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)

Fifteen children (age 1.2 to 9.4 years) with advanced neuroblastoma were treated with myelosuppressive chemotherapy (cyclophosphamide, cisplatin, doxorubicin) followed by 5 (n = 5), 10 (n = 5), or 15 (n = 5) micrograms/kg recombinant granulocyte colony-stimulating factor (rG-CSF) subcutaneously (SC) once daily for 10 days, starting the day after chemotherapy. Serial serum samples obtained on days 1 and 10 were analyzed for G-CSF activity by a specific proliferation assay using NFS-60 cells. G-CSF serum concentration-time data were best described by a one-compartment model, with zero-order absorption and first-order elimination. After SC injection, absorption was prolonged, with peak concentrations of G-CSF (3 to 117 ng/mL) being reached after 4 to 12 hours. The relatively slow absorption, with a mean elimination half-life of 5.8 hours on day 1 and 4.5 hours on day 10, provided measurable G-CSF concentrations for the entire 24-hour dosing interval in all patients at each dosage level. The median apparent clearance of G-CSF on day 10 was significantly higher than on day 1 (0.57 v 0.31 mL/min/kg, P = .02), and was positively correlated with the absolute neutrophil count (ANC) (r2 = .33, P = .003). Systemic exposure to G-CSF was dose-related, but interpatient pharmacokinetic variability yielded overlap in area under the concentration-time curve (AUC) at all three dosage levels. Stepwise regression analysis showed that G-CSF AUC could be predicted by a model that includes rG-CSF dosage and ANC on the day of administration (r2 = .82, P = .0001).
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PMID:Pharmacokinetics of subcutaneous recombinant human granulocyte colony-stimulating factor in children. 137 15

Expression of granulocyte (G) and granulocyte-macrophage (GM) colony stimulating factor (CSF) genes in human cells of astroglial lineage was studied. Primers for CSFs were used to analyze RNA transcripts in 5 cultured human astrocytoma cell lines and 8 fresh brain specimens by polymerase chain reaction. Constitutive expression of mRNA transcripts of GM-CSF could be detected in all astrocytoma and one neuroblastoma cell lines, and two out of 5 unstimulated astrocytomas, U87MG and U138 MG, expressed G-CSF genes. After stimulation with interleukin (IL)-1 beta + tumor necrosis factor (TNF)-alpha, all cell lines expressed G-CSF. In addition to the cultured cells, we examined gene expression within human malignant astrocytoma, peritumoral brain and autopsied normal brains. The results show that some of the tumor and its surrounding reactive lesions express G- and GM-CSF genes but normal brains do not. The concentration of G- and GM-CSF in supernatants of cultured cells was assessed at the protein level by ELISA. A low level of GM-CSF activity was constitutively present in all astrocytomas. G-CSF was detected in unstimulated U87MG and U138MG and other cell lines could synthesize G-CSF after the stimulation of IL-1 beta and TNF-alpha at the level of mRNA. Furthermore, the concentration of CSFs increased markedly upon stimulation with IL-1 beta and/or TNF-alpha in both a time- and dose-dependent fashion. From these results, it is suspected that astroglial cell-derived CSFs may participate in local immune reactions accompanying infection, degeneration and malignancies in the brain.
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PMID:Expression of granulocyte colony stimulating factor and granulocyte-macrophage colony stimulating factor genes in human astrocytoma cell lines and in glioma specimens. 137 84

Expression of the Cytokine genes in human astroglial cell lineage was studied. Primers for 5 different human cytokine, TNF-alpha, -beta, IFN-gamma, G-CSF and GM-CSF, were used to analyze messenger RNA transcripts in 5 cultured human astrocytoma, one neuroblastoma cell lines and fresh brain specimens by polymerase chain reaction (PCR). Three out of 5 unstimulated astrocytomas, U138, U251, U373 MG and IMR32 neuroblastoma cells expressed TNF-alpha genes. After stimulation with IL-1 beta (1000 U/ml) all these cell lines expressed TNF-alpha genes. TNF-beta genes could not be detected in these cell lines even in the presence of any cytokine stimuli. We were able to detect expression of IFN-gamma genes within 2 astrocytoma cell lines (U87MG and A172), which interestingly did not show TNF-alpha activity. Constitutive expression of mRNA transcripts of GM -CSF could be detected in all astrocytoma and two out of 5 unstimulated astrocytomas, U87MG and U138MG, expressed G-CSF genes. After stimulation with IL-1 beta, all cell lines expressed G-CSF. In addition, we also examined gene expression of these cytokines within 4 human malignant astrocytoma specimens, 2 peritumoral brain and 2 autopsied normal brains. The results show that tumor and surrounding lesions express TNF-alpha (4 of 6), TNF-beta (1/6), IFN-gamma (4/6), G-CSF (3/6) and GM-CSF (5/6) but not normal brains. One tumor specimen also expresses TNF-beta as well as TNF-alpha genes (case 2). From these results, it is suspected that astroglial cell-derived cytokines may participate in local immune reactions accompanying glioma in the brain.
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PMID:[Expression of cytokine genes within astrocytoma cell lines and brain specimens]. 179 21

In the past decade there has been an increasing use of high dose of chemo-radiotherapy in the treatment of poor prognosis solid tumors of childhood. The autologous bone marrow transplantation is the most used technique for circumventing the infectious and haemorrhagic complications occurring in the prolonged period of myelotoxicity. The faster recovery assured by the peripheral blood progenitor cells (PBPC) makes this procedure an attractive alternative. The advent of new apheretic modalities and the use of combinations of active antineoplastic drugs with various growth factors, such as G-CSF, GM-CSF and IL-3, has allowed to collect and concentrate the mononuclear fraction of peripheral blood leukocytes. The optimal timing for the collection is a crucial point and the utilization of flow cytometry for the determinations of circulating CD34+ cells in the peripheral blood is so far the best indicator for successful apheresis. The authors describe their experience in 16 children affected by poor prognosis neuroblastoma who had undergone high dose chemotherapy followed by G-CSF administration and PBPC collection. The details of apheretic techniques and the characteristics of conditioning regimen and haematologic recovery after PBPC reinfusion are also presented.
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PMID:[High-dose chemotherapy, G-CSF and the use of peripheral blood progenitor cells in patients with poor-prognosis neuroblastoma]. 752 51

We report the data of 19 children with neuroblastoma (NB) or Ewing's sarcoma (EW) who had peripheral blood stem cells (PBSCs) harvested after mobilization by: (1) cyclophosphamide (CY) + etoposide + G-CSF, (2) CY + GM-CSF, or (3) G-CSF alone. There were no consistent differences in the number of PBSCs collected following these three different mobilization regimens as assessed by CFU-GM. 17 patients were reinfused with PBSCs after myeloablative therapy and had successful haemopoietic recovery. These results show that in children with solid tumours such as NB or EW a sufficient number of PBSCs can be collected after G-CSF alone, and that PBSCs collected following stimulation by G-CSF alone are as effective in reconstituting haemopoiesis as those collected after mobilizing chemotherapy + HGFs.
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PMID:Use of G-CSF alone to mobilize peripheral blood stem cells for collection from children. 752 35

Autologous bone marrow transplantation (ABMT) and peripheral blood stem cell transplantation (PBSCT) are increasingly used to support high-dose chemotherapy for solid tumors of childhood. In this review we described practical aspects of myeloablative chemotherapy rescued by ABMT, PBSCT or combination of ABMT and PBSCT for the treatment of children with high-risk solid tumor, involving our experiences in 15 cases. Indication, method of harvesting bone marrow and peripheral blood stem cells, cryopreservation, transplantation, selection of anti-neoplastic agents for preconditioning, nutritional and G-CSF support, engraftment and outcomes for prognosis were discussed. In comparing the engraftment of stem cells between ABMT and PBSCT, the acceleration of platelet and erythrocyte recovery is less impressive, although there is a tendency to more rapid recovery of granulocyte in PBSCT group. The outcomes are distinctly improved only in patients who showed complete remission after induction chemotherapy, radiation and surgical excision. A better prognosis will be conferred especially in neuroblastoma and entities of small round cell tumor. It is noteworthy that relapses can occur as distant metastasis considerable years after complete clinical remission. This may be largely contributed by contaminated malignant cells in both harvested bone marrow and peripheral blood stem cells. There is no significant difference between the relapse rates after ABMT and PBSCT.
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PMID:[Myeloablative chemotherapy with autologous bone marrow and/or peripheral blood stem cell transplantation in children with high-risk solid tumor]. 757 7

Neuroblastoma is the most common and highly malignant tumor. The 2-year survival rate for NB patients for 1970s was 32% in US and 29% in Japan. But, improvement of prognosis was observed by recent advances in surgery, chemotherapy and numerous other supportive therapies. We introduce the some treatment regimens to patients with neuroblastoma which should be selected by the age and the stage at diagnosis and other prognostic factors such as N-myc amplification, trk overexpression, chromosome anomalies (lp-. double minutes, homogeneous staining region) of neuroblastoma cells and histological pathology. As a general rules, patients under 1 year of age without unfavorable prognostic factors should be treated less intensive regimen, even their tumors are progressive stages. Conversely, patients with progressive stages over 1 year of age without unfavorable factors, it is necessary to treat with intensive protocol. Furthermore, to patients of all age group with unfavorable factors, they are given a very strong intensive treatment through advances in supportive therapies such as the new antiemetics, G-CSF, antibiotics, or IVH etc.. Recent treatment regimens to the patients with neuroblastoma are presented.
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PMID:[Neuroblastoma]. 782 75

The receptor for leukemia inhibitory factor (LIFR), in combination with the signal-transducing subunit for interleukin-6-type cytokine receptors, gp130, and LIF, activates transcription of acute-phase plasma protein genes in human and rat hepatoma cells and the vasoactive intestinal peptide gene in a human neuroblastoma cell line. To identify the regions within the cytoplasmic domain of LIFR that initiate signal transduction independently of gp130, we constructed a chimeric receptor by linking the extracellular domain of the granulocyte colony-stimulating factor receptor (G-CSFR) to the transmembrane and cytoplasmic domain of human LIFR. The function of the chimeric receptor protein in transcriptional activation was assessed by G-CSF-mediated stimulation of cotransfected cytokine-responsive reporter gene constructs in hepatoma and neuroblastoma cells. By using the full-length cytoplasmic domain and mutants with progressive carboxy-terminal deletions, internal deletions, or point mutations, we identified the first 150 amino acid residues of LIFR as the minimal region necessary for signaling. The signaling reaction appears to involve a cooperativity between the first 70-amino-acid region containing the two sequence motifs conserved among hematopoietin receptors (box 1 and box 2) and a critical sequence between residues 141 and 150 (box 3). Analogous analyses of the cytoplasmic domains of G-CSFR and gp130 indicated similar arrangements of functional domains in these receptor subunits and the requirement of a box 3-related motif for signaling.
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PMID:Multiple regions within the cytoplasmic domains of the leukemia inhibitory factor receptor and gp130 cooperate in signal transduction in hepatic and neuronal cells. 826 82

We report the data of CD34+ cell immunoselection from peripheral blood after G-CSF-alone mobilization (10 micrograms/kg/d s.c.) in nine children with neuroblastoma (median age 4-5 years (2-8), median body weight 16 kg (10-20). Leukaphereses were carried out on a Cobe Spectra separator and two consecutive harvests (4 blood volumes processed) were used for immunoselection on a Ceprate column. The yield of CD34+ cells in the purified fraction was 50% (23-80), with a median number of 2.8 x 10(6) CD34+ cells/kg (1-9.4). All patients were reinfused with selected CD34+ cells after busulfan 600 mg/m2 +melphalan 180 mg/m2 and achieved successful haemopoietic recovery.
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PMID:CD34+ cell immunoselection from G-CSF-alone-primed peripheral blood in children with low body mass. 854 90

While PBSC collection has become a safe procedure for adults, only a few reports exist about its efficacy, safety and feasibility in paediatric patients, especially extremely low-weight infants. We describe successful PBSC collection in three infants of less than 10 kg body weight (BW; range: 6.92-9.4 kg) suffering from stage IV neuroblastoma. Harvest of PBSC started after mobilisation with high-dose chemotherapy and G-CSF, as soon as 1.0% CD34+ cells were detected. Collections were performed using a Baxter CS-3000 Plus separator primed with a mixture of irradiated, white cell-depleted and CMV-negative packed red cells resuspended in 5% human albumin and diluted with saline to match the patient's haematocrit. Performing a median of four, (4-7, median, range) procedures we collected at least 4 x 10(8)/kg BW nucleated cells (NC) from all three patients. The infants were not sedated and showed no serious side-effects. All three children were successfully transplanted with myeloid engraftment in 8 (7-9) days, independence from red cell support was achieved in 15 (10-20) days and from platelet transfusions in 25 (14-29) days after PBSC infusion. We conclude that PBSC harvesting using continuous flow cell separators is safe, even in low-weight infants of less than 7 kg BW.
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PMID:Peripheral blood stem cell (PBSC) collection in extremely low-weight infants. 883 90


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