Epigenetic changes such as DNA methylation regulate gene expression in normal development. Methotrexate and Adriamycine are antineoplastic drugs that target DNA and enzymes acting on DNA. We aimed to evaluate their cytotoxic effect on cell lines and on female mice to investigate the in vivo influence of both drugs on the DNA methylation and subsequently the protein expression. The total level of DNA methylation showed a significant reduction from 62.2% to 36.7%, 36.6% as compared to control group, when using different doses of MTX and ADR. Hepatic protein pattern revealed five bands with low MW (16 -6.1 KDa) in acute and LD50 doses. In conclusion DNA methylation is influenced by anticancer drugs in a dose-dependent manner. Some specific protein fragments may be considered as a potential markers associated with high dose of anticancer drugs.
Introduction Several long noncoding RNAs (lncRNAs) have been demonstrated to play a critical role in the tumorigenesis of acute myeloid leukemia (AML), and altered expression of certain lncRNAs has been recognized as a potential prognostic marker in AML patients. Here, we sought to determine whether the expression of the lncRNA colorectal neoplasia differentially expressed (CRNDE) and aldehyde oxidase 2 pseudogene (AOX2P) is associated with clinicopathological features and clinical outcome of patients with AML. Methods CRNDE and AOX2P expression levels were measured in diagnostic blood samples from 200 adult patients with de novo AML, along with 50 healthy control blood samples, using quantitative real‐time polymerase chain reaction (qRT‐PCR). The association of CRNDE and AOX2P expression with the clinicopathological characteristics and outcome of AML patients was analyzed. Results Upregulated CRNDE expression was independently associated with lower complete remission (CR) rates in the whole cohort of AML (P < .001). AOX2P overexpression was identified as an independent adverse prognostic marker for CR in the CN‐AML (P = .009) and non‐t (15;17) AML (P < .001) subgroups. Patients with high CRNDE expression had a significantly shorter event‐free survival (EFS, whole cohort of AML: P = .017; CN‐AML: P = .001; non‐t (15;17) AML: P = .006) and inferior overall survival (OS, whole cohort of AML: P = .002; t(15;17) AML: P = .001) than those with low CRNDE expression. EFS and OS did not differ significantly between patients with high AOX2P expression and those with low expression. Conclusion Aberrantly upregulated CRNDE expression and, to a lesser extent, AOX2P overexpression, are associated with poor prognosis in AML patients, suggesting that the determination of CRNDE and, perhaps, AOX2P, expression level at diagnosis provides valuable prognostic information, allows refinement of risk stratification, and helps clinical decision‐making in AML.
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