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 presence of circulating immune complexes (ICS) in freshly drawn sera of 67 children with neuroblastoma was studied by the Raji cell radioimmunoassay of Theofilopoulos et al. (J. Clin. Invest. 57: 169--182), with particular emphasis on the correlation of levels of ICS with stage of disease and changes attributable to treatment. There was a close correlation between amount of complexes and stage of disease and treatment. Levels of ICS increased as the stage of the disease advanced, and were significantly higher (P less than 0.005) in stage IV than in all other stages combined. When patients with stage IV disease were subdivided into "before," "during," and "after" treatment groups, there was a significant decrease in ICS levels as treatment progressed. Studies of complement and complement components did not give such a clear relationship. A significant decrease of hemolytic C1 values was found in patients with "active disease" compared to normal age-matched controls. Some high C3 levels, determined immunochemically, were associated with low hemolytic levels of C3, which were attributed to C3 cleavage detected by immunoelectrophoresis. Based on our survival data, ICS, which were significantly different in 20 patients now decreased when compared to those of other patients, are very valuable in the prognosis of neuroblastoma.
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PMID:Circulating immune complexes in sera of children with neuroblastoma: correlation with stage of disease. 74 75

The positron-emitting glucose analogue 18F-2-fluoro-2-deoxy-d-glucose (FDG) was evaluated for its accretion into the following subcutaneous human tumor xenografts in nude mice: B-cell lymphoma (Namalwa or Raji), ovarian carcinoma (HTB77), colon cancer (SW948), choriocarcinoma (BEWO), bladder cancer (UM-UC-2), renal cell carcinoma (UM-RC-3), neuroblastoma (Mey), melanoma (HTB63), and small cell lung carcinoma (NCI69). Two hours postinjection, tumor uptakes ranged from 0.027 (colon cancer) to 0.125% kg injected dose/g (melanoma); and was greater than 0.085 in the Namalwa lymphomas and the renal cell carcinomas. Tumor-blood ratios of up to 23:1 were seen 2 hours postinjection (melanoma) with a mean tumor-blood ratio for all tumors of 12.3 +/- 1.8. Uptake in the other tumors was intermediate. When evaluated, tumor uptake was slightly greater at 1 than at 2 hours postinjection, although target-background ratios were generally higher at 2 hours postinjection. This compound, FDG, may have broad applicability as a tracer for positron-emission tomographic imaging of many human malignancies.
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PMID:18F-2-deoxy-2-fluoro-D-glucose uptake into human tumor xenografts. Feasibility studies for cancer imaging with positron-emission tomography. 200 43

The presence of neonatal (cord) lymphokine-activated killer (LAK) cell activity toward natural killer cell resistant Raji and Daudi cell lines has recently been reported from our laboratory. We investigated the future therapeutic use of LAK adoptive immunotherapy by examining LAK in vitro cytotoxicity from both neonatal and adult mononuclear cells against solid tumor cell lines of relevance to pediatric oncology: SH-SY5Y (neuroblastoma), SK-NM-C (neuroblastoma-neuroepithelioma), NEP-1 (Wilms' tumor), SK-ES-1 (Ewing's sarcoma), and A-204 (rhabdomyosarcoma). Cord and adult mononuclear cells were activated by recombinant IL-2 (100 mu/ml) for 5-7 days and added in an effector:target ratio of 40:1 to 51Cr-labeled target cells. Specific cell lysis was determined after a 4-h incubation. There was a significantly high level of cord and adult LAK cytotoxicity against Wilms' (76.4 +/- 9.8 versus 77.3 +/- 6.8%) and Ewing's (84.2 +/- 5.5 versus 71.1 +/- 6.5%) cell lines and significant but moderate LAK activity against neuroepithelioma (52.0 +/- 6.6 versus 55.4 +/- 4.5%) and rhabdomyosarcoma (46.6 +/- 5.7 versus 43.9 +/- 5.2%) cell lines. There was no difference between cord and adult LAK activity toward these targets. However, a differential response toward the more classical neuroblastoma cell line, SH-SY5Y, was noted with significantly more LAK cytotoxicity from cord mononuclear cells than adult mononuclear cells (51.2 +/- 6.9 versus 28.5 +/- 8.2%) (p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lymphokine-activated killer cytotoxicity in neonatal mononuclear cells: in vitro responses to tumor cell lines from pediatric solid tumors. 253 88

The human B-cell line RJ2.2.5, derived by mutagenesis from a Burkitt lymphoma cell line and selected for loss of HLA class II antigen expression, was infected with recombinant retroviruses containing either the Harvey murine sarcoma virus oncogene v-Ha-ras or the human neuroblastoma homolog NRAS. Both activated ras genes partially complemented the regulatory defect in RJ2.2.5 and specifically increased the expression of the DR and DQ subsets of HLA class II genes. Blot-hybridization analysis and RNase mapping indicated that HLA-DQ alpha-chain mRNA in the infected cell lines was increased to a level at least 50% that of the parent B-cell line, Raji. The levels of HLA-DR and -DQ beta-chain RNA also were increased but to a lesser extent. In contrast, we detected no effect of ras on the quantities of other class II, class I, or invariant-chain mRNAs. Fluorescence-activated cell sorter analysis with antibodies recognizing HLA-DR, -DQ, and class I antigens supported these observations. Enhancement of HLA class II gene expression by ras genes may have important implications for regulation of the immune system in response to transformation.
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PMID:Defective HLA class II expression in a regulatory mutant is partially complemented by activated ras oncogenes. 331 16

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

delta 9-tetrahydrocannabinol, the major psychoactive cannabinoid of marijuana modulates immune cells in vivo and in vitro. It is possible that the drug exerts it's effect either by inserting into and disrupting the cell membrane (nonreceptor mechanism) or by binding to a cannabinoid receptor moiety and thus altering cell function through some form of signal transduction. In the present study, we confirm and extend the findings that mouse and human immune cells express specific cannabinoid binding sites and cannabinoid receptor mRNA. Reverse transcription-polymerase chain reaction analysis showed the presence of receptor mRNA not only in the neuroblastoma cell line (N18TG-2), but also in mouse splenocytes and in cell lines such as NKB61A2 (a mouse natural killer-like), CTLL2 (a mouse IL2-dependent T cell), THP-1 (a human monocytic cell) and Raji (a human B cell) but not in Jurkat (a human T cell). Furthermore, the receptor mRNA was expressed in purified populations of resting splenic T and B lymphocytes but not in resting populations of enriched splenic macrophages. Finally, LPS-stimulated Raji and PMA-stimulated THP-1 human cell lines showed increased levels of the cannabinoid receptor mRNA. These results suggest cannabinoid receptors have biological relevance in lymphoid cells because: receptor mRNA is detected in some resting immune cells but not others and the mRNA increases during cell activation. The major psychoactive component of marijuana, delta9-tetrahydrocannabinol (THC), has been shown to modulate human and mouse immune responses both in vitro and in vivo (1,2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of cannabinoid receptor mRNA in murine and human leukocytes. 754 49

Homeoproteins encoded by genes of the Hox family are nuclear proteins believed to act as transcription factors and to participate in the determination of the body plan. Here we show that in several vertebrate cells, they exhibit a subnuclear localisation associated with the nucleolus. We used monoclonal antibodies to study the distribution of three homeoproteins, namely HOXB7, HOXC6 and HOXD4. The immunoreactivity to antibodies against HOXC6 protein in Xenopus laevis embryonic tissues is restricted to one or two spots within the nucleus; this distribution partially overlaps that of fibrillarin, a protein of the fibrillar zone of the nucleoli. Indirect immunofluorescence analysis of the distribution of HOXB7 protein in 3T3 cells, and of HOXD4 protein in human neuroblastoma and Raji lymphoma cell lines and activated lymphocytes, results invariably in a nucleolar localisation. Purified nucleoli from stimulated T lymphocytes, and Raji cells contain an activity capable of binding, in a gel retardation assay, to an oligonucleotide specifically recognised by the HOXD4 homeoprotein. This activity is specifically removed by anti-HOXD4 antibodies and is found associated in southwestern blots with a single band with an apparent M(r) of 30,000, corresponding to that of recombinant HOXD4. The functional significance of the nucleolar localisation of Hox proteins remains to be determined.
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PMID:Nucleolar localisation of three Hox homeoproteins. 773 96

Membranes of a variety of clonal cell lines, including neuroblastoma x glioma hybrid NG108-15, glioma C6, Rat 1 and CHO fibroblasts and the pituitary-derived cell lines alpha T3 and GH3 were immunoblotted with an antiserum (CQ) raised against a synthetic peptide corresponding to the C-terminal decapeptide of the alpha subunits of the phosphoinositidase-C-linked G-proteins Gq and G11. In SDS-PAGE conditions able to resolve these two polypeptides, direct evidence was obtained for co-expression of these two G-proteins in all of the above cell lines. The ratio of these two G-proteins varied substantially (alpha 11/alpha q = 0.25-2.5) between the cell lines. In human platelets and in a range of haemopoietically derived human cell lines including U937 (monoblasts), Raji (Burkitts lymphoma) and Jurkat (mature T cell) expression of G11 alpha was not detected. This was not due to the inability of the antiserum to identify human G11 alpha as other human cell lines co-expressed both G-proteins. A third, unidentified CQ reactive polypeptide of similar mobility was resolved and present in all cell lines examined.
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PMID:Distribution and relative levels of expression of the phosphoinositidase-C-linked G-proteins Gq alpha and G11 alpha: absence of G11 alpha in human platelets and haemopoietically derived cell lines. 821 63

Human gammadelta T lymphocytes play an important role in nonadaptive reactions to infection and early tumor defense. This is the first report that freshly isolated, native gammadelta T cells of some healthy donors can kill human neuroblastoma cells to varying degrees. Their killing ability was increased and maintained during expansion and cultivation with interleukin-2 (IL-2; 400 IU/mL) for as long as 30 days (100% specific lysis at an effector-to-target cell (E:T) ratio of 20:1). gammadelta T lymphocytes without this spontaneous killing ability gained a specific cytolytic activity of 81% +/- 10.4% SD after stimulation with IL-2 for 24 hours. gammadelta cells were isolated from peripheral blood by positive enrichment (using a magnetic cell sorting system; purity, 95.2% +/- 3.2% SD, n = 21). High natural cytotoxic activity against human neuroblastoma cell lines (>50% specific lysis at an E:T ratio of 20:1) was exhibited by one of 11 donors, whereas two of 11 showed medium cytotoxicity (30% to 50% specific lysis). Eight of 11 donors showed very slight or no lytic activity against human neuroblastoma cells (<30% specific lysis). gammadelta T cells were also cytotoxic against Daudi (32.7% specific lysis at an E:T ratio of 20:1), Raji (10.3%), Colo 205 (23.1%), A 204 (54%), K 562 (100%), and SK-N-MC (100%) cells. Isolated gammadelta T cells were grown in Iscove modified Dulbecco medium with IL-2 (400 IU/mL). Increased cell proliferation (38.5% to 182%) was induced with phytohemagglutinin, IL-15, Clodronat, OKT3, or various combinations of these. Results of cold target inhibition assays suggest a natural killer-like activity of the gammadelta T-cell killing mechanism. Peptidase or papain render neuroblastoma cells unsusceptible to gammadelta T-cell killing, suggesting the involvement of antigen peptide(s) in the process of neuroblastoma cell killing. Treatment with acid phosphatase reduced specific lysis by 66.5% +/- 34.1% SD, which suggests a binding to phosphorylated neuroblastoma cell-surface structures in the killing mechanism of gammadelta T cells. Heat shock did not affect the extent of neuroblastoma killing by gammadelta cells. Recognition of neuroblastoma cells by gammadelta cytotoxic T lymphocytes is negatively regulated by major histocompatibility complex I receptors. Evidence for natural and inducible cell cytotoxicity of gammadelta T cells against human neuroblastoma cells, easy propagation, purification, and missing alloreactivity in mixed lymphocytes cultures indicates a role for this subpopulation of T lymphocytes in adoptive immunotherapy.
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PMID:Human gammadelta T lymphocytes exert natural and IL-2-induced cytotoxicity to neuroblastoma cells. 1100 47

Fifteen triterpene acids, viz., seven of the beta-boswellic acids (ursane-type) (1-7), two of the alpha-boswellic acids (oleanane-type) (8, 9), two of the lupeolic acids (lupane-type) (10, 11), and four of the tirucallane-type (12-14, 16), and two cembrane-type diterpenes (17, 18), isolated from the MeOH extract of the resin of Boswellia carteri (Burseraceae), together with a triterpene acid 15 (the acetyl derivative of 14), were examined for their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells and on activation of (+/-)-(E)-methyl-2[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitrogen oxide (NO) donor, and cytotoxic activities against three human neuroblastoma cell lines, IMR-32, NB-39, and SK-N-SH in vitro. On evaluation against the EBV-EA activation induced by TPA, seven compounds, 2, 10, 11, and 13-16, showed potent inhibitory effects on EBV-EA induction. Upon evaluation against activation of NOR 1, five compounds, 7, 13, and 14-16, showed potent inhibitory effects. Further, fifteen compounds, 1-7, 9-11, 13-15, 17, and 18, exhibited potent cytotoxic activities with IC(50) values of 4.1-82.4 muM against all of the three human neuroblastoma cells tested.
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PMID:Cancer chemopreventive effects and cytotoxic activities of the triterpene acids from the resin of Boswellia carteri. 1694 22


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