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Search: WFRF:(Hoyer Soren)

  • Result 1-4 of 4
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1.
  • Hedegaard, Jakob, et al. (author)
  • Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
  • 2016
  • In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:1, s. 27-42
  • Journal article (peer-reviewed)abstract
    • Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
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2.
  • Dengjel, Joern, et al. (author)
  • Identification of Autophagosome-associated Proteins and Regulators by Quantitative Proteomic Analysis and Genetic Screens
  • 2012
  • In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 11:3
  • Journal article (peer-reviewed)abstract
    • Autophagy is one of the major intracellular catabolic pathways, but little is known about the composition of autophagosomes. To study the associated proteins, we isolated autophagosomes from human breast cancer cells using two different biochemical methods and three stimulus types: amino acid deprivation or rapamycin or concanamycin A treatment. The autophagosome- associated proteins were dependent on stimulus, but a core set of proteins was stimulus- independent. Remarkably, proteasomal proteins were abundant among the stimulus- independent common autophagosome- associated proteins, and the activation of autophagy significantly decreased the cellular proteasome level and activity supporting interplay between the two degradation pathways. A screen of yeast strains defective in the orthologs of the human genes encoding for a common set of autophagosome- associated proteins revealed several regulators of autophagy, including subunits of the retromer complex. The combined spatiotemporal proteomic and genetic data sets presented here provide a basis for further characterization of autophagosome biogenesis and cargo selection.
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3.
  • Dyrskjot, Lars, et al. (author)
  • Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer : A Prospective Multicentre Validation Study
  • 2017
  • In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:3, s. 461-469
  • Journal article (peer-reviewed)abstract
    • Background: Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. Objective: To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. Design, setting, and participants: We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. Outcome measurements and statistical analysis: We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. Results and limitations: The progression score was significantly (p < 0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guerin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p < 0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p < 0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R-2 = 0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/ 750 patients). Conclusions: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens. Patient summary: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.
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4.
  • Tolbod, Lars P., et al. (author)
  • Non-invasive quantification of tumor blood flow in prostate cancer using O-15-H2O PET/CT
  • 2018
  • In: American Journal of Nuclear Medicine and Molecular Imaging. - : E-CENTURY PUBLISHING CORP. - 2160-8407. ; 8:5, s. 292-302
  • Journal article (peer-reviewed)abstract
    • Tumor blood flow (TBF) measurements in prostate cancer (PCa) provide an integrative index of tumor growth, which could be important for primary diagnosis and therapy response evaluation. O-15-water PET is the noninvasive gold standard but is technically demanding. The aim of this study was to compare the accuracy of three different non-invasive strategies with an invasively measured arterial input function (BSIF): Using image-derived input functions (IDIF) from either 1) a separate heart scan or 2) the pelvic scan or 3) a populations-based input function (PBIF). Nine patients with biopsy-verified PCa scheduled for prostatectomy were included. All patients were characterized with serum levels of PSA (s-PSA), multiparametric magnetic resonance imaging (mpMRl) and post-surgical histopathology Gleason Grade. Dynamic O-15-water was performed of the heart and the pelvic area 15 minutes apart. TBF estimated from both wash-in (K-1) and wash-out (k(2)) constants was calculated using a one-compartmental model. Results: Mean (range) s PSA was 12 (3-27) ng/mL, Gleason Grade Group was 2.9 (1-5), k(2) was 0.44 (0.007-1.2), and K-1 was 0.24 (0.07-0.55) mL,/mL/min. k(2) (BSIF)correlated with s-PSA (r=0.86, P<0.01) and Gleason Grade Group (rho=0.78, P=0.01). BSIF, heart-IDIF and PBIF provided near-identical k(2) and K-1 (r>0.95, P<0.001) with slopes near unity. The correlations of BSIF and pelvic-IDIF rate constants were good (r>0.95, P<0.001), but individual errors high. In conclusion, non-invasive protocols for O-15-water PET with IDIF or PBIF accurately measures perfusion in prostate cancer and might be useful for evaluation of tumor aggressiveness and treatment response.
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  • Result 1-4 of 4

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