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)

Most studies looking at CD4-independent infection have used laboratory strains or their respective molecular clones. To determine whether primary human immunodeficiency virus type 1 isolates could infect CD4-negative cells, we obtained a panel of 23 clinical isolates and characterized the early steps of the viral life cycle in SK-N-MC cells, a CD4-negative, galactosylceramide-positive neuroblastoma cell line. Eight of 23 isolates established a nonproductive infection; entry and postentry restrictions were noted in the others. We were unable to correlate the infectivity for SK-N-MC cells with established biological phenotypes, such as syncytium induction, or with genetic classifications, suggesting that pantropism is an independent biological variable.
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PMID:Infection of SK-N-MC cells, a CD4-negative neuroblastoma cell line, with primary human immunodeficiency virus type 1 isolates. 879 85

Using a CD4-capture immunoassay for gp120, several strains of human immunodeficiency virus type 1 (HIV-1) grown in CD4-expressing T lymphoblastoid cells were found to contain little CD4-reactive gp120 (0.3-1.0 ng/ml) relative to virus titre (10(3.2)-10(5.0) TCID50/ml) and p24 antigen (80-1000 ng/ml). The measured CD4-reactive gp120 concentrations of HIV-1 suspensions grown in CD4-negative human neuroblastoma cells were 100- to 10,000-fold greater than those of HIV-1 grown in CD4-positive lymphoblastoid cells, even though both virus suspensions contained abundant viral gp120 as shown by immunoblot assay. It was postulated that CD4 derived from host cells might be associated with virions, concealing the binding domains of gp120. CD4 association with HIV-1 virions grown in CD4-positive cells was demonstrated directly by immunoblot assay of sucrose gradient-purified virus suspensions and by specific co-sedimentation of 125I-labelled OKT4 with virions propagated in CD4-expressing cells. CD4 coating of primary HIV-1 isolates grown in peripheral blood mononuclear cells was also observed. The biological significance of CD4 coating of HIV particles remains to be determined.
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PMID:Human immunodeficiency virus grown in CD4-expressing cells is associated with CD4. 881 Sep 98

Human T-lymphotropic virus-I (HTLV-I) has been etiologically linked with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), a neurologic disease. The characteristic pathological finding in HAM/TSP is marked mononuclear infiltration of the CNS with destruction of the long tracts of the spinal cord. An increased expression of HLA surface antigens and cytokines in the CNS is associated with this inflammatory response. Furthermore, there is evidence for the presence of HTLV-I in HAM/TSP CNS specimens using in situ hybridization and polymerase chain reaction techniques. The relationship between HTLV-I infection of CNS cells and the observed upregulation of surface antigens in the CNS is not well understood. It has been previously demonstrated that HTLV-I infection of neuroblastoma cells leads to induction of HLA surface antigens. As an extension of these studies, HFGC and HCN-1a, neuronal cell lines of nontumorigenic origin, were infected with HTLV-I and the effect on HLA upregulation was studied. Infection of the neuronal cells was demonstrated by the presence of HTLV-I gp46 surface antigen on CD4 negative cells and by the in situ presence of HTLV-I RNA in neurofilament positive cells. Concurrent to HTLV-I infection, HLA class II surface antigen was observed on neurofilament positive cells. Upregulation of HLA class II was not observed in neuronal cells grown in the presence of interferon-gamma or tissue necrosis factor-alpha.
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PMID:Induction of HLA class II in HTLV-I infected neuronal cell lines. 922 53

A major goal of tumor immunotherapy is the effective eradication of established metastases associated with the induction of a T cell-mediated protective immunity. We achieved this in a poorly immunogenic murine neuroblastoma model by gene therapy with a single chain interleukin 12 (scIL-12) fusion protein that assures equal expression of its p35 and p40 subunits. Thus, NXS2 hybrid neuroblastoma cells (C1300 x dorsal root ganglion cells), which form experimental bone marrow and liver metastases in syngeneic A/J mice, were transduced with a gene encoding murine interleukin 12, monomerized by introduction of a protein linker between the p35 and p40 protein chains of this heterodimeric cytokine. We demonstrate for the first time that subcutaneous vaccination with these transduced cells induces a protective immunity, as indicated by the complete absence of liver and bone marrow metastasis after challenge with NXS2 wild-type tumor cells. Furthermore, vaccination of animals with established liver and bone marrow metastases completely eradicated liver metastases and suppressed bone marrow metastases. The local and systemic immune response against scIL-12-transduced NXS2 cells is largely dependent on CD8(+) T cells. This was demonstrated in vivo by depletion of immunocompetent A/J mice with monoclonal anti-CD4 and anti-CD8 antibodies and in vitro by specific major histocompatibility complex, class I-restricted CD8(+) T cell-mediated killing of NXS2 and their parental C1300 neuroblastoma cells. In conclusion, we demonstrate successful anti-tumor immunotherapy with an scIL-12 fusion protein that could facilitate clinical application of interleukin 12 gene therapy.
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PMID:Gene therapy with a single chain interleukin 12 fusion protein induces T cell-dependent protective immunity in a syngeneic model of murine neuroblastoma. 948 10

In many different murine models, the immunogenicity of tumor cells can be increased by transduction with a range of immunostimulatory genes, inducing an immune response that causes regression of pre-existing unmodified tumor cells. To investigate the relevance of these animal models to pediatric malignancy, we used autologous unirradiated tumor cells transduced with an adenovirus-IL-2 to immunize 10 children with advanced neuroblastoma. In a dose-escalation study, we found that this tumor immunogen induced a moderate local inflammatory response consisting predominantly of CD4(+) T lymphocytes, and a systemic response, with a rise in circulating CD25(+) and DR+ CD3(+) T cells. Patients also made a specific antitumor response, manifest by an IgG antitumor antibody and increased cytotoxic T-cell killing of autologous tumor cells. Clinically, five patients had tumor responses after the tumor immunogen alone (one complete tumor response, one partial response, and three with stable disease). Four of these five patients were shown to have coexisting antitumor cytotoxic activity, as opposed to only one of the patients with nonresponsive disease. These results show a promising correlation between preclinical observations and clinical outcome in this disease, and support further exploration of the approach for malignant diseases of children.
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PMID:IL-2 adenovector-transduced autologous tumor cells induce antitumor immune responses in patients with neuroblastoma. 973 Oct 51

Genetically engineered, neuroattenuated herpes simplex viruses (HSVs) expressing various cytokines can improve survival when used in the treatment of experimental brain tumors. These attenuated viruses have both copies of gamma(1)34.5 deleted. Recently, we demonstrated increased survival of C57BL/6 mice bearing syngeneic GL-261 gliomas when treated with an engineered HSV expressing IL-4, as compared with treatment with the parent construct (gamma(1)34. 5(-)) alone or with a virus expressing IL-10. Herein, we report construction of a conditionally replication-competent mutant expressing both subunits of mIL-12 (M002) and its evaluation in a syngeneic neuroblastoma murine model. IL-12 induces a helper T cell subset type 1 response, which may induce more durable antitumor effects. In vitro studies showed that, when infected with M002, both Vero cells and murine Neuro-2a neuroblastoma cells produced physiologically relevant levels of IL-12 heterodimers, as determined by ELISA. M002 was cytotoxic for Neuro-2a cells and human glioma cell lines U251MG and D54MG. Neurotoxicity studies, as defined by plaque-forming units/LD(50), performed in HSV-1-sensitive A/J strain mice found that M002 was not toxic even at high doses. When evaluated in an intracranial syngeneic neuroblastoma murine model, median survival of M002-treated animals was significantly longer than the median survival of animals treated with R3659, the parent gamma(1)34.5(-) mutant lacking any cytokine gene insert. Immunohistochemical analysis of M002-treated tumors identified a pronounced influx of CD4(+) T cells and macrophages as well as CD8(+) cells when compared with an analysis of R3659-treated tumors. We conclude that M002 produced a survival benefit via oncolytic effects combined with immunologic effects meditated by helper T cells of subset type 1.
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PMID:Engineered herpes simplex virus expressing IL-12 in the treatment of experimental murine brain tumors. 1068 59

Clinical impact of s.c. administration of IL-2 and/or IFN alpha was studied in 23 pediatric patients with Hodgkin lymphoma (IFN alpha group) and sarcoma, non-Hodgkin lymphoma, peripheral neuroepitelioma, neuroblastoma, and embryonic carcinoma (IL-2 + IFN alpha group) after autologous PBSC transplantation. Expression of CD3, CD4, CD8, CD25, CD38, CD56, CD71, CD122, and HLA-DR antigens, serum level of the soluble IL-2R alpha, and NK activity against K562 cell line were evaluated in 11 patients representative for both types of immunotherapy. T and, more markedly, NK cell proliferation, induction of activation markers on the surface of T and NK subsets, and elevation of sIL-2R alpha concentrations were seen in the IL-2 + IFN alpha subgroup. In the IFN alpha subgroup, the total number of lymphocytes and expression of activation markers remained unchanged, but the number of CD8+ T cells increased at the expense of CD4+ T and NK cells during the therapy. Cytotoxic activity against K562 cells was not influenced by the immunotherapy in either subgroup. No significant clinical benefit of the immunotherapy was seen in these patients compared to 27 control patients with relevant diagnoses who did not receive immunotherapy.
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PMID:Clinical ineffectiveness of IL-2 and/or IFN alpha administration after autologous PBSC transplantation in pediatric oncological patients. 1068 13

The effectiveness of cell-mediated immunotherapy for cancer can be limited by loss-of-antigen mutations that occur during tumor growth. In neuroblastoma, amplification of the MYCN oncogene correlates with rapid tumor progression and a poor prognosis overall. We propose that the MYCN protein, the high-level expression of which is required for maintenance of the malignant phenotype, would be an ideal target for vaccine therapy. The MYCN-derived S9K peptide (amino acids 7-15; STMPGMICK), which contains an HLA-A1 binding motif, was used to generate CTLs from the peripheral blood lymphocytes of an HLA-A1+ healthy donor and an HLA-A1+ patient with MYCN-amplified neuroblastoma These CTL lines specifically lysed HLA-matched, MYCN-amplified neuroblastoma tumor cells. They did not lyse either HLA-mismatched, MYCN-amplified, or matched/nonmatched, non-MYCN-amplified tumor cells. The CTL activity was inhibited by a monoclonal antibody to a class I HLA monomorphic determinant but not by one specific for HLA class II, consistent with a class I-restricted mechanism of cytotoxicity. Antibodies to CD8, but not those to CD4, also inhibited CTL activity, identifying CD8+ lymphocytes as the effector cell population. These results show that MYCN-derived peptides can serve as tumor-specific antigens and suggest a rational approach to cell-mediated immunotherapy for MYCN-amplified neuroblastoma.
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PMID:Lysis of MYCN-amplified neuroblastoma cells by MYCN peptide-specific cytotoxic T lymphocytes. 1076 79

To infect target cells, the human immunodeficiency virus (HIV) type I (HIV-1) must engage not only the well-known CD4 molecule, but it also requires one of several recently described coreceptors. In particular, the CXCR4 (LESTR/fusin) receptor allows fusion and entry of T-tropic strains of HIV, whereas CCR5 is the major coreceptor used by primary HIV-1 strains that infect macrophages and CD4(+) T-helper cells (M-tropic viruses). In addition, the alpha chemokine SDF1alpha and the beta chemokines MIP1alpha, MIP1beta, and RANTES, natural ligands of CXCR4 and CCR5, respectively, are potent soluble inhibitors of HIV infection by blocking the binding between the viral envelope glycoprotein gp120 and the coreceptors. Approximately two-thirds of individuals with acquired immunodeficiency syndrome (AIDS) show neurologic complications, which are referred to a syndrome called AIDS dementia complex or HIV-1-associated cognitive/motor complex. The HIV-1 coat glycoprotein gp120 has been proposed as the major etiologic agent for neuronal damage, mediating both direct and indirect effects on the CNS. Furthermore, recent findings showing the presence of chemokine receptors on the surface of different cell types resident in the CNS raise the possibility that the association of gp120 with these receptors may contribute to the pathogenesis of neurological dysfunction. Here, we address the possible role of alpha and beta chemokines in inhibiting gp120-mediated neurotoxicity using the human neuroblastoma CHP100 cell line as an experimental model. We have previously shown that, in CHP100 cells, picomolar concentrations of gp120 produce a significant increase in cell death, which seems to proceed through a Ca(2+) - and NMDA receptor-dependent cascade. In this study, we gained insight into the mechanism(s) of neurotoxicity elicited by the viral glycoprotein. We found that CHP100 cells constitutively express both CXCR4 and CCR5 receptors and that stimulation with phorbol 12-myristate 13-acetate down-regulates their expression, thus preventing gp120-induced cell death. Furthermore, all the natural ligands of these receptors exerted protective effects against gp120-mediated neuronal damage, although with different efficiencies. These findings, together with our previous reports, suggest that the neuronal injury observed in HIV-1 infection could be due to direct (or indirect) interactions between the viral protein gp120 and chemokine and/or NMDA receptors.
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PMID:gp120 induces cell death in human neuroblastoma cells through the CXCR4 and CCR5 chemokine receptors. 1082 Jan 98

We present a unique case of a 9-month-old infant with a left adrenal neuroblastoma with sarcoid reaction, detected by mass screening. There was no clinical evidence indicating systemic sarcoidosis or pulmonary mycobacterial infection. Histological examination of the resected adrenal tumor revealed many noncaseating epithelioid granulomas with lymphocytic infiltrate, composed of epithelioid cells and few giant cells, arising in tumor parenchyma and fibrovascular stroma. Most of the lymphocytes in the granulomas were CD3- or CD45RO-positive T cells, with fewer being CD20-positive B cells. The lymphocytes in the epithelioid granulomas expressed CD4 or CD8, but not CD56 and CD57. CD4-positive cells were observed more within the granulomas (internal area) than in the surrounding area (external area) of the same granulomas, while most of the CD8-positive cells were seen consistently at the outer margin of the granulomas (marginal zone). CD45RA-positive T cells were observed predominantly in the external area. The results of immunostaining demonstrated that lymphocytes in granulomas of this case showed the same distribution pattern as that seen in systemic sarcoidosis. Although the sarcoid reaction is a phenomenon known to be associated with the region of cancer, granuloma within the primary neuroblastoma is extremely rare. The sarcoid reaction in the present case of neuroblastoma may be associated with a delayed-type hypersensitivity reaction, and its significance and relevance still remain obscure.
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PMID:Sarcoid reaction in primary neuroblastoma: case report. 1100 Mar 36


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