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Astrocytomas are the most common primary brain tumors. They are very resistant to therapies and usually progress rapidly to high-grade lesions. Here, we investigated the potential role of DNA repair genes in astrocytoma progression and resistance. To this aim, we performed a polymerase chain reaction array-based analysis focused on DNA repair genes and searched for correlations between expression patters and survival prognoses. We found 19 genes significantly altered. Combining these genes in all possible arrangements, we found 421 expression signatures strongly associated with poor survival. Importantly, five genes (DDB2, EXO1, NEIL3, BRCA2, and BRIP1) were independently correlated with worse prognoses, revealing single-gene signatures. Moreover, silencing of EXO1, which is remarkably overexpressed, promoted faster restoration of double-strand breaks, while NEIL3 knockdown, also highly overexpressed, caused an increment in DNA damage and cell death after irradiation of glioblastoma cells. These results disclose the importance of DNA repair pathways for the maintenance of genomic stability of high-grade astrocytomas and suggest that EXO1 and NEIL3 overexpression confers more efficiency for double-strand break repair and resistance to reactive oxygen species, respectively. Thereby, we highlight these two genes as potentially related with tumor aggressiveness and promising candidates as novel therapeutic targets.

Objective: To evaluate the effectiveness of an educational program on improvement of fatigue and quality of life of patients with high-grade glioma during radiotherapy and chemotherapy treatment., Method: This is a longitudinal, experimental study. Twenty-three patients with high-grade glioma were randomly assigned to one of two groups. Both groups completed the Functional Assessment of Cancer Therapy: Fatigue questionnaire and the Beck Depression Inventory, and one of the groups received the educational intervention., Results and Conclusions: The groups did not show any change in quality of life and fatigue in this study, for this reason, the educational program did not present any significant difference. However, there was a significant difference in depressive symptoms during the educational program showing positive evidence for its applicability.

Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The unfavorable prognosis of malignant gliomas can also be explained by the incomplete knowledge of their molecular pathways. Studies regarding the regulatory process of apoptosis in glioblastoma (GBM), the most common malignant glioma, are few, and better knowledge of the expression of pro and anti-apoptotic proteins could collaborate with the development of new treatments founded on molecular basis. The objective of this study was to evaluate by immunohistochemistry the expression of caspase-3 and Bcl-2 in 30 samples of GBMs. The expression of caspase-3 (mean 17.67%) was lower than Bcl-2 (mean 30.92%), a statistically significant result (p<0.0001), suggesting low apoptotic activity in these tumors. Other studies of proteins related to the intrinsic and extrinsic pathway of apoptosis are required to provide additional information of this mechanism in GBMs.