Abstract:
OBJECT:Nuclear receptor corepressor (N-CoR) forms a complex that maintains neural stem cells in an undifferentiated state through transcriptional repression. Recently, it has been shown that N-CoR is overexpressed in glioblastoma multiforme (GBM) tumor stem cells and has a putative role in maintaining these cells in an undifferentiated immortal state. To determine the effects of disruption of N-CoR complex function by serine/threonine protein phosphatase 2A (PP2A) inhibition on GBM tumor cell differentiation and proliferation, the authors developed and investigated a competitive small molecule inhibitor (LB1) of PP2A in GBM. METHODS:The authors investigated the effects of LB1 on GBM proliferation and molecular differentiation pathways using in vitro and in vivo studies. RESULTS:The LB1 inhibited PP2A, leading to increased levels of phosphorylated Akt kinase and decreased NCoR expression, as well as dose-dependent antiproliferative activity in cultured U87 and U251 malignant glioma cells (dose range 1-10 microM). Systemic LB1 treatment (1.5 mg/kg/day for 21 days) had significant tumor antiproliferative effects in mice harboring U87 glioma xenografts (73% mean reduction in tumor volume compared with controls; p < 0.001). Moreover, a reduction in PP2A expression and activity after LB1 treatment in vivo correlated with increased Akt phosphorylation, reduced nuclear N-CoR expression and N-CoR cytoplasmic translocation, and increased accumulation of acetylated core histones, which coincided with the appearance of glial fibrillary acidic protein-expressing tumor cells. CONCLUSIONS:These findings indicate that PP2A inhibition effectively disrupts N-CoR complex function/expression and leads to cytoplasmic translocation of N-CoR with subsequent tumor cell differentiation and/or death. Therapeutic paradigms that target N-CoR function in the cancer stem cell component of malignant gliomas may have treatment utility.
journal_name
J Neurosurgjournal_title
Journal of neurosurgeryauthors
Lu J,Zhuang Z,Song DK,Mehta GU,Ikejiri B,Mushlin H,Park DM,Lonser RRdoi
10.3171/2009.11.JNS091272subject
Has Abstractpub_date
2010-08-01 00:00:00pages
225-33issue
2eissn
0022-3085issn
1933-0693journal_volume
113pub_type
杂志文章abstract::Some intracranial aneurysms that might be considered inoperable by open craniotomy are readily treatable by stereotaxic thrombosis. This is possible because the stereotaxic technique requires only that some point on the fundus of the aneurysm can be punctured with a needle. Illustrative cases are given describing the ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1977.47.6.0833
更新日期:1977-12-01 00:00:00
abstract:OBJECT:Survivin, one of the apoptosis inhibitor proteins, has been detected in most cancers in humans. In addition, two splice variants (survivin-2B and survivin-deltaEx3) have been identified. The authors investigated the transcription levels of survivin messenger (m)RNA and its splice variants in nine tumor cell line...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2003.99.4.0738
更新日期:2003-10-01 00:00:00
abstract:OBJECT:Intracranial aneurysms of the anterior circulation might become symptomatic by causing visual deficits. The influence of treatment modality on improvement is still unclear. The objective of this study was to analyze the recovery of visual deficits caused by the mass effect of intracranial aneurysms after surgica...
journal_title:Journal of neurosurgery
pub_type: 杂志文章,评审
doi:10.3171/2011.5.JNS101983
更新日期:2011-10-01 00:00:00
abstract:OBJECT:Delayed vasospasm is a significant cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Proteomic therapeutics offers a new modality in which biologically active proteins or peptides are transduced into cells via covalent linkage to cell permeant peptides (CPPs). The hypothesis of this study was...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2009.7.JNS09730
更新日期:2010-03-01 00:00:00
abstract::The authors report a case of craniopharyngioma presenting in the right cerebellopontine angle. The tumor was removed totally. The purpose of this report is to record this very unusual localization of a craniopharyngioma. ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1984.60.4.0842
更新日期:1984-04-01 00:00:00
abstract:OBJECT:Meningoencephaloceles are congenital malformations that have a high incidence in the population of Southeast Asia. Frontoethmoidal meningoencephaloceles, the most common variety, require surgical treatment. The authors combined neurosurgical and craniofacial approaches for the development of a simple technique t...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/ped.2006.104.5.326
更新日期:2006-05-01 00:00:00
abstract::The authors present the case of a 68-year-old man who experienced acute obstructive hydrocephalus after having suffered an infarction in the occipital lobe. Histopathological and serial neuroimaging examinations revealed that portions of a large disintegrating occipital infarct had entered the lateral ventricle and ob...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2001.95.1.0119
更新日期:2001-07-01 00:00:00
abstract::A rare case of multiple primary hydatid cysts of the brain is reported in a 9-year-old girl. There were five cysts, occupying most of the right supratentorial region. The biggest cyst measured 9 cm across, while the smallest one was 4.5 cm in diameter. The diagnosis was based on computerized tomography findings. The p...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1982.57.3.0413
更新日期:1982-09-01 00:00:00
abstract:OBJECT:The authors analyzed tumor control rates and complications in patients with superficially located meningiomas after gamma knife surgery (GKS). METHODS:Between 1998 and 2003, GKS was performed in 23 patients with 26 lesions in whom follow-up imaging for 1 year or more was available. The male/female ratio was 1:2...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2005.102.s_supplement.0255
更新日期:2005-01-01 00:00:00
abstract::Ventricular asymmetries after shunt surgery were studied. Right and left ventricular areas from pre-and postoperative computerized tomography scans were measured with a computer digitizing technique, and the respective areas were expressed as a ratio. Measurements were made from the scans of 15 hydrocephalic children ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1981.55.2.0183
更新日期:1981-08-01 00:00:00
abstract::Cerebral protection from an ischemic/hypoxic insult implies that tissue injury can be controlled or even prevented by certain therapeutic maneuvers. For example, physiological thresholds may be altered so that tissue vulnerability to the insult is reduced, or the intensity of an insult may be blunted by enhancing brai...
journal_title:Journal of neurosurgery
pub_type: 杂志文章,评审
doi:10.3171/jns.1986.65.5.0579
更新日期:1986-11-01 00:00:00
abstract::The authors report a case of subarachnoid hemorrhage in an 11-month-old infant with tragic outcome. Radiological investigation showed an anterior communicating aneurysm, and postmortem examination confirmed the aneurysm to be a so-called "berry" aneurysm. There were also typical signs of fibromuscular hyperplasia of t...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1978.49.5.0756
更新日期:1978-11-01 00:00:00
abstract:OBJECTIVE:One of the goals in this study was to set up a semiautomatic method to estimate blood-brain barrier disruption obtained in patients with glioblastoma by using an implantable, unfocused, ultrasound device. Another goal was to correlate the probability of significant ultrasound-induced signal enhancement (SUISE...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2018.9.JNS182001
更新日期:2019-02-01 00:00:00
abstract::To evaluate the biology of thyrotropin (TSH)-producing pituitary adenomas, the authors reviewed the charts of 19 patients who underwent transsphenoidal surgery within a 15-year period at the University of California, San Francisco (UCSF). Between 1989 and 1991, the period during which immunostaining techniques were us...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1993.79.4.0521
更新日期:1993-10-01 00:00:00
abstract::OBJECTIVE The posterior subthalamic area (PSA) is a promising target of deep brain stimulation (DBS) for medication-refractory essential tremor (ET). This case series describes a novel adverse effect manifesting as dystonic tics in patients with ET undergoing DBS of the PSA. METHODS Six patients with ET received elect...
journal_title:Journal of neurosurgery
pub_type: 评论,杂志文章
doi:10.3171/2015.12.JNS15915
更新日期:2017-02-01 00:00:00
abstract:OBJECT:The authors undertook this study to identify predictors of persistent postoperative seizures in their group of 28 Dutch pediatric and adolescent patients with medically intractable epilepsy who underwent functional hemispherectomy. METHODS:The records of 28 pediatric and adolescent patients who underwent a func...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/PED-07/10/275
更新日期:2007-10-01 00:00:00
abstract:OBJECT:Bioabsorbable polymeric material coils are being used in the endovascular treatment of aneurysms to achieve better thrombus organization than is possible using bare platinum coils. We used immunohistochemical and molecular biological analysis techniques in experimental aneurysms implanted with three different bi...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/JNS-07/07/0109
更新日期:2007-07-01 00:00:00
abstract:OBJECT:The purpose of this study was to examine patterns of diagnosis and relative survival rates in individuals in whom a primary malignant brain tumor was diagnosed between 1973 and 1997; follow-up review of these patients continued through the end of 1999. METHODS:The study population was composed of 21,493 patient...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2003.99.3.0458
更新日期:2003-09-01 00:00:00
abstract::Among 121 intracerebral aneurysms presenting at one institution between 1984 and 1989, 16 were treated by endovascular means. All 16 lesions were intradural and intracranial, and had failed either surgical or endovascular attempts at selective exclusion with parent vessel preservation. The lesions included four giant ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1991.75.5.0694
更新日期:1991-11-01 00:00:00
abstract::This is a prospective randomized study of the efficacy of steroid therapy in patients with severe head injury. One hundred patients were randomized into two equal groups: the steroid group received 5 mg/kg/day of methylprednisolone, and the nonsteroid group received no drug. The groups were similar in their clinical f...
journal_title:Journal of neurosurgery
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.3171/jns.1981.54.5.0596
更新日期:1981-05-01 00:00:00
abstract:OBJECT:Intracranial hemorrhage associated with cerebral hyperperfusion syndrome (CHS) following carotid endarterectomy (CEA) or carotid artery stenting (CAS) is a rare but potentially devastating complication. In the present study the authors evaluated 4494 patients with carotid artery stenosis who had undergone CEA or...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/JNS-07/12/1130
更新日期:2007-12-01 00:00:00
abstract:OBJECT:Glomus tumors are rare skull base neoplasms that frequently involve critical cerebrovascular structures and lower cranial nerves. Complete resection is often difficult and may increase cranial nerve deficits. Stereotactic radiosurgery has gained an increasing role in the management of glomus tumors. The authors ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章,多中心研究
doi:10.3171/2012.4.JNS11214
更新日期:2012-08-01 00:00:00
abstract::A case of brain-stem hemangioma calcificans is described. The few cases reported in the literature prove the rarity of this tumor, which is considered a benign variant of cerebral cavernous hemangioma. Diagnosis and treatment of these tumors are briefly discussed with a review of the literature including 11 previous c...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1983.59.1.0150
更新日期:1983-07-01 00:00:00
abstract::Four cases of trigeminal neurinoma are reviewed with particular attention to clinical signs and symptoms, lumbar puncture, electroencephalogram, brain scan, plain skull and tomographic radiographs, and angiographic and pneumoencephalographic findings. Pneumoencephalography, with special tomographic projections to iden...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1976.45.5.0568
更新日期:1976-11-01 00:00:00
abstract:OBJECT:Patients with subarachnoid hemorrhage (SAH) and their close friends and family may be excessively fearful that the patient will have a recurrence, and such fears could play a critical role in the poor recovery shown by many patients The authors examined whether these fears could account for significant variance ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2013.5.JNS121688
更新日期:2013-10-01 00:00:00
abstract::OBJECTIVEIntrinsic third ventricular craniopharyngiomas (IVCs) have been reported by some authors to "pose the greatest surgical challenge" of all craniopharyngiomas (CPAs). A variety of open microsurgical approaches have historically been used for resection of these tumors. Despite increased utilization of the endosc...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2018.5.JNS18198
更新日期:2018-11-01 00:00:00
abstract::Chondrolipoangioma is a mesenchymoma primarily composed of cartilage, with adipose tissue and vascular elements present in lesser proportions. Chondrolipoangiomas have been reported to occur in the extremities, chest wall, oral soft tissues, mediastinum, uterus and its round ligament, seminal vesicles, and heart. In t...
journal_title:Journal of neurosurgery
pub_type: 杂志文章,评审
doi:10.3171/jns.2002.97.5.1226
更新日期:2002-11-01 00:00:00
abstract::The authors report an unusual case of a widely metastatic glioblastoma. DNA copy number microarray profile of the resected specimen revealed complex rearrangements found throughout chromosome 6, a phenomenon known as chromothripsis. Such chromothripsis pattern was not observed in 50 nonmetastatic glioblastoma specimen...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2016.4.JNS153052
更新日期:2017-05-01 00:00:00
abstract::OBJECTIVE Hemifacial spasm (HFS) is a movement disorder characterized by involuntary spasms of the facial muscles, and it can negatively impact quality of life (QOL). This retrospective study and systematic review with meta-analysis was conducted to investigate the QOL in patients with HFS following intervention with ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章,meta分析
doi:10.3171/2016.9.JNS161022
更新日期:2018-01-01 00:00:00
abstract::A micro-corrosion technique was used to demonstrate an extensive vasa vasorum network in extracranial vessels but did not reveal this system in intracranial vessels of comparable size in three species of animals. The absence of a vasa vasorum network in cerebral vessels may result in a higher level of susceptibility t...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1984.61.1.0044
更新日期:1984-07-01 00:00:00