Differential radiosensitisation by ZD1839 (Iressa), a highly selective epidermal growth factor receptor tyrosine kinase inhibitor in two related bladder cancer cell lines.

2.50
Hdl Handle:
http://hdl.handle.net/10541/76831
Title:
Differential radiosensitisation by ZD1839 (Iressa), a highly selective epidermal growth factor receptor tyrosine kinase inhibitor in two related bladder cancer cell lines.
Authors:
Maddineni, Satish B; Sangar, Vijay K; Hendry, Jolyon H; Margison, Geoffrey P; Clarke, Noel W ( 0000-0001-7776-8059 )
Abstract:
The epidermal growth factor receptor (EGFR) is expressed in a wide variety of epithelial tumours including carcinoma of the bladder. Stimulation of the EGFR pathway is blocked by ZD1839 (Iressa), a highly selective EGFR tyrosine kinase inhibitor. Radical radiotherapy is an established organ sparing treatment option for muscle invasive bladder cancer and this study has explored the possibility for the use of ZD1839 as a radiosensitiser in this scenario. The effect of combination treatment with ZD1839 (0.01 microM) and ionising radiation in the established bladder cancer cell lines MGH-U1 and its radiosensitive mutant clone S40b was measured by clonogenic assays. A highly significant radiosensitising effect was seen in both cell lines (P < 0.001 for MGH-U1 and S40b cell lines). This effect was independent of the concentration of the drug and the duration of exposure prior to treatment with ionising radiation. Cell cycle kinetics of both cell lines was not significantly altered with ZD1839 (0.01 microM) as a single agent. A modest induction of apoptosis was observed with ZD1839 (0.01 microM) as a single agent, but a marked induction was observed with the combination treatment of ZD1839 and ionising radiation. These results suggest a potentially important role for ZD1839 in combination with radiotherapy in the treatment of muscle invasive bladder cancer.
Affiliation:
Cancer Research-UK Carcinogenesis Group, Paterson Institute for Cancer Research, Wilmslow Road, Manchester M20 4BX, UK. satishandsian@yahoo.co.uk
Citation:
Differential radiosensitisation by ZD1839 (Iressa), a highly selective epidermal growth factor receptor tyrosine kinase inhibitor in two related bladder cancer cell lines. 2005, 92 (1):125-30 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
17-Jan-2005
URI:
http://hdl.handle.net/10541/76831
DOI:
10.1038/sj.bjc.6602299
PubMed ID:
15611794
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMaddineni, Satish B-
dc.contributor.authorSangar, Vijay K-
dc.contributor.authorHendry, Jolyon H-
dc.contributor.authorMargison, Geoffrey P-
dc.contributor.authorClarke, Noel W-
dc.date.accessioned2009-08-10T17:17:02Z-
dc.date.available2009-08-10T17:17:02Z-
dc.date.issued2005-01-17-
dc.identifier.citationDifferential radiosensitisation by ZD1839 (Iressa), a highly selective epidermal growth factor receptor tyrosine kinase inhibitor in two related bladder cancer cell lines. 2005, 92 (1):125-30 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid15611794-
dc.identifier.doi10.1038/sj.bjc.6602299-
dc.identifier.urihttp://hdl.handle.net/10541/76831-
dc.description.abstractThe epidermal growth factor receptor (EGFR) is expressed in a wide variety of epithelial tumours including carcinoma of the bladder. Stimulation of the EGFR pathway is blocked by ZD1839 (Iressa), a highly selective EGFR tyrosine kinase inhibitor. Radical radiotherapy is an established organ sparing treatment option for muscle invasive bladder cancer and this study has explored the possibility for the use of ZD1839 as a radiosensitiser in this scenario. The effect of combination treatment with ZD1839 (0.01 microM) and ionising radiation in the established bladder cancer cell lines MGH-U1 and its radiosensitive mutant clone S40b was measured by clonogenic assays. A highly significant radiosensitising effect was seen in both cell lines (P < 0.001 for MGH-U1 and S40b cell lines). This effect was independent of the concentration of the drug and the duration of exposure prior to treatment with ionising radiation. Cell cycle kinetics of both cell lines was not significantly altered with ZD1839 (0.01 microM) as a single agent. A modest induction of apoptosis was observed with ZD1839 (0.01 microM) as a single agent, but a marked induction was observed with the combination treatment of ZD1839 and ionising radiation. These results suggest a potentially important role for ZD1839 in combination with radiotherapy in the treatment of muscle invasive bladder cancer.en
dc.language.isoenen
dc.subjectCultured Tumour Cellsen
dc.subjectUrinary Bladder Canceren
dc.subject.meshAntineoplastic Agents-
dc.subject.meshApoptosis-
dc.subject.meshCell Cycle-
dc.subject.meshCell Division-
dc.subject.meshEnzyme Inhibitors-
dc.subject.meshHumans-
dc.subject.meshProtein-Tyrosine Kinases-
dc.subject.meshQuinazolines-
dc.subject.meshRadiation-Sensitizing Agents-
dc.subject.meshReceptor, Epidermal Growth Factor-
dc.subject.meshTumor Cells, Cultured-
dc.subject.meshUrinary Bladder Neoplasms-
dc.titleDifferential radiosensitisation by ZD1839 (Iressa), a highly selective epidermal growth factor receptor tyrosine kinase inhibitor in two related bladder cancer cell lines.en
dc.typeArticleen
dc.contributor.departmentCancer Research-UK Carcinogenesis Group, Paterson Institute for Cancer Research, Wilmslow Road, Manchester M20 4BX, UK. satishandsian@yahoo.co.uken
dc.identifier.journalBritish Journal of Canceren
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