2012
DOI: 10.1007/s11060-012-0857-9
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Phenytoin reduces 5-aminolevulinic acid-induced protoporphyrin IX accumulation in malignant glioma cells

Abstract: Epileptic seizures are among the presenting clinical signs of malignant glioma patients, frequently necessitating treatment with antiepileptic drugs (AEDs). The efficacy of 5-aminolevulinic acid (5-ALA)-based intraoperative fluorescence-guided surgery and photodynamic therapy (PDT) in glioblastoma multiforme (GBM) patients depends on the specific accumulation and total amount of intracellularly synthesized protoporphyrin IX (PpIX) in tumour cells. In this study, we investigated the effect of the AEDs phenytoin… Show more

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Cited by 41 publications
(31 citation statements)
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“…This phenomenon is known in the adult literature; however, the implication in the pediatric pathology spectrum is unknown. In addition, steroids and AED (especially phenytoin) may affect 5ALA uptake and various tumor and steroid protocols may influence the results [20].…”
Section: Limitationsmentioning
confidence: 99%
“…This phenomenon is known in the adult literature; however, the implication in the pediatric pathology spectrum is unknown. In addition, steroids and AED (especially phenytoin) may affect 5ALA uptake and various tumor and steroid protocols may influence the results [20].…”
Section: Limitationsmentioning
confidence: 99%
“…The dark toxicity was evaluated under two conditions: 48 h of drug incubation for comparison with cisplatin and 4 h drug incubation for comparison with the clinically used PS 5-aminolevulinic acid (5-ALA). [22,62,63] To study the phototoxic activity of the compounds, the cancer cells were first incubated with the compounds for 4 h, the medium was then replaced with a fresh one before the cells were irradiated at 420 nm light for 20 min (9.27 J cm -2 ). After light irradiation, the cells were incubated for another 44 h. Notably, because of the low solubility of the compounds, the highest concentration that could be reached in cell culture medium for L1 and L2 was 2 μM.…”
Section: Dark Toxicity and Phototoxicitymentioning
confidence: 99%
“…Although the extent to which this may or may not occur is somewhat controversial, there is a need for the development of instruments with increased sensitivity for the detection of intraoperative fluorescence and a need for methods to increase specificity. 21,28 Additional studies are also needed to identify therapeutic agents and intrinsic molecular characteristics that affect the metabolism of 5-ALA, such as has been seen with phenytoin, 16 cadherin 13 expression, 34 aquaporin, 33 and ferrochelatase expression. 36 Other dyes, such as methylene blue, are being studied for their ability to enhance the morphologic image; 46 however, the utility of this approach relies on the surgeon's ability to recognize sometimes subtle morphological characteristics.…”
Section: Discussionmentioning
confidence: 99%
“…4,10,14,27,[39][40][41] Studies designed to identify mechanisms of false-positive and false-negative results have shown effects from differences in the levels of tumor cell metabolism, intraoperative microscope sensitivity, 5-ALA uptake, 5-ALA metabolism (resulting from intrinsic molecular characteristics of the tumor and/or interactions with other therapies), diffusion of protoporphyrin IX, and other factors. 4,8,16,23,27,29,36,[40][41][42] Despite these caveats, the improved patient outcomes reported after use of 5-ALA underscore the utility of tumor markers that can be used intraoperatively to improve tumor cell identification and facilitate more complete resections.…”
mentioning
confidence: 99%