Abstract:
:Most malignant human tumors display a high degree of intratumoral heterogeneity at the time of diagnosis that contributes to treatment failure. This also applies to malignant peripheral nerve sheath tumors (MPNSTs) and aggressive soft tissue sarcomas that arise sporadically or in the context of neurofibromatosis type 1. On average, MPNSTs measure 10 cm in diameter at diagnosis. To explore molecular changes associated with early malignant progression and that may be present in most, if not all, tumor cells, we generated expression profiles of ethylnitrosourea-induced trigeminal MPNSTs in rats. Because these tumors cause increased intracranial pressure, they become detectable when they are comparatively minuscule. Histologic analyses revealed close resemblance to human MPNSTs. Compared with normal trigeminal nerve tissue, 365 genes were markedly upregulated and 310 genes were consistently downregulated in all MPNST samples. The molecular signature characteristic of early-stage MPNSTs included upregulation of proliferation and tissue remodeling-associated genes, downregulation of genes involved in Schwann cell differentiation, and the absence of transcripts associated with neuronal components. The transforming growth factor-β pathway was consistently upregulated in all tumor samples. These data suggest that the signaling pathways underlying early malignant progression of Schwann cells might be targeted to prevent tumor growth and/or to treat more advanced lesions.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Koelsch B,van den Berg L,Grabellus F,Fischer C,Kutritz A,Kindler-Röhrborn Adoi
10.1097/NEN.0b013e31828ea4acsubject
Has Abstractpub_date
2013-05-01 00:00:00pages
404-15issue
5eissn
0022-3069issn
1554-6578journal_volume
72pub_type
杂志文章abstract::Well myelinated cultures of newborn mouse cerebellum, exposed to varying concentrations of sodium diethyldithiocarbamate (DDC), a heavy metal chelating agent, were examined by light and electron microscopy. DDC treatment of cultures for 24-48 hours produced swellings of axons and presynaptic endings, the morphological...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197511000-00007
更新日期:1975-11-01 00:00:00
abstract::Maternal cigarette smoking during pregnancy is associated with a significantly increased risk of Sudden Infant Death Syndrome (SIDS). This study investigated the effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, on the neuroglial and neurochemical development of the medulla in...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/59.3.218
更新日期:2000-03-01 00:00:00
abstract::There is increasing evidence that oxidative damage plays a major role in amyotrophic lateral sclerosis (ALS), but how it contributes to motor neuron degeneration and astrocytic gliosis, two pathologic hallmarks of the disease, is unknown. A few studies have suggested that ALS motor neurons die via apoptosis and show u...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199712000-00006
更新日期:1997-12-01 00:00:00
abstract::Friedreich's Ataxia (FRDA) is caused by a homozygous intronic GAA expansion in the FXN gene. FRDA affects primarily the peripheral nervous system (PNS) with cumulative evidence from postmortem studies and in vitro models suggesting a developmental component of its pathology. In the present study, we aimed at gaining f...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nly100
更新日期:2018-12-01 00:00:00
abstract::Mucopolysaccharidosis IIID (MPS IIID) is one of the rarest of the MPS-III syndromes. To date, the clinical manifestations of 10 patients have been reported, the deficient N-acetylglucosamine 6-sulfatase (G6S) enzyme has been purified, and the G6S gene has been cloned, sequenced and localized. However, morphological ma...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
doi:
更新日期:1997-10-01 00:00:00
abstract::Peripheral polyneuropathies are common and their diagnosis may be challenging. We compared the results from sural-nerve and skin biopsies in 33 patients with a polyneuropathy and neuropathic pain examined in our hospital over a 6-year period. The biopsies were all from the same lower limb of each patient. Intraepiderm...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlv005
更新日期:2016-01-01 00:00:00
abstract::To develop improved therapies for medulloblastoma, we studied the ability of a neuroattenuated HSV-1 ICP34.5 mutant (variant-1716) to replicate within and destory an authentic medulloblastoma cell line known as Med 283 (D283) using immunohistochemistry, in situ hybridization, and viral titrations. In vitro studies sho...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199612000-00010
更新日期:1996-12-01 00:00:00
abstract::Abnormalities were detected by two-dimensional gel electrophoresis in the protein composition of both the dorsal and ventral roots of three of six patients who succumbed to amyotrophic lateral sclerosis (ALS). The abnormalities consisted of a cascade of acidic protein spots on silver-stained gels which were shown by i...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198411000-00005
更新日期:1984-11-01 00:00:00
abstract::Sibling concurrence of pathologically confirmed prion disease has only been reported in association with pathogenic mutation of the prion protein gene (PRNP). Here, we report 2 siblings with classic neuropathologic features of sporadic Creutzfeldt-Jakob disease unexplained by PRNP mutation or known risk factors for ia...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e318182f36e
更新日期:2008-09-01 00:00:00
abstract::After experimental nerve injuries that extensively disrupt axons, such as chronic constriction injury, immune cells invade the nerve, related dorsal root ganglia (DRGs), and spinal cord, leading to hyperexcitability, raised sensitivity, and pain. Entrapment neuropathies, such as carpal tunnel syndrome, involve minimal...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e318298de5b
更新日期:2013-07-01 00:00:00
abstract::In an earlier study we found that a substantial percentage of mice surviving infection with canine distemper virus (CDV) slowly developed a morbid obesity syndrome. In the present study we wished to explore the role of the virus in the development of this syndrome. The distribution of viral antigen(s) in brains of pre...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199201000-00012
更新日期:1992-01-01 00:00:00
abstract::Immunohistochemical identification of myelin basic protein (MBP) is a sensitive method for assessing myelination in the human fetal central nervous system (CNS). However, the temporospatial relationship of expression of two other major myelin proteins, proteolipid protein (PLP) and myelin-associated glycoprotein (MAG)...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199606000-00008
更新日期:1996-06-01 00:00:00
abstract::The development and differentiation of oligodendrocytes (OC) in developing mouse spinal cord (MSC) were investigated by correlative analysis of light and electron microscopy (EM), and immunoperoxidase studies for glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP). The sequential development of glial...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198609000-00003
更新日期:1986-09-01 00:00:00
abstract::Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a familial neurodegenerative disease clinically characterized by progressive cognitive and motor dysfunction. Mutations in the colony-stimulating factor 1 receptor (CSF1R) gene have recently been identified in HDLS patients. The presence of diffuse axonal...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000139
更新日期:2014-12-01 00:00:00
abstract::Intrauterine infection and inflammation have been linked to preterm birth and brain damage. We hypothesized that recombinant human erythropoietin (rhEPO) would ameliorate brain damage in anovine model of fetal inflammation. At 107 +/- 1 day of gestational age (DGA), chronically catheterized fetal sheep received on 3 c...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181d27138
更新日期:2010-03-01 00:00:00
abstract::Genetic and lifestyle-related risk factors for Alzheimer disease (AD) are associated with an increase in oxidative stress, suggesting that oxidative stress is involved at an early stage of the pathologic cascade. Moreover, oxidative stress is mechanistically and chronologically associated with other key features of AD...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
doi:10.1097/01.jnen.0000228136.58062.bf
更新日期:2006-07-01 00:00:00
abstract::This is the fourth recorded patient with extension of syringomyelia into the brain rostral to the mesencephalon verified at autopsy. A syrinx was demonstrated from the low thoracic segments of the spinal cord to the cervico-medullary junction, where a fibrovascular malformation and dural-arachnoid adhesions deformed t...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198111000-00005
更新日期:1981-11-01 00:00:00
abstract::Systemically-administered inorganic mercury localizes to motor neurons, but it is not known if mercury injures these neurons. We therefore looked for signs of damage to the motor and sensory neurons of mice that had been exposed to inorganic mercury. Young adult mice were injected intraperitoneally with either 1 or 2 ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199804000-00009
更新日期:1998-04-01 00:00:00
abstract::The concept of the presence of mucopolysaccharides forming an interstitial ground substance in central nervous tissues is revived. The biochemical reports of both neutral and acid mucopolysaccharides in both gray and white matter of the normal brain are reviewed. The earlier histochemical reports and the histochemical...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198001000-00001
更新日期:1980-01-01 00:00:00
abstract::Spirochetal infections are an important cause of neurological disease. In previous studies of the pathogenesis of spirochetal brain infection, mice inoculated with Borrelia turicatae, an agent of tick-borne relapsing fever in North America, developed mild meningitis and parenchymal activation/infiltration by interleuk...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e318187a279
更新日期:2008-10-01 00:00:00
abstract::Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an autosomal-dominant disorder involving the cerebral, retinal, renal, and other systemic microvessels due to frameshift mutations in the TREX1 gene. Under physiological conditions, the TREX1 protein is localized in the cellular cytoplasm and perinuclear area...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nly115
更新日期:2019-02-01 00:00:00
abstract::The effects of hypoglycemia on cerebrovascular permeability to a protein, horseradish peroxidase (HRP), were studied in mice given 3 or 8 units of crytalline zinc insulin intraperitoneally. HRP (10 mg in 0.1 ml saline) was injected intravenously 15 to 20 minutes prior to sacrifice. Both mildly and severely hypoglycemi...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198005000-00004
更新日期:1980-05-01 00:00:00
abstract::We review the newest advances related to seeking the pathogenic mechanism(s) of sporadic inclusion-body myositis (s-IBM) and present the pathologic diagnostic criteria of s-IBM. We discuss the possible pathogenic role of several themes, such as 1) increased amyloid-beta precursor protein (AbetaPP) and of its fragment ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
doi:10.1093/jnen/60.1.1
更新日期:2001-01-01 00:00:00
abstract::The abundant axonal microtubule-associated protein tau regulates microtubule and actin dynamics, thereby contributing to normal neuronal function. We examined whether mice deficient in tau (Tau(-/-)) or with high levels of human tau differ from wild-type (WT) mice in their susceptibility to neuroaxonal injury in exper...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3182540d2e
更新日期:2012-05-01 00:00:00
abstract::Alpha-synuclein (alpha-syn) is an important component of neuronal and glial inclusions in brains of patients with several neurodegenerative disorders. Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older patients. Its muscle phenotype shows several similarities with Alzheimer...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/59.7.592
更新日期:2000-07-01 00:00:00
abstract::The changes of nitric oxide synthase (NOS) activity and expression in experimental diabetic neuropathy have not been examined. Increases in ganglia NOS might be similar to those that follow axotomy, whereas declines in endothelial NOS (eNOS) and immunological NOS (iNOS) might explain dysfunction of microvessels or mac...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/59.9.798
更新日期:2000-09-01 00:00:00
abstract::Growing evidence indicates that alterations within the peripheral nervous system (PNS) are involved at an early stage in the amyotrophic lateral sclerosis (ALS) pathogenetic cascade. In this study, magnetic resonance imaging (MRI), neurophysiologic analyses, and histologic analyses were used to monitor the extent of P...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000081
更新日期:2014-07-01 00:00:00
abstract::Rates of remyelination decline with age and this has been attributed to slower recruitment of oligodendrocyte progenitor cells (OPCs) into areas of demyelination and slower differentiation of OPCs into remyelinating oligodendrocytes. When considering causes for reduced recruitment rates, intrinsic causes (alterations ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.9.908
更新日期:2003-09-01 00:00:00
abstract::Centrosome amplification is a pivotal mechanism underlying tumorigenesis but its role in gliomas is underinvestigated. The present study specifically examines the expression and distribution of the centrosome-associated cytoskeletal protein gamma-tubulin in 56 primary diffuse astrocytic gliomas (grades II-IV) and in 4...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000229235.20995.6e
更新日期:2006-05-01 00:00:00
abstract::Universally accepted neuropathologic criteria for differentiating Alzheimer disease (AD) from healthy brain aging do not exist. We tested the hypothesis that Bielschowsky silver stained total, cored, and neuritic senile plaques (TSPs, CSPs, and NSPs, respectively), rather than neurofibrillary tangles (NFTs), best disc...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/63.10.1028
更新日期:2004-10-01 00:00:00