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 specific, precise detection of volatile metal chelates has been obtained by coupling the effluent from a gas chromatograph directly to the burner head of a commerical atomic absorption spectrometer (AAS). Quantitation of chromium in the nanogram range has been accomplished with a detection limit of 1.0 ng. The chelation-extraction-gas chromatographic separation procedure coupled with the selective detection by AAS gives a relatively interference-free system that has been used to quantitatively analyse for chromium in standard biological materials NBS SRM 1571 Orchard Leaves and SRM 1569 Brewers Yeast. Metal chelates of iron, copper and cobalt have also been detected by this system.
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PMID:Coupled gas chromatography-atomic absorption spectrometry. 32 71

We developed a high-titer polyclonal antiserum to a glycoprotein tumor-associated antigen (TAA) by immunization of a baboon with the purified glycoprotein antigen. The baboon serum was fractionated into IgG and IgM components by DEAE Affi-Gel blue chromatography. The ability of the baboon IgM anti-TAA antibody to effect tumor cell lysis in the presence of complement was tested using a chromium-release assay. The baboon antibody was able to lyse melanoma target cells (20.8%-71.4% cytolysis), breast carcinoma cells (36.5%-38.9% cytolysis), and a neuroblastoma cell line (35.5% cytolysis) in the presence of complement but did not effect significant lysis of autologous lymphoblastoid cell lines (4.9% cytolysis) or peripheral blood lymphocytes from healthy volunteers (12.6% cytolysis). Cytolysis of melanoma target cells was completely inhibited by preabsorption of the IgM anti-TAA antibody with UCLA-SO-M14 (M14) cells and partially inhibited by preabsorption with several other melanoma cell lines. There was no significant inhibition of tumor cell lysis after preabsorption of the antibody with lymphoblastoid cell lines. Complement-dependent lysis of M14 targets could be blocked by addition of the purified antigen to the antibody prior to incubation with the tumor cells. Our results suggest that the glycoprotein TAA resides on the tumor cell surface and that the baboon IgM anti-TAA antibody recognizes the antigen on the cell surface and is able to fix complement and effect the lysis of the tumor cells.
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PMID:Complement-dependent lysis of tumor cells by a baboon IgM antibody to a tumor-associated antigen. 156 14

Nutritionally supporting the malnourished tumor bearing host may not benefit the disease outcome, but, rather, may preferentially "feed the cancer". We hypothesized that repletion is beneficial only when it augments an anti-tumor immune response. To support this hypothesis, 240 A/J mice were assigned to isocaloric dietary groups (24%, 5%, or 2.5% protein). On day 14 the mice received either immunogenic C1300- neuroblastoma (NB) or non-immunizing TBJ-NB. On day 21 half of the restricted animals were repleted with 24% protein chow. At day 35, chromium-release cell-mediated cytotoxicity was measured. In the group of mice that received 2.5% protein chow, nutritional repletion specifically augmented anti-tumor activity for C1300-NB which elicits a host immune response (33.78 L.U. (repleted) vs 3.47 L.U. (depleted) p less than 0.01), in contrast, nutritional repletion was detrimental for non-immunizing TBJ-NB, where further depression of cytotoxicity was seen (1.37 L.U. (repleted) vs 2.06 L.U. (depleted) 0 less than 0.01). This suggests that the influence of nutritional repletion in tumor nearing animals is dependent on the integrity of host's anti-tumor immunity.
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PMID:Influence of nutrition on anti-tumor activity. 187 54

6-Hydroxydopamine(6-OHDA) and Merocyanine-540(MC-540) have been used clinically for purging of neuroblastoma cells prior to autologous bone marrow transplantation. Both substances were found to be more toxic against neuroblastoma cells than against hematopoietic stem cells. The more pronounced cytotoxic effects of 6-OHDA against neuroblastoma cells were not caused by its selective uptake; the rapid autooxidation at physiological pH leads to the formation of H2O2 already in the incubation medium. Cytotoxic effects were not detected in short-time test systems (4 hour chromium-51 release assay) but only after longer incubation periods. In contrast, MC-540 proved to be toxic almost equally in short- and long-time test systems. 4-Hydroxynonenal(4-HNE) that may be formed in the plasma membrane subsequently to photoactivation of MC-540 was only slightly more toxic to neuroblastoma cells than to hematopoietic cells. Although the use of 6-OHDA and MC-540 in bone marrow purging has some limitations, the sensitivity of neuroblastoma cells against reactive oxygen compounds may be exploited more generally for therapy of this tumor.
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PMID:Cytotoxic effects of 6-hydroxydopamine, merocyanine-540 and related compounds on human neuroblastoma and hematopoietic stem cells. 251 Oct 86

If immunoregulation of cancer is to be effective, the tumor must express immunogenicity and the host immune mechanism must be capable of responding to that stimulus. Though neuroblastoma (NB) might be such a tumor, a systematic assessment of this complex host-tumor interaction is lacking. We report such an analysis using the murine NB system. C1300-NB is highly antigenic, locally growing, and nonmetastasizing, while its clonal counterpart, TBJ-NB, is minimally antigenic and demonstrates not only aggressive local growth but systemic metastases as well. We analyzed A/J mouse antitumor naturally occurring killer lymphocyte (NK cells), cytotoxic lymphocyte (CTL cells), and suppressor lymphocyte (SC cells) function in response to these tumor lines. NK and CTL activity was measured in 40 mice after 3 weeks of growth of either C1300-NB or TBJ-NB using a cold target inhibition test to either the YAC-1 or P815 mastocytoma cell line, respectively. SC activity was analyzed in an additional 24 mice treated with an SC destroying 15 mg/kg of cyclophosphamide (CYA) three days after tumor inoculation. After 4 weeks of tumor growth spleens were harvested, cell-mediated cytotoxicity was measured by chromium 51 release assay and tumor cell lysis was expressed as lytic unit 30 (LU-30), an arbitrary definition of the number of lymphocytes needed to lyse 30% of target cells. By increasing the concentration of the NK-sensitive YAC-1 cold target, there was a 56.8% inhibition of lymphocytotoxicity to C1300-NB, contrasting with this was the lack of inhibition (17.8%) by the non-NK sensitive P815 cell line.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Systematic analysis of the immunoregulation of murine neuroblastoma. 252 62

A method is reported for determination of chromium in foodstuffs. Organic matter is digested with nitric acid, followed by oxidation to Cr(VI) and extraction with methyl isobutyl ketone (MIBK) after HCl addition. Chromium determinations are performed by flame absorption spectroscopy. Absence of interferences is verified and recovery tests are performed on food samples. Quantitation limit (3.8 ng/mL), accuracy (NBS Standard Reference Material 1,573 Tomato Leaves, 4,500 +/- 500 ng/g, found 3,860 +/- 409 ng/g), and precision (CV for vegetable matrix = 9.05%, CV for animal matrix = 14.95%) of the procedure are evaluated.
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PMID:Atomic absorption spectrophotometric determination of chromium in foods. 377 62

Genetically engineered monocytes and macrophages may have potential as effector cells for the adoptive immunotherapy of cancer. As a first step, we have transfected the genes encoding either mouse interferon (IFN)-gamma, human interleukin (IL)-6, mouse IL-4, or mouse tumor necrosis factor (TNF)-alpha into the mouse macrophage cell line, J774A.1 cells using retroviral vectors. In vitro activation of J774A.1 cells by gene modification was assessed by morphological changes, proliferative activity was determined by [3H]-TdR uptake, and cytolytic activity was assessed using an 18-hour chromium-51 (51Cr) release assay. In vivo tumoricidal activity was studied by means of local adoptive immunotherapy using intratumoral injection of transfected effector cells. IFN-gamma gene-transfected J774A.1 [J7(IFN-gamma)] cells developed filamentous processes, increased doubling times, and enhanced tumoricidal activity against three tumor cell lines: the TNF-sensitive fibrosarcoma line WEHI 164 and the TNF-alpha-resistant cell lines B16 melanoma and C1300 neuroblastoma. IL-6-, TNF-alpha-, and IL-4-gene-transfected J774A.1 cells also had augmented tumoricidal activity but did not display any changes in morphology or growth. Cytolytic activity was markedly reduced after the addition of anti-TNF-alpha antibodies. Cytolytic J7(IFN-gamma) cells showed upregulated expression of TNF-alpha messenger RNA. After intratumoral injection of J7(IL-4) and J7(IFN-gamma) cell mixtures, 50% of established B16 melanomas were rejected by C57BL/6 mice, thereby demonstrating synergistic killing. Further studies on gene-transfected macrophages should better define their potential usefulness in tumor immunotherapy.
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PMID:Increased in vitro and in vivo tumoricidal activity of a macrophage cell line genetically engineered to express IFN-gamma, IL-4, IL-6, or TNF-alpha. 762 Dec 59

A serum containing a monoclonal IgM lambda with anti-GM1 and anti-GD1b activity was obtained from a patient with upper motor neuron syndrome. By indirect immunocytochemical techniques with double staining, the patient's IgM strongly stained membranes of neurons in primary cultures of fetal central and peripheral nervous system. It was cytotoxic for neurons in two human neuroblastoma established cell lines in a complement-dependent chromium release assay. These results are in keeping with the hypothesis of a direct pathogenetic role of such monoclonal anti-GM1 and GD1b IgM antibodies.
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PMID:Reactivity of a human monoclonal anti-GM1 and anti-GD1b IgM antibody with human neurons in cultures. 822 8

Trophozoites of 4 species of Acanthamoeba were cytopathic for cultured rat B103 neuroblastoma cells. Cytopathogenicity was evaluated by a chromium release assay and by transmission and scanning electron microscopy. Acanthamoeba culbertsoni, Acanthamoeba castellanii, and Acanthamoeba polyphaga destroyed B103 target cells at 37 C as evidenced by the release of radiolabel. Acanthamoeba astronyxis did not produce cytopathology at 37 C but destroyed nerve cells at 25 C. Transmission and scanning electron microscopy of cocultures maintained at different time periods revealed that all species of Acanthamoeba exhibited long cylindrical structures, termed digipodia, which made contact with target cells. Following this effector cell-target cell contact, membrane blebbing on the nerve cells was observed. These events were followed either by lysis of target nerve cells or ingestion of the target cells via food-cups and their subsequent channeling into intracytoplasmic food vacuoles. Use of the TUNEL (TdT-mediated dUTP nick end labeling) technique indicated that approximately 40% of B103 cells incubated with A. culbertsoni, 20% of B103 cells cocultured with A. castellanii or with A. polyphaga, and less than 1% of B103 cells incubated with A. astronyxis at 37 C were apoptotic after 24 hr of coculture. Studies using electron microscopy indicated that Acanthamoeba trophozoites destroyed nerve cells both by cytolysis and by ingestion of whole nerve cells via food-cups.
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PMID:In vitro destruction of nerve cell cultures by Acanthamoeba spp.: a transmission and scanning electron microscopy study. 888 87

Overexpression of the trans-membrane drug efflux pump P-glycoprotein is one of the major mechanisms by which cancer cells develop multidrug resistance. We demonstrated previously that noncytotoxic doses of various genotoxic chemicals, particularly DNA cross-linking agents, preferentially altered expression of inducible genes. These effects occurred principally at the transcriptional level and were closely correlated temporally with DNA damage. Because the mdr1 gene coding for P-glycoprotein has been reported to be highly inducible, we were interested in the effects of genotoxic cancer chemotherapy agents on its expression. We report that the DNA cross-linking agent mitomycin C significantly suppressed mRNA and protein expression of P-glycoprotein and decreased the rate of drug efflux. Mitomycin C pretreatment also significantly increased the sensitivity of cancer cells to subsequent killing by the P-glycoprotein substrate doxorubicin, decreasing the ED50 by 5- to 10-fold. Suppression of P-glycoprotein expression was also observed with subtoxic doses of the DNA cross-linking agents cisplatin, BMS181174, and chromium(VI). These effects occurred in both human and rodent cell lines; in cell lines derived from colon, breast, leukemia, neuroblastoma, and hepatoma tumors; and under both monolayer and "spheroid" culture conditions. These results suggest the basis for novel clinical cancer chemotherapy regimens aimed at drug-resistant tumors, in which a sub-chemotherapeutic dose of a DNA cross-linking agent is used to modulate the multidrug resistance phenotype prior to treatment with a second cytotoxic agent.
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PMID:Suppression of P-glycoprotein expression and multidrug resistance by DNA cross-linking agents. 981 17


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