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 representative of the glioma microenvironment. Methods:By next-generation sequencing, we analyzed the transcriptional profile of GASC derived from patients who underwent anaplastic transformation either within 48 months (GASC-BAD) or ≥7 years (GASC-GOOD) after surgery. Gene set enrichment and pathway enrichment analyses were applied. The prognostic role of a nuclear factor-kappaB (NF-κB) signature derived from GASC-BAD was tested in 530 newly diagnosed diffuse LGG patients comprised within The Cancer Genome Atlas (TCGA) database. The prognostic value of the GASC upstream regulator p65 NF-κB was assessed, by univariate and multivariate Cox analyses, in a single center case study, including 146 grade II LGGs. Results:The key elements differentiating the transcriptome of GASC isolated from LGG with different prognoses were mostly related to hallmarks of cancer (eg, inflammatory/immune process, NF-κB activation). Consistently, the NF-κB signature extrapolated from the GASC study was prognostic in the dataset of TCGA. Finally, the nuclear expression of the NF-kB-p65 protein, assessed using an inexpensive immunohistochemical method, was an independent predictor of both overall survival and malignant progression-free survival in 146 grade II LGGs. Conclusion:This study demonstrates for the first time the independent prognostic role of NF-kB activation in LGG and outlines the role of patient-based stem cell models as a tool for precision medicine approaches.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
Ius T,Ciani Y,Ruaro ME,Isola M,Sorrentino M,Bulfoni M,Candotti V,Correcig C,Bourkoula E,Manini I,Pegolo E,Mangoni D,Marzinotto S,Radovic S,Toffoletto B,Caponnetto F,Zanello A,Mariuzzi L,Di Loreto C,Beltrami AP,Piadoi
10.1093/neuonc/nox234subject
Has Abstractpub_date
2018-05-18 00:00:00pages
776-787issue
6eissn
1522-8517issn
1523-5866pii
4708291journal_volume
20pub_type
杂志文章相关文献
NEURO-ONCOLOGY文献大全abstract::Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treat...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/noy178
更新日期:2019-01-14 00:00:00
abstract:BACKGROUND:Glioblastoma multiforme with an oligodendroglial component (GBMO) has been recognized in the World Health Organization classification-however, the diagnostic criteria, molecular biology, and clinical outcome of primary GBMO remain unclear. Our aim was to investigate whether primary GBMO is a distinct clinico...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not125
更新日期:2013-12-01 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:Background:Glioblastoma (GBM) is one of the most common, aggressive, and invasive human brain tumors. There are few reliable mechanism-based therapeutic approaches for GBM patients. The transcriptional repressor RE1 silencing transcriptional factor (REST) regulates the oncogenic properties of a class of GBM stem-like c...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now232
更新日期:2017-04-01 00:00:00
abstract::In order to compare in vivo metabolism between malignant gliomas and normal brain, (13)C magnetic resonance (MR) spectroscopic imaging data were acquired from rats with human glioblastoma xenografts (U-251 MG and U-87 MG) and normal rats, following injection of hyperpolarized [1-(13)C]-pyruvate. The median signal-to-n...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nop043
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:The influence of survivin isoforms on outcome in glioblastoma is poorly understood. We analyzed the dominant anti-apoptotic transcript variants of survivin using expression data and modeled them in vivo to determine their impact on glioma formation and progression. METHODS:Using data from low- and high-grad...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou034
更新日期:2014-09-01 00:00:00
abstract:Background:Platelet-derived growth factor (PDGF) signaling is important in gliomagenesis and PDGF receptor-β is expressed on most endothelial cells in glioblastoma specimens. Methods:We report the results of feasibility, phase I, and phase II studies of tandutinib (MLN518), an orally bioavailable inhibitor of type III...
journal_title:Neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1093/neuonc/now185
更新日期:2017-04-01 00:00:00
abstract::Neurofibromatosis type 2 (NF2) is an autosomal-dominant disease that results in the formation of bilateral vestibular schwannomas (VSs) and multiple meningiomas. Treatment options for NF2-associated tumors are limited, and to date, no medical therapies are FDA approved. The ideal chemotherapeutic agent would inhibit b...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor072
更新日期:2011-09-01 00:00:00
abstract::The blood-brain barrier (BBB) excludes the vast majority of cancer therapeutics from normal brain. However, the importance of the BBB in limiting drug delivery and efficacy is controversial in high-grade brain tumors, such as glioblastoma (GBM). The accumulation of normally brain impenetrant radiographic contrast mate...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nox175
更新日期:2018-01-22 00:00:00
abstract:BACKGROUND:Previous pilot studies have shown the feasibility of preoperative chemotherapy in patients with medulloblastoma, but benefits and risks compared with initial surgery have not been assessed. METHODS:Two therapeutic strategies were retrospectively compared in 92 patients with metastatic medulloblastoma treate...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noaa083
更新日期:2020-11-26 00:00:00
abstract::Histone modification has emerged as a promising approach to cancer therapy. We explored the in vivo efficacy of a butyric acid derivative, pivaloyloxymethyl butyrate (AN-9), for the treatment of gliomas. Relative to control and single-modality treatments, the combination of AN-9 and radiation significantly inhibited t...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2006-032
更新日期:2007-04-01 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::Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a "wait and see" policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associa...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nou153
更新日期:2015-03-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) gene amplification and activating mutations are common findings in glioblastomas. EGFR is at the top of a downstream signaling cascade that regulates important characteristics of glioblastoma cells, including cellular proliferation, migration, and survival. Targeting EGFR has th...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nou222
更新日期:2014-10-01 00:00:00
abstract::High-grade gliomas release excitotoxic concentrations of glutamate, which has been shown to enhance tumor proliferation and migration. alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptors are abundantly expressed at the invading edge of glioblastoma specimens, suggesting they may play an...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2008-094
更新日期:2009-06-01 00:00:00
abstract::The signaling pathways that underlie the pathogenesis of pediatric gliomas are poorly understood. We characterized the PI3K/Akt/mTOR pathway in pediatric gliomas of all grades. Using immunohistochemistry, we assessed activation of the PI3K/Akt/mTOR pathway by evaluating the downstream signaling molecules phospho(p)-S6...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos140
更新日期:2012-09-01 00:00:00
abstract::In the present study we described the role of alpha9beta1 integrin in glioblastoma progression following its interaction with nerve growth factor (NGF). The level of expression of alpha9beta1 on astrocytomas is correlated with increased grade of this brain tumor and is highest on glioblastoma, whereas normal astrocyte...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2008-047
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:Temozolomide (TMZ) resistance in Glioblastoma (GBM) is mediated by the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). MGMT promoter methylation (occurs in about 40% patients) is associated with loss of MGMT expression (MGMT-) that compromises DNA repair, leading to a favorable response to ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noab003
更新日期:2021-01-12 00:00:00
abstract::Survival alone is no longer an adequate outcome for persons with brain tumors; the quality of the survivorship experience should be viewed with equal importance. Symptom management is a significant component of quality survivorship care. Regardless of their histology, brain tumors and therapies used to treat them prod...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noy100
更新日期:2018-11-09 00:00:00
abstract::Glioblastoma multiforme (GBM) is a lethal primary malignant brain tumor in adults. R115777 (tipifarnib) is an oral agent with antiproliferative effects, being a potent and selective inhibitor of farnesyltransferase. This multicenter, open-label phase II study was designed to evaluate the efficacy and safety of R115777...
journal_title:Neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1215/15228517-2008-070
更新日期:2008-12-01 00:00:00
abstract::The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving a...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/2.2.114
更新日期:2000-04-01 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::Glioblastoma multiforme, a highly aggressive tumor of the central nervous system, has a dismal prognosis that is due in part to its resistance to radio- and chemotherapy. The protein kinase C (PKC) family of serine threonine kinases has been implicated in the formation and proliferation of glioblastoma multiforme. Mem...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor084
更新日期:2011-07-01 00:00:00
abstract::The long-term follow-up of the RTOG 9802 trial that compared 54 Gy of radiotherapy (RT) with the same RT followed by adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy in high-risk low-grade glioma shows a major increase in survival after adjuvant PCV chemotherapy. Median overall survival increased from 7...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nou297
更新日期:2014-12-01 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::Glial tumors with oligodendroglial components are considered chemo-responsive. Forty newly diagnosed patients (11 anaplastic oligodendrogliomas [OD] and 29 anaplastic oligoastrocytomas [OA]) were enrolled into this multicenter, open-label, single-arm Phase II trial of first-line temozolomide (200 mg/m(2) on days 1-5 e...
journal_title:Neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1093/neuonc/nop065
更新日期:2010-05-01 00:00:00
abstract::Although treatment of medulloblastoma has improved, at least 30% of patients with this tumor die of progressive disease. Unfortunately, many of the children who survive suffer long-term treatment-related morbidity. Previous studies have demonstrated the efficacy of using oncolytic viruses to eradicate brain tumors. Th...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noq057
更新日期:2010-10-01 00:00:00
abstract:BACKGROUND:No more than half of patients with neurofibromatosis type 1 (NF1)-associated optic pathway gliomas (OPGs) develop vision loss. Prospectively identifying those who will require therapy remains challenging, because no reliable factors have yet been identified that predict future vision loss. To determine wheth...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not068
更新日期:2013-08-01 00:00:00
abstract::Stereotactic biopsy is often performed for diagnostic purposes before treating patients whose imaging studies highly suggest glioma. Indications cited for biopsy include diagnosis and/or the "inoperability" of the tumor. This study questions the routine use of stereotactic biopsy in the initial management of gliomas. ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/3.3.193
更新日期:2001-07-01 00:00:00
abstract:BACKGROUND:Promoter methylation of O(6)-methylguanine-DNA methyltransferase (MGMT) is an important predictive biomarker in glioblastoma. The T variant of the MGMT promoter-enhancer single nucleotide polymorphism (SNP; rs16906252) has been associated with the presence of MGMT promoter methylation in other cancers. We ex...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov064
更新日期:2015-12-01 00:00:00