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)

Preliminary clinical trials using cryopreserved autologous bone marrow reinfusion have now been carried out at our institution in 5 children and 2 adults with advanced stages of neuroblastoma, rhabdomyosarcoma, non-Hodgkin's lymphoma and small cell carcinoma of the lung. Normal numbers of in vitro colony forming cells (CFU-C) were obtained from these patients despite prior courses of combination chemotherapy. The dose of marrow cells cryopreserved ranged from 1-6 X 10(8) cells/kg and recovery of CFU-C after thawing averaged 50%. Partial or complete hematologic reconstitution was achieved in all patients. The time for recovery ranged from 10-43 days for leukocytes (greater than 1000 cells/mm3) and 23-45 days for platelets (greater than 50,000/mm3). Two patients have died of interstitial pneumonitis due to cytomegalovirus. Three patients have died of recurrent tumor at 40, 48 and 156 days post-transplant. Two patients have had significant therapeutic benefit. One of these had a stable partial response permitting the use of further post-transplant therapy and is alive and well 16+ months post-transplant. The other patient had a complete response and remains tumor-free 25+ months following therapy. We conclude: 1) Autologous bone marrow reinfusion permits hematologic reconstitution following marrow-ablative therapy. 2) A quantity of marrow sufficient for this purpose remains viable following cryopreservation even when obtained from patients previously exposed to chemotherapy. 3) Autologous bone marrow reinfusion now allows the exploration of more intensive cytoreductive therapy in selected malignancies.
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PMID:Autologous bone marrow transplantation in the treatment of selected human malignancies: The Johns Hopkins Oncology Center Program. 40 Jun 94

While first described as antiviral agents, interferons (IFNs) exhibit significant antiproliferative and antitumor effects as well. IFN alpha has been successfully used in clinical trials to treat several malignancies, including leukemias and certain solid tumors. While many cell types have been studied for IFN alpha receptor expression, very little is known about receptor expression on human neuroendocrine cells. Using a novel anti-IFN alpha receptor monoclonal antibody, we examined IFN alpha receptor expression in 10 human cell lines derived from tumors of neuroendocrine origin, including neuroblastoma, neuroepithelioma and small cell lung carcinoma. All cell lines studied displayed a similar pattern of IFN alpha receptor expression and 5 of 8 cell lines demonstrated reduced thymidine incorporation following IFN alpha treatment. Addition of exogenous IFN alpha caused a decrease in IFN alpha receptor expression, while differentiating agents, such as phorbol esters and retinoic acid, induced an increase in receptor number without altering receptor affinity.
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PMID:Detection of functional interferon alpha receptors in human neuroendocrine tumor cell lines using a new monoclonal antibody. 131 82

A beta subunit of the neuronal nicotinic receptor, sharing 88% homology with the rat beta 4 subunit, has been cloned from a human neuroblastoma cell line. The gene encoding the human beta 4 subunit is expressed in association with the alpha 3 gene in neuroblastoma and small-cell lung carcinoma cell lines. Patch-clamp experiments and radioligand binding assays confirm that these neuroendocrine tumor cell lines express functional neuronal nicotinic receptors. We suggest that these receptors might play a crucial role in the control of neurotransmitter and hormone secretion from neurosecretory human tumors.
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PMID:Neuronal-type nicotinic receptors in human neuroblastoma and small-cell lung carcinoma cell lines. 133 Jun 82

Human neuroblastoma cells of sympathetic origin have been used for studying the effects of diosmin and its metabolite diosmetin (vasotonic agent) on amine reuptake systems. Neuroblastoma cells take up 3H-dopamine in a specific and time-dependent manner. 3H-dopamine uptake was dose-dependently inhibited by the known antagonist desipramine. Diosmin did not affect 3H-dopamine uptake at concentrations as high as 1 mM. On the other hand the aglycone metabolite of diosmin, diosmetin, inhibited 3H-dopamine uptake in a dose-dependent manner (IC50 = 4 microM). Diosmetin inhibited 3H-dopamine uptake in control and differentiated neuroblastoma cells, as well as in small-cell lung carcinoma cells. Furthermore diosmetin also inhibited 3H-serotonin uptake in both cell types. These results demonstrate that some flavonoids act as antagonists of plasma membrane amine transporters at the molecular level and suggest that inhibition of amine reuptake at the level of peripheral sympathetic nerve terminals could be responsible for the increased vascular tone observed in vivo after treatment with these drugs.
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PMID:Amine uptake inhibition by diosmin and diosmetin in human neuronal and neuroendocrine cell lines. 133 24

The c-Myc protein is a potential activator of transcription, with the ability to bind in a heterodimer form with Max to DNA sequences containing the core hexanucleotide sequence CAC(G/A)TG. These properties are shared with L-Myc, a homologous oncoprotein expressed in small cell lung carcinoma cells; with N-Myc, expressed in neuroblastoma cells; and with avian v-Myc, the c-Myc homolog expressed by a chicken retrovirus. The c-Myc, and probably v-Myc, proteins also have nonspecific DNA binding function, which may improve the kinetics of specific DNA binding. Curiously, this domain appears not to be conserved in L-Myc or N-Myc [22]. The data that have accumulated to date are consistent with a model in which a c-Myc/Max heterodimer positively regulates the transcription of growth-related genes, with Max homodimer functioning as a negative regulator of the same genes (Fig. 4) [55]. Max is expressed constitutively at low levels, whereas c-Myc is expressed at low levels in quiescent cells, but high levels of c-Myc are induced by mitogenic stimulation [56]. Thus, in proliferating cells c-Myc/Max heterodimers might bind to the regulatory elements of growth-related genes, where the c-Myc TAD might stimulate transcription. Conversely, in quiescent cells with little c-Myc present, Max homodimers might predominate. They might bind to exactly the same regulatory elements, but due to the apparent absence of a TAD in Max [36], transcription might be repressed. Validation of this model will require the demonstration of clear regulation of a physiological promoter of a growth-related gene by c-Myc/Max. Although it is widely believed that Myc proteins function as transcriptional activators, this hypothesis has only been conclusively supported recently [57, 58]. A theory that c-Myc plays a role in DNA replication is not as well substantiated at this point. It is even possible that Myc might be involved in both transcription and replication. Although the function of these fascinating proteins has been enigmatic for a decade, the rate of progress in our understanding of Myc function is accelerating. Such progress will undoubtedly lead to a deeper appreciation of this protein, which lies at the crossroads of cellular proliferation and oncogenesis.
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PMID:DNA binding by the Myc oncoproteins. 136 64

Human CD34+ hematopoietic stem cells were purified using a new technology in which monoclonal antibodies are covalently immobilized on polystyrene surfaces. The CD34+ cell isolation scheme involved three sequential processes: (1) purification of bone marrow mononuclear cells; (2) enrichment of CD34+ cells using covalently immobilized soybean agglutinin; and (3) positive selection of CD34+ cells using polystyrene surfaces coated with the anti-CD34 monoclonal antibody ICH3. CD34+ cells purified by this process have both low-to-medium forward light scatter and low 90 degrees light-scatter properties. Moreover, the purified CD34+ cells are greater than 85% viable, express appropriate characteristic surface antigens, and are 10-50-fold enriched in short- and long-term hematopoietic activity. CD34+ cells collected in this manner from bone marrow samples contaminated with radiolabeled breast carcinoma, neuroblastoma, acute myelogenous leukemia, or small cell lung carcinoma cells were 99.9% depleted of the tumor cells. The CD34+ cell selection devices are sterile and are easily scaled-up to process clinical scale bone marrow samples.
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PMID:Rapid isolation of human CD34 hematopoietic stem cells--purging of human tumor cells. 137 43

The secretion of insulin-like growth-factor-binding proteins (IGFBPs) and expression of the genes encoding IGFBP-1, IGFBP-2 and IGFBP-3 have been studied in a panel of cell lines derived from breast carcinomas, Wilms' tumour, neuroblastoma, retinoblastoma, colon carcinoma, liver adenocarcinoma, Burkitt's lymphoma and a non-small-cell lung carcinoma. All cell lines, with the exception of the Burkitt's lymphoma cell line, secreted IGFBPs, as detected by affinity labelling. A 34-kDa BP was present in the conditioned media of all IGFBP-secreting cell lines, whereas BPs ranging from 18 kDa to 53 kDa were variably secreted. All IGFBP-secreting cell lines expressed the IGFBP-2 gene as determined by Northern blot analysis. The Wilms' tumour, the neuroblastoma and the retinoblastoma cell line expressed the IGFBP-2 gene only. All other cell lines, with the exception of the Burkitt's lymphoma, expressed the IGFBP-2 gene and, in addition, either the IGFBP-1 gene and/or the IGFBP-3 gene. IGFBP-1 gene expression could be detected by reverse transcriptase polymerase chain reaction only. IGFBP-3 gene expression was detected by Northern blot analysis, but transcripts were less abundant than IGFBP-2 mRNAs. These findings indicate that the expression of multiple BP genes and the secretion of BPs may be a common property of tumour cells.
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PMID:Insulin-like growth-factor-binding protein gene expression and protein production by human tumour cell lines. 137 87

alpha-Bungarotoxin (alpha Bgtx) is a toxin known to interact with muscle nicotinic receptors and with some neuronal nicotinic receptors. We show that alpha Bgtx binding sites are also expressed in nonmuscle and nonneuronal human cells, including small cell lung carcinoma and several epithelial cell lines. These receptors are immunologically related to the alpha Bgtx receptors of unknown function described in the nervous system and in the IMR32 neuroblastoma cell line and are distinct from muscle nicotinic receptors. We have also cloned from IMR32 cells the human alpha 5-nicotinic receptor subunit, which is supposed to participate in the formation of alpha Bgtx receptors. Transcripts corresponding to the alpha 5-subunit gene were found not only in neuroblastoma cells but also in all the cell lines expressing alpha Bgtx receptors, with the exception of the TE671 cell line, whose nicotinic receptor subunits are of the muscle type. We conclude that both alpha Bgtx receptors and the alpha 5-nicotinic subunit gene are not neuron-specific, as previously thought, but are expressed in a number of human cell lines of various origin.
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PMID:Neuronal-type alpha-bungarotoxin receptors and the alpha 5-nicotinic receptor subunit gene are expressed in neuronal and nonneuronal human cell lines. 154 48

N-myc expression has been reported in neuroblastoma, retinoblastoma and small cell lung carcinoma. Increased expression associated with gene amplification in neuroblastoma correlates with disease stage and prognosis. N-myc expression has been observed in diverse murine tissues during early stages of development with loss of expression in later stages. Abelson murine leukemia virus (A-MuLV)-transformed pre-B cells express N-myc, whereas mature B cells do not. To determine whether human B-lymphocyte precursors also have increased N-myc expression, we extracted DNA and RNA from representative cell lines, prepared Southern and Northern blots and examined them with the N-myc probe, pNB-1. RNA from the following B-cell developmental stages were examined. One null, 1 pre-pre-B, 3 pre-B (including pre-B-lymphoblastic leukemia, a poor prognostic category) and 5 mature B. Neuroblastoma cells and tissues served as positive controls; negative controls included human muscle, placenta, epithelial cell lines, monocytic, promyelocytic, and T-cell lines. N-myc expression was detected in neuroblastoma cells, but in none of the mature human B or B-lymphocyte precursor cells. Additional immunocytochemical studies performed for N-myc nuclear protein likewise failed to detect this gene product. We conclude that human pre-B cells, unlike murine B-cell precursors, do not express increased levels of N-myc RNA. Expression of this oncogene in human neoplastic B cells does not appear to correlate with developmental stage or prognostic group.
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PMID:Human B-lymphocyte precursors do not express the N-myc gene. 157 Oct 96

We have tested 36 patients with the Lambert-Eaton myasthenic syndrome for serum antibodies to voltage-gated calcium channels by using an immunoprecipitation assay with [125I] omega-conotoxin-labeled voltage-gated calcium channels extracted from a human neuroblastoma cell line, SKN-SH. Forty-four percent of these patients had significant levels of antibody (30-1,466 pM) compared with healthy control individuals (less than 15 pM). The incidence of positive sera in patients without associated small cell lung carcinoma (61%) was greater than in those patients with small cell lung carcinoma (28%). Results correlated strongly with results obtained using voltage-gated calcium channels extracted from the small cell lung carcinoma line, MAR5. Anti-voltage-gated calcium channel antibody titers did not correlate with disease severity across individuals, but longitudinal studies in 2 patients receiving immunosuppressive therapy showed a clear inverse relation between antibody titer and an electromyographic index of disease severity. The incidence of positive sera among patients with other neurological disorders was not significant, but 8 of 12 patients with rheumatoid arthritis or systemic lupus erythematosus had raised titers (30-82 pM). We conclude that the antibodies detected in this assay are heterogeneous and that some of them are likely to be implicated in this disorder of neuromuscular transmission. The assay should prove useful as an additional diagnostic aid in patients with Lambert-Eaton myasthenic syndrome.
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PMID:Calcium channel autoantibodies in the Lambert-Eaton myasthenic syndrome. 164 44


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