Abstract:
:In search of novel genes associated with glioma pathogenesis, we have previously shown frequent deletions of the KIAA1797/FOCAD gene in malignant gliomas, and a tumor suppressor function of the encoded focadhesin impacting proliferation and migration of glioma cells in vitro and in vivo. Here, we examined an association of reduced FOCAD gene copy number with overall survival of patients with astrocytic gliomas, and addressed the molecular mechanisms that govern the suppressive effect of focadhesin on glioma growth. FOCAD loss was associated with inferior outcome in patients with isocitrate dehydrogenase 1 or 2 (IDH)-mutant astrocytic gliomas of WHO grades II-IV. Multivariate analysis considering age at diagnosis as well as IDH mutation, MGMT promoter methylation, and CDKN2A/B homozygous deletion status confirmed reduced FOCAD gene copy number as a prognostic factor for overall survival. Using a yeast two-hybrid screen and pull-down assays, tubulin beta-6 and other tubulin family members were identified as novel focadhesin-interacting partners. Tubulins and focadhesin co-localized to centrosomes where focadhesin was enriched in proximity to centrioles. Focadhesin was recruited to microtubules via its interaction partner SLAIN motif family member 2 and reduced microtubule assembly rates, possibly explaining the focadhesin-dependent decrease in cell migration. During the cell cycle, focadhesin levels peaked in G2/M phase and influenced time-dependent G2/M progression potentially via polo like kinase 1 phosphorylation, providing a possible explanation for focadhesin-dependent cell growth reduction. We conclude that FOCAD loss may promote biological aggressiveness and worsen clinical outcome of diffuse astrocytic gliomas by enhancing microtubule assembly and accelerating G2/M phase progression.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Brand F,Förster A,Christians A,Bucher M,Thomé CM,Raab MS,Westphal M,Pietsch T,von Deimling A,Reifenberger G,Claus P,Hentschel B,Weller M,Weber RGdoi
10.1007/s00401-019-02067-zsubject
Has Abstractpub_date
2020-01-01 00:00:00pages
175-192issue
1eissn
0001-6322issn
1432-0533pii
10.1007/s00401-019-02067-zjournal_volume
139pub_type
杂志文章abstract::We have recently shown that glioma cell lines, as well as cells of human malignant gliomas in situ, synthesize tropoelastin. In addition, glioma cells degrade tropoelastin using metalloproteinase(s), and the resulting peptides, incapable of assembling in the extracellular fibers, interact with the 67-kDa cell surface ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010051004
更新日期:1999-04-01 00:00:00
abstract::It has been suggested that delayed development in either the peripheral or central nervous system could underlie the sudden infant death syndrome (SIDS). We studied the phrenic nerve in an attempt to find if maturation in this nerve was delayed in SIDS, and to see if fiber size differences could explain the paucity of...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050445
更新日期:1996-01-01 00:00:00
abstract::This report concerns a clinicopathological study of three additional patients with corticobasal degeneration (CBD), described here for the first time, and a clinicopathological correlation between pyramidal signs and upper motor neuron involvement, in ten autopsy cases of CBD, including seven cases reported by us prev...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-004-0966-4
更新日期:2005-04-01 00:00:00
abstract::Glycerol (an atoxic alcohol) and phenol (a toxic monohydroxybenzene) are currently used as neurolytic blocking agents to relieve pain or spasticity. In the present study we compared the endoneurial response of anhydrous glycerol and 7% phenol-aqua after intraneural injection into rat sciatic nerve, using electron micr...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010000349
更新日期:2001-07-01 00:00:00
abstract::The original version of this article unfortunately contained a typesetting error in Fig 3c. The corrected Fig. 3 is given in the following page. ...
journal_title:Acta neuropathologica
pub_type: 杂志文章,已发布勘误
doi:10.1007/s00401-019-02115-8
更新日期:2020-02-01 00:00:00
abstract::The expression of glial fibrillary acidic protein (GFAP), vimentin, S-100 protein (S-100), HNK-1, myelin basic protein (MBP) and fibronectin was investigated immunohistochemically in 51 ethylnitrosourea (ENU)-induced neurinomas of the rat. Additionally, 90 transplantation tumors derived from ENU-induced neurinomas and...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00310927
更新日期:1991-01-01 00:00:00
abstract::A woman of 22 years developed heavy pain in the neck and arms with weakness and paresthesia. She died two days after a myelography which was normal. At autopsy an enterogenous extra- and intra-medullary cyst of the cervical cord (C3, C4) was found. In addition the cervical cord apart from the cyst and the uppermost th...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00691967
更新日期:1977-11-28 00:00:00
abstract::Flow cytofluorometric analysis was used to determine the distribution of the DNA content in cells from selected areas of normal human brain and in benign and malignant brain tumors. Propidium iodide was employed as DNA fluorochrome and the analysis was carried out on a suspension of single cells. Normal, nonstimulated...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00684802
更新日期:1979-04-12 00:00:00
abstract::Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O (6) -methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-015-1403-6
更新日期:2015-04-01 00:00:00
abstract::Inflammatory myopathy with abundant macrophages (IMAM) and dermatomyositis (DM) are considered to represent related disorders, since they share inflammatory infiltrates and skin alterations. In order to get more insight into these disorders, we addressed the cellular composition of the inflammatory infiltrates in musc...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-009-0570-8
更新日期:2009-12-01 00:00:00
abstract::Cavernous malformations (CVMs) and arteriovenous malformations (AVMs) were immunostained for three smooth muscle cell (SMC)-specific protein markers (smooth muscle alpha-actin, SM1 and SM2). Smooth muscle alpha-actin, a widely used marker of SMCs, is reportedly one of the earliest proteins expressed during differentia...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010100362
更新日期:2001-09-01 00:00:00
abstract::In 2011, genome-wide association studies implicated a polymorphism near CD33 as a genetic risk factor for Alzheimer's disease. This finding sparked interest in this member of the sialic acid-binding immunoglobulin-type lectin family which is linked to innate immunity. Subsequent studies found that CD33 is expressed in...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-019-02000-4
更新日期:2019-08-01 00:00:00
abstract::Intermitochondrial septate structures were found in the dystrophic axons of two cases of infantile neuroaxonal dystrophy. Septate structures were previously seen in some tumors (glioblastomas and Schwannomas) and several organs of vertebrates and invertebrates, but never in human central nervous system (CNS). The stru...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688007
更新日期:1980-01-01 00:00:00
abstract::An autopsy case of Nasu-Hakola's disease (membranous lipodystrophy) was reported. A 29-year-old Japanese woman whose younger sister had been affected with typical Nasu-Hakola's disease with skeletal and neuropsychiatric syndromes and membrano-cystic lesions in the bones developed forgetfulness and lack of initiative. ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00689400
更新日期:1981-01-01 00:00:00
abstract::We investigated whether the brainstem is affected by the pathologic process of sporadic Creutzfeldt-Jakob disease (sCJD), with particular attention to brainstem atrophy, neuronal loss, pyramidal tract degeneration, and prion protein (PrP) deposition, in 33 patients with sCJD. Brainstem atrophy, particularly in the pon...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-005-0981-0
更新日期:2005-06-01 00:00:00
abstract::A case of multifocal axonopathy associated with intrathecal methotrexate (IT MTX) and radiation therapy is presented. A 33-year-old woman suffering from meningeal carcinomatosis of breast cancer origin had developed prominent multifocal axonal degeneration in the cerebral white matter after treatment with IT MTX thera...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294671
更新日期:1989-01-01 00:00:00
abstract::The immunoreactivity to the free radical-related enzymes, nitric oxide synthase (NOS) and superoxide dismutase (SOD), was examined in brain tissue in progressive supranuclear palsy (PSP). To determine the relationship between the immunoexpression of these enzymes and tau-positive, argyrophilic cytoplasmic inclusions, ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050808
更新日期:1998-04-01 00:00:00
abstract::A desmoplastic primary cerebral neuroblastoma originating in the frontal lobe of a boy who died at the age of 6 years contained dense core vesicles within the cytoplasm of neoplastic cells as evidence of neuronal differentiation. Sarcomatous transformation had occurred at the time of recurrence. At autopsy, he also ha...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688540
更新日期:1980-01-01 00:00:00
abstract::Peroxiredoxin-ll (Prxll) and glutathione peroxidase-l (GPxl) are regulators of the redox system that is one of the most crucial supporting systems in neurons. This system is an antioxidant enzyme defense system and is synchronously linked to other important cell supporting systems. To clarify the common self-survival ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-005-1019-3
更新日期:2005-08-01 00:00:00
abstract::An 18 month old cat had a 6 month history of abnormal high stepping gait, ataxia, muscle twitching and loss of sensory perception. The clinical course was interrupted by several episodes of temporary remission. The essential pathological features were those of a polyradiculoneuritis with segmental demyelination, focal...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00689561
更新日期:1978-01-19 00:00:00
abstract::The nature and distribution of vascular changes in acute Wernicke's encephalopathy (WE) were analyzed in three autopsy cases. Lesions of the lateral vestibular nucleus of the medulla oblongata (three cases) and lateral ventricular wall (one case) were examined by reconstruction of 200 serial sections, and the capillar...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00307646
更新日期:1995-01-01 00:00:00
abstract::A critical appraisal is presented of nearly two decades of research publications and review articles advocating the bidirectional transcytosis of fluid-phase molecules, most notably native horseradish peroxidase (HRP), through the normal and experimentally modified blood-brain barrier (BBB). Extracellular routes circu...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/BF00294368
更新日期:1989-01-01 00:00:00
abstract::The distribution of apolipoprotein E (ApoE) was studied in the brain tissue of cases of the amyotrophic lateral sclerosis-parkinsonism-dementia complex of Guam, locally known as lytico bodig disease (LB), and compared with cases of Alzheimer's disease (AD) and normal brain tissue. In both LB and AD, strong ApoE immuno...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050533
更新日期:1996-10-01 00:00:00
abstract::Intracerebral C6 glioma xenografts spontaneously develop centrally located necrotic regions that are bordered by densely packed neoplastic cells. Proliferative and metabolic heterogeneity in these perinecrotic regions were assessed by bromodeoxyuridine (BrdU) incorporation, by immunocytological and by histochemical an...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-003-0803-1
更新日期:2004-03-01 00:00:00
abstract::Multiple different pathological protein aggregates are frequently seen in human postmortem brains and hence mixed pathology is common. Mixed dementia on the other hand is less frequent and neuropathologically should only be diagnosed if criteria for more than one full blown disease are met. We quantitatively measured ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-015-1406-3
更新日期:2015-05-01 00:00:00
abstract::We examined the immunohistochemical localization of p35nck5a, the regulatory subunit of cyclin-dependent kinase 5 (cdk5), in brains obtained postmortem from patients with Parkinson's disease (PD) and controls. We found p35nck5a immunoreactivity in Lewy bodies (LB) in the substantia nigra, locus ceruleus, and neocortex...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050687
更新日期:1997-08-01 00:00:00
abstract::Charcot-Marie-Tooth disease type 1 B (CMT1B) is a demyelinating neuropathy caused by mutations in the myelin protein zero (P0) gene (MPZ). A few cases of CMT1B were recently found to be characterized by focally folded myelin sheaths in nerve biopsy specimens; the significance of this association is unknown. Here, we d...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004019900175
更新日期:2000-09-01 00:00:00
abstract::Eleven atypical teratoid/rhabdoid tumors (AT/RT) and 121 primitive neuroectodermal tumors/medulloblastomas (PNET/MB) were included in this study for evaluation of the histopathological features of AT/RT and comparison between AT/RT and PNET/MB. Histopathological studies of AT/RT showed that in addition to the commonly...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010051149
更新日期:2000-05-01 00:00:00
abstract::Double immunofluorescence for paired helical filament (PHF)-tau (AT8) and ubiquitin, enhanced by catalyzed reporter deposition amplification, was combined with thiazin red (TR), a fluorochrome, which has an affinity to fibrillary structures such as neurofibrillary tangles (NFTs). After recording these triple-fluoresce...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010000306
更新日期:2001-06-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) are endoproteases that have been implicated in the pathogenesis of inflammatory and vasculitic neuropathies. In systemic lupus erythematosus (SLE), a peripheral neuropathy is frequently seen that is thought to be caused by ischemic nerve damage due to vasculopathy and/or vasculitis of ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-002-0653-2
更新日期:2003-04-01 00:00:00