Antioxidant enzymes in oligodendroglial brain tumors: association with proliferation, apoptotic activity and survival

Abstract

Purpose of the study was to investigate the relationship between antioxidant enzyme expression and clinicopathological features in oligodendroglial tumors. The expression of antioxidant enzymes and related proteins (AOEs), manganese superoxide dismutase (MnSOD), thioredoxin (Trx), thioredoxin reductase (TrxR) and gammaglutamylcysteine synthetase catalytic and regulatory subunits (GLCL-C and GLCL-R), was studied in 85 oligodendroglial tumors. The material included 71 primary (43 grade II and 28 grade III) and 14 recurrent (6 grade II and 8 grade III) tumors. Fifty-seven cases were pure oligodendrogliomas and 28 were mixed oligoastrocytomas. Immunoreactivity for MnSOD was found in 89%, Trx in 29%, TrxR in 76%, GLCL-C in 70% and GLCL-R in 68% of cases. Increased Trx expression was associated with higher tumor grade, cell proliferation and apoptosis (P=0.006, P=0.001 and P=0.003, Mann-Whitney test). Pure oligodendrogliomas showed more intense staining than oligoastrocytomas, especially for MnSOD (P=0.002, Mann-Whitney test). In the total series Trx was associated with poor prognosis in univariate survival analysis (P=0.0343, log-rank test) and furthermore in Cox multivariate analysis (P=0.009) along with age (P=0.002). The results suggest that the expression of Trx has a correlation to patient outcome and that there may be some association between AOEs, like MnSOD and Trx, and clinicopathological features of oligodendrogliomas.

Glutathione peroxidase, glutathione reductase and protein oxidation in patients with glioblastoma multiforme and transitional meningioma

“…They found that mean serum levels of MDA, CT and GPx were signiWcantly higher for both gliomas and meningiomas when compared to the controls and no diVerences were found between gliomas and meningiomas. Correlation of some types of brain tumors, such as astrocytoma and oligodendroglioma, with some AOEs have also been demonstrated (Sally 2006;Haapasalo 2003).…”

The Emerging Role of the Thioredoxin System in Angiogenesis

“…51 Elevated levels of TRX1 correlate with poor prognosis. 46, 48, 52 When MCF7 breast carcinoma cells overexpressing TRX1 cells were xenotransplanted in mouse there was increased formation of solid tumors, while cells overexpressing a redox-impaired C32S/C35S TRX1 mutant had reduced tumorigenicity. 53 Murine lymphoma xenografts overexpressing TRX1 also formed solid tumors with enhanced capillary networks and increased VEGF levels.…”

Total dietary antioxidant index and survival in patients with glioblastoma multiforme

“…Supporting the first hypothesis, studies showed that glioma cells have amplified antioxidant defense (i.e. increased expression of antioxidant enzymes) [10–13], which is responsible for their resistance to radiation [14–16] and is associated with shorter survival [17, 18]. On the other hand, a recent animal study suggests that aggressiveness of glioma can be reduced by dietary antioxidants [19].…”