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)

Adenosine deaminase (ADA) activity was localized at the surface membrane of the mouse C-1300 neuroblastoma by incubation of a confluent tissue culture monolayer grown on Lux-Permanox cultureware with 6-chloropurine ribonucleoside (CPR). This substrate is dechlorinated by ADA to form Cl-. At loci of ADA activity, Cl- is precipitated with added silver ion (Ag+), and electron dense metallic silver (Ag degree) is formed upon exposure to light. The incubation was conducted in 0.2 M HEPES buffer (277 mOs) at 37 degrees C, pH 7.4, which contained 1 mM CPR, for 5 min (in this buffer, this is four times the Km); the control lacked the substrate. After completion of the incubation, the monolayer was briefly rinsed with 0.2 M HEPES and 2.5% glutaraldehyde in 0.2 M HEPES containing AgNO3 at a final concentration of 2 mM. Dehydration was accomplished in a graded series of ethanol followed by embedment in the L. R. White resin at 60 degrees C overnight. Thin sections (80 to 100 mm), cut parallel to the monolayer, showed ADA activity at the cells' surface membrane with a smaller amount of activity evenly distributed in the subadjacent ectoplasmic zone. The control lacked any silver grain localization. Since in preliminary studies of neuronal tissue the ADA activity was minimal, these findings may contribute to developing a diagnostic cancer screening test.
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PMID:In vitro ultrastructural localization of the catalytic activity of adenosine deaminase in murine C-1300 neuroblastoma. 222 24

Dural sinus thrombosis (DST) has been reported in association with cancer in both adults and children. We describe the seven patients seen with this complication in our centre between 1981 and 1995. Diagnosis was confirmed by either cerebral CT scanning, MRI or angiography. Median age was 13 years (range 8-15). Six patients were boys. Six children were being treated for non-Hodgkin lymphoma and one for neuroblastoma. Presenting symptoms were seizures and transient neurologic deficit, often preceded by headaches. The probable cause of DST was found in two cases. Tumour localisation in the central nervous system (CNS) probably caused DST in one patient who was treated for ki 1 lymphoma. Dehydration in combination with a poor general condition seemed to be the cause of DST in the patient with neuroblastoma. In five children with stage III or IV non-Hodgkin lymphoma (three lymphoblastic lymphoma; two Burkitt's lymphoma), etiology remained unknown. In these children, DST occurred early in the course of therapy. The median interval between start of chemotherapy and onset of symptoms was 19 days (range 8-40). No child had received L-asparaginase. Prognosis was favourable, with symptoms completely disappearing without therapy within 1 to 5 days. The incidence of DST in patients with advanced stage non-Hodgkin lymphoma during induction and consolidation was calculated to be below 3%. We conclude that DST is rarely diagnosed in children with cancer. Occurrence during the initial phase of therapy for non-Hodgkin lymphoma is associated with a benign prognosis.
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PMID:Dural sinus thrombosis in children with cancer. 1211 89

A prospective study was performed on 20 bacteriologically proven pediatric cases of severe shigellosis admitted to the Department of Pediatrics, Chulalongkorn Hospital during March 1989 to March 1990. Fourteen patients were male and six were female. Shigella B was found in 85% and Shigella D in 15% of cases. The major indications for admission were convulsions and dehydration. Fifteen per cent of cases had underlying malignancies and 42.1% had malnutrition. Most patients had a peak of fever between 39.5 and 40.5 degrees C, serum sodium between 128-144 mEq/l. Mild acidosis was detected in 45% and moderate acidosis in 30% of cases. There were no statistical differences in peak of fever and serum sodium between patients who had convulsion and who did not. Shigellemia was found in one case who also had underlying neuroblastoma. One patient died due to necrotizing enterocolitis, septic shock and renal failure. Most of the organisms found resisted to ampicillin and trimethoprim-sulfamethoxazole (TMP-SMX). However, TMP-SMX was prescribed in most immunocompetent patients and they recovered well. All of three patients with underlying malignancy responded well to ceftriaxone.
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PMID:Severe shigellosis in childhood. 1043 56

The serum- and glucocorticoid-dependent kinase SGK1 is regulated by alterations of cell volume, whereby cell shrinkage increases and cell swelling decreases the transcription, expression and activity of SGK1. The kinase is expressed in all human tissues studied including the brain. The present study was performed to localize the sites of SGK1 transcription in the brain, to elucidate the influence of the hydration status on SGK1 transcription and to explore the functional significance of altered SGK1 expression. Northern blot analysis of human brain showed SGK1 to be expressed in all cerebral structures examined: amygdala, caudate nucleus, corpus callosum, hippocampus, substantia nigra, subthalamic nucleus and thalamus. In situ hybridization and immunohistochemistry in the rat revealed increased expression of SGK1 in neurons of the hippocampal area CA3 after dehydration, compared with similar slices from brains of euvolaemic rats. Additionally, several oligodendrocytes, a few microglial cells, but no astrocytes, were positive for SGK1. The abundance of SGK1 mRNA in the temporal lobe, including hippocampus, was increased by dehydration and SGK1 transcription in neuroblastoma cells was stimulated by an increase of extracellular osmolarity. Co-expression studies in Xenopus laevis oocytes revealed that SGK1 markedly increased the activity of the neuronal K+ channel Kv1.3. As activation of K+ channels modifies excitation of neuronal cells, SGK1 may participate in the regulation of neuronal excitability.
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PMID:Cerebral localization and regulation of the cell volume-sensitive serum- and glucocorticoid-dependent kinase SGK1. 1190 29

Prostaglandin D(2) (PGD(2)), a major cyclooxygenase product in a variety of tissues and cells, readily undergoes dehydration to yield the bioactive cyclopentenone-type PGs of the J(2)-series, such as 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). The observation that the level of 15d-PGJ(2) increased in the tissue cells from patients with sporadic amyotrophic lateral sclerosis suggested that the formation of 15d-PGJ(2) may be closely associated with neuronal cell death during chronic inflammatory processes. In vitro experiments using SH-SY5Y human neuroblastoma cells revealed that 15d-PGJ(2) induced apoptotic cell death. An oligonucleotide microarray analysis demonstrated that, in addition to the heat shock-responsive and redox-responsive genes, the p53-responsive genes, such as gadd45, cyclin G1, and cathepsin D, were significantly up-regulated in the cells treated with 15d-PGJ(2). Indeed, the 15d-PGJ(2) induced accumulation and phosphorylation of p53, which was accompanied by a preferential redistribution of the p53 protein in the nuclei of the cells and by a time-dependent increase in p53 DNA binding activity, suggesting that p53 accumulated in response to the treatment with 15d-PGJ(2) was functional. The 15d-PGJ(2)-induced accumulation of p53 resulted in the activation of a death-inducing caspase cascade mediated by Fas and the Fas ligand.
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PMID:15-Deoxy-Delta(12,14)-prostaglandin J(2): the endogenous electrophile that induces neuronal apoptosis. 1203 89

Prostaglandin (PG) D2, a major cyclooxygenase product in a variety of tissues and cells, readily undergoes dehydration to yield the bioactive cyclopentenone-type PGs of the J2 series, such as 15-deoxy-Delta12,14-PGJ2 (15d-PGJ2). We have shown previously that 15d-PGJ2 is a potent electrophile that causes intracellular oxidative stress and redox alteration in human neuroblastoma SH-SY5Y cells. In the present study, based on the observation that the electrophilic center of 15d-PGJ2 was involved in the pro-oxidant effect, we investigated the role of thioredoxin 1 (Trx), an endogenous redox regulator, against 15d-PGJ2-induced oxidative cell injury. It was observed that the 15d-PGJ2-induced oxidative stress was significantly suppressed by the Trx overexpression. In addition, the treatment of SH-SY5Y cells with biotinylated 15d-PGJ2 resulted in the formation of a 15d-PGJ2-Trx adduct, indicating that 15d-PGJ2 directly modified the endogenous Trx in the cells. To further examine the mechanism of the 15d-PGJ2 modification of Trx, human recombinant Trx treated with 15d-PGJ2 was analyzed by mass spectrometry. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis of the 15d-PGJ2-treated human recombinant Trx demonstrated the addition of one molecule of 15d-PGJ2 per protein molecule. Moreover, the electrospray ionization-liquid chromatography/mass spectrometry/mass spectrometry analysis identified two cysteine residues, Cys-35 and Cys-69, as the targets of 15d-PGJ2. These residues may represent the direct sensors of the electrophilic PGs that induce the intracellular redox alteration and neuronal cell death.
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PMID:Thioredoxin as a molecular target of cyclopentenone prostaglandins. 1270 21

Prostaglandin D(2) (PGD(2)), a major cyclooxygenase product in a variety of tissues and cells, readily undergoes dehydration to yield electrophilic PGs, such as 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). We have previously shown that 15d-PGJ(2) potently induces apoptosis of SH-SY5Y human neuroblastoma cells via accumulation of the tumor suppressor gene product p53. In the study presented here, we investigated the molecular mechanisms involved in the 15d-PGJ(2)-induced accumulation of p53. It was observed that 15d-PGJ(2) potently induced p53 protein expression but scarcely induced p53 gene expression. In addition, exposure of the cells to 15d-PGJ(2) resulted in an accumulation of ubiquitinated proteins and in a significant inhibition of proteasome activities, suggesting that 15d-PGJ(2) acted on the ubiquitin-proteasome pathway, a regulatory mechanism of p53 turnover. The effects of 15d-PGJ(2) on the protein turnover were attributed to its electrophilic feature, based on the observations that (i) the reduction of the double bond in the cyclopentenone ring of 15d-PGJ(2) virtually abolished the effects on protein turnover, (ii) overexpression of an endogenous redox regulator, thioredoxin 1, significantly retarded the inhibition of proteasome activities and accumulations of p53 and ubiquitinated proteins induced by 15d-PGJ(2), and (iii) treatment of SH-SY5Y cells with biotinylated 15d-PGJ(2) indeed resulted in the formation of a 15d-PGJ(2)-proteasome conjugate. These data suggest that the modulation of proteasome activity may be involved in the mechanism responsible for the accumulation of p53 and subsequent induction of apoptotic cell death induced by 15d-PGJ(2).
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PMID:An endogenous electrophile that modulates the regulatory mechanism of protein turnover: inhibitory effects of 15-deoxy-Delta 12,14-prostaglandin J2 on proteasome. 1463 64

Combretastatin A-4 is an antitumoral and antitubulin agent that is active only in its cis configuration. In the present manuscript, we have synthesized cis-locked combretastatins embodying a furazan ring (combretafurazans). To achieve this, we have developed a new strategy that exploits the dehydration of vicinal dioximes using the Mitsunobu reaction. Among the advantages of following such a strategy are the mild conditions used for the construction of the diarylfurazan derivatives, allowing for the presence of highly functionalized substrates and deactivated aromatic rings. Combretafurazans are more potent in vitro cytotoxic compounds compared to combretastatins in neuroblastoma cells, yet maintaining similar structure-activity relationship and pharmacodynamic profiles.
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PMID:Synthesis and cytotoxic evaluation of combretafurazans. 1585 32

Neuroblastoma is the most common extracranial solid tumor in childhood. Its presenting signs and symptoms may be highly variable, depending on the location of the primary tumor and its local or metastatic diffusion and, rarely, with paraneoplastic syndrome such as opsoclonus-myoclonus-ataxia syndrome and gastrointestinal disturbances, due to autoantibodies or to aberrant secretion of vasoactive intestinal peptide. Herein we describe a 10-month-old child with neuroblastoma presenting with a complex clinical picture characterized by acute kidney injury manifested by renal insufficiency and signs and symptoms of tubulointerstitial damage, with polyuria, polydipsia, glucosuria, aminoaciduria and hypochloremic metabolic alkalosis, and of glomerular damage with heavy proteinuria. Imaging study documented a suprarenal mass enveloping the aorta and its abdominal and renal ramifications and bilaterally renal veins. This clinical picture shows some analogies with the hyponatremic-hypertensive syndrome concerning the renovascular disease; however, in absence of systemic arterial hypertension, the heavy proteinuria and the polyuria could be explained by sectional increased intraglomerular pressure, due to local renal blood vessels constriction. Hypochloremic metabolic alkalosis probably developed because of local production of renin, responsible of renin-angiotensin-aldosterone system activation, but above all because of chloride loss through sweating. The long lasting dehydration, due to vomiting, sweating and polyuria, caused prolonged prerenal failure evolving in proximal tubular damage manifestations.
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PMID:Neuroblastoma presenting with acute kidney injury, hyponatremic-hypertensive-like syndrome and nephrotic proteinuria in a 10-month-old child. 2194 89

Anesthetic preconditioning occurs when cells previously exposed to inhaled anesthetics are protected against subsequent injury. We hypothesize that inhaled anesthetics may cause slight protein misfolding that involves site-specific dehydration, stimulating cytoprotective mechanisms. Human neuroblastoma cells were exposed to ethanol (as the dehydration agent) followed by quantitative analysis of the expression of five heat shock genes: DNAJC5G, CRYAA, HSPB2, HSF4 and HSF2. There was an ethanol-induced upregulation of all genes except HSF4, similar to previous observations using isoflurane. CRYAA (the gene for alphaA-crystallin) exhibited a 23.19 and 17.15-fold increase at 24 and 48 h post ethanol exposure, respectively. Additionally, we exposed glyceraldehyde 3-phosphate dehydrogenase to ethanol, which altered oligomeric subspecies and caused protein aggregation in a concentration-dependent manner. Ethanol-mediated dehydration-induced protein aggregation was prevented by incubation with alpha-crystallin. These data indicate that ethanol mimics the effects of isoflurane presumably through a cellular preconditioning mechanism that involves dehydration-induced protein aggregation.
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PMID:Protection against protein aggregation by alpha-crystallin as a mechanism of preconditioning. 2198 99


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