Abstract:
:OBJECTIVE Glioblastoma multiforme (GBM) is an aggressive brain cancer with median survival of less than 2 years with current treatment. Glioblastomas exhibit extensive intratumoral and interpatient heterogeneity, suggesting that successful therapies should produce broad anticancer activities. Therefore, the natural nontoxic pleiotropic agent, resveratrol, was studied for antitumorigenic effects against GBM. METHODS Resveratrol's effects on cell proliferation, sphere-forming ability, and invasion were tested using multiple patient-derived GBM stem-like cell (GSC) lines and established U87 glioma cells, and changes in oncogenic AKT and tumor suppressive p53 were analyzed. Resveratrol was also tested in vivo against U87 glioma flank xenografts in mice by using multiple delivery methods, including direct tumor injection. Finally, resveratrol was delivered directly to brain tissue to determine toxicity and achievable drug concentrations in the brain parenchyma. RESULTS Resveratrol significantly inhibited proliferation in U87 glioma and multiple patient-derived GSC lines, demonstrating similar inhibitory concentrations across these phenotypically heterogeneous lines. Resveratrol also inhibited the sphere-forming ability suggesting anti-stem cell effects. Additionally, resveratrol blocked U87 glioma and GSC invasion in an in vitro Matrigel Transwell assay at doses similar to those mediating antiproliferative effects. In U87 glioma cells and GSCs, resveratrol reduced AKT phosphorylation and induced p53 expression and activation that led to transcription of downstream p53 target genes. Resveratrol administration via oral gavage or ad libitum in the water supply significantly suppressed GBM xenograft growth; intratumoral or peritumoral resveratrol injection further suppressed growth and approximated tumor regression. Intracranial resveratrol injection resulted in 100-fold higher local drug concentration compared with intravenous delivery, and with no apparent toxicity. CONCLUSIONS Resveratrol potently inhibited GBM and GSC growth and infiltration, acting partially via AKT deactivation and p53 induction, and suppressed glioblastoma growth in vivo. The ability of resveratrol to modulate AKT and p53, as well as reportedly many other antitumorigenic pathways, is attractive for therapy against a genetically heterogeneous tumor such as GBM. Although resveratrol exhibits low bioavailability when administered orally or intravenously, novel delivery methods such as direct injection (i.e., convection-enhanced delivery) could potentially be used to achieve and maintain therapeutic doses in the brain. Resveratrol's nontoxic nature and broad anti-GBM effects make it a compelling candidate to supplement current GBM therapies.
journal_name
J Neurosurgjournal_title
Journal of neurosurgeryauthors
Clark PA,Bhattacharya S,Elmayan A,Darjatmoko SR,Thuro BA,Yan MB,van Ginkel PR,Polans AS,Kuo JSdoi
10.3171/2016.1.JNS152077subject
Has Abstractpub_date
2017-05-01 00:00:00pages
1448-1460issue
5eissn
0022-3085issn
1933-0693journal_volume
126pub_type
杂志文章abstract:OBJECT:Recurrence of seizures immediately following epilepsy surgery can be emotionally devastating, and raises concerns about the chances of successfully attaining long-term seizure control. The goals of this study were to investigate the frequency of acute postoperative seizures (APOS) occurring in the 1st postoperat...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1998.89.2.0177
更新日期:1998-08-01 00:00:00
abstract:OBJECT:The goal of this study was fourfold: 1) to determine the incidence of traumatic subarachnoid hemorrhage (tSAH) in patients with traumatic brain injury (TBI); 2) to verify agreement in the diagnosis of tSAH in a multicenter study; 3) to assess the incidence of tSAH on the outcome of the patient; and 4) to establi...
journal_title:Journal of neurosurgery
pub_type: 杂志文章,多中心研究
doi:10.3171/jns.2003.98.1.0037
更新日期:2003-01-01 00:00:00
abstract:OBJECT:The goal in this study was to review the effects of treatment plan quality on outcomes after radiosurgery for vestibular schwannoma (VS). METHODS:Between July 1988 and August 2005, 390 patients were treated. The results of this experience have been published recently. In this study the authors looked at dosimet...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/JNS-07/11/0913
更新日期:2007-11-01 00:00:00
abstract:OBJECT:The aim of this study was to target immunotoxin treatment to the high-molecular-weight melanoma-associated antigen (HMW-MAA) and thereby examine any changes in the survival of immunodeficient rats with human glioblastoma multiforme (GBM). METHODS:To target treatment specifically to human glioma cells, Pseudomon...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2004.100.2.0320
更新日期:2004-02-01 00:00:00
abstract::Atretic cephalocele appears as an unimportant and benign lesion. This malformation consists of meningeal and vestigial tissues (arachnoid, glial, or central nervous system rests). The authors report the findings in 16 cases (seven parietal and nine occipital) of rudimentary cephaloceles. Twelve patients presented with...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1992.77.2.0230
更新日期:1992-08-01 00:00:00
abstract:OBJECTIVE:Magnetic resonance-guided focused ultrasound surgery (MRgFUS) was recently introduced as treatment for movement disorders such as essential tremor and advanced Parkinson's disease (PD). Although deep brain target lesions are successfully generated in most patients, the target area temperature fails to increas...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2015.3.JNS142592
更新日期:2016-02-01 00:00:00
abstract:OBJECT:The aim of this study was to assess the effects of median nerve injury and regeneration on neuronal activation in the somatosensory cortex by means of functional magnetic resonance (fMR) imaging and somatosensory evoked potentials (SSEPs). METHODS:Ten injured male patients (mean age 26 years) were examined 15 t...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2003.99.1.0100
更新日期:2003-07-01 00:00:00
abstract:OBJECTIVE:Some adult patients with moyamoya disease (MMD) undergoing revascularization surgery show an improvement or decline in cognition postoperatively. Revascularization surgery for ischemic MMD augments cerebral blood flow (CBF) and improves cerebral oxygen metabolism. However, cerebral hyperperfusion, which is a ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2018.7.JNS18149
更新日期:2018-12-14 00:00:00
abstract::OBJECTIVE Skull base chondrosarcoma is one of the most intractable tumors because of its aggressive biological behavior and involvement of the internal carotid artery and cranial nerves (CNs). One of the most accepted treatment strategies for skull base chondrosarcoma has been surgical removal of the tumor in conjunct...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2017.1.JNS162000
更新日期:2018-05-01 00:00:00
abstract:OBJECT:Recent advances in neuroradiology have made it possible to dilate vasospastic human cerebral arteries after aneurysmal subarachnoid hemorrhage (SAH), but the time window is short and the success rate for reversal of delayed ischemic neurological deficits (DINDs) varies between 31% and 77%. In a dog model of vaso...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1999.91.1.0051
更新日期:1999-07-01 00:00:00
abstract::The mortality rate, risk of rebleeding, relevant subjective and objective symptoms, and daily functional capacity after a verified subarachnoid hemorrhage (SAH) of unknown etiology were evaluated in 44 patients treated during a 5-year period (1978 to 1983). A vascular basis for the SAH had been excluded by bilateral c...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1984.61.6.1029
更新日期:1984-12-01 00:00:00
abstract::A case of giant aneurysmal bone cyst of the skull is reported. Treatment was by total excision in three-staged surgery. The patient made a good recovery. ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1977.47.4.0633
更新日期:1977-10-01 00:00:00
abstract:OBJECT:Disturbance in anorectal function is a major factor restricting the activities of daily living in patients with spinal cord disorders. To detect changes in anorectal motilities due to a tethered spinal cord, anorectal functions were evaluated using a saline enema test and fecoflowmetry before and after patients ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/spi.2003.98.3.0251
更新日期:2003-04-01 00:00:00
abstract:OBJECT:A clearer understanding of the cellular mechanisms involved in the response to ionizing radiation is pivotal to the development of new therapeutic strategies for glioblastoma multiforme (GBM). To gain insight into dynamic functional aspects of cell cycle regulation and the control of apoptosis in GBMs, the autho...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2000.93.5.0863
更新日期:2000-11-01 00:00:00
abstract:OBJECTIVE:Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is characterized by large-artery vasospasm, distal autoregulatory dysfunction, cortical spreading depression, and microvessel thrombi. Large-artery vasospasm has been identified as an independent predictor of poor outcome in numero...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2019.3.JNS183512
更新日期:2019-06-14 00:00:00
abstract:OBJECT:In this paper, the authors' goal was to compare the artifact induced by implanted (in vivo) adjustable shunt valves in spin echo, diffusion weighted (DW), and gradient echo MR imaging pulse sequences. METHODS:The MR images obtained in 8 patients with proGAV and 6 patients with Strata II adjustable shunt valves ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2009.9.JNS09171
更新日期:2010-07-01 00:00:00
abstract:OBJECT:The purpose of this set of studies is to design a minimally invasive, reproducible stroke model in the gyrencephalic brain. This paper provides information on both surgical technique and methods of quantification of ischemic damage to both gray and white matter in the miniature pig. METHODS:Sixteen male miniatu...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/ped.2006.104.2.123
更新日期:2006-02-01 00:00:00
abstract::In clinical follow-up studies after radiosurgery, imaging modalities such as computerized tomography (CT) and magnetic resonance (MR) imaging are used. Accurate determination of the residual lesion volume is necessary for realistic assessment of the effects of treatment. Usually, the diameters rather than the volume o...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2000.93.supplement
更新日期:2000-12-01 00:00:00
abstract::The authors have created an experimental model of regional cerebral ischemia in gerbils that is reproducible and has a low mortality rate. In gerbils, either the posterior communicating artery (PCoA) or the middle cerebral artery (MCA) was occluded, and the distribution of cerebral ischemia from each surgical procedur...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1983.58.3.0362
更新日期:1983-03-01 00:00:00
abstract::Intracranial aneurysms in infants are rare, but are associated with a high risk of rupture and subarachnoid hemorrhage. The authors report a case of an incidentally diagnosed, probably congenital, asymptomatic giant aneurysm of the posterior communicating artery in a 9-month-old girl, which completely thrombosed follo...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2002.97.1.0184
更新日期:2002-07-01 00:00:00
abstract:OBJECT:The goal of this study was to evaluate the outcomes of patients who underwent repeated radiosurgery to treat a residual intracranial arteriovenous malformation (AVM) after an initial radiosurgical treatment failure. METHODS:The authors reviewed the cases of 52 patients who underwent repeated radiosurgery for re...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2003.98.2.0337
更新日期:2003-02-01 00:00:00
abstract:OBJECT:The 201Tl uptake index was evaluated for its usefulness in formulating a diagnosis of hemangioblastoma. Thallium-201-single-photon emission computerized tomography (SPECT) studies were performed in nine patients harboring hemangioblastomas in the posterior fossa and in five patients (six lesions) with gliomas in...
journal_title:Journal of neurosurgery
pub_type: 临床试验,杂志文章
doi:10.3171/jns.2001.95.2.0292
更新日期:2001-08-01 00:00:00
abstract:OBJECT:Pure sylvian fissure arteriovenous malformations (AVMs) are vascular malformations confined to the sylvian fissure without parenchymal involvement. Because the branches of the middle cerebral artery are arteries of passage and the margins between the AVM and the insula cortex may be ill defined, many surgeons re...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2000.92.1.0039
更新日期:2000-01-01 00:00:00
abstract::OBJECTIVE Glioblastoma (GBM) is a highly aggressive malignancy that requires a multidisciplinary therapeutic approach of surgery, chemotherapy, and radiation therapy, but therapy is frequently limited by side effects. The most common adverse effect of chemotherapy with temozolomide (TMZ) is myelosuppression. It remain...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2016.7.JNS16609
更新日期:2017-07-01 00:00:00
abstract:OBJECT:The goal of this study was to determine the tensile strength of cranial pia mater. METHODS:Samples of isolated bovine cranial pia mater were subjected to quasistatic traction to evaluate its tensile strength. The experimental curves of physiological deformation that were obtained can be subdivided into three pa...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2004.100.1.0111
更新日期:2004-01-01 00:00:00
abstract:OBJECT:The formation of cerebral aneurysms involves complex processes and little is known about the mechanisms by which they originate, grow, and rupture. The purpose of this study was to identify early ultrastructural morphological changes that lead to the formation of experimental cerebral aneurysms. METHODS:Twenty ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2005.102.3.0532
更新日期:2005-03-01 00:00:00
abstract::OBJECTIVE Mutations in the isocitrate dehydrogenase (IDH) genes are of proven diagnostic and prognostic significance for cerebral gliomas. The objective of this study was to evaluate the clinical feasibility of using a recently described method for determining IDH mutation status by using magnetic resonance spectrosco...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/2016.10.JNS161793
更新日期:2018-02-01 00:00:00
abstract::Developmental cysts lined by neuroepithelium are a distinctive form of neural tube dysgenesis. Neuropathological study of fourth ventricular cysts that caused symptomatic hydrocephalus indicated its neuroepithelial origin. The cyst arose from the ventral surface of cerebellar vermis. Evagination of the rhombencephalic...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.1977.46.6.0820
更新日期:1977-06-01 00:00:00
abstract:OBJECT:Changes in cortical representation in patients with cerebral lesions may alter the correlation between cortical anatomy and function. This is of potential clinical significance when the extent of cortical resection is based on surface anatomical landmarks. METHODS:Fifty-one patients with supratentorial lesions ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/jns.2000.92.2.0242
更新日期:2000-02-01 00:00:00
abstract:OBJECT:The authors conducted a study to determine the results of decompressive surgery without fusion in selected patients who presented with radicular compression syndromes caused by degenerative lumbar spondylolisthesis and in whom there was no evidence of hypermobility on flexion-extension radiographs. METHODS:The ...
journal_title:Journal of neurosurgery
pub_type: 杂志文章
doi:10.3171/spi.2002.97.3.0281
更新日期:2002-10-01 00:00:00