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)

Although cancer has an annual incidence of only about 150 new cases per 1 million U.S. children, it is the second leading cause of childhood deaths. Early detection and prompt therapy have the potential to reduce mortality. Leukemias, lymphomas and central nervous system tumors account for more than one half of new cancer cases in children. Early in the disease, leukemia may cause nonspecific symptoms similar to those of a viral infection. Leukemia should be suspected if persistent vague symptoms are accompanied by evidence of abnormal bleeding, bone pain, lymphadenopathy or hepatosplenomegaly. The presenting symptoms of a brain tumor may include elevated intracranial pressure, nerve abnormalities and seizures. A spinal tumor often presents with signs and symptoms of spinal cord compression. In children, lymphoma may present as one or more painless masses, often in the neck, accompanied by signs and symptoms resulting from local compression, as well as signs and symptoms of systemic disturbances, such as fever and weight loss. A neuroblastoma may arise from sympathetic nervous tissue anywhere in the body, but this tumor most often develops in the abdomen. The presentation depends on the local effects of the solid tumor and any metastases. An abdominal mass in a child may also be due to Wilms' tumor. This neoplasm may present with renal signs and symptoms, such as hypertension, hematuria and abdominal pain. A tumor of the musculoskeletal system is often first detected when trauma appears to cause pain and dysfunction out of proportion to the injury. Primary care physicians should be alert for possible presenting signs and symptoms of childhood malignancy, particularly in patients with Down syndrome or other congenital and familial conditions associated with an increased risk of cancer.
 ...
PMID:Recognition of common childhood malignancies. 1077 55

Topotecan appears to be relatively unaffected by the most common multidrug resistance mechanisms, may potentiate cytotoxicity of alkylators, has good penetration into the central nervous system, is active against a variety of neoplasms, and has myelosuppression as its paramount toxicity. We present our experience with a myeloablative regimen that includes topotecan. Twenty-one patients with poor-prognosis tumors and intact function of key organs received topotecan 2 mg/m2 by 30-min intravenous (i.v.) infusion on days -8, -7, -6, -5, -4; thiotepa 300 mg/m2 by 3 h i.v. infusion on days -8, -7, -6; and carboplatin by 4 h i.v. infusion on days -5, -4, -3 with a daily dose derived from the pediatric Calvert formula, using a targeted area under the curve of seven mg/ml* min ( approximately 500 mg/m2/day). Stem cell rescue was on day 0. The patients were 1 to 29 (median 4) years old; 18 were in complete remission (CR) and three in partial remission (PR). Early toxicities were severe mucositis and erythema with superficial peeling in all patients and a seizure, hypertension, and renal insufficiency followed by veno-occlusive disease in one patient each. Post-transplant treatment included radiotherapy alone (four patients) or plus biological agents (11 patients with neuroblastoma). With a follow-up of 6+ to 32+ (median 11+) months, event-free survivors include 10/11 neuroblastoma patients (first CR), 4/5 brain tumor patients (second PR or CR), 1/3 patients with metastatic Ewing's sarcoma (first or second CR), and a patient transplanted for multiply recurrent immature ovarian teratoma; a patient with desmoplastic small round-cell tumor (second PR) had progressive disease at 8 months. Favorable results for disease control, manageable toxicity, and the antitumor profiles of topotecan, thiotepa, and carboplatin, support use of this three-drug regimen in the treatment of neuroblastoma and brain tumors; applicability to other tumors is still uncertain.
 ...
PMID:Topotecan combined with myeloablative doses of thiotepa and carboplatin for neuroblastoma, brain tumors, and other poor-risk solid tumors in children and young adults. 1160 67

Parathyroid hormone-related protein (PTHrP) was discovered a dozen years ago as a product of malignant tumors. It is now known that PTHrP is a paracrine factor with multiple biological functions. One such function is to relax smooth muscle by inhibiting calcium influx into the cell. In the central nervous system, PTHrP and its receptor are widely expressed in neurons in the cerebral cortex, hippocampus and cerebellum. The function of PTHrP in the CNS is not known. Previous work has shown that expression of the PTHrP gene is depolarization-dependent in cultured cerebellar granule cells and depends specifically on L-type voltage sensitive calcium channel (L-VSCC) Ca(2+) influx. PTHrP has also been found to be capable of protecting these cells against kainic acid-induced excitotoxicity. Here, we tested the idea that mice with a PTHrP-null CNS might display hypersensitivity to kainic acid excitotoxicity. We found that these mice were six-fold more sensitive than control littermate mice to kainic-acid-induced seizures as well as hippocampal c-Fos expression. PTHrP-null embryonic mixed cerebral cortical cultures were more sensitive to kainic acid than control cultures, and PTHrP addition was found to be protective against kainate toxicity in both PTHrP-null and control cultures. By whole-cell techniques, PTHrP was found to reduce L-VSCC Ca(2+) influx in cultured mouse neuroblastoma cells. We conclude that PTHrP functions as a component of a neuroprotective feedback loop that is structured around the L-type calcium channel. This loop appears to be operative in vivo as well as in vitro.
 ...
PMID:Endogenous parathyroid hormone-related protein functions as a neuroprotective agent. 1187 96

Acute cerebellar ataxia and opsomyoclonus are presenting signs of occult neuroblastoma for a substantial proportion of paediatric patients. Cerebellar ataxia may be due to antibodies against the neuroblastoma cross-reacting with cerebellar tissue. This report is of a 26-month-old boy who presented with encephalitis-like features of ataxia, seizures, decreased consciousness, and involuntary movements. Magnetic resonance imaging of the brain and spine were normal 2 weeks after presentation. The child did not have the classical signs of opsoclonus or myoclonus at any stage of the disease but was found to have occult neuroblastoma. The late demyelinating changes seen on magnetic resonance imaging of the brain support an immunological basis for the paraneoplastic manifestations of occult neuroblastoma in this child. Occult neuroblastoma should be considered as one of the differential diagnoses for children presenting with persisting encephalitis-like features in the presence of normal neuroimaging findings.
 ...
PMID:Unusual neurological presentation of neuroblastoma. 1266 29

Electroencephalographic recordings in cerebral cortex of mice given a single sub-convulsive dose of domoic acid exhibited typical spike and wave discharges. Administration of the anti-epileptic drugs sodium valproate, nimodipine, or 5 alpha-pregnan 3 alpha-ol-20-one as well as pyridoxine simultaneously with or after domoic acid treatment resulted in significantly less spike and wave activity. Administration of these same drugs 45 min prior to the administration of domoic acid also significantly reduced EEG background. Mechanistically, sodium valproate and pyridoxine significantly attenuated domoic acid-induced increase in levels of glutamate, increase in levels of calcium influx, decrease in levels of gamma-aminobutyric acid and increase in levels of the protooncogenes c-fos, jun-B and jun-D. In hippocampal cells, domoic acid-induced increases in glutamate and calcium influx were significantly decreased by pyridoxal phosphate or nimodipine. Similarly in neuroblastoma-glioma hybrid cells (NG 108/15), pyridoxine attenuated domoic acid-induced increases in glutamate, influx of extracellular calcium, and enhanced induction of oncoproteins regardless of whether cells were undifferentiated, differentiated or de-differentiated. Pyridoxine has anti-seizure and neuroprotective actions mediated through mechanisms similar to those targeted by current therapeutic strategies.
 ...
PMID:Neuroprotective actions of pyridoxine. 1268 37

In order to specify the nature of interactions between the analgesic compound nefopam and the glutamatergic system, we examined the effects of nefopam on binding of specific ligands on the three main subtypes ionotropic glutamate receptors: N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), or quisqualic acid (QA) and kainic acid (KA) in rat brain membrane preparations. Functionally, we investigated the effects of nefopam against the seizures induced by agonists of these excitatory glutamate receptors in mice. Since the synaptic release of glutamate mainly depends upon the activation of membrane voltage-sensitive sodium channels (VSSCs), the nature of interactions between nefopam and these ionic channels was studied by evaluating the effects of nefopam on binding of 3H-batrachotoxinin, a specific ligand of the VSSCs in rat brain membrane preparations. The functional counterpart of the binding of nefopam on VSSCs was evaluated by its effects on the 22Na uptake-stimulated by veratridine on human neuroblastoma cells and in the maximal electroshock test in mice. Nefopam showed no affinity for the subtypes of ionotropic glutamate receptors up to 100 microM. On the other hand, nefopam was effective against NMDA, QA and KA induced clonic seizures in mice. Nefopam displaced 3H-batrachotoxinin and inhibited the uptake of 22Na in the micromolar range and it protected mice against electroshock induced seizures. Nefopam may block the VSSCs activity: consequently, at the presynaptic level, this effect led to a reduction of glutamate release and at the postsynaptic level, it led to a decrease of the neuronal excitability following activation of the glutamate receptors.
 ...
PMID:Nefopam blocks voltage-sensitive sodium channels and modulates glutamatergic transmission in rodents. 1519 35

The combination of seizures, hypertensive encephalopathy, and neuroblastoma has not been described before. The authors report one case, which is not only of interest in its own right, but also emphasizes the importance of including blood pressure measurement in the clinical examination of children, especially when hypertension could be the cause of the symptoms.
 ...
PMID:The triad of seizures, hypertension, and neuroblastoma: the first described case. 1528 92

The notion of emergency with regards to pediatric neuroimaging requires a strong knowledge of clinical indications. In children under 2 years of age, head trauma requires a CT scan in case of repeated or prolonged or rapidly increasing vomiting, focal signs, loss of consciousness, unusual behavior, seizures, clinical signs of skull fracture or polytrauma. The "shaken baby syndrome" is usually suspected in case of loss of consciousness or seizures before 8 months of age. The hematomas that are observed are subdural in location, diffuse and deeply located. Imaging is only mandatory for headache suggesting underlying space occupying lesion: permanent or increasing pain, nocturnal headache, headache during postural changes or efforts, associated to seizures or abnormal neurological examination. No imaging is indicated in case of first epileptic seizure associated to normal neurological examination and without any particular context. The presence of trauma, intracranial hypertension, persisting disturbances of consciousness or associated focal sign necessitates urgent neuroimaging. No imaging is indicated in case of typical febrile seizures, i.e. generalized, brief and occurring between 1 and 5 years of age. Spinal cord symptoms require immediate MRI evaluation. The most frequent tumor is neuroblastoma. In the absence of spinal tumor, brain abnormalities must be excluded (inflammatory disease). In neonates, CT scan or MRI must be readily performed in case of seizures or loss of consciousness to exclude ischemic, traumatic or infectious lesions.
 ...
PMID:[Pediatric neuroimaging emergencies]. 1554 39

There is clear evidence that an inflammatory reaction is mounted within the CNS following trauma, stroke, infection and seizures, thus augmenting brain damage. Furthermore, chronic inflammation of the CNS is implicated in many neurodegenerative disorders. However, the effects of products of inflammation on neuronal cells are poorly understood. Herein, we characterize the effects of a neurotoxic product of inflammation, prostaglandin J2 (PGJ2), on catechol-O-methyltransferase (COMT) in human dopaminergic-like neuroblastoma SK-N-SH cells and rat (P2) cortical neurons. COMT metabolizes catechols and catecholamines, a pathway relevant to neurodegeneration. PGJ2 treatment reduced the expression and activity of COMT, induced its sequestration into perinuclear aggregates and potentiated dopamine toxicity. The large COMT aggregates were co-localized with the centrosome, suggesting an aggresome-like structure. Our results indicate that COMT impairment induced by PGJ2 treatment may increase the concentration of dopamine (or its metabolites) to neurotoxic levels. Thus, COMT impairment following pro-inflammatory events may be a potential risk factor in neurodegeneration.
 ...
PMID:Prostaglandin J2 reduces catechol-O-methyltransferase activity and enhances dopamine toxicity in neuronal cells. 1640 50

The nuclear envelope (NE) enclosing the cell nucleus, although morphologically and chemically distinct from the plasma membrane, has certain features in common with the latter including the presence of GM1 as an important modulatory molecule. This ganglioside influences Ca(2+) flux across both membranes, but by quite different mechanisms. GM1 in the NE contributes to regulation of nuclear Ca(2+) through potentiation of a Na(+)/Ca(2+) exchanger in the inner nuclear membrane, whereas in the cell membrane, it regulates cytosolic Ca(2+) through modulation of a nonvoltage-gated Ca(2+) channel. Studies with neuroblastoma cells suggest GM1 concentration becomes elevated in the NE with onset of axonogenesis. However, the nuclear GM1/exchanger complex is not limited to neuronal cells but also occurs in NE of astrocytes, C6 cells, and certain non-neural cells. Immunoprecipitation and immunoblot experiments have shown high affinity association of the nuclear Na(+)/Ca(2+) exchanger with GM1, in contrast to Na(+)/Ca(2+) exchangers of the plasma membrane, which bind GM1 less avidly or not at all. This is believed to be due to different isoforms of the exchanger and a difference in topology of GM1 relative to the large inner loop of the exchanger in the 2 membranes. Cultured neurons from mice genetically engineered to lack GM1 suffered Ca(2+) dysregulation as seen in their high vulnerability to Ca(2+)-induced apoptosis. They were rescued by GM1 and more effectively by LIGA20, a membrane-permeant derivative of GM1. The mutant animals were highly susceptible to kainate-induced seizures, which are also a reflection of Ca(2+) dysregulation. The seizures were effectively attenuated by LIGA20 in parallel with the ability of this agent to enter brain cells, insert into the NE, and potentiate Na(+)/Ca(2+) exchange activity in the nucleus. The Na(+)/Ca(2+) exchanger of the NE, in association with nuclear GM1, is thus seen contributing to independent regulation of Ca(2+) by the nucleus in a manner that provides cytoprotection against Ca(2+)-induced apoptosis.
 ...
PMID:GM1 ganglioside: another nuclear lipid that modulates nuclear calcium. GM1 potentiates the nuclear sodium-calcium exchanger. 1690 85


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