Drug resistance-associated factors in primary and secondary glioblastomas and their precursor tumors

Malignant gliomas are largely resistant to current chemotherapeutic strategies often displaying a multidrug-resistant phenotype. Mechanisms involved in drug resistance are reduced cellular drug accumulation through membrane efflux pumps, drug detoxification as well as alterations in drug target spec...

Full description

Saved in:
Bibliographic Details
Published in:Journal of neuro-oncology 2000-12, Vol.50 (3), p.227-237
Main Authors: TEWS, Dominique S, NISSEN, Anja, KÜLGEN, Claudia, GAUMANN, Andreas K. A
Format: Article
Language:English
Subjects:
Adult
Aged
Antibodies, Monoclonal
Antigens, Neoplasm
Antineoplastic agents
Antineoplastic Agents - therapeutic use
ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism
ATP-Binding Cassette Transporters - metabolism
Biological and medical sciences
Brain Neoplasms - drug therapy
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Brain Neoplasms - secondary
Cell Membrane - chemistry
Chemotherapy
DNA Topoisomerases, Type II - metabolism
DNA-Binding Proteins
Drug Resistance, Neoplasm
Glioblastoma - metabolism
Glioblastoma - pathology
Humans
Immunoenzyme Techniques
Isoenzymes - metabolism
Medical sciences
Metallothionein - metabolism
Middle Aged
Multidrug Resistance-Associated Proteins
Neoplasm Proteins - metabolism
Neurology
Pharmacology. Drug treatments
Tumors of the nervous system. Phacomatoses
Vault Ribonucleoprotein Particles - metabolism
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Malignant gliomas are largely resistant to current chemotherapeutic strategies often displaying a multidrug-resistant phenotype. Mechanisms involved in drug resistance are reduced cellular drug accumulation through membrane efflux pumps, drug detoxification as well as alterations in drug target specificity. In 27 primary and 17 secondary glioblastomas and their astrocytic precursor tumors, we studied the immunohistochemical expression profile of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), metallothionein, and topoisomerase II alpha. Glial tumor cells in all glioblastomas showed constant up-regulation of LRP, MRP, and topoisomerase II alpha. P-gp was found in 90% of the primary and 60% of the secondary glioblastomas. In precursor tumors, these drug resistance-related factors were expressed in varying proportions. Metallothionein, also found in normal and activated astrocytes, was retained in all neoplastic phenotypes. Furthermore, metallothionein, P-gp, LRP, and topoisomerase II alpha were strongly expressed by normal and neoplastic vessels which may confer to impaired penetration of therapeutic agents through the blood-brain and blood-tumor barrier. However, the expression profiles of drug resistance-related proteins neither differed between primary and secondary glioblastomas nor revealed any correlation to precursor or recurrent tumors. Nevertheless, inhibition of these factors may be promising approaches to the management of malignant gliomas.
ISSN:0167-594X
1573-7373
DOI:10.1023/A:1006491405010