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)

This paper reports late effects and health status of 198 children who had cancer or leukemia diagnosed under 2 years of age and their therapies electively withdrawn. This series (92 neuroblastoma [NBL], 57 Wilms' tumor [WT], 46 acute lymphoblastic leukemia [ALL], and 3 non-Hodgkin's lymphoma) was followed for 1-12 years after discontinuation of therapy. Thirty-three children were diagnosed before 1973, 92 between 1973 and 1977, and 73 after 1977 in 16 Italian Pediatric Oncology Centers. As of December 1983, 176 children were reported to be alive and without evidence of primary cancer by physicians responsible for their care. One child died from a second primary tumor, two from late recurrences of the primary cancer, and three from other causes; eight were alive with evidence of primary cancer; and eight were lost to follow-up. Kyphoscoliosis was found in 22 children and other musculoskeletal anomalies in 8. Neurological sequelae were observed in 8 out 35 children with ALL treated with radiotherapy (RT) and intrathecal methotrexate. All but one were in continuous complete remission when they developed seizures (three cases), leukoencephalopathy (three cases), or intracerebral calcifications (two cases). One child had cardiomyopathy and subsequently died from cardiac failure: he had received doxorubicin (400 mg/m2) and mediastinal RT (13 Gy) for NBL. Growth impairments were observed in children with NBL and WT.
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PMID:Health status of young children with cancer following discontinuation of therapy. 347 May 93

During a 4-year period, 26 children with systemic malignancies suffered cerebrovascular accidents. These occurred in 17 patients with lymphoreticular malignancy and nine patients with solid tumors. They were the presenting signs of malignancy in three patients and were the direct cause of death in six. Cerebrovascular accidents were directly related to disseminated intravascular coagulation in eight patients, to chemotherapy in eight patients, to metastatic tumor in three patients, to thrombocytopenia in three patients, and to fungal meningitis in one patient. All patients with disseminated intravascular coagulation had leukemia and at times, cerebrovascular thrombosis predated systemic or laboratory evidence of disseminated intravascular coagulation. This review indicates that four major syndromes are apparent in children with cancer: vascular thrombosis associated with disseminated intravascular coagulation, acute arterial or sagittal sinus thrombosis secondary to L-asparaginase in children with leukemia, acute neurologic dysfunction in patients with osteogenic sarcoma treated with high-dose methotrexate, and obtundation, seizures, and focal neurologic deficits in patients with neuroblastoma metastatic to the torcular region. Although elevated WBC counts and thrombocytopenia occur frequently in children with cancer, in themselves they uncommonly result in strokes. It is concluded that cerebrovascular accidents are a relatively frequent cause of acute neurologic compromise in children with cancer and that certain types of malignancies and their treatment predispose patients to this complication.
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PMID:Cerebrovascular accidents in children with cancer. 386 Jul 96

Phenytoin (diphenylhydantoin) inhibits the calcium-dependent increases in guanosine 3':5'-monophosphate (cGMP) produced by high potassium depolarization and by muscarinic receptor activation in N1E-115 neuroblastoma cells. The inhibition of the cGMP response to depolarization is half-maximal at 40 microM, similar to the plasma concentration associated with an optimal therapeutic response. The cGMP increase produced by the cationophore A23187 is insensitive to phenytoin blockade, indicating that the enzymatic machinery responsible for calcium-stimulated cGMP accumulation is not affected. The calcium concentration-response curve for the cGMP response to high potassium showed that phenytoin acted primarily to reduce the maximal response. The corresponding curve for the cGMP response to acetylcholine showed apparent competitive inhibition by phenytoin whereas the acetycholine concentration-response curve showed noncompetitive inhibition by phenytoin. The results suggest that phenytoin inhibits cGMP responses by blocking calcium influx. The ability to block the depolarization-induced cGMP response is shared by other anticonvulsants which are effective against generalized tonic-clonic and cortical focal seizures but not by those effective against absence seizures.
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PMID:Phenytoin inhibition of cyclic guanosine 3':5'-monophosphate (cGMP) accumulation in neuroblastoma cells by calcium channel blockade. 625 31

The inhibitory action of a number of clinically effective anticonvulsants on neurotoxin-activated sodium channels in cultured neuroblastoma cells and rat brain synaptosomes has been examined. Diphenylhydantoin (KI = 35 microM) and carbamazepine (KI = 41 microM) inhibited batrachotoxin-activated 22Na+ influx in N18 cells. Similarly, batrachotoxin-activated 22Na+ influx in rat brain synaptosomes was also inhibited by diphenylhydantoin (KI = 38 microM) and carbamazepine (KI = 22 microM). Comparison of KI values with mean brain levels of these drugs achieved during prevention of electroshock seizures indicates that diphenylhydantoin and carbamazepine occupy 35% and 50%, respectively, of their receptor sites associated with sodium channels at mean therapeutic concentrations. Diazepam (KI = 51 to 63 microM) and phenobarbital (KI = 1.2 to 1.3 mM) inhibited batrachotoxin-activated 22Na+ flux in N18 cells and synaptosomes at concentrations in excess of mean therapeutic central nervous system levels. Carbamazepine, like diphenylhydantoin, acts as a competitive inhibitor of sodium channel activation by the full agonist batrachotoxin, but produces mixed inhibition of veratridine-activated channels. This finding is consistent with the conclusion that both carbamazepine and diphenylhydantoin act as allosteric inhibitors of neurotoxin-activated sodium channels. The dose-response relationships for carbamazepine and diphenylhydantoin inhibition of 22Na+ flux in N18 cells are shifted 1.5-fold to higher concentrations when 22Na+ flux measurements are made in the presence of physiological concentrations of sodium and calcium ions. These results suggest that anticonvulsant inhibition of neurotoxin-activated 22Na+ flux in our standard ion flux media, containing low concentrations of Na+ and no Ca2+, is likely to reflect an effect of these agents expected in vivo. The results of this study provide further evidence to support the hypothesis that diphenylhydantoin and carbamazepine, both of which possess similar therapeutic profiles in the treatment of grand mal and partial seizures, may exert their pharmacological effects by occupancy of receptor sites associated with the activation of voltage-sensitive sodium channels in the central nervous system.
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PMID:Inhibition of voltage-sensitive sodium channels in neuroblastoma cells and synaptosomes by the anticonvulsant drugs diphenylhydantoin and carbamazepine. 632 45

A 20-month-old infant with Turner syndrome presented with opsoclonus-myoclonus and tonic pupils in association with an abdominal neuroblastoma. Despite complete removal of the tumor, the child developed progressive hearing loss, areflexia, and seizures. Immunohistochemical and Western blot studies of serum and cerebrospinal fluid revealed the presence of anti-Hu antineuronal antibody, which cross-reacted with areas of the patient's tumor. Treatment with intravenous immunoglobulin coincided with the resolution of opsoclonus-myoclonus and the cessation of new neurologic symptoms. This case provides direct support for the autoimmune basis of paraneoplastic symptoms associated with neuroblastoma and suggests that treatment with intravenous immunoglobulin may be of value.
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PMID:Anti-Hu antibody in a neuroblastoma-associated paraneoplastic syndrome. 806 57

The voltage-dependent calcium channel current (ICa) in the neuroblastoma cell line of human origin (NB-I) was studied by the whole-cell clamp recording. Three types of ICa were identified in NB-I cells. Our electrophysiological and pharmacological findings have suggested that these three types of ICa are consistent with the T-, N- and L-type ICa, respectively. Phenytoin (PHT) inhibited T-type ICa by 13.0% at a concentration of 5 microM, and L-type ICa by 6.3% at a concentration of 100 microM. At a concentration of 100 microM, carbamazepine (CBZ) inhibited T- and L-type ICa by 6.0% and 5.9%, respectively. At a concentration of 50 microM, sodium valproate (VPA) blocked T- and L-type ICa by 6.1% and 47.5%, respectively. At a concentration of 50 microM, zomisamide (ZNS) inhibited T- and L-type ICa by 38.3% and 41.9%, respectively. Na+ channel blockade has been reported to be responsible for the clinical efficacy of PHT or CBZ. Inhibition of T-type ICa by PHT may enhance the efficacy of its anticonvulsant action. CBZ had little effect on ICa. The anticonvulsant activity may be related to the blockade of T-type ICa in the case of VPA and ZNS.
Seizure 1994 Jun
PMID:Antiepileptic drugs--calcium current interaction in cultured human neuroblastoma cells. 808 41

Chlordiazepoxide is a benzodiazepine that is widely used as a minor tranquilizer. It is also effective in the treatment of acute alcohol withdrawal. In this setting, chlordiazepoxide acts as a sedative and prevents the development of epileptiform activity. Although benzodiazepines are known to augment gamma-aminobutyric acid-activated chloride channels, an action which at least partially accounts for their anticonvulsant properties, there is some evidence to suggest that voltage-activated calcium channels may also be the target of these agents. We therefore studied the effect of chlordiazepoxide in blocking two distinct types of voltage-activated calcium channels in N1E-115 neuroblastoma cells. Chlordiazepoxide reversibly blocked calcium channels in both closed and open configurations. It was slightly more potent in blocking the transient (T-type or type I) than the long-lasting (L-type or type II) type of calcium channels with apparent Ki values of 311 and 398 microM, respectively. In the presence of chlordiazepoxide, the currents of both types of calcium channel currents decayed more quickly than control, an observation that suggests open channel block. Chlordiazepoxide-induced block of T-type calcium channels was use dependent, increasing with an increase in stimulus frequency. This was due primarily to the acceleration of current decay and slowing of recovery from inactivation by chlordiazepoxide. These calcium channel blocking actions could contribute some to the sedative and anticonvulsant properties of chlordiazepoxide in patients suffering from acute alcohol withdrawal and in electric shock-induced seizures in animal models.
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PMID:Chlordiazepoxide block of two types of calcium channels in neuroblastoma cells. 838 Aug 61

U-54494A, 3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzamide, has been shown to be a potent and long-acting anticonvulsant without analgesic or sedative effects on intact animals. The persistence of anticonvulsant activity after a decline in its concentration in the brain implies the conversion of the parent drug into active metabolites. In this study, two major metabolites of U-54494A, U-83892E [cis-N-(2-aminocyclohexyl)-3,4-dichlorobenzamide] and U-83894A [cis-N-(2-methylaminocyclohexyl)-3,4-dichlorobenzamide], were identified. The synthetic metabolites displayed anticonvulsant activity against electric shock in experimental animals and blocked voltage-gated sodium channel in N1E-115 neuroblastoma cells in voltage- and use-dependent manner by interacting with the inactivated channels as well as with the channels in the resting state (like the parent compound). These observations may provide one explanation for the long duration of the anticonvulsant activity of the parent compound U-54494A and further underscore the importance of voltage-dependent sodium channels in neuronal excitability, especially during seizures.
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PMID:Two metabolites of anticonvulsant U-54494A: their anticonvulsant activity and interaction with sodium channel. 838 24

Serum neuron-specific enolase (NSE) levels were studied by an enzymo-immunoassay method in 2 groups of patients: a group of epileptic patients, and a group of patients with refractory major depression after electroconvulsive therapy (ECT). In patients without organic neurological disease (n = 274) the mean serum NSE level (+/- S.D.) was 8.4 +/- 3.4 micrograms/l. No correlation with sex or age was observed. No significant difference was observed between epileptic patients without seizure or major electroencephalogram (EEG) abnormality, and a reference group. Significant increases were observed in 32 samples collected from patients with interictal EEG without spikes and waves before the 7th day after a seizure, in whom mean NSE was 21.5 +/- 9.4 micrograms/l, and in 26 samples from 4 patients without seizures but with spikes and waves in the interictal EEG, whose mean NSE was 20.6 +/- 11.5 micrograms/l. The increases of serum NSE levels in epileptic patients seem therefore to be linked to seizures and/or to EEG abnormalities. The consequences of these observations for the survey of epileptic patients, and for the diagnosis of cerebral tumors (mainly neuroblastoma) or for monitoring treatment after surgical resection, are discussed. In only 1 patient out of 6, an increase in serum NSE levels was observed with a peak about 12 h after ECT. No significant correlation with the ECT features (length of seizures, one- or two-sided electrodes) was observed.
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PMID:Increased serum levels of neuron-specific enolase in epileptic patients and after electroconvulsive therapy--a preliminary report. 871 37

We investigated the effects of zonisamide, a new antiepileptic drug, on voltage-dependent T-type calcium current (ICa) in cultured neuroblastoma cells of human origin (NB-I). Zonisamide reduced T-type ICa in a concentration-dependent manner without evoking any change in its inactivation kinetics or voltage dependence of action. The mean percent reduction was 38.3 +/- 5.8% at 50 microM. Further, zonisamide shifted the inactivation curve approximately 20 mV negative compared to the control. These resting blocking actions suggest that zonisamide shifts the channel population toward the inactivation state, allowing fewer channels to open during membrane depolarization. The blockade of T-type calcium channels by zonisamide could suppress an important component of inward current that underlies epileptiform cellular bursting, thereby inhibiting the spread of seizure activity.
Seizure 1996 Jun
PMID:Mechanisms of T-type calcium channel blockade by zonisamide. 879 26


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