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 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.
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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

We have previously reported the isolation of a 66 kDa melanoma-associated antigen, identified by autologous antibody, in serum and unfractionated spent tissue culture media by Western blot analysis. The antigen, detected by autologous serum S150, was found to be broadly represented on melanoma, glioma, renal cell carcinoma, neuroblastoma and head and neck carcinoma cell lines. S150 did not react with bladder or colon carcinoma, fetal fibroblasts, pooled platelets, lymphocytes and red blood cells, autologous cultured lymphocytes or fetal calf serum. To further characterize the antigen, spent tissue culture media, obtained from autologous melanoma cell line, Y-Mel 84:420, was separated by an isoelectric focusing column. Unabsorbed control serum S150 was noted to have a maximum titer of 1:2040 against autologous melanoma cells as measured by protein A hemadsorption. Following isoelectric focusing the greatest decrease in autologous antibody titer (30-fold) occurred with fractions having a pI between 2 and 3. Further resolution of the antigen was accomplished with high-pressure ion-exchange chromatography. One of these fractions showed a significantly higher concentration of antigen and was distinctly resolved from bulk serum albumin. Subsequent Western blot analysis, with autologous antibody, of the isolated antigen-containing fraction, confirmed the presence of a single 66 kDa band. Exposure of the antigen, purified by high-pressure ion-exchange chromatography, to neuraminidase ablated recognition by autologous antibody and suggests that sialic acid is present on the protein and may be part of the antigenic epitope. Binding of antigen, obtained following DEAE anion exchange chromatography, was noted to lectins derived from Triticum vulgaris, Dolichos biflorus and Lycopersicon esculentum. Preparative purification of the antigen was accomplished by anion exchange followed by lectin affinity chromatography with a Dolichos biflorus column. Antigen obtained following lectin affinity chromatography subjected to SDS-PAGE and silver stain revealed a single band at 66 kDa. We conclude that a melanoma-associated antigen detected by autologous antibody in spent tissue culture media is an unusually acidic glycoprotein (pI 2-3).
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PMID:Purification and partial characterization of a shed 66 kDa melanoma-associated antigen identified by autologous antibody. 193 77

The efficacy of systemic interleukin-2 (IL-2) immunotherapy is dependent on a competent host immune response. This study demonstrated that protein-calorie malnutrition (PCM) inhibited the generation of an antitumor response to IL-2. A/J mice received an isocaloric diet of 2.5% or 24% casein 8 weeks before inoculation with C1300 neuroblastoma cells. Three weeks later lymphocytes from tumor-bearing mice were harvested for determination of cytotoxic T-lymphocyte generation and natural killer cell cytotoxicity. PCM produced a significant reduction in total body weight (p less than 0.001) and serum albumin concentration (p less than 0.001). PCM inhibited generation of cytotoxic T lymphocytes (p less than 0.001), T-lymphocyte response in mixed lymphocyte reaction (p less than 0.001), and in vitro activation of natural killer cell cytotoxicity with IL-2 (p less than 0.001). A second experiment was performed to evaluate whether the in vitro deficits in tumor-specific and natural immunity in the animal model of PCM would diminish the efficacy of systemic high-dose IL-2 (3 x 10(6) units/kg three times daily for 5 days). The mean percent inhibition of C1300 growth with IL-2 was only 15% in mice with PCM compared with 60% in well-nourished mice (p less than 0.01). Median host survival time was greater in well-nourished animals (55 days) compared with animals with PCM (39 days) that received IL-2 (p less than 0.05). These data suggest that nutritional status is a critically important variable in tumoricidal response to systemic IL-2.
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PMID:Protein-calorie malnutrition inhibits antitumor response to interleukin-2 immunotherapy. 214 20

Neuroblastoma is a pediatric malignancy with a poor prognosis at least partly attributable to an early pattern of dissemination. New approaches to treatment of micrometastases include targeted radiotherapy using radiolabeled antibodies or molecules which are taken up preferentially by tumor cells. Multicellular tumor spheroids (MTS) resemble micrometastases during the avascular phase of their development. A human neuroblastoma cell line (NBl-G) was grown as MTS and incubated briefly with a radiolabeled monoclonal antibody (131I-UJ13A) directed against neuroectodermal antigens. Spheroid response was evaluated in terms of regrowth delay or proportion sterilized. A dose-response relationship was demonstrated in terms of 131I activity or duration of incubation. Control experiments using unlabeled UJ13A, radiolabeled nonspecific antibody (T2.10), radiolabeled human serum albumin, and radiolabeled sodium iodide showed these to be relatively ineffective compared to 131I-UJ13A. The cell line NBl-G grown as MTS has also been found to preferentially accumulate the radiolabeled catecholamine precursor molecule m-[131I]iodobenzylguanidine compared to cell lines derived from other tumor types. NBl-G cells grown as MTS provide a promising laboratory model for targeted radiotherapy of neuroblastoma micrometastases using radiolabeled antibodies or m-iodobenzylguanidine.
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PMID:Tumor spheroid model for the biologically targeted radiotherapy of neuroblastoma micrometastases. 229 11

Chronic treatment of neuroblastoma X glioma NG108-15 hybrid cells with opiate agonist resulted in loss of the acute opiate inhibition of adenylate cyclase activity with a concomitant increase in the enzymatic activity observable on addition of the antagonist naloxone. The role of membrane lipids in the cellular expression of these chronic opiate effects was investigated by the hydrolysis of phospholipids with various lipases. Treatment with phospholipase C from Clostridium welchii produced an enzyme concentration-dependent decrease of prostaglandin E1-stimulated adenylate cyclase activity in control or etorphine-treated (1 microM for 4 h) hybrid cells. In addition, incubation of hybrid cells with phospholipase C concentrations of greater than or equal to 0.5 U/ml completely abolished the compensatory increase in adenylate cyclase activity after chronic opiate treatment. This attenuation of the increase in adenylate cyclase activity by phospholipase C could be prevented by inclusion of phosphatidylcholine but not of phosphatidic acid during the enzymatic incubations. The specificity of the phospholipids involved in expression of the chronic opiate effect could be demonstrated further by the absence of effect exhibited by phospholipase C from Bacillus cereus and phospholipase D. Hydrolysis of the acyl side chains of phospholipids with phospholipase A2 did not alter the chronic opiate effect after removal of lysophosphatides with bovine serum albumin. Because the guanylylimidodiphosphate- and NaF-sensitive adenylate cyclase activities were not affected by these phospholipase treatments, the expression of the compensatory increase in adenylate cyclase activity is mediated via an increase in the coupling between hormonal receptor and adenylate cyclase with the participation of the polar head groups of the phospholipids and not the hydrophobic side chains.
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PMID:Effect of phospholipases on chronic opiate action in neuroblastoma X glioma NG108-15 hybrid cells. 301 58

Fura-2 AM is an esterified cell-permeant form of the Ca2+ indicator fura-2 (1-[2-(5-carboxyoxal-2-yl)-6-aminobenzofuran-5-oxyl]-2-(2'-a mino-5'- methylphenoxy)-ethane-N,N,N',N'-tetraacetic acid). Fura-2 AM has been reported to be completely cleaved by cellular esterases to fura-2 which is trapped within cells and is used to measure intracellular free Ca2+ concentration by a fluorescence ratio method. Successful application of the method requires that fura-2 be the major cellular fluorescent metabolite of fura-2 AM. We have used high-performance liquid chromatography to study fura-2 AM hydrolysis by cells. Murine N1E-115 neuroblastoma cells incubated with 10 microM fura-2 AM formed fura-2 at a rate of 9.7 pmol/min/10(6) cells. The concentration of fura-2 in the cells after 60 min, assuming uniform distribution, was 137 microM. Smaller amounts of at least four other metabolites were present, as well as large amounts of unhydrolyzed fura-2 AM. Washing the cells with medium containing 2% bovine serum albumin decreased the concentration of fura-2 to 40 microM and that of fura-2 AM to 90 microM. The half-time for loss of fura-2 from neuroblastoma cells after washing was 34 min. Human pulmonary artery endothelial (HPAE) cells formed fura-2 at a rate of 2.6 nmol/min/10(6) cells and the concentration of fura-2 after 60 min of incubation and washing with albumin containing medium was 130 microM, and the concentration of fura-2 AM was 58 microM. The half-time for loss of fura-2 from washed HPAE cells was 74 min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Incomplete hydrolysis of the calcium indicator precursor fura-2 pentaacetoxymethyl ester (fura-2 AM) by cells. 336 79

The possibility that bilirubin can diffuse through lipid bilayers is investigated with liposomes prepared from dipalmitoylphosphatidylcholine (DPPC), egg phosphatidylcholine (egg PC) with 22 mole percent cholesterol, and a lipid extract preparation from N115 neuroblastoma cells. Liposomes were prepared with internalized bilirubin and bovine or human serum albumin, and bilirubin efflux into an exogenous solution of human serum albumin was measured. Efflux from DPPC liposomes was significantly higher above the phase transition temperature than below it. This change was dependent on the lipid undergoing a phase transition and could not be accounted for by 6 K change in temperature. Maximum bilirubin efflux from egg PC-cholesterol liposomes was found to depend on the relative internal and external albumin pools, suggesting an equilibrium distribution of bilirubin between them. These observations demonstrate that bilirubin can diffuse freely through these lipid membranes.
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PMID:Bilirubin diffusion through lipid membranes. 375 60

A fraction of the alpha-globulins (NHG) from normal human serum was cytotoxic for mouse L-cells in culture and Meth A tumors in mice. NHG inhibited the growth in vitro of human colon cancer (HT-29), melanoma (RPMI 7931) and a neuroblastoma cell line. Survival of HeLa S-3 cell colonies after 24 h exposure to 25, 50, 75 or 100 micrograms NHG/ml medium was 86%, 77%, 40% and 10%, respectively. Whole human serum or purified serum albumin had no anti-HeLa cell activity. These results confirm the presence of a protein in human serum with antitumor activity. An assay for NHG using HeLa S-3 tumor cells is described.
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PMID:A protein fraction (NHG) from serum of normal humans which is cytotoxic for HeLa cells in culture. 617 Apr 26

A trypsin-degradable nerve growth factor (NGF) receptor associated with the phospholipid component of the surface membrane has been detected on F98 anaplastic glioma cells. NGF also bound to the nucleus of F98 cells. Bound NGF was not displaceable by insulin, cytochrome C, growth hormone, or bovine serum albumin. Specific binding of NGF occurred with a Kd of 8.79 X 10(-12) M as determined by Scatchard analysis with approximately 34,000 receptors per cell. Specific NGF binding was also evident to C6 rat glioma cells and IMR-32 human neuroblastoma cells, but not to 3T3 mouse fibroblasts. These observations coupled with previous findings suggest that the NGF receptor may be a marker found on cells of neural derivation. As little as 1 ng/ml NGF caused an increase in the adhesiveness of F98 cells to culture flasks. Increased adhesiveness could be observed in as little as 5 min and was apparent for at least 45 min. At 25 min in NGF-containing medium, 24 +/- 3% of the cells adhered to the flasks compared to 13 +/- 1% of control cells. The NGF-induced increase in adhesiveness was not duplicated by epidermal growth factor, insulin, cytochrome c, bovine serum albumin, dibutyryl cyclic AMP, or sodium butyrate. Oxidized NGF blocked the effect of native NGF, but had little or no adhesion-promoting activity itself. Pretreatment of the cells with NGF was also effective in promoting adhesion, even though nerve growth factor was not added to the binding medium. The effect of this pretreatment was reversible; when NGF-pretreated cells were grown in medium without supplemental NGF, the adhesiveness of the cells returned to control levels or lower.
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PMID:Increased adhesion response of anaplastic glioma cells to nerve growth factor and the presence of specific receptors. 631 24

To evaluate the relationship between tumor burden and circulating immune complexes (IC) in children with neuroblastoma (NBL), we studied sera collected at intervals from patients with disseminated (Stage III or IV) NBL. Sera from 10 of 12 patients contained IC by the Raji cell assay at some time during the first 9 to 11 months of the study. Higher IC levels were observed in sera of female patients. Fluid-phase C1q binding tests detected IC in only 16% of sera. IC measurements by either assay did not correlate with tumor burden. However, serum IC levels, as measured by the Raji cell assay, correlated significantly with serum antibody to bovine serum albumin (BSA) (rs = 0.54; p less than 0.001, rs = r as determined by Spearman rank correlation test). Measurement of anti-BSA antibodies in sera from the 12 patients, tested serially for circulating IC, and from five additional patients revealed that these had significantly higher anti-BSA activity than was found in sera from 13 age-matched controls. Sera from females also had relatively high levels of anti-BSA. Levels of antibody to bovine gamma-globulin and casein were not abnormal. Three sera with high IC levels (greater than 800 micrograms equivalents of heat-aggregated IgG) and relatively low anti-BSA activity appeared to contain "hidden" antibodies to BSA. These were demonstrated by measuring the increase in the ability of sera to bind 125I-BSA after they had been briefly acidified and then neutralized in the presence of the labeled BSA. The possible relevance of these results to the pathophysiology of NBL is discussed in light of earlier work that reported that serum IC levels correlate with the stage of the disease in NBL.
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PMID:Correlation of immune complexes in disseminated neuroblastoma with serum antibody to bovine serum albumin. 633 61


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