Abstract:
BACKGROUND:Diffuse midline glioma (DMG) is a pediatric malignancy with poor prognosis. Most children die less than one year after diagnosis. Recently, mutations in histone H3 have been identified and are believed to be oncogenic drivers. Targeting this epigenetic abnormality using histone deacetylase (HDAC) inhibitors such as panobinostat (PS) is therefore a novel therapeutic option currently evaluated in clinical trials. METHODS:BH3 profiling revealed engagement in an irreversible apoptotic process of glioma cells exposed to PS confirmed by annexin-V/propidium iodide staining. Using proteomic analysis of 3 DMG cell lines, we identified 2 proteins deregulated after PS treatment. We investigated biological effects of their downregulation by silencing RNA but also combinatory effects with PS treatment in vitro and in vivo using a chick embryo DMG model. Electron microscopy was used to validate protein localization. RESULTS:Scaffolding proteins EBP50 and IRSp53 were upregulated by PS treatment. Reduction of these proteins in DMG cell lines leads to blockade of proliferation and migration, invasion, and an increase of apoptosis. EBP50 was found to be expressed in cytoplasm and nucleus in DMG cells, confirming known oncogenic locations of the protein. Treatment of glioma cells with PS together with genetic or chemical inhibition of EBP50 leads to more effective reduction of cell growth in vitro and in vivo. CONCLUSION:Our data reveal a specific relation between HDAC inhibitors and scaffolding protein deregulation which might have a potential for therapeutic intervention for cancer treatment.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
Capdevielle C,Desplat A,Charpentier J,Sagliocco F,Thiebaud P,Thézé N,Fédou S,Hooks KB,Silvestri R,Guyonnet-Duperat V,Petrel M,Raymond AA,Dupuy JW,Grosset CF,Hagedorn Mdoi
10.1093/neuonc/noz215subject
Has Abstractpub_date
2020-04-15 00:00:00pages
550-562issue
4eissn
1522-8517issn
1523-5866pii
5618834journal_volume
22pub_type
杂志文章相关文献
NEURO-ONCOLOGY文献大全abstract::Effective treatment of glioblastoma (GBM) remains a formidable challenge. Survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics. There is considerable evidence that most of these therapeutics do not reach their targets in the brain when administered...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nou354
更新日期:2015-03-01 00:00:00
abstract:BACKGROUND:Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. METHODS:This pivotal phase III ra...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noz232
更新日期:2020-05-15 00:00:00
abstract::Intradural spinal tumors are rare tumors of the central nervous system. Due to the eloquence of the spinal cord and its tracts, the compact architecture of the cord and nerves, and the infiltrative nature of some of these tumors, surgical resection is difficult to achieve without causing neurological deficits. Likewis...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nox230
更新日期:2018-05-18 00:00:00
abstract:BACKGROUND:Primary central nervous system tumors (PCNST) among adolescents and young adults (AYA, 15-39 y) have rarely been reported. We present a nationwide report of PCNST histologically confirmed in the French AYA population between 2008 and 2013. METHODS:Patients were identified through the French Brain Tumor Data...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noz227
更新日期:2020-06-09 00:00:00
abstract:BACKGROUND:Glioblastoma multiforme, a World Health Organization grade IV glioma, has a poor prognosis in humans despite current treatment options. Here, we present magnetic resonance imaging (MRI) data regarding the regression of aggressive rat F98 gliomas and human U87 glioma xenografts after treatment with the nitron...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos337
更新日期:2013-03-01 00:00:00
abstract::Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, micr...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/4.1.26
更新日期:2002-01-01 00:00:00
abstract::A growing body of epidemiologic and tumor genomic research has identified an important role for telomere maintenance in glioma susceptibility, initiation, and prognosis. Telomere length has long been investigated in relation to cancer, but whether longer or shorter telomere length might be associated with glioma risk ...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nov082
更新日期:2015-11-01 00:00:00
abstract:BACKGROUND:Cognitive dysfunction is common among patients with brain tumors and can be associated with the disease and treatment with radiotherapy and chemotherapy. However, little is known about genetic risk factors that may moderate the vulnerability for developing cognitive dysfunction. In this study, we examined th...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now057
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:Antiangiogenic therapy of vestibular schwannoma (VS) in type 2 neurofibromatosis can produce tumor shrinkage with response rates of 40%-60%. This study examines the predictive value of parameter-derived MRI in this setting. METHODS:Twelve patients with 20 VSs were recruited. Each had at least one rapidly gr...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov168
更新日期:2016-02-01 00:00:00
abstract::In patients with parenchymal brain masses of uncertain origin responsive to corticosteroids, primary CNS lymphoma (PCNSL) should be considered. PCNSL is a rare but aggressive brain tumor that is highly sensitive to high-dose methotrexate (HDMTX)-based chemotherapy. We report a series of six patients with brain masses ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2006-037
更新日期:2007-04-01 00:00:00
abstract::Allergies and the use of anti-inflammatory medication appear to be associated with reduced glioblastoma risk. However, these observations may merely reflect systemic immunosuppression induced by the tumor. To better understand the effect of this tumor on allergies and inflammation, we used CD133 mRNA expression as an ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nop035
更新日期:2010-04-01 00:00:00
abstract::Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by radiation used to treat medulloblastoma. We hypothesized that GST polymorphisms may be responsible, in part, for individual differences in toxicity a...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2008-089
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:Optimal extent of surgical resection (EOR) of high-grade gliomas (HGGs) remains uncertain in the elderly given the unclear benefits and potentially higher rates of mortality and morbidity associated with more extensive degrees of resection. METHODS:We undertook a meta-analysis according to a predefined prot...
journal_title:Neuro-oncology
pub_type: 杂志文章,meta分析,评审
doi:10.1093/neuonc/nou349
更新日期:2015-06-01 00:00:00
abstract:BACKGROUND:Cisplatin-Induced Peripheral Neuropathy (CIPN) is a frequent serious dose-dependent adverse event that can determine dosage limitations for cancer treatment. CIPN severity correlates with the amount of platinum detected in sensory neurons of the dorsal root ganglia (DRG). However, the exact pathophysiology o...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noaa151
更新日期:2020-06-29 00:00:00
abstract::Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients wi...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor169
更新日期:2012-01-01 00:00:00
abstract::Radiotherapy is ubiquitous in the treatment of patients with both primary brain tumors as well as disease which is metastatic to the brain. This therapy is not without cost, however, as cognitive decline is frequently associated with cranial radiation, particularly with whole brain radiotherapy (WBRT). The precise mec...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nox195
更新日期:2018-04-09 00:00:00
abstract:BACKGROUND:We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lu...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now037
更新日期:2016-04-01 00:00:00
abstract:Background:While recent genome-wide association studies have suggested novel low-grade glioma (LGG) stratification models based on a molecular classification, we explored the potential clinical utility of patient-derived cells. Specifically, we assayed glioma-associated stem cells (GASC) that are patient-derived and re...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nox234
更新日期:2018-05-18 00:00:00
abstract::The Pediatric Oncology Group conducted a phase II study to evaluate the activity of carboplatin in children 5 years or younger with progressive optic pathway tumors (OPTs). Of the 51 patients accrued to this study, 1 was not eligible because the child was older than 6 years. Fifty patients were eligible and had either...
journal_title:Neuro-oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1093/neuonc/2.4.213
更新日期:2000-10-01 00:00:00
abstract::Death receptor targeting has emerged as one of the promising novel approaches of cancer therapy. The activation of one such prototypic death receptor, CD95 (Fas/APO-1), has remained controversial because CD95 agonistic molecules have exhibited either too strong toxicity or too little activity. The natural CD95 ligand ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noq176
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND:Expression of programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) across glioma grades is undocumented, and their interactions with commonly expressed genetic and epigenetic alterations are undefined but nonetheless highly relevant to combinatorial treatments. METHODS:Patients with CNS ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now132
更新日期:2016-10-01 00:00:00
abstract::The effects of combining histone deacetylase (HDAC) inhibitors and proteasome inhibitors were evaluated in both established glioblastoma multiforme (GBM) cell lines and short-term cultures derived from the Mayo Clinic xenograft GBM panel. Coexposure of LBH589 and bortezomib at minimally toxic doses of either drug alon...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2007-063
更新日期:2008-06-01 00:00:00
abstract:BACKGROUND:Detection of glioma with MRI contrast agent is limited to cases in which the blood-brain barrier (BBB) is compromised as contrast agents cannot cross the BBB. Thus, an early-stage infiltrating tumor is not detectable. Interleukin-13 receptor alpha 2 (IL-13Rα2), which has been shown to be overexpressed in gli...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov263
更新日期:2016-05-01 00:00:00
abstract:Background:Craniopharyngiomas are neoplasms of the sellar/parasellar region that are classified into adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP) subtypes. Surgical resection of craniopharyngiomas is challenging, and recurrence is common, frequently leading to profound morbidity. BRAF ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noy035
更新日期:2018-07-05 00:00:00
abstract::This study estimated the maximum tolerated dose (MTD) of imatinib with irradiation in children with newly diagnosed brainstem gliomas, and those with recurrent malignant intracranial gliomas, stratified according to use of enzyme-inducing anticonvulsant drugs (EIACDs). In the brainstem glioma stratum, imatinib was ini...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2006-031
更新日期:2007-04-01 00:00:00
abstract::Identification of the epidermal growth factor receptor variant III (EGFRvIII) mutation in glioblastoma has become increasingly relevant in the optimization of therapy. Traditionally, determination of tumor EGFRvIII-expression has relied on tissue-based diagnostics. Here, we assess the accuracy of magnetic resonance pe...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos073
更新日期:2012-05-01 00:00:00
abstract::Brain metastasis, which occurs in 20% to 40% of all cancer patients, is an important cause of neoplastic morbidity and mortality. Successful invasion into the brain by tumor cells must include attachment to microvessel endothelial cells, penetration through the blood-brain barrier, and, of relevance, a response to bra...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1215/s115285170300067x
更新日期:2004-04-01 00:00:00
abstract::The 2007 World Health Organization (WHO) classification of brain tumors did not use molecular abnormalities as diagnostic criteria. Studies have shown that genotyping allows a better prognostic classification of diffuse glioma with improved treatment selection. This has resulted in a major revision of the WHO classifi...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/now277
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND:Isocitrate dehydrogenase (IDH) mutation status has emerged as an important prognostic marker in gliomas. Currently, reliable IDH mutation determination requires invasive surgical procedures. The purpose of this study was to develop a highly accurate, MRI-based, voxelwise deep-learning IDH classification netw...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noz199
更新日期:2020-03-05 00:00:00
abstract:BACKGROUND:Temporal muscle thickness (TMT) was described as a surrogate marker of skeletal muscle mass. This study aimed to evaluate the prognostic relevance of TMT in patients with progressive glioblastoma. METHODS:TMT was analyzed on cranial MR images of 596 patients with progression of glioblastoma after radiochemo...
journal_title:Neuro-oncology
pub_type: 杂志文章,随机对照试验
doi:10.1093/neuonc/noz131
更新日期:2019-12-17 00:00:00