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)

We report the nucleotide sequence of the mouse ret proto-oncogene (proto-ret) and the deduced amino acid sequence. It encodes a transmembrane tyrosine kinase of 1115 amino acids that shows 83% homology with the human proto-Ret protein. The amino acid sequence revealed that the structures of the extracellular domain as well as the tyrosine kinase domain are similar in human and mouse proto-Ret proteins. Interestingly, the extracellular domains of both human and mouse proto-Ret proteins contain a cadherin-related sequence that is known to be important for Ca(2+)-dependent homophilic binding of the cadherins. When we examined transcription of the proto-ret gene in a variety of mouse tissues, it was detected in lymph nodes of C3H/HeJ-gld/gld mice and in normal mouse spinal cord. Furthermore, its transcription was found in the Neuro-2a mouse neuroblastoma cell line but not in 13 other rodent cell lines surveyed. Western blot analysis showed that proto-Ret proteins are expressed as 140-kDa and 160-kDa glycoproteins in Neuro-2a cells.
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PMID:cDNA cloning of mouse ret proto-oncogene and its sequence similarity to the cadherin superfamily. 845 36

Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages were analyzed for the expression of 2 proto-oncogenes: trk, which encodes a tyrosine-kinase receptor for nerve growth factor (NGF) and ret, another receptor-type tyrosine kinase whose ligand is unknown. The mRNA expression of the trk gene was detected in 67.4% of cases, with increased frequency in I, II and IVs Evans' stages and in patients with favorable prognosis according to the Shimada classification. Moreover, trk expression inversely correlated with Nmyc-gene amplification. ret mRNA was found in 36.8% of cases and equally distributed in the different stages. In addition, ngfR (low-affinity NGF receptor)-gene expression was present in 9 out of 25 cases. The simultaneous presence of mRNA related to both forms of the NGF receptor, while not proving the presence of a functional receptor, indicates the existence of a sub-set of neuroblastoma cells potentially responsive to NGF.
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PMID:trk and ret proto-oncogene expression in human neuroblastoma specimens: high frequency of trk expression in non-advanced stages. 851 46

Composite pheochromocytomas (CP) account for only 3% of all pheochromocytomas. We analyzed the clinical, immunohistochemical, ultrastructural, DNA content, and 634 ret mutation features in a 56-year-old Mexican woman with CP localized in the right adrenal gland and associated to a blood pressure of 140/90 mmHg. Clinical symptoms were absent after surgery. The tumor showed pheochromocytoma and neuroblastoma components. This dual phenotype was supported by light microscopy and corroborated by immunohistochemistry and ultrastructural findings. Flow cytometric analysis showed that both components were diploid. A genetic mutational analysis of the ret oncogene in exon 11 showed no 634 mutation. This case demonstrates the indolent behavior of neuroblastoma associated to a sporadic-type CP in an adult patient.
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PMID:Sporadic type composite pheochromocytoma with neuroblastoma: clinicomorphologic, DNA content and ret gene analysis. 1174 55

Oxidative injury and the resulting death of neurons is a major pathological factor involved in numerous neurodegenerative diseases. However, the development of drugs that target this mechanism remains limited. The goal of this study was to test a compound library of approved Food and Drug Administration drugs against a hydrogen peroxide-induced oxidant injury model in neuroblastoma cells. We identified 26 neuroprotective compounds, of which megestrol, meclizine, verapamil, methazolamide, sulindac, and retinol were examined in greater detail. Using large-scale oligonucleotide microarray analysis, we identified genes modulated by these drugs that might underlie the cytoprotection. Five key genes were either uniformly upregulated or downregulated by all six drug treatments, namely, tissue inhibitor of matrix metalloproteinase (TIMP1), ret-proto-oncogene, clusterin, galanin, and growth associated protein (GAP43). Exogenous addition of the neuropeptide galanin alone conferred survival to oxidant-stressed cells, comparable to that seen with the drugs. Our approach, which we term "interventional profiling," represents a general and powerful strategy for identifying new bioactive agents for any biological process, as well as identifying key downstream genes and pathways that are involved.
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PMID:Discovery of molecular mechanisms of neuroprotection using cell-based bioassays and oligonucleotide arrays. 1238 92

In the present study we review ENT tumor pathology in childhood. Only the most salient aspects are emphasized and the variety of entities reviewed was restricted. Molecular biology techniques reveal infection by human papilloma virus (types 6 and 11) in 50 % of papillomas, while immunohistochemical techniques are less effective in papilloma virus detection. The myofibroblastic nature of nasal angiofibroma has been demonstrated and its incidence is 25 times more frequent in patients with familial polyposis of the colon. Overexpression of p53 occurs in the initial stages of nasopharyngeal carcinoma, while overexpression of c-myc is correlated with an unfavorable prognosis. Recently, olfactory neuroblastoma has been shown not to express the protein product of the MIC-2 gene (antibody 12E7), thus the hypothesis that it could be a member of the Ewing tumor family (neuroectodermal peripheral tumors) has not been confirmed, although it is a primitive neural tumor. The head and neck rhabdomyosarcoma with the best prognosis is that located in the orbit, and cytogenetic studies have shown chromosomic translocation t(2;13) in 50 % of these childhood tumors when they are of the alveolar-type, while trisomy of chromosome 2 or 20 is more characteristic of the embryonic-type. Currently, any classifying features of ENT lymphomas must be based on the Revised European-American Classification of Lymphoid Neoplasms (REAL). Papillary and medullary carcinomas are the most common histological types of thyroid carcinoma in childhood. Alterations in ret/PTC play a significant role in the pathogenesis of both.
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PMID:[Advances in the diagnosis of ENT tumors in childhood]. 1272 79

Glial cell line-derived neurotrophic factor (GDNF), a potent survival and trophic factor for various neuronal cells, has been measured by assaying its bioactivity based on neurite outgrowth or cell proliferation. We describe herein a sensitive and simple non-radioactive quantitative bioassay for GDNF family proteins based on their ability to induce tyrosine hydroxylase (TH) gene expression. Human neuroblastoma SK-N-MC cells were stably transfected with expression constructs of c-ret and with a luciferase reporter gene driven by 2 kb of the rat TH gene promoter region. In the presence of GDNF, luciferase activity increased with 20 h of incubation. A dose-dependent increase in luciferase activity was observed in the presence of GDNF between 1 and 300 ng/ml. This assay was also applicable for the quantification of the bioactivity of neurturin, another member of the GDNF family showing an even more sensitive profile of dose dependency than GDNF. Typical culture media were applicable in this assay. This method can be easily applied to numerous samples of conditioned medium in a short time.
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PMID:A rapid assay for glial cell line-derived neurotrophic factor and neurturin based on transfection of cells with tyrosine hydroxylase promoter-luciferase construct. 1273 7

The effects of TGF alpha and EGF on a human neuroblastoma cell line expressing EGF receptor were studied. Both growth factors were mitogenic for neuroblastoma and, at the same time, induced a morphological differentiation. TGF alpha treatment (10 ng/ml) determined an increase in the expression of laminin and neurofilaments, both markers typical of neuronal phenotype. Hovewer, unlike the differentiation induced by retinoic acid treatment, TGF alpha modulation of neuroblastoma neuronal markers was not mediated by an increase in the expression of the ret oncogene. Moreover, TGF alpha appeared to stimulate an autocrine production of TGF alpha itself, as evaluated by an increase in mRNA at three days of treatment. These data suggest a possible involvement of EGF and TGF alpha in a paracrine and autocrine control of neuroblastoma, possibly each accomplishing similar but complementary functions.
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PMID:Transforming growth-factor-alpha modulates replication and differentiation markers on a human neuroblastoma cell-line. 2155 11

Receptor tyrosine kinases play important roles in the control of normal cell growth and differentiation. Molecular alterations such as point mutations and rearrangements result in activation of these genes as oncogenes. The ret proto-oncogene (proto-ret) encodes a receptor tyrosine kinase that contains a cadherin-related sequence in the extracellular domain. Transcription of the proto-ret gene has been frequently detected in human tumors such as neuroblastoma, pheochromocytoma and thyroid medullary carcinoma, all of which originate from neural crest cells. When expression of the proto-Ret protein was examined immunohistochemically in normal rat tissues, it was observed in some of peripheral ganglion cells. These findings strongly support the view that the proto-ret gene might be involved in the differentiation and proliferation of neural crest cells. The proto-ret gene was assigned to chromosome 10q11.2. Genes for multiple endocrine neoplasia type 2A and type 2B (MEN2A and MEN2B) and Hirschsprung disease have also been mapped to the proximal long arm of chromosome 10 and closely linked to the locus of the proto-ret gene. MEN2A and MEN2B are characterized by the development of pheochromocytoma and thyroid medullary carcinoma and Hirschsprung disease represents a congenital disorder associated with intestinal aganglionosis. Recently, germ line mutations were found to be present in the extracellular domain of the proto-ret gene in most of MEN2A families. These findings suggested the proto-ret gene as a candidate for MEN and Hirschsprung genes. In addition, rearrangement of the proto-ret gene have frequently been detected in thyroid papillary carcinomas.
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PMID:Ret protooncogene and human-diseases - review. 2156 93


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