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Sökning: WFRF:(Viklund Björn)

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11.
  • Karlsson, Jenny, et al. (författare)
  • Four evolutionary trajectories underlie genetic intratumoral variation in childhood cancer
  • 2018
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:7, s. 944-950
  • Tidskriftsartikel (refereegranskat)abstract
    • A major challenge to personalized oncology is that driver mutations vary among cancer cells inhabiting the same tumor. Whether this reflects principally disparate patterns of Darwinian evolution in different tumor regions has remained unexplored1–5. We mapped the prevalence of genetically distinct clones over 250 regions in 54 childhood cancers. This showed that primary tumors can simultaneously follow up to four evolutionary trajectories over different anatomic areas. The most common pattern consists of subclones with very few mutations confined to a single tumor region. The second most common is a stable coexistence, over vast areas, of clones characterized by changes in chromosome numbers. This is contrasted by a third, less frequent, pattern where a clone with driver mutations or structural chromosome rearrangements emerges through a clonal sweep to dominate an anatomical region. The fourth and rarest pattern is the local emergence of a myriad of clones with TP53 inactivation. Death from disease was limited to tumors exhibiting the two last, most dynamic patterns.
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12.
  • Köster, Jan, et al. (författare)
  • Genomic and transcriptomic features of dermatofibrosarcoma protuberans : Unusual chromosomal origin of the COL1A1-PDGFB fusion gene and synergistic effects of amplified regions in tumor development
  • 2020
  • Ingår i: Cancer Genetics. - : ELSEVIER SCIENCE INC. - 2210-7762 .- 2210-7770. ; 241, s. 34-41
  • Tidskriftsartikel (refereegranskat)abstract
    • The dermatofibrosarcoma protuberans family of tumors (DPFT) comprises cutaneous soft tissue neoplasms associated with aberrant PDGFBR signaling, typically through a COL1A1-PDGFB fusion. The aim of the present study was to obtain a better understanding of the chromosomal origin of this fusion and to assess the spectrum of secondary mutations at the chromosome and nucleotide levels. We thus investigated 42 tumor samples from 35 patients using chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, and/or massively parallel sequencing (gene panel, whole exome and transcriptome sequencing) methods. We confirmed the age-associated differences in the origin of the COL1A1-PDGFB fusion and could show that it in most cases must arise after DNA synthesis, i.e., in the S or G2 phase of the cell cycle. Whereas there was a non-random pattern of secondary chromosomal rearrangements, single nucleotide variants seem to have little impact on tumor progression. No clear genomic differences between low-grade and high-grade DPFT were found, but the number of chromosomes and chromosomal imbalances as well as the frequency of 9p deletions all tended to be greater among the latter. Gene expression profiling of tumors with COL1A1-PDGFB fusions associated with unbalanced translocations or ring chromosomes identified several transcriptionally up-regulated genes in the amplified regions of chromosomes 17 and 22, including TBX2, PRKCA, MSI2, SOX9, SOX10, and PRAME.
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13.
  • 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. ; 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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14.
  • Mandahl, Nils, et al. (författare)
  • Scattered genomic amplification in dedifferentiated liposarcoma
  • 2017
  • Ingår i: Molecular Cytogenetics. - : Springer Science and Business Media LLC. - 1755-8166. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Atypical lipomatous tumor (ALT), well differentiated liposarcoma (WDLS) and dedifferentiated liposarcoma (DDLS) are cytogenetically characterized by near-diploid karyotypes with no or few other aberrations than supernumerary ring or giant marker chromosomes, although DDLS tend to have somewhat more complex rearrangements. In contrast, pleomorphic liposarcomas (PLS) have highly aberrant and heterogeneous karyotypes. The ring and giant marker chromosomes contain discontinuous amplicons, in particular including multiple copies of the target genes CDK4, HMGA2 and MDM2 from 12q, but often also sequences from other chromosomes. Results: The present study presents a DDLS with an atypical hypertriploid karyotype without any ring or giant marker chromosomes. SNP array analyses revealed amplification of almost the entire 5p and discontinuous amplicons of 12q including the classical target genes, in particular CDK4. In addition, amplicons from 1q, 3q, 7p, 9p, 11q and 20q, covering from 2 to 14 Mb, were present. FISH analyses showed that sequences from 5p and 12q were scattered, separately or together, over more than 10 chromosomes of varying size. At RNA sequencing, significantly elevated expression, compared to myxoid liposarcomas, was seen for TRIO and AMACR in 5p and of CDK4, HMGA2 and MDM2 in 12q. Conclusions: The observed pattern of scattered amplification does not show the characteristics of chromothripsis, but is novel and differs from the well known cytogenetic manifestations of amplification, i.e., double minutes, homogeneously staining regions and ring chromosomes. Possible explanations for this unusual distribution of amplified sequences might be the mechanism of alternative lengthening of telomeres that is frequently active in DDLS and events associated with telomere crisis.
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15.
  • Mayrhofer, Markus, et al. (författare)
  • 1p36 deletion is a marker for tumour dissemination in microsatellite stable stage II-III colon cancer
  • 2014
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14, s. 872-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The clinical behaviour of colon cancer is heterogeneous. Five-year overall survival is 50-65% with all stages included. Recurring somatic chromosomal alterations have been identified and some have shown potential as markers for dissemination of the tumour, which is responsible for most colon cancer deaths. We investigated 115 selected stage II-IV primary colon cancers for associations between chromosomal alterations and tumour dissemination. Methods: Follow-up was at least 5 years for stage II-III patients without distant recurrence. Affymetrix SNP 6.0 microarrays and allele-specific copy number analysis were used to identify chromosomal alterations. Fisher's exact test was used to associate alterations with tumour dissemination, detected at diagnosis (stage IV) or later as recurrent disease (stage II-III). Results: Loss of 1p36.11-21 was associated with tumour dissemination in microsatellite stable tumours of stage II-IV (odds ratio = 5.5). It was enriched to a similar extent in tumours with distant recurrence within stage II and stage III subgroups, and may therefore be used as a prognostic marker at diagnosis. Loss of 1p36.11-21 relative to average copy number of the genome showed similar prognostic value compared to absolute loss of copies. Therefore, the use of relative loss as a prognostic marker would benefit more patients by applying also to hyperploid cancer genomes. The association with tumour dissemination was supported by independent data from the The Cancer Genome Atlas. Conclusion: Deletions on 1p36 may be used to guide adjuvant treatment decisions in microsatellite stable colon cancer of stages II and III.
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16.
  • Mayrhofer, Markus, et al. (författare)
  • Rawcopy: Improved copy number analysis with Affymetrix arrays
  • 2016
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 36158-
  • Tidskriftsartikel (refereegranskat)abstract
    • Microarray data is subject to noise and systematic variation that negatively affects the resolution of copy number analysis. We describe Rawcopy, an R package for processing of Affymetrix CytoScan HD, CytoScan 750k and SNP 6.0 microarray raw intensities (CEL files). Noise characteristics of a large number of reference samples are used to estimate log ratio and B-allele frequency for total and allele-specific copy number analysis. Rawcopy achieves better signal-to-noise ratio and higher proportion of validated alterations than commonly used free and proprietary alternatives. In addition, Rawcopy visualizes each microarray sample for assessment of technical quality, patient identity and genome-wide absolute copy number states. Software and instructions are available at http://rawcopy.org.
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17.
  • Sjöström, Björn, et al. (författare)
  • Characteristics and definitive outcomes of COVID-19 patients admitted to a secondary hospital intensive care unit in Sweden
  • 2021
  • Ingår i: Health Science Reports. - : John Wiley & Sons. - 2398-8835. ; 4:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: Most published reports of COVID-19 Intensive Care Unit (ICU) patients are from large tertiary hospitals and often present short-term or incomplete outcome data. There are reports indicating that ICUs with fewer beds are associated with higher mortality. This study aimed to investigate the definitive outcome and patient characteristics of the complete first wave of COVID-19 patients admitted to ICU in a secondary hospital.Methods: In this prospective observational study, all patients with respiratory failure and a positive SARS-CoV-2 test admitted to Västerås Hospital ICU between 24 March and July 22, 2020 were included. The primary outcome was defined as 90-day mortality. Secondary outcomes included ICU length of stay, hospital length of stay, number of days with invasive ventilation, need for vasopressors/inotropes, and use of renal replacement therapy.Results: Fifty-three patients were included. Median age (range) was 59 (33-76) and 74% were men. Obesity and hypertension were the most common comorbidities and 45% of the patients were born outside Europe. Ninety-day mortality was 30%. Median ICU length of stay (interquartile range) was 14 (5-24) days and the duration of invasive mechanical ventilation 16 (12-26) days. No patients received dialysis at 90-day follow-up.Conclusion: In this cohort of COVID-19 patients treated in a secondary hospital ICU, mortality rates were low compared to early studies from China, Italy, and the United States, but similar to other government-funded hospitals in Scandinavia. A preparatory reorganization enabled an increase in ICU capacity, hence avoiding an overwhelmed intensive care organization.
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18.
  • Viklund, Emilia, et al. (författare)
  • Current smoking alters phospholipid- and surfactant protein A levels in small airway lining fluid: An explorative study on exhaled breath
  • 2021
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 16:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Small airways are difficult to access. Exhaled droplets, also referred to as particles, provide a sample of small airway lining fluid and may reflect inflammatory responses. We aimed to explore the effect of smoking on the composition and number of exhaled particles in a smoker-enriched study population. We collected and chemically analyzed exhaled particles from 102 subjects (29 never smokers, 36 former smokers and 37 current smokers) aged 39 to 83 years (median 63). A breathing maneuver maximized the number exhaled particles, which were quantified with a particle counter. The contents of surfactant protein A and albumin in exhaled particles was quantified with immunoassays and the contents of the phospholipids dipalmitoyl- and palmitoyl-oleoyl- phosphatidylcholine with mass spectrometry. Subjects also performed spirometry and nitrogen single breath washout. Associations between smoking status and the distribution of contents in exhaled particles and particle number concentration were tested with quantile regression, after adjusting for potential confounders. Current smokers, compared to never smokers, had higher number exhaled particles and more surfactant protein A in the particles. The magnitude of the effects of current smoking varied along the distribution of each PEx-variable. Among subjects with normal lung function, phospholipid levels were elevated in current smokers, in comparison to no effect of smoking on these lipids at abnormal lung function. Smoking increased exhaled number of particles and the contents of lipids and surfactant protein A in the particles. These findings might reflect early inflammatory responses to smoking in small airway lining fluid, also when lung function is within normal limits.
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