Differences in Mitochondrial Function and Antioxidant Systems between Regions of Human Glioma

Santandreu, Francisca M.; Brell, Marta; Gene, Alexandra H; Guevara, Rocío; Oliver, Jordi; Couce, Marta; Roca, Pilar

doi:10.1159/000185559

Cited by 29 publications

(16 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The network also contained GFAP, upregulated in young GBM, which has long been considered a fundamental and diagnostic feature of glioma [23]. The network included heat shock proteins (HSPD1, HSPA8, HSPB1), and a group of downregulated proteins involved in ATP homeostasis and energy metabolism (ALDOA, ATP6V1E1, CKB, CKMT1A), consistent with existing evidence but also identifying for the first time specific protein networks that may be involved in the dysregulation of energy metabolism in malignant glioma [24]. Lastly a cluster of upregulated proteins, integral to the immunoproteosome (PSME1, PSME2, 20 s/26 s proteosome, PSMB7), was highlighted in the top network.…”

Section: Resultssupporting

confidence: 67%

The proteomic response in glioblastoma in young patients

et al. 2014

View full text Add to dashboard Cite

Increasing age is an important prognostic variable in glioblastoma (GBM). We have defined the proteomic response in GBM samples from 7 young patients (mean age 36 years) compared to peritumoural-control samples from 10 young patients (mean age 32 years). 2-Dimensional-gel-electrophoresis, image analysis, and protein identification (LC/MS) were performed. 68 proteins were significantly altered in young GBM samples with 29 proteins upregulated and 39 proteins downregulated. Over 50 proteins are described as altered in GBM for the first time. In a parallel analysis in old GBM (mean age 67 years), an excellent correlation could be demonstrated between the proteomic profile in young GBM and that in old GBM patients (r2 = 0.95) with only 5 proteins altered significantly (p < 0.01). The proteomic response in young GBM patients highlighted alterations in protein–protein interactions in the immunoproteosome, NFkB signalling, and mitochondrial function and the same systems participated in the responses in old GBM patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-014-1474-6) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultssupporting

confidence: 67%

The proteomic response in glioblastoma in young patients

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Isolation of mitochondria from GBM tumors was performed as previously described [13]. Briefly, each piece of tumor was weighed, minced, and suspended with ice-cold isolation buffer (250 mM sucrose, 10 mM Tris-HCl, 0.5 mM EDTA; pH 7.4), then manually homogenized.…”

Section: Methodsmentioning

confidence: 99%

Prognostic Relevance of Cytochrome c Oxidase in Primary Glioblastoma Multiforme

et al. 2013

View full text Add to dashboard Cite

Patients with primary glioblastoma multiforme (GBM) have one of the lowest overall survival rates among cancer patients, and reliable biomarkers are necessary to predict patient outcome. Cytochrome c oxidase (CcO) promotes the switch from glycolytic to OXPHOS metabolism, and increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure. Thus, we investigated the relationship between tumor CcO activity and the survival of patients diagnosed with primary GBM. A total of 84 patients with grade IV glioma were evaluated in this retrospective cohort study. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test, and univariate and multivariate analyses were performed with the Cox regression model. Mitochondrial CcO activity was determined by spectrophotometrically measuring the oxidation of cytochrome c. High CcO activity was detected in a subset of glioma tumors (∼30%), and was an independent prognostic factor for shorter progression-free survival and overall survival [P = 0.0087 by the log-rank test, hazard ratio = 3.57 for progression-free survival; P<0.001 by the log-rank test, hazard ratio = 10.75 for overall survival]. The median survival time for patients with low tumor CcO activity was 14.3 months, compared with 6.3 months for patients with high tumor CcO activity. High CcO activity occurs in a significant subset of high-grade glioma patients and is an independent predictor of poor outcome. Thus, CcO activity may serve as a useful molecular marker for the categorization and targeted therapy of GBMs.

show abstract

“…The enzyme glutathione reductase uses NADPH to reduce glutathione disulfide to glutathione. Low levels of glutathione/glutathione disulfide have been demonstrated in highly proliferative glioma samples 80. Thus, therapeutic targets to control ROS levels can also be exploited to selectively kill cancer cells.…”

Section: Metabolic Modifications In Cancer Cells and Potential Targetmentioning

confidence: 99%

Metabolism and Brain Cancer

Marie

Shinjo

2011

Clinics

114

View full text Add to dashboard Cite

Cellular energy metabolism is one of the main processes affected during the transition from normal to cancer cells, and it is a crucial determinant of cell proliferation or cell death. As a support for rapid proliferation, cancer cells choose to use glycolysis even in the presence of oxygen (Warburg effect) to fuel macromolecules for the synthesis of nucleotides, fatty acids, and amino acids for the accelerated mitosis, rather than fuel the tricarboxylic acid cycle and oxidative phosphorylation. Mitochondria biogenesis is also reprogrammed in cancer cells, and the destiny of those cells is determined by the balance between energy and macromolecule supplies, and the efficiency of buffering of the cumulative radical oxygen species. In glioblastoma, the most frequent and malignant adult brain tumor, a metabolic shift toward aerobic glycolysis is observed, with regulation by well known genes as integrants of oncogenic pathways such as phosphoinositide 3-kinase/protein kinase, MYC, and hypoxia regulated gene as hypoxia induced factor 1. The expression profile of a set of genes coding for glycolysis and the tricarboxylic acid cycle in glioblastoma cases confirms this metabolic switch. An understanding of how the main metabolic pathways are modified by cancer cells and the interactions between oncogenes and tumor suppressor genes with these pathways may enlighten new strategies in cancer therapy. In the present review, the main metabolic pathways are compared in normal and cancer cells, and key regulations by the main oncogenes and tumor suppressor genes are discussed. Potential therapeutic targets of the cancer energetic metabolism are enumerated, highlighting the astrocytomas, the most common brain cancer.

show abstract

Differences in Mitochondrial Function and Antioxidant Systems between Regions of Human Glioma

Cited by 29 publications

References 62 publications

The proteomic response in glioblastoma in young patients

The proteomic response in glioblastoma in young patients

Prognostic Relevance of Cytochrome c Oxidase in Primary Glioblastoma Multiforme

Metabolism and Brain Cancer

Contact Info

Product

Resources

About