Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Neuroectodermal Tumors, Primitive”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,423 records · Page 79Linked to original sources
PubMedDate not supplied

Protein gene product (PGP) 9.5 in diagnostic (neuro-) oncology. An immunomorphological study.

Most likely identical to ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), protein gene product (PGP) 9.5 is one of the major constituents of cytoplasmic polypeptides in neurons. The antigen seems to be expressed almost exclusively in neuronal and neuroendocrine tissues and their neoplasms. PGP 9.5 is also present in undifferentiated embryonic neoplasms like primitive neuroectodermal tumors (PNETs). However, the significance of PGP 9.5 as a marker in diagnostic (neuro-) oncology has not been systematically evaluated yet. In the present study the sensitivity and specificity of the widely used antiserum against PGP 9.5 has been retrospectively examined on 290 formalin-fixed, paraffin-embedded tumors of the nervous system and small round blue cell tumors. The presence of the antigen in tumors of neuronal (24/24) and neuroendocrine (63/73) differentiation confirm PGP 9.5 as a sensitive marker of these tumor groups, particularly in the diagnosis of pituitary adenomas where the expression was neither related to the staining behavior of the tumors in the PAS-orange G-reaction nor to their degree of polypeptide- and glycoprotein hormone activity. The nearly constant immunostaining of medulloblastomas (18/19) and other PNETs (5/6) demonstrate the role of PGP 9.5 as an additional marker in the detection of these embryonic tumors as this peptide was not or only weakly found in glial (11/58), meningeal (5/29), and nerve sheath neoplasms (1/28). On the other hand, the significance in the differential diagnosis of small round blue cell tumors seems to be limited because of positive immunoreactions in neuroblastomas (7/7) and oat cell carcinomas of the lung (7/7) although rhabdomyosarcomas (1/6) and malignant Non-Hodgkin-lymphomas (0/13) react completely negative in our series.

Autonomic Nervous System Diseases↗
PubMed1995

A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1.

Most Ewing's sarcomas or related primitive neuroectodermal tumors have the (11;22)(q24;q12) or less frequently the (21;22)(q22;q12) translocation. These rearrangements fuse the EWS gene on chromosome 22q12 to either the FLI1 or ERG genes, both members of the ETS family of transcription factors. Simple variant chromosomal translocations have been occasionally described in these tumors. We have identified a third Ewing's sarcoma translocation, the t(7;22)(p22;q12), that fuses EWS to the human homologue of the murine ETS gene ER81. This gene, designated ETV1 (for ETS Translocation Variant), is located on chromosome band 7p22. Identical EWS nucleotide sequences found in the majority of EWS-FLI1 and EWS-ERG chimeric transcripts are fused to a portion of ETV1 encoding an ETS domain with sequence specific DNA-binding activity. These findings confirm that the fusion of EWS to different ETS family members can result in a similar tumor phenotype.

Adult↗
PubMed1995

[Stereotactic brain biopsy].

During a 3-year period starting in 1991, 49 patients with brain lesions underwent 50 stereotactic brain biopsy procedures. The average age was 46 years (range 4-74). Specimens were taken from various brain regions, particularly from the deep aspect of the cerebral hemispheres and midline structures. The pathologic entities included 27 gliomas (13 glioblastomas, 6 astrocytomas, 3 anaplastic astrocytomas, 1 pilocytic astrocytoma and 4 oligodendrogliomas), 5 lymphomas, 2 germinomas, 1 primitive neuroectodermal tumor, 2 metastatic tumors and 11 non-neoplastic lesions (4 demyelination, 2 infarcts, 1 hematoma, 1 brain abscess, 1 radiation necrosis, 1 Alzheimer's disease and in 1 case no diagnosis). The diagnostic success of the stereotactic brain biopsies in this series was 96% (in 98% of the patients). The mean hospital stay was 3 days. 1 patient with a multifocal bilateral glioblastoma died due to early postoperative hematoma of the basal ganglia (2%). Another 2 patients underwent craniotomy due to post-biopsy hematoma. They continued to suffer from hemiparesis after discharge. Transient Horner's syndrome was noted in 1 patient. Thus the permanent morbidity rate was 4%. We conclude that stereotactic brain biopsy can be performed relatively safely, has a high diagnostic yield, and facilitates planning of treatment.

Adolescent↗
PubMed1993

D-CECaT: a breakthrough for patients with neuroblastoma.

In view of the high relapse rate following chemotherapy for patients with advanced neuroblastoma (NB) and primitive neuroectodermal tumors (PNET), we designed a novel chemotherapy program which incorporated the iron chelator deferoxamine. The purpose of the deferoxamine was to sensitize the cells to standard chemotherapy. The D-CECaT regimen contained (in mg/m2): deferoxamine 4500 during days 1-5; cyclophosphamide 600 mg over days 6 and 7; etoposide 300 mg over days 7 and 8; carboplatin 100 mg over days 7 and 8; and thiotepa 30 mg over days 6-8. Between October 1989 and May 1992 we entered 23 advanced NB and two PNET patients. Sepsis occurred in four courses, nausea and vomiting in 30 courses, and 50 courses required blood and platelets. Responses observed in previously untreated patients with stage III NB: six out of six CR (17+ to 41+ months), with stage IV NB, nine out of 11 CR (14+ to 28+ months), two out of 11 VGPR (22+ months), with stage IV PNET two out of two CR (1+ to 35+ months). With previously treated and failed stage IV NG, two out of six VGPR for 19+ and 20 months, and four out of six PR 1, 8, 9 and 11 months. Median survival for 19 new patients was 22+ months (6 to 41+ months; two patients in CR died at 7 months during adjuvant autologous marrow transplant). In conclusion, D-CECaT is an effective initial cytoreductive regimen for advanced stage NB/PNET patients. Additional patients and studies are required to determine its use as an alternative to autologous bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Co-expression of low molecular weight neurofilament protein and glial fibrillary acidic protein in established human glioma cell lines.

This report describes the expression of glial and neuronal cytoskeletal proteins and their messenger RNAs (mRNAs) in established cell lines derived from human primitive neuroectodermal tumors (PNETs) and malignant gliomas. Northern blot analyses revealed neurofilament (NF) protein mRNAs in 6 of 7 PNET cell lines but no glial fibrillary acidic protein (GFAP) mRNA. Six of these cell lines contained mRNA for the microtubule-associated protein (MAP) known as MAP1b, whereas MAP2 mRNAs were detected only in 1 of the PNET cell lines. These findings closely paralleled previously published data on the expression of these cytoskeletal proteins in the same group of PNET cell lines. Although GFAP mRNA was detected in only 2 of 5 glioma cell lines, 4 of these cell lines contained mRNAs for the low-molecular-weight (M(r)) NF protein (NF-L). Western blot analysis confirmed the expression of both GFAP and NF-L protein in 2 of the glioma cell lines (U251 MG and U373 MG) that contained GFAP and NF-L mRNAs. Further, double immunofluorescence studies showed that GFAP and NF-L co-localized in the same glioma cells. In contrast, neither the middle- (NF-M) or high- (NF-H) M(r) NF proteins or their mRNAs were detected in any of these glioma cell lines. Finally, MAP1b mRNA was expressed in all 5 glioma cell lines, whereas MAP2 mRNAs were detected in only 3 of the cell lines. This is the first documentation of the expression of both glial-specific and neuron-specific cytoskeletal proteins in human malignant glioma-derived cell lines. These data may reflect the aberrant induction of neuron-specific gene products in some neoplastic glial cell lines. Alternatively, our findings may indicate that some glioma cell lines correspond to transformed bipotential human central nervous system precursors of cells restricted to a neuronal or glial lineage.

Central Nervous System Neoplasms↗
PubMed1996

The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator.

Molecular characterization of malignant melanoma of soft parts or soft tissue clear cell sarcoma which shares t(12;22) chromosome translocation revealed fusion of EWS with a transcriptional factor gene ATF-1. The EWS gene, which encodes an RNA binding protein, was also shown to be involved in Ewing sarcoma, related primitive neuroectodermal tumors and desmoplastic small round cell tumors. In order to understand the functional role of EWS-ATF-1 chimeric protein in human solid tumors, we have cloned the aberrant human ATF-1 (EWS-ATF-1) cDNA and studied its DNA binding, transcriptional activation properties and compared with normal ATF-1 protein. Our results demonstrate that EWS-ATF-1 binds weakly to DNA in vitro but functions as an efficient constitutive transcriptional activator unlike the normal ATF-1 which needs to be induced with cAMP. Deletion analysis revealed that EWS-fusion domain functions as a regulatory domain for the transcriptional activation properties of EWS-ATF-1 chimeric protein. Deletion of leucine zipper domain results in a loss of transcriptional activation of EWS-ATF-1 chimeric protein suggesting that protein-protein interaction play a role in the transcriptional activation properties of EWS-ATF-1. We demonstrate that EWS-fusion domain negatively regulates the DNA binding activity of EWS-ATF-1 chimeric protein. Therefore replacement of part of the amino-terminal kinase regulatory domain of ATF-1 protein with EWS regulatory domain results in an altered DNA binding, protein-protein interactions and transcriptional activation properties of EWS-ATF-1 causing deregulated gene expression which may be responsible for the genesis of t(12;22) chromosome translocation-bearing human solid tumors. Targeting the transcriptional cofactors (CBP, etc) by EWS-fusion proteins could be one of the mechanisms of activation of EWS-fusion proteins in human neoplasia.

Activating Transcription Factor 1↗
PubMedDate not supplied

A novel PNET cell line with melanotic differentiation.

The primitive neuroectodermal tumor (PNET) cell line, ONS-99, was established from a human melanotic neuroectodermal tumor of infancy (MNTI). ONS-99 cells were polygonal adherent cells and transplantable to BALB/c-nu/nu mouse. ONS-99 cells were positive for NSE, HMB-45 (melanoma-associated antigen) and N-myc, but lacked the antigenic features of terminally differentiated neurons or glias. ONS-99 cells had many intermediate filaments in the cytoplasm and tight intercellular junctions with scant cytoplasmic structures by electron microscopy. To date, ONS-99 is the only example of an established PNET cell line with melanotic differentiation.

Animals↗
PubMed1996

Profiles of neuronal thread protein expression in Alzheimer's disease.

Neuronal thread proteins (NTPs) comprise a family of molecules expressed in brain and primitive neuroectodermal tumor cell lines. In Alzheimer's disease (AD), increased CNS levels of the 21 kD NTP species are correlated with dementia. The present study characterizes the nature and distribution of NTP expression using recently generated brain-derived polyclonal and monoclonal antibodies (MoAbs) to recombinant AD7c-NTP protein. In AD, high levels of NTP immunoreactivity were detected in neuronal perikarya, neuropil fibers, and white matter fibers (axons). In addition, 4 of the 23 AD7c-NTP MoAbs labeled degenerating neurons (with or without neurofibrillary tangles), axonal spheroids, dystrophic neurites, or irregular, wavy threadlike neuropil fibers in AD. Increased neuronal AD7c-NTP immunoreactivity in AD colocalized with perikaryal accumulations of tau-1, phosphorylated neurofilament, and the ganglioside, A2B5. In addition, AD7c-NTP immunoreactivity was detected in early neuritic plaques along with beta-amyloid-containing fibrils, but not in mature plaques, nor was it colocalized in beta A4-immunoreactive fibrils. This study demonstrates the profiles of NTP overexpression in relation to paired helical filament-associated neurodegenerative lesions in AD.

Aged↗
PubMedDate not supplied

Unusual cerebellar ganglioglioma with marked cytologic atypia.

Neuronal differentiation is well documented in cerebellar primitive neuroectodermal tumors but is uncommon in other cerebellar neoplasms. Although rare, gangliogliomas and gangliocytomas have been previously described in the cerebellum. We report a cerebellar ganglioglioma in a 14-year-old boy, which revealed bizzare markedly pleomorphic cells with extremely pronounced nuclear atypia but less than one mitosis per 50 high-power fields and no necrosis. The tumor showed glial as well as neuronal differentiation, with abundant bi- and multinucleated ganglion cells. There were abundant Rosenthal fibers, eosinophilic granular bodies, focal calcification, and perivascular lymphocytic infiltrates. There has been no evidence of tumor recurrence or neurological deterioration 21 years after surgery, although the marked nuclear atypia led to an initial diagnosis of an anaplastic glioma. We stress the need for careful evaluation of cerebellar gliomas in children that show only nuclear atypia or endothelial hyperplasia in the absence of other features of malignancy.

Adolescent↗
PubMed1998

Total parenteral nutrition on energy metabolism in children undergoing autologous peripheral blood stem cell transplantation.

The resting energy expenditure (REE) and the respiratory quotient (RQ) were measured longitudinally using indirect calorimetry to examine the effects of total parenteral nutrition (TPN) on energy metabolism in children undergoing autologous peripheral blood stem cell transplantation (PBSCT). There were six children (two males and four females) and the age ranged from five to 13 years (median, eight yrs). The diagnosis included acute lymphocytic leukemia (ALL; 4), neuroblastoma (NBL; 1) and primitive neuroectodermal tumor (PNET; 1). TPN was started after the patients were stabilized following PBSCT (group A; n = 3) or before the initiation of high-dose cytoreductive chemotherapy (HCC) (group B; n = 3). Duration of HCC before PBSCT was identical between the two groups (six to eight days). Average total calorie and protein intake during HCC was significantly higher for group B than for group A. The %REE, the percentage of REE to the predicted basal energy expenditure (BEE), in group A showed 133 +/- 19%, 129 +/- 14% and 146 +/- 11% during three periods of HCC (days -8 to -1 of PBSCT), bone marrow suppression (days 0 to 11 of PBSCT) and bone marrow recovery (days 12 to 22 of PBSCT), respectively. In contrast, those in group B were 10% to 20% lower than those in group A at all periods. Carbohydrate oxidation rates during HCC in group A were significantly lower than those in group B, and those were not different between both groups during post-PBSCT periods. Fat oxidation rates in both groups were similar at all stages of periods. In contrast, protein degradation rates in group A were significantly higher than those in group B at all stages of the period. From these results, we concluded that commencement of TPN administration prior to HCC in the patients undergoing PBSCT provides beneficial effects to maintain better energy metabolic and nutritional status.

Adolescent↗
PubMed1996

Correlation of chromosome 17p loss with clinical outcome in medulloblastoma.

Medulloblastomas are primitive neuroectodermal tumors that arise in the cerebella of children. Cytogenetic and loss of heterozygosity (LOH) studies have shown that deletions on the short arm of chromosome 17 occur in 25-50% of cases, suggesting that loss of a tumor suppressor gene located on 17p plays a role in the genesis or progression of medulloblastoma. We report here on an LOH analysis of 21 patients with medulloblastoma using markers for 15 polymorphic loci previously ordered on chromosome 17 by meiotic break point mapping. Although the frequency of LOH in our patients (48%) was consistent with previous reports, our maps showed much larger deletions, the smallest spanning a 38-cM genetic distance distal to marker UT49 (D17S731). Survival analysis did not show a significant association between LOH on 17p and survival, although the sample size was too small to rule out a difference of less than 10-fold. Clinical risk factors were better prognostic indicators than LOH, with significantly prolonged survival in patients free of craniospinal metastasis following gross total tumor resection.

Adolescent↗
PubMed2000

Atypical teratoid/rhabdoid tumor of the central nervous system: a comparative study with primitive neuroectodermal tumor/medulloblastoma.

Eleven atypical teratoid/rhabdoid tumors (AT/RT) and 121 primitive neuroectodermal tumors/medulloblastomas (PNET/MB) were included in this study for evaluation of the histopathological features of AT/RT and comparison between AT/RT and PNET/MB. Histopathological studies of AT/RT showed that in addition to the commonly recognized components, i.e., rhabdoid cells, small (PNET/MB) cells, spindle cells and epithelial components, there was a previously unrecognized component, sickle-shaped embracing cells, which were present in all cases and could be useful as a histological marker of this tumor. Immunohistochemical studies showed divergent differentiation of the tumor cells and among the 16 antibodies studied, vimentin, neuron-specific enolase, epithelial membrane antigen and glial fibrillary acidic protein were most commonly reactive. The frequency of AT/RT expressed as a ratio of AT/RT to PNET/MB was 1:11 in general and increased to 1:3.8 among patients younger than 3 years old. The AT/RT patients were younger than those with PNET/MB and had a female predominance. The MIB-1 labeling index of AT/RT was significantly higher than that of PNET/MB (mean 63.9 vs 40.1), which correlated with a shorter survival in patients with AT/RT than those with PNET/MB (median survival time 15.4 months vs 156.4 months).

Antigens, Nuclear↗
PubMed2001

Medullomyoblastoma: case report.

This 7-year-old boy presented with a 2-week history of headache, nausea, vomiting, anorexia, lethargy, and unsteadiness of gait. Brain magnetic resonance imaging (MRI) revealed a cystic mass within the vermis of the cerebellum. A suboccipital craniectomy was performed to remove a tumor that contained primitive neuroectodermal cells with florid skeletal muscle differentiation. Immunohistochemical studies and electron microscopy confirmed the presence of both a primitive neuroectodermal component and rhabdomyoblastic differentiation, consistent with the diagnosis of medullomyoblastoma. This exceedingly rare tumor of the cerebellar vermis of children is characterized by two components: primitive neuroectodermal tumor cells and skeletal muscle. Although the histogenesis remains uncertain, advances in immunohistochemistry and electron microscopy suggest the origin of this tumor from a multipotential stem cell precursor.

Child↗
PubMed1981

Neuroepithelioma--a rare malignant peripheral nerve tumor of primitive origin: report of two new cases and a review of the literature.

Two cases of primitive neuroectodermal primary peripheral nerve tumors (neuroepitheliomas) are presented. They both demonstrated the rosette pattern described by Homer Wright indicating their neuroectodermal origin, and were unlike Schwann cell tumors. In one case, intensive chemotherapy with local radiotherapy had resulted in a disease-free interval of 30 months at the time of this report. These cases support the existence of neuroepithelioma as a distinct tumor type.

Adult↗
PubMed1991

MRI and pathological findings in two cases of Askin tumors.

Askin tumors are primitive peripheral neuroectodermal tumors (PPNET) located in the thoracopulmonary region. This entity was first proposed in 1979 by Askin et al. These highly malignant tumors occur primarily in children and young adults. Pre- und postoperative MRI findings are presented for two pathologically proven cases. MRI is the most appropriate imaging modality for the diagnosis and eventual follow-up for these tumors. They appear homogenous, and iso- or discretely hypointense in comparison to the spinal cord on T1-weighted images and hyperintense on proton density and T2-weighted images. They show a very stark contrast enhancement after i.v. injection of paramagnetic contrast agents. Sharp tissue borders, and exact tumor extension were shown in both cases. The high signal intensity on T2-weighted images was not altered by chemotherapy.

Adult↗
PubMed2000

Spontaneous apoptosis and retinoic acid receptor incidence in neuroblastomas and peripheral neuroectodermal tumors.

Twelve cases of neuroblastoma (NB) (7 boys and 5 girls) and 4 cases of primitive peripheral neuroectodermal tumor (PNET) (3 boys and 1 girl) were investigated for the presence of apoptosis and retinoic acid receptor (RAR) by immunhistochemical method. The apoptotic index in NB was zero or 1% in 8 children and relatively low (2-4.8%) in the other 4 cases, while it was higher (4.1-10.5%) in PNET. The RAR index determined by immunoperoxidase reaction in NB was zero or 3% in 5 cases and 9-34% in 7 children. RAR index in PNET was 16-68% in all the 4 cases. Good correlation (r = .47 according to Pearson-Bravis) was found between the number of RAR and spontaneous apoptosis. These results suggest that the RAR index in untreated NB and PNET shows great individual variation since its determination is necessary for the evaluation of the efficacy of retinoic acid treatment.

Apoptosis↗
PubMed2004

Immunohistochemical analysis of hSNF5/INI1 in pediatric CNS neoplasms.

Atypical teratoid/rhabdoid tumor (AT/RT) may be misdiagnosed as primitive neuroectodermal tumor/medulloblastoma (PNET) and occasionally as other tumors. Molecular genetic analysis of AT/RT demonstrates deletion and mutation of the hSNF5/INI1 gene in most cases, with decreased or absent expression at the RNA or protein level. Immunohistochemistry with an antibody to INI1 was performed to determine whether this would be a sensitive and specific means of assessing INI1 loss in pediatric brain tumors. Fifty-three tumors consisting of 20 AT/RTs, 10 PNETs, and 23 other central nervous system tumors were examined. No nuclear staining was found in all 20 AT/RTs. Most other central nervous system tumors demonstrated nuclear staining. Eight cases in which classification as AT/RT or PNET was difficult were also examined. Seven cases had no chromosome 22 deletion or INI1 mutation; INI1 antibody showed nuclear staining in these cases. One case was a recurrent tumor with features consistent with an AT/RT. INI1 immunostaining was negative in this case, and a mutation in INI1 was subsequently identified. Immunohistochemical staining with an INI1 antibody correlates with molecular findings in AT/RT and may be useful in confirming the histologic diagnosis. INI1 immunostaining may have particular utility in the analysis of tumors with indeterminate histologic features or atypical immunophenotypic profiles.

Adolescent↗
PubMed2002

Primitive neuroectodermal tumors/medulloblastoma.

The therapy for medulloblastoma/primitive neuroectodermal tumors of the central nervous system is surgery, followed by combination chemo-radiotherapy. The radiation field is the entire craniospinal axis, which is only avoided when treating infants. The treatment is, therefore, lengthy and toxic. Less aggressive therapy is given to patients who clinically appear to have less evidence of disease. Intensive basic research has begun to identify genetic factors of the disease, but these remain far from clinical application.

Brain Neoplasms↗