Rapid induction of long-lasting drug efflux activity in brain vascular endothelial cells but not malignant glioma following irradiation
| Autor: | Håkan Hedman, Roger Henriksson, Ulrika Andersson, A. T. Bergenheim, Parviz Behnam-Motlagh, Kjell Grankvist |
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| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
ATP Binding Cassette Transporter Subfamily B medicine.medical_treatment Drug resistance Pharmacology Blood–brain barrier Immunoenzyme Techniques chemistry.chemical_compound Glioma medicine Tumor Cells Cultured Animals Humans ATP Binding Cassette Transporter Subfamily B Member 1 RNA Messenger P-glycoprotein DNA Primers Chemotherapy biology Brain Neoplasms Reverse Transcriptase Polymerase Chain Reaction Hematology General Medicine medicine.disease Calcium Channel Blockers Fluoresceins Rats Calcein Endothelial stem cell medicine.anatomical_structure Oncology chemistry Verapamil Drug Resistance Neoplasm biology.protein ATP-Binding Cassette Transporters Efflux Endothelium Vascular |
| Zdroj: | Medical oncology (Northwood, London, England). 19(1) |
| ISSN: | 1357-0560 |
| Popis: | The influence of radiotherapy on malignant glioma multidrug resistance to chemotherapy was evaluated because patients with glioma often are treated with a combination of radiotherapy and chemotherapy. Multidrug resistance gene (MDR1, mdr1a, and mdr1b) transcripts were found in human and rat glioma cell lines. P-Glycoprotein (Pgp) was immunohistochemically detected in glioma cell lines and in the rat brain vascular endothelial cell line (RBE4). A multidrug resistance pump efflux activity assay demonstrated increased calcein efflux of RBE4 endothelial cells, but not glioma cells, 2 h after irradiation and still increased 14 d after irradiation. The increased efflux was equally inhibited by verapamil with or without irradiation. In the rat intracranial glioma model (BT4C), Pgp was demonstrated in capillary endothelial cells of the tumor tissue and surrounding normal brain, but not in tumor cells. The expression of gene transcripts or Pgp was not affected by irradiation. The results indicate that long-lasting verapamil-resistant drug efflux mechanisms are activated in brain endothelial cells after irradiation. The results might explain the poor efficacy of chemotherapy following radiotherapy and contribute to consideration of new treatment strategies in the management of malignant glioma. |
| Databáze: | OpenAIRE |
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