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Träfflista för sökning "WFRF:(Viklund B) srt2:(2015-2019)"

Sökning: WFRF:(Viklund B) > (2015-2019)

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  • Binzer-Panchal, Amrei, et al. (författare)
  • Integrated molecular analysis of undifferentiated uterine sarcomas reveals clinically relevant molecular subtypes
  • 2019
  • Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 25:7, s. 2155-2165
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Undifferentiated uterine sarcomas (UUS) are rare, extremely deadly, sarcomas with no effective treatment. The goal of this study was to identify novel intrinsic molecular UUS subtypes using integrated clinical, histopathologic, and molecular evaluation of a large, fully annotated, patient cohort. Experimental Design: Fifty cases of UUS with full clinicopathologic annotation were analyzed for gene expression (n ¼ 50), copy-number variation (CNV, n ¼ 40), cell morphometry (n ¼ 39), and protein expression (n ¼ 22). Gene ontology and network enrichment analysis were used to relate over- and underexpressed genes to pathways and further to clinicopathologic and phenotypic findings. Results: Gene expression identified four distinct groups of tumors, which varied in their clinicopathologic parameters. Gene ontology analysis revealed differential activation of pathways related to genital tract development, extracellular matrix (ECM), muscle function, and proliferation. A multi-variable, adjusted Cox proportional hazard model demonstrated that RNA group, mitotic index, and hormone receptor expression influence patient overall survival (OS). CNV arrays revealed characteristic chromosomal changes for each group. Morphometry demonstrated that the ECM group, the most aggressive, exhibited a decreased cell density and increased nuclear area. A cell density cutoff of 4,300 tumor cells per mm 2 could separate ECM tumors from the remaining cases with a sensitivity of 83% and a specificity of 94%. IHC staining of MMP-14, Collagens 1 and 6, and Fibronectin proteins revealed differential expression of these ECM-related proteins, identifying potential new biomarkers for this aggressive sarcoma subgroup. Conclusions: Molecular evaluation of UUS provides novel insights into the biology, prognosis, phenotype, and possible treatment of these tumors.
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3.
  • Ameur, Adam, et al. (författare)
  • SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
  • 2017
  • Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
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4.
  • Ljungkvist, Göran, 1949, et al. (författare)
  • Two techniques to sample non-volatiles in breath-exemplified by methadone.
  • 2018
  • Ingår i: Journal of breath research. - : IOP Publishing. - 1752-7163 .- 1752-7155. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The particles in exhaled breath provide a promising matrix for the monitoring of pathological processes in the airways, and also allow exposure to exogenous compounds to be to assessed. The collection is easy to perform and is non-invasive. The aim of the present study is to assess if an exogenous compound-methadone-is distributed in the lining fluid of small airways, and to compare two methods for collecting methadone in particles in exhaled breath. Exhaled particles were collected from 13 subjects receiving methadone maintenance treatment. Two different sampling methods were applied: one based on electret filtration, potentially collecting exhaled particles of all sizes, and one based on impaction, collecting particles in the size range of 0.5-7 μm, known to reflect the respiratory tract lining fluid from the small airways. The collected samples were analyzed by liquid chromatography mass spectrometry, and the impact of different breathing patterns was also investigated. The potential contribution from the oral cavity was investigated by rinsing the mouth with a codeine solution, followed by codeine analysis of the collected exhaled particles by both sampling methods. The results showed that methadone was present in all samples using both methods, but when using the method based on impaction, the concentration of methadone in exhaled breath was less than 1% of the concentration collected by the method based on filtration. Optimizing the breathing pattern to retrieve particles from small airways did not increase the amount of exhaled methadone collected by the filtration method. The contamination from codeine present in the oral cavity was only detected in samples collected by the impaction method. We conclude that methadone is distributed in the respiratory tract lining fluid of small airways. The samples collected by the filtration method most likely contained a contribution from the upper airways/oral fluid in contrast to the impaction method.
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