Impact of DNA damage repair defects and aggressive variant features on response to carboplatin-based chemotherapy in metastatic castration-resistant prostate cancer

Platinum-based chemotherapy is not standard of care for unselected or genetically selected metastatic castration-resistant prostate cancer (mCRPC) patients. A retrospective assessment of 71 patients was performed on platinum use in the Netherlands. Genetically unselected patients yielded low response rates. For a predefined subanalysis of all patients with comprehensive next-generation sequencing, 30 patients were grouped based on the presence of pathogenic aberrations in genes associated with DNA damage repair (DDR) or aggressive variant prostate cancer (AVPC). Fourteen patients (47%) were DDR deficient (DDRd), of which seven with inactivated BRCA2 (BRCA2mut). Six patients classified as AVPC. DDRd patients showed beneficial biochemical response to carboplatin, largely driven by all BRCA2mut patients having >50% prostate-speci

The role of the prostate cancer gene 3 urine test in addition to serum prostate-specific antigen level in prostate cancer screening among breast cancer, early-onset gene mutation carriers

Objective: To evaluate the additive value of the prostate cancer gene 3 (PCA3) urine test to serum prostate-specific antigen (PSA) in prostate cancer (PC) screening among breast cancer, early-onset gene (BRCA) mutation carriers. This study was performed among the Dutch participants of IMPACT, a large international study on the effectiveness of PSA screening among BRCA mutation carriers. Materials and methods: Urinary PCA3 was measured in 191 BRCA1 mutation carriers, 75 BRCA2 mutation carriers, and 308 noncarriers. The physicians and participants were blinded for the results. Serum PSA level≥3.0. ng/ml was used to indicate prostate biopsies. PCA3 was evaluated (1) as an independent indicator for prostate biopsies and (2) as an indicator for prostate biopsies among men with an elevated

Социальные и культурные проблемы эксплуатации водных ресурсов на примере Томской области

Context: Serum testosterone measurement has no widely accepted place in the management of patients with prostate cancer (PCa). However, several potential clinical applications of serum testosterone determination can be envisaged. Objective: To review the role of testosterone and the androgen axis in the natural history of PCa and evaluate the evidence for the clinical application of serum testosterone measurement in patient screening, diagnosis, and management. Evidence acquisition: A Medline search retrieved original research and review articles relating to the androgen axis in PCa and the use of testosterone measurement for (1) assessing PCa risk in the general population, (2) adding to the specificity of prostate-specific antigen (PSA) testing, (3) determining tumour aggressiveness, (4) assessing the efficacy of androgen-deprivation therapy (ADT), and (5) optimising the scheduling of intermittent ADT. Relevant data were reviewed during a roundtable discussion, and consensus recommendations were agreed. Evidence synthesis: A body of data implicates the androgen axis in PCa throughout its natural history. Based on current evidence, serum testosterone measurement cannot be recommended for determining PCa risk, increasing specificity of PSA testing, or assessing tumour aggressiveness. In contrast, for patients receiving ADT, there is a clear rationale for serum testosterone monitoring to ensure that castration levels are achieved. Practical recommendations for testosterone measurement during ADT are outlined. If PSA is rising while on ADT, castration levels of serum testosterone must be demonstrated before hormonal independence can be assumed. Serum testosterone levels might be considered an additional trigger for therapy reinitiation in intermittent ADT schedules. Finally, future prospective studies should further evaluate the potential relevance of testosterone measurement as an independent assessment of prognosis and treatment decision in different disease stages. Conclusions: As a therapeutic target, serum testosterone levels should be monitored to verify response to ADT and confirm suspected castration independence. © 2010 European Association of Urology.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Urinary Molecular Biomarker Test Impacts Prostate Biopsy Decision Making in Clinical Practice

Item does not contain fulltex

A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate

In parallel with the inconsistency in observational studies and chemoprevention trials, the molecular mechanisms by which selenium may affect prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled intervention trial to examine the effects of a short-term intervention with selenized yeast on whole-genome expression profiles in non-malignant prostate tissue. Twenty-three men receiving prostate biopsies were randomly assigned to take 300 µg selenized yeast per day (n=12) or placebo (non-selenized yeast, n=11) during a median intervention period of 35 (interquartile range: 31-35) days. Prostate specimens, collected from the transition zone before and after intervention, of 15 participants (n=8 selenium, n=7 placebo) were available for analysis using Affymetrix GeneChip Human 1.0 ST Arrays. Pathway and gene set enrichment analyses revealed that the intervention with selenium resulted in a down-regulated expression of genes involved in signaling pathways related to cellular adhesion, migration, invasion, remodeling and immune responses. Specifically, expression of the well-established epithelial marker E-cadherin was up-regulated, while mesenchymal markers, such as vimentin and fibronectin, were down-regulated after the intervention with selenium. This implies an effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium affected expression of genes involved in wound healing and inflammation, processes which are both related to EMT. In conclusion, our data showed that selenium affected expression of genes implicated in EMT, mainly represented by a change in the direction of the epithelial rather than the mesenchymal phenotype

A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate

In parallel with the inconsistency in observational studies and chemoprevention trials, the mechanisms by which selenium affects prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled trial to examine the effects of a short-term intervention with selenium on gene expression in non-malignant prostate tissue. Twenty-three men received 300 μg selenium per day in the form of selenized yeast (n=12) or a placebo (n=11) during 5 weeks. Prostate biopsies collected from the transition zone before and after intervention were analysed for 15 participants (n=8 selenium, n=7 placebo). Pathway analyses revealed that the intervention with selenium was associated with down-regulated expression of genes involved in cellular migration, invasion, remodeling and immune responses. Specifically, expression of well-established epithelial markers, such as E-cadherin and epithelial cell adhesion molecule EPCAM, was up-regulated, while the mesenchymal markers vimentin and fibronectin were down-regulated after intervention with selenium. This implies an inhibitory effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium was associated with down-regulated expression of genes involved in wound healing and inflammation; processes which are both related to EMT. In conclusion, our explorative data showed that selenium affected expression of genes implicated in EMT in the transition zone of the prostate.</p