<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml"><bold>Background.</bold> Tumour hypoxia occurs as a result of an inadequate supply of blood-borne oxygen due to the disorganized and chaotic vascular network that develops in tumours. Because tumour hypoxia has been associated with a more aggressive phenotype and lower cure rate, there is a recognized need for a method of measuring tumour hypoxia that is suitable for widespread clinical use. The aim of the current study was to compare the expression of Glut-1 with the binding of the bioreductive hypoxia marker pimonidazole and to elucidate the characteristics and pitfalls when they are used as hypoxic markers.<bold>Materials and methods.</bold> In the study, SA-1 solid subcutaneous tumours in A/J mice were treated by bleomycin given i.v. (1 mg/kg), or the application of electric pulses (8 pulses, 1400 V, 100 μs, 1Hz), or a combination of the two - electrochemotherapy. Pimonidazole was injected 16 hours before tumour excision. Tumours were excised at different time points (0.5, 1, 2, 8, 14 and 24 hours) after therapy. Immunohistochemistry for Glut-1 and pimonidazole adduct was carried out on two consecutive tumour sections and the percentages of positive staining areas were determined.<bold>Results.</bold> Glut-1 staining was membranous and typically expressed peri-necrotically, whereas pimonidazole staining, although showing substantial co-localisation with Glut-1, was cytoplasmatic. More than 65% of the stained areas showed a high degree of colocalization when the two markers were compared. Our results show that Glut-1 expression significantly correlates with the level of pimonidazole binding (r = 0.41; p = 0.028).<bold>Conclusions.</bold> Our study confirms that HIF-1 regulated genes, such as Glut-1, have potential for future use as predictors of a decreased sensitivity of tumours to radio- and chemotherapy mediated by hypoxia.</abstract>

Background. Tumour hypoxia occurs as a result of an inadequate supply of blood-borne oxygen due to the disorganized and chaotic vascular network that develops in tumours. Because tumour hypoxia has been associated with a more aggressive phenotype and lower cure rate, there is a recognized need for a method of measuring tumour hypoxia that is suitable for widespread clinical use. The aim of the current study was to compare the expression of Glut-1 with the binding of the bioreductive hypoxia marker pimonidazole and to elucidate the characteristics and pitfalls when they are used as hypoxic markers.Materials and methods. In the study, SA-1 solid subcutaneous tumours in A/J mice were treated by bleomycin given i.v. (1 mg/kg), or the application of electric pulses (8 pulses, 1400 V, 100 μs, 1Hz), or a combination of the two - electrochemotherapy. Pimonidazole was injected 16 hours before tumour excision. Tumours were excised at different time points (0.5, 1, 2, 8, 14 and 24 hours) after therapy. Immunohistochemistry for Glut-1 and pimonidazole adduct was carried out on two consecutive tumour sections and the percentages of positive staining areas were determined.Results. Glut-1 staining was membranous and typically expressed peri-necrotically, whereas pimonidazole staining, although showing substantial co-localisation with Glut-1, was cytoplasmatic. More than 65% of the stained areas showed a high degree of colocalization when the two markers were compared. Our results show that Glut-1 expression significantly correlates with the level of pimonidazole binding (r = 0.41; p = 0.028).Conclusions. Our study confirms that HIF-1 regulated genes, such as Glut-1, have potential for future use as predictors of a decreased sensitivity of tumours to radio- and chemotherapy mediated by hypoxia.

Comparison between hypoxic markers pimonidazole and glucose transporter 1 (Glut-1) in murine fibrosarcoma tumours after electrochemotherapy

College of Health Care Izola, University of Primorska, Izola, Slovenia

Institute of Oncology Ljubljana, Zaloska 2, Ljubljana, Slovenia

Radiology and Oncology

Background. Tumour hypoxia occurs as a result of an inadequate supply of blood-borne oxygen due to the disorganized and chaotic vascular network that develops...

Comparison between hypoxic markers pimonidazole and glucose transporter 1 (Glut-1) in murine fibrosarcoma tumours after electrochemotherapy

Data publikacji: 14 wrz 2009

Zakres stron: 195 - 202

DOI: https://doi.org/10.2478/v10019-009-0029-5

Słowa kluczowe
hypoxia, pimonidazole, Glut-1, electrochemotherapy

This content is open access.

Comparison between hypoxic markers pimonidazole and glucose transporter 1 (Glut-1) in murine fibrosarcoma tumours after electrochemotherapy

Data publikacji: 14 wrz 2009

Zakres stron: 195 - 202

DOI: https://doi.org/10.2478/v10019-009-0029-5

Słowa kluczowehypoxia, pimonidazole, Glut-1, electrochemotherapy

This content is open access.

Słowa kluczowe
hypoxia, pimonidazole, Glut-1, electrochemotherapy