期刊
JOURNAL OF NEURO-ONCOLOGY
卷 144, 期 1, 页码 33-41出版社
SPRINGER
DOI: 10.1007/s11060-019-03204-0
关键词
Glioblastoma; Blood-brain barrier; Ultrasound; Carboplatin
资金
- Investissements d'avenir [ANR-10-IAIHU-06]
- Institut Universitaire de Cancerologie
- Fondation ARC pour la recherche sur le cancer
- Association pour la Recherche sur les Tumeurs Cerebrales
- Ligue Nationale Contre le Cancer
- CarThera (Paris, France)
- French National Cancer Institute [INCA-DGOS-Inserm_12560 SiRIC CURAMUS]
- French Ministry of Solidarity and Health [INCA-DGOS-Inserm_12560 SiRIC CURAMUS]
- INSERM [INCA-DGOS-Inserm_12560 SiRIC CURAMUS]
- CarThera [INCA-DGOS-Inserm_12560 SiRIC CURAMUS]
IntroductionGlioblastoma (GBM) is the most common and aggressive primary brain cancer in adults. Few cytotoxic chemotherapies have been shown to be effective against GBM, due in part to the presence of the blood-brain barrier (BBB), which reduces the penetration of chemotherapies from the blood to the brain. Ultrasound-induced BBB opening (US-BBB) has been shown to increase the penetration of multiple chemotherapeutic agents in the brain in animal models. In the current study, the anti-tumor activity of carboplatin chemotherapy with and without US-BBB was investigated in several GBM mouse models.MethodsFirst, the IC50 of two commercial (U87 and U251) and six patient-derived GBM cell lines (PDCL) to carboplatin was measured. Next, U87 was subcutaneously grafted to a nude mouse model to test the in vivo response of the tumor to carboplatin in the absence of the BBB. Lastly, nude mice bearing orthotopically xenografted GBM cell lines (U87 or a PDCL) were randomized to four experimental groups: (i) untreated, (ii) US-BBB alone, (iii) carboplatin alone and, (iv) carboplatin+US-BBB. Mice were treated once weekly for 4 weeks and monitored for toxicity, tumor growth, and survival.ResultsCarboplatin plus US-BBB enhanced survival (p=0.03) and delayed tumor growth (p<0.05) of GBM-bearing mice compared to carboplatin alone, with a 4.2-fold increase of carboplatin penetration in the brain, without evidence of significant neurological or systemic toxicity.ConclusionsCarboplatin efficacy was enhanced in GBM mouse models with US-BBB and appears to be a promising chemotherapy for this approach.
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