Circulating biomarkers in blood may provide an interesting alternative to risky tissue biopsies in the diagnosis and follow-up of glioblastoma patients. We have assessed MGMT methylation status in blood and tissue samples from unresected glioblastoma patients who had been included in the randomized GENOM-009 trial. Paired blood and tissue samples were assessed by methylation-specific PCR (MSP) and pyrosequencing (PYR). After establishing the minimum PYR cut-off that could yield a significant difference in overall survival, we assessed the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the analyses. Methylation could be detected in cfDNA by both MSP and PYR but with low concordance with results in tissue. Sensitivity was low for both methods (31% and 38%, respectively), while specificity was higher for MSP in blood than for PYR in plasma (96% vs 76%) and NPV was similar (56 vs 57%). Concordance of results in tissue by MSP and PYR was 84.3% (P < 0.001) and correlated with outcome. We conclude that detection of cfDNA in the blood of glioblastoma patients can be an alternative when tumor tissue is not available but methods for the detection of cfDNA in blood must improve before it can replace analysis in tumor tissue.
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http://dx.doi.org/10.1038/s41598-019-47642-2 | DOI Listing |
PLoS One
January 2025
Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Background: Glioblastoma is characterized by neovascularization and diffuse infiltration into the adjacent tissue. T2*-based dynamic susceptibility contrast (DSC) MR perfusion images provide useful measurements of the biomarkers associated with tumor perfusion. This study aimed to distinguish infiltrating tumors from vasogenic edema in glioblastomas using DSC-MR perfusion images.
View Article and Find Full Text PDFMedicine (Baltimore)
January 2025
Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.
The presence of specific genetic mutations in patients with glioblastoma multiforme (GBM) is associated with improved survival outcomes. Disruption of the DNA damage response (DDR) pathway in tumor cells enhances the effectiveness of radiotherapy drugs, while increased mutational burden following tumor cell damage also facilitates the efficacy of immunotherapy. The ATRX gene, located on chromosome X, plays a crucial role in DDR.
View Article and Find Full Text PDFCell Rep
January 2025
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China; National Center for Neurological Disorders, Shanghai 200040, China; Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai 200040, China; Neurosurgical Institute of Fudan University, Shanghai 200040, China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai 200040, China. Electronic address:
Glioblastoma (GBM) is a highly lethal malignant brain tumor with poor survival rates, and chemoresistance poses a significant challenge to the treatment of patients with GBM. Here, we show that transketolase (TKT), a metabolic enzyme in the pentose phosphate pathway (PPP), attenuates the chemotherapy sensitivity of glioma cells in a manner independent of catalytic activity. Mechanistically, chemotherapeutic drugs can facilitate the translocation of TKT protein from the cytosol into the nucleus, where TKT physically interacts with XRN2 to regulate the resolution and removal of R-loops.
View Article and Find Full Text PDFNeuro Oncol
January 2025
Childhood Cancer & Cell Death team (C3 team), Consortium South-ROCK, LabEx DEVweCAN, Institut Convergence Plascan, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, 69008 Lyon, France.
Background: Brain tumors are the deadliest solid tumors in children and adolescents. Most of these tumors are glial in origin and exhibit strong heterogeneity, hampering the development of effective therapeutic strategies. In the past decades, patient-derived tumor organoids (PDT-O) have emerged as powerful tools for modeling tumoral cell diversity and dynamics, and they could then help defining new therapeutic options for pediatric brain tumors.
View Article and Find Full Text PDFCells
January 2025
Department of Molecular Medicine and Pathology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.
The overall goal of this work was to assess the ability of Natural Killer cells to kill cultures of patient-derived glioblastoma cells. Herein we report impressive levels of NK-92 mediated killing of various patient-derived glioblastoma cultures observed at ET (effector: target) ratios of 5:1 and 1:1. This enabled direct comparison of the degree of glioblastoma cell loss across a broader range of glioblastoma cultures.
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