This retrospective study examined the prognostic significance and treatment effect of promoter methylation of O6- methyl guanine methyl transferase (MGMT) and meth-ylation of CpG 1, CpG2, CpG3 and CpG4 in glioblastoma (GB) patients received postoperative radiotherapy (PORT), with or without adjuvant temozolomide (TMZ). One hundred patients with GB who received PORT with concomitant TMZ plus adjuvant TMZ or PORT alone, were included. The MGMT promoter methylation of CpG1, CpG2, CpG3 and CpG4 islands were examined. Overall, MGMT-methylation emerged as a significant prognostic factor for better overall survival (OS) and progression-free survival (PFS) [odds ratio (OR): 0.609, 95% confidence interval (95% CI): 0.395-0.939, p = 0.02; OR: 0.662,95% CI: 0.430-1019, p = 0.5, respectively]. The methylation of each CpG1, CpG2, CpG3 and CpG4 islands was found to have no significant effects on OS and the methylation of each CpGl, CpG2 and CpG4 islands had no significant effect on PFS (p <0.05 for all). On the other hand, the methylation of CpG3 had a positive prognostic effect on PFS (OR: 2.1, 95% CI: 0.99-4.67, p = 0.04). In the group that only received radiotherapy (RT), CpG1 and CpC3 methylations were found to have a positive prognostic significance in terms of PFS (OR: 266, 95% CI: 1.05-6.75, p -0.03 for CpG1; OR: 2.4, 95% CI: 1.01-5.92, p = 0.04 for CpG3). The MGMT promoter methylation represents an important biomarker for predicting response to therapy. Individual islands, particularly CpG3, deserves further investigation as a prognostic marker. Further studies need to be done with larger sample sizes to clarify the results.
Background: In this study, expression level analysis of genes associated with Attention Deficit Hyperactivity Disorder (ADHD) (SLC6A3, SLC6A4, SLC1A2, VMAT2, MAOA, COMT, GLYAT, GRM5, DRD4, TPH1, and ADRA2C) by pre-treatment and post-treatment with Atomoxetine and Methylphenidate was investigated. Methods: Forty-three ADHD diagnosed children and 38 healthy children were included to study. Forty-three patients with ADHD were divided into two groups, of which 35 patients used methylphenidate and 8 patients use atomoxetine. Five main study groups were generated: A control group, a group that includes methylphenidate pre-treatment samples, a group includes methylphenidate post-treatment samples, a group that includes atomoxetine pre-treatment samples and a group that includes atomoxetine post-treatment samples. Blood samples (10 ml each) were taken from everyone in study groups into EDTA tubes and RNA isolation was performed. mRNA expression levels of 11 determined candidate genes were showed via reverse transcription quantitative PCR method. Results: The expression levels of SLC6A3 (DAT) of ADHD diagnosed children were significantly higher than the control group, while the mRNA expression levels of SLC6A4, SLC1A2, VMAT2, MAOA, COMT, GLYAT, and TPH1 genes were significantly lower (t- test, p≤0.01).Conclusion: The expression level differences of these genes were determined to be useful as biomarkers in the diagnosis of ADHD. More patient numbers and studies with different groups are needed to fully reveal the relationship between these genes and the disease and its treatment.
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