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)

Genomic amplification of the oncogene N-myc is associated with rapid tumor progression and poor prognosis in patients with neuroblastoma (NB). However, 40% of NBs which lack N-myc amplification are also clinically aggressive. Factors other than N-myc copy number must therefore play a role in determining tumor progression in these NBs. We have established an unusual human NB cell line (NBL-S) from the primary tumor of a patient with rapidly progressive disease which lacks N-myc amplification. The doubling time in vitro (48 h) and the time from injection of 2 x 10(7) cells to detectable tumors in nude mice (46 days) in similar to NB cell lines with amplified N-myc. However, karyotype analysis reveals no evidence of double minutes (DMs), homogeneously staining regions (HSRs), or chromosome 1p deletions, features commonly seen in NB cell lines. The cells have the cell surface phenotype typical of N-myc amplified NB (HLA-A,B,C negative and HSAN 1.2 positive), and similar to other NB cell lines, N-myc RNA and protein are expressed. Interestingly, the half-life of the N-myc protein in NBL-S is prolonged (approximately 100 min) compared to the short N-myc protein half-life previously described in N-myc amplified NB cell lines (approximately 30 min). Because N-myc protein is thought to have a regulatory role, prolongation of the half-life of this protein may be an important factor in the regulation of growth in NBs which lack N-myc amplification and rapidly progress.
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PMID:Prolonged N-myc protein half-life in a neuroblastoma cell line lacking N-myc amplification. 228 1

Immunological analysis is complementary to morphological investigation to detect bone marrow (BM) metastases in neuroblastoma patients. It is essential at time of BM harvest for an autograft, since it is the only examination which allows a precise evaluation of the graft contamination by malignant cells. Simple indirect immunofluorescence staining with anti-neuroblastoma monoclonal antibodies (UJ13A and HSAN 1-2) allows a final detection of about 1% malignant cells in the BM, and 1% when cells are gathered in clumps. The use of an immunocytochemical method (alkaline phosphatase) together with double immunofluorescence staining permits to detect as few as one residual neuroblastoma cell in 10(4) normal ones. These two methods used together have allowed to assess the neuroblastoma nature of rare isolated cells with pseudo-lymphocytic aspect.
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PMID:[The significance of immunological analysis for the detection of residual neuroblasts in bone marrow]. 328 68

The derivation of an IgG1k monoclonal antibody (HSAN 1.2) recognizing a cell membrane determinant on human neuroblastoma cells is reported. The determinant was found on all 17 cultured human neuroblastoma cells that were tested, but the density of the antigen varied widely on different cell lines. The antibody also bound to fresh and cultured Wilm's tumor cells, retinoblastoma cells, and one of two Ewing's sarcoma cell lines tested, it did not bind to mouse neuroblastoma cells, normal fibroblasts, blood, or bone marrow. Tumor cells that did not stain with HSAN 1.2 included glioma, medulloblastoma, melanoma, rhabdomyosarcoma, mesenchymoma, leukemia, and lymphoma cells. The distribution of the HSAN 1.2 antigen in normal tissues was confined to brain and newborn kidney. As few as 0.1% tumor cells in bone marrow aspirates were detectable by fluorescein-conjugated HSAN 1.2 antibody and flow cytometry. This antibody should be useful for the discrimination of neuroblastoma from other pediatric malignancies, for the detection of tumor cells in metastatic sites such as bone marrow, and for selective removal of neuroblastoma cells from marrow harvested for autologous transplantation.
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PMID:Monoclonal antibody recognizing a human neuroblastoma-associated antigen. 332 7

On 80 occasions 4 iliac biopsy trephines and 4 iliac aspirations were performed in 37 children with neuroblastoma at various stages of the disease. In 38 of these procedures, tumour cells were detected. In 24% of cases, both trephines and aspirates were positive, whereas in 63% neuroblastoma cells were detected only on the trephines and in 13% only on the aspirates. In addition, in 37% of the stagings, only one out of the 8 investigations was abnormal. Only in one of 33 pathological cases, was BM involvement diagnosed on trephine imprint. No involvement was ever observed on tibial and sternal aspirates without iliac involvement. Immunological studies with two monoclonal antibodies HSAN 1-2 and UJ13A were performed on 56 occasions. Cytohistological and immunological studies were concordant in 39. In 3 studies, the antigens recognized by the two monoclonal antibodies were not expressed by the initial tumour and in 3 additional studies immunological results were falsely negative; but in 11 cases monoclonal antibodies identified residual malignancy despite normal cytohistology. From this study, biopsies appear more helpful to detect malignant cells than aspirates. Immunological staining clearly leads to a better definition of tumour cells in aspirates.
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PMID:Histological, cytological and immunological analyses are complementary for the detection of neuroblastoma cells in bone marrow. 353 65

Variables effecting removal of neuroblastoma cells from bone marrow using monoclonal antibodies and magnetic immunobeads were studied. Human neuroblastoma cell lines were labeled with the supravital DNA stain Hoechst 33342, seeded into normal bone marrow, incubated with monoclonal antibodies recognizing neuroblastoma cell surface antigens (HSAN 1.2, antibody 459, antibody 390, BA-1, and Leu-7), and then mixed with magnetic microspheres coated with goat anti-mouse immunoglobulin. Tumor cells that attached to the magnetic immunobeads were then removed from the marrow with magnets. The efficacy of tumor cell removal depended on the amount of monoclonal antibody bound to tumor cells and the immunobead/tumor cell ratio. In addition, two cycles of purging with both monoclonal antibodies and immunobeads was superior to one cycle. Using a cocktail of the five antibodies, 3 to 4 logs of tumor cells could be depleted from marrow with good recovery of viable hematopoietic cells.
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PMID:Model system for removing neuroblastoma cells from bone marrow using monoclonal antibodies and magnetic immunobeads. 375 28

The majority of human neuroblastomas express low to undetectable levels of major histocompatibility complex (MHC) class I and II antigens (MHC-I and -II). We studied the effects of gamma interferon (gamma-IFN) transduction on expression of these antigens in six human neuroblastoma cell lines with and without genomic amplification of the N-myc oncogene. All six were stably transduced with an MoMLV-based gamma-IFN retroviral vector (DAh gamma-IFN). G418-resistant cells were assayed for MHC-I, MHC-II, B7-1, and neuroblastoma-associated antigen expression, as well as for gamma-IFN levels in cell culture supernatants. Sustained gamma-IFN production, 2 to > 1000 units/10(6) cells/d, was attained for five of six transduced cell lines and persisted for up to 9 months. This resulted in marked upregulation of MHC-I and MHC-II expression in LA-N-1, LA-N-6, and CHLA-127 cells and moderate upregulation in SK-N-Fi and SK-N-AS cells. One cell line (LA-N-1) had marked induction of MHC-I and MHC-II despite marginal levels of gamma-IFN production. Expression of CD28 ligand B7-1 (as determined by BB1 antibody) remained unchanged in all gamma-IFN-transduced cell lines tested. Expression of several neuroblastoma-associated antigens (NKH1A, 126-4, HSAN 1.2, HNK, 459, and 390) was upregulated in some of the gamma-IFN-transduced cell lines. These results demonstrate that preparation of gamma-IFN expressing neuroblastoma cells for immunotherapeutic purposes is feasible and that gamma-IFN transduction results in phenotypic changes that may improve immunogenicity of human neuroblastoma cells.
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PMID:Sustained cytokine production and immunophenotypic changes in human neuroblastoma cell lines transduced with a human gamma interferon vector. 852 60

The aim of this study was to evaluate the specificity of a number of monoclonal antibodies (MAbs) used for immunological in vitro purging of stem cell grafts from neuroblastoma patients. The extent of cross-reactivity of 10 neuroblastoma-specific MAbs (NB-MAb) with CD34+ stem cells from 14 leukapheresis products was analyzed. The level of cross-reactivity was analyzed on a Coulter (Fullerton, CA) flow cytometer using biotinylated NB-MAbs. There was a marked difference in the reactivity of the ten NB-MAbs with CD34+ stem cells. The antibodies could be divided into three groups with increasing levels of cross reactivity. Four antibodies (126-4, 5.1 H11, UJ127.11, and 14.G2a) all reacted with median levels of less than 2% (range 0.0 to 5.4) of CD34+ stem cells (median of 14 patients). Another three antibodies reacted with a median of 3.1-4.1% of the stem cells (UJ13A, Ab390, and Ab459) but with a wide range (0.2 to 25.6). Finally, M340, HSAN 1.2, and antiThy-1 reacted with a median of 9-16% of the stem cells (range 0.6 to 51.5). We conclude that there is a significant variation in the proportion of CD34+ stem cells reacting with each of the ten neuroblastoma antibodies investigated in this study. Therefore, to avoid a significant loss of CD34+ cells from the stem cell product, we find it important to carefully consider which antibodies to use for immunomagnetic purging.
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PMID:Monoclonal antibodies with neuroblastoma specificity: a flow cytometric analysis of cross-reactivity with CD34+ hematopoietic stem cells. 1117 99