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

Abstract	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.
Authors	D S Tews, A Nissen, C Külgen, A K Gaumann
Journal	Journal of neuro-oncology (J Neurooncol) Vol. 50 Issue 3 Pg. 227-37 (Dec 2000) ISSN: 0167-594X [Print] United States
PMID	11263502 (Publication Type: Journal Article)
Chemical References	ATP Binding Cassette Transporter, Subfamily B, Member 1 ATP-Binding Cassette Transporters Antibodies, Monoclonal Antigens, Neoplasm Antineoplastic Agents DNA-Binding Proteins Isoenzymes Multidrug Resistance-Associated Proteins Neoplasm Proteins Vault Ribonucleoprotein Particles major vault protein Metallothionein DNA Topoisomerases, Type II
Topics	ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism) ATP-Binding Cassette Transporters (metabolism) Adult Aged Antibodies, Monoclonal Antigens, Neoplasm Antineoplastic Agents (therapeutic use) Brain Neoplasms (drug therapy, metabolism, pathology, secondary) Cell Membrane (chemistry) DNA Topoisomerases, Type II (metabolism) DNA-Binding Proteins Drug Resistance, Neoplasm Glioblastoma (metabolism, pathology) Humans Immunoenzyme Techniques Isoenzymes (metabolism) Metallothionein (metabolism) Middle Aged Multidrug Resistance-Associated Proteins Neoplasm Proteins (metabolism) Vault Ribonucleoprotein Particles (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!