Acta Scientific Pharmaceutical Sciences

Research ArticleVolume 2 Issue 9

Effect of O6 -Methylguanine-DNA Methyltransferase Resistance to Temozolomide in Gliomas or Brain Metastases of Melanoma

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).

Abstract

  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.



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