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)

Three new tissue culture cell lines, CHP-100, CHP-126, and CHP-134, have been established from explant cultures of human neuroblastoma. The cell lines have been characterized with respect to morphology, chromosomes constitution, growth, neural enzyme content, and their ability to grow in nude mice. The cells grow as dense masses comprised of fibroblast-or neuroblast-like cells with small processes. The cell lines differ in their neural enzyme acitivity. The chromosomal content of the 3 cell lines is near diploid, and all are capable of forming tumors in nude mice. The morphological findings indicate that the cells in culture resemble those found in the tumor, and the enzyme activities are consistent with those of nervous tissue. This the morphological, biochemical, and tumorigenic properties confirm that the 3 cell lines are neoplastic cells of neural origin.
Cancer Res 1976 Sep
PMID:Establishment and characterization of human neuroblastoma cell lines. 1 79

Adenosine 3',5'-cyclic monophosphate (cAMP) may be one of the important factors in regulating the expression of many differentiated functions in neuroblastoma cells, but some of these functions can be induced by agents that do not increase the intracellular level of cAMP. An elevation of the intracellular level of guanosine 3',5'-cyclic monophosphate (cGMP) neither induced differentiation nor antagonized the effects of cAMP. Neuroblastoma cells increased the level of cAMP-binding proteins during differentiation, whereas glial cells and L-cells did not. This might have accounted in part for an increase in the intracellular level of cAMP even in the presence of high phosphodiesterase activity in neuroblastoma cells, since the protein-bound with the same proteins, but cAMP had about 10 times higher affinity than did cGMP. cAMP promoted the organization of microtubules and microfilaments necessary for the expression of differentiated phenotypes. The extension of neurites required the synthesis of new protein, but it did not need the synthesis of new RNA. cAMP induced differentiation in neuroblastoma cells by increasing the expression of some genetic information while suppressing the expression of others; e.g., the activities of neural enzymes increased, whereas the synthesis of histone and the phosphorylation of H1-histone markedly decreased in differentiated cells. A hypothesis was offered: An increase in cAMP phosphodiesterase activity as a result of mutation in the regulatory gene for phosphodiesterase in a single, or group of, dividing nerve cell(s) is the primary lesion that leads to malignancy. Based on the concept that selective cytocytoxic drugs should be used with agents that cause differentiation, a new therapeutic approach was suggested for the treatment of neuroblastoma. This involved administration of sodium butyrate followed by L-DOPA or prostaglandin E1 in the presence of cAMP phosphodiesterase inhibitor followed by the less immunosuppressive vincristine and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide.
J Natl Cancer Inst 1976 Sep
PMID:Cyclic nucleotides in the regulation of expression of differentiated functions in neuroblastoma cells. 1 Apr 49

Previous studies indicating the importance of catecholamine metabolism in neuroblastoma were briefly reviewed. Metabolic pathways were presented showing how the major urinary metabolites 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxy-phenylacetic acid (HVA) are formed from norepinephrine and from dopamine plus 3,4-dihydroxyphenylalanine (DOPA), respectively. For 289 neuroblastoma patients at the time of diagnosis, the urinary excretion of VMA was significantly elevated in 75%, and HVA was elevated in 80%. Periodic assay of these metabolites during the course of the disease revealed that the excretion trends were of prognostic value with 80-90% reliability. By contrast, when the excretion in only the initial urine specimens was considered, the survival rate was the same for patients with normal, and with significantly elevated, excretion. Review of the results of tracer studies aimed at elucidating the in vivo metabolic origins of the urinary metabolites suggested that a) in neuroblastoma, the catecholamines were largely inactivated by intracellular metabolism in the tumor cells; b) there was excess production and excretion of the norepinephrine precursors, DOPA and dopamine; and c) in the tumors of most neuroblastoma patients, the initial enzyme in catecholamine synthesis, tyrosine hydroxylase, had an activity comparable with that in normal adrenal glands. The importance of the metabolism of catecholamines in patients with neuroblastoma was stressed: a) The excretion of elevated levels of urinary catecholamine metabolites were useful in diagnosis and in following the course of the disease, and b) study of the catecholamine metabolism in these patients permitted examination of possible relationships between the activity of the enzymes involved in catecholamine synthesis and the malignancy of this tumor.
J Natl Cancer Inst 1976 Sep
PMID:Catecholamine metabolism in neuroblastoma. 1 Apr 50

Cultured human neuroblastoma cell lines were assayed for biochemical characteristics of neuonal function. Cell lines studied included LA-N-1, LA-N-2, IMR-32, SK-N-SH, and SK-N-MC. Veratridine-dependent uptake of 22Na+ implied the presence of the action potential Na+ ionophore in LA-N-1, LA-N-2, IMR-32, and SK-N-SH. The time course of 22Na+ uptake and inhibition of uptake by tetrodotoxin supported this. SK-N-MC had no veratridine-dependent 22Na+ uptake. Tyrosine hydroxylase (EC 1.14.10.), glutamic acid decarboxylase (EC 4.1.1.15), and acetylcholine contents in neuroblastoma cells were compared to those in brain. LA-N-1 and IMR-32 contained 15 and 5 times as much tyrosine hydroxylase, respectively, whereas LA-N-2, SK-N-SH, and SK-N-MC contained only 0.5 to 5% of that in brain. Acetylcholine was present in -LA-N-2 in 15- to 20-fold greater quantities than in brain; other lines had only 10 to 50% of that in brain. None of the cell lines contained glutamic acid decarboxylase. Thus, continuously propogated human neuroblastoma cell lines may have the action potential Na+ ionophore and may be adrenergic (LA-N-1 and IMR-32), cholinergic (LA-N-2), or inactive (SK-N-SH and SK-N-MC). This is the first demonstration of the action potential Na+ ionophore and of acetylcholine production in human neuroblastoma cell lines.
Cancer Res 1977 May
PMID:Adrenergic, cholinergic, and inactive human neuroblastoma cell lines with the action-potential Na+ ionophore. 1 22

Circulation in the blood stream of neuroblastoma cells was confirmed by establishment of a cell line from the peripheral blood of a child with disseminated disease. The morphologic, enzymatic, and chromosomal pattern of this cell line was similar to a cell line established from the primary tumor on a previous occasion. The peripheral blood smear did not demonstrate tumor cells but increased numbers of atypical monocytes; lymphoblasts were evident, which may have been unrecognized neuroblasts.
Cancer 1977 Jun
PMID:Isolation and characterization of a neuroblastoma cell line from peripheral blood in a patient with disseminated disease. 1 66

Three tissue culture clones of neuroblastoma cells derived from the C-1300 tumor in strain A/J mice were found to contain type-C virus-specific gas antigen. None of the clones spontaneously released mouse-tropic type-C viruses although one clone, N-4, spontaneously released a xenotropic virus. Two clones, NB-2A and N-4, could be induced by treatment with 5-iododeoxyuridine and dexamethasone phosphate to produce B-tropic type-C virus, but clone N-18 failed to release either ecotropic or xenotropic virus under several different induction conditions. Karyotype analysis did not reveal specific chromosome deletions in clone N-18.
Int J Cancer 1976 Aug 15
PMID:Murine neuroblastoma clones with varying degrees of C-type virus expression. 6 Feb 88

Spleen lymphoid cells from A/J mice recognize specific antigenic differences on the surface membranes of syngeneic C1300 neuroblastoma cells and incorporate 3H-thymidine into DNA in unidirectional mixed cell cultures in the absence of isologous serum. The response requires an optimal ratio of responder to stimulator cells, and is detectable after 24 h. It is specifically blocked by the presence of a papain-solubilized crude membrane extract from the same neuroblastoma cells, the extent of inhibition being dependent on the concentration of the extract and the time when it is added to the cultures. Spleen cells from mice bearing the neuroblastoma respond earlier and incorporate more 3H-thymidine than cells from unsensitized mice. The enhanced response of the primed spleen cells to the stimulator cells is similar to a secondary immune response and can be induced by soluble crude tumor extracts in the absence of stimulator cells.
Int J Cancer 1976 Oct 15
PMID:In vitro stimulation of mouse lymphoid cells by C1300 neuroblastoma cells or tumor membrane extracts. 6 46

Four cell lines, SK-N-SH, SK-N-MC, SK-N-BE(2), and IMR-32, established in vitro from tumor tissue of patients with neuroblastoma were analyzed by trypsin-Giemsa banding methods. In two of the lines a large, abnormally staining chromosome region was observed. This "homogeneously staining region" (HSR) was considerably longer than any of the bands present in normal human cells and, as revealed by both G- and Q-banding, stained with an intermediate intensity. It was located on chromosomes No 6, 10, 17, or 19 of the SK-N-BE(2) cell line and on chromosome No 1 of the IMR-32 line. In concurrent studies, long HSR's were also observed in Chinese hamster sublines that had been exposed to and had developed high levels of resistance to methotrexate or methasquin and high levels of activity of target enzyme dihydrofolate reductase. For several sublines with the highest levels of enzyme activity, approximately 2% of the total cell protein was dihydrofolate reductase. Of 13 independently derived sublines with acquired resistance to antifolate, only those 7 with greater than 100-fold increases in enzyme activity consistently exhibited HSR's. These regions comprised 2-5% of the total length of the chromosome complement and were specifically localized, as demonstrated by G-banding. Analysis of chromosome replication patterns of the HSR in human neuroblastoma and in drug-resistant Chinese hamster cells by tritiated thymidine radioautography indicated that the long, abnormally staining region replicated relatively rapidly and synchronously and terminated replication before the midpoint of the S phase. The HSR thus appeared to represent a novel chromosome abnormality that may be present in cells with specialized functions. Drug-resistant Chinese hamster cells were characterized by overproduction of target enzyme, whereas human neuroblastoma cells had phenotypes of normal neuronal cells. Whether the HSR is transcriptionally active was not elucidated.
J Natl Cancer Inst 1976 Sep
PMID:A novel chromosome abnormality in human neuroblastoma and antifolate-resistant Chinese hamster cell lives in culture. 6 55

The cytotoxic potential of heterologous rabbit antibody directed against mouse serum albumin (MSA) and alpha-fetoprotein (AFP) was investigated in vitro with a cell line (Hepa) derived from the mouse hepatoma BW7756. Anti-AFP in the presence of complement could kill Hepa cells at concentrations of anti-MSA that were virtually nontoxic. The specificity of the anti-AFP was defined by demonstrating that Hepa cell toxicity was dependent upon and paralleled the secretion of AFP in synchronized cultures. Furthermore, neither antiserum could be shown to be significantly toxic to mouse neuroblastoma cells (Neuro-2A). Immunoglobulin purified from pools of antisera was also highly effective in producing cytotoxicity even in a complement-free system. This reaction proceeded more slowly, requiring nearly 48 hr to reach maximum effect in comparison to the 12 hr for complement-mediated toxicity. MSA and AFP are secreted during different phases of the cell cycle. In cultures arrested by isoleucine starvation, labeled AFP appears in the medium 10 hr after release of the blockade in association with S phase. The appearance of labeled MSA is delayed until the first mitosis. Cytotoxic effects of anti-AFP parallel the secretion of AFP in synchronous cultures. Both antisera could be inhibitory to the secretion and synthesis of the proteins of their antigenic specificity. MSA synthesis was more susceptible to this inhibition than was AFP synthesis. The significance of this phenomenon and its association with the differential cytotoxicity of the antiserum are discussed.
Cancer Res 1977 Mar
PMID:The influence of antisera specific for alpha-fetoprotein and mouse serum albumin on the viability and protein synthesis of cultured mouse hepatoma cells. 6 16

Brain-associated antigens have been detected on human and mouse thymocytes. Also, murine neuroblasts and brain cells have common antigens. In this study we compared the reactivity of rabbit anti-human brain (HB) serum with neoplastic neuroblasts and normal and neoplastic lymphoid cells. The binding of HB antiserum to viable cells was assessed by immunofluorescence and an indirect radiolabeled antibody assay. HB antiserum reacted with greater than 80% of neuroblasts derived from two human cell lines and five children with neuroblastoma, but with less than 1% of human thymocytes, bone marrow lymphoid cells, and lymphocytic leukemia cells. HB antiserum also reacted with 5 to 10% of peripheral blood lymphocytes. Absorption with neuroblasts did not alt-r this reactivity. Rabbit antisera raised against normal human thymocytes and leukemic T-cells specifically bound to thymocytes but did not bind to neuroblasts. The reactivity of anti-HB serum against SK-N-SH neuroblasts was removed by absorption with HB, but not with human kidney or liver, or mouse and guinea pig brain. We conclude that human neuroblastoma cells possess cell-surface antigens that are present on HB. These antigens appear to be species specific and are not present on normal or malignant thymic cells. Conversely, thymus-associated antigens are not expressed on neuroblasts.
Cancer Res 1977 Jun
PMID:Reactivity of human brain antiserum with neuroblastoma cells and nonreactivity with thymocytes and lymphoblasts. 6 86


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