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Human brain tumors: multidrug-resistance P-glycoprotein expression in tumor cells and intratumoral capillary endothelial cells

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Abstract

Malignant brain tumor is a lethal disease with currently available treatment options having a limited impact on outcome. Nevertheless, novel therapeutic approaches combined with genetic prediction of chemosensitivity have, in the last decade, significantly improved clinical benefit for the treated patients. The fine characterization of the MDR1 gene encoding for P-glycoprotein (MDR1–Pgp) in brain tumors may be a crucial determinant for evaluating the long-term efficiency of specific anti-cancer compounds. By using a very high specific monoclonal antibody, the MDR1–Pgp was immunodetected in 34 out of 43 grade IV, 6 out of 10 grade III, 4 out of 7 grade II, and 1 out 3 grade I brain tumors. MDR1–Pgp resulted hyper-expressed, both in vessels and in neoplastic cells from the majority of tumors examined, compared to normal parenchyma. This study demonstrates that the MDR1 gene can be detected in all grade tumor brain malignancies and in endothelial cells of newly formed capillaries, thus, impairing drug access at the tumor cell level. Although the role of MDR1–Pgp in tumor blood vessels needs to be further examined and more clearly defined, drug resistance in malignant brain tumors may result from characteristics not only of tumor vasculature but also of neoplastic cells.

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Acknowledgment

We thank Mrs. Katia De Ieso for the immunohistochemistry studies. This work was supported partly by an ISS–NIH research grant.

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Authors and Affiliations

  1. Pathological Anatomy III, Department of Surgery, University of Pisa, 56100, Pisa, Italy

    Silvia Fattori, Francesca Becherini, Maurizio Cianfriglia, Giuliano Parenti, Antonella Romanini & Maura Castagna

  2. Department of Drug Research and Evaluation, Istituto Superiore di Sanità, 00161, Rome, Italy

    Maurizio Cianfriglia

  3. Department of Neurosurgery, University of Pisa, 56100, Pisa, Italy

    Giuliano Parenti

  4. Division of Medical Oncology and Plastic Surgery, University Hospital, 56100, Pisa, Italy

    Antonella Romanini

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  1. Silvia Fattori
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  2. Francesca Becherini
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  3. Maurizio Cianfriglia
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  4. Giuliano Parenti
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  5. Antonella Romanini
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  6. Maura Castagna
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Correspondence to Silvia Fattori.

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Fattori, S., Becherini, F., Cianfriglia, M. et al. Human brain tumors: multidrug-resistance P-glycoprotein expression in tumor cells and intratumoral capillary endothelial cells. Virchows Arch 451, 81–87 (2007). https://doi.org/10.1007/s00428-007-0401-z

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  • DOI: https://doi.org/10.1007/s00428-007-0401-z

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