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)

The antigenic cell surface component NS-5 (nervous system antigen-5) is recognized by antiserum raised in C3H.SW/Sn mice against cerebellum of 4-day-old C57BL/6J mice. When analyzed in the cytotoxicity test the antiserum detects a cell surface antigen or set of antigens present not only an cerebellum but also other parts of the central nervous system, including retina, as well as on mature spermatozoa and to a lesser degree on kidney. All other non-neural tissues tested, liver, splee, thymocytes, muscle, testis, adrenal gland and epidermis do not express detectable amounts of the antigen. Among seven murine tumors of the nervous system, medulloepithelioma shows high levels of NS-5 expression, whereas neuroblastoma Cl300, glioma G26, glioblastome, ependymoblastoma, ependymoblastoma EPA and glioblastoma G26l do not carry detectable NS-5. All mouse strains tested (C57BL/6J, C3H.SW/Sn, C3H/HeDiSn, A/J, AKR/J, BALB/cJ and DBA/2) express similar levels of NS-5. The antigen is demonstrable not only on postnatal day 4 neural tissue, but also in lower amounts on adult nervous system. On embryonic day 9, the earliest stage tested, and at all subsequent stages during embryonic development, NS-K is already present in brain and spinal cord, but not in gut.
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PMID:Nervous system antigen-5, an antigenic cell surface component of neuroectodermal origin. 18 79

Selective killing of nonhematopoietic tumor cells in bone marrow harvested for autologous bone marrow transplantation was studied using cultured neuroblastoma cells, monoclonal antibody 6-19, and baby rabbit serum as a source of complement. Monoclonal antibody 6-19, a murine IgG2a antibody, was selected for binding to a cell surface antigen on cultured human neuroblastoma cells that is not expressed by hematopoietic cells. The antigen is an 80-kd sialoglycoprotein present on a wide variety of nonhematopoietic tumors, and it is expressed by normal fibroblast and endothelial cells. The effect of the presence or absence of bone marrow mononuclear cells on target cell survival was evaluated using Hoechst 33342-stained neuroblastoma cells, trypan blue exclusion, and fluorescence microscopy. More than 4 logs of neuroblastoma cells were destroyed in the presence of a more than tenfold excess of bone marrow cells following two incubations with monoclonal antibody 6-19 and complement for 30 min at 37 degrees C. Monoclonal antibody concentrations greater than 5-10 micrograms/ml did not increase cell lysis. The destruction of tumor cells was limited by depletion of complement activity. Tumor cell killing increased with complement concentration and incubation duration but there was no additional cell lysis with incubations greater than 30 min. The percentage of target cells killed was significantly decreased when the target cells were treated in the presence of increasing concentrations of bone marrow mononuclear cells. This decrease in target cell destruction is a result of additional depletion of complement activity by bone marrow mononuclear cells. These results suggest that optimal purging of tumor cells by antibody and complement will be achieved following multiple brief incubations with fresh antibody and complement.
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PMID:Complement depletion in vitro limits monoclonal antibody 6-19-dependent complement-mediated killing of tumor cells in bone marrow. 189 61

An epithelial cell surface antigen is described which is defined by monoclonal antibody HEA125 (IgG1). The antibody was raised against the colon carcinoma cell line HT-29. Under reducing conditions HEA125 immunoprecipitates a surface glycoprotein of Mr 34,000 which was designated Egp34. The antigen does not contain disulfide-linked subunits. A slightly different migration behavior under non-reducing conditions (Mr 39,000) may be due to intrachain disulfide bonds. After enzymatic cleavage of N-linked carbohydrate residues the apparent molecular weight of the antigen was 29,000. Egp34 is a major cell surface component of HT-29 cells (10(6) molecules per cell). No antigen could be detected in the sera of colorectal cancer patients. A panel of malignant cell lines and normal cells was studied for surface expression of the antigen. 17/17 carcinoma lines of 6 different origins expressed the antigen, whereas 16/16 melanoma, neuroblastoma, sarcoma and lymphoma/leukaemia were unreactive as it was the case for normal fibroblasts and blood cells. Immunoperoxidase staining of frozen tissue sections with HEA125 demonstrated the presence of Egp34 in almost all normal epithelia and tumours derived therefrom. No reactivity with non-epithelial tissues was observed. Undifferentiated carcinomas of various origins homogeneously expressed Egp34. Therefore, HEA125 may become a valuable tool for the immunohistochemical diagnosis of carcinoma.
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PMID:Epithelium-specific surface glycoprotein of Mr 34,000 is a widely distributed human carcinoma marker. 244 34

The histogenesis of Ewing's sarcoma (EW) and extraskeletal Ewing's sarcoma (EEW) is still disputable. Their relationship to the so-called Askin's tumor, neuroectodermal tumor of bone, and peripheral neuroblastoma remains to be established. In an attempt to clarify these points, immunocytochemical and ultrastructural studies were done on tissues from 14 cases of EW, 4 cases of EEW, and 9 cases of primitive neuroectodermal tumor (PNET) and compared with neuroblastoma and olfactory neuroblastoma. Six tumors categorized initially as EW and EEW on biopsy, turned out to be PNET by extensive histologic and/or ultrastructural observations. Abundant glycogen was recognized not only in 16 of 18 cases of EW and EEW, but also in seven of nine cases of PNET. Fine fibrillar cell processes were seen between tumor cells, at least in limited areas even in cases of EW and EEW. Immunocytochemically, neuron-specific enolase (NSE), neuroblastoma cell surface antigen (NBCA), neuron cell surface antigen (NCSA), and neurofilament (NF) were demonstrated not only in neuroblastoma, but also frequently in cases of EW, EEW, and PNET. The results seem to suggest that EW and EEW represent the most immature forms of neuroectodermal tumor. Electron microscopic study showed predominantly primitive cells with occasional areas of cell processes, neurosecretory granules, and microtubules, suggesting a neuroectodermal origin.
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PMID:Immunocytochemical and ultrastructural studies of the histogenesis of Ewing's sarcoma and putatively related tumors. 254 95

Neuroblastoma is one of the most common solid tumors of childhood and is notable for its ability to spontaneously regress and, in some instances, to differentiate to less malignant ganglioneuromas. Since immune mechanisms may account for these phenomena, identification of in vivo immune responses to tumor cell surface antigens may be important to the progression of the disease. As determined by analysis on the fluorescence-activated cell sorter, sera from 10 of 18 neuroblastomas patients were found to contain antibodies to a cell surface antigen present on subpopulations of cells from human neuroblastoma cell lines maintained in vitro. Eight human neuroblastoma cell lines were examined and found to vary in reactivity with sera. Induction of differentiation of cell lines with retinoic acid (RA) in vitro resulted in most cell lines bearing higher percentages of positive cells but with a decreased mean cell fluorescence. Preliminary Western blot analysis of lysates of the human cell lines NMB/N7, SMS-KAN, and SK-N-MC showed two principal antigen bands on reducing gels. Comparison of sera from different individuals on lysates of cell lines showed reactivity principally with bands of 105-110 kD and 65-70 kD and an additional minor band of slightly lower molecular weight with the higher titer sera. The ability of different sera to recognize a common antigen pattern suggests that this represents an immunodominant cell surface antigen. Examination of reactivity of other cell lines in this system showed that positive sera reacted with all neuroblastoma lines examined, one neuroepithelioma (SK-N-MC), two melanoma lines (MeWo, G361), and one adrenal-derived adenocarcinoma (SW-13).
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PMID:Recognition of an in vivo immune response to human neuroblastoma modulation of antigen expression by retinoic acid. 268 27

Three murine monoclonal antibodies (Mab) against a cell surface antigen, the disialoganglioside GD2, were investigated for detecting bone marrow metastasis in patients with neuroblastoma (NB) by indirect immunofluorescence (IF). As few as 0.01% NB cells could be detected. No Mab reactivity was found in 60 non-NB marrows. Thirty-five marrows from patients with stage III and stage IV NB at diagnosis were examined during the course of their disease. Tumor involvement was found in 74% by Mab, 55% by the two-layer soft agar clonogenic assay (CA), and 27% by conventional histochemical stains. All marrows containing NB histologically were positive for tumor by Mab; 71% were also positive by CA. Of histologically negative marrows, 63% were Mab positive, the majority (78%) of which were also positive by CA. All Mab nonreactive samples were negative histologically and by CA. We conclude that these antibodies are highly sensitive and specific in detecting NB metastasis in bone marrow.
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PMID:Detection of neuroblastoma cells in bone marrow using GD2 specific monoclonal antibodies. 308 91

Most NMR contrast agents suggested to date have been paramagnetic. These agents, which include the transition and lanthanide metal ions as well as stable organic free radicals, do not provide effective contrast at concentrations much below 1 mM. However, the use of macromolecular ferromagnetic and superparamagnetic particles provides, for the first time, an NMR relaxation agent that is effective at subnanomolar concentrations. Two different sized superparamagnetic particles have been coupled to monoclonal antibodies with high affinity for a neuroblastoma-specific cell surface antigen. The specific binding of these particles, both in vivo and in vitro is demonstrated and the consequences for immunospecific NMR contrast are discussed.
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PMID:Immunospecific NMR contrast agents. 366 49

Two neuroblastoma cell lines established from tumor tissue taken from one individual are described. The first of these was established from a bone marrow aspirate (RT-BM) and the other from a right axillary lymph node (RT-LN) of a 1-yr 2-mo-old patient with Stage IV disease. The original lines were cloned in soft agar to yield six clones of the bone marrow-derived line (RT-BM 1-6) and 12 of the lymph node line (RT-LN 1-12). Chromosomal analysis of the original lines and clones showed they all have either identical or very similar karyotypes, with a deletion of chromosome 1p. Transmission electron microscopy indicates all contain neurosecretory (dense core) granules and neurotubules. In addition catecholamine metabolites of dopamine and noradrenaline have been identified. Different growth characteristics of the lymph node and bone marrow lines have been identified. RT-LN lines grow in a single cell layer with neurite processes, whereas bone marrow-derived lines form focal aggregates with neurite processes. In addition the colony-plating efficiency of the lymph node-derived lines is higher than those derived from bone marrow. Comparison of the cell surface antigen profile of the original tumor tissue, parent lines, and clones demonstrates they all bind seven of a panel of nine monoclonal antibodies. The expression of these antigens has remained stable in vitro for 25 passages undertaken over a 2-yr period. The definition of antigens that are expressed on the membranes of neuroblastoma cells in a stable form can aid in the differential diagnosis of neuroblastoma from other "small round cell tumors of childhood" and hopefully contribute to a greater understanding of the biology of this highly malignant tumor.
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PMID:Identical expression of cell surface membrane antigens on two parent and eighteen cloned cell lines derived from two different neuroblastoma metastases of the same patient. 373 Nov 24

We have used serologic, biochemical, and genetic methods to characterize two stage-specific human differentiation antigens of neural and melanocytic cells: A42 (57,000 Mr glycoprotein) and J143 (140,000/30,000 Mr glycoprotein). The genes determining A42 and J143 cell surface expression in rodent-human hybrids were chromosomally mapped, and the respective human chromosomes were introduced into rodent cells derived from distinct differentiation lineages. Serologic analysis of the resulting hybrid clones has permitted the identification of two types of regulatory signals determining A42 and J143 expression. First, both antigens are expressed in hybrids constructed with antigen-positive human cells and also in certain hybrids constructed with antigen-negative human cells, indicating that intrinsic signals provided by the differentiation program of the rodent fusion partner induce antigen expression. Second, a series of human-mouse neuroblastoma hybrids, which are A42- or J143- when cultured on plastic surfaces, can be induced to express the antigens when cultured on substrates coated with extracellular matrix (ECM) produced by bovine corneal endothelial cells or fibronectin. This induction of antigen expression by extrinsic, ECM-derived signals is accompanied in the neuroblastoma hybrids by increased substrate adhesiveness and cell spreading and by characteristic changes in cell morphology. A similar program of phenotypic changes is also seen in spontaneous variants of human neuroblastoma and Ewing's sarcoma cells and in ECM-induced Ewing's sarcoma cells. These findings suggest that ECM-derived signals have a role analogous to mitogens and soluble differentiation factors in modulating differentiation phenotypes and tissue-specific patterns of cell surface antigen expression.
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PMID:Extracellular matrix-modulated expression of human cell surface glycoproteins A42 and J143. Intrinsic and extrinsic signals determine antigenic phenotype. 377 96

A monoclonal antibody 6DS1 against a human glioblastoma multiforme cell line U-87MG recognizes a tumor-specific, cell surface antigen of human glioblastoma cell lines. Partial cross-reactivity is observed with two human neuroblastoma cell lines, SK-N-SH and SK-N-MC, with little or no reactivity towards a rat glioma cell line C6 or normal human adult and fetal brain tissues. The antibody recognizes an antigen of molecular mass 38 kDa as inferred from Western blot analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoprecipitate. The monoclonal antibody 6DS1 inhibits both the attachment to substratum and growth of U-87MG cells. It strongly cross-reacts with xenotransplants of U-87MG cells and inhibits tumorigenesis (subcutaneous implants of U-87MG cells) in nude mice.
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PMID:Monoclonal antibody against human glioblastoma multiforme (U-87MG) immunoprecipitates a protein of molecular mass 38 kDa and inhibits tumor growth in nude mice. 782 86


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