Abstract:
:We previously showed that inhibition of the platelet-derived growth factor receptor (PDGFR) blocks the survival and migration of medulloblastoma cells. Identification of in vitro PDGFR-targeting pharmacologic agents that are suitable for preclinical testing in medulloblastoma models in vivo will be critical for efficiently translating these agents to clinical investigation in children with medulloblastoma. In this study, we investigated whether the multi-tyrosine kinase inhibitor sunitinib, effectively inhibits PDGFR signaling required for medulloblastoma cell migration. Daoy and D556 human medulloblastoma cells pre-treated for 1 h with 0.2 μM sunitinib demonstrated induction of PTEN expression and significant inhibition of PDGFR signaling activity and transactivation of EGFR, in a RAS-independent manner, in response to PDGF-BB stimulation. Sunitinib pre-treatment markedly reduced medulloblastoma cell migration in response to both PDGF-BB and 10% serum at 4 and 24 h after treatment. Pre-treatment with sunitinib for 1 h also resulted in detachment and decreased viability of D556, but not Daoy, cells and only after 48 h following treatment. However, sunitinib did not induce apoptosis in either cell line at any time point, indicating that the anti-migratory effects of sunitinib were not due to impeding cell survival. Sunitinib similarly inhibited PDGFR signaling and migration of primary murine Smo/Smo medulloblastoma cells, suggesting that the Smo/Smo mouse is an appropriate model for preclinical testing of sunitinib. These results indicate that sunitinib may be an important pharmacologic agent for the treatment of invasive medulloblastoma, particularly given evidence of its ability to cross the blood-brain barrier to target tumor cells, and thus warrants further in vivo testing for confirmation of efficacy.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Abouantoun TJ,Castellino RC,MacDonald TJdoi
10.1007/s11060-010-0259-9subject
Has Abstractpub_date
2011-01-01 00:00:00pages
215-26issue
2eissn
0167-594Xissn
1573-7373journal_volume
101pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:We aimed to compare three-dimensional conformal radiotherapy (3D-CRT) with intensity-modulated radiotherapy (IMRT) for the treatment of glioblastoma. MATERIALS AND METHODS:Retrospective study of 220 patients with glioblastoma, treated with 3D-CRT or IMRT, with or without surgery. Dosimetric para...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2735-y
更新日期:2018-04-01 00:00:00
abstract::Intracranial atypical teratoid/rhabdoid tumors (AT/RT) are rare with a poor prognosis. We report one case of a 7-year old girl living over 17 months after the diagnosis of AT/RT in the left frontal lobe. Treatment was partial surgical resection and post-operative radiation therapy. Radiation therapy resulted in comple...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-004-3120-1
更新日期:2005-03-01 00:00:00
abstract::This study retrospectively reviewed our single institute experience to clarify the optimal indication and timing of salvage surgery. Retrospective analysis of 159 consecutive cases with germ cell tumors identified 20 cases with salvage surgery. These cases were classified based on the radiological response to neoadjuv...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2827-3
更新日期:2018-07-01 00:00:00
abstract::Gamma Knife surgery (GKS) has emerged as a valuable adjuvant treatment modality for recurrent or residual craniopharyngioma. However, prognostic factors pertaining to progression-free survival (PFS) remain poorly understood. A study was conducted to address this issue. A total of 37 consecutive patients undergoing 39 ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-010-0494-0
更新日期:2011-08-01 00:00:00
abstract::Cancer related stroke may have different phenotypes from non-cancer stroke, especially in terms of stroke progression and recurrence. We performed a case-control study to identify their incidences and risk factors in cancer related stroke. Between January 2001 and December 2009, we conducted a retrospective review of ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-012-1011-4
更新日期:2013-02-01 00:00:00
abstract:INTRODUCTION:The standard treatment for primary central nervous system lymphoma (PCNSL) involves induction methotrexate-based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). As WBRT carries a substantial risk for cognitive impairment, alternative consolidation treatments have been used to re...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-019-03257-1
更新日期:2019-09-01 00:00:00
abstract::To explore the antitumor mechanism of bacterial cytosine deaminase plus 5-fluorocytosine (CD/5-FCyt) in combination with interferons (IFNs), glioma cells were transduced with recombinant retroviruses expressing CD. The transduced glioma cells become sensitive to the nontoxic prodrug 5-FCyt. Apoptosis, DNA damage, byst...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005883128175
更新日期:1998-02-01 00:00:00
abstract::We report on the long-term results of a phase II study of pre-irradiation temozolomide followed by concurrent temozolomide and radiotherapy (RT) in patients with newly diagnosed anaplastic oligodendroglioma (AO) and mixed anaplastic oligoastrocytoma. Pre-RT temozolomide was given for up to 6 cycles. RT with concurrent...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s11060-015-1845-7
更新日期:2015-09-01 00:00:00
abstract::The labeling index (LI) of 216 cases of human brain tumors was determined by the immunohistochemical technique with monoclonal antibody to bromodeoxyuridine (BrdU). The proliferative potential of 110 cases was estimated using the intra-operative intravenous infusion of BrdU at a dose of 200 mg/sq m. In another 106 cas...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1007/BF01059949
更新日期:1995-01-01 00:00:00
abstract::ERCC1 and ERCC2 have been known to belong to the nucleotide excision repair (NER) pathway and are essential to the repair of cisplatin DNA adducts. In the present study, we have examined the potential correlation of ERCC1, ERCC2 mRNA expression and single nucleotide polymorphism (SNP) to chemotherapy drug cytotoxicity...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-006-9290-2
更新日期:2007-05-01 00:00:00
abstract::Two patients with metastasis from lung carcinoma of the midbrain are presented. The computerized tomographic (CT) findings mimicked a primary pineal tumor, but autopsy confirmed a metastatic nodule in the midbrain in both cases. The rational approach to posterior third ventricular tumors seen on CT in adulthood is dis...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00165161
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:To analyze patterns of failure according to treatment modalities and evaluate the adequacy of an institution's current volume of postoperative radiotherapy (PORT) for World Health Organization (WHO) grade II or III meningiomas. PATIENTS AND METHODS:Data of 98 patients treated by either surgery and PORT (PORT g...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-019-03232-w
更新日期:2019-09-01 00:00:00
abstract::We prospectively addressed whether EGFR and KRAS mutations, EML4-ALK, ROS1 and RET rearrangements, or wild-type (WT), affects radiosurgery outcomes and overall survival (OS) in non-small cell lung cancer (NSCLC) patients with brain metastases (BM). Of 326 patients with BM treated in 2012-2014 with Gamma Knife radiosur...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-1986-8
更新日期:2016-02-01 00:00:00
abstract::The Hedgehog (Hh) signaling pathway has been implicated in the most common childhood brain tumor, medulloblastoma (MB). Given the toxicity of post-surgical treatments for MB, continued need exists for new, targeted therapies. Based upon our finding that Neuropilin (Nrp) transmembrane proteins are required for Hh signa...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-013-1216-1
更新日期:2013-11-01 00:00:00
abstract::We describe a 61-year-old man with a multiple neurologic complication of Merkel cell carcinoma, a rare skin cancer. An enhancing brain mass, and cytologically proven leptomeningeal disease produced a succession of symptoms including seizures, bilateral radiculopathies, myoclonus, a cauda equina syndrome and altered me...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF01052924
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:Intracranial glioblastomas with simultaneous spinal lesions prior to chemoradiation therapy or craniotomy, defined as initial spinal metastasis, are not well understood. Herein, we investigated intracranial glioblastoma and demonstrated the importance of spinal screening using gadolinium enhanced spinal magneti...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-03036-4
更新日期:2019-01-01 00:00:00
abstract::We aimed to assess the efficacy of stereotactic irradiation for patients with recurrent high-grade glioma (HGG) and identify predictive factors of progression-free survival (PFS) and overall survival (OS) following reirradiation. We identified 32 patients with recurrent brain HGG who had been treated with either singl...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2669-4
更新日期:2018-01-01 00:00:00
abstract:OBJECT:Etoposide, a topoisomerase-II inhibitor promotes DNA damage and apoptosis of cancer cells. In this study, we have examined the ability of the histone deacetylase inhibitor, valproic acid (VPA) to modulate gene expression and sensitize glioblastoma cell lines to the cytotoxic effects of etoposide in vitro. METHO...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-007-9402-7
更新日期:2007-11-01 00:00:00
abstract::We have investigated the anti-tumor activity of ex vivo activated and expanded T cells which had been sensitized in vivo to one of two different syngeneic rat glioma cell lines; D74 or RT-2. Rats were sensitized by inoculation of irradiated tumor cells into each hind foot pad. After 10 days, the tumor-draining lymph n...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005771717409
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND:Prior studies have highlighted infratentorial tumor location as a prognostic factor for solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) of the central nervous system (CNS), and spinal location is considered a positive prognostic factor for other tumors of the CNS. While SFT/HPC of the CNS is known ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-019-03177-0
更新日期:2019-07-01 00:00:00
abstract::The aim of the present study was to evaluate the spectrum of late effects in a large cohort of pediatric patients with low-grade gliomas (WHO grade I and II) during an observation period of 20 years. Eighty-seven patients with low-grade gliomas grouped according to tumor location (cerebellum: n=28; cerebral hemisphere...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-005-9091-z
更新日期:2006-06-01 00:00:00
abstract::Recurrent pediatric high-grade glioma is a leading cause of cancer-related death in children. We report results of a systematic review and meta-analysis investigating survival outcome in pediatric patients with recurrent high-grade glioma over the last 20 years. MEDLINE/PubMed, EMBASE, Web of Science and Cochrane Revi...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,meta分析
doi:10.1007/s11060-017-2701-8
更新日期:2018-03-01 00:00:00
abstract:INTRODUCTION:Clinical trials directed at mechanistic target of rapamycin (mTOR) inhibition have yielded disappointing results in glioblastoma (GBM). A major mechanism of resistance involves the activation of a salvage pathway stimulating internal ribosome entry site (IRES)-mediated protein synthesis. PRMT5 activity has...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-019-03274-0
更新日期:2019-10-01 00:00:00
abstract:PURPOSE:The purpose of our study was to determine the statistical significance of thresholds of relative cerebral blood volume (rCBV), apparent diffusion coefficient (ADC) and ADC ratios in grading cerebral gliomas. MATERIALS AND METHODS:In this retrospective study, 51 patients with histopathologically confirmed prima...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,收录出版
doi:10.1007/s11060-009-9807-6
更新日期:2009-08-01 00:00:00
abstract::The type III mutant epidermal growth factor receptor (EGFR) is expressed on the cell surface of a subset of glioma, but not of normal tissues. In this study, we investigated the in vivo kinetics of 3C10 mouse monoclonal antibody (mAb), specifically recognizing the type III mutant EGFR (EGFRvIII), using athymic nude mi...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1024320516341
更新日期:2003-07-01 00:00:00
abstract::The value of perfusion and diffusion-weighted MRI in differentiating histological subtypes according to the 2007 WHO glioma classification scheme (i.e. astrocytoma vs. oligodendroglioma) and genetic subtypes according to the 2016 WHO reclassification (e.g. 1p/19q co-deletion and IDH1 mutation status) in WHO grade II a...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2506-9
更新日期:2017-08-01 00:00:00
abstract::Boron neutron capture therapy (BNCT) is an experimental form of radiation therapy for malignant brain tumors and peripheral melanoma. The micro-distribution of the boron compound is critical to determine the radiation effects for both tumors and normal tissue. In the current dose calculation of BNCT, normal brain tiss...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-007-9494-0
更新日期:2008-03-01 00:00:00
abstract:INTRODUCTION:High hospital case volumes are associated with improved treatment outcomes for numerous diseases. We assessed the association between academic non-profit hospital case volume and survival of adult glioblastoma patients. METHODS:From the nationwide Finnish Cancer Registry, we identified all adult (≥ 18 yea...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-020-03428-5
更新日期:2020-04-01 00:00:00
abstract::There is considerable interest in the role of the TRK family of neurotrophin receptors in regulating the survival, growth and differentiation of normal and neoplastic nerve cells. Indeed, there is increasing evidence that TRK genes play an important role in the biology and clinical behavior of neuroblastomas, tumors o...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005729329526
更新日期:1997-01-01 00:00:00
abstract:OBJECTIVE:Radiation necrosis is a well-known complication of radiotherapy for malignant brain tumors. Although surgery was once considered the mainstay of treatment, no recent reports have evaluated the use of intraoperative magnetic resonance imaging (IOMRI) and frameless stereotaxis during surgical resection of radia...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/b:neon.0000024744.16031.e9
更新日期:2004-05-01 00:00:00