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Åke Borg

Åke Borg

Principal investigator

Åke Borg

Substantial intrinsic variability in chemoradiosensitivity of newly established anaplastic thyroid cancer cell-lines

Author

  • Sigurdur Gretarsson
  • Alexander Nygren
  • Ann H Rosendahl
  • Nektaria Mylona
  • Elisabeth Kjellén
  • Yuesheng Jin
  • Kajsa Paulsson
  • Åke Borg
  • Eva Brun
  • Jan Tennvall
  • Anders Bergenfelz
  • Lennart Greiff
  • Johan Wennerberg
  • Lars Ekblad

Summary, in English

Background: Well characterized human cell lines are needed for preclinical treatment studies of anaplastic thyroid cancer (ATC).Aims/Objectives: The aim was to establish, verify and characterize a panel of ATC cell lines.Material and methods: Cell lines were established from ATC fine-needle aspiration biopsies and characterized genetically and functionally regarding treatment sensitivities.Results: Eight cell lines were established in vitro and the anaplastic thyroid origin was verified. Seven of the cell lines were also grown as xenografts. The cell lines harboured complex karyotypes with modal numbers in hyperdiploid to near-pentaploid range. Five were TP53 mutated and three carried the BRAFV600E mutation. None had rearrangements of RET. For doxorubicin, IC50 ranged from 0.42 to 46 nmol/L and for paclitaxel from 1.6 to 196 nmol/L. Radiation sensitivity varied between 2.6 and 6.3 Gy. Two of the BRAF mutated cell lines displayed high sensitivity to vemurafenib, while the third was similar to the wild-type ones.Conclusions and significance: We describe a series of new ATC cell lines demonstrating large heterogeneity in the response to cytostatic drugs and the BRAF inhibitor vemurafenib. The observations are relevant to future attempts to optimize treatment combinations for ATC.

Department/s

  • Head and Neck Cancer Research Group
  • Otorhinolaryngology (Lund)
  • LUCC: Lund University Cancer Centre
  • Breast cancer prevention & intervention
  • Division of Clinical Genetics
  • Aneuploidy in cancer
  • Familial Breast Cancer
  • Tumor microenvironment
  • Endocrine and Sarcoma Surgery
  • Breastcancer-genetics

Publishing year

2020-01-10

Language

English

Pages

337-343

Publication/Series

Acta Oto-Laryngologica

Volume

140

Issue

4

Document type

Journal article

Publisher

Taylor & Francis

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Head and Neck Cancer Research Group
  • Breast cancer prevention & intervention
  • Aneuploidy in cancer
  • Familial Breast Cancer
  • Endocrine and Sarcoma Surgery

ISBN/ISSN/Other

  • ISSN: 1651-2251