Abstract:
BACKGROUND:Nonfunctioning pituitary adenoma (NFPA) and growth hormone pituitary adenoma (GHPA) are major subtypes of pituitary adenomas (PAs). The primary treatment is surgical resection. However, radical excision remains challenging, and few effective medical therapies are available. It is urgent to find novel targets for the treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic regulator that leads to aberrant transcriptional activation of oncogenes. Herein, we investigated the pathological role of BRD4 and evaluated the effectiveness of BRD4 inhibitors in the treatment of NFPA and GHPA. METHODS:The expression of BRD4 was detected in NFPA, GHPA, and normal pituitary tissues. The efficacies of BRD4 inhibitors were evaluated in GH3 and MMQ cell lines, patient-derived tumor cells, and in vivo mouse xenograft models of PA. Standard western blots, real-time PCR, and flow cytometry experiments were performed to investigate the effect of BRD4 inhibitors on cell cycle progression, apoptosis, and the expression patterns of downstream genes. RESULTS:Immunohistochemistry studies demonstrated the overexpression of BRD4 in NFPA and GHPA. In vitro and in vivo studies showed that treatment with the BRD4 inhibitor ZBC-260 significantly inhibited the proliferation of PA cells. Further mechanistic studies revealed that ZBC-260 could downregulate the expression of c-Myc, B-cell lymphoma 2 (Bcl2), and related genes, which are vital factors in pituitary tumorigenesis. CONCLUSION:In this study, we determined the overexpression of BRD4 in NFPA and GHPA and assessed the effects of BRD4 inhibitors on PA cells in vitro and in vivo. Our findings suggest that BRD4 is a promising therapeutic target for NFPA and GHPA.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
Shi C,Ye Z,Han J,Ye X,Lu W,Ji C,Li Z,Ma Z,Zhang Q,Zhang Y,He W,Chen Z,Cao X,Shou X,Zhou X,Wang Y,Zhang Z,Li Y,Ye H,He M,Chen H,Cheng H,Sun J,Cai J,Huang C,Ye F,Luo C,Zhou B,Ding H,Zhao Ydoi
10.1093/neuonc/noaa084subject
Has Abstractpub_date
2020-08-17 00:00:00pages
1114-1125issue
8eissn
1522-8517issn
1523-5866pii
5815718journal_volume
22pub_type
杂志文章相关文献
NEURO-ONCOLOGY文献大全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::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::Difficulties of drug delivery across the blood-brain barrier (BBB) and failure to eliminate cancer stem cells (CSCs) are believed to be the major causes of tumor recurrences in children with medulloblastoma (MB). Seneca Valley virus-001 (SVV-001) is a naturally occurring oncolytic picornavirus that can be systemically...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noq148
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Brain-derived neurotrophic factor (BDNF), a neurotrophin that regulates neuronal function and development, is implicated in several neurodegenerative conditions. Preliminary data suggest that a reduction of BDNF concentrations may lead to postchemotherapy cognitive impairment. We hypothesized that a single n...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov162
更新日期:2016-02-01 00:00:00
abstract::Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) that has efficacy in recurrent malignant gliomas, particularly in combination with irinotecan. However, responses are rarely durable. Continuation of bevacizumab in combination with another chemotherapeutic agent may demon...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2009-006
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND:The Cancer Genome Atlas (TCGA) project is a large-scale effort with the goal of identifying novel molecular aberrations in glioblastoma (GBM). METHODS:Here, we describe an in-depth analysis of gene expression data and copy number aberration (CNA) data to classify GBMs into prognostic groups to determine cor...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not024
更新日期:2013-07-01 00:00:00
abstract::The purpose of this study was to define the maximum tolerated dose of erlotinib and characterize its pharmaco-kinetics and safety profile, alone and with temozolomide, with and without enzyme-inducing antiepileptic drugs (EIAEDs), in patients with malignant gliomas. Patients with stable or progressive malignant primar...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/S1522851705000451
更新日期:2006-01-01 00:00:00
abstract::Oxidative stress is believed to play a key role in tumor formation. Although this mechanism could be especially pertinent for brain tumors given the high oxygen consumption of the brain, very little has been published regarding brain tumor risk with respect to genes mediating oxidative stress. Using data from non-Hisp...
journal_title:Neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1215/15228517-2008-037
更新日期:2008-10-01 00:00:00
abstract:BACKGROUND:We report a phase I study to examine the pharmacokinetics, safety, and recommended dosage of weekly intravenous bolus 5-fluorouracil (5-FU) in children and young adults with recurrent ependymoma. METHODS:Patients 22 years of age or less with recurrent ependymoma were treated with bolus dosage 5-FU weekly fo...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov181
更新日期:2015-12-01 00:00:00
abstract:Background:There have been few treatment advances for patients with glioblastoma (GBM) despite increasing scientific understanding of the disease. While factors such as intrinsic tumor biology and drug delivery are challenges to developing efficacious therapies, it is unclear whether the current clinical trial landscap...
journal_title:Neuro-oncology
pub_type: 杂志文章,meta分析
doi:10.1093/neuonc/noy027
更新日期:2018-07-05 00:00:00
abstract:BACKGROUND:Controversy exists as to what may be defined as standard of care (including markers for stratification) for patients with atypical teratoid/rhabdoid tumors (ATRTs). The European Rhabdoid Registry (EU-RHAB) recruits uniformly treated patients and offers standardized genetic and DNA methylation analyses. METH...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noz244
更新日期:2020-07-07 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:BACKGROUND:Diagnostic accuracy in previous studies of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in patients with suspected recurrent glioma may be influenced by prolonged dynamic PET acquisitions, heterogeneous populations, different non-standard-of-care therapies, and PET scans performed at different time point...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noz166
更新日期:2019-12-17 00:00:00
abstract:BACKGROUND:Resection of motor pathway gliomas requires the intraoperative recognition of essential cortical-subcortical motor structures. The degree of involvement of motor structures is variable, and increases as result of treatments patients are submitted to. Intraoperative neurophysiology offers various stimulation ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not327
更新日期:2014-08-01 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::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: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::In photodynamic diagnosis, 5-aminolevulinic acid (5-ALA) is widely used for the fluorescence-guided resection of malignant brain tumors, where 5-ALA is converted to protoporphyrin IX, which exhibits strong fluorescence. Little is known, however, about the detailed molecular mechanisms underlying 5-ALA-induced fluoresc...
journal_title:Neuro-oncology
pub_type: 杂志文章,收录出版
doi:10.1093/neuonc/nor116
更新日期:2011-11-01 00:00:00
abstract:BACKGROUND:Diffuse intrinsic pontine glioma (DIPG) is associated with poor survival regardless of therapy. We used volumetric apparent diffusion coefficient (ADC) histogram metrics to determine associations with progression-free survival (PFS) and overall survival (OS) at baseline and after radiation therapy (RT). MET...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov256
更新日期:2016-05-01 00:00:00
abstract:INTRODUCTION:Overexpression of the Polycomb repressive complex 2 (PRC2) subunit Enhancer of Zeste 2 (EZH2) occurs in several malignancies, including prostate cancer, breast cancer, medulloblastoma, and glioblastoma multiforme. Recent evidence suggests that EZH2 may also have a role in rhabdoid tumors. Atypical teratoid...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos285
更新日期:2013-02-01 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: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::Glioblastoma multiforme (GBM) continues to be a difficult therapeutic challenge. Our study was conducted to determine whether improved survival and tumor control could be achieved with modern delivery of fast neutron radiation using three-dimensional treatment planning. Ten patients were enrolled. Eligibility criteria...
journal_title:Neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1215/15228517-2007-044
更新日期:2008-02-01 00:00:00
abstract::Karenitecin is a highly lipophilic camptothecin analogue with a lactone ring that is relatively resistant to inactivating hydrolysis under physiologic conditions. This phase I clinical trial was conducted to determine the maximum tolerated dose (MTD) of karenitecin in adults with recurrent malignant glioma (MG), to de...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2008-030
更新日期:2008-08-01 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::Akt, one of the major downstream effectors of phosphatidylinositol 3-kinase, is hyper-expressed and activated in a variety of cancers including glioblastoma. However, the expression profiles of the Akt isoforms Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma and their functional roles in malignant glioma are not well u...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nop026
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND:To examine the efficacy of valproic acid (VPA) given either with or without levetiracetam (LEV) on seizure control and on survival in patients with glioblastoma multiforme (GBM) treated with chemoradiation. METHODS:A retrospective analysis was performed on 291 patients with GBM. The efficacies of VPA and LE...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not057
更新日期:2013-07-01 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:Background:The mesenchymal phenotype in glioblastoma (GBM) and other cancers drives aggressiveness and treatment resistance, leading to therapeutic failure and recurrence of disease. Currently, there is no successful treatment option available against the mesenchymal phenotype. Methods:We classified patient-derived GB...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nox119
更新日期:2018-01-22 00:00:00
abstract:Background:CNS tumors, including medulloblastoma and pediatric glioblastoma (pGBM) account for the majority of solid pediatric malignancies. There remains an unmet need to identify novel treatment approaches in poor prognosis and relapsed pediatric brain tumors, where therapeutic options are limited. Small-molecule B-c...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nox134
更新日期:2018-01-22 00:00:00