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Dexamethasone alone and in combination with desipramine, phenytoin, valproic acid or levetiracetam interferes with 5-ALA-mediated PpIX production and cellular retention in glioblastoma cells

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Abstract

Extent of resection of glioblastoma (GBM) correlates with overall survival. Fluorescence-guided resection (FGR) using 5-aminolevulinic acid (5-ALA) can improve the extent of resection. Unfortunately not all patients given 5-ALA accumulate sufficient quantities of protoporphyrin IX (PpIX) for successful FGR. In this study, we investigated the effects of dexamethasone, desipramine, phenytoin, valproic acid, and levetiracetam on the production and accumulation of PpIX in U87MG cells. All of these drugs, except levetiracetam, reduce the total amount of PpIX produced by GBM cells (p < 0.05). When dexamethasone is mixed with another drug (desipramine, phenytoin, valproic acid or levetiracetam) the amount of PpIX produced is further decreased (p < 0.01). However, when cells are analyzed for PpIX cellular retention, dexamethasone accumulated significantly more PpIX than the vehicle control (p < 0.05). Cellular retention of PpIX was not different from controls in cells treated with dexamethasone plus desipramine, valproic acid or levetiracetam, but was significantly less for dexamethasone plus phenytoin (p < 0.01). These data suggest that medications given before and during surgery may interfere with PpIX accumulation in malignant cells. At this time, levetiracetam appears to be the best medication in its class (anticonvulsants) for patients undergoing 5-ALA-mediated FGR.

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Authors and Affiliations

  1. Upper Michigan Brain Tumor Center, Northern Michigan University, 1401 Presque Isle Ave, Marquette, MI, 49855, USA

    Johnathan E. Lawrence, Robert J. Belton Jr. & Robert J. Winn

  2. College of Human Medicine, Michigan State University, 965 Fee Rd, Room A-110, Lansing, MI, 48824, USA

    Christopher J. Steele

  3. Aurora Neuroscience Innovation Institute, Aurora Health Care, 2801 W Kinnickinnic River Pkwy, Milwaukee, WI, 53215, USA

    Richard A. Rovin

Authors
  1. Johnathan E. Lawrence
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  3. Richard A. Rovin
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  4. Robert J. Belton Jr.
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  5. Robert J. Winn
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Correspondence to Robert J. Winn.

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Lawrence, J.E., Steele, C.J., Rovin, R.A. et al. Dexamethasone alone and in combination with desipramine, phenytoin, valproic acid or levetiracetam interferes with 5-ALA-mediated PpIX production and cellular retention in glioblastoma cells. J Neurooncol 127, 15–21 (2016). https://doi.org/10.1007/s11060-015-2012-x

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