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• W4361943670 abstract "<div>Abstract<p><b>Purpose:</b> Brain metastases are a common preterminal event in patients with metastatic melanoma and require radiation therapy. Our group has previously shown that human GRM1 (hGRM1) expressing melanoma cells release excess extracellular glutamate and are growth inhibited by riluzole, an inhibitor of glutamate release. Riluzole-treated cells accumulate in G₂/M phase of the cell cycle at 24 hours, and then undergo apoptotic cell death. We evaluated whether riluzole enhanced radiosensitivity in melanoma cells.</p><p><b>Experimental Design:</b> Clonogenic assays were performed to evaluate clonogenic survival after treatment in hGRM1 expressing and nonexpressing melanoma cells. Western immunoblots were performed to confirm apoptotic cell death. A xenograft mouse model was used to validate the <i>in vitro</i> experiments. Tumors harvested from the xenografts were fixed and stained for apoptosis and DNA damage markers.</p><p><b>Results:</b> In the hGRM1-positive cell lines C8161 and UACC903, riluzole enhanced the lethal effects of ionizing radiation; no difference was seen in the hGRM1-negative UACC930 cell line. C8161 cells treated with riluzole plus irradiation also showed the highest levels of the cleaved forms of PARP and caspase-3; excised C8161 xenografts showed the greatest number of apoptotic cells by immunohistochemistry (<i>P</i> < 0.001). On cell cycle analysis, a sequence-dependent enrichment in the G₂/M phase was shown with the combination of riluzole and irradiation. Xenografts treated with riluzole and weekly radiation fractions showed significant growth inhibition and revealed markedly increased DNA damage.</p><p><b>Conclusions:</b> We have shown, <i>in vitro</i> and <i>in vivo</i>, that the combination of riluzole and ionizing radiation leads to greater cytotoxicity. These results have clinical implications for patients with brain metastases receiving whole brain radiation therapy. <i>Clin Cancer Res; 17(7); 1807–14. ©2011 AACR</i>.</p></div>" @default.
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• W4361943670 date "2023-03-31" @default.
• W4361943670 modified "2023-10-14" @default.
• W4361943670 title "Data from Riluzole Enhances Ionizing Radiation–Induced Cytotoxicity in Human Melanoma Cells that Ectopically Express Metabotropic Glutamate Receptor 1 <i>In Vitro</i> and <i>In Vivo</i>" @default.
• W4361943670 doi "https://doi.org/10.1158/1078-0432.c.6519486" @default.
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