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Sökning: WFRF:(Dearnaley David)

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  • Bancroft, Elizabeth K, et al. (författare)
  • Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study
  • 2014
  • Ingår i: European urology. - 1873-7560. ; 66:3, s. 489-499
  • Tidskriftsartikel (refereegranskat)abstract
    • Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations.
  • Carducci, Michael A., et al. (författare)
  • A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer
  • 2007
  • Ingår i: Cancer. - John Wiley and Sons Inc.. - 1097-0142. ; 110:9, s. 1959-1966
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND. The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone- refractory prostate cancer (HRPC). METHODS. This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. RESULTS. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence interval, 0.76-1.04; P =.136). Most patients progressed radiographically at the first 12-week bone scan without concomitant clinical progression. In exploratory analyses, increases from baseline to final bone alkaline phosphatase (BAP) and prostate-specific antigen (PSA) levels were significantly lower with atrasentan treatment (P <.05 for each). The median time to BAP progression (> 50% increase from nadir) was twice as long with atrasentan treatment (505 days vs 254 days; P <.01). The delay in time to PSA progression did not reach statistical significance. Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism. CONCLUSIONS. Atrasentan did not delay disease progression in men with metastatic HRPC despite evidence of biologic effects on PSA and BAP as markers of disease burden.
  • Chi, Kim N., et al. (författare)
  • Castration-resistant Prostate Cancer: From New Pathophysiology to New Treatment Targets
  • 2009
  • Ingår i: European Urology. - Elsevier. - 1873-7560. ; 56:4, s. 594-605
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Castration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited. Objective: To review the concepts and rationale behind targeted agents currently in late-stage clinical testing for patients with CRPC. Evidence acquisition: Novel targeted therapies in clinical trials were identified from registries. The MEDLINE database was searched for all relevant reports published from 1996 to October 2009. Bibliographies of the retrieved articles and major international meeting abstracts were hand-searched to identify additional studies. Evidence synthesis: Advances in our understanding of the molecular mechanisms underlying prostate cancer (PCa) progression has translated into a variety of treatment approaches. Agents targeting androgen receptor (AR) activation and local steroidogenesis, angiogenesis, immunotherapy, apoptosis, chaperone proteins, the insulin-like growth factor (IGF) pathway, RANK-ligand, endothelin receptors, and the Src family kinases are entering or have recently completed accrual to phase 3 trials for patients with CRPC. Conclusions: A number of new agents targeting mechanisms of PCa progression with early promising results are in clinical trials and have the potential to provide novel treatment options for CRPC in the near future. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  • Tedersoo, Leho, et al. (författare)
  • Global diversity and geography of soil fungi
  • 2014
  • Ingår i: Science. - 0036-8075. ; 346:6213, s. artikel nr 1256688
  • Tidskriftsartikel (refereegranskat)abstract
    • Fungi play major roles in ecosystem processes, but the determinants of fungal diversity and biogeographic patterns remain poorly understood. Using DNA metabarcoding data from hundreds of globally distributed soil samples, we demonstrate that fungal richness is decoupled from plant diversity. The plant-to-fungus richness ratio declines exponentially toward the poles. Climatic factors, followed by edaphic and spatial variables, constitute the best predictors of fungal richness and community composition at the global scale. Fungi show similar latitudinal diversity gradients to other organisms, with several notable exceptions. These findings advance our understanding of global fungal diversity patterns and permit integration of fungi into a general macroecological framework.
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