Abstract：
:Mutations of isocitrate dehydrogenase 1 (IDH1) gene are most common in glioma, arguably preceding all known genetic alterations during tumor development. IDH1 mutations nearly invariably target the enzymatic active site Arg132, giving rise to the predominant IDH1R132H. Cells harboring IDH1 R132H -heterozygous mutation produce 2-hydroxyglutarate (2-HG), which results in histone and DNA hypermethylation. Although exogenous IDH1 R132H transduction has been shown to promote anchorage-independent growth, the biological role of IDH1R132H in glioma remains debatable. In this study, we demonstrate that heterozygous IDH1 R132H suppresses but hemizygous IDH1 R132H promotes anchorage-independent growth. Whereas genetic deletion of the wild-type allele in IDH1 R132H -heterozygous cells resulted in a pronounced increase in neurosphere genesis, restoration of IDH1 expression in IDH1 R132H -hemizygous cells led to the contrary. Conversely, anchorage-independent growth was antagonistic to the mutant IDH1 function by inhibiting gene expression and 2-HG production. Furthermore, we identified that in contrast to IDH1 R132H -hemizygous neurosphere, IDH1 R132H -heterozygous cells maintained a low level of reducing power to suppress neurosphere genesis, which could be bypassed, however, by the addition of reducing agent. Taken together, these results underscore the functional importance of IDH1 mutation heterozygosity in glioma biology and indicate functional loss of mutant IDH1 as an escape mechanism underlying glioma progression and the pathway of redox homeostasis as potential therapeutic targets.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Tiburcio PDB,Xiao B,Berg S,Asper S,Lyne S,Zhang Y,Zhu X,Yan H,Huang LEdoi
10.1007/s00401-017-1800-0subject
Has Abstractpub_date
2018-02-01 00:00:00pages
285-298issue
2eissn
0001-6322issn
1432-0533pii
10.1007/s00401-017-1800-0journal_volume
135pub_type
杂志文章abstract：:Widespread damage to axons in the white matter of the brain is a well-recognised consequence of non-missile head injury. This diffuse axonal injury is characterised by a gradual swelling of the axon associated with an accumulation of cellular organelles and proteins. We have investigated the relationship between the s...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010051069
更新日期：1999-08-01 00:00:00
abstract：:Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded trinucleotide CAG repeat in the gene coding for huntingtin. Deregulation of chromatin remodeling is linked to the pathogenesis of HD but the mechanism remains elusive. To identify what genes are deregulated by trimethyla...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-013-1103-z
更新日期：2013-05-01 00:00:00
abstract：:The post-mortem diagnosis of lysosomal storage diseases can be confounded by the unavailability of suitable material. Here we report the diagnosis of GM1-gangliosidosis in a cross-bred dog, from which only formalin-fixed brain was available, by a combination of electron microscopy and the detection of elevated levels ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010000187
更新日期：2000-10-01 00:00:00
abstract：:The growth potential of 65 pituitary adenomas was determined by histochemical analysis with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs) determined by Ki-67 an...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00311392
更新日期：1992-01-01 00:00:00
abstract：:The pathological changes in the nucleus basalis of Meynert (nbM) in 10 autopsied cases with Pick's disease were studied in comparison with 15 age-matched controls. Both the number and density of nerve cells and the degree of fibrillary gliosis were examined at the anterior, intermediate, and posterior divisions of the...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687402
更新日期：1989-01-01 00:00:00
abstract：:We present the neuropathological findings in a female patient with clinically definite multiple sclerosis (MS), who at autopsy had multifocal amyloid deposits in the white matter of the brain without other signs of amyloidosis. The patient had relapsing/remitting MS between the ages of 26 and 45, and during her last 1...
journal_title：Acta neuropathologica
pub_type： 杂志文章,评审
doi：10.1007/s004010050604
更新日期：1997-02-01 00:00:00
abstract：:Nine dogs with canine distemper encephalitis (CDE) were examined with immunological techniques including demonstration of antibodies against canine distemper virus (CDV) in the serum and against myelin basic protein (MBP) in serum and in CSF. Mitogen stimulation tests of lymphocytes were also done. The brains were exa...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00691174
更新日期：1982-01-01 00:00:00
abstract：:Neuronal accumulation of oligomeric amyloid-beta (Alphabeta) is considered the proximal cause of neuronal demise in Alzheimer disease (AD) patients. Blood-borne macrophages might reduce Abeta stress to neurons by immigration into the brain and phagocytosis of Alphabeta. We tested migration and export across a blood-br...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-008-0481-0
更新日期：2009-02-01 00:00:00
abstract：:The binding of carbon disulphide sulphur was studied in the spinal cord and its axons of four control and four phenobarbitone pretreated adult rats 3 and 6 h after an intraperitoneal injection of 650 mumol of CS2 in olive oil. The binding of CS2 carbon was measured in the same fractions of two adult control rats 4.5 h...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00685369
更新日期：1976-11-15 00:00:00
abstract：:Using a fluorescent antibody technique, sections of the brains of patients with senile dementia or Alzheimer's disease containing senile plaques were treated with rabbit antihuman immunoglobulins labelled with FITC (fluorescein isothiocyanate, BBL). The senile plaques and the cerebral amyloid angiopathy (drusige Entar...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00689569
更新日期：1975-08-11 00:00:00
abstract：:The caudate nucleus and putamen belong to the selectively vulnerable brain regions which incur neuronal damage in clinical and experimental settings of both hypoglycemia and ischemia. We have previously documented the density and distribution of the hypoglycemic damage in rat caudoputamen, but the evolution of the inj...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688122
更新日期：1985-01-01 00:00:00
abstract：:Keratan sulphate proteoglycan (KSPG) is a developmentally regulated barrier molecule, directing axonal growth during central nervous system (CNS) formation. The possible re-expression and functional significance of KSPG in preventing axon regeneration following spinal cord injury (SCI) is poorly understood. In the pre...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-002-0589-6
更新日期：2002-12-01 00:00:00
abstract：:In a study designed to identify the neuropathological features typical of chronic inflammatory demyelinating polyneuropathy (CIDP), we reviewed the sural nerve biopsy findings in 105 patients with this disorder. The patients' mean age at biopsy was 49 years. In 65% of patients the disease had a progressive and in 35% ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050941
更新日期：1998-12-01 00:00:00
abstract：:It is well established that the binding of pathogenic aquaporin-4 (AQP4)-specific autoantibodies to astrocytes may initiate a cascade of events culminating in the destruction of these cells and in the formation of large tissue-destructive lesions typical for patients with neuromyelitis optica spectrum disorders (NMOSD...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-018-1950-8
更新日期：2019-03-01 00:00:00
abstract：:A 50-year-old carpenter died in Western Pennsylvania of rabies on January 4, 1979. He had been hospitalized in an intensive care unit for 28 days. The diagnosis was made postmortem from light and electron microscopic examination of central nervous system tissue. Immunofluorescence studies confirmed the diagnosis later...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687393
更新日期：1980-01-01 00:00:00
abstract：:Two cases out of a sample of 41 fetuses and infants with prosencephalic malformation, observed at the Institute of Pathology and Department of Neuropathology of the University of Heidelberg, are described here in detail. These cases presented grossly with microcephaly and missing forebrain, appearing to be cases of ap...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/pl00007438
更新日期：2000-03-01 00:00:00
abstract：:This report presents the ultrastructural nerve study of a patient with sensorimotor neuropathy by a shoe glue containing an association of n-hexane and methylethylketone. Giant axons, distended by microfilamentous proliferation typical of such cases of neuropathy, were found in significant amounts. An unusual histolog...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690990
更新日期：1981-01-01 00:00:00
abstract：:This report illustrates a case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) masquerading as neurofibromatosis due to multifocal enlargements of spinal nerve roots. The patient initially complained of intermittent numbness of the hands and leg weakness at age 62. Nerve conduction velocities were ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-002-0616-7
更新日期：2003-02-01 00:00:00
abstract：:Neuropathological studies have revealed that the brains of HIV-1-infected AIDS patients show the typical encephalitis and, in addition, neuronal loss. More recently, this neuronal cell loss has been thought to take place via programmed cell death (apoptosis) which has been demonstrated by an in situ end labelling (ISE...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050409
更新日期：1996-01-01 00:00:00
abstract：:The mechanisms underlying neurodegenerative diseases are the outcome of pathological alterations of evolutionary conserved molecular and cellular cascades. For this reason, Drosophila and C. elegans serve as useful model systems to study various aspects of neurodegenerative diseases. Here, we introduce the advantageou...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-010-0689-7
更新日期：2010-08-01 00:00:00
abstract：:Amplification of the epidermal growth factor receptor (EGFR) gene is found in about 40% of glioblastomas (GBMs) but is rarely detected in GBM cell lines. We confirmed that the exceptional SKMG-3 GBM cell line retained amplified EGFR genes in vitro, and found that these sequences were concentrated on extra-chromosomal ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010000332
更新日期：2001-06-01 00:00:00
abstract：:Morphometric observations have been made on the medial plantar division of the tibial nerve (MPD) and on the motor branches of the tibial nerve to the calf muscles (MBC) in rats ranging in age from weaning (3 weeks) to 12 months. Axon size, assessed by measurements of circumference and cross-sectional area, increased ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00308712
更新日期：1990-01-01 00:00:00
abstract：:In 54 cats experimental brain tumors were produced by xenotransplantation of the blastomatous glial cell clone RG2 into the internal capsule of the left hemisphere. Fifteen of these animals were treated with dexamethasone for 1 week and four animals for 2 h. The occurrence of glial fibrillary acidic (GFA) protein in t...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687613
更新日期：1984-01-01 00:00:00
abstract：:In G93A mice, the most popular model of amyotrophic lateral sclerosis (ALS), neuronal Lewy-body-like hyaline inclusions (LBHIs) and mitochondria-derived vacuoles are observed in addition to motor neuron loss. Although LBHIs are thought to be toxic, the significance of the mitochondria-derived vacuoles has not been ful...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-006-0056-x
更新日期：2006-07-01 00:00:00
abstract：:In looking for a possible influence of nuclear inclusions (NIs) on neurodegeneration in human brains, we quantified morphological features of pontine neurons of three unrelated cases of neuronal intranuclear inclusion disease (NIID) and five control cases. Cross-sectional area of each neuronal nucleus and the indices ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-002-0614-9
更新日期：2003-02-01 00:00:00
abstract：:An experiment was designed to examine the course of degeneration, phagocytosis, and regeneration in the central nervous system following surgical deafferentation. The anterior cerebellar vermis was ablated in young male rats. The animals were sacrificed by perfusion at postoperative times ranging from 24 hrs to 6 mont...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688396
更新日期：1975-12-19 00:00:00
abstract：:Inflammatory processes have been implicated in the formation of senile plaques in the cerebral cortex of patients with dementia of the Alzheimer type (DAT), since several inflammation-induced proteins are present within these plaques. The relation between inflammatory components and other amyloid beta protein (A beta)...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050474
更新日期：1996-01-01 00:00:00
abstract：:MicroRNAs are recognized as important regulators of many facets of physiological brain function while also being implicated in the pathogenesis of several neurological disorders. Dysregulation of miR155 is widely reported across a variety of neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-020-02185-z
更新日期：2020-09-01 00:00:00
abstract：:Basal ganglionic lesions in three young infants were found in a prospective search for early stages of status marmoratus. The lesions had formed and had passed into glial scars well before myelination of the basal ganglia commenced. The myelinating fibers crossing the scarred tissue were disoriented; however, fiber st...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688558
更新日期：1977-05-16 00:00:00
abstract：:A 65-year-old woman was admitted to our hospital for forgetfulness, depression and eccentric behavior that had been first noticed 2 years prior to admission. She showed memory impairment, perseveration and repeated violent actions, but no limb-kinetic apraxia. She died 12 years after the onset of symptoms. At autopsy,...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010100460
更新日期：2002-03-01 00:00:00
