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

A monoclonal antibody (mAb) (T-199) of IgG1 isotype was raised against medulloblastoma by immunizations of mice with the medulloblastoma cell line TE-671. Studies of the specificity of mAb T-199 on cell lines as well as fresh frozen sections of normal and malignant tissues revealed the antigen in high amounts on the cell surface of neuroectodermally derived tumors such as medulloblastoma, neuroblastoma, retinoblastoma, and astrocytoma. Some melanomas and a subgroup of rhabdomyosarcomas also expressed the antigen. In contrast, mesenchymal tumors, osteosarcomas, and Ewing's sarcomas did not bear the T-199 antigen. Reactivity of T-199 with normal tissues has not been found with few exceptions; in certain areas of the brain, especially in the cerebellum and part of the hypothalamus, in the adrenal glands, and in the pancreatic islet cells small amounts of antigen were detectable. Natural killer cells could also be demonstrated to express the T-199 antigen similar to the NKH-1 antigen. However, despite some striking similarities, the antigens or antigen epitopes recognized by mAbs T-199 and NKH-1 are not identical. Therefore, mAb T-199 seems to detect a unique differentiation antigen on neuroectodermal tumors, coexpressed in low amounts on normal neuroectodermally derived cells and natural killer cells. The pattern of reactivity and the biochemical properties of the T-199 antigen are different from other cell surface markers for neuroectodermal cells coexpressed on natural killer cells or T-cells (HNK-1, NKH-1, or Thy-1). Biochemical analysis of the T-199 antigen showed that it is a heat-labile protein.
 ...
PMID:Monoclonal antibody T-199 directed against human medulloblastoma: characterization of a new antigenic system expressed on neuroectodermal tumors and natural killer cells. 274 22

The histogenesis of Ewing's sarcoma, the second most frequent primary bone tumor in humans, remains controversial. Ten Ewing cell lines were analyzed by immunological methods. Surface antigens recognized on Ewing cells were found to be related to the neuroectoderm lineage. They included ganglioside GD2, a marker of neuroectodermal tissues and tumors, and an acidic glycolipid detected by monoclonal antibody HNK-1 in the nervous system. The P61 rat monoclonal antibody that reacts with a peptide moiety of neural cell adhesion molecule (N-CAM) and a rabbit antiserum raised to purified mouse N-CAM also stained Ewing cells. Flow cytometry analysis performed using these reagents allowed the definition of four distinct Ewing phenotypes: all reagents equally stained group 1 lines; group 2 lines were strongly reactive with anti-N-CAM reagents, by contrast with a fainter staining with HNK-1 and anti-GD2 antibodies; all reagents but P61 were strongly reactive with group 3 lines; in group 4, Ewing lines were stained by P61 but only poorly by the anti-N-CAM antiserum. Several antibodies to melanoma and neuroblastoma associated antigens including two monoclonal antibodies to the nerve growth factor receptor were also found to react with Ewing cells. By contrast, all antibodies detecting antigens specifically expressed in hematopoietic cell lineages were totally unreactive. HLA class II antigens were never detected while the level of expression of class I antigens varied to a large extent. Ewing cells are characterized by a specific t(11;22)(q23-24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor. Thus, Ewing's sarcoma cells share antigenic and karyotypic features with derivatives of the neuroectoderm possibly indicating a related histogenesis.
 ...
PMID:Neuroectoderm-associated antigens on Ewing's sarcoma cell lines. 302 14

Ewing's sarcoma (ES) of bone may occasionally display rosette-like textures mimicking Homer-Wright ones, as seen in neuroectodermic neoplasms (neuroblastoma, peripheral neuroepithelioma). Of a group of 39 cases of ES, reviewed with electron microscopic study, the authors have isolated five atypical ES, which histologically also possessed neuroectodermic traces. These tumors were composed of small round blue cells with rosette-like figures and cytoplasmic glycogen. The immunohistochemical analysis showed positivity for neuron-specific enolase (NSE) as well as for HNK-1 (leu-7) monoclonal antibody. Electron microscopic examination confirmed the tumor cell as being of small round type, with a dense chromatine pattern and the presence of isolated dendritic processes, as well as synaptic-like buttons; intermediate filaments, neurotubuli, and dense-core neurosecretory granules also were seen. Moreover, in two cases basement-like condensations surrounded some cells. Scanning electron microscopic study in one case confirmed the presence of rosette-like figures and cell elongations with short dendritic projections of the cytoplasm. Clinically and radiologically these cases showed features similar to ES of bone; one case, located in the chest wall, had a local relapse after treatment, with the histologic features of a pleomorphic neuroblastoma. The authors conclude that these tumors resemble closely immature neuroepithelioma of soft tissue but, being primary to bone, are superimposable on those described as "neuroectodermal tumors of bone."
 ...
PMID:Small round blue cell sarcoma of bone mimicking atypical Ewing's sarcoma with neuroectodermal features. An analysis of five cases with immunohistochemical and electron microscopic support. 311 17

Cell surface molecules have been implicated in cell interactions which underlie formation of the nervous system. The analysis of the functional properties of such molecules has profited from the combined use of antibodies and cell culture systems. It has been suggested that the interplay between these molecules modulates cell-to-cell interaction at critical developmental stages. In the mouse, N-CAM and L1 antigen have been shown to mediate Ca2+-independent adhesion among neural cells. N-CAM plays a role in fasciculation of neurites and formation of neuromuscular junction. L1 is apparently not involved in synaptogenesis, but in migration of granule cell neurones in the developing mouse cerebellar cortex. The two antigens are distinct molecular and functional entities which act synergistically in aggregation of neuroblastoma and early postnatal cerebellar cells. In view of a certain similarity in function between the two groups of molecules, it was not surprising to find that structural similarities are detectable by the monoclonal antibody L2. We show here that a carbohydrate moiety recognized by L2 and HNK-1 monoclonal antibodies, is present in mouse N-CAM and L1. The L2 epitope appears on all major neural cell types but not all N-CAM molecules express it. This heterogeneity points to a previously undetected molecular diversity which may have functional implications for modulating cell adhesion during development.
 ...
PMID:Neural cell adhesion molecules and myelin-associated glycoprotein share a common carbohydrate moiety recognized by monoclonal antibodies L2 and HNK-1. 620

The HNK-1 antibody recognizes a carbohydrate epitope expressed by many cell adhesion molecules in the nervous system that has been proposed to be an important adhesive determinant. This epitope is particularly prominent on the myelin-associated glycoprotein (MAG) and is related to the antigenic target in an autoimmune mediated demyelinating neuropathy. Elucidation of the mechanisms underlying the biosynthesis and regulation of expression of the HNK-1 epitope is therefore likely to have important functional and clinical implications. In order to investigate its biosynthesis and the regulation of its expression, we have expressed both human and rat MAG in several different cell lines by retroviral infection. These studies indicate that the cellular milieu determines whether the HNK-1 epitope is expressed on the MAG polypeptide and provide an explanation for the significant variation in HNK-1 levels that has been noted in different species. Using a transfected human neuroblastoma line, we have determined that this epitope is present on the fourth and/or fifth immunoglobulin-like domain of rat MAG and that it is added intracellularly, probably in the trans Golgi. Finally we have found that expression of the HNK-1 epitope is increased by activation of different second messenger systems, providing direct evidence that its expression can be regulated independently from that of the MAG polypeptide.
 ...
PMID:Biosynthesis and regulation of expression of the HNK-1 epitope on myelin-associated glycoprotein in a transfected cell model system. 754 57

The prognosis of children with neuroblastoma (NB) is dependent upon the patient's age at diagnosis, the location of the primary tumor, and histologic tumor cell differentiation. These characteristics, as well as the presumption that NB results from clonal expansion of primitive cells involved in sympathetic nervous system (SNS) development, predict that a model of tumorigenesis based upon normal fetal SNS histogenesis might indicate tumor progenitor status and define biologic and clinical behavior. Immunohistochemistry and in situ hybridization were used to examine a panel of marker gene products predicted or shown to be expressed during SNS development in the normal human fetal SNS from 8 to 24 weeks' gestational age. A similar analysis was performed in a selection of clinical NB tumors, and the results were compared. In a subset of differentiating, often extra-adrenal NB tumors in patients who frequently had a favorable outcome; advancing morphologic tumor cell differentiation spatially paralleled an advancing fetal extra-adrenal chromaffin marker gene expression phenotype (ie, increasing TrkA, TrkC, TH, IGF-2, and neuron-specific enolase expression but a lack of phenylethanolamine N-methyltransferase expression). In these tumors, expression of gene products associated with normal fetal sympathetic ganglionic differentiation (ie, Bcl-2, HNK-1, and neuropeptide Y) was lost with morphologic tumor cell differentiation. In contrast, undifferentiated tumors, the majority of which were high stage, adrenal in origin, and prognostically unfavorable, displayed marker expression characteristics mirroring that of an early fetal ganglionic lineage. Thus, we show that morphologic differentiation in stroma-poor NB tumors, long held as an important prognostic feature in tumor grading systems, often corresponds to an extra-adrenal chromaffin rather than a ganglion cell or adrenal medullary chromaffin phenotype. Understanding the biology of extra-adrenal chromaffin tissues may provide an explanation for the clinically less aggressive nature of differentiating NB tumors and suggest potential mechanisms for spontaneous regression and/or treatment response.
 ...
PMID:A developmental model of neuroblastoma: differentiating stroma-poor tumors' progress along an extra-adrenal chromaffin lineage. 894 Dec 12

Olfactory neuroblastoma (esthesioneuroblastoma) is a very rare tumour of the olfactory mucosa. Morphological features and cytogenetic studies strongly suggest a neuro-ectodermal origin. Up to now, cytogenetic studies are inconsistent. Some of them have proposed that the tumour belongs to the pPNET family. In the present study we describe genomic imbalances in olfactory neuroblastoma in a 46-year-old woman by using the molecular cytogenetic technique--comparative genomic hybridization (CGH)--in order to define the spectrum of genetic abnormalities in the tumour. The anatomical location and morphological findings were the basis for the diagnosis of esthesionearoblastoma. Immunohistochemical reactions for NSE, synaptophysin, chromogranin A, HNK-1/Leu-7 and S-100 revealed a characteristic immunophenotype. The CGH analysis showed multiple changes including DNA overrepresentations of chromosomes 4, 8, 11 and 14, partial DNA gains of the long arms of chromosomes 1 and 17, deletions of the entire chromosomes 16, 18, 19 and X, and partial losses of chromosomes 5q and 17p. This study represents an early utilisation of the CGH technique in olfactory neuroblastoma and demonstrates that the tumour carries complex chromosomal aberrations.
 ...
PMID:Olfactory neuroblastoma: detection of genomic imbalances by comparative genomic hybridization. 935 88

Comparisons of the developing human sympathetic nervous system (SNS) to tumors presumed to derive from these cells may suggest tumor progenitors and predict tumor biologic behavior. Classic neuroblastoma (NB) and its more highly differentiated stroma-rich subtypes, extra-adrenal sympathetic paraganglioma, and pheochromocytoma were examined for the presence of the developmentally characterized gene products NSE, S-100, CD44, Bcl-2, HNK-1, PNMT, TrkA, IGF2, and tyrosine hydroxylase. The marker gene expression profiles of these tumors were compared with those similarly determined for a number of normal prenatal and postnatal human SNS cell types. Sympathetic paraganglioma, pheochromocytoma, and stroma-rich NB display marker expression profiles mimicking those of childhood sympathetic paraganglia, adrenal chromaffin cells, and sympathetic neurons, respectively. A selection of differentiating, extra-adrenal NB tumors with prognostically favorable features possess marker gene expression profiles paralleling that observed for fetal extra-adrenal sympathetic paraganglia/small intensely fluorescent cells. In contrast, undifferentiated, clinically aggressive NB tumors manifest characteristics mirroring that of embryonic/early fetal sympathetic neuroblasts of sympathetic ganglia and of the adrenal gland. These findings suggest that clinical features, such as primary tumor location and age at diagnosis, provide prognostic information for NB patients by virtue of the existence and biology of the presumed tumor progenitor cell type.
 ...
PMID:Developmental gene expression of sympathetic nervous system tumors reflects their histogenesis. 946 Nov 20

A correctly glycosylated myelin-associated glycoprotein (MAG) must express the carbohydrate epitope HNK-1, which is the target antigen for IgM antibodies in some patients with neuropathy. We transfected a human MAG cDNA clone into the neuroblastoma cell line SK-N-SH and verified by immunoblot the expression of the HNK-1 epitope on the recombinant molecule. By the same method and by indirect immunofluorescence we did not find any reactivity of human anti-MAG IgM antibodies with glycosylated recombinant MAG and transfected neuroblastoma cells. These findings suggest that the mere presence of the HNK-1 epitope is probably not sufficient for MAG to be recognized by human antibodies and that other factors such as the concentration or fine structure of this epitope in MAG, which mostly depend on the cellular context, may be also critical for this reactivity.
 ...
PMID:Expression of glycosylated recombinant human myelin-associated glycoprotein on a neuroblastoma cell line and its reactivity with HNK-1 but not human anti-MAG antibodies. 979 16

The HNK-1 carbohydrate epitope is expressed in neural and natural killer cells and is a mediator of cell adhesion. It is well documented that acetylcholinesterase has a secondary function in cell adhesion and differentiation. The presence of HNK-1 on isoforms of Torpedo and Electrophorus acetylcholinesterase, as well as isoforms from the bovine central nervous system has been described. In this paper, we have investigated the association of the epitope with acetylcholinesterase from human neuroblastoma cells. Acetylcholinesterase was extracted, with or without detergent, purified on immunoaffinity columns and the isoforms separated by sucrose density gradient sedimentation. Secreted acetylcholinesterase, from spent serum-free culture medium, was similarly treated. The presence of the HNK-1 epitope was determined by ELISA using the anti-HNK-1 and Elec 39 monoclonal antibodies. The epitope was found to be associated with the detergent-soluble G4 isoform, but not with the hydrophilic G1 nor the secreted hydrophilic G4 isoforms. Likewise, no HNK-1 was observed associated with human erythrocyte acetylcholinesterase. These results indicate that acetylcholinesterase-G4, anchored in the extracellular membrane, is capable of mediating cell-substrate adhesion through HNK-1.
 ...
PMID:Association of the HNK-1 epitope with the detergent-soluble G4 isoform of acetylcholinesterase from human neuroblastoma cells. 1137 3


<< Previous 1 2 3 Next >>