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Sökning: WFRF:(Bergström Sara 1987)

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1.
  • Borgenvik, Anna, 1987-, et al. (författare)
  • Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma
  • 2022
  • Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 82:24, s. 4586-4603
  • Tidskriftsartikel (refereegranskat)abstract
    • Relapse is the leading cause of death in patients with medulloblas-toma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastoma was developed, in which MYC expression was redirected in vivo from treatment-sensitive bulk cells to dormant SOX9-positive cells using doxycycline treatment. SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial-mesenchymal transition, and immune escape. p53 and DNA repair pathways were downregulated in recurrent tumors, whereas MGMT was upregulated. Recurrent tumor cells were found to be sensitive to treatment with an MGMT inhibitor and doxorubicin. These findings suggest that recurrence-specific targeting coupled with DNA repair inhibition comprises a potential therapeutic strategy in patients affected by medulloblastoma relapse.Significance: SOX9 facilitates therapy escape and recurrence in medulloblastoma via temporal inhibition of MYC/MYCN genes, revealing a strategy to specifically target SOX9-positive cells to prevent tumor relapse.
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2.
  • Eriksson, Karin, 1965, et al. (författare)
  • Aspects of rating communicative interaction: Effects on reliability and agreement
  • 2014
  • Ingår i: Journal of Interactional Research in Communication Disorders/Equinox. - : Equinox Publishing. - 2040-5111 .- 2040-512X. ; 5:2, s. 245-267
  • Tidskriftsartikel (refereegranskat)abstract
    • Communication partner training can be effective in improving communication in aphasia. However, further research is needed on how to measure the outcome of such interventions. In this paper we discuss the phenomenon of reliability in assessments in relation to the results of analyses using a rating scale designed to measure the ability to support a person with aphasia in natural conversational interaction. The scale was used by four assessors to rate 45 video recordings. Calculations of reliability and agreement produced varying results but were mostly satisfactory. However, the results highlight how interaction between factors such as complexity of assessments; design of the rating scale; factors inherent in the individual assessor; and the statistical measures used to analyse the outcome may result in a conflict between aspects of validity and reliability. Interpretations of outcome obtained with rating scales thus need to be based on knowledge about factors influencing the results.
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