CAT<sub>3</sub>, a prodrug of 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro[9,10-b]-indolizidine, circumvents temozolomide-resistant glioblastoma via the Hedgehog signaling pathway, independently of O<sup>6</sup>-methylguanine DNA methyltransferase expression
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منابع مشابه
O6-Methylguanine DNA methyltransferase protein expression in tumor cells predicts outcome of temozolomide therapy in glioblastoma patients.
O(6)-Methylguanine DNA methyltransferase (MGMT) is implicated as a major predictive factor for treatment response to alkylating agents including temozolomide (TMZ) of glioblastoma multiforme (GBM) patients. However, whether the MGMT status in GBM patients should be detected at the level of promoter methylation or protein expression is still a matter of debate. Here, we compared promoter methyla...
متن کاملPrognostic significance of O6-methylguanine-DNA methyltransferase protein expression in patients with recurrent glioblastoma treated with temozolomide.
BACKGROUND Temozolomide (TMZ) is active against newly diagnosed glioblastoma (GBM), and O(6)-methylguanine-DNA methyltransferase (MGMT) is implicated in resistance to TMZ and nitrosoureas. We evaluated the efficacy and safety of the standard 5-day TMZ regimen in patients with recurrent GBM after initial therapy including nitrosourea-based chemotherapy, in conjunction with an analysis of the pro...
متن کاملIFN-B sensitizes neuroblastoma to the antitumor activity of temozolomide by modulating O-methylguanine DNA methyltransferase expression
Although temozolomide has shown clinical activity against neuroblastoma, this activity is likely limited by the DNA repair enzyme O-methylguanine DNA methyltransferase (MGMT). We hypothesized that IFN-B could sensitize neuroblastoma cells to the cytotoxic effects of temozolomide through its ability to down-regulate MGMT expression. In vitro proliferation of three neuroblastoma cell lines treate...
متن کاملRegulation of expression of O6-methylguanine-DNA methyltransferase and the treatment of glioblastoma (Review)
O-6-methylguanine-DNA methyltransferase (MGMT) is an abundantly expressed nuclear protein dealkylating O6-methylguanine (O6-MG) DNA residue, thus correcting the mismatches of O6-MG with a thymine residue during DNA replication. The dealkylating effect of MGMT is relevant not only in repairing DNA mismatches produced by environmental alkylating agents promoting tumor pathogenesis, but also when ...
متن کاملRegulation of expression of the DNA repair gene O6-methylguanine-DNA methyltransferase via protein kinase C-mediated signaling.
O6-Alkylguanine is the major mutagenic and cytotoxic DNA lesion induced by alkylating agents, including 2-chloroethyl-N-nitrosourea-based antitumor drugs. This lesion is repaired by O6-methylguanine-DNA methyltransferase (MGMT), the expression of which is highly variable in both normal tissues and in tumor cells. The promoter of the human MGMT gene was found to contain two putative activator pr...
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ژورنال
عنوان ژورنال: OncoTargets and Therapy
سال: 2018
ISSN: 1178-6930
DOI: 10.2147/ott.s163535