Time and dose-dependent radiosensitization of the glioblastoma multiforme U251 cells by the EGF receptor tyrosine kinase inhibitor ZD1839 ('Iressa')

Baldassarre Stea; Ryan Falsey; Kerri Kislin; Jay Patel; Heather Glanzberg; Steven Carey; Aaron A. Ambrad; Emmanuelle J. Meuillet; Jesse D. Martinez

doi:10.1016/j.canlet.2003.07.006

Time and dose-dependent radiosensitization of the glioblastoma multiforme U251 cells by the EGF receptor tyrosine kinase inhibitor ZD1839 ('Iressa')

Baldassarre Stea, Ryan Falsey, Kerri Kislin, Jay Patel, Heather Glanzberg, Steven Carey, Aaron A. Ambrad, Emmanuelle J. Meuillet, Jesse D. Martinez

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

Abstract

Hyperactive epidermal growth factor receptor (EGFR) signaling, which promotes unregulated cell growth and inhibits apoptosis, is believed to contribute to clinical radiation resistance of glioblastoma multiforme (GBM). Blockage of the EGFR signalling pathways may offer an attractive therapeutic target to increase the cytotoxic effects of radiotherapy. We report the effects of ZD1839 ('Iressa'), a selective EGFR tyrosine kinase inhibitor on the radiation sensitivity of the U251 GBM cell line, which expresses high levels of EGFR. In radiation survival experiments, 5 μM of ZD1839 had a significant radiosensitizing effect and increased cell death was observed at doses of 5Gy in the presence of ZD1839. Dose and schedule of drug administration in combination with radiation appeared to be a crucial element to obtain radiosensitization of the cells. These studies suggest novel therapeutic strategies in the treatment of GBM.

Original language	English (US)
Pages (from-to)	43-51
Number of pages	9
Journal	Cancer Letters
Volume	202
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2003.07.006
State	Published - Dec 8 2003

Keywords

Brain tumors
Clonogenic assay
Glioblastoma
Ionizing radiation
ZD1839

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.canlet.2003.07.006

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@article{48fbb73f1c6248cb825d9ed818c94288,

title = "Time and dose-dependent radiosensitization of the glioblastoma multiforme U251 cells by the EGF receptor tyrosine kinase inhibitor ZD1839 ('Iressa')",

abstract = "Hyperactive epidermal growth factor receptor (EGFR) signaling, which promotes unregulated cell growth and inhibits apoptosis, is believed to contribute to clinical radiation resistance of glioblastoma multiforme (GBM). Blockage of the EGFR signalling pathways may offer an attractive therapeutic target to increase the cytotoxic effects of radiotherapy. We report the effects of ZD1839 ('Iressa'), a selective EGFR tyrosine kinase inhibitor on the radiation sensitivity of the U251 GBM cell line, which expresses high levels of EGFR. In radiation survival experiments, 5 μM of ZD1839 had a significant radiosensitizing effect and increased cell death was observed at doses of 5Gy in the presence of ZD1839. Dose and schedule of drug administration in combination with radiation appeared to be a crucial element to obtain radiosensitization of the cells. These studies suggest novel therapeutic strategies in the treatment of GBM.",

keywords = "Brain tumors, Clonogenic assay, Glioblastoma, Ionizing radiation, ZD1839",

author = "Baldassarre Stea and Ryan Falsey and Kerri Kislin and Jay Patel and Heather Glanzberg and Steven Carey and Ambrad, {Aaron A.} and Meuillet, {Emmanuelle J.} and Martinez, {Jesse D.}",

note = "Funding Information: The authors wish to thank AstraZeneca for providing the ZD1839 ({\textquoteleft}Iressa{\textquoteright}). {\textquoteleft}Iressa{\textquoteright} is a trademark of the AstraZeneca group of companies. Supported by an Institutional Research Grant from the University of Arizona and the National Institute of Health short term training grant #Hl0479",

year = "2003",

month = dec,

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doi = "10.1016/j.canlet.2003.07.006",

language = "English (US)",

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pages = "43--51",

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AU - Stea, Baldassarre

AU - Falsey, Ryan

AU - Kislin, Kerri

AU - Patel, Jay

AU - Glanzberg, Heather

AU - Carey, Steven

AU - Ambrad, Aaron A.

AU - Meuillet, Emmanuelle J.

AU - Martinez, Jesse D.

N1 - Funding Information: The authors wish to thank AstraZeneca for providing the ZD1839 (‘Iressa’). ‘Iressa’ is a trademark of the AstraZeneca group of companies. Supported by an Institutional Research Grant from the University of Arizona and the National Institute of Health short term training grant #Hl0479

PY - 2003/12/8

Y1 - 2003/12/8

N2 - Hyperactive epidermal growth factor receptor (EGFR) signaling, which promotes unregulated cell growth and inhibits apoptosis, is believed to contribute to clinical radiation resistance of glioblastoma multiforme (GBM). Blockage of the EGFR signalling pathways may offer an attractive therapeutic target to increase the cytotoxic effects of radiotherapy. We report the effects of ZD1839 ('Iressa'), a selective EGFR tyrosine kinase inhibitor on the radiation sensitivity of the U251 GBM cell line, which expresses high levels of EGFR. In radiation survival experiments, 5 μM of ZD1839 had a significant radiosensitizing effect and increased cell death was observed at doses of 5Gy in the presence of ZD1839. Dose and schedule of drug administration in combination with radiation appeared to be a crucial element to obtain radiosensitization of the cells. These studies suggest novel therapeutic strategies in the treatment of GBM.

AB - Hyperactive epidermal growth factor receptor (EGFR) signaling, which promotes unregulated cell growth and inhibits apoptosis, is believed to contribute to clinical radiation resistance of glioblastoma multiforme (GBM). Blockage of the EGFR signalling pathways may offer an attractive therapeutic target to increase the cytotoxic effects of radiotherapy. We report the effects of ZD1839 ('Iressa'), a selective EGFR tyrosine kinase inhibitor on the radiation sensitivity of the U251 GBM cell line, which expresses high levels of EGFR. In radiation survival experiments, 5 μM of ZD1839 had a significant radiosensitizing effect and increased cell death was observed at doses of 5Gy in the presence of ZD1839. Dose and schedule of drug administration in combination with radiation appeared to be a crucial element to obtain radiosensitization of the cells. These studies suggest novel therapeutic strategies in the treatment of GBM.

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KW - Clonogenic assay

KW - Glioblastoma

KW - Ionizing radiation

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Time and dose-dependent radiosensitization of the glioblastoma multiforme U251 cells by the EGF receptor tyrosine kinase inhibitor ZD1839 ('Iressa')

Abstract

Keywords

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