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Drug Resistance-associated Factors in Primary and Secondary Glioblastomas and their Precursor Tumors

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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 α. Glial tumor cells in all glioblastomas showed constant up-regulation of LRP, MRP, and topoisomerase II α. 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 α 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.

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Authors and Affiliations

  1. Division of Neuropathology, Johannes Gutenberg-University Medical Center, Mainz, Germany

    Dominique S. Tews, Anja Nissen & Claudia Külgen

  2. Department of Pathology, Johannes Gutenberg-University Medical Center, Mainz, Germany

    Andreas K.A. Gaumann

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  1. Dominique S. Tews
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  2. Anja Nissen
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Tews, D.S., Nissen, A., Külgen, C. et al. Drug Resistance-associated Factors in Primary and Secondary Glioblastomas and their Precursor Tumors. J Neurooncol 50, 227–237 (2000). https://doi.org/10.1023/A:1006491405010

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