Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the short-term efficacy and toxicity of high doses of intravenous deferoxamine (DFO) in children with recurrent neuroblastoma. Ten children (3 2/12-20 years, median 6 5/12 years) had measurable recurrent disease following 1-3 prior treatment regimens. DFO (120-240 mg/kg/d) was planned as a continuous i.v. infusion for five days every other week. Serum ferritins at the start of this therapy ranged from 133-->5000 ng/ml (median 611 ng/ml). Of eight patients begun at a dose of 120-150 mg/kg/d, a single patient experienced visual disturbances which resolved after DFO was discontinued. Two patients begun at 240 mg/kg/d (with serum ferritins levels of 505 and 717 ng/ml) both experienced dose-limiting toxicity including lethargy, dizziness, blurred vision and leg cramps. Although decreases in serum ferritin levels of a least 10% were noted in 4 patients, there were no partial or complete response. DFO given at a dose of 150 mg/kg/d i.v. according to this schedule appears to be ineffective as a single agent against neuroblastoma. Starting doses of 240 mg/kg/d have unacceptable short-term toxicity.
 ...
PMID:Deferoxamine in children with recurrent neuroblastoma. 784 May 8

Neuroblasma-and other malignant cells often contain elevated amounts of iron-rich ferritin and H2O2 and may therefore be a potential target for pro-oxidative effects of ascorbic acid (AA), generating cytotoxic products e.g. by lipid peroxidation (LPO). The influence of H2O2 and iron, either in its free form or bound to ferritin, on AA induced LPO was first investigated using erythrocyte ghosts as a model system. Results of these experiments showed that AA induced LPO not only in the presence of free available iron but also in the presence of ferritin. Similarly, AA induced significant LPO in neuroectodermal SK-N-LO cells with elevated intracellular ferritin levels. These LPO promoting effects of ferritin in the presence of AA on SK-N-LO cells could also be observed using ferritin-immunoconjugates: for this purpose, ferritin was bound to human monoclonal antibodies (MAb-ferritin) recognizing ganglioside GD2 which is present in large quantities on cell surfaces of SK-N-LO and many neuroblastoma cells. We conclude that the pro-oxidative effects of AA could be exploited in the treatment of ferritin rich neuroblastoma in combination with chemotherapy or with MAb-ferritin immunoconjugates.
 ...
PMID:Ascorbic acid induces lipid peroxidation on neuroectodermal SK-N-LO cells with high endogenous ferritin content and loaded with MAb-ferritin immunoconjugates. 784 24

By means of a retrospective study made of multiple centres, it was aimed to determine which variables could be influential at the moment of diagnosis in the prognostic of patients suffering neuroblastoma and medullary bone affection. Fifty four cases of patients belonging to a total of ten hospital centers have been revised in a period of five years. The ages under study spanned from three months to eight years of age (mean = 2.83 years). For the analysis of the patients, they were divided into two groups: one being composed of the deceased patients and the other of the surviving. The deceased patients were of a more advanced age, the delay in the diagnosis was greater, the primitive tumor was found to be more frequently located in the adrenal glands, the metastasis appeared more readily in multiples, and the effectiveness of the treatment was less, resulting in lower cases of remission and a less radical surgery. The only difference with respect to other publications is that in the case of surviving patients, the number of cases of enolase and ferritin is more frequently pathological.
 ...
PMID:[Neuroblastoma with bone marrow invasion. A multicenter study. Work Group of the Spanish Society of Pediatric Surgery]. 786 59

The mechanisms of iron uptake from transferrin and the effects of iron chelators on these processes were investigated in human neuroblastoma cells. This study was performed because numerous reports have indicated that neuroblastoma cells contain iron-rich ferritin and are also especially sensitive to iron chelation by deferoxamine. The mechanisms of iron and transferrin uptake were examined in the human neuroblastoma cell line SK-N-MC by using human transferrin labeled with iodine 125 and iron 59. Internalized and membrane-bound 59Fe and 125I-transferrin were separated with the protease pronase. Total internalized and membrane 125I-transferrin uptake was biphasic with time, whereas total and internalized 59Fe uptake was linear. Iron uptake from transferrin was prevented by incubation at 4 degrees C and also by lysosomotrophic agents. In addition, 59Fe uptake occurred by two processes. The first process was consistent with receptor-mediated endocytosis involving internalization of transferrin bound to specific binding sites. Iron uptake also occurred by a second process, which was not saturable up to a transferrin concentration of 0.06 mg/ml. In terms of quantitative iron uptake, however, the second process was far less important than receptor-mediated endocytosis. Deferoxamine (0.25 mmol/L) only slightly increased 59Fe release from prelabeled cells; the orally effective iron chelator pyridoxal isonicotinoyl hydrazone (0.25 mmol/L) was six times more effective. Moreover, when pyridoxal isonicotinoyl hydrazone (0.2 mmol/L) was added together with labeled transferrin over a 2-hour incubation, 59Fe uptake from transferrin decreased to 18% of the control value, whereas deferoxamine (0.2 mmol/L) had no appreciable effect. Even though deferoxamine (0.1 mmol/L) had little effect on 59Fe uptake or release, it reduced uptake of tritiated thymidine to 33% of the control value after a 24-hour incubation. Three analogs of pyridoxal isonicotinoyl hydrazone, pyridoxal benzoyl hydrazone (#101), pyridoxal p-methoxybenzoyl hydrazone (#107), and pyridoxal m-fluorobenzoyl hydrazone (#109), had chelation activities comparable to that of pyridoxal isonicotinoyl hydrazone and were more effective than either deferoxamine or pyridoxal isonicotinoyl hydrazone at preventing tritiated thymidine uptake. These results suggest that the pyridoxal isonicotinoyl hydrazone analogs have potential as effective antiproliferative agents and deserve further investigation.
 ...
PMID:The iron metabolism of the human neuroblastoma cell: lack of relationship between the efficacy of iron chelation and the inhibition of DNA synthesis. 796 24

Of 567 children with neuroblastoma diagnosed between November 1984 and May 1993 in 21 Italian institutions, 235 (41%) have been evaluated for MYCN oncogene amplification. The amplification (3 or more copies of the gene) was found in 39 patients (17%) and was more frequent in patients aged more than one year, abdominal primary site of the tumor, advanced stages, normal urinary excretion of vanillylmandelic acid (VMA), and high level of LDH, NSE and ferritin. The five-year survival of the 235 patients (62%) was significantly better in patients with normal copy number of MYCN (69% versus 29%). By correlating genomic amplification with clinical and biochemical characteristics, MYCN amplification was found associated with a worse prognosis even when patients were subdivided for age (under and above one year), disease extension (localized operable, localized but inoperable, and disseminated) with exception for Stage IV-S, VMA and homovanillic acid excretion, serum levels of NSE and ferritin, but not of LDH. These data confirm the unfavourable prognostic meaning of MYCN amplification, but are unable to define if it represents a new independent variable.
 ...
PMID:[The prognostic effect of amplification of the MYCN oncogene in neuroblastoma. The preliminary results of the Italian Cooperative Group for Neuroblastoma (GCINB)]. 797 42

The survival for infants less than 1 year of age with neuroblastoma is twice that of older children. This report describes 70 babies with neuroblastoma who experienced an 84% survival. Survival was 100% for stages I, II, and III, 81% for stage IV-S, and 50% for stage IV. Most survivors had favorable biologic characteristics including spontaneous regression, favorable Shimada histology, normal first chromosome, aneuploid tumors, absent or low N-myc oncogene expression, and normal serum ferritin levels.
 ...
PMID:Neuroblastoma in the first year of life: clinical and biologic factors influencing outcome. 806 21

Ascorbic acid at pharmacologically attainable concentrations effectively inhibited the growth of the catecholamine-positive neuroblastoma cell line SK-N-SH; it inhibited LS cells to a smaller extent and catecholamine-negative SK-N-LO cell growth least effectively. In all three cell lines high concentrations of H2O2 were found. Since ascorbic acid was shown to release iron from ferritin in vitro and to keep it in the reduced state, we suggested that it acted as a pro-oxidant in ferritin-rich neuroblastoma cells in the presence of H2O2 and Fe2+ (Fenton reaction), implying iron release from cellular ferritin. We show here that iron could be mobilized from cellular ferritin by 1 mM ascorbic acid in iron-59-preloaded SK-N-SH and LS cells, but not in SK-N-LO cells. In agreement with these results, DNA strand break formation by ascorbate was only observed in SK-N-SH and LS cells. In SK-N-LO cells, DNA strand breaks could be induced by a combination of 1 mM ascorbic acid and 100 microM H2O2. Since cell-damaging effects caused by chemotherapy further facilitate iron release from ferritin, we conclude that ascorbate could be a powerful enhancer of some cytostatic drugs in neuroblastoma therapy.
 ...
PMID:Ascorbic-acid-mediated iron release from cellular ferritin and its relation to the formation of DNA strand breaks in neuroblastoma cells. 818 35

Neuroblastoma accounts for 24 of 109 patients who have been managed by the pediatric tumor outpatient clinic of our university hospital. Among the malignant solid tumors, neuroblastomas are the most numerous. We investigated neuroblastomas found by mass screening oncologically and epidemiologically. Up until March 31, 1991, seven cases were detected from 64,885 infants who received mass screening by the Kitakyushu City System which we had introduced in 1985. This system is based on an individual health survey program for infants in the city. Six of seven cases found by the screening were treated in our department. None of them, including stage III and stage IV cases, showed any conventional risk factors such as high serum levels of neuron specific enolase, ferritin, amplification of N-myc gene, nor cytogenetic abnormalities. Histopathological studies revealed that ganglioneuroblastoma was observed in 9 of 13 cases over one year of age, whereas it was observed only in two screened cases out of 11 cases under one year of age. According to the classification of Shimada et al., there was one stroma-rich tumor, which is rare in infants and usually a matured type, in the screened cases. Interestingly, another one of the six screened cases regressed spontaneously without any treatment. These cases suggested that some neuroblastomas in the process of maturation or spontaneous regression could be detected by mass screening. On the other hand, 9 of 13 non-screened cases over one-year-old died. Although mass screening at six months of age decreased the mortality rate by neuroblastoma in infancy, the prognosis of neuroblastoma in patients over one-year-old remained still poor. Mass screening should be carried out in a health survey program at one year and six months of age in order to improve the outcome.
 ...
PMID:Different characteristics of neuroblastomas in cases found by mass screening and non-screening: evaluation of mass screening for neuroblastoma in Kitakyushu City. 826 87

In patients with neuroblastoma, elevated serum ferritin is correlated with adverse outcome. In this investigation, three human neuroblastoma cell lines have been characterised in terms of their levels of both intracellular and secreted ferritin and their response to the iron-chelating agent, desferrioxamine (deferoxamine). The cell lines differed markedly in respect of ferritin production as determined by radioimmunoassay. Intracellular and secreted ferritin concentrations for SH-SY5Y and BE(2)-C cells were several fold higher than that determined for IMR-32 cells. IMR-32 cells were most sensitive to desferrioxamine, BE(2)-C intermediate and SH-SY5Y the most resistant to the drug in terms of the respective ID50 values. Combining the differentiating agent retinoic acid with desferrioxamine did not enhance cytotoxicity in the neuroblastoma cells. The present data suggest that neuroblastoma cells secreting a relatively low levels of ferritin may be most responsive to iron chelating agents.
 ...
PMID:Ferritin production and desferrioxamine cytotoxicity in human neuroblastoma cell lines. 831 3

Iron (Fe) is known to be necessary for cellular proliferation. Previous studies have suggested that neuroblastoma cells appear to be relatively sensitive to growth inhibition by a specific Fe chelator, deferrioxamine (DFO), in vitro. Also, DFO has been recently used for the treatment of neuroblastoma patients. In this paper we demonstrate that neuroblastoma cell proliferation in vitro is extremely sensitive to inhibition by DFO as compared to another cell line with almost identical growth kinetics. Neuroblastoma cells treated with DFO adapt appropriately to Fe chelation as measured by marked upregulation of transferrin receptor mRNA, increased functional transferrin receptor, and decreased cellular ferritin concentration. Further studies that quantitated cellular incorporation of 59Fe from added transferrin-59Fe in the presence of DFO indicated that neuroblastoma cells were more sensitive to inhibition of Fe incorporation by the chelator as compared to the other cell line. Neuroblastoma cells treated with DFO showed a consistent arrest in the G1 phase of the cell cycle. For cells taken from the "resting" state this block occurred before the vast majority of cells had entered S or G2-M phases of the cell cycle. Further evidence that neuroblastoma cells were arrested before the G1-S interface was provided when cells inhibited by DFO and released into aphidicolin exhibit arrest at the G1-S interface, whereas release from aphidicolin into DFO resulted in entry into S phase. Also, DFO-treated cells exhibited a decrease in both p34cdc2 immunoreactive protein as well as kinase activity. The results of these latter studies strongly indicate evidence for a Fe requirement for malignant cell proliferation before the onset of DNA synthesis. Our results also provide a basis for further studies that will better define a therapeutic approach to patients with neuroblastoma utilizing DFO treatment.
 ...
PMID:Neuroblastoma sensitivity to growth inhibition by deferrioxamine: evidence for a block in G1 phase of the cell cycle. 835 25


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>