Abstract:
:The effects of combining histone deacetylase (HDAC) inhibitors and proteasome inhibitors were evaluated in both established glioblastoma multiforme (GBM) cell lines and short-term cultures derived from the Mayo Clinic xenograft GBM panel. Coexposure of LBH589 and bortezomib at minimally toxic doses of either drug alone resulted in a striking induction of apoptosis in established U251, U87, and D37 GBM cell lines, as well as in GBM8, GBM10, GBM12, GBM14, and GBM56 short-term cultured cell lines. Synergism of apoptosis induction was also observed in U251 cells when coexposing cells to other HDAC inhibitors, including LAQ824 and trichostatin A, with the proteasome inhibitor MG132, thus demonstrating a class effect. In U251 cells, bortezomib alone or in combination with LBH589 decreased Raf-1 levels and suppressed Akt and Erk activation. LBH589 or bortezomib alone increased expression of the cell cycle regulators p21 and p27. Additionally, the combination, but not the individual agents, markedly enhanced JNK activation. Synergistic induction of apoptosis after exposure to LBH589 and bortezomib was partially mediated by Bax translocation from the cytosol to the mitochondria resulting from Bax conformational changes. Bax translocation precedes cytochrome c release and apoptosis, and selective down-regulation of Bax using siRNA significantly mitigates the cytotoxicity of LBH589 and bortezomib. This combination regimen warrants further preclinical and possible clinical study for glioma patients.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
Yu C,Friday BB,Yang L,Atadja P,Wigle D,Sarkaria J,Adjei AAdoi
10.1215/15228517-2007-063subject
Has Abstractpub_date
2008-06-01 00:00:00pages
309-19issue
3eissn
1522-8517issn
1523-5866pii
15228517-2007-063journal_volume
10pub_type
杂志文章相关文献
NEURO-ONCOLOGY文献大全abstract::Functional diffusion mapping (fDM) has shown promise as a sensitive imaging biomarker for predicting survival in initial studies consisting of a small number of patients, mixed tumor grades, and before routine use of anti-angiogenic therapy. The current study tested whether fDM performed before and after radiochemothe...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor220
更新日期:2012-03-01 00:00:00
abstract::Neuroblastomas, an embryonic cancer of the sympathetic nervous system, often occur in young children. Honokiol, a small-molecule polyphenol, has multiple therapeutic effects and pharmacological activities. This study was designed to evaluate whether honokiol could pass through the blood-brain barrier (BBB) and induce ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor217
更新日期:2012-03-01 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:Antiangiogenic therapy of vestibular schwannoma (VS) in type 2 neurofibromatosis can produce tumor shrinkage with response rates of 40%-60%. This study examines the predictive value of parameter-derived MRI in this setting. METHODS:Twelve patients with 20 VSs were recruited. Each had at least one rapidly gr...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov168
更新日期:2016-02-01 00:00:00
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: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::Secreted protein acidic and rich in cysteine (SPARC) has a suppressive effect on U87 glioma cell proliferation when assessed in vitro and in vivo using parental U87T2 and U87T2-derived SPARC-transfected clones. Since SPARCinteracts with extracellular matrix (ECM) proteins, we examined the effect of SPARC secretion on ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/5.4.244
更新日期:2003-10-01 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::Carmustine is used in the treatment of glioblastomas as locally applied chemotherapy in the form of biodegradable wafers, which are lined on the walls of the resection cavity at the end of the resection, to increase local concentrations and decrease systemic toxicity. A total of 44 patients with glioblastoma with gros...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos003
更新日期:2012-04-01 00:00:00
abstract::Treatment for newly diagnosed anaplastic oligodendroglial tumors is controversial. Radiotherapy (RT) alone and in combination with chemotherapy (CT) are the most well studied strategies. However, CT alone is often advocated, especially in cases with 1p19q codeletion. We retrospectively identified 1013 adults diagnosed...
journal_title:Neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1093/neuonc/nor040
更新日期:2011-06-01 00:00:00
abstract::Patients with the most common and aggressive form of high-grade glioma, glioblastoma multiforme, have poor prognosis and few treatment options. In 2 immunocompetent mouse brain tumor models (CT26-BALB/c and Tu-2449-B6C3F1), we showed that a nonlytic retroviral replicating vector (Toca 511) stably delivers an optimized...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor199
更新日期:2012-02-01 00:00:00
abstract:BACKGROUND:Temporal muscle thickness (TMT) was described as a surrogate marker of skeletal muscle mass. This study aimed to evaluate the prognostic relevance of TMT in patients with progressive glioblastoma. METHODS:TMT was analyzed on cranial MR images of 596 patients with progression of glioblastoma after radiochemo...
journal_title:Neuro-oncology
pub_type: 杂志文章,随机对照试验
doi:10.1093/neuonc/noz131
更新日期:2019-12-17 00:00:00
abstract::Histone modification has emerged as a promising approach to cancer therapy. We explored the in vivo efficacy of a butyric acid derivative, pivaloyloxymethyl butyrate (AN-9), for the treatment of gliomas. Relative to control and single-modality treatments, the combination of AN-9 and radiation significantly inhibited t...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2006-032
更新日期:2007-04-01 00:00:00
abstract::We examined DNA damage responses and repair in four human glioma cell lines (A7, U87, T98G, and U373) and normal human astrocytes (NHAs) after clinically relevant radiation doses to establish whether we could identify differences among them that might suggest new approaches to selective radiosensitization. We used pho...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2007-030
更新日期:2007-10-01 00:00:00
abstract:BACKGROUND:Meningiomas are the most commonly diagnosed primary intracranial neoplasms. Despite significant advances in modern therapies, the management of malignant meningioma and skull base meningioma remains a challenge. Thus, the development of new treatment modalities is urgently needed for these difficult-to-treat...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not007
更新日期:2013-06-01 00:00:00
abstract::We explored the associations of aberrant DNA methylation patterns in 12 candidate genes with adult glioma subtype, patient survival, and gene expression of enhancer of zeste human homolog 2 (EZH2) and insulin-like growth factor-binding protein 2 (IGFBP2). We analyzed 154 primary glioma tumors (37 astrocytoma II and II...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noq190
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:Glioblastomas with a specific mutation in the isocitrate dehydrogenase 1 (IDH1) gene have a better prognosis than gliomas with wild-type IDH1. METHODS:Here we compare the IDH1 mutational status in 172 contrast-enhancing glioma patients with the invasion profile generated by a patient-specific mathematical m...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou027
更新日期:2014-06-01 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::A phase I trial of an engineered poliovirus for the treatment of recurrent glioblastoma (GBM) has attracted attention due to 8 survivors reaching the 24-month and 5 reaching the 36-month survival landmarks.1 Genetically engineered viruses (oncolytic viruses) have been in trials for GBM for almost two decades.2 These r...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/noy170
更新日期:2019-01-01 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:Both the epidermal growth factor receptor and vascular endothelial growth factor pathways are frequently overexpressed in glioblastoma multiforme. This study combined bevacizumab, a vascular endothelial growth factor inhibitor, and erlotinib, an epidermal growth factor receptor inhibitor, with standard radia...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou029
更新日期:2014-07-01 00:00:00
abstract::Medulloblastomas are the most common malignant tumors of the central nervous system during childhood. Radiation-induced medulloblastoma tumor recurrences are aggressive and metastatic in nature. In the present study, we demonstrate that Gadd45a expression can sensitize medulloblastoma cells to radiotherapy. We have el...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor109
更新日期:2011-10-01 00:00:00
abstract::Angiogenesis is necessary for tumor growth beyond a volume of approximately 2 mm(3). This observation, along with the accessibility of tumor vessels to therapeutic targeting, has resulted in a research focus on inhibitors of angiogenesis. A number of endogenous inhibitors of angiogenesis are found in the body. Some of...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1215/S115285170400119X
更新日期:2005-04-01 00:00:00
abstract:Background:Sonidegib (LDE225) is a potent, selective hedgehog (Hh) inhibitor of Smoothened. This study explored the safety and pharmacokinetics of sonidegib in children with relapsed/recurrent tumors followed by a phase II trial in pediatric and adult patients with relapsed medulloblastoma (MB) to assess tumor response...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nox109
更新日期:2017-10-19 00:00:00
abstract:Background:Children with brain tumors treated with cranial radiation therapy (RT) often exhibit cognitive late effects, commonly associated with reduced white matter (WM) volume and decreased neurogenesis. The impact of radiation damage in particular regions or tissues on brain development as a whole has not been eluci...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nox211
更新日期:2018-05-18 00:00:00
abstract:Background:While recent genome-wide association studies have suggested novel low-grade glioma (LGG) stratification models based on a molecular classification, we explored the potential clinical utility of patient-derived cells. Specifically, we assayed glioma-associated stem cells (GASC) that are patient-derived and re...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nox234
更新日期:2018-05-18 00:00:00
abstract:BACKGROUND:Assessment of treatment response by measuring tumor size is known to be a late and potentially confounded response index. Serial diffusion MRI has shown potential for allowing earlier and possibly more reliable response assessment in adult patients, with limited experience in clinical settings and in pediatr...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not034
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND:Fatigue is common among glioma patients undergoing radiotherapy (RT) and impacts quality of life (QOL). We evaluated whether armodafinil, a wakefulness-promoting medication, improves fatigue in glioma patients undergoing RT. METHODS:Eligibility criteria included age ≥18 years, Karnofsky performance status ≥...
journal_title:Neuro-oncology
pub_type: 杂志文章,随机对照试验
doi:10.1093/neuonc/now007
更新日期:2016-06-01 00:00:00
abstract::Although external beam radiation is an essential component to the current standard treatment of primary brain tumors, its application is limited by toxicity at doses more than 80 Gy. Recent studies have suggested that brachytherapy with liposomally encapsulated radionuclides may be of benefit, and we have reported met...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos060
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND:The majority of WHO grades II and III gliomas harbor a missense mutation in the metabolic gene isocitrate dehydrogenase (IDH) and accumulate the metabolite R-2-hydroxyglutarate (R-2HG). Prior studies showed that this metabolite can be detected in vivo using proton magnetic-resonance spectroscopy (MRS), but t...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov307
更新日期:2016-02-01 00:00:00