AI Article Synopsis
- The study investigated the effectiveness of PARP inhibitor MK-4827 combined with radiation to treat neuroblastoma.
- Treatment with MK-4827 showed reduced survival of neuroblastoma cells and had additive effects when combined with radiation.
- In animal models, this combination not only prolonged survival but also increased indicators of tumor cell death, suggesting it could be a promising therapy for high-risk neuroblastoma in children.
Article Abstract
Background/aim: To assess poly (ADP-ribose) polymerase (PARP) inhibitor MK-4827 together with radiation for the treatment of neuroblastoma.
Materials And Methods: Clonogenic survival assays were used to assess MK-4827, radiation and combination thereof in four neuroblastoma cell lines. In vivo efficacy was tested in a murine xenograft model of metastatic neuroblastoma. In vivo targeted inhibition and biological effects included measurement of cleaved caspase-3, γ-H2AX, and Ki 67 by immunohistochemistry (IHC) and poly-ADP-ribose by Enzyme-Linked Immunosorbent Assay.
Results: Treatment of neuroblastoma cell lines reduced clonogenicity and resulted in additive effects with radiation. In vivo treatment with MK-4827 and radiation prolonged survival (p<0.01) compared to single modalities. In vivo superiority of MK-4827 plus radiation was further documented by significant elevations of cleaved caspase-3 and γ-H2AX in tumors from the combination group compared to single modality cohorts.
Conclusion: Combination of MK-4827 and radiation might provide effective therapy for children with high-risk neuroblastoma.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684561 | PMC |
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