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Mutations in the gene isocitrate dehydrogenase 1 (IDH1) are present in up to 86% of grade II and III gliomas and secondary glioblastoma. Arginine 132 (R132) mutations in the enzyme IDH1 result in excess production of the metabolite 2-hydroxyglutarate (2HG), which could be used as a biomarker for this subset of gliomas. Here, we use optimized in vivo spectral-editing and two-dimensional (2D) correlation magnetic resonance spectroscopy (MRS) methods to unambiguously detect 2HG noninvasively in glioma patients with IDH1 mutations. By comparison, fitting of conventional 1D MR spectra can provide false-positive readouts owing to spectral overlap of 2HG and chemically similar brain metabolites, such as glutamate and glutamine. 2HG was also detected using 2D high-resolution magic angle spinning MRS performed ex vivo on a separate set of glioma biopsy samples. 2HG detection by in vivo or ex vivo MRS enabled detailed molecular characterization of a clinically important subset of human gliomas. This has implications for diagnosis as well as monitoring of treatments targeting mutated IDH1.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720836 | PMC |
http://dx.doi.org/10.1126/scitranslmed.3002693 | DOI Listing |
Cell Mol Life Sci
December 2024
Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Background: Glioblastoma (GB) is the stage IV of glioma and mesenchymal GB represents the most common and malignant subtype characterized with elevated expression of a mesenchymal marker YKL-40 and resistance to immune drug therapy. Here, we determined if YKL-40 regulates kynurenine (Kyn) pathway (KP) metabolism that contributes to establishing an immune suppressive microenvironment in GB.
Methods: Tumor cells expressing YKL-40 from GB patients were isolated and activated cellular metabolisms were identified via gene microarray analysis.
Naunyn Schmiedebergs Arch Pharmacol
December 2024
Department of Neurosurgery, the Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang City, Jiangxi, 330006, China.
In clinical settings, glioma patients often develop secondary resistance to first-line chemotherapy drugs. Vincristine has been reported for its application in cancer chemotherapy, but its molecular mechanism of action remains unclear. This study aimed to identify potential targets of vincristine in glioma using network pharmacology and to experimentally validate the possible molecular mechanisms against glioma.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200241, P. R. China.
Brain metastases (BrMs) and gliomas are two typical human brain tumors with high incidence of mortalities and distinct clinical challenges, yet the understanding of these two types of tumors remains incomplete. Here, a multidimensional proteomic landscape of BrMs and gliomas to infer tumor-specific molecular pathophysiology at both tissue and plasma levels is presented. Tissue sample analysis reveals both shared and distinct characteristics of brain tumors, highlighting significant disparities between BrMs and gliomas with differentially activated upstream pathways of the PI3K-Akt signaling pathway that have been scarcely discussed previously.
View Article and Find Full Text PDFCancer Imaging
December 2024
Department of Radiology, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, 7 Weiwu Road, Zhengzhou, 450000, PR China.
Objective: This study aims to evaluate the effectiveness of deep learning features derived from multi-sequence magnetic resonance imaging (MRI) in determining the O-methylguanine-DNA methyltransferase (MGMT) promoter methylation status among glioblastoma patients.
Methods: Clinical, pathological, and MRI data of 356 glioblastoma patients (251 methylated, 105 unmethylated) were retrospectively examined from the public dataset The Cancer Imaging Archive. Each patient underwent preoperative multi-sequence brain MRI scans, which included T1-weighted imaging (T1WI) and contrast-enhanced T1-weighted imaging (CE-T1WI).
Cancer Cell Int
December 2024
Sezione di Farmacologia, Dipartimento di Medicina Interna, Università di Genova, Genova, Italy.
Background: Cellular prion protein (PrP) is a widely expressed membrane-anchored glycoprotein, which has been associated with the development and progression of several types of human malignancies, controlling cancer stem cell activity. However, the different molecular mechanisms regulated by PrP in normal and tumor cells have not been characterized yet.
Methods: To assess the role of PrP in patient-derived glioblastoma stem cell (GSC)-enriched cultures, we generated cell lines in which PrP was either overexpressed or down-regulated and investigated, in 2D and 3D cultures, its role in cell proliferation, migration, and invasion.
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