IDH1-R132H mutation radiosensitizes U87MG glioma cells via epigenetic downregulation of TIGAR.

IDH1-R132H mutation radiosensitizes U87MG glioma cells via epigenetic downregulation of TIGAR. Oncol Lett. 2020 Feb;19(2):1322-1330 Authors: Yin N, Xie T, Zhang H, Chen J, Yu J, Liu F Abstract Isocitrate dehydrogenase 1 (IDH1) is the most frequently mutated gene in World Health Organization grade II-III and secondary glioma. The majority of IDH1 mutation cases involve the substitution from arginine to histidine at codon 132 (IDH1-R132H). Although the oncogenic role of IDH1-R132H has been confirmed, patients with IDH1-R132H brain tumors exhibit a better response to radiotherapy compared with those with wild-type (WT) IDH1. In the present study, the potential mechanism of radiosensitization mediated by IDH1-R132H was investigated by overexpressing IDH1-R132H in U87MG glioma cells. The results demonstrated decreased clonogenic capacity of IDH1-R132H-expressing cells, as well as delayed repair of DNA double-strand breaks compared with IDH1-WT. Data from The Cancer Genome Atlas were analyzed, which demonstrated that the expression of TP53-induced glycolysis and apoptosis regulator (TIGAR) was lower in patients with glioma harboring IDH1 mutations compared with that in patients with IDH1-WT. TIGAR-knockdown increases the radiosensitivity of glioma cells; in U87MG cells, IDH1-R132H suppressed TIGAR expression. Chromatin immunoprecipitation assays revealed increased levels of repressive H3K9me3 markers at the TIGAR promoter in IDH1-R132H compared with IDH1-WT. Th...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research

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AbstractCancer predisposition syndromes are associated with an increased risk of developing primary malignancies. Here we discuss those which are associated with an increased risk of tumors of the central nervous system (CNS) and gastrointestinal (GI) tract. These can be grouped into those in which the CNS tumors predominate versus those in which the GI cancers predominate. The former include constitutional mismatch repair deficiency (CMMRD) syndrome, Li –Fraumeni syndrome (LFS), and Cowden syndrome (CS) while the latter include familial adenomatosis polyposis 1 (FAP1), Lynch syndrome and polymerase proofreading-asso...
Source: Acta Neuropathologica - Category: Neurology Source Type: research
Abstract Glioblastoma multiforme (GBM) is among the deadliest cancers, owing in part to complex inter- and intra-tumor heterogeneity and the presence of a population of stem-like cells called brain tumor stem cells (BTSCs/BTICs). These cancer stem cells survive treatment and confer resistance to the current therapies-namely, radiation and the chemotherapeutic, temozolomide (TMZ). TMZ induces cell death by alkylating DNA, and BTSCs resist this mechanism via a robust DNA damage response. Hence, recent studies aimed to sensitize BTSCs to TMZ using combination therapy, such as inhibition of DNA repair machinery. We ha...
Source: Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Biochem Cell Biol Source Type: research
ConclusionsIO seems to be ineffective in HmGB with somatic mut regardless the onset of diagnosis (newly/recurrent) or type of Hm phenotype. However, germline HmGB may have durable responses to IO. Further investigation is needed to determine the potential antitumor immune response in this population.Legal entity responsible for the studyThe authors.FundingThis work was supported in part by the Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy, and the MD Anderson Cancer Center Support grant (P30 CA016672) MD Anderson Cancer Center.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Conclusions1. Glioblastoma, anaplastic glioma and neuroblastoma cell lines have a high sensitivity to Cabazitaxel in vitro. 2. Cell lines with MGMT methylation and MMR expression (A172 and LN 229) are the most sensitive. Of them, line A172 presents a p53 wild type, and therefore, a greater sensitivity to Cabazitaxel. 3. The expression of CD133 correlates inversely with the values of IC50 to Cabazitaxel, and may also be a predictor of response.Legal entity responsible for the studyUGR.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Conclusion: Polymorphisms involved in cell cycle, telomere protection and stability and DNA repair are not associated with gliomas. On the other hand, alcohol consumption and SAH stand out as independent risk factors for the disease. Low-grade gliomas, response to treatment and the combination of chemotherapy with Temozolomide and radiation therapy show increased survival of patients. PMID: 31450905 [PubMed - in process]
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
In this study, we data-mined in silico databases to evaluate aldolase family members’ mRNA expression in glioblastoma patient cohorts for determining its prognostic values. After that, we also performed immunohistochemical stain (IHC) analysis to evaluate protein expression levels of ALDOC in glioblastoma tissues. From The Cancer Genome Atlas (TCGA) database analyses, higher mRNA expression levels in normal brain tissue compared to glioblastoma was observed. In addition, compared to low-grade glioma, ALDOC expression was significantly downregulated in high-grade glioblastoma. Besides, the expression level of ALDO...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract High-grade gliomas (HGGs) are aggressive primary brain tumors that confer poor prognoses. Despite aggressive combined modality treatment, HGGs invariably recur. Considerable research efforts and resources have focused on identification of novel therapies for HGGs; however, standard treatments have not changed significantly in more than 10 years, since the introduction of concurrent chemoradiation therapy with temozolomide. Hyperthermia (HT) has been shown to enhance the efficacy of radiation treatment (RT) in numerous cancer types through multiple mechanisms, including impairment of DNA repair pathways,...
Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology - Category: Radiology Authors: Tags: Radiother Oncol Source Type: research
This study used a lentiviral-mediated knockdown of TET1 to further dissect the contribution of TET1 to the DNA damage response in glial cell lines by evaluating its role in DNA repair. TET1-deficient glial cell lines displayed attenuated cytotoxicity compared to non-targeted knockdown after treatment with IR but these differences were not observed between control and TET1 deficient in response to inhibitors of Na+/K+-ATPase. Additionally, the percentage of glial cells displaying γH2A.x foci was greatly reduced in TET1-deficient glial cells compared to non-targeted knockdown conditions in response to IR and topoisomer...
Source: Toxicology and Applied Pharmacology - Category: Toxicology Authors: Tags: Toxicol Appl Pharmacol Source Type: research
Authors: Natsume A, Hirano M, Ranjit M, Aoki K, Wakabayashi T Abstract Glioblastoma (GBM), the most common primary brain tumor, is the most aggressive human cancers, with a median survival rate of only 14.6 months. Temozolomide (TMZ) is the frontline chemotherapeutic drug in GBM. Drug resistance is the predominant obstacle in TMZ therapy. Drug resistance occurs via multiple pathways such as DNA mismatch repair and base excision repair systems, by which glioma cells acquire chemoresistance to some extent (5% and 95%, respectively). Histone3 Lysin27 residue-acetylation (H3K27ac) status regulates cis-regulatory elemen...
Source: Neurologia Medico-Chirurgica - Category: Neurosurgery Tags: Neurol Med Chir (Tokyo) Source Type: research
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Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
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