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)

Neuroblastoma is the most common extracranial solid tumour of childhood and comprises up to 50% of malignancies among infants. There is a great need of designing novel therapeutic strategies and proteome analysis is one approach for defining markers useful for tumour diagnosis, as well as molecular targets for novel experimental therapies. We started by comparing healthy adrenal glands (which are the election organs developing primary neuroblastoma, NB, tumours) and adrenal glands carrying primary NB tumours, taken from nude mice. Standard maps of healthy and tumour samples were generated by analysis with the PDQuest software. The comparison between such maps showed up- and down-regulation of 84 polypeptide chains, out of a total of 700 spots detected by a fluorescent stain, Sypro Ruby. Spots that were differentially expressed between the two groups, were analysed by MALDI-TOF mass spectrometry and 14 of these spots were identified so far. Among these proteins, of particular interest are the down-regulated proteins adrenodoxin (21-folds), carbonic anhydrase III (eight-folds) and aldose reductase related protein I (eight-folds), as well as the up-regulated protein peptidyl-propyl cis-trans isomerase A (five-folds). Moreover new proteins, which were absent in control samples, were expressed in tumour samples, such as nucleophosmin (NPM) and stathmin (oncoprotein 18).
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PMID:Proteomic analysis of an orthotopic neuroblastoma xenograft animal model. 1526 22

BACKGROUND: Chaperones (CH) play an important role in tumor biology but no systematic work on expressional patterns has been reported so far. The aim of the study was therefore to present an analytical method for the concomitant determination of several CH in human tumor cell lines, to generate expressional patterns in the individual cell lines and to search for tumor and non-tumor cell line specific CH expression.Human tumor cell lines of neuroblastoma, colorectal and adenocarcinoma of the ovary, osteosarcoma, rhabdomyosarcoma, malignant melanoma, lung, cervical and breast cancer, promyelocytic leukaemia were homogenised, proteins were separated on two-dimensional gel electrophoresis with in-gel digestion of proteins and MALDI-TOF/TOF analysis was carried out for the identification of CH. RESULTS: A series of CH was identified including the main CH groups as HSP90/HATPas_C, HSP70, Cpn60_TCP1, DnaJ, Thioredoxin, TPR, Pro_isomerase, HSP20, ERP29_C, KE2, Prefoldin, DUF704, BAG, GrpE and DcpS. CONCLUSIONS: The ten individual tumor cell lines showed different expression patterns, which are important for the design of CH studies in tumor cell lines. The results can serve as a reference map and form the basis of a concomitant determination of CH by a protein chemical rather than an immunochemical method, independent of antibody availability or specificity.
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PMID:Expressional patterns of chaperones in ten human tumor cell lines. 1559 46

The search for new structures in tumors by genomics and proteomics methods is a major goal in tumor biology and may lead to the detection of markers or antigens for the generation of tumor vaccines. The aim of this study was to identify proteins that have been predicted so far based upon their nucleic acid sequence only or show poor identity to known proteins in tumor cell lines. Cell lines of neuroblastoma, colorectal, cervix carcinoma, adenocarcinoma of the ovary, lung and breast cancer, promyelocytic leukaemia, rhabdomyosarcoma, osteosarcoma and malignant melanoma were used. Cell lysates were run on 2D gel electrophoresis with subsequent in-gel digestion and MALDI-TOF-TOF analysis. A series of 10 hypothetical proteins (HPs) were observed and three of these proteins, hypothetical protein (Q9BTE6), CGI-83 protein (Q9Y392) and similar to CG11334 (Q9BV20), were so far described in tumors exclusively. The other seven proteins were already detected at the transcriptional level in normal and tumor cell lines or tissues. In conclusion, the three HPs observed in lung cancer and malignant melanoma may be candidates for development of tumor markers and generation of tumor vaccines.
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PMID:Detection of hypothetical proteins in 10 individual human tumor cell lines. 1568 Feb 40

Serological proteins of neuroblastoma were profiled and analyzed by ProteinChip-SELDI-TOF MS technology with five types of protein chips. By comparing with normal control, a number of protein or polypeptide signals were found significantly and consistently different in their intensities (expression levels) in tumor sera. Interestingly, nine polypeptide peaks in these proteomic features can be simultaneously detected with consistent variations by more than one type of protein chips. None of the expression differences of these nine polypeptides was found in similar comparisons between healthy controls and hepatomas. Preliminary protein identification showed hints for that some of these proteomic alterations may be closely related to the tumorigenesis of neuroblastoma. These results demonstrated the potential of serological biomarker identification for neuroblastoma by ProteinChip-SELDI technology.
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PMID:Serological protein profiling of neuroblastoma by ProteinChip SELDI-TOF technology. 1575 80

Although alpha-synuclein is the main structural component of the insoluble filaments that form Lewy bodies in Parkinson disease (PD), its physiological function and exact role in neuronal death remain poorly understood. In the present study, we examined the possible functional relationship between alpha-synuclein and several forms of matrix metalloproteinases (MMPs) in the human dopaminergic neuroblastoma (SK-N-BE) cell line. When SK-N-BE cells were transiently transfected with alpha-synuclein, it was secreted into the extracellular culture media, concomitantly with a significant decrease in cell viability. Also the addition of nitric oxide-generating compounds to the cells caused the secreted alpha-synuclein to be digested, producing a small fragment whose size was similar to that of the fragment generated during the incubation of alpha-synuclein with various MMPs in vitro. Among several forms of MMPs, alpha-synuclein was cleaved most efficiently by MMP-3, and MALDI-TOF mass spectra analysis showed that alpha-synuclein is cleaved from its C-terminal end with at least four cleavage sites within the non-Abeta component of AD amyloid sequence. Compared with the intact form, the protein aggregation of alpha-synuclein was remarkably facilitated in the presence of the proteolytic fragments, and the fragment-induced aggregates showed more toxic effect on cell viability. Moreover, the levels of MMP-3 were also found to be increased significantly in the rat PD brain model produced by the cerebral injection of 6-hydroxydopamine into the substantia nigra. The present study suggests that the extracellularly secreted alpha-synuclein could be processed via the activation of MMP-3 in a selective manner.
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PMID:Proteolytic cleavage of extracellular secreted {alpha}-synuclein via matrix metalloproteinases. 1586 97

Neuroblastoma, the most common extracranial solid tumour in children, is characterised by highly heterogeneous clinical behaviour; patients are stratified into risk categories according to a combination of clinical and biological markers. However, identifying non-invasive prognostic markers predicting outcome independently from current risk-stratification features remains critical for better disease monitoring. Using the SELDI-TOF-MS technology (surface-enhanced laser desorption/ionization time-of-flight mass spectrometry), we found a serum biomarker that strongly correlates with prognosis in neuroblastoma patients. Subsequent peptide mapping identified this biomarker as SAA protein. In support of this observation, high SAA levels were detected by ELISA in the sera of patients with poor prognosis neuroblastoma. Based on this finding, promises and limitations of the approach are discussed.
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PMID:Protein chip array profiling analysis of sera from neuroblastoma patients. 1592 9

Involvement of individual antioxidant proteins (AOXP) and antioxidants in the differentiation process has been already reported. A systematic search strategy for detecting differentially regulated AOXP in neuronal differentiation, however, has not been published so far. The aim of this study was to provide an analytical tool identifying AOXP and to generate a differentiation-related AOXP expressional pattern. The undifferentiated N1E-115 neuroblastoma cell line was switched into a neuronal phenotype by DMSO treatment and used for proteomic experiments: We used two-dimensional gel electrophoresis followed by unambiguous mass spectrometrical (MALDI-TOF-TOF) identification of proteins to generate a map of AOXP. 16 AOXP were unambiguously determined in both cell lines; catalase, thioredoxin domain-containing protein 4 and hypothetical glutaredoxin/glutathione S-transferase C terminus-containing protein were detectable in the undifferentiated cells only. Five AOXP were observed in both, undifferentiated and differentiated cells and thioredoxin, thioredoxin-like protein p19, thioredoxin reductase 1, superoxide dismutases (Mn and Cu-Zn), glutathione synthetase, glutathione S-transferase P1 and Mu1 were detected in differentiated cells exclusively. Herein a differential expressional pattern is presented that reveals so far unpublished antioxidant principles involved in neuronal differentiation by a protein chemical approach, unambiguously identifying AOXP. This finding not only shows concomitant determination of AOXP but also serves as an analytical tool and forms the basis for design of future studies addressing AOXP and differentiation per se.
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PMID:The neuronal differentiation process involves a series of antioxidant proteins. 1598 80

The pathological role of ApoE4 in Alzheimer's disease (AD) is not fully elucidated yet but there is strong evidence that ApoE is involved in Abeta deposition, which is an early hallmark of AD neuropathology. Overexpression of ApoE in neuroblastoma cells (Neuro2a) leads to the generation of an intracellular 13 kDa carboxy-terminal fragment of ApoE comparable to fragments seen in brains of AD patients. ApoE4 generates more of this fragment than ApoE2 and E3 suggesting a potential pathological role of these fragments in Alzheimer's disease. Analysis of this intracellular ApoE4 fragment by protease digest followed by MALDI-TOF mass spectrometry showed the proteolytic cleavage site close to residue 187 of ApoE. We have engineered and expressed the corresponding ApoE fragments in vitro. The recombinant 13 kDa carboxy-terminal fragment inhibited fibril formation of Abeta; this contrasts with the full-length ApoE and the corresponding amino-terminal ApoE fragment. Moreover, we show that the 13 kDa carboxy-terminal fragment of ApoE stabilizes the formation of Abeta hexamers. Complexes of Abeta with the 13 kDa carboxy-terminal ApoE fragment show toxicity in PC12 cells comparable to Abeta fibrils. These data suggest that cleavage of ApoE, leading to the generation of this fragment, contributes to the pathogenic effect of ApoE4 in AD.
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PMID:A 13 kDa carboxy-terminal fragment of ApoE stabilizes Abeta hexamers. 1601 42

Several protein cascades, including signaling, cytoskeletal, chaperones, metabolic, and antioxidant proteins, have been shown to be involved in the process of neuronal differentiation (ND) of neuroblastoma cell lines. No systematic approach to detect hitherto unknown and unnamed proteins or structures that have been predicted upon nucleic acid sequences in ND has been published so far. We therefore decided to screen hypothetical protein (HP) expression by protein profiling. Two-dimensional gel electrophoresis with subsequent matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/TOF) identification was used for expression analysis of undifferentiated and dimethylsulfoxide-induced neuronally differentiated N1E-115 cells. We unambiguously identified six HPs: Q8C520, Q99LF4, Q9CXS1, Q9DAF8, Q91WT0, and Q8C5G2. A prefoldin domain in Q91WT0, a t-SNARE domain in Q9CXS1, and a bromodomain were observed in Q8C5G2. For the three remaining proteins, no putative function using Pfam, BLOCKS, PROSITE, PRINTS, InterPro, Superfamily, CoPS, and ExPASy could be assigned. While two proteins were present in both cell lines, Q9CXS1 was switched off (i.e., undetectably low) in differentiated cells only, and Q9DAF8, Q91WT0, and Q8C5G2 were switched on in differentiated cells exclusively. Herein, using a proteomic approach suitable for screening and identification of HP, we present HP structures that have been only predicted so far based upon nucleic acid sequences. The four differentially regulated HPs may play a putative role in the process of ND.
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PMID:Differentiation-dependent expression of hypothetical proteins in the neuroblastoma cell line N1E-115. 1642 88

Dopaminergic neurons are known to be vulnerable to age-related neuronal disorders due to reactive oxygen species (ROS) generated during dopamine metabolism. However, it remains unclear what kinds of proteins are involved in the response to oxidative stress. We examined changes in whole proteins and phosphoproteins in the human dopaminergic neuroblastoma cell line SH-SY5Y under oxidative stress induced by the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). Proteins of SH-SY5Y cells at various stages of oxidative stress were separated by two-dimensional gel electrophoresis for comparative analysis. Increase in glutathione-S-transferase pi was detected on SYPRO Ruby-stained gels by computer-aided image analysis. Stress-induced alterations in phosphoproteins were detected by Pro-Q Diamond staining. Elongation factor 2, lamin A/C, T-complex protein 1, and heterogeneous nuclear ribonucleoprotein H3 were identified by MALDI-TOF mass spectrometry as stress-responsive elements.
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PMID:Phosphoproteomic profiling of human SH-SY5Y neuroblastoma cells during response to 6-hydroxydopamine-induced oxidative stress. 1694 64


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