Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The computed tomography (CT) and magnetic resonance imaging (MRI) studies of 22 patients with a histologically proven olfactory neuroblastoma were retrospectively reviewed. The tumours displayed a variety of imaging characteristics and aggressiveness. The expansile tendency of olfactory neuroblastoma is characterised by bowing of the sinus walls. The destructive aspect is manifested as tumour replacing the turbinates, septum, and sinus walls with extension into contiguous areas. The density/signal and enhancement characteristics are non-specific. Olfactory neuroblastoma should be suspected in all ages following identification of a mass in the superior nasal cavity demonstrating both expansile and destructive growth patterns. The otorhinolaryngologist and the radiologist should be aware of this tumour entity, as early diagnosis appropriately guides therapy and predicts survival.
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PMID:Computed tomography and magnetic resonance imaging features of olfactory neuroblastoma: an analysis of 22 cases. 1054 31

Inhibition of the RGD-binding integrins, alpha(v)beta3 and alpha(v)beta5, prevents endothelial cell anchorage and induces endothelial apoptosis, which results in disruption of tumor angiogenesis and inhibition of tumor growth in animal models. In this study, we demonstrate by immunohistochemical analysis that integrin alpha(v)beta3 was expressed by 61% (mean) of microvessels in high-risk neuroblastomas (stage IV and MYCN-amplified stage III; n = 28) but only by 18% (mean) of microvessels in low-risk tumors (stages I and II and non-MYCN-amplified stage III; n = 12). Integrin alpha(v)beta5 was found on 60% (mean) of microvessels in 21 Stage IV tumors. These data suggest that neuroblastomas may be targeted for antiangiogenic treatment directed against endothelial integrins alpha(v)beta3 and alpha(v)beta5. In cell culture, inhibition of integrin-dependent endothelial cell anchorage to vitronectin by RGDfV, an RGD function-blocking cyclic peptide, induced apoptosis in bovine brain endothelial cells compared with the control peptide, RADfV (37.5% versus 8.7%, respectively), as detected by chromatin condensation and nuclear fragmentation. Treatment with RGDfV but not with RADfV, which prevented attachment of endothelial cells to vitronectin or fibronectin, was associated with up to a 50% increase in endogenous ceramide, a lipid second messenger that can mediate cell death. Furthermore, exogenous C2-ceramide was cytotoxic to bovine brain endothelial cells and induced activation of C-jun N-terminal kinase (JNK), a MAP kinase that can be activated in stress-induced apoptosis pathways. This suggests that ceramide may function in detachment-induced endothelial cell apoptosis, originating from inhibition of vitronectin binding to integrins such as alpha(v)beta3 and alpha(v)beta5. This is the first report to demonstrate expression of integrins alpha(v)beta3 and alpha(v)beta5 by microvascular endothelium of a childhood tumor and association of their expression with neuroblastoma aggressiveness. Furthermore, our data provide the first suggestion that inhibition of endothelial cell anchorage, resulting from specific blockade of RGD-binding integrins, increases endogenous ceramide, which may contribute to endothelial cell death.
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PMID:Integrins alpha(v)beta3 and alpha(v)beta5 are expressed by endothelium of high-risk neuroblastoma and their inhibition is associated with increased endogenous ceramide. 1067 58

CD44 gene products are potential markers of aggressiveness in different tumor models, a result which prompted us to study clinical neuroblastoma (NB) specimens. CD44 expression was determined by immunostaining of 52 NB with a monoclonal antibody (J173) directed against an epitope common to all CD44 isoforms. All tumors were from patients (pts) with newly diagnosed NB treated with standardized protocols. They were classified according to international criteria [11]. CD44 immunoreactivity was detected in 37 tumors (71%). CD44 was expressed in 100% of favorable NB stages (1, 2 or 4S), but only 50% of advanced NB (stages 3 and 4) (p = 0.0001), suggesting that the absence rather that the overexpression of CD44 is a signal of tumor aggressiveness. The cumulative event-free survival was significantly longer in pts with CD44-positive tumors as compared to pts with CD44-negative tumors (p < 10(-5)). More importantly, progression-free survival was also significantly higher in CD44-positive pts within the high-risk group (p < 0.01). In univariate analyses, we tested the prognostic value of tumor expression of CD44 in comparison with tumor stage, age, tumor histology and presence or absence of N-myc proto-oncogene amplification. All five measures had significant prognostic value. The expression of CD44 and the absence of N-myc amplification were the most powerful predictors of a favorable clinical outcome. In a multivariate analysis of these measures, CD44 expression and tumor stage were the only independent prognostic factors for the prediction of patient survival. NB is the first clinical model described in which tumor aggressiveness correlates with a repression rather than a stimulation of CD44 expression. We recommend the use of CD44 as an additional biological marker in the initial staging of neuroblastoma.
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PMID:[CD44 expression: a new prognostic factor in neuroblastoma]. 1084 30

Central neurocytoma is a rare neuronal tumor affecting young adults and usually located in the lateral ventricles. Post-operative prognosis is generally good. Histologically, central neurocytoma is composed of isomorphous small round or ovoid cells alternating with irregularly shaped patches of fibrillary matrix similar to the neuropile. In a series of 10 cases, two central neurocytomas were histologically "atypical" at first examination. One was intra-ventricular, and the second had an intra-parenchymatous juxta-ventricular location. Both were highly cellular with mitotic activity, and tumor necrosis was seen in one. Neuronal differentiation was assessed by synaptophysin immunoreactivity in all 10 cases and by ultrastructural examination in four, including the two "atypical" forms. Neuronal differentiation was less marked in these "atypical" forms, one also presenting focal GFAP immunoreactivity. The proliferative potential was determined by MIB-1 labeling index and compared with clinical outcome. The eight classical central neurocytomas had a MIB-1 labeling index < 2.3%, whereas the two "atypical" forms had a MIB-1 labeling index > 5.2% and both recurred. We think that there is a spectrum of small-cell neuronal tumors. The two extremes could be the central neurocytoma and the primary cerebral neuroblastoma, while the intermediate forms might be qualified as "atypical neurocytoma". In our series, the histological and immunohistochemical criteria of biological aggressiveness appeared to be high mitotic activity, tumor necrosis, loss of neuronal differentiation and high MIB-1 labelling index.
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PMID:Histopathological variants of central neurocytoma: Report of 10 cases. 1114 51

The clinical aggressiveness of neuroblastoma, a childhood embryonal tumour of neuroectodermal cells derived from the neural crest, is considered to be dictated by the competitive interactions between cell proliferation, differentiation and apoptosis. Caspase-9 is a central effector enzyme in the apoptotic mechanism. Recent studies with caspase-9 (CASP9) knockout mice indicate a primary defect in the brain caused by decreased apoptosis during the early stages of nervous system development. It is our hypothesis that silencing of CASP9 through genetic mutations may promote neuroblastoma tumorigenesis. Here, we report the outcome of screening neuroblastoma tumours for silencing mutations in CASP9. cDNA prepared from RNA isolated from 22 neuroblastoma tumours representing the full range of neuroblastoma clinicopathological disease stages was sequenced. Single nucleotide changes were detected in all neuroblastoma tumours, but were found not to represent silencing mutations, but rather sequence polymorphisms. These polymorphisms did not associate with the clinicopathological stages of disease or the predicted clinical outcomes of the patients. Silencing mutations of CASP9 are therefore unlikely to be causal to neuroblastoma tumorigenesis.
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PMID:The potential tumour suppressor role for caspase-9 (CASP9) in the childhood malignancy, neuroblastoma. 1167 10

Malignant melanoma cells show high aggressiveness and metastatic potential. Tumor cells as they become more metastatic, gradually lose their dependence on both adhesion and serum. Thus, in the process of tumor progression cells undergo series of changes that allow them to adapt to different tissue milieu. This implies that during this process, points on the integrin pathway may become constitutively activated. In the present study we investigated the possible role of FAK, being one of the key members of the integrin-signaling pathway, in the multistep progression towards a malignant phenotype in human melanoma. In our study we show that in melanoma cells there is neither an increase in the amount of FAK nor in its phosphorylation capacity, but rather in its levels of constitutive activation. Indeed, in all melanoma cells tested and not in nevus and neuroblastoma cells, we observed various degrees of constitutive activation of FAK. Our results also suggest that FAK constitutive activation is regulated at least in part by the cytoskeleton, implying that steps along the integrin signaling pathway involving FAK could be among the oncogenic mechanisms that operate in melanoma and may account for the highly aggressive, anchorage independent phenotype of this tumor.
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PMID:The focal adhesion kinase (P125FAK) is constitutively active in human malignant melanoma. 1203 79

Neuroblastoma is a neural crest-derived tumor of childhood with a serious prognosis; only 20% of patients with stage 4 disease survive 5 years from diagnosis. Mechanisms involved in neuroblastoma development are unclear, but the engagement of many neuroblastoma-related gene(s) is suggested by specific chromosomal alterations. Most prominent among these is the amplification of the MYCN oncogene and the deletion of the 1p36 region. Other genetic aberrations have been discovered over the years such as deletions of 11q and 14q and gain of 17q. Although tumor aggressiveness greatly depends on the most frequent genetic abnormalities, to date no neuroblastoma-related gene has been discovered. Neuroblastoma usually occurs sporadically, but 1.5% of all diagnosed cases show familial recurrence with an autosomal dominant inheritance and incomplete penetrance. A comparison between hereditary and sporadic neuroblastomas led Knudson and Strong to gather that the two-hit hypothesis, proposed for retinoblastoma, could be applied to neuroblastoma. To determine if the 1p36 region harbors a predisposition gene for familial neuroblastoma, we carried out linkage analysis at 1p36 loci in two families with recurrent neuroblastoma. Similarly, we analyzed loci of chromosome 16, where a predisposition locus was recently mapped. We also analyzed markers located close to several candidate genes (RET, NF1, GDNF, GFRA1, EDNRB, and EDN3) involved to a different extent in other neurocristopathies. Our findings indicate that the candidate chromosomal regions and genes analyzed are not in linkage with neuroblastoma.
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PMID:Linkage analysis in families with recurrent neuroblastoma. 1209 31

Tumor cells avoid immune recognition by subverting the ability of the immune system to mount an inflammatory response that generates cytotoxic effector cells. This can be achieved through cytokine production by the tumor itself. Our objective was to determine the cytokine profile of neuroblastoma (NB) lesions in tumor vaccine models. We found that the murine NB cell line, Neuro2a, secretes macrophage migration inhibitory factor, MIF, a multifunctional cytokine with the potential to block effective immune responses to a tumor. Patient-derived NB cell lines were also found to produce MIF. MIF production by NB was documented at the level of RNA by RNAse protection, soluble cytokine production by ELISA, and in a macrophage migration assay. Our studies also confirmed reports of IL-6 production by human NB cell lines. NB culture-derived MIF was also shown to activate tumor cell migration. This supports the hypothesis that MIF is a tumor-derived cytokine that may play a role in NB aggressiveness and evasion of immune recognition.
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PMID:Production of macrophage migration inhibitory factor by human and murine neuroblastoma. 1221 92

Neuroblastoma is the most frequent solid extracranial neoplasm of childhood, with a median age of presentation of under 2 years. This tumour is highly malignant in patients older than 12 months of age with metastatic disease. Clinical studies have confirmed that amplification of the MYCN proto-oncogene is one of the best prognostic indicators of poor outcome. Approximately 30% of neuroblastoma tumours present MYCN amplification at diagnosis. Far less is known about the incidence and consequences of overrepresentation of the gene due to duplication or rearrangement of the chromosome arm in which the gene is situated. This study has analysed 110 neuroblastomas by FISH and has detected a gain of 1-3 copies per cell of MYCN in 8% of MYCN-non-amplified tumours. In these primary tumours, cells gained small numbers of additional MYCN genes by two mechanisms: formation of an isochromosome 2p, or an unbalanced translocation involving the short arm of chromosome 2 (with MYCN) and various partner chromosomes. Quantitative RT-PCR showed three- to seven-fold elevated MYCN expression in three tumours. Although the follow-up time to date is still short, clinical outcome suggests that low-level overexpression of the MYCN gene does not enhance tumour aggressiveness and rapidity of disease progression, as is often seen in neuroblastoma with MYCN amplification. It is hypothesized that the small elevation in MYCN expression could alter the regulation of apoptosis, as has been shown in experimental models.
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PMID:MYCN gene overrepresentation detected in primary neuroblastoma tumour cells without amplification. 1243 19

Advances in the immunohistochemical detection of neuron-specific and neuronal-associated antigens have resulted in the discovery of neuronal elements in certain primary human brain tumors. The results have been not only to expand what neuropathologists commonly recognize as gangliogliomas, including the tumors now known as glioneurocytic tumor with neuropil rosettes and papillary ganglioneuroma, but also to expand the spectrum of tumor types to now include tumors such as central neurocytoma, dysembryoplastic neuroepithelial tumor, and desmoplastic infantile ganglioglioma. These discoveries have helped us to better understand the biology of these tumors and to refine our classification of them. Distinctions among these tumors include sites of predilection, such as the temporal lobe with the dysembryoplastic neuroepithelial tumors, and a spectrum of clinical aggressiveness that spans indolent "quasi-hamartomatous" lesions, such as the dysembryoplastic neuroepithelial tumor, to high-grade, highly aggressive tumors, such as the supratentorial primitive neuroectodermal tumor (World Health Organization Grade IV). Many of these tumors also commonly exhibit a glial component, as determined by both their histologic appearance and their immunoreactivity for glial fibrillary acidic protein. This review covers these recently described lesions, including the desmoplastic infantile ganglioglioma, the dysembryoplastic neuroepithelial tumor, the papillary glioneuronal tumor, the glioneuronal tumor with neuropil rosettes, and the mixed glioblastoma-cerebral neuroblastoma (supratentorial primitive neuroectodermal tumor), as well as the known tumors, ganglioglioma, medulloepithelioma, and medulloblastoma. For pathologists confronted by this growing array of tumors and subtypes, it is appropriate to focus on them and understand the differential diagnosis to be considered when confronted by them.
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PMID:Glioneuronal tumors of the central nervous system. 1262 33


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