TY - JOUR
T1 - Treatment of cultured glioma cells with the EGFR-TKI gefitinib ("Iressa", ZD1839) increases the uptake of astatinated EGF despite the absence of gefitinib-mediated growth inhibition
AU - Sundberg, Åsa Liljegren
AU - Almqvist, Ylva
AU - Tolmachev, Vladimir
AU - Carlsson, Jörgen
N1 - Funding Information:
Zeneca, Macclesfield, UK. Financial support was provided by the Swedish Cancer Society.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - The EGFR-TKI (epidermal growth factor receptor tyrosine kinase inhibitor) gefitinib ("Iressa", ZD1839), a reversible growth inhibitor of EGFRexpressing tumour cells, has been shown to enhance the antitumour effect of ionising radiation, and also to increase the uptake of radioiodinated EGF. Thus, combination of gefitinib treatment and radionuclide targeting is an interesting option for therapy of brain tumours that are difficult to treat with conventional methods. The aim of this study was to evaluate how pre-treatment with gefitinib affects binding of astatinated EGF (211At-EGF) to cultured glioma U343 cells, which express high levels of EGFR. The growth of U343 cells in the presence of gefitinib was investigated, and it was found that gefitinib does not significantly inhibit the growth of these cells. Nevertheless, the uptake of 211At-EGF in U343 cells was markedly increased (up to 3.5 times) in cells pre-treated with gefitinib (1 μM). This indicates that a combination of gefitinib treatment and radionuclide targeting to EGFR might be a useful therapeutic modality, even for patients who do not respond to treatment with gefitinib alone.
AB - The EGFR-TKI (epidermal growth factor receptor tyrosine kinase inhibitor) gefitinib ("Iressa", ZD1839), a reversible growth inhibitor of EGFRexpressing tumour cells, has been shown to enhance the antitumour effect of ionising radiation, and also to increase the uptake of radioiodinated EGF. Thus, combination of gefitinib treatment and radionuclide targeting is an interesting option for therapy of brain tumours that are difficult to treat with conventional methods. The aim of this study was to evaluate how pre-treatment with gefitinib affects binding of astatinated EGF (211At-EGF) to cultured glioma U343 cells, which express high levels of EGFR. The growth of U343 cells in the presence of gefitinib was investigated, and it was found that gefitinib does not significantly inhibit the growth of these cells. Nevertheless, the uptake of 211At-EGF in U343 cells was markedly increased (up to 3.5 times) in cells pre-treated with gefitinib (1 μM). This indicates that a combination of gefitinib treatment and radionuclide targeting to EGFR might be a useful therapeutic modality, even for patients who do not respond to treatment with gefitinib alone.
KW - EGFR
KW - Gefitinib
KW - Glioma
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U2 - 10.1007/s00259-003-1129-x
DO - 10.1007/s00259-003-1129-x
M3 - Article
C2 - 12740721
AN - SCOPUS:0037569521
VL - 30
SP - 727
EP - 729
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
SN - 1619-7070
IS - 5
ER -