Emad Y Moawad*
Researcher Graduated, Department of Engineering, Ain Shams University, Cairo, Egypt
*Corresponding Author: Emad Y Moawad, Researcher Graduated, Department of Engineering, Ain Shams University, Cairo, Egypt
Received: July 19, 2018; Published: August 02, 2018
Citation: Emad Y Moawad. “Effect of O6 -Methylguanine-DNA Methyltransferase Resistance to Temozolomide in Gliomas or Brain Metastases of Melanoma”. Acta Scientific Pharmaceutical Sciences 2.9 (2018).
The aim of this study is to investigate the resistance of O6-methylguanine-DNA methyltransferase (MGMT) in gliomas or brain metastases of melanoma to Temozolomide (TMZ) therapy. The in-vivo effects of standard, metronomic and dose-dense TMZ regimens in animal models were monitored to identify efficacy of those regimens with respect to suppression of MGMT-resistance in tumor cells. MGMT-resistance is dependent mainly on the TMZ dose/day of the applied regimen, observed when applying standard regimens of 2.45 mg/kg bw/day for 5days every 28 days and maximized by increasing dose/day to 6.74 mg/kg bw/day for 5days every 28 days. Afterwards, MGMT-resistance decreased gradually until being suppressed by increasing the received dose/day in standard regimen to 8.88 mg/kg bw/day for 5 days every 28 days. Standard regimen of dose less than 4.37 mg/kg bw/day for 5 days every 28 days is more efficient than the metronomic one of dose/day less than 0.78 mg/kg bw/day for 28 days in early stages of primary tumors. While the metronomic regimen of dose/day lies between 0.78 and 1.6 mg/kg bw/day for 28 days is more efficient than the standard one of administered dose lies between 4.37 and 8.96 mg/kg bw/day for 5days every 28 days in the moderate stages of recurrent tumors of higher MGMT-resistance. Dose-dense regimens with standard schedule of dose/day higher than 8.96 mg/kg bw/ day for 5 days every 28 days or metronomic schedule of dose/day higher than 1.6 mg/kg bw/ day for 28 days suppress MGMT-mediated resistance in advanced stages of high-grade tumors by depleting MGMT in tumor cells.
Keywords: Temozolomide; O6-Methylguanine-DNA Methyltransferase; Gliomas; Brain Metastases of Melanoma
Copyright: © 2018 Emad Y Moawad. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.