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)

Friend mouse erythroleukemia cells (T3c1-2 and its subline 5000) can be induced to synthesize hemoglobin after treatment with 1.5% (vol/vol) dimethylsulfoxide. When these cells are fused with nonerythroid cells (namely, mouse neuroblastoma or L cells) hemoglobin induction is extinguished. In order to determine if the nucleus of the nonerythroid cell is necessary for this extinction, fusions were performed between mouse erythroleukemia cells and enucleated neuroblastoma or L cells. Hemoglobin induction was reduced or eliminated in clones of these hybrids even after 6 months of continuous culture. These results suggest that the cytoplasm of nonerythroid cells contains factor(s) that extinguish hemoglobin inducibility in erythroleukemic cells and that this new phenotype can be inherited.
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PMID:Extinction of hemoglobin inducibility in Friend erythroleukemia cells by fusion with cytoplasm of enucleated mouse neuroblastoma or fibroblast cells. 26 3

The immunogenicity of the antigen molecule is a prerequisite for active specific immunotherapy for melanoma. Since most of the melanoma-associated antigens recognized by the murine immune system are known to be not immunogenic in man, a detection and analysis system for melanoma-associated antigens is required to reflect in vivo immune responses in patients with melanoma. One of the promising approaches, an attempt to develop human monoclonal antibodies from B lymphocytes of patients with melanoma, has met with limited success due to the difficulties of producing large amounts of antibodies and using them in immunochemical assays, because most of them belong to the IgM class and have low affinity. Our approach is to utilize the screening of a cDNA expression library constructed from mRNA extracted from cultured melanoma cells with antibodies from patients with melanoma. The cloned cDNA, designated as D-1, had 1029 bp and showed no significant homology with viral and mammalian sequences stored in GENETYX. cDNA D-1 hybridized to a 2.0 kb mRNA species from 3 different cell lines of human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cells, but not from a renal carcinoma cell line, normal peripheral lymphocytes, or normal fibroblasts. The in vivo expression and distribution of mRNA related to cDNA D-1 has been examined in tissue specimens by in situ hybridization and shown to be rather restricted on melanoma cells. The polypeptide antigen encoded by cDNA D-1 may be a valuable immunogen for implementing active specific immunotherapy in patients with melanoma.
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PMID:Melanoma-associated antigen synthesized in vitro for active specific immunotherapy. 129 70

The purpose of this study was to identify human melanoma-associated Ag (MAA) that are immunogenic in patients, because these molecules may be useful immunogens to implement active specific immunotherapy. To this end, an expression cDNA library constructed from the human melanoma cell line A375 was screened with sera from patients with melanoma. A 1029-bp cDNA (designated D-1) was isolated. Its nucleotide sequence showed no significant homology with viral and mammalian sequences stored in GE-NETYX. cDNA D-1 hybridized to a 2.0-kb mRNA species from human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cell lines but not from a renal carcinoma cell line, PBL, and cultured skin fibroblasts. The D-1 clone produced a fusion protein that displayed a significantly higher reactivity with sera from patients with melanoma than from healthy controls. Furthermore, D-1 fusion protein induced in mice antibodies that immunoprecipitated a 50-kDa component from cultured human melanoma cells. The structural properties of D-1 MAA are different from those of previously described MAA. These results suggest that the approach we have applied may be useful to identify novel MAA expressed by melanoma cells. Furthermore, the immunogenicity of recombinant D-1 protein suggests that it may be a valuable immunogen to implement active specific immunotherapy in patients with melanoma, if additional experiments show that it has the appropriate tissue distribution.
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PMID:Cloning and in vitro expression of a melanoma-associated antigen immunogenic in patients with melanoma. 186 Oct 72

Natural killer (NK) cells and NK cell activity were determined in three groups (newly diagnosed [n = 21], on therapy [n = 21], and off therapy [n = 18]) of children with various types of malignant solid tumors and in a control group (n = 26) by means of Leu-7 and Leu-11b monoclonal antibodies and a 4-hour 51Cr-release assay, respectively. The erythroleukemia cell line K562 was used as a target cell. The newly diagnosed group included eight patients with localized disease (Stage I-II), ten with bulky but nonmetastatic disease (Stage III), and three with metastases (Stage IV). The mean percent of NK cell activity in the newly diagnosed group was significantly higher than that of the control group. Children with Stage III tumors at diagnosis had higher mean NK cell function than those with Stage I-II and Stage IV. On therapy patients had significantly fewer NK cells and lower NK cell cytotoxicity than those in the other groups studied. We also studied the following: (1) the in vitro effect of recombinant interferon-alpha (rIFN-alpha) and recombinant interleukin-2 (rIL-2) on NK cell function of peripheral blood lymphocytes (PBL) from children with solid malignancies; and (2) the susceptibility of neuroblastoma-derived (CHP-126 and SKNSH) and rhabdomyosarcoma-derived (A-204) cell lines to NK cell lysis. Both rIFN-alpha and rIL-2 enhanced NK cell activity of PBL from children with malignancies and healthy children against K562 and solid tumor cell lines. The enhancing effect or rIL-2 was greater than that of rIFN-alpha. CHP-126 and SKNSH cell lines were susceptible to NK cell lysis mediated by the PBL of children with neuroblastoma and the control group. The A-204 cell line was less sensitive than K562 to NK cell cytotoxicity. Our results suggest a potential therapeutic role for both cytokines in the treatment of malignant solid tumors of childhood.
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PMID:Natural killer cells in children with malignant solid tumors. Effect of recombinant interferon-alpha and interleukin-2 on natural killer cell function against tumor cell lines. 278 77

Anthracyclines such as Adriamycin (ADR) and daunomycin markedly inhibit cell growth in vivo and in vitro. These studies demonstrate that 30 microM hemin, which induces hemoglobin synthesis in human and murine erythroleukemia cells in culture, markedly decreases the cytotoxicity of ADR in a variety of hemopoietic cell lines (K562, HEL-1, MEL-745, HL-60, and U937) and in erythroid burst-forming cells from normal human marrow. Hemin failed to protect four of the five nonhemopoietic cell lines tested, including MCF-, breast adenocarcinoma cells, C-205 colon carcinoma cells, mouse 3T3 fibroblasts, and mouse kidney VERO cells. Hemin did protect human neuroblastoma IMP-32 cells from ADR cytotoxicity; however, this nonhemopoietic cell line undergoes dendrite formation in response to hemin induction. Cytofluorographic analysis of cellular ADR content and labeling studies with [3H]daunomycin demonstrated that hemin decreases the intracellular accumulation of these anthracyclines by more than 50% in K562 erythroleukemia cells. These studies indicate that small doses of hemin prevent intracellular accumulation of anthracyclines and thereby markedly reduce anthracycline toxicity to cells. Since this protective effect is observed preferentially with hemopoietic cells, it is possible that this finding could be exploited to protect the bone marrow from the cytotoxic action of anthracyclines during therapy for nonhemopoietic tumors.
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PMID:Prevention of anthracycline-induced cytotoxicity in hemopoietic cells by hemin. 370 75

Nafazatrom (Bay g 6575) has been shown to be a potent inhibitor of tumor metastasis in preclinical models. It is believed to work by stimulating endogenous prostacyclin production. The drug has also been shown to inhibit the growth of certain experimental tumors, to be cytostatic for certain cell lines in tissue culture, and to induce differentiation in HL-60, neuroblastoma, and Friend erythroleukemia cell lines. Furthermore, no toxicity has been seen in animals or human volunteers. We report here a clinical trial of oral nafazatrom at five dose levels in patients with advanced cancer. Thirty patients with a wide variety of advanced malignancies were treated for 26-638+ days (median 82 days). No tumor responses were seen. Toxicity included two cases with mild skin rashes, one case with nausea and vomiting, and one case with diarrhea. Nafazatrom is a safe and well-tolerated agent. Maximum activity would be predicted to occur in the adjuvant treatment of cancer and we feel that further efforts should proceed to identify the appropriate dose for such a trial.
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PMID:A clinical trial of nafazatrom (Bay g 6575) in advanced cancer. 371 82

Using anticholeragen antibodies and 125I-protein A, we developed a specific and quantitative assay for measuring choleragen on the surfaces of cultured cells. When neuroblastoma cells containing bound toxin were incubated at 37 degrees C, surface toxin disappeared with a half-life of approximately 2 h and a significant loss was detected by 10 min. When cells were incubated with 125I-choleragen in order to measure toxin degradation, cell-associated radioactivity disappeared with time and a corresponding amount of TCA-soluble label appeared in the culture medium with a half-life of 4-6 h. No degradation was detected until 45 min. Although there was a lag of 15 min before bound choleragen activated adenylate cyclase, the enzyme became maximally activated between 45 and 60 min. Similar results were obtained with Friend erythroleukemia cells. Internalization, degradation, and activation all were blocked when the cells were maintained at 4 degrees C. At 22 degrees C, internalization and activation occurred, albeit at a slower rate, whereas degradation was effectively inhibited. These results indicated that choleragen does not have to be degraded by intact cells in order for it to activate adenylate cyclase. Some internalization of the toxin, however, appears to precede the activation process.
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PMID:Internalization and degradation of cholera toxin by cultured cells: relationship to toxin action. 628 36

Chromosomal high mobility group (HMG) proteins HMG1 and HMG2 from mouse neuroblastoma cells and Friend erythroleukemic cells were analyzed by acetic acid/urea/polyacrylamide gel electrophoresis. Compared to rapidly growing cells, levels of HMG1 and HMG2 were decreased in mouse neuroblastoma cells that had been induced to differentiate by serum deprivation. This comparison revealed a reciprocal relationship between these HMG proteins and H10, a histone known to be in higher concentrations in nondividing cells. When cell growth was inhibited by means of density inhibition, however, HMG1 and -2 levels were not affected in either HeLa or mouse neuroblastoma cells, even though H10 did not accumulate. This observation establishes that HMG1 and -2 contents are not correlated with mitotic rate per se. Treatment of mouse neuroblastoma by sodium butyrate, which stops cell division without commitment to differentiation, had no effect on the level of HMG1 and -2. However, the level was decreased by dibutyryl cyclic AMP and dimethyl sulfoxide treatments, which, like serum deprivation, induced irreversible morphological differentiation in the neuroblastoma cells. Moreover, induction of differentiation (hemoglobin synthesis) in Friend erythroleukemic cells by dimethyl sulfoxide showed a decrease in the contents of HMG1 and -2. These observations suggest that preferential loss of HMG1 and -2 in mouse neuroblastoma and Friend erythroleukemia cells may be related to commitment of these cells to differentiation.
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PMID:Loss of chromosomal high mobility group proteins HMG1 and HMG2 when mouse neuroblastoma and Friend erythroleukemia cells become committed to differentiation. 645 11

Because certain antiganglioside monoclonal antibodies can facilitate antibody-dependent cellular cytotoxicity against GD2+ ganglioside-bearing human and canine tumor cells, we wished to determine if clinically relevant antiganglioside monoclonal antibodies (Mabs) could also fix canine complement to lyse tumor cells in vitro. Using flow cytometry, human tumor cell lines (M21 melanoma and OHS osteosarcoma) were shown to highly express ganglioside GD2 and, to a lesser degree, GD3. In 51Cr release assays, M21 cells were lysed with canine serum, as a source of complement, plus either Mab 14.G2a or its mouse-human chimera, ch 14.18, specific for GD2. Heating canine serum abrogated its lytic activity and addition of rabbit complement reconstituted M21 lysis. Similar results were obtained with M21 cells when Mab R24 (against GD3) and canine serum were used. OHS cells were also lysed with canine serum plus Mab 14.G2a and lytic activity was abolished by heating canine serum but reconstituted with rabbit complement. Alone, canine serum or Mabs were not lytic to M21 or OHS cells. Conversely, human neuroblastoma (LAN-5) and K562 erythroleukemia cells were lysed by canine serum alone which was shown by flow cytometry to contain naturally occurring canine IgM antibodies that bound LAN-5 and K562 cells. The lytic activity of canine serum for LAN-5 or K562 cells was abolished by heating and restored by addition of either human or rabbit complement. Thus, human tumor cell lines can be lysed with antiganglioside Mabs through fixation and activation of canine complement-dependent lytic pathways. Canine xenoantibodies also mediate complement-dependent cytotoxicity of some human tumor cell lines. Together, these results are significant because they demonstrate an antitumor effect of the canine immune system which is of potential importance for cancer immunotherapy in a promising animal model.
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PMID:Lysis of human tumor cell lines by canine complement plus monoclonal antiganglioside antibodies or natural canine xenoantibodies. 854 51

The wasp venom, mastoparan (MP), is a direct activator of reconstituted pertussis toxin-sensitive G-proteins and of purified nucleoside diphosphate kinase (NDPK) [E.C. 2.6.4.6.]. In HL-60 membranes, MP activates high-affinity GTPase [E.C. 3.6.1.-] and NDPK-catalyzed GTP formation, but not photolabeling of G-protein alpha-subunits with GTP azidoanilide; this suggests that the venom activates G-proteins in this system indirectly via stimulation of NDPK. Moreover, the MP analogue, mastoparan 7 (MP 7), is a much more effective activator of reconstituted G-proteins than MP, whereas with regard to NDPK and GTPase in HL-60 membranes, the two peptides are similarly effective. In our present study, we investigated NDPK- and G-protein activation by MP in membranes of the human neuroblastoma cell line, SH-SY5Y, the human erythroleukemia cell line, HEL, the rat basophilic leukemia cell line, RBL 2H3, and the hamster ductus deferens smooth muscle cell line, DDT1MF-2. All these membranes exhibited high NDPK activities that were increased by MP. Compared to basal GTP formation rates, basal rates of high-affinity GTP hydrolysis in cell membranes were low. MP activated high-affinity GTP hydrolysis in cell membranes but did not enhance incorporation of GTP azidoanilide into G-protein alpha-subunits. As with HL-60 membranes, MP and MP 7 were similarly effective activators of NDPK and GTPase in SH-SY5Y membranes. Pertussis toxin inhibited MP-stimulated GTP hydrolyses in SH-SY5Y- and HEL membranes, whereas NDPK activations by MP were pertussis toxin-insensitive. Our data suggest that indirect G-protein activation via NDPK is not restricted to HL-60 membranes but is a more general mechanism of MP action in cell membranes. Pertussis toxin-catalyzed ADP-ribosylation of alpha-subunits may inhibit the transfer of GTP from NDPK to G-proteins. NDPK may play a much more important role in transmembrane signal transduction than was previously appreciated and, moreover, the GTPase of G-protein alpha-subunits may serve as GDP-synthase for NDPK.
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PMID:Activation of GTP formation and high-affinity GTP hydrolysis by mastoparan in various cell membranes. G-protein activation via nucleoside diphosphate kinase, a possible general mechanism of mastoparan action. 857 86


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