicated upon PSA lies the possibility of using PSA as the foundation for managing daily nuclear power plant operations.

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

The French Revolution.

ERIC Educational Resources Information Center

Baltimore City Public Schools, MD.

This outline on the French Revolution is designed to illustrate how this period of French history influenced various aspects of contemporary culture. Four main sections are treated: (1) ideas that led to the Revolution, (2) the reigns of the Bourbon kings, (3) the Revolution, and (4) the rise of Napoleon as a reaction to chaos. A list of 16mm…

Estimate of population coverage with the prostate specific antigen (PSA) test to screen for prostate cancer in a metropolitan area of northern Italy.

PubMed

Russo, A; Autelitano, M; Bellini, A; Bisanti, L

2002-01-01

The use of the prostate specific antigen (PSA) test in the period 1999-2000 in a population of 311 822 men, aged 40 years or more, resident in Milan, Italy, was examined. Data were drawn from the outpatient database of the local health information system. A total of 139 350 PSA tests were used in 83 943 subjects. Overall, 26.9% of the male population aged 40 or older, with no history of prostate cancer, received a PSA test in the 2 year study period. For subjects older than 50 the rate rose to 34%. Results show a high coverage of the male population in northern Italy with screening using the PSA test for prostate cancer.

Patients with elevated serum PSA and indwelling catheter after acute urinary retention: prospective study of 63 patients with 7-year follow-up.

PubMed

Kravchick, Sergey; Bunkin, Igor; Peled, Ronit; Yulish, Eugeny; Ben-Dor, David; Kravchenko, Yakov; Cytron, Shmuel

2007-10-01

Elevated PSA value in the presence of an indwelling catheter is still an enigma. The aims of this prospective study were: to investigate the reliability of elevated PSA levels in patients with normal DRE and indwelling catheter after AUR; to assess the impact of preoperative TRUS-biopsy in detecting prostate cancer in such circumstances; to estimate the crucial duration of follow-up period. 63 patients were included in the study. PSA was assessed 5 days after catheter insertion. All patients failed to void without catheter and have been scheduled for surgery. TRUS-biopsy was performed before operation. All patients underwent surgery at least two weeks after prostate biopsies. Postoperative follow-up visits continued for at least 7 years. Biopsies were taken when indicated by persistently elevated PSA or an abnormal DRE. Mean PSA before catheter insertion differed significantly from PSA obtained on the 5(th) day after AUR (p = 0.001). Mean prostate volume calculated on TRUS was 80.5 +/- 28 ml. Mean duration of indwelling catheter placement was 37.8 +/- 7.97 days. Mean delay in operative treatment as a result of preoperative evaluation was 23.548 +/- 2.487 days. Carcinoma was detected in 13 patients, while clinically insignificant cancer was present in 31% (4 patients). It must be also emphasized that 38% of patients with carcinoma were >70 year-old. Preoperative TRUS-biopsy and postoperative pathologic exam diagnosed carcinoma in 5 patients (2 and 3 respectively). During 42 months of 7-year follow-up cancer was revealed in 8 patients. Mean PSA value in the follow-up period was significantly elevated in patients with carcinoma: 5.99 +/- 3.34 v/s 2.34 +/- 1.68 ng/ml (p = 0.007) and was the strongest predictor for cancer detection (p = 0.001). The detection rate of clinically significant cancer on preoperative biopsies postoperative pathologic exam in patients with AUR and indwelling catheter is low. These patients could be safely operated on without any delay. However

Anticancer activities of emetine prodrugs that are proteolytically activated by the prostate specific antigen (PSA) and evaluation of in vivo toxicity of emetine derivatives.

PubMed

Akinboye, Emmanuel S; Rosen, Marc D; Bakare, Oladapo; Denmeade, Samuel R

2017-12-15

Emetine is a small molecule protein synthesis inhibitor that is toxic to all cell types and therefore suitable for complete killing of all types of heterogeneous cancer cells within a tumor. It becomes significantly inactive (non-toxic) when derivatized at its N-2' secondary amine. This provides a strategy for targeting emetine to cancerous tumor without killing normal cells. In this report, PSA activatable peptide prodrugs of emetine were synthesized. To overcome steric hindrances and enhance protease specific cleavage, a 2-stage prodrug activation process was needed to release emetine in cancer cells. In this 2-stage process, emetine prodrug intermediates are coupled to PSA peptide substrate (Ac-His-Ser-Ser-Lys-Leu-Gln) to obtain the full prodrug. Both prodrug intermediates 10 (Ala-Pro-PABC-Emetine) and 14 (Ser-Leu-PABC-Emetine) were evaluated for kinetics of hydrolysis to emetine and potency [Where PABC = p-aminobenzyloxycarbonyl]. While both intermediates quantitatively liberate emetine when incubated under appropriate conditions, upon coupling of PSA substrate to give the full prodrugs, only prodrug 16, the prodrug obtained from 14 was hydrolyzable by PSA. Cytotoxicity studies in PSA producing LNCaP and CWR22Rv1 confirm the activation of the prodrug by PSA with an IC 50 of 75 nM and 59 nM respectively. The cytotoxicity of 16 is significantly reduced in cell lines that do not produce PSA. Further, in vivo toxicity studies are done on these prodrugs and other derivatives of emetine. The results show the significance of conformational modulation in obtaining safe emetine prodrugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-02-01

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

Voluntary Health Registry of French Nationals after the Great East Japan Earthquake, Tsunami, and Fukushima Daiichi Nuclear Power Plant Accident: Methods, Results, Implications, and Feedback.

PubMed

Motreff, Yvon; Pirard, Philippe; Lagrée, Céline; Roudier, Candice; Empereur-Bissonnet, Pascal

2016-06-01

Introduction The 11th of March 2011, a magnitude 9.0 earthquake struck alongside the north-east coast of Honshu Island, Japan, causing a tsunami and a major nuclear accident. The French Institute for Public Health Surveillance (InVS) set up, within one week after the triple catastrophe, an Internet-based registry for French nationals who were in Japan at the time of the disasters. In this string of disasters, in this context of uncertainties about the nuclear risks, the aim of this registry was to facilitate the: (1) realization of further epidemiologic studies, if needed; and (2) contact of people if a medical follow-up was needed. The purpose of this report was to describe how the health registry was set up, what it was used for, and to discuss further utilization and improvements to health registries after disasters. The conception of the questionnaire to register French nationals was based on a form developed as part of the Steering Committee for the management of the post-accident phase in the event of nuclear accident or a radiological emergency situation (CODIRPA) work. The questionnaire was available online. The main objective was achieved since it was theoretically possible to contact again the 1,089 persons who completed the form. According to the data collected on their space-time budget, to the result of internal contamination measured by the French Institute for Radiological Protection and Nuclear Safety (IRSN) and dosimetric expertise published by the World Health Organization (WHO), it was not suitable to conduct an epidemiologic follow-up of adverse effects of exposure to ionizing radiations among them. However, this registry was used to launch a qualitative study on exposure to stress and psychosocial impact of the Great East Japan Earthquake on French nationals who were in Japan in March 2011. Setting a registry after a disaster is a very important step in managing the various consequences of a disaster. This experience showed that it is quickly

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

PubMed

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

2012-12-01

Prostate-specific antigen (PSA) testing for prostate cancer is controversial, with concerning rates of both overscreening and underscreening. 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 for screening. A nationally representative sample of men 57-85 years old without prostate cancer (N = 1169) from the National Social life, Health and Aging Project was analyzed. The independent relationship of validated psychological health scales measuring stress, anxiety, and depression to PSA testing rates was assessed using multivariable logistic regression analyses. PSA screening rates were significantly lower for men with higher perceived stress [odds ratio (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 once those with higher anxiety were less likely to be screened (OR = 0.65, P = 0.04). Conversely, those who visited the doctor 10+ times with higher anxiety were more likely to be screened (OR = 1.71, P = 0.04). Perceived stress significantly lowers PSA screening likelihood, and it seems 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.

Formulation of the bivalent prostate cancer vaccine with surgifoam elicits antigen-specific effector T cells in PSA-transgenic mice.

PubMed

Karan, Dev

2017-10-13

We previously developed and characterized an adenoviral-based prostate cancer vaccine for simultaneous targeting of prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA). We also demonstrated that immunization of mice with the bivalent vaccine (Ad 5 -PSA+PSCA) inhibited the growth of established prostate tumors. However, there are multiple challenges hindering the success of immunological therapies in the clinic. One of the prime concerns has been to overcome the immunological tolerance and maintenance of long-term effector T cells. In this study, we further characterized the use of the bivalent vaccine (Ad 5 -PSA+PSCA) in a transgenic mouse model expressing human PSA in the mouse prostate. We demonstrated the expression of PSA analyzed at the mRNA level (by RT-PCR) and protein level (by immunohistochemistry) in the prostate lobes harvested from the PSA-transgenic (PSA-Tg) mice. We established that the administration of the bivalent vaccine in surgifoam to the PSA-Tg mice induces strong PSA-specific effector CD8 + T cells as measured by IFN-γ secretion and in vitro cytotoxic T-cell assay. Furthermore, the use of surgifoam with Ad 5 -PSA+PSCA vaccine allows multiple boosting vaccinations with a significant increase in antigen-specific CD8 + T cells. These observations suggest that the formulation of the bivalent prostate cancer vaccine (Ad 5 -PSA+PSCA) with surgifoam bypasses the neutralizing antibody response, thus allowing multiple boosting. This formulation is also helpful for inducing an antigen-specific immune response in the presence of self-antigen, and maintains long-term effector CD8 + T cells. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Association between Serum Testosterone and PSA Levels in Middle-Aged Healthy Men from the General Population.

PubMed

Elzanaty, Saad; Rezanezhad, Babak; Dohle, Gert

2017-04-01

The aim of the present study was to evaluate the association between serum testosterone and PSA levels in middle-aged healthy men from the general population. Based on 119 healthy men from the general population, total testosterone and PSA levels were measured. Demographic data regarding BMI, waist-to-hip ratio, smoking, and alcohol consumption were also collected. Men were classified into two groups according to testosterone levels; hypogonadal (testosterone ≤ 12 nmol/l), and eugonadal (testosterone > 12 nmol/l). The mean age of the subjects was 55 years (range 46-60 years). No significant correlation between serum testosterone and PSA levels was found (p = 0.60). PSA levels were similar when compared between hypogonadal and eugonadal men (1.4 µg/l vs. 1.4 µg/l, p = 0.90). When using a multivariate analysis model adjusted for the age of the subjects, BMI, waist-to-hip ratio, smoking, and alcohol consumption, a positive significant association between testosterone and PSA levels was found (β = 0.03, 95 % CI = 0.003-0.062, p = 0.03). Only after adjusted multivariate analysis, our results indicated that testosterone was associated with PSA levels in middle-aged healthy men.

Teaching for Content: Greek Mythology in French.

ERIC Educational Resources Information Center

Giauque, Gerald S.

An intermediate-level university French course in Greek mythology was developed to (1) improve student skills in reading, writing, speaking, and comprehending French, (2) familiarize students with Greek mythology, and (3) prepare students to deal better with allusions to Greek mythology in French literature. The texts used are a French translation…

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

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

PubMed

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

2017-09-10

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

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.

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

Culture Curriculum: French, Level II.

ERIC Educational Resources Information Center

Hall, Ruth Wellman

This teacher's guide to cultural instruction at level 2 integrates materials derived from several sources. The guide is based on: (1) suggestions from "French for Secondary Schools," New York State Education Department; (2) general information concerning the geography, products, industries, regions, cities of France, the French Union, and the city…

Detection of prostate specific antigen (PSA) in human saliva using an ultra-sensitive nanocomposite of graphene nanoplatelets with diblock-co-polymers and Au electrodes.

PubMed

Khan, M S; Dighe, K; Wang, Z; Srivastava, I; Daza, E; Schwartz-Dual, A S; Ghannam, J; Misra, S K; Pan, D

2018-02-26

Prostate-specific antigen (PSA) is a commonly used biomarker for the detection of prostate cancer (PCa) and there are numerous data available for its invasive detection in the serum and whole blood. In this work, an electrochemical sensing method was devised to detect traces of PSA in human saliva using a hybrid nanocomposite of graphene nanoplatelets with diblock co-polymers and Au electrodes (GRP-PS 67 -b-PAA 27 -Au). The pure graphitic composition on filter paper provides significantly high electrical and thermal conductivity while PS 67 -b-PAA 27 makes an amphiphilic bridge between GRP units. The sensor utilizes the binding of an anti-PSA antibody with an antigen-PSA to act as a resistor in a circuit providing an impedance change that in turn allows for the detection and quantification of PSA in saliva samples. A miniaturized electrical impedance analyzer was interfaced with a sensor chip and the data were recorded in real-time using a Bluetooth-enabled module. This fully integrated and optimized sensing device exhibited a wide PSA range of detection from 0.1 pg mL -1 to 100 ng mL -1 (R 2 = 0.963) with a lower limit of detection of 40 fg mL -1 . The performance of the biosensor chip was validated with an enzyme-linked immunosorbent assay technique with a regression coefficient as high as 0.940. The advantages of the newly developed saliva-PSA electrical biosensor over previously reported serum-PSA electrochemical biosensors include a faster response time (3-5 min) to achieve a stable electrical signal for PSA detection, high selectivity, improved sensitivity, no additional requirement of a redox electrolyte for electron exchange and excellent shelf life. The presented sensor is aimed for clinical commercialization to detect PSA in human saliva.

The posterior semantic asymmetry (PSA): An early brain electrical signature of semantic activation from written words.

PubMed

Koppehele-Gossel, Judith; Schnuerch, Robert; Gibbons, Henning

2018-06-06

This study replicates and extends the findings of Koppehele-Gossel, Schnuerch, and Gibbons (2016) of a posterior semantic asymmetry (PSA) in event-related brain potentials (ERPs), which closely tracks the time course and degree of semantic activation from single visual words. This negativity peaked 300 ms after word onset, was derived by subtracting right- from left-side activity, and was larger in a semantic task compared to two non-semantic control tasks. The validity of the PSA in reflecting the effort to activate word meaning was again attested by a negative correlation between the meaning-specific PSA increase and verbal intelligence, even after controlling for nonverbal intelligence. Extending prior work, current source density (CSD) transformation was used. CSD results were consistent with a left temporo-parietal cortical origin of the PSA. Moreover, no PSA was found for pictorial material, suggesting that the component reflects early semantic processing specific to verbal stimuli. Copyright © 2018 Elsevier Inc. All rights reserved.

Year of treatment as independent predictor of relapse-free survival in patients with localized prostate cancer treated with definitive radiotherapy in the PSA era.

PubMed

Kupelian, Patrick; Thames, Howard; Levy, Larry; Horwitz, Eric; Martinez, Alvaro; Michalski, Jeff; Pisansky, Thomas; Sandler, Howard; Shipley, William; Zelefsky, Michael; Zietman, Anthony; Kuban, Deborah

2005-11-01

To study the use of the year of therapy as an independent predictor of outcomes, serving as a proxy for time-related changes in therapy and tumor factors in the treatment of prostate cancer. Accounting for these changes would facilitate the retrospective comparison of outcomes for patients treated in different periods. Nine institutions combined data on 4,537 patients with Stages T1 and T2 adenocarcinoma of the prostate who had a pretherapy prostate-specific antigen (PSA) level and biopsy Gleason score, and who had received > or = 60 Gy external beam radiotherapy without neoadjuvant androgen deprivation or planned adjuvant androgen deprivation. All patients were treated between 1986 and 1995. Two groups were defined: those treated before 1993 (Yr < or = 92) vs. 1993 and after (Yr > or = 93). Patients treated before 1993 had their follow-up truncated to make the follow-up time similar to that for patients treated in 1993 and after. Therefore, the median follow-up time was 6.0 years for both groups (Yr < or = 92 and Yr > or = 93). Two separate biochemical failure endpoints were used. Definition A consisted of the American Society for Therapeutic Radiology Oncology endpoint (three PSA rises backdated, local failure, distant failure, or hormonal therapy). Definition B consisted of PSA level greater than the current nadir plus two, local failure, distant failure, or hormonal therapy administered. Multivariate analyses for factors affecting PSA disease-free survival (PSA-DFS) rates using both endpoints were performed for all cases using the following variables: T stage (T1b, T1c, T2a vs. T2b, T2c), pretreatment PSA (continuous variable), biopsy Gleason score (continuous variable), radiation dose (continuous variable), and year of treatment (continuous variable). The year variable (defined as the current year minus 1960) ranged from 26 to 35. To evaluate the effect of radiation dose, the multivariate analyses were repeated with the 3,897 cases who had received < 72 Gy

The value of multimodality imaging in the investigation of a PSA recurrence after radical prostatectomy in the Irish hospital setting.

PubMed

McLoughlin, L C; Inder, S; Moran, D; O'Rourke, C; Manecksha, R P; Lynch, T H

2018-02-01

The diagnostic evaluation of a PSA recurrence after RP in the Irish hospital setting involves multimodality imaging with MRI, CT, and bone scanning, despite the low diagnostic yield from imaging at low PSA levels. We aim to investigate the value of multimodality imaging in PC patients after RP with a PSA recurrence. Forty-eight patients with a PSA recurrence after RP who underwent multimodality imaging were evaluated. Demographic data, postoperative PSA levels, and imaging studies performed at those levels were evaluated. Eight (21%) MRIs, 6 (33%) CTs, and 4 (9%) bone scans had PCa-specific findings. Three (12%) patients had a positive MRI with a PSA <1.0 ng/ml, while 5 (56%) were positive at PSA ≥1.1 ng/ml (p = 0.05). Zero patient had a positive CT TAP at a PSA level <1.0 ng/ml, while 5 (56%) were positive at levels ≥1.1 ng/ml (p = 0.03). Zero patient had a positive bone at PSA levels <1.0 ng/ml, while 4 (27%) were positive at levels ≥1.1 ng/ml (p = 0.01). The diagnostic yield from multimodality imaging, and isotope bone scanning in particular, in PSA levels <1.0 ng/ml, is low. There is a statistically significant increase in the frequency of positive findings on CT and bone scanning at PSA levels ≥1.1 ng/ml. MRI alone is of investigative value at PSA <1.0 ng/ml. The indication for CT, MRI, or isotope bone scanning should be carefully correlated with the clinical question and how it will affect further management.

Processing Focus Structure in L1 and L2 French: L2 Proficiency Effects on ERPs

ERIC Educational Resources Information Center

Reichle, Robert V.; Birdsong, David

2014-01-01

This study examined the event-related potentials (ERPs) elicited by focus processing among first language (L1) speakers and second language (L2) learners of French. Participants read wh-questions containing explicit focus marking, followed by responses instantiating contrastive and informational focus. We hypothesized that L2 proficiency would…

Patterns of clinical response to PSA elevation in American Indian/Alaska Native men: a multi-center pilot study.

PubMed

Tilburt, Jon C; Koller, Kathryn; Tiesinga, James J; Wilson, Robin T; Trinh, Anne C; Hill, Kristin; Hall, Ingrid J; Smith, Judith Lee; Ekwueme, Donatus U; Petersen, Wesley O

2013-11-01

To assess clinical treatment patterns and response times among American Indian/Alaska Native men with a newly elevated PSA. We retrospectively identified men ages 50-80 receiving care in one of three tribally-operated clinics in Northern Minnesota, one medical center in Alaska, and who had an incident PSA elevation (> 4 ng/ml) in a specified time period. A clinical response was considered timely if it was documented as occurring within 90 days of the incident PSA elevation. Among 82 AI/AN men identified from medical records with an incident PSA elevation, 49 (60%) received a timely clinical response, while 18 (22%) had no documented clinical response. One in five AI/AN men in our study had no documented clinical action following an incident PSA elevation. Although a pilot study, these findings suggest the need to improve the documentation, notification, and care following an elevated PSA at clinics serving AI/AN men.

Validation of Association of Genetic Variants at 10q with PSA Levels in Men at High Risk for Prostate Cancer

PubMed Central

Chang, Bao-Li; Hughes, Lucinda; Chen, David Y. T.; Gross, Laura; Ruth, Karen; Giri, Veda N.

2013-01-01

Objectives Men with a family history of prostate cancer and African American men are at increased risk for prostate cancer and stand to benefit from individualized interpretation of PSA to guide screening strategies. The purpose of this study was to validate six previously identified markers among high-risk men enrolled in the Prostate Cancer Risk Assessment Program - a prostate cancer screening study. Patients and Methods Eligibility for PRAP includes men ages 35–69 years with a family history of prostate cancer, any African American male regardless of family history, and men with known BRCA gene mutations. GWAS markers assessed included rs2736098 (5p15.33), rs10993994 (10q11), rs10788160 (10q26), rs11067228 (12q24), rs4430796 (17q12), and rs17632542 (19q13.33). Genotyping methods included either Taqman® SNP Genotyping Assay (Applied Biosystems) or pyrosequencing. Linear regression models were used to evaluate the association between individual markers and log-transformed baseline PSA levels, while adjusting for potential confounders. Results 707 participants (37% Caucasian, 63% African American) with clinical and genotype data were included in the analysis. Rs10788160 (10q26) strongly associated with PSA levels among high-risk Caucasian participants (p<0.01), with a 33.2% increase in PSA level with each A-allele carried. Furthermore, rs10993994 (10q11) demonstrated an association to PSA level (p=0.03) in high-risk Caucasian men, with a 15% increase in PSA with each T-allele carried. A PSA adjustment model based on allele carrier status at rs10788160 and rs10993994 is proposed specific to high-risk Caucasian men. Conclusion Genetic variation at 10q may be particularly important in personalizing interpretation of PSA for high-risk Caucasian men. Such information may have clinical relevance in shared decision-making and individualized prostate cancer screening strategies for high-risk Caucasian men. Further study is warranted. PMID:23937305

The New Planetary Science Archive (PSA): Exploration and Discovery of Scientific Datasets from ESA's Planetary Missions

NASA Astrophysics Data System (ADS)

Heather, David; Besse, Sebastien; Vallat, Claire; Barbarisi, Isa; Arviset, Christophe; De Marchi, Guido; Barthelemy, Maud; Coia, Daniela; Costa, Marc; Docasal, Ruben; Fraga, Diego; Grotheer, Emmanuel; Lim, Tanya; MacFarlane, Alan; Martinez, Santa; Rios, Carlos; Vallejo, Fran; Saiz, Jaime

2017-04-01

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://psa.esa.int. 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. As of the end of 2016, the PSA is hosting data from all of ESA's planetary missions. This includes ESA's first planetary mission Giotto that encountered comet 1P/Halley in 1986 with a flyby at 800km. Science data from Venus Express, Mars Express, Huygens and the SMART-1 mission are also all available at the PSA. The PSA also contains all science data from Rosetta, which explored comet 67P/Churyumov-Gerasimenko and asteroids Steins and Lutetia. The year 2016 has seen the arrival of the ExoMars 2016 data in the archive. In the upcoming years, at least three new projects are foreseen to be fully archived at the PSA. The BepiColombo mission is scheduled for launch in 2018. Following that, the ExoMars Rover Surface Platform (RSP) in 2020, and then the JUpiter ICy moon Explorer (JUICE). All of these will archive their data in the PSA. In addition, a few ground-based support programmes are also available, especially for the Venus Express and Rosetta missions. 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 customized 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 also be up

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

PubMed Central

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

2014-01-01

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

Management of neutropenic patients in the intensive care unit (NEWBORNS EXCLUDED) recommendations from an expert panel from the French Intensive Care Society (SRLF) with the French Group for Pediatric Intensive Care Emergencies (GFRUP), the French Society of Anesthesia and Intensive Care (SFAR), the French Society of Hematology (SFH), the French Society for Hospital Hygiene (SF2H), and the French Infectious Diseases Society (SPILF).

PubMed

Schnell, David; Azoulay, Elie; Benoit, Dominique; Clouzeau, Benjamin; Demaret, Pierre; Ducassou, Stéphane; Frange, Pierre; Lafaurie, Matthieu; Legrand, Matthieu; Meert, Anne-Pascale; Mokart, Djamel; Naudin, Jérôme; Pene, Frédéric; Rabbat, Antoine; Raffoux, Emmanuel; Ribaud, Patricia; Richard, Jean-Christophe; Vincent, François; Zahar, Jean-Ralph; Darmon, Michael

2016-12-01

Neutropenia is defined by either an absolute or functional defect (acute myeloid leukemia or myelodysplastic syndrome) of polymorphonuclear neutrophils and is associated with high risk of specific complications that may require intensive care unit (ICU) admission. Specificities in the management of critically ill neutropenic patients prompted the establishment of guidelines dedicated to intensivists. These recommendations were drawn up by a panel of experts brought together by the French Intensive Care Society in collaboration with the French Group for Pediatric Intensive Care Emergencies, the French Society of Anesthesia and Intensive Care, the French Society of Hematology, the French Society for Hospital Hygiene, and the French Infectious Diseases Society. Literature review and formulation of recommendations were performed using the Grading of Recommendations Assessment, Development and Evaluation system. Each recommendation was then evaluated and rated by each expert using a methodology derived from the RAND/UCLA Appropriateness Method. Six fields are covered by the provided recommendations: (1) ICU admission and prognosis, (2) protective isolation and prophylaxis, (3) management of acute respiratory failure, (4) organ failure and organ support, (5) antibiotic management and source control, and (6) hematological management. Most of the provided recommendations are obtained from low levels of evidence, however, suggesting a need for additional studies. Seven recommendations were, however, associated with high level of evidences and are related to protective isolation, diagnostic workup of acute respiratory failure, medical management, and timing surgery in patients with typhlitis.

U.S.-French Commercial Ties

DTIC Science & Technology

2008-05-19

Z39-18 U.S.- French Commercial Ties Summary U.S. commercial ties with France are extensive, mutually profitable, and growing. With over $1.2 billion...relationship. The scale of sales of U.S.-owned companies operating in France and French -owned companies operating in the United States outweighs trade...with investments valued at $65.9 billion was the number one foreign investor in France . During that same year, French companies had direct

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.

Long-term prediction of prostate cancer diagnosis and death using PSA and obesity related anthropometrics at early middle age: data from the malmö preventive project.

PubMed

Assel, Melissa J; Gerdtsson, Axel; Thorek, Daniel L J; Carlsson, Sigrid V; Malm, Johan; Scardino, Peter T; Vickers, Andrew; Lilja, Hans; Ulmert, David

2018-01-19

To evaluate whether anthropometric parameters add to PSA measurements in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and death. After adjusting for PSA, both BMI and weight were significantly associated with an increased risk of PCa death with the odds of a death corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p = 0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs did not meaningfully increase with the addition of weight or BMI to prediction models including PSA. In 1974 to 1986, 22,444 Swedish men aged 44 to 50 enrolled in Malmö Preventive Project, Sweden, and provided blood samples and anthropometric data. Rates of PSA screening in the cohort were very low. Documentation of PCa diagnosis and disease-specific death up to 2014 was retrieved through national registries. Among men with anthropometric measurements available at baseline, a total of 1692 men diagnosed with PCa were matched to 4190 controls, and 464 men who died of disease were matched to 1390 controls. Multivariable conditional logistic regression was used to determine whether diagnosis or death from PCa were associated with weight and body mass index (BMI) at adulthood after adjusting for PSA. Men with higher BMI and weight at early middle age have an increased risk of PCa diagnosis and death after adjusting for PSA. However, in a multi-variable numerical statistical model, BMI and weight do not importantly improve the predictive accuracy of PSA. Risk-stratification of screening should be based on PSA without reference to anthropometrics.

Driving in French for American Tourists.

ERIC Educational Resources Information Center

Grosse, Philip

This booklet is intended to assist the English-speaking tourist driving in a French-speaking country to communicate with service station attendants and to read road signs. The booklet is divided into three sections: (1) an English-French listing of parts of the car and useful expressions; (2) common European road signs; and (3) a French-English…

Prostate cancer screening by prostate-specific antigen (PSA); a relevant approach for the small population of the Cayman Islands.

PubMed

Jyoti, Shravana Kumar; Blacke, Camille; Patil, Pallavi; Amblihalli, Vibha P; Nicholson, Amanda

2018-01-01

The common tool for diagnosing prostate cancer is prostate-specific antigen (PSA), but the high sensitivity and low specificity of PSA testing are the problems in clinical practice. There are no proper guidelines to investigate the suspected prostate cancer in the Cayman Islands. We correlated PSA levels with the incidence of prostate cancers by tissue diagnosis and proposed logical protocol for prostate screening by using PSA test in this small population. A total of 165 Afro Caribbean individuals who had prostate biopsy done after the investigations for PSA levels from year 2005 to 2015 were studied retrospectively. The patients were divided into subgroups by baseline PSA levels as follows: <4, 4.1-10, 10.1-20, 20.1-50, 50.1-100, and >100 ng/mL and were correlated to the age and presence of cancer. Benign lesions had lower PSA levels compared to cancer which generally had higher values. Only three cases that had less than 4 ng/mg were turned out to be malignant. When PSA value was more than 100 ng/mL, all the cases were malignant. Between PSA values of 4-100 ng/mL, the probability of cancer diagnosis was 56.71% (76 cancers out of 134 in this range). Limitation of PSA testing has the risk of over diagnosis and the resultant negative biopsies owing to poor specificity. Whereas the cutoff limit for cancer diagnosis still remains 4 ng/mL from our study, most of the patients can be assured of benign lesion below this level and thus morbidity associated with the biopsy can be prevented. When the PSA value is greater than 100 ng, biopsy procedure was mandatory as there were 100% cancers above this level. On the background of vast literature linking PSA to prostate cancer and its difficulty in implementing in clinical practice, we studied literature of this conflicting and complex topic and tried to bring relevant protocols to the small population of Cayman Islands for the screening of prostate cancer. In this study, a total of 165 Afro Caribbean individuals who

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

PubMed

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

2016-09-01

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

NADiA® ProsVue™ PSA Slope Is an Independent Prognostic Marker for Identifying Men at Reduced Risk for Clinical Recurrence of Prostate Cancer after Radical Prostatectomy

PubMed Central

Moul, Judd W.; Lilja, Hans; Semmes, O. John; Lance, Raymond S.; Vessella, Robert L.; Fleisher, Martin; Mazzola, Clarisse; Sarno, Mark J.; Stevens, Barbara; Klem, Robert E.; McDermed, Jonathan E.; Triebell, Melissa T.; Adams, Thomas H.

2015-01-01

Objectives To validate the hypothesis that men displaying serum PSA slopes ≤2.0 pg/mL/month postprostatectomy, measured with a new immuno-PCR diagnostic test (NADiA® ProsVue™) were at a reduced risk of clinical recurrence as determined by positive biopsy, imaging or death due to prostate cancer. Methods From 4 clinical sites, we selected a cohort of 304 men followed up to 17.6 years postprostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/month against established risk factors to identify men at very low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analysis. Results The univariate HR (95% CI) of a PSA slope >2.0 pg/mL/month was 18.3 (10.6–31.8), compared to a slope ≤2.0 pg/mL/month (P <0.0001). Median disease-free survival was 4.8 years versus >10 years in the 2 groups (P <0.0001). Multivariate HR for PSA slope with the covariates of preprostatectomy PSA, pathologic stage and Gleason score was 9.8 (5.4–17.8), an 89.8% risk reduction, for men with PSA slopes ≤2.0 pg/mL/month (P <0.0001). Gleason Score (<7 vs. ≥7) was the only other significant predictor (HR 5.4, 2.1–13.8, P = 0.0004). Conclusions Clinical recurrence following radical prostatectomy is often difficult to predict since established factors do not reliably stratify risk. We demonstrate that a NADiA ProsVue slope ≤2.0 pg/mL/month postprostatectomy is prognostic for reduced risk of prostate cancer recurrence and adds predictive power to established risk factors. PMID:23107099

A comparative Study of Aptasensor Vs Immunosensor for Label-Free PSA Cancer Detection on GQDs-AuNRs Modified Screen-Printed Electrodes.

PubMed

Srivastava, Monika; Nirala, Narsingh R; Srivastava, S K; Prakash, Rajiv

2018-01-31

Label-free and sensitive detection of PSA (Prostate Specific Antigen) is still a big challenge in the arena of prostate cancer diagnosis in males. We present a comparative study for label-free PSA aptasensor and PSA immunosensor for the PSA-specific monoclonal antibody, based on graphene quantum dots-gold nanorods (GQDs-AuNRs) modified screen-printed electrodes. GQDs-AuNRs composite has been synthesized and used as an electro-active material, which shows fast electron transfer and catalytic property. Aptamer or anti-PSA has immobilized onto the surface of modified screen printed electrodes. Three techniques are used simultaneously, viz. cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedence spectroscopy (EIS) to investigate the analytical performance of both PSA aptasensor and PSA immunosensor with its corresponding PSA antigen. Under optimum conditions, both sensors show comparable results with an almost same limit of detection (LOD) of 0.14 ng mL -1 . The results developed with aptasensor and anti-PSA is also checked through the detection of PSA in real samples with acceptable results. Our study suggests some advantages of aptasensor in terms of better stability, simplicity and cost effectiveness. Further our present work shows enormous potential of our developed sensors for real application using voltammetric and EIS techniques simultaneous to get reliable detection of the disease.

Validation of CESAR Thermal-hydraulic Module of ASTEC V1.2 Code on BETHSY Experiments

NASA Astrophysics Data System (ADS)

Tregoures, Nicolas; Bandini, Giacomino; Foucher, Laurent; Fleurot, Joëlle; Meloni, Paride

The ASTEC V1 system code is being jointly developed by the French Institut de Radioprotection et Sûreté Nucléaire (IRSN) and the German Gesellschaft für Anlagen und ReaktorSicherheit (GRS) to address severe accident sequences in a nuclear power plant. Thermal-hydraulics in primary and secondary system is addressed by the CESAR module. The aim of this paper is to present the validation of the CESAR module, from the ASTEC V1.2 version, on the basis of well instrumented and qualified integral experiments carried out in the BETHSY facility (CEA, France), which simulates a French 900 MWe PWR reactor. Three tests have been thoroughly investigated with CESAR: the loss of coolant 9.1b test (OECD ISP N° 27), the loss of feedwater 5.2e test, and the multiple steam generator tube rupture 4.3b test. In the present paper, the results of the code for the three analyzed tests are presented in comparison with the experimental data. The thermal-hydraulic behavior of the BETHSY facility during the transient phase is well reproduced by CESAR: the occurrence of major events and the time evolution of main thermal-hydraulic parameters of both primary and secondary circuits are well predicted.

NO2 possible effects on human health in French Guiana

NASA Astrophysics Data System (ADS)

Gobinddass, Marie-Line; Dendele, Beatrice; Molinie, Jack; panechou-pulcherie, Kathy; Gatineau, Alexandre

2016-04-01

The International Agency for Research on Cancer (IARC) recently declared air pollution carcinogenic to humans. Humans are continuously exposed to nitrogen dioxide (NO2) emissions, a strong oxidizing pollutant commonly found in urban air and homes with unvented combustion appliances. Children and Individuals with asthma have been reported to be more sensitive to NO2exposure. Long-term exposure to NO2 pollution has been reported to induce defective pulmonary function, inflammation, irritations, respiratory infections like bronchitis, lung fibrosis, asthma exacerbation and an increase in inhalational allergies. Pollution peaks are responsible for older people premature death in city. According to W H O guideline values for NO2 emissions, a 1-hour level of 200 μg/m3 (0.1 ppm) and daily annual average of 40 μg/m3 (0.02 ppm) can be a real danger to human health. In general, current exposures in Europe are below this range. However, climate warming changes NO2 emissions and can become a real public health problem in few years. We will study here the temporal series of NO2 variation from data measurement campaigns of 2010 and 2014 in Cayenne city, the French Guiana capital. In this urban zone, NO2 is mainly created by cars traffic. Only 40% comes from combustion in thermal electric plan. A statistical approach will be used to compare NO2 Cayenne level to the daily and the annual threshold. Finally the NO2 evolution related to the climate warming and the growth of road traffic in French Guiana for the next year will be discussed.

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

PubMed Central

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

2014-01-01

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

Contribution of 11C-Choline PET/CT in prostate carcinoma biochemical relapse with serum PSA level below 1 ng/ml.

PubMed

Gómez-de la Fuente, F J; Martínez-Rodríguez, I; de Arcocha-Torres, M; Quirce, R; Jiménez-Bonilla, J; Martínez-Amador, N; Banzo, I

11 C-choline PET/CT has demonstrated good results in the restaging of prostate cancer (PCa) with high serum prostate specific antigen (PSA), but its use in patients with low serum PSA is controversial. Our aim was to evaluate the contribution of 11 C-choline PET/CT in patients with PCa, biochemical relapse and PSA <1 ng/ml. Fifty consecutive patients (mean age: 65.9±5.6 years) with biochemical relapse of PCa and serum PSA <1ng/ml were evaluated retrospectively. PET/CT was performed 20min after intravenous administration of 555-740 MBq of 11 C-choline. Minimum follow up time was 30 months. Twenty-one out of 50 patients (42%) had an abnormal 11 C-choline PET/CT. In 7 out of 21 patients (14%) tumor was confirmed (4 in prostatic bed, 4 in pelvic lymph nodes, 2 in mediastinal lymph nodes and one synchronous sigmoid carcinoma), and in all cases the initial therapeutic planning was modified. In 2 patients (4%) subsequent tests diagnosed a benign disease (one sarcoidosis, one tuberculosis sequelae) and in 3 patients (6%) they ruled out pathology. The other 9 patients (18%) had no further assessment (7 mediastinal and 4 pelvic lymph nodes). Twenty-nine out of 50 patients (58%) had a normal PET/CT. At 30 months, follow up recurrence was confirmed only in 2 of these patients. 11 C-choline PET/CT proved its usefulness in demonstrating tumor in 14% of patients with BR of PCa and serum PSA <1ng/ml, with therapeutic implications. In 4% of patients a benign condition was detected. A normal 11 C-choline PET/CT was associated with a very low rate of recurrence at 30 months. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: evidence from patients in Northwestern China.

PubMed

Wu, Kai-Jie; Pei, Xin-Qi; Tian, Ge; Wu, Da-Peng; Fan, Jin-Hai; Jiang, Yu-Mei; He, Da-Lin

2018-01-01

Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS). In these patients, the median of TTN was 17 weeks. Patients with TTN ≥17 weeks had a longer response time to chemotherapy compared to TTN <17 weeks (42.83 vs 21.50 weeks, P < 0.001). The time to PSA progression in patients with TTN ≥17 weeks was 11.44 weeks compared to 5.63 weeks when TTN was <17 weeks. We found several factors to be associated with OS, including TTN (hazard ratio [HR]: 3.937, 95% confidence interval [CI]: 1.502-10.309, P = 0.005), PSA level at the diagnosis of cancer (HR: 4.337, 95% CI: 1.616-11.645, P = 0.004), duration of initial androgen deprivation therapy (HR: 2.982, 95% CI: 1.104-8.045, P = 0.031), neutrophil-to-lymphocyte ratio (HR: 3.963, 95% CI: 1.380-11.384, P = 0.011), and total PSA response (Class 1 [<0 response] compared to Class 2 [0-50% response], HR: 3.978, 95% CI: 1.278-12.387, P = 0.017). In conclusion, TTN of PSA remains an important prognostic marker in predicting therapeutic outcome in Chinese population who receive chemotherapy for mCRPC and have >50% PSA remission.

[Survival is associated with time to reach PSA nadir (DAN) and the ratio DAN/nadir value after androgen deprivation for prostate cancer].

PubMed

Gagnat, A; Larré, S; Fromont, G; Pirès, C; Doré, B; Irani, J

2011-05-01

The objective of this study was to assess the prognostic decrease rate of PSA in patients treated with androgen suppression (AS) for prostate cancer (PCa). We identified in our database CaP patients with histologically documented, treated with SA alone and for whom vital status with a minimum follow-up of 6 months (except death beforehand) was established. Patient characteristics and CaP and PSA at baseline, PSA nadir, time of reaching the nadir PSA (DAN) and the ratio of the DAN/nadir value (ratio DAN/Nadir) were analyzed in relation to progression-free survival, specific and overall survival. One hundred ninety eight patients met the inclusion criteria and the median was 61.5 months (range 4.8 to 233). The median PSA at the start of the SA were 37.1 ng/mL and the median nadir PSA was 0.48 ng/mL. The median time to progression was 23.6 months. The median specific and overall survivals were 94 and 78 months, respectively. In univariate analysis, predictors of progression-free survival were PSA before SA, PSA nadir, DAN, DAN ratio/nadir, Gleason score, the percentage of core positive prostate biopsy and the status of bone scintigraphy. Except for PSA before SA which was no longer significant, predictors of specific and overall survival were similar and added the biochemical response (decrease of more than 50% of PSA) to a second hormonal manipulation during the biological progression. In multivariate analysis, the nadir PSA and the ratio DAN/Nadir remained significant predictors. These results have confirmed in one hand the predictive value of survival in patients DAN SA for CaP: achieving faster nadir PSA was associated with shorter survival. They have introduced in the other hand the new concept of DAN/Nadir PSA which provides independent prognostic information. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Validation of a French-Canadian adaptation of the Intuitive Eating Scale-2 for the adult population.

PubMed

Carbonneau, Elise; Carbonneau, Noémie; Lamarche, Benoît; Provencher, Véronique; Bégin, Catherine; Bradette-Laplante, Maude; Laramée, Catherine; Lemieux, Simone

2016-10-01

Intuitive eating is an adaptive eating style based on the reliance on physiological cues to determine when, what, and how much to eat. The Intuitive Eating Scale-2 (IES-2) is a validated four-subscale tool measuring the degree of adherence to intuitive eating principles. The present series of studies aimed at evaluating the psychometric properties of a French-Canadian adaptation of the IES-2 for the adult population. The factor structure, the reliability (internal consistency and test-retest), the construct validity, and the discriminant validity were evaluated in 334 women and 75 men from the Province of Québec, Canada, across two studies. A confirmatory factor analysis upheld that the four-factor structure of the original IES-2 was adequate for the present sample of French-Canadians. The scale demonstrated adequate internal consistency and test-retest reliability. Construct validity evidence was obtained with the significant associations between intuitive eating and psychological and eating-related variables. Intuitive eating was negatively associated with eating disorder symptomatology and with food- and weight-preoccupation, and positively associated with body-esteem and well-being. The French-Canadian IES-2 was also able to discriminate between genders and body mass index categories. The properties of this new version of the IES-2 are demonstrative of a reliable and valid tool to assess intuitive eating in the French-Canadian adult population of the Province of Québec. Copyright © 2016 Elsevier Ltd. All rights reserved.

PSA discriminator influence on (222)Rn efficiency detection in waters by liquid scintillation counting.

PubMed

Stojković, Ivana; Todorović, Nataša; Nikolov, Jovana; Tenjović, Branislava

2016-06-01

A procedure for the (222)Rn determination in aqueous samples using liquid scintillation counting (LSC) was evaluated and optimized. Measurements were performed by ultra-low background spectrometer Quantulus 1220™ equipped with PSA (Pulse Shape Analysis) circuit which discriminates alpha/beta spectra. Since calibration procedure is carried out with (226)Ra standard, which has both alpha and beta progenies, it is clear that PSA discriminator has vital importance in order to provide precise spectra separation. Improvement of calibration procedure was done through investigation of PSA discriminator level and, consequentially, the activity of (226)Ra calibration standard influence on (222)Rn efficiency detection. Quench effects on generated spectra i.e. determination of radon efficiency detection were also investigated with quench calibration curve obtained. Radon determination in waters based on modified procedure according to the activity of (226)Ra standard used, dependent on PSA setup, was evaluated with prepared (226)Ra solution samples and drinking water samples with assessment of measurement uncertainty variation included. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-term prediction of prostate cancer diagnosis and death using PSA and obesity related anthropometrics at early middle age: data from the malmö preventive project

PubMed Central

Assel, Melissa J.; Gerdtsson, Axel; Thorek, Daniel L.J.; Carlsson, Sigrid V.; Malm, Johan; Scardino, Peter T.; Vickers, Andrew; Lilja, Hans; Ulmert, David

2018-01-01

Objectives To evaluate whether anthropometric parameters add to PSA measurements in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and death. Results After adjusting for PSA, both BMI and weight were significantly associated with an increased risk of PCa death with the odds of a death corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p = 0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs did not meaningfully increase with the addition of weight or BMI to prediction models including PSA. Materials and Methods In 1974 to 1986, 22,444 Swedish men aged 44 to 50 enrolled in Malmö Preventive Project, Sweden, and provided blood samples and anthropometric data. Rates of PSA screening in the cohort were very low. Documentation of PCa diagnosis and disease-specific death up to 2014 was retrieved through national registries. Among men with anthropometric measurements available at baseline, a total of 1692 men diagnosed with PCa were matched to 4190 controls, and 464 men who died of disease were matched to 1390 controls. Multivariable conditional logistic regression was used to determine whether diagnosis or death from PCa were associated with weight and body mass index (BMI) at adulthood after adjusting for PSA. Conclusions Men with higher BMI and weight at early middle age have an increased risk of PCa diagnosis and death after adjusting for PSA. However, in a multi-variable numerical statistical model, BMI and weight do not importantly improve the predictive accuracy of PSA. Risk-stratification of screening should be based on PSA without reference to anthropometrics. PMID:29464033

The Growth of Complexity and Accuracy in L2 French: Past Observations and Recent Applications of Developmental Stages

ERIC Educational Resources Information Center

Agren, Malin; Granfeldt, Jonas; Schlyter, Suzanne

2012-01-01

This chapter addresses the question of the growth of accuracy and complexity in L2 French from the perspective of developmental sequences of morphosyntax, developmental stages and linguistic profiling. The six developmental stages for L2 French proposed by Bartning and Schlyter (2004) are presented and exemplified and new results are added to the…

Interoperability in the Planetary Science Archive (PSA)

NASA Astrophysics Data System (ADS)

Rios Diaz, C.

2017-09-01

The protocols and standards currently being supported by the recently released new version of the 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. We explore these protocols in more detail providing scientifically useful examples of their usage within the PSA.

French for Marketing. Using French in Media and Communications.

ERIC Educational Resources Information Center

Batchelor, R. E.; Chebli-Saadi, M.

The textbook, entirely in French, is designed to help prepare anglophone students for French language usage in the media and telecommunications. It is organized according to two major themes. The first part addresses the French of advertising; chapter topics include the actors in advertising (agencies, announcers, supports), forms of advertising,…

TREM2 mutations are rare in a French cohort of patients with frontotemporal dementia.

PubMed

Lattante, Serena; Le Ber, Isabelle; Camuzat, Agnès; Dayan, Sarah; Godard, Chloé; Van Bortel, Inge; De Septenville, Anne; Ciura, Sorana; Brice, Alexis; Kabashi, Edor

2013-10-01

Homozygous mutations in TREM2 have been recently identified by exome sequencing in families presenting with frontotemporal dementia (FTD)-like phenotype. No study has evaluated the exact frequency of TREM2 mutations in cohorts of FTD patients so far. We sequenced TREM2 in 175 patients with pure FTD, mostly French, to test whether mutations could be implicated in the pathogenesis of the disease. No disease-causing mutation was identified in 175 individuals from the French cohort of FTD patients. We did not identify the polymorphism p.R47H (rs75932628), strongly associated with an increased risk of developing Alzheimer's disease. We conclude that TREM2 mutations are extremely rare in patients with pure FTD, although further investigation in larger populations is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

"Pour nos petits Manitobains," Exposure Package for Grade 2 Basic/Conversational French Program.

ERIC Educational Resources Information Center

Manitoba Dept. of Education, Winnipeg. Bureau of French Education.

This guide outlines the Manitoban Department of Education's conversational French-as-a-second-language curriculum for second grade. The program is designed to introduce young children to the French language and culture through the learning of French sounds, vocabulary, and some sentence patterns. An introductory section explains the program's…

Strong association of common variants in the CDKN2A/CDKN2B region with type 2 diabetes in French Europids.

PubMed

Duesing, K; Fatemifar, G; Charpentier, G; Marre, M; Tichet, J; Hercberg, S; Balkau, B; Froguel, P; Gibson, F

2008-05-01

Genome-wide association studies (GWASs) recently identified common variants in the CDKN2A/CDKN2B region on chromosome 9p as being strongly associated with type 2 diabetes. Since these association signals were not picked up by the French-Canadian GWAS, we sought to replicate these findings in the French Europid population and to further characterise the susceptibility variants at this novel locus. We genotyped 20 single nucleotide polymorphisms (SNPs) spanning the CDKN2A/CDKN2B locus in our type 2 diabetes case-control cohort. The association between CDKN2A/CDKN2B SNPs and quantitative metabolic traits was also examined in the normoglycaemic participants comprising the control cohort. We report replication of the strong association of rs10811661 with type 2 diabetes found in the GWASs (P= 3.8 X 10(-7); OR 1.43 [95% CI 1.24-1.64]). The other CDKN2A/CDKN2B susceptibility variant, rs564398, did not attain statistical significance (p = 0.053; OR 1.11 [95% CI 1.00-1.24]) in the present study. We also obtained several additional nominal association signals (p < 0.05) at the CDKN2A/CDKN2B locus; however, only the rs3218018 result (p = 0.002) survived Bonferroni correction for multiple testing (adjusted p = 0.04). Our comprehensive association study of common variation spanning the CDKN2A/CDKN2B locus confirms the strong association between the distal susceptibility variant rs10811661 and type 2 diabetes in the French population. Further genetic and functional studies are required to identify the aetiological variants at this locus and determine the cellular and physiological mechanisms by which they act to modulate type 2 diabetes susceptibility.

Baseline PSA in a Spanish male population aged 40-49 years anticipates detection of prostate cancer.

PubMed

Angulo, J C; Viñas, M A; Gimbernat, H; Fata, F Ramón de; Granados, R; Luján, M

2015-12-01

We researched the usefulness of optimizing prostate cancer (PC) screening in our community using baseline PSA readings in men between 40-49 years of age. A retrospective study was performed that analyzed baseline PSA in the fifth decade of life and its ability to predict the development of PC in a population of Madrid (Spain). An ROC curve was created and a cutoff was proposed. We compared the evolution of PSA from baseline in patients with consecutive readings using the Friedman test. We established baseline PSA ranges with different risks of developing cancer and assessed the diagnostic utility of the annual PSA velocity (PSAV) in this population. Some 4,304 men aged 40-49 years underwent opportunistic screening over the course of 17 years, with at least one serum PSA reading (6,001 readings) and a mean follow-up of 57.1±36.8 months. Of these, 768 underwent biopsy of some organ, and 104 underwent prostate biopsy. Fourteen patients (.33%) were diagnosed with prostate cancer. The median baseline PSA was .74 (.01-58.5) ng/mL for patients without PC and 4.21 (.76-47.4) ng/mL for those with PC. The median time from the reading to diagnosis was 26.8 (1.5-143.8) months. The optimal cutoff for detecting PC was 1.9ng/mL (sensitivity, 92.86%; specificity, 92.54%; PPV, 3.9%; NPV, 99.97%), and the area under the curve was 92.8%. In terms of the repeated reading, the evolution of the PSA showed no statistically significant differences between the patients without cancer (p=.56) and those with cancer (P=.64). However, a PSAV value >.3ng/mL/year revealed high specificity for detecting cancer in this population. A baseline PSA level ≥1.9ng/mL in Spanish men aged 40-49 years predicted the development of PC. This value could therefore be of use for opportunistic screening at an early age. An appropriate follow-up adapted to the risk of this population needs to be defined, but an annual PSAV ≥.3ng/mL/year appears of use for reaching an early diagnosis. Copyright © 2015 AEU

The French Revolution and the French Language: A Paradox?

ERIC Educational Resources Information Center

Djite, Paulin

1992-01-01

Explores the relationship between revolutionary ideals and the subsequent expansion and promotion of the French language. It is shown, through a linguistic and sociopolitical history of the French Revolution and the French language, that there is no incompatibility between the two and that the movement of Francophonie is a continuation of France's…

Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality: The CAP Randomized Clinical Trial.

PubMed

Martin, Richard M; Donovan, Jenny L; Turner, Emma L; Metcalfe, Chris; Young, Grace J; Walsh, Eleanor I; Lane, J Athene; Noble, Sian; Oliver, Steven E; Evans, Simon; Sterne, Jonathan A C; Holding, Peter; Ben-Shlomo, Yoav; Brindle, Peter; Williams, Naomi J; Hill, Elizabeth M; Ng, Siaw Yein; Toole, Jessica; Tazewell, Marta K; Hughes, Laura J; Davies, Charlotte F; Thorn, Joanna C; Down, Elizabeth; Davey Smith, George; Neal, David E; Hamdy, Freddie C

2018-03-06

Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment. To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer-specific mortality. The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016. An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice. Primary outcome: prostate cancer-specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic. Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, -0.013 per 1000 person-years [95% CI, -0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4

Evolution of the prevalence of intestinal parasitic infections among the French armed forces in French Guiana.

PubMed

Christen, Jacques-Robert; Mura, Marie; Roudaut, Gwenaëlle; Drogoul, Anne-Sophie; Demar, Magalie; Briolant, Sébastien; Garnotel, Eric; Simon, Fabrice; Pommier De Santi, Vincent

2016-07-01

Two cross-sectional studies were performed 2 years apart in French military personnel deployed from France to French Guiana. In 2011, military medical centres in French Guiana reported 40 cases of intestinal parasitism in service members returning from illegal gold mining sites in the rainforest. In 2013, 48 out of 132 service members returning from French Guiana after a 4-month mission had eosinophilia and seven were infected with hookworm. A presumptive first-line treatment with albendazole could be the most pragmatic strategy. © International Society of Travel Medicine, 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Trichosanthes kirilowii Exerts Androgenic Activity via Regulation of PSA and KLK2 in 22Rv1 Prostate Cancer Cells.

PubMed

Jeong, Soo-Jin; Choi, Ji-Yoon; Dong, Mi-Sook; Seo, Chang-Seob; Shin, Hyeun-Kyoo

2017-01-01

The androgen comprises a group of hormones that play roles in male reproductive activity as well as personal characteristics. We investigated the androgenic activity of various herbal medicines in human prostate cancer 22Rv1 cells. 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. 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. Taken together, TK-enhanced AR-mediated transcriptional activity might be an attractive candidate drug for treating androgen-related diseases. 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 Type Culture Collection; FBS: fetal bovine serum; PBS: phosphate

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

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

PubMed

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. 11 C-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 11 C-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. 11 C-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.

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

PubMed

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

2015-10-01

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

Avoidance of anticipated regret: the ordering of prostate-specific antigen tests.

PubMed

Sorum, Paul C; Mullet, Etienne; Shim, Junseop; Bonnin-Scaon, Sylvie; Chasseigne, Gérard; Cogneau, Joël

2004-01-01

When making decisions, people are known to try to minimize the regret that would be provoked by unwanted consequences of these decisions. The authors explored the strength and determinants of such anticipated regret in a study of physicians' decisions to order prostate-specific antigen (PSA) tests. 32 US and 33 French primary care physicians indicated the likelihood they would order a PSA for 32 hypothetical men presenting for routine physical exams. They then indicated how much regret they would feel if they found advanced prostate cancer in 12 other patients for whom they had chosen not to order PSAs several years before. The latter patients differed according to age (55, 65, or 75 years), a prior request or not for PSA testing, and no or some irregularity of the prostate on the earlier rectal exam. ANOVA found that regret was higher when the patient had requested a PSA, the prostate was irregular, and the patient was younger. Shape had less effect when the patient had requested a PSA. US physicians had more regret than the French, patient request had a greater impact on the Americans, and increasing patient age reduced regret more among the French. In a 1-way correlation, the regret score was associated with the likelihood of ordering PSAs for both the French (r = 0.64, P < 0.005) and the Americans (r = 0.42, P< 0.02). In a regression analysis too, the regret score was the most important predictor of the likelihood of ordering a PSA (beta = 0.37, P < 0.0001). Regret over failing to diagnose aggressive prostate cancer is associated with a policy of ordering PSAs. This regret appears to be culturally sensitive.

Relationships between serum PSA levels, Gleason scores and results of 68Ga-PSMAPET/CT in patients with recurrent prostate cancer.

PubMed

Sanli, Yasemin; Kuyumcu, Serkan; Sanli, Oner; Buyukkaya, Fikret; İribaş, Ayça; Alcin, Goksel; Darendeliler, Emin; Ozluk, Yasemin; Yildiz, Sevda Ozel; Turkmen, Cüneyt

2017-11-01

To investigate the relationship between serum PSA level, Gleason score of PCa and the outcomes of Ga 68 -PSMA PET/CT in patients with recurrent PCa. A total of 109 consecutive patients (median age 71 years; range 48-89 years) who had PSA recurrence after RP and/or hormonotherapy and/or radiotherapy were included in this study. Local recurrences, lymph node metastasis (pelvic, abdominal and/or supradiaphragmatic), bone metastases (oligometastatic/multimetastatic) and other metastatic sites (lung, liver, brain, etc) were documented. In 91(83.4%) patients at least one lesion characteristic for PCa was detected by 68 Ga-PSMA PET/CT. The median serum total PSA (tPSA) was 6.5 (0.2-640) ng/ml.There was a significant difference between 68 Ga-PSMA PET/CT positive and negative patients in terms of serum total PSA value. No statistical significance was found between positive and negative 68 Ga-PSMA PET/CT findings in terms of Gleason score. Local recurrence was detected in 56 patients. whereas lymph node metastases were demonstrated in 46 patients. Pelvic nodal disease was the most frequent presentation followed by abdominal and supradiaphragmaticnodal involvement. Bone metastases [oligometastasis, (n = 20); multimetastasis, (n = 35)⦌ were also detected in 55 patients. In the ROC analysis for the study cohort, the optimal cut-off value of total serum PSA was determined as 0.67 ng/ml for distinguishing between positive and negative 68 Ga-PSMA PET/CT images, with an area under curve of 0.952 (95% CI 0.911-0.993). 68 Ga-PSMA PET/CT was found to be an effective tool for the detection of recurrent PCa. Even though no relationship was detected between the GS and 68 Ga-PSMA PET/CT findings, serum total PSA values may be used for estimating the likelihood of positive 68 Ga-PSMA PET/CT results.

Potato and french fry consumption and risk of type 2 diabetes in women.

PubMed

Halton, Thomas L; Willett, Walter C; Liu, Simin; Manson, Joann E; Stampfer, Meir J; Hu, Frank B

2006-02-01

Potatoes, a high glycemic form of carbohydrate, are hypothesized to increase insulin resistance and risk of type 2 diabetes. The objective was to examine prospectively the relation between potato consumption and the risk of type 2 diabetes. We conducted a prospective study of 84,555 women in the Nurses' Health Study. At baseline, the women were aged 34-59 y, had no history of chronic disease, and completed a validated food-frequency questionnaire. The participants were followed for 20 y with repeated assessment of diet. We documented 4496 new cases of type 2 diabetes. Potato and french fry consumption were both positively associated with risk of type 2 diabetes after adjustment for age and dietary and nondietary factors. The multivariate relative risk (RR) in a comparison between the highest and the lowest quintile of potato intake was 1.14 (95% CI: 1.02, 1.26; P for trend = 0.009). The multivariate RR in a comparison between the highest and the lowest quintile of french fry intake was 1.21 (95% CI: 1.09, 1.33; P for trend < 0.0001). The RR of type 2 diabetes was 1.18 (95% CI: 1.03, 1.35) for 1 daily serving of potatoes and 1.16 (95% CI: 1.05, 1.29) for 2 weekly servings of french fries. The RR of type 2 diabetes for substituting 1 serving potatoes/d for 1 serving whole grains/d was 1.30 (95% CI: 1.08, 1.57). The association between potato consumption and risk of type 2 diabetes was more pronounced in obese women. Our findings suggest a modest positive association between the consumption of potatoes and the risk of type 2 diabetes in women. This association was more pronounced when potatoes were substituted for whole grains.

French Modular Impoundment: Final Cost and Performance Evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drown, Peter; French, Bill

This report comprises the Final Cost and Performance Report for the Department of Energy Award # EE0007244, the French Modular Impoundment (aka the “French Dam”.) The French Dam is a system of applying precast modular construction to water control structures. The “French Dam” is a term used to cover the construction means/methods used to construct or rehabilitate dams, diversion structures, powerhouses, and other hydraulic structures which impound water and are covered under FDE’s existing IP (Patents # US8414223B2; US9103084B2.)

Prostate-specific antigen (PSA) bounce and other fluctuations: which biochemical relapse definition is least prone to PSA false calls? An analysis of 2030 men treated for prostate cancer with external beam or brachytherapy with or without adjuvant androgen deprivation therapy.

PubMed

Pickles, Tom

2006-04-01

To determine the false call (FC) rate for prostate-specific antigen (PSA) relapse according to nine different PSA relapse definitions after a PSA fluctuation (bounce) has occurred after external beam radiation therapy (EBRT) or brachytherapy, with or without adjuvant androgen deprivation therapy. An analysis of a prospective database of 2030 patients was conducted. Prostate-specific antigen relapse was scored according to the American Society for Therapeutic Radiology and Oncology (ASTRO), Vancouver, threshold + n, and nadir + n definitions for the complete data set and then compared against a truncated data set, with data subsequent to the height of the bounce deleted. The FC rate was calculated for each definition. The bounce rate, with this very liberal definition of bounce, was 58% with EBRT and 84% with brachytherapy. The FC rate was lowest with nadir + 2 and + 3 definitions (2.2% and 1.6%, respectively) and greatest with low-threshold and ASTRO definitions (32% and 18%, respectively). The ASTRO definition was particularly susceptible to FC when androgen deprivation therapy was used with radiation (24%). New definitions of biochemical non-evidence of disease that are more robust than the ASTRO definition have been identified. Those with the least FC rates are the nadir + 2 and nadir + 3 definitions, both of which are being considered to replace the ASTRO definition by the 2005 meeting of the Radiation Therapy Oncology Group-ASTRO consensus panel.

Clinical and Patient-reported Outcomes in Patients with Psoriatic Arthritis (PsA) by Body Surface Area Affected by Psoriasis: Results from the Corrona PsA/Spondyloarthritis Registry.

PubMed

Mease, Philip J; Karki, Chitra; Palmer, Jacqueline B; Etzel, Carol J; Kavanaugh, Arthur; Ritchlin, Christopher T; Malley, Wendi; Herrera, Vivian; Tran, Melody; Greenberg, Jeffrey D

2017-08-01

Psoriatic arthritis (PsA) is commonly comorbid with psoriasis; the extent of skin lesions is a major contributor to psoriatic disease severity/burden. We evaluated whether extent of skin involvement with psoriasis [body surface area (BSA) > 3% vs ≤ 3%] affects overall clinical and patient-reported outcomes (PRO) in patients with PsA. Using the Corrona PsA/Spondyloarthritis Registry, patient characteristics, disease activity, and PRO at registry enrollment were assessed for patients with PsA aged ≥ 18 years with BSA > 3% versus ≤ 3%. Regression models were used to evaluate associations of BSA level with outcome [modified minimal disease activity (MDA), Health Assessment Questionnaire (HAQ) score, patient-reported pain and fatigue, and the Work Productivity and Activity Impairment questionnaire score]. Adjustments were made for age, sex, race, body mass index, disease duration, and history of biologics, disease-modifying antirheumatic drug, and prednisone use. This analysis included 1240 patients with PsA with known BSA level (n = 451, BSA > 3%; n = 789, BSA ≤ 3%). After adjusting for potential confounding variables, patients with BSA > 3% versus ≤ 3% had greater patient-reported pain and fatigue and higher HAQ scores (p = 2.33 × 10 -8 , p = 0.002, and p = 1.21 × 10 -7 , respectively), were 1.7× more likely not to be in modified MDA (95% CI 1.21-2.41, p = 0.002), and were 2.1× more likely to have overall work impairment (1.37-3.21, p = 0.0001). These Corrona Registry data show that substantial skin involvement (BSA > 3%) is associated with greater PsA disease burden, underscoring the importance of assessing and effectively managing psoriasis in patients with PsA because this may be a contributing factor in PsA severity.

PSA-NCAM-Negative Neural Crest Cells Emerging during Neural Induction of Pluripotent Stem Cells Cause Mesodermal Tumors and Unwanted Grafts

PubMed Central

Lee, Dongjin R.; Yoo, Jeong-Eun; Lee, Jae Souk; Park, Sanghyun; Lee, Junwon; Park, Chul-Yong; Ji, Eunhyun; Kim, Han-Soo; Hwang, Dong-Youn; Kim, Dae-Sung; Kim, Dong-Wook

2015-01-01

Summary Tumorigenic potential of human pluripotent stem cells (hPSCs) is an important issue in clinical applications. Despite many efforts, PSC-derived neural precursor cells (NPCs) have repeatedly induced tumors in animal models even though pluripotent cells were not detected. We found that polysialic acid-neural cell adhesion molecule (PSA-NCAM)− cells among the early NPCs caused tumors, whereas PSA-NCAM+ cells were nontumorigenic. Molecular profiling, global gene analysis, and multilineage differentiation of PSA-NCAM− cells confirm that they are multipotent neural crest stem cells (NCSCs) that could differentiate into both ectodermal and mesodermal lineages. Transplantation of PSA-NCAM− cells in a gradient manner mixed with PSA-NCAM+ cells proportionally increased mesodermal tumor formation and unwanted grafts such as PERIPHERIN+ cells or pigmented cells in the rat brain. Therefore, we suggest that NCSCs are a critical target for tumor prevention in hPSC-derived NPCs, and removal of PSA-NCAM− cells eliminates the tumorigenic potential originating from NCSCs after transplantation. PMID:25937368

Tactical UAV’s in the French Army

DTIC Science & Technology

2003-09-02

French Army Technical Service, France 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR... FRENCH ARMY PROJECTION PLATOON Platoon Maintenance Facilities (1st & 2nd echelons) Platoon HQ Launching System Ground Control Station / Remote Data...Tactical UAV’s in the French Army LtCol Pierre-Yves HENRY, Technical Service of the French Army, Program Officer for Battlefield Surveillance Report

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

PubMed Central

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

2012-01-01

Recently, selected reaction monitoring mass spectrometry (SRM-MS) has been more frequently applied to measure low abundance biomarker candidates in tissues and biofluids, owing to its high sensitivity and specificity, simplicity of assay configuration, and exceptional multiplexing capability. In this study, we report for the first time the development of immunoaffinity depletion-based workflows and SRM-MS assays that enable sensitive and accurate quantification of total and free prostate-specific antigen (PSA) in serum without the requirement for specific PSA antibodies. Low ng/mL level detection of both total and free PSA was consistently achieved in both PSA-spiked female serum samples and actual patient serum samples. Moreover, comparison of the results obtained when SRM PSA assays and conventional immunoassays were applied to the same samples showed good correlation in several independent clinical serum sample sets. These results demonstrate that the workflows and SRM assays developed here provide an attractive alternative for reliably measuring candidate biomarkers in human blood, without the need to develop affinity reagents. Furthermore, the simultaneous measurement of multiple biomarkers, including the free and bound forms of PSA, can be performed in a single multiplexed analysis using high-resolution liquid chromatographic separation coupled with SRM-MS. PMID:22846433

Building an information model (with the help of PSL/PSA). [Problem Statement Language/Problem Statement Analyzer

NASA Technical Reports Server (NTRS)

Callender, E. D.; Farny, A. M.

1983-01-01

Problem Statement Language/Problem Statement Analyzer (PSL/PSA) applications, which were once a one-step process in which product system information was immediately translated into PSL statements, have in light of experience been shown to result in inconsistent representations. These shortcomings have prompted the development of an intermediate step, designated the Product System Information Model (PSIM), which provides a basis for the mutual understanding of customer terminology and the formal, conceptual representation of that product system in a PSA data base. The PSIM is initially captured as a paper diagram, followed by formal capture in the PSL/PSA data base.

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

PubMed Central

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

2017-01-01

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

Double PALB2 and BRCA1/BRCA2 mutation carriers are rare in breast cancer and breast-ovarian cancer syndrome families from the French Canadian founder population.

PubMed

Ancot, Frédéric; Arcand, Suzanna L; Mes-Masson, Anne-Marie; Provencher, Diane M; Tonin, Patricia N

2015-06-01

French Canadian families with breast cancer and breast-ovarian cancer syndrome harbor specific BRCA1, BRCA2 and PALB2 germline mutations, which have been attributed to common founders. Mutations in these genes confer an increased risk to breast and ovarian cancers, and have been identified to play a role in and directly interact with the common homologous recombination DNA repair pathways. Our previous study described the case of a female diagnosed with breast cancer at 45 years old, who harbored the PALB2:c.2323C>T [p.Q775X] and BRCA2:c.9004G>A [p.E3002K] germline mutations, which have been found to recur in the French Canadian cancer families. As the frequency of double heterozygous carriers of breast-ovarian cancer susceptibility alleles is unknown, and due to the possibility that there may be implications for genetic counseling and management for these carriers, the present study investigated the co-occurrence of BRCA1/BRCA2 and PALB2 mutations in the French Canadian cancer families. The PALB2:c.2323C>T [p.Q775X] mutation, which is the only PALB2 mutation to have been identified in French Canadian cancer families, was screened in 214 breast cancer cases and 22 breast-ovarian cancer cases from 114 BRCA1/BRCA2 mutation-positive French Canadian breast cancer (n=61) and breast-ovarian cancer (n=53) families using a tailored polymerase chain reaction-based TaqMan® SNP Genotyping Assay. No additional PALB2:c.2323C>T [p.Q775X] mutation carriers were identified among the BRCA1/BRCA2 mutation carriers. The results suggest that carriers of the PALB2:c.2323C>T [p.Q775X] mutation rarely co-occur in French Canadian breast cancer and breast-ovarian cancer families harboring BRCA1 or BRCA2 mutations.

[Prostate cancer screening at Tatebayashi City in Gunma prefecture--results of screening with PSA alone between 2003 and 2005].

PubMed

Nakamura, Toshiyuki; Etsunaga, Toru; Sasaki, Yasushi; Nitta, Takashi; Okugi, Yasunobu; Okazaki, Hiroshi; Katou, Nobuo; Yamamoto, Takumi; Suzuki, Kazuhiro

2007-05-01

Since 2003, a basic health checkup has involved prostate cancer screening with prostate specific antigen (PSA) alone. We investigated the results between 2003 and 2005. Among males aged over 50 years who underwent a basic health checkup, the subjects were those who desired prostate cancer screening. Cancer screening with PSA alone was performed; mass screening or individual screening in hospitals in the city. We employed PSA with respect to age stratification. On the primary screening, written informed consent regarding the analysis of the screening results was obtained. In 2003, there were 15,303 males aged over 50 years in Tatebayashi City. In 2003, 2004, and 2005, 11.8%, 12.2%, and 12.7% of the males underwent PSA screening, respectively. The rate of elevated PSA levels between 2003 and 2005 was 20.6%. Furthermore, 208, 165, and 179 males required secondary screening, and 80.3%, 61.2%, and 55.3% of the males underwent secondary screening, respectively. Of the males who underwent secondary screening, prostate biopsy was performed in 123 (73.2%), 54 (53.5%), and 38 (38.4%). Prostate cancer was detected in 60, 28, and 16 males, respectively. These values corresponded to 3.4%, 1.5%, and 0.8% of the males who underwent primary screening. The incidence of prostate cancer was 1.85% during the 3 years, and 3.2% in males who underwent the initial health checkup. Of 101 males in whom the stage was evaluated, the clinical stage was evaluated as B in 86 (85.1%), C in 9 (8.9%), and D in 6 (5.9%). Of the 101 males, endocrine therapy was performed in 46 (45.5%), surgery in 31 (30.7%), external irradiation in 5 (5.0%), and followup without treatment in 6 (5.9%). In addition, 7 (6.3%) desired treatment in another hospital, and 6 (5.9%) refused treatment. Prostate cancer was detected in 1.85% of males who underwent primary screening between 2003 and 2005. Of 101 males in whom the stage was evaluated, the clinical stage was evaluated as B in 86 (85.1%), and the early treatment of

Investigative clinical study on prostate cancer part II: on the role of the pretreatment total PSA to free testosterone ratio as a marker assessing prostate cancer prognostic groups after radical retropubic prostatectomy.

PubMed

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

2010-01-01

To explore the significance of the pretreatment total prostate-specific antigen (PSA) to free testosterone (FT) ratio (PSA/FT) as a marker for assessing the pathologic Gleason sum (pGS) and levels of tumor extension (pT) in prostatectomy specimens. 128 of 135 consecutive patients diagnosed with prostate cancer underwent radical prostatectomy. Simultaneous pretreatment serum samples were obtained to measure serum total testosterone, FT and total PSA levels. The statistical design of the study included 2 sections: the first part trying to explore the role of the PSA/FT ratio in clustering patients with different pathologic prognostic factors, and the second to investigate the PSA/FT ratio distribution in different groups of patients according to the pathologic stage and pGS of the specimen after radical prostatectomy. The average age was 65.80 (range 51.21-77.26) years, mean PSA was 8.88 (range 1.22-44.27) μg/l, mean FT was 35.32 (range 13.70-69.30) pmol/l, and the mean PSA/FT ratio was 0.27 (range 0.04-1.48). The PSA/FT ratio significantly clustered both the pT and pGS groups. Analysis of variance for the distribution of the PSA/FT ratio was significant for the pT model groups. The mean PSA/FT ratio increased as the tumor extended and grew through the prostate gland (high-stage disease). Analysis of variance for the different distributions of the PSA/FT ratio was significant for all model pGS groups. In our investigation we also found (data not shown) that a PSA/FT ratio of ≥0.40 was strongly correlated with large extensive (pT3b+pT4) and high-grade cancers (pGS8+pGS9). Prostate cancer patients may be classified into 3 different pathologic prognostic groups according to the PSA/FT ratio: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40), and high risk (PSA/FT >0.40 and ≤1.5). The PSA/FT ratio may be considered as the marker expressing different biology groups of prostate cancer patients, and it is strongly associated with pT and p

A Positive Family History as risk factor for Prostate Cancer in a Population-based Study with organized PSA-Screening: Results of the Swiss ERSPC (Aarau)

PubMed Central

Randazzo, Marco; Müller, Alexander; Carlsson, Sigrid; Eberli, Daniel; Huber, Andreas; Grobholz, Rainer; Manka, Lukas; Mortezavi, Ashkan; Sulser, Tullio; Recker, Franz; Kwiatkowski, Maciej

2016-01-01

Objective To assess the value of positive family history (FH) as a risk factor for prostate cancer (PCa) incidence and grade among men undergoing organized PSA-screening in a population-based study. Patients and Methods The study cohort comprised all attendees of the Swiss arm of the European Randomized Study of Screening for Prostate Cancer (ERSPC) with systematic PSA-tests every 4 years. Men reporting first-degree relative(s) diagnosed with PCa were considered to have a positive FH. Biopsy was exclusively PSA-triggered with a threshold of 3 ng/ml. Primary endpoint was PCa diagnosis. Kaplan-Meier and Cox regression analyses were used. Results Of 4,932 attendees with a median age of 60.9 (IQR 57.6–65.1) years, 334 (6.8%) reported a positive FH. Median follow-up duration was 11.6 years (IQR 10.3–13.3). Cumulative PCa incidence was 60/334 (18%, positive FH) and 550/4,598 (12%, negative FH) (OR 1.6, 95% CI 1.2–2.2, p=0.001), respectively. In both groups, most PCa diagnosed had a low grade. There were no significant differences in PSA at diagnosis, biopsy Gleason score or Gleason score on pathologic specimen among men who underwent radical prostatectomy between both groups, respectively. On multivariable analysis, age (HR 1.04, 95% CI 1.02–1.06), baseline PSA (HR 1.13 95% CI 1.12–1.14), and FH (HR 1.6, CI 1.24–2.14) were independent predictors for overall PCa incidence (p<0.0001 each). Only baseline PSA (HR 1.14, 95% CI 1.12–1.16, p<0.0001) was an independent predictor of Gleason score ≥7 PCa on prostate biopsy. The proportion of interval PCa diagnosed in between the screening rounds was non-significantly different. Conclusion Irrespective of the FH status, the current PSA-based screening setting detects the majority of aggressive PCa and missed only a minority of interval cancers with a 4-year screening algorithm. Our results suggest that men with a positive FH are at increased risk for low grade but not aggressive PCa. PMID:26332304

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

PubMed

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

2017-02-01

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. 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. 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). 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.

PSA-stratified detection rates for [68Ga]THP-PSMA, a novel probe for rapid kit-based 68Ga-labeling and PET imaging, in patients with biochemical recurrence after primary therapy for prostate cancer.

PubMed

Derlin, Thorsten; Schmuck, Sebastian; Juhl, Cathleen; Zörgiebel, Johanna; Schneefeld, Sophie M; Walte, Almut C A; Hueper, Katja; von Klot, Christoph A; Henkenberens, Christoph; Christiansen, Hans; Thackeray, James T; Ross, Tobias L; Bengel, Frank M

2018-06-01

[ 68 Ga]Tris(hydroxypyridinone)(THP)-PSMA is a novel radiopharmaceutical for one-step kit-based radiolabelling, based on direct chelation of 68 Ga 3+ at low concentration, room temperature and over a wide pH range, using direct elution from a 68 Ge/ 68 Ga-generator. We evaluated the clinical detection rates of [ 68 Ga]THP-PSMA PET/CT in patients with biochemically recurrent prostate cancer after prostatectomy. Consecutive patients (n=99) referred for evaluation of biochemical relapse of prostate cancer by [ 68 Ga]THP-PSMA PET/CT were analyzed retrospectively. Patients underwent a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified cohorts of positive PET/CT results, standardized uptake values (SUVs) and target-to-background ratios (TBRs) were analyzed, and compared between standard and delayed imaging. At least one lesion suggestive of recurrent or metastatic prostate cancer was identified on PET images in 52 patients (52.5%). Detection rates of [ 68 Ga]THP-PSMA PET/CT increased with increasing PSA level: 94.1% for a PSA value of ≥10 ng/mL, 77.3% for a PSA value of 2 to <10 ng/mL, 54.5% for a PSA value of 1 to <2 ng/mL, 14.3% for a PSA value of 0.5 to <1 ng/mL, 20.0% for a PSA value of >0.2 to <0.5, and 22.2% for a PSA value of 0.01 to 0.2 ng/mL. [ 68 Ga]THP-PSMA uptake (SUVs) in metastases decreased over time, whereas TBRs improved. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 2% of [ 68 Ga]THP-PSMA PET/CT scans. Detection rate was higher in patients with a Gleason score ≥8 (P=0.02) and in patients receiving androgen deprivation therapy (P=0.003). In this study, [ 68 Ga]THP-PSMA PET/CT showed suitable detection rates in patients with biochemical recurrence of prostate cancer and PSA levels ≥ 2 ng /mL. Detections rates were lower than in previous studies evaluating other PSMA ligands, though prospective direct radiotracer comparison studies are mandatory particularly in

GIS Technologies for the Planetary Science Archive (PSA)

NASA Astrophysics Data System (ADS)

Docasal, R.

2017-09-01

In my abstract I try to show how a GIS and 3D visual tools architecture could handle the different approaches for visualizing the spatial info, depending on the nature and shape of the object (planet, satellite, comet...etc) to be mapped in a multi-mission website such as the new PSA.

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…

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China.

PubMed

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-02

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients.

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China

PubMed Central

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-01

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients. PMID:29416625

The combination of ovarian volume and outline has better diagnostic accuracy than prostate-specific antigen (PSA) concentrations in women with polycystic ovarian syndrome (PCOs).

PubMed

Bili, Eleni; Bili, Authors Eleni; Dampala, Kaliopi; Iakovou, Ioannis; Tsolakidis, Dimitrios; Giannakou, Anastasia; Tarlatzis, Basil C

2014-08-01

The aim of this study was to determine the performance of prostate specific antigen (PSA) and ultrasound parameters, such as ovarian volume and outline, in the diagnosis of polycystic ovary syndrome (PCOS). This prospective, observational, case-controlled study included 43 women with PCOS, and 40 controls. Between day 3 and 5 of the menstrual cycle, fasting serum samples were collected and transvaginal ultrasound was performed. The diagnostic performance of each parameter [total PSA (tPSA), total-to-free PSA ratio (tPSA:fPSA), ovarian volume, ovarian outline] was estimated by means of receiver operating characteristic (ROC) analysis, along with area under the curve (AUC), threshold, sensitivity, specificity as well as positive (+) and negative (-) likelihood ratios (LRs). Multivariate logistical regression models, using ovarian volume and ovarian outline, were constructed. The tPSA and tPSA:fPSA ratio resulted in AUC of 0.74 and 0.70, respectively, with moderate specificity/sensitivity and insufficient LR+/- values. In the multivariate logistic regression model, the combination of ovarian volume and outline had a sensitivity of 97.7% and a specificity of 97.5% in the diagnosis of PCOS, with +LR and -LR values of 39.1 and 0.02, respectively. In women with PCOS, tPSA and tPSA:fPSA ratio have similar diagnostic performance. The use of a multivariate logistic regression model, incorporating ovarian volume and outline, offers very good diagnostic accuracy in distinguishing women with PCOS patients from controls. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Comparing Written Competency in Core French and French Immersion Graduates

ERIC Educational Resources Information Center

Lappin-Fortin, Kerry

2014-01-01

Few studies have compared the written competency of French immersion students and their core French peers, and research on these learners at a postsecondary level is even scarcer. My corpus consists of writing samples from 255 students from both backgrounds beginning a university course in French language. The writing proficiency of core French…

The Renewal of the French Amphibious Doctrine

DTIC Science & Technology

2003-01-01

The forces ashore must be sustained and supported by fires. These requirements may seem obvious, but in the case of the French armed forces, the new...0 The Renewal of the French Amphibious Doctrine EWS 2003 Subject Area Topical Issues THE RENEWAL OF THE FRENCH AMPHIBIOUS DOCTRINE CG#2...FACAD: Major Ralston Submitted by Capt L.Danigo, Troupes de Marine. France Report Documentation Page Form

Teaching, Learning, and Developing L2 French Sociolinguistic Competence: A Sociocultural Perspective

ERIC Educational Resources Information Center

van Compernolle, Remi A.; Williams, Lawrence

2012-01-01

The study reported in this article investigates the development of sociolinguistic competence among second-year (US university-level) L2 learners of French who were given systematic instruction on sociolinguistic variation as part of their normal coursework. We focus on the variable use of the negative morpheme "ne" in verbal negation. Drawing…

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caster, Joseph M.; Falchook, Aaron D.; Hendrix, Laura H.

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 biopsymore » 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

Light-regulated translation of chloroplast proteins. I. Transcripts of psaA-psaB, psbA, and rbcL are associated with polysomes in dark-grown and illuminated barley seedlings

PubMed Central

1988-01-01

We have previously observed (Klein, R. R., and J. E. Mullet, 1986, J. Biol. Chem. 261:11138-11145) that translation of two 65-70-kD chlorophyll a-apoproteins of Photosystem I (gene products of psaA and psaB) and a 32-kD quinone-binding protein of Photosystem II (gene product of psbA) was not detected in plastids of dark-grown barley seedlings even though transcripts for these proteins were present. In the present study it was found that nearly all of the psaA-psaB transcripts in plastids of dark-grown plants were associated with membrane-bound polysomes. Membrane-associated polysomes from plastids of dark-grown plants synthesized the 65-70-kD chlorophyll a-apoproteins at low levels when added to a homologous in vitro translation extract capable of translation elongation. However, when etioplast membranes were disrupted with detergent, in vitro synthesis of the 65-70-kD chlorophyll a-apoproteins increased to levels observed with polysomes of plastids from illuminated plants. These results suggest that synthesis of the chlorophyll a-apoproteins of Photosystem I is arrested on membrane-bound polysomes at the level of polypeptide chain elongation. In addition to the selective activation of chlorophyll a- apoprotein translation, illumination also caused an increase in chloroplast polysomes (membrane-associated and stromal) and induced a recruitment of psbA and rbcL transcripts into chloroplast polysomes. These results indicate that in conjunction with the selective activation of chlorophyll a-apoprotein elongation, illumination also caused a general stimulation of chloroplast translation initiation. PMID:3339092

Identification of the psaA Gene, Coding for Pneumococcal Surface Adhesin A, in Viridans Group Streptococci other than Streptococcus pneumoniae

PubMed Central

Jado, Isabel; Fenoll, Asunción; Casal, Julio; Pérez, Amalia

2001-01-01

The gene encoding the pneumococcal surface adhesin A (PsaA) protein has been identified in three different viridans group streptococcal species. Comparative studies of the psaA gene identified in different pneumococcal isolates by sequencing PCR products showed a high degree of conservation among these strains. PsaA is encoded by an open reading frame of 930 bp. The analysis of this fragment in Streptococcus mitis, Streptococcus oralis, and Streptococcus anginosus strains revealed a sequence identity of 95, 94, and 90%, respectively, to the corresponding open reading frame of the previously reported Streptococcus pneumoniae serotype 6B strain. Our results confirm that psaA is present and detectable in heterologous bacterial species. The possible implications of these results for the suitability and potential use of PsaA in the identification and diagnosis of pneumococcal diseases are discussed. PMID:11527799

PSA-NCAM expression in the teleost optic tectum is related to ecological niche and use of vision in finding food.

PubMed

Labak, I; Pavić, V; Zjalić, M; Blažetić, S; Viljetić, B; Merdić, E; Heffer, M

2017-08-01

In this study, tangential migration and neuronal connectivity organization were analysed in the optic tectum of seven different teleosts through the expression of polysialylated neural cell adhesion molecule (PSA-NCAM) in response to ecological niche and use of vision. Reduced PSA-NCAM expression in rainbow trout Oncorhynchus mykiss optic tectum occurred in efferent layers, while in pike Esox lucius and zebrafish Danio rerio it occurred in afferent and efferent layers. Zander Sander lucioperca and European eel Anguilla anguilla had very low PSA-NCAM expression in all tectal layers except in the stratum marginale. Common carp Cyprinus carpio and wels catfish Silurus glanis had the same intensity of PSA-NCAM expression in all tectal layers. The optic tectum of all studied fishes was also a site of tangential migration with sustained PSA-NCAM and c-series ganglioside expression. Anti-c-series ganglioside immunoreactivity was observed in all tectal layers of all analysed fishes, even in layers where PSA-NCAM expression was reduced. Since the optic tectum is indispensable for visually guided prey capture, stabilization of synaptic contact and decrease of neurogenesis and tangential migration in the visual map are an expected adjustment to ecological niche. The authors hypothesize that this stabilization would probably be achieved by down-regulation of PSA-NCAM rather than c-series of ganglioside. © 2017 The Fisheries Society of the British Isles.

Minimally Informative Prior Distributions for PSA

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 themore » 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

Cognate Awareness in French Immersion Students: Contributions to Grade 2 Reading Comprehension

ERIC Educational Resources Information Center

Hipfner-Boucher, Kathleen; Pasquarella, Adrian; Chen, Xi; Deacon, S. Hélène

2016-01-01

Cognate awareness is the ability to recognize the cognate relationship between words in two etymologically related languages. The current study examined the development of cognate awareness and its contribution to French (second language) reading comprehension among Canadian French immersion children. Eighty-one students were tested at the end of…

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

PubMed

Pron, G

2015-01-01

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

French for Business: A Case Study.

ERIC Educational Resources Information Center

McCullough, Brenda

The paper discusses the development and evolution of the French for Business undergraduate language course at Oregon State University, focusing on: (1) instructor preparation; (2) course structure; (3) course content; (4) the business student as teacher and mentor; (5) cultural exchanges with French-speaking business students; (6) oral and written…

An examination of the factor structure and sex invariance of a French translation of the Body Appreciation Scale-2 in university students.

PubMed

Kertechian, Sevag; Swami, Viren

2017-06-01

The Body Appreciation Scale-2 (BAS-2) is a measure of positive body image that has been found that have a one-dimensional factor structure in a number of different cultural groups. Here, we examined the factor structure and sex-based measurement invariance of a French translation of the BAS-2. A total of 652 university students (age M=21.33, SD=3.18) completed a newly-translated French version of the BAS-2. Exploratory factor analyses with a randomly selected split-half subsample revealed that the BAS-2 had a one-dimensional factor structure in both sexes. Confirmatory factor analyses with a second split-half subsample indicated that the one-dimensional factor structure had adequate fit following modifications and was invariant across sex. French BAS-2 scores had adequate internal consistency and men had significantly higher body appreciation than women (ds=.16-.23). These results provide preliminary support for the factorial validity of the French BAS-2. Copyright © 2017 Elsevier Ltd. All rights reserved.

Longitudinal tracking of subpopulation dynamics and molecular changes during LNCaP cell castration and identification of inhibitors that could target the PSA-/lo castration-resistant cells.

PubMed

Rycaj, Kiera; Cho, Eun Jeong; Liu, Xin; Chao, Hsueh-Ping; Liu, Bigang; Li, Qiuhui; Devkota, Ashwini K; Zhang, Dingxiao; Chen, Xin; Moore, John; Dalby, Kevin N; Tang, Dean G

2016-03-22

We have recently demonstrated that the undifferentiated PSA-/lo prostate cancer (PCa) cell population harbors self-renewing long-term tumor-propagating cells that are refractory to castration, thus representing a therapeutic target. Our goals here are, by using the same lineage-tracing reporter system, to track the dynamic changes of PSA-/lo and PSA+ cells upon castration in vitro, investigate the molecular changes accompanying persistent castration, and develop large numbers of PSA-/lo PCa cells for drug screening. To these ends, we treated LNCaP cells infected with the PSAP-GFP reporter with three regimens of castration, i.e., CDSS, CDSS plus bicalutamide, and MDV3100 continuously for up to ~21 months. We observed that in the first ~7 months, castration led to time-dependent increases in PSA-/lo cells, loss of AR and PSA expression, increased expression of cancer stem cell markers, and many other molecular changes. Meanwhile, castrated LNCaP cells became resistant to high concentrations of MDV3100, chemotherapeutic drugs, and other agents. However, targeted and medium-throughput library screening identified several kinase (e.g., IGF-1R, AKT, PI3K/mTOR, Syk, GSK3) inhibitors as well as the BCL2 inhibitor that could effectively sensitize the LNCaP-CRPC cells to killing. Of interest, LNCaP cells castrated for >7 months showed evidence of cyclic changes in AR and the mTOR/AKT signaling pathways potentially involving epigenetic mechanisms. These observations indicate that castration elicits numerous molecular changes and leads to enrichment of PSA-/lo PCa cells. The ability to generate large numbers of PSA-/lo PCa cells should allow future high-throughput screening to identify novel therapeutics that specifically target this population.

Risk assessment models to evaluate the necessity of prostate biopsies in North Chinese patients with 4-50 ng/mL PSA.

PubMed

Zhao, Jing; Liu, Shuai; Gao, Dexuan; Ding, Sentai; Niu, Zhihong; Zhang, Hui; Huang, Zhilong; Qiu, Juhui; Li, Qing; Li, Ning; Xie, Fang; Cui, Jilei; Lu, Jiaju

2017-02-07

Prostate-specific antigen (PSA) is widely used for prostate cancer screening, but low specificity results in high false positive rates of prostate biopsies. To develop new risk assessment models to overcome the diagnostic limitation of PSA and reduce unnecessary prostate biopsies in North Chinese patients with 4-50 ng/mL PSA. A total of 702 patients in seven hospitals with 4-10 and 10-50 ng/mL PSA, respectively, who had undergone transrectal ultrasound-guided prostate biopsies, were assessed. Analysis-modeling stage for several clinical indexes related to prostate cancer and renal function was carried out. Multiple logistic regression analyses were used to develop new risk assessment models of prostate cancer for both PSA level ranges 4-10 and 10-50 ng/mL. External validation stage of the new models was performed to assess the necessity of biopsy. The new models for both PSA ranges performed significantly better than PSA for detecting prostate cancers. Both models showed higher areas under the curves (0.937 and 0.873, respectively) compared with PSA alone (0.624 and 0.595), at pre-determined cut-off values of 0.1067 and 0.6183, respectively. Patients above the cut-off values were recommended for immediate biopsy, while the others were actively observed. External validation of the models showed significantly increased detection rates for prostate cancer (4-10 ng/mL group, 39.29% vs 17.79%, p=0.006; 10-50 ng/mL group, 71.83% vs 50.0%, p=0.015). We developed risk assessment models for North Chinese patients with 4-50 ng/mL PSA to reduce unnecessary prostate biopsies and increase the detection rate of prostate cancer.

Left Dislocation in Near-Native French

ERIC Educational Resources Information Center

Donaldson, Bryan

2011-01-01

The present study is concerned with the upper limits of SLA--specifically, mastery of the syntax-discourse interface in successful endstate learners of second-language (L2) French (near-native speakers). Left dislocation (LD) is a syntactic means of structuring spoken French discourse by marking topic. Its use requires speakers to coordinate…

Gender Differences in Motivation to Learn French

ERIC Educational Resources Information Center

Kissau, Scott

2006-01-01

There is concern among second language educators in Canada that male students are losing interest in studying French as a second language (FSL). In response, in the fall of 2003, a study was conducted to investigate gender differences in second language (L2) motivation among Grade 9 core French students. Building upon the traditional model of L2…

Invitation Refusals in Cameroon French and Hexagonal French

ERIC Educational Resources Information Center

Farenkia, Bernard Mulo

2015-01-01

Descriptions of regional pragmatic variation in French are lacking to date the focus has been on a limited range of speech acts, including apologies, requests, compliments and responses to compliments. The present paper, a systematic analysis of invitation refusals across regional varieties of French, is designed to add to the research on…

The impact of sociodemographic factors and PSA screening among low-income Black and White men: data from the Southern Community Cohort Study.

PubMed

Moses, K A; Zhao, Z; Bi, Y; Acquaye, J; Holmes, A; Blot, W J; Fowke, J H

2017-12-01

Variation in PSA screening is a potential source of disparity in prostate cancer survival, particularly among underserved populations. We sought to examine the impact of race and socioeconomic status (SES) on receipt of PSA testing among low-income men. Black (n=22 167) and White (n=9588) men aged ⩾40 years completed a baseline questionnaire from 2002 to 2009 as part of the Southern Community Cohort Study. Men reported whether they had ever received PSA testing and had testing within the prior 12 months. To evaluate the associations between SES, race and receipt of PSA testing, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from the multivariable logistic models where age, household income, insurance status, marital status, body mass index and educational level were adjusted. Black men were younger, had a lower income, less attained education and were more likely to be unmarried and uninsured (all P<0.001). Percentages of men having ever received PSA testing rose from <40% under the age of 45 years to ~90% above the age of 65 years, with Whites >50 more likely than Blacks to have received testing. Lower SES was significantly associated with less receipt of PSA testing in both groups. After adjustment for SES, White men had significantly lower odds of PSA testing (OR 0.81; 95% CI: 0.76-0.87). Greater PSA testing among White than Black men over the age of 50 years in this low-income population appears to be mainly a consequence of SES. Strategies for PSA screening may benefit from tailoring to the social circumstances of the men being screened.

An endoglycosidase-assisted LC-MS/MS-based strategy for the analysis of site-specific core-fucosylation of low-concentrated glycoproteins in human serum using prostate-specific antigen (PSA) as example.

PubMed

Lang, Robert; Leinenbach, Andreas; Karl, Johann; Swiatek-de Lange, Magdalena; Kobold, Uwe; Vogeser, Michael

2018-05-01

Recently, site-specific fucosylation of glycoproteins has attracted attention as it can be associated with several types of cancers including prostate cancer. However, individual glycoproteins, which might serve as potential cancer markers, often are very low-concentrated in complex serum matrices and distinct glycan structures are hard to detect by immunoassays. Here, we present a mass spectrometry-based strategy for the simultaneous analysis of core-fucosylated and total prostate-specific antigen (PSA) in human serum in the low ng/ml concentration range. Sample preparation comprised an immunoaffinity capture step to enrich total PSA from human serum using anti-PSA antibody coated magnetic beads followed by consecutive two-step on-bead partial deglycosylation with endoglycosidase F3 and tryptic digestion prior to LC-MS/MS analysis. The method was shown to be linear from 0.5 to 60 ng/ml total PSA concentrations and allows the simultaneous quantification of core-fucosylated PSA down to 1 ng/ml and total PSA lower than 0.5 ng/ml. The imprecision of the method over two days ranged from 9.7-23.2% for core-fucosylated PSA and 10.3-18.3% for total PSA depending on the PSA level. The feasibility of the method in native sera was shown using three human specimens. To our knowledge, this is the first MS-based method for quantification of core-fucosylated PSA in the low ng/ml concentration range in human serum. This method could be used in large patient cohorts as core-fucosylated PSA may be a diagnostic biomarker for the differentiation of prostate cancer and other prostatic diseases, such as benign prostatic hyperplasia (BPH). Furthermore, the described strategy could be used to monitor potential changes in site-specific core-fucosylation of other low-concentrated glycoproteins, which could serve as more specific markers ("marker refinement") in cancer research. Copyright © 2018 Elsevier B.V. All rights reserved.

PSA velocity does not aid the detection of prostate cancer in men with a prior negative biopsy: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden and Rotterdam, Netherlands

PubMed Central

Vickers, Andrew J.; Wolters, Tineke; Savage, Caroline J.; Cronin, Angel M.; O’Brien, M. Frank; Roobol, Monique J.; Aus, Gunnar; Scardino, Peter T.; Hugosson, Jonas; Schröder, Fritz H.; Lilja, Hans

2012-01-01

Purpose Prostate specific antigen (PSA) velocity has been proposed as a marker to aid detection of prostate cancer. We sought to determine whether PSA velocity could predict the results of repeat biopsy in men with persistently elevated PSA after initial negative biopsy. Materials and Methods We identified 1,837 men who participated in the Göteborg or Rotterdam section of the European Randomized Screening study of Prostate Cancer (ERSPC), and who had one or more subsequent prostate biopsies after an initial negative finding. We evaluated whether PSA velocity improved predictive accuracy beyond that of PSA alone. Results There were a total of 2579 repeat biopsies, of which 363 (14%) were positive for prostate cancer, and 44 (1.7%) were high grade (Gleason score ≥7). Although PSA velocity was statistically associated with cancer risk (p<0.001), it had very low predictive accuracy (area-under-the-curve [AUC] of 0.55). There was some evidence that PSA velocity improved AUC compared to PSA for high grade cancer. However, the small increase in risk associated with high PSA velocity – from 1.7 % to 2.8% as velocity increased from 0 to 1 ng / ml / year - is of questionable clinical relevance. Conclusions Men with a prior negative biopsy have a lower risk for prostate cancer at subsequent biopsies, with high grade disease particularly rare. We found little evidence to support the use of PSA velocity to aid decisions about repeat biopsy for prostate cancer. PMID:20643434

Object Clitics and Their Omission in Child L2 French: The Contributions of Processing Limitations and L1 Transfer

ERIC Educational Resources Information Center

Gruter, Theres; Crago, Martha

2012-01-01

This article explores the widely documented difficulty with object clitics in the acquisition of French. The study investigates the effects of L1 transfer and processing limitations on the production and comprehension of object clitics in child L2 learners of French with different L1 backgrounds (Chinese, Spanish). The Spanish-speaking learners…

Understanding L2 French Teaching Strategies in a Non-Target Language Classroom Context

ERIC Educational Resources Information Center

Sun, Peijian; Yuan, Rui; Teng, Lin

2015-01-01

This research explored the congruence and disparity between teachers' and students' attitudes towards French as a second language (L2) teaching strategies in a non-target language classroom context in the USA. The findings suggest students' and teachers' attitudes towards the direct and indirect teaching strategies were generally consistent, but…

Validation of the French translation-adaptation of the impact of cancer questionnaire version 2 (IOCv2) in a breast cancer survivor population.

PubMed

Blanchin, Myriam; Dauchy, Sarah; Cano, Alejandra; Brédart, Anne; Aaronson, Neil K; Hardouin, Jean-Benoit

2015-07-29

The Impact of Cancer version 2 (IOCv2) was designed to assess the physical and psychosocial health experience of cancer survivors through its positive and negative impacts. Although the IOCv2 is available in English and Dutch, it has not yet been validated for use in French-speaking populations. The current study was undertaken to provide a comprehensive assessment of the reliability and validity of the French language version of the IOCv2 in a sample of breast cancer survivors. An adapted French version of the IOCv2 as well as demographic and medical information were completed by 243 women to validate the factor structure divergent/divergent validities and reliability. Concurrent validity was assessed by correlating the IOCv2 scales with measures from the SF-12, PostTraumatic Growth Inventory and Fear of Cancer Recurrence Inventory. The French version of the IOCv2 supports the structure of the original version, with four positive impact dimensions and four negative impact dimensions. This result was suggested by the good fit of the confirmatory factor analysis and the adequate reliability revealed by Cronbach's alpha coefficients and other psychometric indices. The concurrent validity analysis revealed patterns of association between IOCv2 scale scores and other measures. Unlike the original version, a structure with a Positive Impact domain consisting in the IOCv2 positive dimensions and a Negative Impact domain consisting in the negative ones has not been clearly evidenced in this study. The limited practical use of the conditional dimensions Employment Concerns and Relationship Concerns, whether the patient is partnered or not, did not make possible to provide evidence of validity and reliability of these dimensions as the subsets of sample to work with were not large enough. The scores of these conditional dimensions have to be used with full knowledge of the facts of this limitation of the study. Integrating IOCv2 into studies will contribute to evaluate the

Reading Speed of Contracted French Braille

ERIC Educational Resources Information Center

Laroche, Louise; Boule, Jacinthe; Wittich, Walter

2012-01-01

This study was designed to address three hypotheses: (1) The reading speed of both readers of French braille and readers of French print will be faster in the silent condition; however, this gain in speed will be larger for print readers; (2) Individuals who acquired braille before age 10 will display faster reading speeds at lower error rates…

MMPI-2 Profile of French Transsexuals: The Role of Sociodemographic and Clinical Factors. A cross-sectional design.

PubMed

Bonierbale, Mireille; Baumstarck, Karine; Maquigneau, Aurélie; Gorin-Lazard, Audrey; Boyer, Laurent; Loundou, Anderson; Auquier, Pascal; Lançon, Christophe

2016-04-12

The assessment of co-existing psychological and psychiatric disorders is advocated in the Standards of Care for the health of transsexual people. This study aimed to determine the psychopathological characteristics of transsexuals based on a large sample of French individuals and to identify whether these characteristics differed according to the individual's sociodemographic or clinical characteristics. The aim of this study was to determine the psychopathological characteristics of transsexuals from a large sample of French individuals and whether these differed by sociodemographic or clinical characteristics. This cross-sectional study was conducted in a French public university hospital. The inclusion criteria were 18 years or older, diagnosis of gender dysphoria, and eligibility for a standardized sex reassignment procedure. Personality characteristics were assessed using the Minnesota Multiphasic Personality Inventory 2 (MMPI-2). A total of 108 individuals provided a valid MMPI-2 between January 2007 and December 2010. The final sample had a median age of 31 years and included 54 (50%) Female-to-Male individuals. In multivariate models, hormonal therapy status was significantly related to the scales of MMPI-2 (Psychasthenia and Masculinity/Femininity). Personality assessment can help a multidisciplinary gender dysphoria team detect potential psychopathological factors of vulnerability.

Negation in Near-Native French: Variation and Sociolinguistic Competence

ERIC Educational Resources Information Center

Donaldson, Bryan

2017-01-01

This study investigated how adult second language (L2) speakers of French with near-native proficiency realize verbal negation, a well-known sociolinguistic variable in contemporary spoken French. Data included 10 spontaneous informal conversations between near-native speakers of French and native speakers (NSs) closely acquainted with them.…

A method for optimum PSA setting in the absence of a pure α or β emitter and its application in the determination of (237)Np/(233)Pa.

PubMed

Feng, Xiao-gui; He, Qian-ge; Wang, Jian-chen; Chen, Jing

2014-11-01

In the application of liquid scintillation counting (LSC), the α/β discrimination is carried out with the function of pulse shape analysis (PSA), which requires the setting of the optimum PSA level. The optimum PSA are usually determined by the generation of cross-over plots, whereby a pair of vials, one containing a pure α emitter and the other a pure β emitter, is counted. However, in some cases such as the determination of (237)Np/(233)Pa, a pure α emitter or a pure β emitter is not available. Therefore, we have developed a new approach to set the optimum PSA by measuring the sample itself of mixed α/β emitters. The count rate of the sample in the α-multi-channel analyzer changes monotonically with the increase of the PSA, and there is always an inflection point which is related to the optimum PSA. By fitting the data near the inflection point with the function y=ax(3)+bx(2)+cx+d, we can obtain the optimum PSA as -b/(3a), which can be used to determine the radioactivity of (237)Np/(233)Pa. The results obtained with this new approach were in good agreement with those obtained by HPGe γ spectrometry that was calibrated with an LSC sample of (237)Np/(233)Pa under a radioactive secular equilibrium. The new approach is promising to be used in simultaneous determination of gross α and β emitters, especially in the absence of a pure α or β emitter. Copyright © 2014 Elsevier Ltd. All rights reserved.

Use of prostate-specific antigen (PSA) to measure semen exposure resulting from male condom failures: implications for contraceptive efficacy and the prevention of sexually transmitted disease.

PubMed

Walsh, Terri L; Frezieres, Ron G; Peacock, Karen; Nelson, Anita L; Clark, Virginia A; Bernstein, Leslie; Wraxall, Brian G D

2003-02-01

Accurate measurement of semen exposure resulting from condom failures can refine public health messages and improve predictions of condom efficacy in preventing pregnancy and HIV transmission. Eight hundred and thirty couples enrolled in a condom efficacy study were asked to collect a baseline sample of ejaculate from the inside of the first study condom they used and to collect a postcoital vaginal sample whenever a study condom broke or slipped off during intercourse. All samples were quantitatively tested for prostate-specific antigen (PSA), a substance found only in human semen, using rocket immunoelectrophoresis, and inspected microscopically for presence of sperm. Sixty-eight baseline ejaculate samples collected from the inside of the first study condom by couples who subsequently experienced a condom failure averaged 13.4 microg PSA per swab and 79% of the samples averaged one or more sperm per high power field (hpf). Seventy-nine postcoital vaginal samples obtained after a condom break averaged 5.7 microg PSA per swab and only 38% averaged one or more sperm per hpf. The PSA results indicated a 50% reduction in semen exposure compared to baseline levels (p = 0.0001). Seventeen samples obtained after a condom slip-off averaged 2.5 microg PSA per swab and none of the samples averaged one or more sperm per hpf. The PSA results indicated an 80% reduction in semen exposure compared to baseline levels (p = 0.0001). Our results suggest that even condoms that fail reduce the risk of pregnancy and the transmission of sexually transmitted disease compared to unprotected intercourse. We also used PSA results to adjust a model designed to predict consistent-use pregnancy rates from condom breakage and slippage data.

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

Predictive simulations and optimization of nanowire field-effect PSA sensors including screening

NASA Astrophysics Data System (ADS)

Baumgartner, Stefan; Heitzinger, Clemens; Vacic, Aleksandar; Reed, Mark A.

2013-06-01

We apply our self-consistent PDE model for the electrical response of field-effect sensors to the 3D simulation of nanowire PSA (prostate-specific antigen) sensors. The charge concentration in the biofunctionalized boundary layer at the semiconductor-electrolyte interface is calculated using the propka algorithm, and the screening of the biomolecules by the free ions in the liquid is modeled by a sensitivity factor. This comprehensive approach yields excellent agreement with experimental current-voltage characteristics without any fitting parameters. Having verified the numerical model in this manner, we study the sensitivity of nanowire PSA sensors by changing device parameters, making it possible to optimize the devices and revealing the attributes of the optimal field-effect sensor.

The French Strategic Dilemma.

DTIC Science & Technology

1984-03-01

THE FRENCH STRATEGIC DILEMMA This paper identifies a basic strategic dilemma for France . On the one hand, French leaders identify the political purpose...are inducing a need for France to provide a more explicit definition of the role of French nuclear weapons in the West European security system. In...defense policy in France . This section concludes with an assessment of the alternative scenarios for the evolution of French defense policy in the 1980s

Impact of Prostate-specific Antigen (PSA) Screening Trials and Revised PSA Screening Guidelines on Rates of Prostate Biopsy and Postbiopsy Complications.

PubMed

Gershman, Boris; Van Houten, Holly K; Herrin, Jeph; Moreira, Daniel M; Kim, Simon P; Shah, Nilay D; Karnes, R Jeffrey

2017-01-01

Prostate biopsy and postbiopsy complications represent important risks of prostate-specific antigen (PSA) screening. Although landmark randomized trials and updated guidelines have challenged routine PSA screening, it is unclear whether these publications have affected rates of biopsy or postbiopsy complications. To evaluate whether publication of the 2008 and 2012 US Preventive Services Task Force (USPSTF) recommendations, the 2009 European Randomized Study of Screening for Prostate Cancer and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, or the 2013 American Urological Association (AUA) guidelines was associated with changes in rates of biopsy or postbiopsy complications, and to identify predictors of postbiopsy complications. This quasiexperimental study used administrative claims of 5279315 commercially insured US men aged ≥40 yr from 2005 to 2014, of whom 104584 underwent biopsy. Publications on PSA screening. Interrupted time-series analysis was used to evaluate the association of publications with rates of biopsy and 30-d complications. Logistic regression was performed to identify predictors of complications. From 2005 to 2014, biopsy rates fell 33% from 64.1 to 42.8 per 100000 person-months, with immediate reductions following the 2008 USPSTF recommendations (-10.1; 95% confidence interval [CI], -17.1 to -3.0; p<0.001), 2012 USPSTF recommendations (-13.8; 95% CI, -21.0 to -6.7; p<0 .001), and 2013 AUA guidelines (-8.8; 95% CI, -16.7 to -0.92; p=0.03). Concurrently, complication rates decreased 10% from 8.7 to 7.8 per 100000 person-months, with a reduction following the 2012 USPSTF recommendations (-2.5; 95% CI, -4.5 to -0.45; p=0.02). However, the proportion of men undergoing biopsy who experienced complications increased from 14% to 18%, driven by nonsepsis infectious complications (p<0.001). Predictors of complications included prior fluoroquinolone use (odds ratio [OR]: 1.27; 95% CI, 1.22-1.32; p<0.001), anticoagulant use (OR: 1

PSA response to cabazitaxel is associated with improved progression-free survival in metastatic castration-resistant prostate cancer: the non-interventional QoLiTime study.

PubMed

Hammerer, Peter; Al-Batran, Salah-Eddin; Windemuth-Kieselbach, Christine; Keller, Martin; Hofheinz, Ralf-Dieter

2018-03-01

To evaluate the association between prostate-specific antigen (PSA) response and progression-free and overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. Men with mCRPC receiving cabazitaxel (25 mg/m 2 , every 3 weeks) plus oral prednis(ol)one (10 mg/day) were enrolled in the non-interventional, prospective QoLiTime study. Main outcome measures were progression-free survival and overall survival, in all patients and in those who showed a ≥ 50 or a ≥ 30% decrease in PSA relative to baseline after four cycles of cabazitaxel, as well as quality-of-life parameters. Of the 527 men (median age 72 years), 266 received ≥ 4 cycles of cabazitaxel and had PSA response data. After four cycles, 34.6% of men achieved a PSA decrease ≥ 50% and 49.6% a decrease ≥ 30%. Median progression-free survival was 7.7 (95% CI 6.2, 9.5) months, and overall survival was 19.5 (95% CI 16.0, 30.9) months, corresponding to 1-year event rates of 39.4 and 78.8%, respectively. Median progression-free survival was longer in PSA responders versus non-responders (15.7 vs 5.5 months at 50% cut-off; 15.7 vs 5.3 months for 30% cut-off; both P < 0.0001). Overall survival (50% cut-off) was 23.3 months in responders and 16.0 months in non-responders (P = 0.068); corresponding data at the 30% cut-off are 21.7 and 16.0 months (P = 0.057). Overall, 55.4% of men experienced ≥ 1 adverse event, 59.6% of whom had a serious adverse event. PSA response after four cycles of cabazitaxel is associated with improved progression-free survival in men with mCRPC treated with cabazitaxel plus prednis(ol)one.

Validation of the French version of the Child Post-Traumatic Stress Reaction Index: psychometric properties in French speaking school-aged children.

PubMed

Olliac, Bertrand; Birmes, Philippe; Bui, Eric; Allenou, Charlotte; Brunet, Alain; Claudet, Isabelle; Sales de Gauzy, Jérôme; Grandjean, Hélène; Raynaud, Jean-Philippe

2014-01-01

Although the reliable and valid Child Post-Traumatic Stress Reaction Index (CPTS-RI) is a widely used measure of posttraumatic stress disorder (PTSD) symptoms in children, it has not been validated in French-speaking populations. The present study aims to assess the psychometric properties of the CPTS-RI in three samples of French-speaking school-children. Data was obtained from three samples. Sample 1 was composed of 106 children (mean (SD) age = 11.7(0.7), 50% females) victims of an industrial disaster. Sample 2 was composed of 50 children (mean (SD) age = 10.8(2.6), 44% females) who had received an orthopaedic surgical procedure after an accident. Sample 3 was composed of 106 children (mean (SD) age = 11.7(2.2), 44% females) admitted to an emergency department after a road traffic accident. We tested internal consistency using Cronbach's alpha. We examined test-retest reliability using intraclass correlation coefficient. In order to assess the convergent validity of the French version of the CPTS-RI and the Clinician Administered PTS Scale-Child and Adolescent (CAPS-CA), spearman-correlation coefficient was computed. To verify the validity of the cut-off scores, a ROC curve was constructed which evaluated the sensitivity and specificity of each score compared to the diagnosis with the CAPS-CA. We also used principal components analysis with varimax rotation to study the structure of the French version of the CPTS-RI. Cronbach's alpha coefficient was 0.87 for the French version of the CPTS-RI. Two-week test-retest intraclass correlation coefficient (n = 30) was 0.67. The French version of the CPTS-RI was well correlated with the CAPS-CA (r = 0.76, p < 0.001). Taking the CAPS-CA as the diagnostic reference, with a diagnostic cut-off of >24 for the CPTS-RI, the sensitivity and specificities were 100% and 62.6%, respectively. The French version of the CPTS-RI demonstrated a three-factor structure. The CPTS-RI is reliable and valid in French-speaking children.

A trust-region algorithm for the optimization of PSA processes using reduced-order modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarwal, A.; Biegler, L.; Zitney, S.

2009-01-01

The last few decades have seen a considerable increase in the applications of adsorptive gas separation technologies, such as pressure swing adsorption (PSA); the applications range from bulk separations to trace contaminant removal. PSA processes are based on solid-gas equilibrium and operate under periodic transient conditions [1]. Bed models for these processes are therefore defined by coupled nonlinear partial differential and algebraic equations (PDAEs) distributed in space and time with periodic boundary conditions that connect the processing steps together and high nonlinearities arising from non-isothermal effects and nonlinear adsorption isotherms. As a result, the optimization of such systems for eithermore » design or operation represents a significant computational challenge to current nonlinear programming algorithms. Model reduction is a powerful methodology that permits systematic generation of cost-efficient low-order representations of large-scale systems that result from discretization of such PDAEs. In particular, low-dimensional approximations can be obtained from reduced order modeling (ROM) techniques based on proper orthogonal decomposition (POD) and can be used as surrogate models in the optimization problems. In this approach, a representative ensemble of solutions of the dynamic PDAE system is constructed by solving a higher-order discretization of the model using the method of lines, followed by the application of Karhunen-Loeve expansion to derive a small set of empirical eigenfunctions (POD modes). These modes are used as basis functions within a Galerkin's projection framework to derive a low-order DAE system that accurately describes the dominant dynamics of the PDAE system. This approach leads to a DAE system of significantly lower order, thus replacing the one obtained from spatial discretization before and making optimization problem computationally efficient [2]. The ROM methodology has been successfully applied to a 2-bed 4

68Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour.

PubMed

Uprimny, Christian; Kroiss, Alexander Stephan; Decristoforo, Clemens; Fritz, Josef; von Guggenberg, Elisabeth; Kendler, Dorota; Scarpa, Lorenza; di Santo, Gianpaolo; Roig, Llanos Geraldo; Maffey-Steffan, Johanna; Horninger, Wolfgang; Virgolini, Irene Johanna

2017-06-01

Prostate cancer (PC) cells typically show increased expression of prostate-specific membrane antigen (PSMA), which can be visualized by 68 Ga-PSMA-11 PET/CT. The aim of this study was to assess the intensity of 68 Ga-PSMA-11 uptake in the primary tumour and metastases in patients with biopsy-proven PC prior to therapy, and to determine whether a correlation exists between the primary tumour-related 68 Ga-PSMA-11 accumulation and the Gleason score (GS) or prostate-specific antigen (PSA) level. Ninety patients with transrectal ultrasound biopsy-proven PC (GS 6-10; median PSA: 9.7 ng/ml) referred for 68 Ga-PSMA-11 PET/CT were retrospectively analysed. PET images were analysed visually and semiquantitatively by measuring the maximum standardized uptake value (SUV max ). The SUV max of the primary tumour and pathologic lesions suspicious for lymphatic or distant metastases were then compared to the physiologic background activity of normal prostate tissue and gluteal muscle. The SUV max of the primary tumour was assessed in relation to both PSA level and GS. Eighty-two patients (91.1%) demonstrated pathologic tracer accumulation in the primary tumour that exceeded physiologic tracer uptake in normal prostate tissue (median SUV max : 12.5 vs. 3.9). Tumours with GS of 6, 7a (3+4) and 7b (4+3) showed significantly lower 68 Ga-PSMA-11 uptake, with median SUV max of 5.9, 8.3 and 8.2, respectively, compared to patients with GS >7 (median SUV max : 21.2; p < 0.001). PC patients with PSA ≥10.0 ng/ml exhibited significantly higher uptake than those with PSA levels <10.0 ng/ml (median SUV max : 17.6 versus 7.7; p < 0.001). In 24 patients (26.7%), 82 lymph nodes with pathologic tracer accumulation consistent with metastases were detected (median SUV max : 10.6). Eleven patients (12.2%) revealed 55 pathologic osseous lesions suspicious for bone metastases (median SUV max : 11.6). The GS and PSA level correlated with the intensity of tracer accumulation in the primary

People’s War: The French in Indochina

DTIC Science & Technology

1990-04-02

AUTHOR: Thomas L. Phelps, Lt Col, USAF TITLE: People’s War: The French in Indochina FORMAT: Individual Study Project DATE: 2 April 1990 PAGES: 47...though opposed to French control, often had close economic and social ties to France . Vietnamese leaders influenced by socialist or communist ideas wanted...benefits of Indochina and left the political administration of the region to France . However, French difficulties increased because the Japanese

The French Revolution on Film: American and French Perspectives

ERIC Educational Resources Information Center

Harison, Casey

2005-01-01

It is not hard to locate negative or condescending images of the French Revolution in aspects of popular American culture, including film. Despite a handful of instances where nuanced or ambiguous "messages" may be identified, the number of American film interpretations of the French Revolution that might be judged historically…

French Dictionaries. Series: Specialised Bibliographies.

ERIC Educational Resources Information Center

Klaar, R. M.

This is a list of French monolingual, French-English and English-French dictionaries available in December 1975. Dictionaries of etymology, phonetics, place names, proper names, and slang are included, as well as dictionaries for children and dictionaries of Belgian, Canadian, and Swiss French. Most other specialized dictionaries, encyclopedias,…

Reduction in PSA messenger-RNA expression and clinical recurrence in patients with prostatic cancer undergoing neoadjuvant therapy before radical prostatectomy

PubMed Central

Grasso, Marco; Lania, Caterina; Blanco, Salvatore; Baruffi, Marco; Mocellin, Simone

2004-01-01

Background We assessed the incidence of micro-metastases at surgical margins (SM) and pelvic lymph nodes (LN) in patients submitted to radical retropubic prostatectomy (RP) after neoadjuvant therapy (NT) or to RP alone. We compared traditional staging to molecular detection of PSA using Taqman-based quantitative real-time PCR (qrt-PCR) never used before for this purpose. Methods 29 patients were assigned to NT plus RP (arm A) or RP alone (arm B). Pelvic LN were dissected for qrt-PCR analysis, together with right and left lateral SM. Results 64,3% patients of arm B and 26.6% of arm A had evidence of PSA mRNA expression in LN and/or SM. 17,2% patients, all of arm B, had biochemical recurrence. Conclusions Qrt-PCR may be more sensitive, compared to conventional histology, in identifying presence of viable prostate carcinoma cells in SM and LN. Gene expression of PSA in surgical periprostatic samples might be considered as a novel and reliable indicator of minimal residual disease after NT. PMID:15104791

L2 Reading Research and Pedagogical Considerations in the Teaching of French and Francophone Theater

ERIC Educational Resources Information Center

Edwards, Carole; Taylor, Alan M.

2012-01-01

Little research on improving second language (L2) reading comprehension of French and francophone theater has been conducted. This study provides insight into enhancing L2 comprehension of drama by combining L2 research with examples from L'accent grave by Jacques Prevert, Ton beau capitaine by Simone Schwarz-Bart (1987), Un Touareg s'est marie a…

Screening UBQLN-2 in French frontotemporal lobar degeneration and frontotemporal lobar degeneration-amyotrophic lateral sclerosis patients.

PubMed

Lattante, Serena; Le Ber, Isabelle; Camuzat, Agnès; Pariente, Jérémie; Brice, Alexis; Kabashi, Edor

2013-08-01

The ubiquilin-2 gene (UBQLN-2) is the only amyotrophic lateral sclerosis (ALS)-related gene mapping on the X chromosome. Mutations in the PXX domain of UBQLN-2 have been first described in ALS patients with a mutational frequency of 2.6% in familial ALS cases with no evidence of male-to-male transmission. Different populations have been further tested with mutations largely distributed in the gene and lower frequency of positive cases. To determine the genetic contribution of UBQLN-2 in frontotemporal lobar degeneration (FTLD) and FTLD-ALS, we screened a cohort of 136 French patients, identifying a missense variant (c.1006A>G; p.T336A) in 1 FTLD patient whose biological relevance to disease is questionable. We conclude that UBQLN-2 mutations related to ALS/FTLD are extremely rare in French FTLD and FTLD-ALS patients and should not be analyzed systematically. Copyright © 2013. Published by Elsevier Inc.

MMPI-2 Profile of French Transsexuals: The Role of Sociodemographic and Clinical Factors. A cross-sectional design

PubMed Central

Bonierbale, Mireille; Baumstarck, Karine; Maquigneau, Aurélie; Gorin-Lazard, Audrey; Boyer, Laurent; Loundou, Anderson; Auquier, Pascal; Lançon, Christophe

2016-01-01

The assessment of co-existing psychological and psychiatric disorders is advocated in the Standards of Care for the health of transsexual people. This study aimed to determine the psychopathological characteristics of transsexuals based on a large sample of French individuals and to identify whether these characteristics differed according to the individual’s sociodemographic or clinical characteristics. The aim of this study was to determine the psychopathological characteristics of transsexuals from a large sample of French individuals and whether these differed by sociodemographic or clinical characteristics. This cross-sectional study was conducted in a French public university hospital. The inclusion criteria were 18 years or older, diagnosis of gender dysphoria, and eligibility for a standardized sex reassignment procedure. Personality characteristics were assessed using the Minnesota Multiphasic Personality Inventory 2 (MMPI-2). A total of 108 individuals provided a valid MMPI-2 between January 2007 and December 2010. The final sample had a median age of 31 years and included 54 (50%) Female-to-Male individuals. In multivariate models, hormonal therapy status was significantly related to the scales of MMPI-2 (Psychasthenia and Masculinity/Femininity). Personality assessment can help a multidisciplinary gender dysphoria team detect potential psychopathological factors of vulnerability. PMID:27068099

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

PubMed

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

2014-06-10

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

Percent free prostate-specific antigen for prostate cancer diagnosis in Chinese men with a PSA of 4.0-10.0 ng/mL: Results from the Chinese Prostate Cancer Consortium.

PubMed

Chen, Rui; Xie, Liping; Cai, Xiaobing; Huang, Yiran; Zhou, Liqun; Ma, Lulin; Gao, Xu; Xu, Chuanliang; Ren, Shancheng; Shao, Pengfei; Xu, Danfeng; Xu, Kexin; Ye, Zhangqun; Liu, Chunxiao; Ye, Dingwei; Lu, Li; Fu, Qiang; Hou, Jianquan; Yuan, Jianlin; He, Dalin; Zhou, Tie; Wang, Fubo; He, Biming; Sun, Yinghao

2015-04-01

To test the diagnostic performance of percent free prostate-specific antigen (%fPSA) in predicting any prostate cancer (PCa) and high-grade prostate cancer (HGPCa) in a retrospective multi-center biopsy cohort with a PSA level of 4.0-10.0 ng/mL in China. Consecutive patients with a PSA of 4.0-10.0 ng/mL who underwent transrectal ultrasound-guided biopsy were enrolled at 16 Chinese medical centers from January 1st, 2010 to December 31st, 2013. Total and free serum PSA determinations were performed using three types of electro-chemiluminescence immunoassays recalibrated to the World Health Organization (WHO) standard. The diagnostic accuracy of PSA, %fPSA, and %fPSA in combination with PSA (%fPSA + PSA) was determined using the area under the receiver operating characteristic (ROC) curve (AUC). A total of 2310 consecutive men with PSA levels between 4.0 and 10.0 ng/mL were included, and the detection rate of PCa was 25.1%. The AUC of %fPSA and %fPSA + PSA in predicting any PCa was superior to PSA alone in men aged ≥60 years (0.623 vs. 0.534, p  < 0.0001) but not in men aged 40-59 years (0.517 vs. 0.518, p  = 0.939). Similar result was yield in predicting HGPCa. In a clinical setting of Chinese men with 4.0-10.0 ng/mL PSA undergoing initial prostate biopsy, adding %fPSA to PSA can moderately improve the diagnostic accuracy for any PCa and HGPCa compared with PSA alone in patients ≥60 but not in patients aged 40-59 years.

French Phonology for Teachers: A Programmed Introduction.

ERIC Educational Resources Information Center

Green, Jerald R.; Poulin, Norman A.

This programed, self-instructional course has the following terminal objectives: (1) to present some notions of the science of linguistics and the major branches of linguistics, (2) to teach the segmental and suprasegmental phonemes of French, (3) to identify the major articulatory problems of French for the native speaker of English, (4) to…

Deliberative democracy and cancer screening consent: a randomised control trial of the effect of a community jury on men's knowledge about and intentions to participate in PSA screening.

PubMed

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

2014-12-24

Prostate-specific antigen (PSA) screening is controversial. A community jury allows presentation of complex information and may clarify how participants view screening after being well-informed. We examined whether participating in a community jury had an effect on men's knowledge about and their intention to participate in PSA screening. Random allocation to either a 2-day community jury or a control group, with preassessment, postassessment and 3-month follow-up assessment. Participants from the Gold Coast (Australia) recruited via radio, newspaper and community meetings. Twenty-six men aged 50-70 years with no previous diagnosis of prostate cancer. The control group (n=14) received factsheets on PSA screening. Community jury participants (n=12) received the same factsheets and further information about screening for prostate cancer. In addition, three experts presented information on PSA screening: a neutral scientific advisor provided background information, one expert emphasised the potential benefits of screening and another expert emphasised the potential harms. Participants discussed information, asked questions to the experts and deliberated on personal and policy decisions. Our primary outcome was change in individual intention to have a PSA screening test. We also assessed knowledge about screening for prostate cancer. Analyses were conducted using intention-to-treat. Immediately after the jury, the community jury group had less intention-to-screen for prostate cancer than men in the control group (effect size=-0.6 SD, p=0.05). This was sustained at 3-month follow-up. Community jury men also correctly identified PSA test accuracy and considered themselves more informed (effect size=1.2 SD, p<0.001). Evidence-informed deliberation of the harms and benefits of PSA screening effects men's individual choice to be screened for prostate cancer. Community juries may be a valid method for eliciting target group input to policy decisions. Australian and New

Deliberative democracy and cancer screening consent: a randomised control trial of the effect of a community jury on men's knowledge about and intentions to participate in PSA screening

PubMed Central

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

2014-01-01

Objective Prostate-specific antigen (PSA) screening is controversial. A community jury allows presentation of complex information and may clarify how participants view screening after being well-informed. We examined whether participating in a community jury had an effect on men's knowledge about and their intention to participate in PSA screening. Design Random allocation to either a 2-day community jury or a control group, with preassessment, postassessment and 3-month follow-up assessment. Setting Participants from the Gold Coast (Australia) recruited via radio, newspaper and community meetings. Participants Twenty-six men aged 50–70 years with no previous diagnosis of prostate cancer. Intervention The control group (n=14) received factsheets on PSA screening. Community jury participants (n=12) received the same factsheets and further information about screening for prostate cancer. In addition, three experts presented information on PSA screening: a neutral scientific advisor provided background information, one expert emphasised the potential benefits of screening and another expert emphasised the potential harms. Participants discussed information, asked questions to the experts and deliberated on personal and policy decisions. Main outcome and measures Our primary outcome was change in individual intention to have a PSA screening test. We also assessed knowledge about screening for prostate cancer. Results Analyses were conducted using intention-to-treat. Immediately after the jury, the community jury group had less intention-to-screen for prostate cancer than men in the control group (effect size=−0.6 SD, p=0.05). This was sustained at 3-month follow-up. Community jury men also correctly identified PSA test accuracy and considered themselves more informed (effect size=1.2 SD, p<0.001). Conclusions Evidence-informed deliberation of the harms and benefits of PSA screening effects men's individual choice to be screened for prostate cancer. Community

The Development of Complexity, Accuracy and Fluency in the Written Production of L2 French

ERIC Educational Resources Information Center

Gunnarsson, Cecilia

2012-01-01

The present longitudinal case study investigated the development of fluency, complexity and accuracy--and the possible relationships between them--in the written production of L2 French. We assessed fluency and complexity in five intermediate learners by means of conventional indicators for written L2 (cf. Wolfe-Quintero et al. 1998), while…

Development of Gender Typicality and Felt Pressure in European French and North African French Adolescents.

PubMed

Hoffman, Adam J; Dumas, Florence; Loose, Florence; Smeding, Annique; Kurtz-Costes, Beth; Régner, Isabelle

2017-11-14

Trajectories of gender identity were examined from Grade 6 (M age  = 11.9 years) to Grade 9 in European French (n = 570) and North African French (n = 534) adolescents, and gender and ethnic group differences were assessed in these trajectories. In Grade 6, boys of both ethnic groups reported higher levels of gender typicality and felt pressure for gender conformity than girls. European French girls and boys and North African French girls reported decreasing gender typicality from Grade 6 to Grade 9, whereas North African French boys did not change. Felt pressure decreased among girls, did not change in European French boys, and increased in North African French boys. Ethnic and gender differences in gender identity development are discussed. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

French Interim MALE UAV Program

DTIC Science & Technology

2003-09-02

MINISTÈRE DE LA DÉFENSE June, 13th 2002 Lcl Monsterleet FAF Staff J. Caron EADS S&DE-ISR FRENCH INTERIM MALE UAV PROGRAM 4 INDUSTRIAL STATUS Report...2003 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE French Interim Male UAV Program 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) EADS

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.

Evaluation of the French Immersion Weekends, French Centre, University of Calgary, 1979-80.

ERIC Educational Resources Information Center