| Autor: |
Charles Dupin, Jade Sutter, Samuel Amintas, Marie-Alix Derieppe, Magalie Lalanne, Soule Coulibaly, Joris Guyon, Thomas Daubon, Julian Boutin, Jean-Marc Blouin, Emmanuel Richard, François Moreau-Gaudry, Aurélie Bedel, Véronique Vendrely, Sandrine Dabernat |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cancers, Vol 14, Iss 17, p 4244 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2072-6694 |
| DOI: |
10.3390/cancers14174244 |
| Popis: |
Radiosensitization of glioblastoma is a major ambition to increase the survival of this incurable cancer. The 5-aminolevulinic acid (5-ALA) is metabolized by the heme biosynthesis pathway. 5-ALA overload leads to the accumulation of the intermediate fluorescent metabolite protoporphyrin IX (PpIX) with a radiosensitization potential, never tested in a relevant model of glioblastoma. We used a patient-derived tumor cell line grafted orthotopically to create a brain tumor model. We evaluated tumor growth and tumor burden after different regimens of encephalic multifractionated radiation therapy with or without 5-ALA. A fractionation scheme of 5 × 2 Gy three times a week resulted in intermediate survival [48–62 days] compared to 0 Gy (15–24 days), 3 × 2 Gy (41–47 days) and, 5 × 3 Gy (73–83 days). Survival was correlated to tumor growth. Tumor growth and survival were similar after 5 × 2 Gy irradiations, regardless of 5-ALA treatment (RT group (53–67 days), RT+5-ALA group (40–74 days), HR = 1.57, p = 0.24). Spheroid growth and survival were diminished by radiotherapy in vitro, unchanged by 5-ALA pre-treatment, confirming the in vivo results. The analysis of two additional stem-like patient-derived cell lines confirmed the absence of radiosensitization by 5-ALA. Our study shows for the first time that in a preclinical tumor model relevant to human glioblastoma, treated as in clinical routine, 5-ALA administration, although leading to important accumulation of PpIX, does not potentiate radiotherapy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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