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. Members of the protein kinase D (PKD) family, which consists of PKD1, -2 and, -3, are prominent downstream targets of PKCs and could play a major role in glioblastoma growth. PKD2 was highly expressed in both low-grade and high-grade human gliomas. The number of PKD2-positive tumor cells increased with glioma grading (P < .001). PKD2 was also expressed in CD133-positive glioblastoma stem cells and various glioblastoma cell lines in which the kinase was found to be constitutively active. Inhibition of PKDs by pharmacological inhibitors resulted in substantial inhibition of glioblastoma proliferation. Furthermore, specific depletion of PKD2 by siRNA resulted in a marked inhibition of anchorage-dependent and -independent proliferation and an accumulation of glioblastoma cells in G0/G1, accompanied by a down-regulation of cyclin D1 expression. In addition, PKD2-depleted glioblastoma cells exhibited substantially reduced tumor formation in vivo on chicken chorioallantoic membranes. These findings identify PKD2 as a novel mediator of glioblastoma cell growth in vitro and in vivo and thereby as a potential therapeutic target for this devastating disease.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
Azoitei N,Kleger A,Schoo N,Thal DR,Brunner C,Pusapati GV,Filatova A,Genze F,Möller P,Acker T,Kuefer R,Van Lint J,Baust H,Adler G,Seufferlein Tdoi
10.1093/neuonc/nor084subject
Has Abstractpub_date
2011-07-01 00:00:00pages
710-24issue
7eissn
1522-8517issn
1523-5866pii
nor084journal_volume
13pub_type
杂志文章相关文献
NEURO-ONCOLOGY文献大全abstract:BACKGROUND:Several lines of evidence suggest a T cell-mediated immune response in paraneoplastic neurological syndromes with anti-Hu antibodies (Hu-PNS). In order to investigate whether suppression of T cell-mediated immune responses in Hu-PNS patients improved their neurological outcome, we performed a prospective ope...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou126
更新日期:2015-01-01 00:00:00
abstract:Background:Glioblastoma (GBM) is one of the most common, aggressive, and invasive human brain tumors. There are few reliable mechanism-based therapeutic approaches for GBM patients. The transcriptional repressor RE1 silencing transcriptional factor (REST) regulates the oncogenic properties of a class of GBM stem-like c...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now232
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND:Anaplastic oligodendroglial tumors are rare, and median survival varies widely. Analysis of 1p19q deletion is performed commonly and is an important prognostic factor. However, age and other clinical variables also carry prognostic value, and it is unclear how to incorporate them into clinical decision makin...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou083
更新日期:2014-11-01 00:00:00
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:BACKGROUND:Mutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Mos...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not015
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Nonfunctioning pituitary adenoma (NFPA) and growth hormone pituitary adenoma (GHPA) are major subtypes of pituitary adenomas (PAs). The primary treatment is surgical resection. However, radical excision remains challenging, and few effective medical therapies are available. It is urgent to find novel targets...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noaa084
更新日期:2020-08-17 00:00:00
abstract:BACKGROUND:A cDNA library made from 2 glioma cell lines, U87MG and T98G, was screened by serological identification of antigens by recombinant cDNA expression (SEREX) using serum from a glioblastoma patient. Elongation factor Tu GTP binding domain containing protein 1 (EFTUD1), which is required for ribosome biogenesis...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou132
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND:Cisplatin-Induced Peripheral Neuropathy (CIPN) is a frequent serious dose-dependent adverse event that can determine dosage limitations for cancer treatment. CIPN severity correlates with the amount of platinum detected in sensory neurons of the dorsal root ganglia (DRG). However, the exact pathophysiology o...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noaa151
更新日期:2020-06-29 00:00:00
abstract:Background:Copy number alterations form prognostic molecular subtypes of glioblastoma with clear differences in median overall survival. In this study, we leverage molecular data from several glioblastoma cohorts to define the distribution of copy number subtypes across random cohorts as well as cohorts with selection ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noy108
更新日期:2018-09-03 00:00:00
abstract:BACKGROUND:RTOG 0625/ACRIN 6677 is a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma (GBM). This study investigated whether early posttreatment progression on FLAIR or postcontrast MRI assessed by central reading predicts overall survival (OS). METHODS:O...
journal_title:Neuro-oncology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1093/neuonc/not049
更新日期:2013-07-01 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::Stereotactic biopsy is often performed for diagnostic purposes before treating patients whose imaging studies highly suggest glioma. Indications cited for biopsy include diagnosis and/or the "inoperability" of the tumor. This study questions the routine use of stereotactic biopsy in the initial management of gliomas. ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/3.3.193
更新日期:2001-07-01 00:00:00
abstract:BACKGROUND:Recent molecular characterization studies have identified clinically relevant molecular subtypes to coexist within the same histological entities of glioma. Comparative studies between serum-supplemented and serum-free (SF) culture conditions have demonstrated that SF conditions select for glioma stem-like c...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not116
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:The transcription factor homeobox C9 (HOXC9) plays a crucial role in developmental regulatory systems, where it determines the specific positional identities of cells along the anteroposterior axis. The expression of HOXC9 has been found to be dysregulated in some cancers such as lung cancer, breast cancer, ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov281
更新日期:2016-06-01 00:00:00
abstract::Ependymal tumors are rare CNS tumors and may occur at any age, but their proportion among primary brain tumors is highest in children and young adults. Thus, the level of evidence of diagnostic and therapeutic interventions is higher in the pediatric compared with the adult patient population.The diagnosis and disease...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nox166
更新日期:2018-03-27 00:00:00
abstract:BACKGROUND:We report a phase I study to examine the pharmacokinetics, safety, and recommended dosage of weekly intravenous bolus 5-fluorouracil (5-FU) in children and young adults with recurrent ependymoma. METHODS:Patients 22 years of age or less with recurrent ependymoma were treated with bolus dosage 5-FU weekly fo...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov181
更新日期:2015-12-01 00:00:00
abstract::The blood-brain barrier (BBB) excludes the vast majority of cancer therapeutics from normal brain. However, the importance of the BBB in limiting drug delivery and efficacy is controversial in high-grade brain tumors, such as glioblastoma (GBM). The accumulation of normally brain impenetrant radiographic contrast mate...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nox175
更新日期:2018-01-22 00:00:00
abstract:BACKGROUND:Altered expression of micro(mi)RNAs has been shown to be associated with tumorigenesis and tumor progression. The expression of phosphatase and tensin homolog (PTEN) plays an important role in glioma and is regarded as a prognostic marker of glioma patients. The goal of this study was to investigate the func...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not107
更新日期:2013-11-01 00:00:00
abstract:Background:Craniopharyngiomas are neoplasms of the sellar/parasellar region that are classified into adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP) subtypes. Surgical resection of craniopharyngiomas is challenging, and recurrence is common, frequently leading to profound morbidity. BRAF ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noy035
更新日期:2018-07-05 00:00:00
abstract:BACKGROUND:The influence of survivin isoforms on outcome in glioblastoma is poorly understood. We analyzed the dominant anti-apoptotic transcript variants of survivin using expression data and modeled them in vivo to determine their impact on glioma formation and progression. METHODS:Using data from low- and high-grad...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou034
更新日期:2014-09-01 00:00:00
abstract:BACKGROUND:Micro (mi)RNAs are key regulators of gene expression and offer themselves as biomarkers for cancer development and progression. Meningioma is one of the most frequent primary intracranial tumors. As of yet, there are limited data on the role of miRNAs in meningioma of different histological subtypes and the ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nov014
更新日期:2015-09-01 00:00:00
abstract::The individualized care of glioma patients ought to benefit from imaging biomarkers as precocious predictors of therapeutic efficacy. Contrast enhanced MRI and [(18)F]-fluorodeoxyglucose (FDG)-PET are routinely used in clinical settings; their ability to forecast the therapeutic response is controversial. The objectiv...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos260
更新日期:2013-01-01 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: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
abstract::Glutathione S-transferases (GSTs) are polymorphic enzymes that catalyze the glutathione conjugation of alkylating agents, platinum compounds, and free radicals formed by radiation used to treat medulloblastoma. We hypothesized that GST polymorphisms may be responsible, in part, for individual differences in toxicity a...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1215/15228517-2008-089
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:Isocitrate dehydrogenase (IDH) mutation status has emerged as an important prognostic marker in gliomas. Currently, reliable IDH mutation determination requires invasive surgical procedures. The purpose of this study was to develop a highly accurate, MRI-based, voxelwise deep-learning IDH classification netw...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noz199
更新日期:2020-03-05 00:00:00
abstract::The objective of this study was to evaluate whether longitudinal levels of serum YKL-40 correlate with disease status or survival in adults with gliomas. Patients with histologically confirmed gliomas were eligible for this longitudinal study. Serum samples were collected prospectively and concurrently with MRI scans ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor117
更新日期:2011-11-01 00:00:00
abstract::The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving a...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/2.2.114
更新日期:2000-04-01 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::Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, micr...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/4.1.26
更新日期:2002-01-01 00:00:00