Glioblastoma (GBM) is uniformly lethal due to profound treatment resistance. Altered cellular metabolism is a key mediator of GBM treatment resistance. Uptake of the essential sulfur-containing amino acid methionine is drastically elevated in GBMs compared to normal cells, however, it is not known how this methionine is utilized or whether it relates to GBM treatment resistance.
View Article and Find Full Text PDFBackground: Meningiomas are the most frequent primary intracranial tumor. While histological grade and grade of excision are established predictors of recurrence, the predictive ability of other clinical features, such as the role of radical excision of dural attachment and postoperative radiation therapy in intermediate-risk groups, remains unknown.
Methods: Clinical and radiological features and surgical details were analyzed in 451 World Health Organization (WHO) grade 1 intracranial meningiomas and 248 WHO grade 2 meningiomas operated on between 2010 and 2015.
Unlabelled: How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a guanine nucleotide-binding protein, which promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5).
View Article and Find Full Text PDFThe transfer of intact mitochondria between heterogeneous cell types has been confirmed in various settings, including cancer. However, the functional implications of mitochondria transfer on tumor biology are poorly understood. Here we show that mitochondria transfer is a prevalent phenomenon in glioblastoma (GBM), the most frequent and malignant primary brain tumor.
View Article and Find Full Text PDFBackground: IDH-mutant astrocytomas include CNS WHO grade 2 (A2), grade 3 (A3) and grade 4 (A4), of which A3 and A4 are high-grade. A3 has a heterogenous clinical outcome that cannot be explained entirely by the existing molecular biomarkers. We comprehensively studied the transcriptome profile of A3 to determine clinical significance.
View Article and Find Full Text PDFHow cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a G protein, that promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5).
View Article and Find Full Text PDFObjectives: We aimed to evaluate the expression pattern of chitinase 3-like 2 (CHI3L2) in the tumor core and peritumoral brain zone (PBZ) of newly diagnosed glioblastoma (GBM) in recurrent tumors and its association with patient prognosis.
Methods: The study was conducted on three sample sets derived from different patient cohorts. Messenger RNA (mRNA) expression of CHI3L2 in the tumor core and PBZ (n = 34) compared with control (n = 20) tissues was studied by quantitative polymerase chain reaction in sample set 1.
Purpose: Glioblastoma (GBM) is a highly invasive tumor. Despite advances in treatment modalities, tumor recurrence is common, seen mainly in the peritumoral brain zone (PBZ). We aimed to molecularly characterize PBZ, to understand the pathobiology of tumor recurrence.
View Article and Find Full Text PDFIntroduction: Mitochondrial DNA (mtDNA) content in several solid tumors was found to be lower than in their normal counterparts. However, there is paucity of literature on the clinical significance of mtDNA content in glioblastoma and its effect on treatment response. Hence, we studied the prognostic significance of mtDNA content in glioblastoma tumor tissue and the effect of mtDNA depletion in glioblastoma cells on response to treatment.
View Article and Find Full Text PDFIntroduction: Recent advances in the molecular biology of adult diffuse gliomas have brought about a paradigm shift in their diagnostic criteria, as witnessed in the World Health Organization (WHO) 2016 guidelines for central nervous system tumors. It is now mandatory to perform several molecular tests to reach a definitive integrated diagnosis in most of the cases. This comes with additional cost and higher turnaround time, which is not always affordable in developing countries like India.
View Article and Find Full Text PDFSupratentorial ependymomas (ST EPNs) are molecularly characterized, of which the RELA fusion positive tumors are the most common and aggressive subgroup. Moreover, histologically, anaplastic ST EPN (ST-AE) often mimic other central nervous system primary high-grade tumors resulting in a diagnostic dilemma. We aimed to study a cohort of ST-AE; evaluate the expression of two RELA fusion-associated markers-L1CAM and p65 (NF-κB); and correlate their expression with clinical and histological parameters.
View Article and Find Full Text PDFOligodendrogliomas are diffuse gliomas characterised by IDH mutation and 1p/19q co-deletion. Classical oligodendrocytes, minigemistocytes, gliofibrillary oligodendrocytes, granular cells, and mucocytes are morphologic cell types described in oligodendroglioma. Even though the occurrence of granular cells in oligodendroglioma is known, exact nature of these cells and their molecular characteristics remain undetermined.
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