Abstract:
Background:Depending on the level, differentiation state, and tumor stage, reactive nitrogen and oxygen species inhibit or increase cancer growth and tumor initiating cell maintenance. The rate-limiting enzyme in a pathway that can regulate reactive species production but has not been thoroughly investigated in glioblastoma (GBM; grade IV astrocytoma) is guanosine triphosphate (GTP) cyclohydrolase 1 (GCH1). We sought to define the role of GCH1 in the regulation of GBM growth and brain tumor initiating cell (BTIC) maintenance. Methods:We examined GCH1 mRNA and protein expression in patient-derived xenografts, clinical samples, and glioma gene expression datasets. GCH1 levels were modulated using lentiviral expression systems, and effects on cell growth, self-renewal, reactive species production, and survival in orthotopic patient-derived xenograft models were determined. Results:GCH1 was expressed in GBMs with elevated but not exclusive RNA and protein levels in BTICs in comparison to non-BTICs. Overexpression of GCH1 in GBM cells increased cell growth in vitro and decreased survival in an intracranial GBM mouse model. In converse experiments, GCH1 knockdown with short hairpin RNA led to GBM cell growth inhibition and reduced self-renewal in association with decreased CD44 expression. GCH1 was critical for controlling reactive species balance, including suppressing reactive oxygen species production, which mediated GCH1 cell growth effects. In silico analyses demonstrated that higher GCH1 levels in glioma patients correlate with higher glioma grade, recurrence, and worse survival. Conclusions:GCH1 expression in established GBMs is pro-tumorigenic, causing increased growth due, in part, to promotion of BTIC maintenance and suppression of reactive oxygen species.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
Tran AN,Walker K,Harrison DG,Chen W,Mobley J,Hocevar L,Hackney JR,Sedaka RS,Pollock JS,Goldberg MS,Hambardzumyan D,Cooper SJ,Gillespie Y,Hjelmeland ABdoi
10.1093/neuonc/noy012subject
Has Abstractpub_date
2018-07-05 00:00:00pages
1055-1067issue
8eissn
1522-8517issn
1523-5866pii
4835145journal_volume
20pub_type
杂志文章相关文献
NEURO-ONCOLOGY文献大全abstract::The exact incidence of pineal germ-cell tumors is largely unknown. The tumors are rare, and the number of patients with these tumors, as reported in clinical series, has been limited. The goal of this study was to describe pineal germ-cell tumors in a large number of patients, using data from available brain tumor dat...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2007-054
更新日期:2008-04-01 00:00:00
abstract::Medulloblastoma (MB) is the most common pediatric brain cancer. Several important developmental pathways have been implicated in MB formation, but fewer therapeutic targets have been identified. To locate frequently overexpressed genes, we performed a comprehensive gene expression survey of MB. Our comparison of 20 pr...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2008-038
更新日期:2008-10-01 00:00:00
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 ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noz215
更新日期:2020-04-15 00:00:00
abstract::Survivorship has become a significant topic within oncologic care. The tools and means by which the provision of survivorship care can be implemented and delivered are in development and are the focus of significant research oncology-wide. These tools and methods include innovations of survivorship care delivery, surv...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noy110
更新日期:2018-11-09 00:00:00
abstract:BACKGROUND:This study aimed to evaluate the prognostic significance of co-polsomy of chromosome 1q and 19p in 1p/19q codeleted oligodendroglial tumors (ODGs). METHODS:In a series of 148 ODGs with 1p/19q deletion, co-polysomy of 1q and 19p was detected by fluorescence in situ hybridization (FISH). Log-rank analysis and...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not092
更新日期:2013-09-01 00:00:00
abstract::Diffuse intrinsic pontine glioma (DIPG) has proven to be one of the most challenging of all pediatric cancers. Owing to a historical reticence to obtain tumor tissue for study, and based on an erroneous assumption that the biology of DIPG would mirror that of supratentorial high-grade astrocytomas, innumerable studies...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nox021
更新日期:2017-08-01 00:00:00
abstract::This paper explicates the impact of tumor capillary permeability for glioma World Health Organization (WHO) grades II to IV on brain-penetrant drug entry and distribution within the tumor and the brain adjacent to tumor (leading edge). In addition, we consider the distribution of non-brain penetrant drugs and how, in ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noy018
更新日期:2018-04-09 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:Background:Molecular profile of glioblastoma multiforme (GBM) revealed 4 subtypes, 2 of which, proneural and mesenchymal, have been predominantly observed, with the latter displaying a more aggressive phenotype and increased therapeutic resistance. Single-cell RNA sequencing revealed that multiple subtypes actually res...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now253
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND:Diffuse midline glioma (DMG), H3 K27M-mutant occurs in both adult and pediatric populations. The characteristics of the two DMG groups were systematically explored in this study. METHODS: One-hundred-sixteen patients diagnosed with H3 K27M-mutant DMG in Beijing Tiantan Hospital from May 2016 to December 201...
journal_title:Neuro-oncology
pub_type: 杂志文章,收录出版
doi:10.1093/neuonc/noz152
更新日期:2019-08-24 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::Background Notch signaling is deregulated in human gliomas and may play a role in their malignancy. However, the role of each Notch receptor in glioma cell differentiation and progression is not clear. We examined the expression pattern of Notch receptors and compared it with differentiation markers in glioma cell lin...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not168
更新日期:2014-01-01 00:00:00
abstract::The Atlas of Cancer Mortality in the United States, 1950-94 (Devesa et al.) published in 1999 by the National Institutes of Health suggests that there are elevated rates of brain and other nervous system cancer in the northwestern, north central, and southeastern parts of the country. Being descriptive in nature, the ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/S1152851703000450
更新日期:2004-07-01 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::Protein kinase C alpha (PKC-alpha) is a cytoplasmic serine threonine kinase involved in regulating cell differentiation and proliferation. Aprinocarsen is an antisense oligonucleotide against PKC-alpha that reduces PKC-alphain human cell lines and inhibits a human glioblastoma tumor cell line in athymic mice. In this ...
journal_title:Neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1215/S1152851703000353
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Altered expression of micro(mi)RNAs has been shown to be associated with tumorigenesis and tumor progression. The expression of phosphatase and tensin homolog (PTEN) plays an important role in glioma and is regarded as a prognostic marker of glioma patients. The goal of this study was to investigate the func...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not107
更新日期:2013-11-01 00:00:00
abstract::PDGFRA is a critical gene in glioma biology. Similar to EGFR, PDGFRA has been shown to be overexpressed, amplified, mutated, or truncated in gliomas, particularly glioblastomas. In addition, PDGFRA has been recently shown to be rearranged in glioblastoma. However, the frequency, cooccurrence, and clinical value of PDG...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos217
更新日期:2012-11-01 00:00:00
abstract::Vestibular schwannomas (VS) arising sporadically or in patients with neurofibromatosis type 2 (NF2) consistently lack expression of Merlin, a tumor suppressor. Conventional treatment options include surgery and radiotherapy but there is no validated medical option. Recent evidence suggests that Merlin deficiency may r...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noq012
更新日期:2010-08-01 00:00:00
abstract::Cytotoxic chemotherapy that induces lymphopenia is predicted to ablate the benefits of active antitumor immunization. Temozolomide is an effective chemotherapeutic agent for patients with glioblastoma multiforme, but it induces significant lymphopenia. Although there is monthly fluctuation of the white blood cell coun...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2007-046
更新日期:2008-02-01 00:00:00
abstract::Recurrence of primary central nervous system lymphoma (PCNSL) after initial diagnosis and treatment occurs within 2 years in most patients, and relapse after 5 years is rare. We evaluated late relapse in our PCNSL population. We identified 10 patients from our database of 378 patients (268 achieved a complete response...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor014
更新日期:2011-05-01 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:BACKGROUND:Whole-brain radiotherapy (WBRT) in patients with brain metastases (BM) is associated with neurocognitive decline. Given its crucial role in learning and memory, efforts to mitigate this toxicity have mostly focused on sparing radiation to the hippocampus. We hypothesized that BM are not evenly distributed ac...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noz023
更新日期:2019-05-06 00:00:00
abstract:BACKGROUND:Anaplastic oligodendroglial tumors are rare, and median survival varies widely. Analysis of 1p19q deletion is performed commonly and is an important prognostic factor. However, age and other clinical variables also carry prognostic value, and it is unclear how to incorporate them into clinical decision makin...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou083
更新日期:2014-11-01 00:00:00
abstract:BACKGROUND:Genetic and epigenetic profiling of glioblastomas has provided a comprehensive list of altered cancer genes of which only O(6)-methylguanine-methyltransferase (MGMT) methylation is used thus far as a predictive marker in a clinical setting. We investigated the prognostic significance of genetic and epigeneti...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou005
更新日期:2014-09-01 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:Young age is a favorable prognostic factor for patients with glioblastoma multiforme (GBM). We reviewed the outcomes and molecular tumor characteristics of adolescent and young adult patients with GBM treated in 2 Austrian centers. PATIENTS AND METHODS:Data on patients with histologically proven primary GBM...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos283
更新日期:2013-01-01 00:00:00
abstract::Medulloblastomas are the most common malignant tumors of the central nervous system during childhood. Radiation-induced medulloblastoma tumor recurrences are aggressive and metastatic in nature. In the present study, we demonstrate that Gadd45a expression can sensitize medulloblastoma cells to radiotherapy. We have el...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor109
更新日期:2011-10-01 00:00:00
abstract::We explored the associations of aberrant DNA methylation patterns in 12 candidate genes with adult glioma subtype, patient survival, and gene expression of enhancer of zeste human homolog 2 (EZH2) and insulin-like growth factor-binding protein 2 (IGFBP2). We analyzed 154 primary glioma tumors (37 astrocytoma II and II...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noq190
更新日期:2011-03-01 00:00:00
abstract::Multiphoton excitation fluorescent microscopy is a laser-based technology that allows subcellular resolution of native tissues in situ. We have recently applied this technology to the structural and photochemical imaging of cultured glioma cells and experimental gliomas ex vivo. We demonstrated that high microanatomic...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2006-034
更新日期:2007-04-01 00:00:00
abstract::Functional diffusion mapping (fDM) has shown promise as a sensitive imaging biomarker for predicting survival in initial studies consisting of a small number of patients, mixed tumor grades, and before routine use of anti-angiogenic therapy. The current study tested whether fDM performed before and after radiochemothe...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor220
更新日期:2012-03-01 00:00:00