Abstract:
PURPOSE:A major challenge to developing new therapies for patients with malignant brain tumors is that relatively few small molecule anticancer drugs penetrate the blood-brain barrier (BBB) well enough to provide therapeutically effective concentrations in brain tissue before drug exposure in non-CNS tissues results in unacceptable toxicity. METHODS:KX2-361, a member of a novel family of compounds with Src-kinase and tubulin polymerization inhibitory activity, demonstrates good oral bioavailability and readily crosses the BBB in mice. The objective of this study was to investigate the activity of KX2-361 against human and murine glioma cells and assess its therapeutic effect in a syngeneic orthotopic model of glioblastoma. RESULTS:In addition to reducing the level of Src autophosphorylation in the GL261 murine glioblastoma cell line, KX2-361 binds directly to tubulin and disrupts microtubule architecture in glioma cells maintained in culture. CONCLUSIONS:The drug is active in vivo against orthotopic GL261 gliomas in syngeneic C57BL/6 mice. Long term survival is not observed in mice lacking an adaptive immune system, indicating that KX2-361 works in concert with the host immune system to control tumor growth and promote long-term survival in the GL261 glioma model.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Ciesielski MJ,Bu Y,Munich SA,Teegarden P,Smolinski MP,Clements JL,Lau JYN,Hangauer DG,Fenstermaker RAdoi
10.1007/s11060-018-2992-4subject
Has Abstractpub_date
2018-12-01 00:00:00pages
519-527issue
3eissn
0167-594Xissn
1573-7373pii
10.1007/s11060-018-2992-4journal_volume
140pub_type
杂志文章abstract:BACKGROUND:The diagnosis of sarcomatous transformation of plexiform neurofibromas in Neurofibromatosis-1 (NF 1) is a clinical and radiological challenge. Considerable overlap exists in the clinical and the radiological characteristics between the benign enlarging neurofibromas and their counterparts undergoing malignan...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-006-9161-x
更新日期:2006-10-01 00:00:00
abstract::The diagnosis of a high-grade glioma usual is followed by functional impairment(s), cognitive decline and an impaired psycho-social well-being. This might well have a significant and negative impact on the health related quality of life. The purpose of this study was to explore physical activity levels, prevalence and...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-1821-2
更新日期:2015-09-01 00:00:00
abstract::Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or its ligand (PD-L1) have been shown to be effective in treating patients with a variety of cancers. Biomarker studies have found positive associations between clinical response rates and PD-L1 expression on tumor cells, as well as the presence of ...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2788-6
更新日期:2018-05-01 00:00:00
abstract::Unexpected early epidural spinal metastasis in a case of osteosarcoma occurred in a patient receiving treatment with cis-diamminedichloroplatinum-II (cisplatin). The initial neurologic symptomatology manifested as paresthesias in the feet which developed 2 months after initiation of treatment (cumulative dose of cispl...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00165378
更新日期:1986-01-01 00:00:00
abstract:INTRODUCTION:Central nervous system (CNS) involvement, especially involvement of the cerebrospinal fluid (CSF), is common in several haematological malignancies. Intrathecal (IT) chemotherapy can be used to manage CSF involvement. METHODS:Here we evaluated the effectiveness of IT chemotherapy among 80 patients with ha...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2849-x
更新日期:2018-08-01 00:00:00
abstract::Intracranial Hodgkin's lymphoma (ICHL) in the HIV positive population is a rarely reported event with only three prior cases reported in the literature. In these prior reports, the outcome of the patients was uncertain or very poor. We report here the case of an HIV seropositive patient with an isolated intracranial r...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-008-9587-4
更新日期:2008-08-01 00:00:00
abstract::Pilocytic astrocytomas are rare intracranial gliomas that are typically treated with surgical extirpation. Our aim was to report the radiologic and clinical outcomes of patients treated with stereotactic radiosurgery (SRS) for pilocytic astrocytoma in the primary and salvage setting. Patients with pilocytic astrocytom...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-017-2521-x
更新日期:2017-09-01 00:00:00
abstract::'Benign' brain tumors are a heterogeneous group of primary neoplasms representing 40% of primary brain tumors. Amongst neuroepithelial tumors, astrocytic neoplasms predominate, followed by oligodendroglial and mixed glial and glial-neuronal neoplasms. Less common are tumors of the ependyma, choroid plexus and neuroepi...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1023/b:neon.0000041871.46785.53
更新日期:2004-08-01 00:00:00
abstract:PURPOSE:Meningiomas comprise up to 30% of primary brain tumors. The majority of meningioma patients enjoy high rates of control after conventional therapies. However, patients with recurrent disease previously treated with radiotherapy have few options for salvage treatment, and systemic interventions have proven large...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-03011-z
更新日期:2019-01-01 00:00:00
abstract::Meningiomas, when benign, are commonly treated with surgical resection alone. However, the optimal treatment for patients with subtotally resected or recurrent World Health Organization (WHO) grade I tumors, or WHO grade II and III tumors, regardless of the extent of resection, is not well defined, with both a paucity...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-010-0375-6
更新日期:2010-09-01 00:00:00
abstract:PURPOSE:The uptake of the boron compound Na2B12H10-SH (BSH) in tumor and normal tissues was investigated in the frame of the EORTC phase I trial 'Postoperative treatment of glioblastoma with BNCT at the Petten Irradiation Facility' (protocol 11961). METHODS AND MATERIALS:The boron concentration in blood, tumor, normal...
journal_title:Journal of neuro-oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/BF02699941
更新日期:2003-03-01 00:00:00
abstract::High-grade gliomas release excitotoxic concentrations of glutamate which contributes to their malignant phenotype. To improve our understanding of the mechanisms by which glutamate enhances tumor growth and invasion, we examined alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-mediated signaling in glio...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-008-9552-2
更新日期:2008-06-01 00:00:00
abstract::Glioblastomas (GBM) may originate de novo (primary), or following transformation from a lower grade glioma (secondary), and it has been postulated that these tumors may have different biological behaviors. We performed a correlative analysis involving 204 patients with glioma treated prospectively on NCCTG clinical tr...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-010-0476-2
更新日期:2011-08-01 00:00:00
abstract::The objective of this study was to investigate racial/ethnic differences in survival for pediatric high-grade glioma (HGG) and medulloblastoma in the state of California. We obtained data from the California Cancer Registry on 552 high-grade glioma patients (110 brainstem, 442 non-brainstem) and 648 medulloblastoma pa...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-018-2773-0
更新日期:2018-05-01 00:00:00
abstract::Following surgical resection for brain metastases, fractionated stereotactic radiotherapy (FSRT) has been used as an alternative to single dose treatment for large cavities and to reduce risks of late toxicity. The purpose of this study was to evaluate the outcomes of patients treated with FSRT to the post-operative b...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-014-1417-2
更新日期:2014-05-01 00:00:00
abstract::A case of a functioning invasive pituitary oncocytoma in a 50-year-old man is reported. The serum prolactin was increased and immunocytochemical staining was positive for prolactin. In addition to numerous mitochondria within the neoplastic cells, structurally abnormal mitochondria with crystalline inclusions were als...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00165379
更新日期:1986-01-01 00:00:00
abstract::The human glioma cell line, NP-1, expresses IL-8 mRNA and constitutively secretes IL-8 protein. Administration of recombinant IL-8 increased the proliferation of NP-1 cells in a dose-dependent manner. In the presence of anti-IL-8 antiserum, the IL-8 mediated proliferation of NP-1 cell growth was inhibited. Further, NP...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF01054723
更新日期:1995-01-01 00:00:00
abstract::The aim of this study is to investigate the anti-cancer effect of the bispecific diphtheria toxin (DT) based immunotoxin DTATEGF, which targets both the epidermal growth factor (EGF) receptor (EGFR) and the urokinase-type plasminogen activator (uPA) receptor (uPAR) in vitro and in vivo when delivered by convection-enh...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-012-0904-6
更新日期:2012-09-01 00:00:00
abstract::The toxicity of IL-2 and/or C. Parvum when injected directly into the mouse brain was examined by survival and histopathology using different numbers of injections, different doses of IL-2, different solvents for the IL-2, and different doses and routes of administration of C. Parvum. Two injections was found signific...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/BF00172920
更新日期:1989-09-01 00:00:00
abstract::Hot spot mutations in the promoter region of telomerase reverse transcriptase (TERT promoter mutations) occur frequently in tumors of neuroectodermal origin such as melanoma and glioma. Many of these tumors are of neuroectodermal or ectomesenchymal origin which is suggestive of TERT promoter mutations playing a role i...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-014-1553-8
更新日期:2014-11-01 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::The diagnosis of brain metastases is associated with a poor prognosis reflecting uncontrolled primary disease that has spread to the relative sanctuary of the central nervous system. 20 % of brain metastases occur in the posterior fossa and are associated with significant morbidity. The risk of acute hydrocephalus and...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2254-2
更新日期:2016-12-01 00:00:00
abstract::Supratentorial primitive neuroectodermal tumors (sPNET) occurring in adults are rare. Only 56 such cases have been previously reported. This report documents a 56-year-old male who presented with the chief complaint of right facial palsy. Magnetic resonance imaging (MRI) revealed left frontal and bilateral periventric...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章,评审
doi:10.1007/s11060-007-9466-4
更新日期:2008-01-01 00:00:00
abstract:OBJECT:Prophylactic cranial irradiation (PCI) is commonly offered to patients with limited stage primary small cell lung cancer following a complete response. METHODS:We present the unique case of a 76-year-old woman treated with PCI with a dose of 30 Gy in 15 fractions, at 200 cGy per fraction who developed progressi...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-007-9384-5
更新日期:2007-10-01 00:00:00
abstract:PURPOSE:To assess the neurocognitive function and neurological toxicity of frameless linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) in patients with 10 or more brain metastases (BM). PATIENTS AND METHODS:Forty consecutive adult patients who received SRS for ten or more 10 BM < 3 cm in maximum size we...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-020-03442-7
更新日期:2020-05-01 00:00:00
abstract::Extensive surgical resection of centrally localized, newly diagnosed glioblastoma can lead to opening ventricles and therefore carries a potential risk of spreading tumor cells into the cebrospinal fluid. However, whether ventricle opening consequently implies a greater frequency of distant tumor recurrence after radi...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-016-2068-2
更新日期:2016-05-01 00:00:00
abstract::Anaplastic mixed gliomas are rare tumors that occur mostly in the cerebral hemispheres. They have a distinctive histological appearance characterized by the presence of two or more glial cellular constituents. The incidence of malignant mixed glioma of the brainstem and posterior fossa is extremely low. The authors re...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1005969429013
更新日期:1998-04-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The postoperative cerebellar mutism syndrome (CMS) is an unique acute postoperative complication characterized by transient decrease in speech output (often mutism), apathy, irritability as well as global cerebellar dysfunction. As much as 25% of patients undergoing a resection of a cerebellar...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1023/a:1006483531811
更新日期:2000-05-01 00:00:00
abstract::This study aims to evaluate the cost-effectiveness of surgical resection (S) and Cesium-131 (Cs-131) [S + Cs-131] intraoperative brachytherapy versus S and stereotactic radiosurgery (SRS) [S + SRS] for the treatment of brain metastases. Treatment records as well as hospital and outpatient charts of 49 patients with br...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-2026-4
更新日期:2016-03-01 00:00:00
abstract::Leptomeningeal disease (LMD) is a highly aggressive and usually rapidly fatal condition. The purpose of this study is to identify clinical factors that can serve to predict for LMD at the time of stereotactic radiosurgery (SRS) for brain metastases from breast carcinoma. We conducted a retrospective review of patients...
journal_title:Journal of neuro-oncology
pub_type: 杂志文章
doi:10.1007/s11060-015-1854-6
更新日期:2015-09-01 00:00:00