| Popis: |
Glioblastoma Multiforme (GBM) is a diffuse malignant brain tumor with rapid growth and infiltration, high resistance to available therapies, and poor survival rate. The current standard of care only provides patients with an average survival of 12–14 months. Platelet-Activating Factor (PAF) is a strong mediator of inflammation, and its receptor, PAF-R, is over-activated in the microenvironment of different tumors as part of an enhanced neuroinflammatory response. PAF-R antagonists are beneficial in experimental ischemic stroke and counteract epileptogenesis. The purpose of this study was to determine if the PAF-R antagonist, LAU-0901, could delay GBM progression and improve survival. METHODS: U87MG cells were implanted in the right dorsal CA3 hippocampal region of BALB/c (nu/nu) mice. Intracranial tumor growth was quantified using in vivo bioluminescent imaging on days 10 and 25, and then every 2 weeks. Saline (vehicle, n=6) or LAU-0901 (60mg/kg/day; IP, n= 6) was administered daily from days 10 to 15 post GBM implantation. RESULTS: Tumor size before treatment on day 10 was identical in both groups. A large GBM mass was present in saline-treated mice and most of these mice died within 6 weeks; only two animals survived for the 10-week survival period. In contrast, tumor size was dramatically reduced by LAU-0901 treatment during the survival period. LAU-0901 treatment diminished tumor size by 80% on day 25, compared to saline-treated group. In addition, body weight increased by 30–45% in LAU-0901-treated mice at weeks 8 and 10. CONCLUSION: We have demonstrated that treatment with PAF-R antagonist, LAU-0901, decreased tumor growth, increased body weight and improved survival in a GBM mouse model. This novel experimental therapy can provide future avenues for GBM treatment. ABSTRACTS FROM THE 3(rd) CNS ANTICANCER DRUG DISCOVERY AND DEVELOPMENT CONFERENCE |
