The value of screening tests in the detection of prostate cancer. Part II: Retrospective analysis of free/total prostate-specific analysis ratio, age-specific reference ranges, and PSA density

Objectives: The ratio between free and total prostate-specific antigen (PSA) in serum (F/T ratio) was shown to improve the specificity of total serum PSA for the detection of prostate carcinoma in selected populations. In this study, the value of the F/T ratio for screening of prostate cancer was compared with that of age-specific reference ranges for PSA and PSA density (PSAD) by a simulation experiment. Methods: In 1726 men between 55 and 76 years old, 67 prostate carcinomas were detected by application of digital rectal examination (DRE), transrectal ultrasonography (TRUS), and tota

The value of screening tests in the detection of prostate cancer. Part I: Results of a retrospective evaluation of 1726 men

Objectives: The ratio between free and total prostate-specific antigen (PSA) in serum (F/T ratio) was shown to improve the differentiation between prostate carcinoma and benign conditions in selected series of patients. In this study the F/T ratio was analyzed for its ability to improve the specificity of total serum PSA, digital rectal examination (DRE), and transrectal ultrasonography (TRUS) for the detection of prostate cancer in an unselected screening population of men identified in the Rotterdam popu

Prostate specific antigen in a community-based sample of men without prostate cancer: Correlations with prostate volume, age, body mass index, and symptoms of prostatism

The correlation between both prostate specific antigen levels (PSA) and prostate specific antigen density (PSAD) and age, prostate volume parameters, body mass index, and the International Prostate Symptom Score (IPSS) were studied in a community‐based population. A sample of 502 men aged 55 through 74 years was evaluated, excluding those with a serum PSA above 10 ng/ml, those with biopsy proven prostate cancer, and those who had previously undergone a prostate operation. PSA and PSAD did not correlate with the body mass index. Weak correlations were found betwe

Errors in transrectal ultrasonic planimetry of the prostate: Computer simulation of volumetric errors applied to a screening population

Three systemic errors in routine ultrasonic planimetric volume measurements of the prostate were assessed. A computer model using ellipsoids was used to simulate the step section technique and different forms of rotational movements of the prostate during planimetry. The planimetric volume was up to 12% smaller than the exact volume, depending on the degree of rotational movement, the shape, and the length of the ellipsoid. In vivo study of a screening popul

The effect of SH3 domains on dynamin activity and oligomerisation

Dynamin is a GTPase enzyme that mediates vesicle fission during endocytosis to release new vesicles into the cell cytoplasm. It is recruited to sites of endocytosis in cells where it promotes vesicle fission by assembling into a collar around the vesicle neck. Dynamin is regulated by binding to proteins containing src homology 3 (SH3) domain, which stimulate its oligomerisation into rings with an associated increase in dynamin GTPase activity. However, each SH3 domain has been inconsistently studied in isolation from the others and sometimes as part of the full-length protein. This study revealed important new insights into dynamin modulation, isoform functional diversity and therefore potential function in endocytosis. Through a systematic approach, the observations overturn conclusions of several previous studies and reveal many new insights into dynamin activation and the remarkable diversity in the way SH3 domains stimulate dynamin. The existence of a previously unknown assembly independent allosteric mechanism to stimulate dynamin GTPase is revealed. The work highlights the SH3 domain of SNX9 as the most potent and consistent in vitro regulator of dynamin oligomerisation and activity. It also mapped the unique binding mechanism for SNX9 on dynamin I and revealed that this interaction is potentially phospho-regulated

Comparison of two assays for human kallikrein 2

BACKGROUND: We compared two recently developed research assays for the measurement of human kallikrein 2 (hK2) in serum: one fully automated assay (Beckman Coulter Access immunoanalyzer) and one manual assay based on the DELFIA technology. METHODS: We used two subsets of clinical specimens consisting of 48 samples from prostate cancer patients and 210 samples from participants in an ongoing screening study (ERSPC). Both subsets were measured in the Rotterdam laboratory, and the prostate cancer samples were used for analytical comparison with the originating sites for the assays: Beckman Coulter Research Department (San Diego, CA) and Turku University (Turku, Finland). RESULTS: Both the Beckman Coulter and the Turku assays performed very similarly between the Rotterdam laboratory and the originating sites: the R(2) value for both comparisons was 0.99, and the slope difference between sites was <20%. Deming regression analysis of the DELFIA (y) and Access (x) assays yielded the following: for the prostate cancer group, y = 1.17x - 0.01 (R(2) = 0.88; n = 48); and for the ERSPC group, y = 0.62x - 0.01 (R(2) = 0.77). Breakdown of the latter group into subgroups (nondiseased, benign prostatic hyperplasia, and prostate cancer samples) gave only minor differences. The Access calibrators were underrecovered by 13% in the DELFIA assay, whereas the DELFIA calibrators were overrecovered by 45% in the Access assay. CONCLUSION: The DELFIA and Access assays for hK2, which have similar analytical features, show differences that cannot be explained by calibration

Chiral corrections to kaon-nucleon scattering lengths

We calculate the threshold T-matrices of kaon-nucleon and antikaon-nucleon scattering to one loop order in SU(3) heavy baryon chiral perturbation theory. To that order the complex-valued isospin-1 $\bar KN$ threshold T-matrix can be successfully predicted from the isospin-0 and 1 $KN$ threshold T-matrices. As expected perturbation theory fails to explain the isospin-0 $\bar KN$ threshold T-matrix which is completely dominated by the nearby subthreshold $\Lambda^*(1405)$-resonance. Cancelations of large terms of second and third chiral order are observed as they seem to be typical for SU(3) baryon chiral perturbation theory calculations. We also give the kaon and eta loop corrections to the $\pi N$ scattering lengths and we investigate $\pi\Lambda$ scattering to one-loop order. The second order s-wave low-energy constants are all of natural size and do not exceed 1 GeV$^{-1}$ in magnitude.Comment: 8 pages, 2 figures, published in Phys. Rev. C64, 045204 (2001), corrections of numerical prefactors in Eqs.(10,11,12

Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: Results from the randomised, placebo-controlled avodart after radical therapy for Prostate Cancer Study (ARTS)

Background: Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical recurrence is controversial. Objective: To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy. Design, setting, and participants: Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries. Intervention: The 5α-reductase inhibitor, dutasteride. Outcome measurements and statistical analysis: The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression. Results and limitations: Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p < 0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35-76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p < 0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53-75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study. Conclusions: Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience. Clinical trial registry: ClinicalTrials.gov, NCT00558363

Harmonisation of short-term in vitro culture for the expansion of antigen-specific CD8(+) T cells with detection by ELISPOT and HLA-multimer staining.

Ex vivo ELISPOT and multimer staining are well-established tests for the assessment of antigen-specific T cells. Many laboratories are now using a period of in vitro stimulation (IVS) to enhance detection. Here, we report the findings of a multi-centre panel organised by the Association for Cancer Immunotherapy Immunoguiding Program to investigate the impact of IVS protocols on the detection of antigen-specific T cells of varying ex vivo frequency. Five centres performed ELISPOT and multimer staining on centrally prepared PBMCs from 3 donors, both ex vivo and following IVS. A harmonised IVS protocol was designed based on the best-performing protocol(s), which was then evaluated in a second phase on 2 donors by 6 centres. All centres were able to reliably detect antigen-specific T cells of high/intermediate frequency both ex vivo (Phase I) and post-IVS (Phase I and II). The highest frequencies of antigen-specific T cells ex vivo were mirrored in the frequencies following IVS and in the detection rates. However, antigen-specific T cells of a low/undetectable frequency ex vivo were not reproducibly detected post-IVS. Harmonisation of the IVS protocol reduced the inter-laboratory variation observed for ELISPOT and multimer analyses by approximately 20 %. We further demonstrate that results from ELISPOT and multimer staining correlated after (P &lt; 0.0001 and R (2) = 0.5113), but not before IVS. In summary, IVS was shown to be a reproducible method that benefitted from method harmonisation