GLUT-1 and CAIX as intrinsic markers of hypoxia in carcinoma of the cervix: relationship to pimonidazole binding.

2.50
Hdl Handle:
http://hdl.handle.net/10541/78774
Title:
GLUT-1 and CAIX as intrinsic markers of hypoxia in carcinoma of the cervix: relationship to pimonidazole binding.
Authors:
Airley, R; Loncaster, Juliette A; Raleigh, James A; Harris, Adrian L; Davidson, Susan E; Hunter, Robin D; West, Catharine M L; Stratford, Ian J
Abstract:
The presence of hypoxia in tumours results in the overexpression of certain genes, which are controlled via the transcription factor HIF-1. Hypoxic cells are known to be radioresistant and chemoresistant, thus, a reliable surrogate marker of hypoxia is desirable to ensure that treatment may be rationally applied. Recently, the HIF-1-regulated proteins Glut-1 and CAIX were validated as intrinsic markers of hypoxia by comparison with pO(2) measured using oxygen electrodes. We compare the expression of Glut-1 and CAIX with the binding of the bioreductive drug hypoxia marker pimonidazole. Pimonidazole was administered to 42 patients with advanced carcinoma of the cervix, 16 hr before biopsy. Sections of single or multiple biopsies were then immunostained for Glut-1 and CAIX, and the area of staining scored by eye, using a "field-by-field" semi-quantitative averaging system. Using 1 biopsy only, Glut-1 (r = 0.54, p = <0.001) correlated with the level of pimonidazole binding, and Glut-1 and CAIX expression also correlated significantly (r = 0.40, p = <0.009). Thus, our study has shown that HIF-1 regulated genes have potential for future use as predictors of the malignant changes mediated by hypoxia, and warrant further investigation as indicators of response to cancer therapy.
Affiliation:
School of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, United Kingdom. R.Airley@livjm.ac.uk
Citation:
GLUT-1 and CAIX as intrinsic markers of hypoxia in carcinoma of the cervix: relationship to pimonidazole binding. 2003, 104 (1):85-91 Int. J. Cancer
Journal:
International Journal of Cancer
Issue Date:
10-Mar-2003
URI:
http://hdl.handle.net/10541/78774
DOI:
10.1002/ijc.10904
PubMed ID:
12532423
Type:
Article
Language:
en
ISSN:
0020-7136
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorAirley, R-
dc.contributor.authorLoncaster, Juliette A-
dc.contributor.authorRaleigh, James A-
dc.contributor.authorHarris, Adrian L-
dc.contributor.authorDavidson, Susan E-
dc.contributor.authorHunter, Robin D-
dc.contributor.authorWest, Catharine M L-
dc.contributor.authorStratford, Ian J-
dc.date.accessioned2009-08-26T16:11:35Z-
dc.date.available2009-08-26T16:11:35Z-
dc.date.issued2003-03-10-
dc.identifier.citationGLUT-1 and CAIX as intrinsic markers of hypoxia in carcinoma of the cervix: relationship to pimonidazole binding. 2003, 104 (1):85-91 Int. J. Canceren
dc.identifier.issn0020-7136-
dc.identifier.pmid12532423-
dc.identifier.doi10.1002/ijc.10904-
dc.identifier.urihttp://hdl.handle.net/10541/78774-
dc.description.abstractThe presence of hypoxia in tumours results in the overexpression of certain genes, which are controlled via the transcription factor HIF-1. Hypoxic cells are known to be radioresistant and chemoresistant, thus, a reliable surrogate marker of hypoxia is desirable to ensure that treatment may be rationally applied. Recently, the HIF-1-regulated proteins Glut-1 and CAIX were validated as intrinsic markers of hypoxia by comparison with pO(2) measured using oxygen electrodes. We compare the expression of Glut-1 and CAIX with the binding of the bioreductive drug hypoxia marker pimonidazole. Pimonidazole was administered to 42 patients with advanced carcinoma of the cervix, 16 hr before biopsy. Sections of single or multiple biopsies were then immunostained for Glut-1 and CAIX, and the area of staining scored by eye, using a "field-by-field" semi-quantitative averaging system. Using 1 biopsy only, Glut-1 (r = 0.54, p = <0.001) correlated with the level of pimonidazole binding, and Glut-1 and CAIX expression also correlated significantly (r = 0.40, p = <0.009). Thus, our study has shown that HIF-1 regulated genes have potential for future use as predictors of the malignant changes mediated by hypoxia, and warrant further investigation as indicators of response to cancer therapy.en
dc.language.isoenen
dc.subjectUterine Cervical Canceren
dc.subjectCancer Proteinsen
dc.subject.meshAdult-
dc.subject.meshAntigens, Neoplasm-
dc.subject.meshBiological Markers-
dc.subject.meshBiopsy-
dc.subject.meshCarbonic Anhydrases-
dc.subject.meshCarcinoma, Squamous Cell-
dc.subject.meshCell Hypoxia-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshEnergy Metabolism-
dc.subject.meshFemale-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshGlucose Transporter Type 1-
dc.subject.meshHumans-
dc.subject.meshHypoxia-Inducible Factor 1-
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subunit-
dc.subject.meshMicroelectrodes-
dc.subject.meshMiddle Aged-
dc.subject.meshMonosaccharide Transport Proteins-
dc.subject.meshNeoplasm Proteins-
dc.subject.meshNitroimidazoles-
dc.subject.meshNuclear Proteins-
dc.subject.meshObserver Variation-
dc.subject.meshOxygen-
dc.subject.meshPartial Pressure-
dc.subject.meshRadiation-Sensitizing Agents-
dc.subject.meshReproducibility of Results-
dc.subject.meshTranscription Factors-
dc.subject.meshUterine Cervical Neoplasms-
dc.titleGLUT-1 and CAIX as intrinsic markers of hypoxia in carcinoma of the cervix: relationship to pimonidazole binding.en
dc.typeArticleen
dc.contributor.departmentSchool of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, United Kingdom. R.Airley@livjm.ac.uken
dc.identifier.journalInternational Journal of Canceren

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