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Results for “Neuroectodermal Tumors, Primitive, Peripheral”

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PubMed1981

The diagnosis and surgical management of olfactory neuroblastoma: the role of craniofacial resection.

The diagnosis and clinical management of olfactory neuroblastoma are discussed. Computerized tomography is a valuable means of assessing the pre-operative extent of disease and the efficacy of subsequent major surgery. The tissue diagnosis is facilitated by electron microscopy, demonstrating the presence of dense core vesicles and cytoplasmic filaments. Radiotherapy followed by craniofacial resection is the treatment of choice for olfactory neuroblastomas that are locally extensive at presentation.

Adolescent↗
PubMed1983

Olfactory neuroblastoma. A case report in an African child.

The case is described of an eight-year-old Nigerian boy who died from olfactory neuroblastoma which presented with nasal obstruction and epistaxis. Autopsy showed intracranial extension of the tumour into the frontal lobe, and histology revealed undifferentiated neuroblasts, forming rosettes in some areas and producing tangled neurofibrils in others. The histogenesis of the tumour and its diagnosis are briefly discussed.

Child↗
PubMed1991

Pneumocephalus following treatment of esthesioneuroblastoma.

The course of a patient with an olfactory neuroblastoma treated with conventional doses of chemotherapeutic agents and radiotherapy is presented. The patient survived 34 months after tumour necrosis with resultant pneumocephalus requiring surgical intervention.

Combined Modality Therapy↗
PubMed2004

Cyclic AMP-mediated upregulation of the expression of neuronal NO synthase in human A673 neuroepithelioma cells results in a decrease in the level of bioactive NO production: analysis of the signaling mechanisms that are involved.

The expression level of neuronal nitric oxide synthase (nNOS) can vary depending on the (patho)physiological conditions. Here we document a marked induction of nNOS mRNA, protein, and total NO production in response to dibutyryl cyclic AMP (db-cAMP) in human A673 neuroepithelial cells. However, the upregulation of nNOS was associated with a decreased level of production of bioactive NO and by an increase in the level of generation of reactive oxygen species (ROS). ROS production could be prevented by the NOS inhibitor L-NAME, suggesting nNOS itself is involved in ROS generation. Sepiapterin supplementation of db-cAMP-treated A673 cells could restore full bioactive NO production, most likely by preventing the uncoupling of nNOS. nNOS was upregulated by other stable analogues of cAMP, by the activator of adenylyl cyclase forskolin, by isoproterenol or by dopamine through activation of D1 receptors, and by inhibitors of phosphodiesterase. cAMP did not change the half-life of the nNOS mRNA. Inhibitors of protein kinase A (PKA), H-89 and R(p)-cAMPS, produced a partial inhibition of basal and cAMP-induced nNOS expression. cAMP response element binding and modulator transcription factors (CREB and CREM), typical target proteins of PKA, were expressed in A673 cells, as was the coactivator CREB binding protein (CBP). cAMP-stimulated induction of nNOS was significantly enhanced in A673 cells stably transfected with wild-type CREB and almost abolished in cells transfected with KCREB (containing a mutation of the DNA binding domain). In A673 cells transfected with CREB(133) (containing a mutation of the phosphorylatable serine 133), the overall level of nNOS expression was reduced, but the expressional stimulation by cAMP remained. This suggests that CREB bypasses, in part, the classical requirement for phosphorylation and association with CBP. Three members of the recently described four-and-a-half-LIM-domain proteins (FHL1-FHL3) were found to be expressed in A673 cells; FHL-1 and FHL-3 were upregulated by cAMP. These proteins can provide direct activation function to both CREB and CREM, and may be responsible for the PKA-independent component of CREB and CREM activity.

Animals↗
PubMed1997

Phosphodiesterase specific inhibitors control cell growth of a human neuroepithelioma cell line.

The effects of cyclic nucleotide phosphodiesterase (PDE) inhibitors on cell proliferation of SK-N-MC human neuroepithelioma cell line was studied. Clonal density experiments in the presence of 100 microM rolipram and zaprinast showed respectively 27% and 91% inhibition. The effects of PDE inhibitors were then investigated on crude cell extracts; the calculated IC50 were 32 microM for zaprinast and 16 nM for DC-TA-46; the latter inhibitor was used instead of rolipram for its higher efficacy. Dose-response experiments in clonal density conditions showed IC50 of 5 microM and 1.8 microM in the presence respectively of zaprinast and rolipram. These data show that both inhibitors are effective in reducing cell growth, although the response was quantitatively different.

Cell Division↗
PubMed2002

Pleomorphic primitive neuroectodermal tumor with glial and neuronal differentiation: clinical, pathological, cultural, and chromosomal analysis of a case.

This paper examines a case of pleomorphic primitive neuroectodermal tumor (PNET) with glial and neuronal differentiation in a 7-year-old girl who was clinicopathologically reported with immunohistochemical and chromosomal analysis. Clinically, a highly aggressive behavior leading to early recurrence with cerebrospinal fluid seedings was characteristic despite total removal and chemoradiation therapy. Pathologically, severe pleomorphism was noted and large ganglioid cells were predominant. Immunohistochemically, the expression of low-molecular neurofilament was recognized in the surgical specimens and increased in the recurrence. Coexpression of vimentin and neurofilament/GFAP was recognized in the culture. Chromosomal analysis showed near-diploidy, but different karyotype from that PNETs previously reported. These findings suggested that PNETs with pleomorphism and differentiation into both glial and neuronal lineages may show aggressiveness and require more aggressive therapy.

Brain Neoplasms↗
PubMed2003

Primary intraspinal primitive neuroectodermal tumor: report of two cases and review of the literature.

BACKGROUND: Primary intraspinal primitive neuroectodermal tumor (PNET) is a very rare tumor entity. The optimal therapeutic approach is not known yet. We report on two women with primary intraspinal PNETs and review the literature. We describe the typical course of the disease, compare our patients to the other 17 cases reported until today, and discuss therapeutic options. PATIENTS AND METHOD: Case A: In a 49-year-old woman with an intraspinal PNET at L2, laminectomy and a gross tumor removal was accomplished. Postoperative radiation was performed from T12 to L3 to a dose of 50.4 Gy. Subsequently she was treated with chemotherapy containing vincristine, cisplatinum and lomustine. Case B: A 29-year-old woman presented with intramedullary PNET lesions at T1-3 and T10-11. Due to the multifocal location, she received a primary craniospinal axis irradiation to a dose of 35.2 Gy plus a boost to the tumor region to a total dose of 53.2 Gy. RESULTS: Both patients developed multilocular intraspinal relapses with meningeosis neoplastica 17 and 6 months from radiation therapy and underwent palliative chemotherapy. Case A died 23 months, case B 17 months after primary diagnosis. CONCLUSION: Despite modern treatment with microsurgery, irradiation and chemotherapy in primary intraspinal PNETs, local relapse or dissemination in most cases lead to death within a few months. An improvement of treatment outcome can only be achieved by intensification through multidisciplinary treatment.

Adult↗
PubMed2003

The growth-inhibitory Ndrg1 gene is a Myc negative target in human neuroblastomas and other cell types with overexpressed N- or c-myc.

A major prognostic marker for neuroblastoma (Nb) is N-myc gene amplification, which predicts a poor clinical outcome. We sought genes differentially expressed on a consistent basis between multiple human Nb cell lines bearing normal versus amplified N-myc, in hopes of finding target genes that might clarify how N-myc overexpression translates into poor clinical prognosis. Using differential display, we find the previously described growth-inhibitory gene Ndrg1 is strongly repressed in all tested Nb cell lines bearing N-myc amplification, as well as in a neuroepithelioma line with amplified c-myc. Overexpression of N-myc in non-amplified Nb cells leads to repression of Ndrg1, as does activation of an inducible c-myc transgene in fibroblasts. Conversely, N-myc downregulation in N-myc-amplified Nb cells results in re-expression of the Ndrg1, and stimuli known to induce Ndrg1 do so in Nb cells while simultaneously down-regulating N-myc. Relevant to these results, we demonstrate an in vitro interaction of Myc protein with the Ndrg1 core promoter. We also find that Ndrg1 levels increase dramatically during in vitro differentiation of two cell lines modeling neural and glial development, while c- and N-myc levels decline. Our results combined with previous information on the Ndrg1 gene product suggest that downregulation of this gene is an important component of N-Myc effects in neuroblastomas with poor clinical outcome. In support of this notion, we find that re-expression of Ndrg1 in high-Myc Nb cells results in smaller cells with reduced colony size in soft-agar assays, further underscoring the functional significance of this gene in human neuroblastoma cells.

Agar↗
PubMed2003

Primary primitive neuroectodermal tumor (PNET) of the kidney with venous thrombus.

Primitive neuroectodermal tumors of the kidney are rare, the diagnosis usually being made at histopathology. A young adult presented with a painful left renal mass. CT Scan of the abdomen revealed a large necrotic tumor of the left kidney. At surgery the patient was found to have a venous thrombus confined to the renal vein. Radical nephrectomy was done. Histopathology showed a round cell neoplasm with typical Homer Wright rosette formation and positive staining for neuron specific enolase (NSE) and MIC-2 on immunohistochemistry. The patient is undergoing multidrug chemotherapy and is alive and well at a follow up of nine months.

Adult↗
PubMed1994

DNA ploidy and proliferative activity (S-phase) in childhood soft-tissue sarcomas: their value as prognostic indicators.

The value of DNA ploidy as a prognostic indicator is well established in many cancers, but recent studies in childhood rhabdomyosarcoma (RMS) have been contradictory. In a retrospective study of 128 cases of soft-tissue sarcoma (STS) diagnosed since 1980, the prognostic value of clinical, histological and flow cytometric parameters was compared, using univariate and multivariate methods. Eighty-one RMSs, 18 extraosseous Ewing's (EOE)/peripheral neuroectodermal tumours (PNETs) and 29 other non-RMS STSs were histologically and clinically reviewed. Five year actuarial survival was 63.4% for all STSs and 69.4% for RMSs. Paraffin-embedded tissue blocks were available for flow cytometry in 90 cases. Of the RMSs, 65.5% were aneuploid [DNA index (DI) > 1.1] compared with 23% of the EOE/PNETs and 31% of non-RMS STSs. Median S-phase was also significantly higher in RMSs (17.0%) than in other STSs (10.8%) (P = 0.0023). Univariate analysis in RMSs showed that stage, ploidy status, S-phase, site and tumour size all had a significant impact on survival. In multivariate analysis of 59 cases of RMS, one clinical and two flow cytometric parameters were independently associated with poor prognosis. These were stage (IV), nonhyperdiploidy (DI < 1.10 and > 1.8) and a high rate of proliferative activity (S-phase > 14.0%). These results confirm that ploidy and S-phase are important new prognostic indicators in rhabdomyosarcoma.

Adolescent↗
PubMed2006

Molecular diagnosis of Ewing sarcoma/primitive neuroectodermal tumor in routinely processed tissue: a comparison of two FISH strategies and RT-PCR in malignant round cell tumors.

Ewing sarcoma/primitive neuroectodermal tumor (EWS/PNET) is a diagnostically challenging malignant round cell tumor with signature translocations involving the EWS gene. These translocations are detectable with both reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) in formalin-fixed paraffin-embedded tissue. However, RT-PCR is less sensitive in formalin-fixed paraffin-embedded than frozen tissue. Similarly, commercial FISH probes have recently become available, but have yet to be rigorously tested in the clinical setting. Therefore, we have compared RT-PCR with FISH using 'home brew' fusion probes for Ewing sarcoma (EWS)-FLI1 and a commercial EWS break apart probe set in 67 archival round cell tumors, including 27 EWS/PNETs. Sensitivities and specificities for both FISH assays were 91 and 100%, respectively, whereas RT-PCR had a sensitivity of 54% and a specificity of 85%. The break apart strategy was easier to interpret than probe fusion approach. We conclude that FISH is a more sensitive and reliable ancillary technique than RT-PCR for the diagnosis of EWS/PNET in formalin-fixed paraffin-embedded tissue, although the latter provides additional information regarding fusion transcript subtype and prognosis. The commercial break apart probe set is both readily available and easy to interpret, making it particularly attractive. Nonetheless, complex round cell tumors often benefit from molecular testing with multiple methods.

Adolescent↗
PubMed1999

Ceramide accumulation precedes caspase-dependent apoptosis in CHP-100 neuroepithelioma cells exposed to the protein phosphatase inhibitor okadaic acid.

The protein phosphatase inhibitor okadaic acid (OA) dose-dependently induced apoptosis in CHP-100 neuroepithelioma cells when administered for 24 h at concentrations ranging from 10 - 100 nM. Apoptosis was largely, albeit not completely, dependent on cystein protease (caspase) activation. CPP32 processing and poly(ADP-ribose) polymerase (PARP) cleavage started to be observed only at 20 nM OA; moreover, the caspase inhibitor Z-Val-Ala-DL-Asp-fluoromethylketone (Z-VAD.fmk) (100 microM) had negligible effect on apoptosis induced by 10 nM OA, but rescued from death an increasing cell fraction as OA concentration was raised from 20 - 100 nM. Cell treatment for 24 h with OA induced ceramide accumulation; the phenomenon started to be evident at 20 nM OA and reached its maximum at 50 - 100 nM OA. In cells exposed to 50 nM OA, ceramide was already elevated by 5 h; at this time, however, PARP cleavage and apoptosis were not yet observed. Z-VAD.fmk (100 microM) had no effect on ceramide elevation induced by 50 nM OA within 5 h, but markedly reduced ceramide accumulation as the incubation was prolonged to 24 h. The latter phenomenon was accompanied by elevation of glucosylceramide levels, thus suggesting that a caspase-dependent reduction of glucosylceramide synthesis might contribute to late ceramide accumulation. Short-chain ceramide (30 microM) induced apoptosis in CHP-100 cells and its effect was additive with that evoked by OA (10 - 20 nM). These results suggest that ceramide generation might be an important mechanism through which sustained protein phosphatase inhibition induces caspase activation and apoptosis in CHP-100 cells.

Apoptosis↗
PubMed1997

Cell scattering of SK-N-MC neuroepithelioma cells in response to Ret and FGF receptor tyrosine kinase activation is correlated with sustained ERK2 activation.

The c-ret proto-oncogene encodes a receptor tyrosine kinase which plays an important role in kidney and enteric nervous system development. Germline mutations in c-ret are responsible for the dominantly inherited cancer syndromes, multiple endocrine neoplasia types 2A and 2B and familial medullary thyroid carcinoma as well as the developmental disorder Hirschsprung's disease. Using SK-N-MC neuroepithelioma cells stably transfected with an EGFR/Ret chimeric receptor, we have studied cellular consequences and signalling events following activation of exogenous EGFR/Ret and endogenous FGF and PDGF receptor tyrosine kinases in cells of neuroectodermal origin. Here we report that Ret activation led to cell scattering, growth inhibition and loss of anchorage-independent growth. Basic FGF, but not PDGF, evoked similar responses in those cells. Nevertheless, activation of all three receptor tyrosine kinases led to ERK2 activation. Analysis of the kinetics of ERK2 activation and downstream events revealed that Ret and FGF receptor activation led to sustained ERK2 activation and SRE transactivation, while PDGF treatment led to transient ERK2 activation and failed to induce SRE transactivation. Our results suggest that sustained, but not transient ERK2 activation may be involved in cell scattering.

Animals↗
PubMed1998

Involvement of Myc targets in c-myc and N-myc induced human tumors.

The myc proto-oncogenes are transcription factors that directly regulate the expression of other genes, by binding to the specific DNA sequence, CACGTG. Among the target genes for c-Myc regulation are ECA39, p53, ornithine decarboxylase (ODC), alpha-prothymosin and Cdc25A. In this study we examined the involvement of c-Myc target genes in human oncogenesis induced by c-myc or N-myc. In MCF-7 breast cancer cells, the induction of c-myc expression by estrogen was followed by the induction of all the Myc targets that we examined, indicating that those genes can serve as c-Myc targets in human oncogenesis. Moreover, in breast tumors exhibiting c-myc overexpression, several Myc targets were also overexpressed. A clear correlation between the expression of c-myc and its targets was also detected in Burkitt's lymphomas, which involve a specific translocation of c-myc gene, but not in other lymphoma cells. Yet, in cells derived from a neuronal origin the pattern of expression of Myc targets was more complex. In a neuroepithelioma cell line that overexpresses c-myc, only some targets were expressed. In addition in neuroblastomas, in which N-myc is amplified and overexpressed, only ODC was overexpressed in all cell lines, while all other target genes were expressed in only some of the cell lines. The more complex expression pattern found for the Myc targets in neuroblastomas suggests that genes that were identified originally as targets for c-Myc regulation may be regulated by N-Myc, but other cell specific factors are also needed for transcription of the target genes.

Breast Neoplasms↗
PubMed2002

The mechanism of nitrogen monoxide (NO)-mediated iron mobilization from cells. NO intercepts iron before incorporation into ferritin and indirectly mobilizes iron from ferritin in a glutathione-dependent manner.

Nitrogen monoxide (NO) is a cytotoxic effector molecule produced by macrophages that results in Fe mobilization from tumour target cells which inhibits DNA synthesis and mitochondrial respiration. It is well known that NO has a high affinity for Fe, and we showed that NO-mediated Fe mobilization is markedly potentiated by glutathione (GSH) generated by the hexose monophosphate shunt [Watts, R.N. & Richardson, D.R. (2001) J. Biol. Chem. 276, 4724-4732]. We hypothesized that GSH completes the coordination shell of an NO[bond]Fe complex that is released from the cell. In this report we have extended our studies to further characterize the mechanism of NO-mediated Fe mobilization. Native PAGE 59Fe-autoradiography shows that NO decreased ferritin-59Fe levels in cells prelabelled with [59Fe]transferrin. In prelabelled cells, ferritin-59Fe levels increased 3.5-fold when cells were reincubated with control media between 30 and 240 min. In contrast, when cells were reincubated with NO, ferritin-59Fe levels decreased 10-fold compared with control cells after a 240-min reincubation. However, NO could not remove Fe from ferritin in cell lysates. Our data suggest that NO intercepts 59Fe on route to ferritin, and indirectly facilitates removal of 59Fe from the protein. Studies using the GSH-depleting agent, L-buthionine-(S,R)-sulphoximine, indicated that the reduction in ferritin-59Fe levels via NO was GSH-dependent. Competition experiments with NO and permeable chelators demonstrated that both bind a similar Fe pool. We suggest that NO requires cellular metabolism in order to effect Fe mobilization and this does not occur via passive diffusion down a concentration gradient. Based on our results, we propose a model of glucose-dependent NO-mediated Fe mobilization.

Adenocarcinoma↗
PubMed1994

Agonist-specific calcium signaling and phosphoinositide hydrolysis in human SK-N-MCIXC neuroepithelioma cells.

Fura-2 digital imaging microfluorimetry was used to evaluate the Ca2+ signals generated in single clonal human neuroepithelioma cells (SK-N-MCIXC) in response to agonists that stimulate phosphoinositide hydrolysis. Addition of optimal concentrations of either endothelin-1 (ET-1), ATP, oxotremorine-M (Oxo-M), or norepinephrine (NE) all resulted in an increase in the concentration of cytosolic calcium (Ca2+i) but of different magnitudes (ET-1 = ATP > Oxo-M > NE). The Ca2+ signals elicited by the individual agonists also differed from each other in terms of their latency of onset, rate of rise and decay, and prevalence of a sustained phase of Ca2+ influx. The Ca2+ signals that occurred in response to ATP had a shorter latency and more rapid rates of rise and decay than those observed for the other three agonists. Furthermore, a sustained plateau phase of the Ca2+ signal, which was characteristic of the response to Oxo-M, was observed in < 40% of cells stimulated with ET-1 and absent from Ca2+ signals elicited after NE addition. Removal of extracellular Ca2+ enhanced the rate of decay of Ca2+ signals generated by ATP, ET-1, or Oxo-M and, when evident, abolished the sustained phase of Ca2+ influx. In the absence of extracellular Ca2+, NE elicited asynchronous multiple Ca2+ transients. In either the absence or presence of extracellular Ca2+-, > 94% of cells responded to ET-1 or ATP, whereas corresponding values for Oxo-M and NE were approximately 74 and approximately 48%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗