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)

Three independent hybrid cell lines were isolated from the fusion of clonal lines of embryonal carcinoma and neuroblastoma. A series of subclones was subsequently derived from the original hybrid clones. In early hybrid generations all hybrid lines showed enhancement of alkaline phosphatase activity, expressing 2--8 times the activity of the teratoma parental line. The overexpression of APase appears to take place in the stationary phase of the growth cycle. Segregation for very high levels of APase activity was observed among subclones of one hybrid line. Specific activities of the segregants ranged from 0.1 to 133. Results of heat denaturation studies are consistent with the hypothesis that it is the embryonal carcinoma APase that is being expressed in the hybrids.
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PMID:Enhanced expression of alkaline phosphatase in hybrids between neuroblastoma and embryonal carcinoma. 60 81

Quantitative changes in the total mass and the molecular species of 1,2-diacyl-sn-glycerol (DAG) and phosphatidic acid (PA) formed upon muscarinic receptor activation were studied in cultured human SK-N-SH neuroblastoma cells. DAG was isolated from the total lipid extracts of carbachol (CCh)-stimulated and unstimulated cells and after benzoylation, was subjected to reverse phase high performance liquid chromatography to separate the component species. The molecular species of DAG were identified by analyzing the fatty acid composition of each separated fraction by gas chromatography, and their total and individual masses were quantified from the known amount of an internal standard, 1,2-distearoyl-sn-glycerol, added during the extraction of the lipid. Relatively high basal levels of DAG (1.5 nmol/mg protein) are present in these cells, and addition of CCh elicited a 50-60% increase in the total amounts of DAG within 5 min. The increase was biphasic: an initial major peak at 5 min was followed by a sustained increase that persisted for at least 30 min. An increase in DAG was elicited by both full and partial muscarinic agonists and was blocked by atropine. The presence of extracellular Ca2+ was necessary for muscarinic receptor-activated formation of DAG. To determine the source of the DAG, the molecular species of the major phospholipids present in SK-N-SH cells were also analyzed. The phospholipids were first enzymatically hydrolyzed to DAGs which were then analyzed as described above. A number of unusual fatty acids, the major one being 20:3 (n-9), were present in these lipids especially in the phosphoinositides and also in the DAG formed after CCh stimulation. Within 5 s of CCh stimulation there were transient increases in the DAG species representative of phosphoinositides. By 5 min the newly formed molecular species of DAG resembled a mixture of phosphoinositides and phosphatidylcholine (PC). Quantitative comparison of the molecular species compositions of phosphoinositides, PC, and newly formed DAGs indicated that at time periods up to 10 min, approximately 30% of the DAG originated from the phosphoinositides and the rest from PC. At longer intervals (greater than 20 min), most (85%) of DAGs originated from PC. Activation of muscarinic receptors in SK-N-SH cells also elicited an increase in PA (200% in 5 min). A quantitative molecular species analysis, using 1,2-distearoyl-sn-glycerol-3-P as internal standard, was performed by enzymatic (alkaline phosphatase) hydrolysis of PA to DAG and subsequent analysis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Quantitative analysis of molecular species of diacylglycerol and phosphatidate formed upon muscarinic receptor activation of human SK-N-SH neuroblastoma cells. 174 76

Recently, great interest has been shown in the histological identification of small cell tumours of childhood--nephroblastoma (Wilms' tumour), neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma--using immunohistochemical methods. However, several antigens operationally specific for leucocyte typing in blood and marrow are also expressed on cells of epithelial and neural origin. We undertook phenotypic characterization of 17 non-haemopoietic small cell tumours of childhood using a panel of 30 monoclonal antibodies to leucocyte, epithelial and cytoskeletal antigens using a sensitive alkaline phosphatase-anti-alkaline phosphatase technique on cryostat sections of fresh tumour. Our results demonstrated frequent expression of the leucocyte-associated antigens CD10 (CALLA), CD9 (p24) and CDw32 (FcRII) in these small cell tumours and occasional expression of MHC class II (HLA-DR) and HNK-1 antigens. However, the leucocyte-associated antigens CD45 (leucocyte common), CD22 (pan B-cell), CD11b (C3bi receptor), CD15 (Lewisx) or CDw42 (platelet gp Ib) were not detected on any tumour. Aberrant expression of desmin, neurofilament and UJ13A antigen was found in nephroblastoma and of epithelial-associated markers (CIBr17 and 43-9F) in neuroblastoma. Our results also demonstrated broad reactivity in frozen section with two monoclonal antibodies specific for melanoma (NKI/C-3) or epithelial cells (OM-1) in paraffin sections. Hence, it is necessary to include monoclonal antibodies to CD45 and pan-epithelial antigens, e.g. LP34 (cytokeratin) or HEA125 for the precise immunohistochemical identification of small round cell malignancies of childhood.
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PMID:Phenotypic characterization of non-haemopoietic small cell tumours of childhood with monoclonal antibodies to leucocytes, epithelial cells and cytoskeletal proteins. 254

In about 50% of patients with stage IV neuroblastoma, micrometastases are present in the bone marrow when it is harvested for an autograft to follow induction therapy, and the risk of graft contamination by neuroblastoma cells has been the rationale for the use of a purging procedure. However, bone marrow metastases are detected with trephine biopsies which only explore the sites biopsied and do not reflect potential contamination of the pooled marrow harvested for autograft. A two-colour fluorochrome labelling method is described which permits as few as 1 neuroblastoma cell in 100,000 normal bone marrow cells from the autograft to be detected. Three monoclonal antibodies (UJ13A, H11 and 11.14) which react with neuroblastoma cells are used as single reagent in combination with a fourth anti-panleucocyte antibody. This method requires only 2 h for the analysis of three million marrow cells from the autograft, and is more effective than alkaline phosphatase staining with the same monoclonal antibodies. Results were compared with conventional techniques (four biopsies and four aspirates) carried out at the same time in 34 consecutive patients. Of 18 cases with negative aspirates and biopsies, neuroblastoma cells were detected in two autografts by the immunological method. Of 16 cases with positive aspirates and/or biopsies, 10 autografts were positive by the immunological method and six were negative. Thus, marrow micrometastases were detected in 16 of the 34 patients, but the autograft contained malignant cells in only 12 of these patients and the immunological analysis demonstrated that the use of a purging procedure allowed the elimination of neuroblastoma cells from the autograft before its reinjection to the patients.
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PMID:Immunological detection of neuroblastoma cells in bone marrow harvested for autologous transplantation. 266 Aug 96

Immuno-alkaline phosphatase staining (APAAP technique) has been used to identify neuroblastoma cells on bone marrow samples from 12 children at various stages of the disease. On 72 occasions immunological analyses were performed using a panel of monoclonal antibodies which selectively bind to cells of neuroectodermal origin. In 57 of these procedures, tumor cells were detected, whereas histological and cytological analyses revealed pathological cells in 45 and 37 cases respectively. Reactivity of minimal residual tumor cells--mainly with three MAbs (UJ13A, UJ167.11, A2B5)--points to the fact that these cells belong to a resistant neuroblastoma clone, which remains in bone marrow despite intense therapy. Our study demonstrates that immunological staining may identify and define a small number of neuroblastoma cells which are not yet detectable by traditional histological and cytological criteria.
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PMID:[Immunologic identification of undetectable neuroblastoma cells by current cytohistological studies of bone marrow samples]. 268 99

Immunological staining by the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique has been used to recognize low levels of neuroblastoma cells in bone marrow mononuclear cells. Immunological phenotyping with 11 well characterized monoclonal antibodies was performed on 16 children with neuroblastoma and BM involvement during or after therapy. Neuroblasts were detected in 11 of 16 patients (0.1-5%), whereas BM biopsies on six of these patients were classified as normal. Aspirates, stained conventionally, were positive for pathological cells in three patients only. The comparison of the phenotype of the neuroblastoma cells at the time of diagnosis to the phenotype of the residual cells within one patient revealed differences. The phenotype of residual disease in different patients on the other hand showed a unique pattern. The above mentioned results lead to the conclusion that the immunological procedure is particularly suitable for the analysis of minimal residual neuroblastoma since the technique allows very minor cell populations to be identified in BM samples.
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PMID:Immunological detection and definition of minimal residual neuroblastoma disease in bone marrow samples obtained during or after therapy. 269 3

A total of 452 cases of childhood malignant solid tumors were treated over the last twenty years at the National Children's Hospital. These included 175 cases of neuroblastoma, 64 cases of Wilms' tumor, 65 cases of malignant lymphoma, 45 cases of soft tissue sarcoma, 31 cases of hepatoma, 20 cases of malignant teratoma, 17 cases of testicular tumor, 7 cases of ovarian tumor and 28 cases of other forms of malignant solid tumor. Bone metastasis was observed in 62 of 175 cases of neuroblastoma, 3 of 64 cases of Wilms' tumor, one of 65 cases of malignant lymphoma, 4 of 45 cases of soft tissue sarcoma, one case of pulmonary blastoma and one case of osteogenic sarcoma, giving a total occurrence of bone metastasis in 72 of the 452 cases. The main sites of bone metastasis in neuroblastoma were the skull (61.4%), femur (56.8%), orbit (27.3%) and spine (22.7%). The average values of serum calcium and alkaline phosphatase activity showed no significant difference. The patients with bone metastasis were treated with a combination of radiation therapy and intensive chemotherapy, resulting in temporary improvement. The survival of patients with stage IV neuroblastoma with bone metastasis was worse than that of similar patients without bone metastasis.
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PMID:[Bone metastasis of malignant solid tumors in childhood]. 303 15

Immunological analysis is complementary to morphological investigation to detect bone marrow (BM) metastases in neuroblastoma patients. It is essential at time of BM harvest for an autograft, since it is the only examination which allows a precise evaluation of the graft contamination by malignant cells. Simple indirect immunofluorescence staining with anti-neuroblastoma monoclonal antibodies (UJ13A and HSAN 1-2) allows a final detection of about 1% malignant cells in the BM, and 1% when cells are gathered in clumps. The use of an immunocytochemical method (alkaline phosphatase) together with double immunofluorescence staining permits to detect as few as one residual neuroblastoma cell in 10(4) normal ones. These two methods used together have allowed to assess the neuroblastoma nature of rare isolated cells with pseudo-lymphocytic aspect.
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PMID:[The significance of immunological analysis for the detection of residual neuroblasts in bone marrow]. 328 68

Cholinergic neurons are unique among cells since they alone utilize choline not only as a component of major membrane phospholipids, such as phosphatidylcholine (Ptd-Cho), but also as a precursor of their neurotransmitter acetylcholine (AcCho). It has been hypothesized that choline-phospholipids might serve as a storage pool of choline for AcCho synthesis. The selective vulnerability of cholinergic neurons in certain neurodegenerative diseases (e.g., Alzheimer disease, motor neuron disorders) might result from the abnormally accelerated liberation of choline (to be used as precursor of AcCho) from membrane phospholipids, resulting in altered membrane composition and function and compromised neuronal viability. However, the proposed metabolic link between membrane turnover and AcCho synthesis has been difficult to demonstrate because of the heterogeneity of the preparations used. Here we used a population of purely cholinergic cells (human neuroblastoma, LA-N-2), incubated in the presence of [methyl-3H]methionine to selectively label PtdCho synthesized by methylation of phosphatidylethanolamine, the only pathway of de novo choline synthesis. PtdCho, purified by thin-layer chromatography, contained 90% of the label incorporated into lipids, demonstrating that LA-N-2 cells contained phosphatidylethanolamine N-methyltransferase. Three peaks of radioactive material that cochromatographed with authentic Ac-Cho, choline, and phosphocholine were observed when the water-soluble metabolites of the [3H]PtdCho were purified by high-performance liquid chromatography. Their identities were ascertained by subjecting them to enzymatic modifications with acetylcholinesterase, choline oxidase, and alkaline phosphatase, respectively. The results demonstrate that AcCho can be synthesized from choline derived from the degradation of endogenous PtdCho formed de novo by methylation of phosphatidylethanolamine.
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PMID:Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line. 347 63

A purified plasma membrane fraction was isolated from cultured neuroblastoma (N1E-115) cells on a discontinuous gradient of 5, 25 and 35% Percoll within 1 h of cell disruption by nitrogen cavitation. Yield of plasma membrane, banding in the 25% Percoll (d = 1.051), was high as judged by the recoveries of the marker enzymes, 5'-nucleotidase (58.0 +/- 5.4%, n = 5), alkaline phosphatase (46.0 +/- 3.0%, n = 4) and Mg2+-stimulated neutral sphingomyelinase (48.0 +/- 4.2%, n = 3); enrichment of specific activities of these enzymes relative to total cell homogenate (lysate) were 10.9 +/- 1.0-, 9.1 +/- 1.0- and 9.6 +/- 0.4-fold, respectively. Levels of marker enzymes for other organelles were less than 3% of total activity, except for microsomes (less than 9%). The plasma membrane fraction was further characterized by 2-, 5- and 6-fold higher content (nmol/mg protein) of total phospholipids, free cholesterol and sphingomyelin, respectively, compared to lysate. Ratios of free cholesterol to phospholipids and of sphingomyelin to phosphatidylcholine in the plasma membrane fraction were about 2-fold greater than that of lysate. The cholesterol ester content of plasma membrane (36 +/- 8 nmol/mg protein) was 2-3-fold higher than that of lysate. Sphingomyelin of the plasma membrane fraction had a higher concentration of long-chain fatty acids (more than 18 carbon atoms) relative to lysate or microsomes. Significant differences also were observed in the fatty acyl composition of diphosphatidylglycerol, cholesterol esters and triacylglycerol of plasma membrane. Thus, we have devised a rapid and reliable method for isolation of highly purified plasma membranes of cultured neuroblastoma cells that is suitable for comparison of metabolic relationships between the plasma membrane and other cellular organelles.
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PMID:Rapid isolation of neuroblastoma plasma membranes on Percoll gradients. Characterization and lipid composition. 396 13


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