El-Khatib, Mustafa and Tepe, Carolin and Senger, Brigitte and Dibue-Adjei, Maxine and Riemenschneider, Markus Johannes and Stummer, Walter and Steiger, Hans Jakob and Cornelius, Jan Frederick (2015) Aminolevulinic Acid-Mediated Photodynamic Therapy of Human Meningioma: An in Vitro Study on Primary Cell Lines. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 16 (5). pp. 9936-9948. ISSN 1422-0067,
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Objective: Five-aminolevulinic acid (5-ALA)-induced porphyrins in malignant gliomas are potent photosensitizers. Promising results of ALA-PDT (photodynamic therapy) in recurrent glioblastomas have been published. Recently, 5-ALA-induced fluorescence was studied in meningioma surgery. Here, we present an experimental study of ALA-PDT in an in vitro model of primary meningioma cell lines. Methods: We processed native tumor material obtained intra-operatively within 24 h for cell culture. Epithelial membrane antigen (EMA) immunohistochemistry was performed after the first passage to confirm that cells were meningioma cells. For 5-ALA-PDT treatment, about 5000 cells per well were seeded in 20 wells of a blank 96-well plate. Each block of 4 wells was inoculated with 150 mu L of 0, 25, 50 and 100 mu g/mL 5-ALA solutions; one block was used as negative control without 5-ALA and without PDT. Following incubation for 3 h PDT was performed using a laser (635 nm, 18.75 J/cm(2)). The therapeutic response was analyzed by the water soluble tetrazolium salt (WST-1) cell viability assay 90 min after PDT. Results: 5-ALA-PDT was performed in 14 primary meningioma cell lines. EMA expression was verified in 10 primary cell cultures. The remaining 4 were EMA negative and PDT was without any effect in these cultures. All 10 EMA-positive cell lines showed a significant and dose-dependent decrease in viability rate (p < 0.001). Cell survival at 5-ALA concentrations of 12.5, 25, 50 and 100 g/mL was 96.5% +/- 7.6%, 67.9% +/- 29.9%, 24.0% +/- 16.7% and 13.8% +/- 7.5%, respectively. For the negative controls (no 5-ALA/PDT and ALA/no PDT), the viability rates were 101.72% +/- 3.5% and 100.17% +/- 3.6%, respectively. The LD50 for 5-ALA was estimated between 25 and 50 mu g/mL. Conclusion: This study reveals dose-dependent cytotoxic effects of 5-ALA-PDT on primary cell lines of meningiomas. Either 5-ALA or PDT alone did not affect cell survival. Further efforts are necessary to study the potential therapeutic effects of 5-ALA-PDT in vivo.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FLUORESCENCE-GUIDED RESECTION; PROTOPORPHYRIN-IX FLUORESCENCE; 5-AMINOLEVULINIC ACID; MALIGNANT GLIOMA; ALA; RADIOSURGERY; RECURRENCE; MECHANISMS; SURGERY; CLASSIFICATION; 5-ALA; aminolevulinic acid; PDT; photodynamic therapy; meningioma; in vitro; primary cell culture |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Neuropathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Jul 2019 09:45 |
| Last Modified: | 18 Jul 2019 09:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5536 |
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