Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cell line AG-F was isolated from the marrow of a neuroblastoma patient undergoing myeloablative treatment and autologous bone marrow rescue. A year later, the patient developed a Hodgkin's type lymphoma. AG-F cell line demonstrated an unusual phenotype, lacking surface CD2 and CD3, but expressing high levels of CD4, CD5, CD7, CD29, and CD45RO. Markers associated with Hodgkin's lymphoma cells, CD15 and CD30, were also positive. AG-F cells grow in suspension in clusters of 50-200 cells, with a doubling time of 9 h. They can also grow in serum-free medium and form tumors in nude mice. AG-F cells have amplified N-myc and c-myc and high levels of the corresponding mRNA transcripts. Cytogenetic analysis revealed a DNA index by flow cytometry of near tetraploid cells and a karyotype of 85-87 chromosomes, with consistent abnormalities in chromosomes 1, 5, and 9. Gene rearrangement studies revealed rearrangement of the beta gene of the T-cell receptor. AG-F cells secrete high levels of IL-6, IL-8, IL-10, and GM-CSF. Cell adherence and formation of long processes could be induced by fibronectin and were enhanced by exposure to PMA. Cells exposed to phorbol myristate acetate (PMA) had increased expression of CD11a, CD11b, CD18, CD45RO, and HLA-DR, whereas expression of CD15 and CD30 was markedly decreased. Similarly, the level of c-myc and N-myc oncoproteins and the levels of the cytoskeletal proteins, actin, tubulin, and vimentin markedly decreased early after PMA-induced differentiation.
...
PMID:Isolation and characterization of an early T-helper/inducer cell line with a unique pattern of surface phenotype, constitutive cytokine secretion and myc oncogene expression. 825 4

Fifteen children 4 years of age or under (8-46 months), weight 7.8 to 17 kg, underwent 44 peripheral blood stem cell (PBSC) collections. Diagnoses included PNET/medulloblastoma (five), neuroblastoma (five), and others (five). PBSCs were collected following G-CSF/GM-CSF or chemotherapy plus G-CSF/GM-CSF mobilization. All PBSC collections were well tolerated. The average yield per collection was 6.80 x 10(8) mononuclear cells/kg (1.1-30 x 10(8)/kg) or 57.60 x 10(6) CD34+/kg (1.37 to 480 x 10(6)/kg). Eight patients underwent stem cell transplantation following myeloablative chemotherapy. Six of the eight children who received PBSC following myeloablative therapy also received autologous bone marrow (0.7 to 3.6 x 10(8) MNC/kg). One heavily pretreated patient experienced delayed hematologic reconstitution, while the remaining seven patients had a median ANC recovery to > 0.5 x 10(3)/microliter by day +10 (9-11 days) and platelets > 50 x 10(3)/microliter by day +15 (12-17 days). Seven patients received PBSCs following repetitive submyeloablative chemotherapy (ICE: ifosfamide 1.8 g/m2/day, etoposide 100 mg/m2/day x 5, carboplatin 400 mg/m2/day x 2) or other similar combination chemotherapy. Median days to recover ANC > or = 1 x 10(3)/microliter and platelets > or = 100 x 10(3)/microliter in children receiving ICE + PBSCs were 10 and 14 days, respectively, compared with 16 and 22 days in children receiving ICE + G-CSF in historical controls. In conclusion, collection and use of PBSCs to support either myeloablative chemotherapy or multicycle submyeloablative chemotherapy is well tolerated and may enhance hematological recovery in young children and infants.
...
PMID:Collection and use of peripheral blood stem cells in young children with refractory solid tumors. 902 45

We have examined the antitumor effect of murine neuroblastoma cells (C1300) engineered to produce cytokines. Retrovirally transduced cells with human interleukin-2 (IL-2) or murine GM-CSF gene, but not murine IL-4 gene, abolished their tumorigenicity in syngeneic mice, although their in vitro growth rate and expression of class I antigens of the major histocompatibility complex were unchanged. Inoculation of wild-type cells into the mice, which had rejected IL-2 or GM-CSF producers, did not develop tumors, indicating that protective immunity was induced. In an experimental hematogenous metastasis model, we found that the numbers of metastatic foci in the liver caused by intravenous administration of IL-2 or GM-CSF producers were significantly reduced compared with those by the injection of wild-type or vector virus-transduced cells. No significant differences in their adhesiveness to extracellular matrices and ability to differentiate were observed among parent and transduced cells. Thus, these results indicate that IL-2 or GM-CSF secretion, in the vicinity of neuroblastoma cells, produced antitumor effect and reduced metastatic ability.
...
PMID:Impaired tumorigenicity and decreased liver metastasis of murine neuroblastoma cells engineered to secrete interleukin-2 or granulocyte macrophage colony-stimulating factor. 957 Feb 97

Localized cytokine therapies with recombinant monoclonal antibody-cytokine fusion proteins, designated immunocytokines, have become of increasing interest for tumor immunotherapy, since they direct immunomodulatory cytokines into the tumor microenvironment. To investigate their mechanisms of action in a variety of syngeneic tumor models, recombinant mouse cytokines IL2 and GM-CSF were engineered as fusion proteins to the carboxyl terminus of a chimeric rat/mouse antitransferrin receptor antibody, ch17217 and expressed in stable-transfected Chinese hamster ovary cells. The recombinant immunocytokines were readily purified by affinity chromatography and their binding characteristics were identical to those shown for the ch17217 antibody. The IL2 immunocytokine had an activity similar to recombinant mouse IL2, whereas the GM-CSF immunocytokine had enhanced cytokine activity relative to recombinant mouse GM-CSF. The clearance rates of ch17217 and the GM-CSF and IL2 immunocytokines were relatively similar with elimination phases (t1/2alpha) of 1.8 h and distribution phases (t1/2beta) of 83, 88, and 91 h, respectively. Both immunocytokines demonstrated effective antitumor activity by suppressing the growth of hepatic metastases of mouse neuroblastoma and pulmonary metastases of mouse colon carcinoma in syngeneic A/J and BALB/c mice, respectively. These results indicate that biologically effective IL2 and GM-CSF immunocytokines combine the targeting ability of an antitransferrin receptor monoclonal antibody with the immunomodulatory functions of each cytokine. Because of the universal expression of the transferrin receptor on mouse tumor cell lines, these constructs should prove useful to determine their efficacy in a wide variety of syngeneic mouse tumor models and to perform detailed studies of their modes of action.
...
PMID:Recombinant immunocytokines targeting the mouse transferrin receptor: construction and biological activities. 966 50

Leptomeningeal (LM) neoplastic metastases are painful, debilitating and inevitably lethal. Intrathecal (IT) anti-tumor antibodies may have therapeutic potential. We evaluated 3F8, an anti-G(D2) murine IgG(3) monoclonal antibody (MAb) in the treatment of human melanoma (SKMEL-1) and neuroblastoma (NMB7) xenografts in athymic rats. Both tumors were lysed efficiently in vitro by 3F8 in the presence of rat neutrophils or rat complement. Antibody-dependent cellular cytotoxicity (ADCC) was not augmented by recombinant human GM-CSF (rhGM-CSF), rhG-CSF, recombinant rat MIP-2 (rrMIP-2) or lipopolysaccharide (LPS). In vivo, continuous intraventricular administration of 3F8 and LPS prevented tumor engraftment, retarded tumor growth and eradicated 3-day-old established xenografts whereas 3F8 alone, LPS alone or F(ab)'(2) plus LPS had no or only marginal effects. Tumor establishment in brain was completely prevented in 36% of animals implanted with SKMEL-1 and 65% of animals implanted with NMB7. Twenty percent of established xenografts around the brain were eradicated but all animals had persistent tumor in the lumbosacral meninges despite treatment. Continuous intraventricular infusion of LPS produced a variable polymorphonuclear (PMN) pleocytosis that was dose-dependent. Continuous intraventricular infusion of 3F8 produced immunohistochemically detectable attachment to 86% of persistent brain deposits of tumor but <1% of spinal lumbosacral deposits. We conclude that regional therapy with anti-G(D2) MAb could target neutrophils to inhibit LM tumor growth. However, optimal activation and mobilization of neutrophils into the cerebrospinal fluid (CSF) and improved penetration of MAb to tumor sites remain critical variables.
...
PMID:Treatment of neoplastic meningeal xenografts by intraventricular administration of an antiganglioside monoclonal antibody, 3F8. 1040 68

We examined whether antitumor immunity could be generated by the inoculation of cytokine-producing murine neuroblastoma cells (C1300), and whether the immunity might be effective for the established tumors of wild-type (wt) cells. For that purpose, we transduced low immunogenic C1300 cells with interleukin-2 (IL-2), GM-CSF, or IL-4 genes. A loss of tumorigenicity in syngeneic mice was observed using IL-2- and GM-CSF- but not IL-4-producing C1300 cells, although their in vitro growth rates were not affected by the transduction. The syngeneic mice that had rejected IL-2 or GM-CSF producers did not develop tumors of wt cells inoculated subsequently, but formed tumors of irrelevant syngeneic mammary tumor cells. Accordingly, the inoculation of IL-2 or GM-CSF producers into immunocompetent mice generated tumor-specific acquired immunity. The induced immunity using IL-2 or GM-CSF producers was also effective in eradicating established subcutaneous tumors of wt cells and in reducing the number of preexisting metastatic foci in the liver. These data suggest a potential application of IL-2- or GM-CSF-producing syngeneic tumor cells for the treatment of low immunogenic neuroblastomas.
...
PMID:Induced immunity by expression of interleukin-2 or GM-CSF gene in murine neuroblastoma cells can generate antitumor response to established tumors. 1050 49

Neutrophils and mononuclear cells (MNC) can mediate antibody-dependent cellular cytotoxicity (ADCC) against cancer cells. To study cytotoxicity and growth inhibition of neuroblastoma cells by neutrophils and MNC with chimeric anti-disialoganglioside (GD2) monoclonal antibody (mAb) ch14.18, we developed digital image microscopy scanning (DIMSCAN) assays that measure fluorescence of target cells in 96-well plates after 6-18 h (cytotoxicity assay) or 7 days (growth assay). Neuroblastoma cell lines (GD2-positive: SMS-KCN, SMS-LHN, LA-N-1; GD2-negative: SK-N-SH) were preloaded with calcein acetoxymethyl ester for the cytotoxicity assay or labeled in situ after 7 days of culture with fluorescein diacetate in the growth assay. Fluorescence, as quantified by DIMSCAN, was correlated with neuroblastoma cell number in both assays (100-2000 cells/well). In the cytotoxicity test, both neutrophils and MNC effectively mediated ADCC of GD2-positive but not GD2-negative neuroblastoma cell lines. Cytotoxicity of both neutrophils and MNC increased with effector to target cell (E:T) ratio (5-50:1) and mAb ch.14.18 dose (0.1-10 microg/ml). ADCC of neutrophils, but not MNC, increased with addition of GM-CSF. Neutrophils, especially with rhGM-CSF, significantly suppressed growth of GD2-positive cell lines at a high E:T ratio (50:1) and mAb dose (10 microg/ml). Without antibody, neutrophils inhibited growth of one cell line (LA-N-1) but stimulated growth of two others (SMS-KCN, SMS-LHN). If neuroblastoma cells did not express GD2 (SK-N-SH), neutrophils stimulated growth whether or not antibody was present. Neutrophil culture supernatants increased growth of SK-N-SH, LA-N-1, and SMS-KCN cells, and MNC culture supernatants increased growth of SK-N-SH. In conclusion, neutrophils can mediate cytotoxicity and growth inhibition with a chimeric anti-GD2 antibody but also can promote tumor cell growth if antibody is not present or if GD2 is not expressed.
...
PMID:Neutrophils are cytotoxic and growth-inhibiting for neuroblastoma cells with an anti-GD2 antibody but, without cytotoxicity, can be growth-stimulating. 1066 7

In previous studies, we demonstrated that human neuroblastoma cells are equipped with the machinery to direct their homing to bone marrow. These tumor cells express the CXCR4 receptor for the bone marrow stroma-derived chemokine CXCL12 (SDF-1) and secrete the CXCL12 ligand. The present study was undertaken to explore possible differences in gene-expression patterns between neuroblastoma variants that over-express CXCR4 (designated STH cells) and those which express very little of this receptor (STL cells). The results of the study clearly indicate that these variants show a differential gene-expression profile. They differ in expression of some integrins such as VLA2, VLA3 and VLA6, of neuroendocrine-markers such as CD56 and synaptophysin, in the expression of c-kit and in the secretion of certain cytokines and growth factors such as TNFalpha, SDF-1, VEGF, IL-8, GM-CSF and IP-10. We hypothesize that these differences are due to an autocrine SDF-1alpha-CXCR4 axis.
...
PMID:The tumor microenvironment: CXCR4 is associated with distinct protein expression patterns in neuroblastoma cells. 1508 41

Human gammadelta T cells are a small fraction of T cells that have been shown to exert major histocompatibility (MHC)-unrestricted natural cytotoxicity against a variety of solid tumors and some subsets of leukemias and lymphomas. They are also involved in the immune response to certain bacterial, viral, and parasitic infections and expand significantly in CMV- or HSV-infected organ allografts. They are able to mediate antibody-dependent cytotoxicity and are not alloreactive, which makes them attractive candidates for cell-based immunotherapy. However, their frequency in peripheral blood is low and ex vivo expansion of gammadelta T cells is labor-extensive, does not always yield cells with full innate cytotoxic power, and has the potential for microbial contamination. Therefore, the authors developed a clinical-scale, automated cell purification method for the efficient enrichment of gammadelta T cells from leukapheresis products. Six leukapheresis products were purified for gammadelta T cells using a single-step immunomagnetic method. Purity and phenotype were assessed by flow cytometry. A standard Europium release assay was performed to determine the cytotoxic capacity of the cells. Cytokine production was measured using a multiplex sandwich immunoassay. The mean percentage of gammadelta T cells in the final product was 91%, with an average recovery of 63%. The cells showed a high co-expression of CD8, CD56, CD28, and CD11b/CD18. In some products an unusually high proportion of Vgamma9Vdelta1 T cells was found. The isolated cells were cytotoxic against the neuroblastoma cell line NB1691 and the erythroleukemic line K562 in vitro. They were able to produce a variety of immunomodulatory cytokines such as IFNgamma, TNFalpha, and MIP-1beta, but also GM-CSF and G-CSF when co-incubated in culture with and without various stimuli. In summary, the authors describe a rapid, automated, and efficient method for the large-scale enrichment of human gammadelta T cells. The cytotoxic properties of the cells were preserved. This method yields sufficient purified gammadelta T cells for use in adoptive immunotherapy as well as laboratory investigations and animal studies.
...
PMID:Human gammadelta T cells from G-CSF-mobilized donors retain strong tumoricidal activity and produce immunomodulatory cytokines after clinical-scale isolation. 1561 47

We have prepared the map of regional distribution of cervical cancer in Hungary. Serial HPV genotyping of sexual partners provided evidence for the sexually transmitted infections. Molecular epidemiology studies revealed activating c-kit mutation in bilateral testicular cancers. A cost-effective molecular staging method was introduced to the management of breast cancer patients. Genomic profiling identified the gene signature of Herceptin and taxane sensitivity of breast cancer. In colon cancer patients we have determined the mutational spectrum of hMLH1 and hMSH2 genes in Hungary. The prognostic power of SHMT and MTHFR polymorphism was determined in colorectal cancer patients. In head and neck cancer the gene signature of cisplatin sensitivity and the EGFR polymorphism was determined. We have introduced a cost-effective in vitro assay to determine the drug resistance of pediatric leukemias. The prognostic power of N-myc genotyping was determined in neuroblastoma patients. A phase I trial for gene therapy of brain cancer was started by using a GM-CSF adenoviral vector system. Using global genomic approaches the gene signature of malignant melanoma and its metastatic disease was determined. We have found that Ca-channel blockers and EGFR tyrosine kinase inhibitors are effective in preclinical human melanoma models in breaking the apoptosis resistance of this tumor.
...
PMID:[Activity of the National Oncology R&D Consortium in 2004]. 1590 26


<< Previous 1 2 3 4 Next >>

---