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)

The t(11.22)(q24.q12) results in expression of a chimeric RNA product, EWS-FLI1. This RNA product is expressed in over 85% of tumours belonging to the Ewing's family, and is increasingly used as a definitive characteristic of these tumours. In this study, we evaluated reverse transcriptase-polymerase chain (RT-PCR) for EWS-FLI1 fusion transcripts in 18 neurally derived small round cell tumours. These included six Ewing's family tumours and 12 neuroblastomas. EWS-FLI1 fusion transcripts were identified in all six Ewing's tumours, but also in two of the 12 neuroblastomas. One neuroblastoma contained the classic type 1 fusion transcript, and the second a type 1 transcript containing a 66 bp (base pair) insert that was not derived from the EWS or FLI1 gene. The presence of EWS-FLI1 fusion products in RNA extracted from primary neuroblastoma suggests the identification of EWS-FLI1 fusion transcripts is not pathognomonic for tumours of the Ewing's family. The clinical significance of these fusion transcripts in neuroblastoma is not known.
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PMID:EWS-FLI1 fusion transcripts identified in patients with typical neuroblastoma. 913 95

Human neuroblastoma (NB) cell lines have at least three morphological appearance of neuroblastic (N-type), substrate-adhessive (S-type) and intermediate(I) cells. Our previous study revealed S-type cells expressed alpha-smooth muscle actin, desmin and/or basic-calponin, indicating the plausible smooth muscle cell characteristics of S-type cells. In this study, a new human NB cell line, MP-N-MS, was established from bone marrow metastasis of a one year and six-month old girl with advanced NB, originating from right adrenal gland. Morphology of this cell line is composed of S-type cells. MP-N-MS was identified as a NB cell line by surface membrane antigen analysis and MYCN gene amplification. EWS-FLI1 and EWS-ERG chimeric products, observed in Ewing family tumors, were not detected by RT-PCR (reverse transcriptase-polymerase chain reaction). In cytoskeletal protein analysis, alpha-smooth muscle actin and basic calponin of smooth muscle cell markers were detected. Furthermore, smooth myosin of SM1 isoform was identified in MP-N-MS cell line by immunofluorescence, Western blot and RT-PCR, whereas smooth myosin of SM2 was detected by RT-PCR. MP-N-MS is the first cell line, showing SM1 and SM2 isoforms. The presence of smooth muscle myosin of SM1 and SM2 isoforms in MP-N-MS demonstrated the mature smooth muscle phenotype of this NB cell line, and the ability of NB cells to differentiate into smooth muscle cell.
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PMID:[Smooth muscle myosin of SM1 and SM2 isoforms expressing human neuroblastoma cell line of MP-N-MS]. 1045 5

We present an adrenal Ewing's sarcoma family of tumor (ESFT) arising in an 11-year-old Japanese boy. Although intensive chemoradiotherapy and radical surgery were performed, the patient died of obstinate disease 1 year and 3 months after the initial presentation. The primary site (adrenal gland) with radiologic findings (with foci of calcification), high titer of serum neuron specific enolase, and sheets of monotonous primitive rounded cells on histology mostly favored neuroblastoma. However, a diagnosis of ESFT was confirmed by immunohistochemical profile, including MIC2-positivity and molecular study disclosing EWS-FLI1 chimera gene verified by direct sequencing. Recognition of adrenal ESFT and use of newly developed diagnostic techniques are required for differential diagnosis of undifferentiated small round cell tumor of the adrenal gland.
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PMID:Ewing's sarcoma family of tumor arising in the adrenal gland--possible diagnostic pitfall in pediatric pathology: histologic, immunohistochemical, ultrastructural, and molecular study. 1156 33

Neural differentiation with the appearance of ganglion-like cells has been reported in untreated primitive neuroectodermal tumor/Ewing sarcoma (PNET/EWS) at peculiar sites, such as the cauda equina, and following treatment. The case is presented here of a 17-year-old girl with a tumor in the iliac bone. An open biopsy was diagnosed as PNET/EWS of the bone. The tumor had the typical morphology of this tumor type and showed diffuse membranous immunoreactivity for CD99, intense immunoreactivity for synaptophysin, and focal immunoreactivity for neuron-specific enolase and S-100 protein. Occasional reactivity for vimentin was evident, while no immunoreactivity for NB84a, Hu, chromogranins A and B, neurofilaments, cytokeratins, and desmin was present. The patient underwent chemotherapy and radiotherapy, followed by right internal hemipelvectomy. The post-treatment residual viable tumor showed a morphologic appearance resembling a neuroblastoma, with immunoreactivity for NB84a, Hu, synaptophysin, and chromogranins A and B, but not for CD99. RT-PCR performed on tumor tissue before and after therapy showed the presence of the EWS-FLI1 fusion transcript, type I in both samples. This case of PNET/EWS is unique in the sense of showing the typical fusion transcript associated with this tumor both in the morphologically typical pretherapy tumor and in the sample from the post-therapy specimen showing neuroblastoma-like features.
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PMID:Evidence of neural differentiation in a case of post-therapy primitive neuroectodermal tumor/Ewing sarcoma of bone. 1288 51

Ewing family tumors (EFTs) are small round blue cell tumors that show features of neuroectodermal differentiation. However, the histogenetic origin of EFTs is still a matter of debate. We used high-density DNA microarrays for the identification of EFT-specific gene expression profiles in comparison with normal tissues of diverse origin. We identified 37 genes that are up-regulated in EFTs compared with normal tissues and validated expression of these genes in EFTs by both conventional and quantitative reverse transcription-polymerase chain reaction. The expression pattern of EFT-associated genes in normal tissues indicated a high similarity between EFTs and fetal and neuronal as well as endothelial tissues and supports the concept that a primitive neural crest-derived progenitor at the transition to mesenchymal and endothelial differentiation is transformed in EFTs. EFT-associated genes could be used for molecular discrimination between EFTs and other small round blue cell tumors and clearly identified a cell line (SK-N-MC) that was initially established as neuroblastoma as being an EFT. Ectopic expression of the EFT-specific EWS-FLI1 fusion protein in human embryonic kidney (HEK293) cells was not sufficient to induce the complete EFT-specific gene expression signature, suggesting that the EFT-specific gene expression profile is not just a consequence of EWS-FLI1 expression but depends on the histogenetic background of the EFT stem cell.
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PMID:DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets. 1554 87

The Ewing family of tumors harbors chromosomal translocations that join the N-terminal region of the EWS gene with the C-terminal region of several transcription factors of the ETS family, mainly FLI1, resulting in chimeric transcription factors that play a pivotal role in the pathogenesis of Ewing tumors. To identify downstream targets of the EWS/FLI1 fusion protein, we established 293 cells expressing constitutively either the chimeric EWS/FLI1 or wild type FLI1 proteins and used cDNA arrays to identify genes differentially regulated by EWS/FLI1. DAX1 (NR0B1), an unusual orphan nuclear receptor involved in gonadal development, sex determination and steroidogenesis, showed a consistent up-regulation by EWS/FLI1 oncoprotein, but not by wild type FLI1. Specific induction of DAX1 by EWS/FLI1 was confirmed in two independent cell systems with inducible expression of EWS/FLI1. We also analyzed the expression of DAX1 in Ewing tumors and derived cell lines, as well as in other nonrelated small round cell tumors. DAX1 was expressed in all Ewing tumor specimens analyzed, and in seven out of eight Ewing tumor cell lines, but not in any neuroblastoma or embryonal rhabdomyosarcoma. Furthermore, silencing of EWS/FLI1 by RNA interference in a Ewing tumor cell line markedly reduced the levels of DAX1 mRNA and protein, confirming that DAX1 up-regulation is dependent upon EWS/FLI1 expression. The high levels of DAX1 found in Ewing tumors and its potent transcriptional repressor activity suggest that the oncogenic effect of EWS/FLI1 may be mediated, at least in part, by the up-regulation of DAX1 expression.
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PMID:The orphan nuclear receptor DAX1 is up-regulated by the EWS/FLI1 oncoprotein and is highly expressed in Ewing tumors. 1620 64

We report the case of an 11-year-old girl with a retroperitoneal tumor in the left upper quadrant. The girl was admitted to hospital with weight loss and a painless abdominal mass that on biopsy was diagnosed as a peripheral primitive neuroectodermal tumor/Ewing sarcoma (pPNET/EWS) of the soft tissue. The patient underwent chemotherapy followed by surgical resection of the tumor 5 months after diagnosis. The posttreatment residual viable tumor showed a morphologic appearance resembling a neuroblastoma. Interphase and metaphase fluorescent in situ hybridization (FISH) studies performed on the pretreatment and posttreatment samples showed the presence of a t(11;22) rearrangement resulting in EWSR1/FLI1 gene fusion consistent with pPNET/EWS in both specimens. This case is unusual in the sense of showing the typical gene fusion for pPNET/EWS both in the pretherapy sample with the typical morphological appearance of this tumor and in the posttherapy specimen showing neural differentiation suggestive of a neuroblastoma.
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PMID:Peripheral primitive neuroectodermal tumor with postchemotherapy neuroblastoma-like differentiation. 1694 72

Supratentorial primitive neuroectodermal tumors (S-PNET) that develop in children have recently been classified into two types: central-type PNET (C-PNET), which has been reported over the years, and peripheral-type PNET (P-PNET), which develops intracranially and was referred to as Ewing's sarcoma in the past. P-PNET is fundamentally a malignant tumor, but the patient reported here represents a case of long-term survival from onset without recurrence. At the age of 21 months, a male infant developed a cranial bone deformity and symptoms of high intracranial pressure. A CT scan revealed a cystic tumor attaching to the falx, and cyst drainage operation was immediately performed. The intracranial tumor was then resected. The tumor was an intradural extramedullary tumor, and it was totally excised with the falx attachment. The tumor was initially diagnosed as a neuroblastoma, and postoperative treatment consisted of administration of radiotherapy and chemotherapy using cyclophosphamide and vincristine. Twenty years have now passed without any recurrence. Recent repeated performance of histopathological analysis resulted in a diagnosis of P-PNET. In recent years, studies in molecular biology have demonstrated that P-PNET involves the EWS-FLI1 chimeric gene, and immunohistochemical staining has shown P-PNET to be MIC2 positive. P-PNET also differs from C-PNET with regard to prognosis, and for this reason it is believed that P-PNET and C-PNET should be considered separate entities. That is, in spite of the fact that P-PNET is a malignant tumor, patient survival can be comparatively long. Because P-PNET originates intracranially, it is fundamentally an intradural extramedullary tumor. For this reason, treatment should consist of surgical excision that is as complete as possible, followed by appropriate radiotherapy and chemotherapy. This approach can be expected to result in the patient's long-term survival.
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PMID:An infant case of intracranial peripheral-type primitive neuroectodermal tumor with long-term survival. 1809 34

Ewing's sarcoma (ES) is one of the most malignant tumors of bone and soft tissue in children and young adults. ES belongs to a group of small round cell tumors (SRCTs) that also includes neuroblastoma, rhabdomyosarcoma, and malignant lymphoma. However, ES exhibits several specific chimeric genes (EWS-FLI1, EWS-ERG, EWS-ETV1, EWS-E1AF, and EWS-FEV) caused by chromosomal translocations that are not shared by other SRCTs. These chimeric genes regulate the expression of various other genes; that is, they activate inhibitors of DNA binding 2 (Id2) gene expression or they suppress transforming growth factor beta II (TbetaRII) receptor gene expression. The regulation of these chimeric genes may affect critical cell signal transductions, such as signals involved in cell cycle and apoptosis in ES tumor cells. Using an antisense oligodeoxynucleotide against a sequence containing the ATG initiation codon of the EWS-FLI1 chimeric gene that specifically reacts with the EWS-FLI1 and EWS-ERG chimeric genes, we were able to regulate the cell cycle through the down-regulation of Id2. Here, we report that treatment with an antisense oligodeoxynucleotide against this chimeric gene was very useful for inducing the regression of ES tumor growth; thus, this chimeric gene may be an important target for the treatment of ES patients.
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PMID:Treatment of Ewing's sarcoma using an antisense oligodeoxynucleotide to regulate the cell cycle. 1831 Aug 98

Purpose. Recently we showed that the 68-kDa fusion protein derived from the EWS/FLI1 hybrid gene can be specifically detected by Western blotting using a polyclonal antibody to the C-terminal of FLI1 on biopsy material from Ewing's sarcoma. The aim of this study was to investigate whether this antibody also could be used for immunocytochemistry and immunohistochemistry in diagnosis of Ewing's sarcoma.Methods. Immunostaining on paraffin-embedded archival material, fine-needle aspirates and tumour touch imprints from Ewing's sarcomas and primitive neuroectodermal tumours (PNET) for detection of the fusion protein was performed. Most cases were also analysed by Western blotting.Tumours of differential diagnostic importance were also included.Results. Eighty per cent (12/15 cases) of the Ewing tumours exhibited a positive immunoreactivity for the FLI1 antibody. The signal was mainly localised in the nuclei of the tumour cells, which seems reasonable since EWS/FLI1 is a transcription factor. The signal was found to be specific since it did not appear when the blocking peptide was added to the antibody solution.Moreover, two other types of small-round cell tumours (i.e. neuroblastoma and alveolar rhabdomyosarcoma) were negative as well as most normal tissues.Discussion. Immunostaining of histological and cytological specimens with the FLI1 antibody can be of diagnostic relevance in Ewing tumours carrying t(11;22).The absence of immunoreactivity in non-Ewing cells is most likely due to a low expression of the wild-type FLI1 protein.
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PMID:Detection of EWS/FLI-1 by Immunostaining. An Adjunctive Tool in Diagnosis of Ewing's Sarcoma and Primitive Neuroectodermal Tumour on Cytological Samples and Paraffin-Embedded Archival Material. 1852 Dec 61


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