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)

In vitro granulocyte colony formation has been studied using the methylcellulose system in 22 children with neuroblastoma, 13 of them having bone marrow invasion. Only one third exhibited normal results. There were various disturbances of granulopoiesis in vitro: colony forming cells were decreased or increased and in the amplification compartment either an ineffective leucopoiesis or an increase in the number of mitosis was present. The abnormalities are not correlated to bone marrow invasion.
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PMID:[In vitro granulocyte colony formation in children with neuroblastoma (author's transl)]. 89 58

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

Accumulation of macrophages in brain tissue as observed in nervous system injury may be due to local production of hematopoietic colony-stimulating factors (CSF). The present work shows human neuroblastoma cells and murine neurons, namely granule cells of the cerebellum, to produce macrophage (M)-CSF which guides expansion and differentiation of macrophage lineage cells. The mRNA-encoding M-CSF but not the respective protein is present in mouse brain including cerebellum. Neither granulocyte M-CSF nor IL-3 is produced by cerebellar neurons or neuroblastoma. By their production of M-CSF, neurons may regulate the macrophage response and lead to local expansion and enhanced function of macrophages in inflammatory diseases of the central nervous system.
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PMID:Neurons and neuroblastoma as a source of macrophage colony-stimulating factor. 139 61

Thirty patients with relapsed pediatric solid tumors received high-dose carboplatin and etoposide with autologous marrow support in a dose-escalation trial. These patients had received extensive prior treatment, which included both cisplatin and etoposide in 25 cases. Six patient cohorts received carboplatin in doses of 1200-2100 mg/m2 and etoposide in doses of 960-1500 mg/m2. All courses were associated with severe neutropenia and thrombocytopenia. The median times from bone marrow infusion to granulocyte recovery (> 0.5 x 10(9)/l) and platelet recovery (> 50 x 10(9)/l) were 33 and 28 days, respectively, with similar findings for all dosage levels. The frequency of non-hematologic toxicities was generally low, although hyponatremia (Na+ < 129 mEq/l) was seen in one-third of the courses. Hepatoxicity was dose-limiting and was significantly associated with the cumulative prior cisplatin dose (p = 0.006). There were four toxic deaths (CNS hemorrhage, alfa-streptococcal sepsis, Candida sepsis, and enterocolitis). Eleven patients received a second course of therapy; toxicity profiles and times to hematologic recovery were similar for the two courses. Clinical responses were observed at all dosage levels. Eleven of 26 evaluable patients achieved a clinical response (one complete, 10 partial). The majority of responses were in patients with neuroblastoma (six of 16) or Hodgkin's disease (two of three). For phase II clinical trials, we recommend dosages of 2100 mg/m2 of carboplatin and 1500 mg/m2 of etoposide for children with prior cumulative cisplatin exposure < 960 mg/m2. This carboplatin dose represents a three- to four-fold increase over pediatric doses tolerated without bone marrow support.
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PMID:Escalating sequential high-dose carboplatin and etoposide with autologous marrow support in children with relapsed solid tumors. 146 10

The CD34 antigen is expressed by 1% to 4% of human and baboon marrow cells, including virtually all hematopoietic progenitors detectable by in vitro assays. Previous work from our laboratory has shown that CD34+ marrow cells can engraft lethally irradiated baboons. Because the CD34 antigen has not been detected on most solid tumors, positive selection of CD34+ cells may be used to provide marrow cells capable of engraftment, but depleted of tumor cells. In seven patients with stage IV breast cancer and two patients with stage IV neuroblastoma, 2.5 to 17.5 x 10(9) marrow cells were separated by immunoadsorption with the anti-CD34 antibody 12-8 and 50 to 260 x 10(6) positively selected cells were recovered that were 64 +/- 16% (range 35% to 92%) CD34+. The patients received 1.0 to 5.2 x 10(6) CD34-enriched cells/kg after marrow ablative therapy. Six patients engrafted, achieving granulocyte counts of greater than 500/mm3 at 34 +/- 10 (range 21 to 47) days and platelets counts of greater than 20,000/mm3 at 46 +/- 14 (range 28 to 66) days posttransplant. Five of these patients showed durable engraftment until the time of death 82 to 386 days posttransplant. One patient failed to sustain engraftment associated with metastatic marrow disease. Three patients died at days 14, 14, and 17 posttransplant, two of whom had evidence of early engraftment. These studies suggest that CD34+ marrow cells are capable of reconstituting hematopoiesis in humans.
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PMID:Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma. 170 96

The role of diagnostic [131I/123I]metaiodobenzylguanidine (*I-MIBG) scintigraphy in the management of pheochromocytoma and neuroblastoma is established, but for other neural crest tumors is less defined. Radiopharmaceutical therapy of all these tumors with large activities of suitably radiolabeled MIBG is a compelling concept. In the five years since the first workshop on 131I-MIBG therapy held in Rome, the initial therapeutic promise appears to have been maintained for neuroblastoma and pheochromocytoma. A significant fraction of patients enter partial remission but complete remission is rare and relapse frequent. To date, experience with other neuroendocrine tumors and the use of 125I in place of 131I remains limited. Many promising areas remain incompletely explored. These include development of appropriate in vitro cultures and animal models, basic pharmacological mechanisms, drug interactions, macro- and microdosimetry and human clinical trials. The latter includes determining dose-limiting toxicity of 131I- and 125I-MIBG, treatment of patients at earlier times or stages of disease, optimal integration with other therapy including granulocyte-stimulating factor and marrow transplant rescue from otherwise limiting myelotoxicity. Progress to date has been slow and painstaking, but nevertheless significant, while the future holds both challenges and promise.
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PMID:Summary, conclusions, and future directions of [131I]metaiodobenzylguanidine therapy in the treatment of neural crest tumors. 182 58

Twenty-nine children (median age: 41 months) with advanced solid tumors received, as consolidation therapy, two consecutive courses of high-dose chemotherapy (HDC) followed by mafosfamide-purged autologous marrow transplantation (ABMT) with a 3- to 4-month interval between each course. The malignancies were neuroblastoma (n = 22), Ewing's sarcoma (n = 5) and rhabdomyosarcoma (n = 2). Patients received a preparatory regimen consisting of combined high-dose melphalan before each ABMT, with the exception of five patients who received busulfan and cyclophosphamide before the second ABMT. Prior to HDC, bone marrow sufficient for two transplantations was harvested in remission, treated with mafosfamide (50 micrograms/ml) and cryopreserved. Following incubation with the drug, a consistent inhibition (greater than 99%) of granulocyte and macrophage colony-forming units was observed. Despite the elimination of measurable hematopoietic progenitors, all patients underwent engraftment within a similar period of time after the first and the second ABMT. However, peripheral leukocyte and granulocyte recovery was delayed (median 26 and 28 days, respectively, after the first graft; median 27 and 28 days after the second graft). No difference was observed in the bacterial infections following the first and second ABMT. One patient died after the second transplant with diffuse aspergillosis. Recovery to 50 x 10(9) platelets/l occurred after a median 42 days (range 19-71) after the first ABMT and 43 days (range 14-110) after the second. Two patients died of recurrent disease before attaining a normal platelet level. One patient remained thrombocytopenic and died from visceral failure at day 200. These results demonstrate the feasibility of repeated ABMT with mafosfamide-treated marrow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemopoietic reconstitution after repeated autologous transplantation with mafosfamide-purged marrow. 279 Mar 32

Circulating hematopoietic stem cells were collected by three consecutive leukaphereses during post-chemotherapy expansion of the stem cell pool in a 3-year-old boy with advanced and therapy-resistant neuroblastoma. The cells were fractionated by discontinuous Percoll gradient centrifugation, frozen in a programmed freezer and then stored in liquid nitrogen. Following high-dose chemotherapy, the cells were thawed rapidly and re-infused into the patient. Early evidence of marrow recovery was first noted at day 13 and the times required to achieve a granulocyte count of greater than 0.5 x 10(9)/L and a platelet count of greater than 50 x 10(9)/L were 21 days and 30 days, respectively. This new marrow-rescue operation may have potential in cancer therapy as an alternative to bone marrow transplantation and further clinical investigation is warranted.
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PMID:[Attempted marrow rescue with cryopreserved circulating stem cells following high-dose chemotherapy]. 289 91

The case histories of 72 subsequently treated patients - 44 with acute leukemia, 10 with chronic myeloid leukemia, 16 with severe aplastic anemia and 2 with neuroblastoma - were analyzed after bone marrow transplantation (BMT) with respect to pulmonary diseases. Thirty-eight patients suffered from a total of 51 pulmonary complications, which led to death in 20. Of 13 patients, 3 died of bacterial pneumonia, all of them during granulocytopenia; 2 of 6 patients died of fungal pneumonia and 2 out of 3 of a mixed bacterial-mycotic infection. Adult respiratory distress syndrome (ARDS) led to death in 2 patients. A granulocyte count under 500/microliter correlated significantly (P less than 0.002) with the fatal outcome of bacterial, fungal and ARDS pneumonia as well as with bronchitis. Viral pneumonia led to death in 8 of 9 patients; in each there was a significant correlation (P less than 0.05) with graft-versus-host disease (GvHD). Patients with repeated episodes of pulmonary illness had significantly more chronic GvHD (P less than 0.05); several of these patients displayed a reduction in helper T cells and an increase in suppressor T cells in the peripheral blood. The natural killer (NK) cells were reduced and the percentage of activated NK cell level lay between 6% and 69%. B-cells were absent or deficient. These findings explain in part the absence of specific antibody reactivity. Five of these patients also contracted GvHD-associated obstructive bronchiolitis, which did not respond to therapy. Pulmonary infiltrates of unknown origin (including idiopathic interstitial pneumonia) occurred in 8 of the patients (11.1%), with a fatal outcome in 3 patients. Significant changes (P less than 0.05) in lung function after BMT appeared in the form of reduced vital capacity (VC) increased residual volume (RV) and an increase in RV expressed as the percentage of total lung capacity. Pulmonary diseases were the most common complication and cause of death in our patients after BMT.
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PMID:Lung diseases after bone marrow transplantation. Results of a clinical, radiological, histological, immunological and lung function study. 352 53

Bone marrow is the commonest site of metastasis in neuroblastoma. This results in minimal to total bone marrow suppression. To establish the mechanism of neuroblastoma suppression of granulopoiesis, the effects of murine C-1300 neuroblastoma cells on granulopoietic activity of normal syngeneic mice was examined. Using a double layer agar system, intact tumor cells, media conditioned by the culture of neuroblastoma cells (NCM) and homogenate of these cells were found to have significant suppressive effects on granulocyte macrophage colony formation (CFU-GM). The rate of production of the NCM was gradual, reaching a plateau by day 4 of the culture. No cell-cell contact was necessary to elicit the CFU-GM depression i.e. regardless of the location of the intact tumor cells or their homogenate in the same or separate layer of the culture, there was a significant linear suppression of CFU-GM (p less than .0005). This suppression proved to be dose dependent. NCM also caused a similar decline in colony formation (p less than 0.005) indicating the suppression is due to diffusible factor(s). The CFU-GM suppressive factor(s) are not dialyzable and cannot withstand 56 degrees C for 15 min. The granulopoietic suppression seen in neuroblastoma may be, at least in part, due to the suppressive effects of these factor(s).
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PMID:Suppressive effects of neuroblastoma cells and conditioned media on in vitro granulopoiesis. 374 44


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