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PubMed1988

Diabetes affects sorbitol and myo-inositol levels of neuroectodermal tissue during embryogenesis in rat.

ATP, ADP, phosphocreatine (PCr), creatine (Cr), glucose, malate, sorbitol, and myo-inositol (MI) were measured by quantitative histochemical techniques in pure neuroectodermal tissue of rat embryos of gestation days 11 and 12 that were dissected from normal and streptozocin-induced diabetic mothers. Neither gestational age nor maternal diabetes affected the tissue's energy potential (ATP-to-ADP and PCr-to-Cr ratios). Diabetes resulted in a fourfold rise in the embryonic glucose and a 25% increase in neuroectodermal malate content. Maternal hyperglycemia caused a rise in fetal sorbitol at days 11 and 12 of gestation. The MI content of the neuroectoderm was not affected by the maternal diabetic state in perfusion embryos (day 11); however, the near doubling of MI that occurs from day 11 to day 12 during normal development was prevented. Thus, embryos isolated from diabetic mothers on gestation day 12 had 30% less MI than embryos isolated from normal mothers. From these data we conclude that a rise in tissue sorbitol is not always accompanied by a fall in tissue MI. These results and recent information in the literature implicate involvement of decreased MI concentrations in the process leading to malformation of the nervous system in diabetic embryopathy.

Adenosine Diphosphate↗
PubMed1992

Development of multidrug resistance in a primitive neuroectodermal tumor cell line.

Drug resistance remains a formidable obstacle to the successful treatment of pediatric primitive neuroectodermal tumors. Resistance to chemotherapeutic agents may be related, in part, to expression of the multidrug resistance gene 1 (MDR1). The protein product of this gene, P-glycoprotein, confers resistance to multiple unrelated antineoplastic drugs. The cell line DAOY, derived from a primitive neuroectodermal tumor, was used as an in vitro model to examine the development of drug resistance. Cell lines resistant to actinomycin D were developed by the growth of DAOY in increasing concentrations of the drug. The IC50 (concentration of drug needed to induce a 50% reduction in cell growth) of the resultant lines to actinomycin D was more than 10 times that of the parental line. The resistant lines were cross-resistant to VP-16 (etoposide), despite lack of previous exposure to this drug. The resistance to actinomycin D was attenuated in the presence of verapamil, a known inhibitor of P-glycoprotein. The MDR1 gene was not expressed by the parental DAOY line at the messenger ribonucleic acid (RNA) and protein level. Expression of the MDR1 gene was documented in the resistant lines by RNA blot and immunoblot techniques. These results suggest that exposure to chemotherapeutic drugs can induce classical multidrug resistance in primitive neuroectodermal tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

[Expression of immunohistochemical differentiation markers in normal and transformed neoplastic neuroectodermal stem cells].

The cells of primitive neuroectodermal tumours may undergo differentiation and, eventually, may be transformed to neurons, glial cells, and ependymal cells. Early stages of neuroectodermal differentiation may primarily be determined by means of immunohistochemical methods. Immunohistochemical investigations were performed on brains of human foetuses obtained from the 18th to 36th weeks of pregnancy, with a view to elucidating the process of maturation during foetal development and to determining the antigens identifiable in cells in the course of differentiation, following fixation in formalin and embedding in paraffin. Gliafibrillar acid protein (GFAP) and vimentin proved to be of particularly high stability and, consequently, were easily detectable from paraffin material. The same antigens were focally recordable also from eight of 17 primitive neuroectodermal tumours. Clues were rare in these tumours as to neuronal differentiation. This was attributed to instability of neurofilament proteins under conditions of formalin fixation and paraffin embedding.

Adult↗
PubMed1992

Evidence for a 17p tumor related locus distinct from p53 in pediatric primitive neuroectodermal tumors.

Primitive neuroectodermal tumors of the central nervous system are the most common malignant brain tumors in children. Cytogenetic analysis of these tumors has demonstrated alterations of chromosome 17, in particular isochromosome 17q, as the most frequent chromosomal abnormality detected. Since the consistent loss of a specific chromosomal region in a given tumor type most likely indicates the presence of a tumor related gene in that region, we undertook a combined molecular and cytogenetic approach to examine alterations of chromosome 17 in primitive neuroectodermal tumors. Seven of 14 tumors analyzed demonstrated loss of alleles for loci on 17p. In three of the seven tumors tested, a loss in copy number was observed for only the most telomeric locus on 17p13.3, D17S34. Limited sequence analysis of the same seven tumors did not reveal mutations in four highly conserved coding regions of the p53 gene. These data suggest a new tumor associated locus on 17p distinct from and distal to TP53, which is involved in the initiation or progression of at least a subset of primitive neuroectodermal tumors.

Amino Acid Sequence↗
PubMed1991

Nerve growth factor receptor expression in peripheral and central neuroectodermal tumors, other pediatric brain tumors, and during development of the adrenal gland.

Nerve growth factor (NGF) is important to the survival, development, and differentiation of neurons. Its action is mediated by a specific cell surface transmembrane glycoprotein, nerve growth factor receptor (NGFR). In this study, NGFR expression by human fetal and adult adrenal medullary tissue, peripheral nervous system (PNS) neuroectodermal tumors (neuroblastoma, ganglioneuroblastoma, ganglioneuroma), pediatric primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS), and CNS gliomas was examined by an immunohistochemical technique. Sixty-nine tumors in total were probed in this manner. Nerve growth factor receptor immunoreactivity was confined to nerve fibers and clusters of primitive-appearing cells in the fetal adrenal, and to nerve fibers and ganglion cells of the adult adrenal medulla; adrenal chromaffin cells were negative. In PNS neuroectodermal tumors, there was NGFR expression in tumor cells of 6 of 11 neuroblastomas and 6 of 6 ganglioneuroblastomas or ganglioneuromas. Thirteen of thirty-five CNS PNETs showed NGFR positivity. In most CNS PNETs, NGFR was restricted to scattered single or small groups of cells, but two tumors with astroglial differentiation showed much more extensive immunoreactivity. Most astrocytomas (11 of 14) and all ependymomas (3 of 3) were intensely NGFR positive.

Adolescent↗
PubMed1990

Reduction to homozygosity and gene amplification in central nervous system primitive neuroectodermal tumors of childhood.

The loss of genetic material from specific chromosomal locations has been identified for a number of pediatric tumors. This loss has been taken as evidence for the importance of tumor suppressor genes at these loci in the genesis of these tumors. One of these pediatric tumors, the primitive neuroectodermal tumor of the central nervous system, has not been well studied. In this report, an analysis of primitive neuroectodermal tumors for allelic deletions on chromosomes 1p, 7q, 10, 11p, 13q, and 17p has been performed. One of ten tumors was found to have increased copies of c-myc. Three different patients were found to reduce to homozygosity at one of three different locations. Significantly, however, three of nine informative patients showed a reduction to homozygosity on chromosome 17p. Thus, primitive neuroectodermal tumor is one of a growing number of tumor types in which deletions in the short arm of chromosome 17 might be important in oncogenesis.

Brain Neoplasms↗
PubMed1984

Neuroectoderm of the early embryonic rat eye. Scanning electron microscopy.

A more accurate description of the changes that occur in the neuroectodermal portion of the developing eye is possible if the surface ectoderm and its underlying mesectoderm are dissected away prior to scanning electron microscopic analysis. A clean preparation of the basal surface of the neuroectoderm with its basal lamina can be prepared by this method. The primitive eyes form during day 11 as lateral diverticula from the forebrain in the rat embryo. These optic vesicles initially have a broad attachment to the diencephalon. By day 12, a true optic stalk connects the optic vesicle to the brain. As the vesicle approaches the surface ectoderm, it involutes to form the optic cup. During day 13, the cup deepens and creates a prominent rim on all but its ventral side. This cleft in the ventral portion of the optic cup is known as the optic fissure. Three portions of the neuroectodermal eye are apparent at this stage: the optic cup, optic stalk, and a short narrow region that joins these two--the collum. The optic fissure extends into the collum but ends abruptly at the junction of the collum with the stalk. The fissure closes on day 14. Its only remnants at this time are a shallow groove in the optic cup and a small patent portion in the collum that permits passage of the intraocular vessels.

Animals↗
PubMed1996

Peripheral primitive neuroectodermal tumors. CT and MRI evaluation.

The clinical, radiographic, and pathologic features of 17 patients with documented peripheral primitive neuroectodermal tumor (PNET) were evaluated in a retrospective study. The age at diagnosis ranged from 9 months to 46 years (median, 15.8 years). Primary sites of involvement were the abdomen (n = 8), extremities (n = 5), chest (n = 1), temporal bone (n = 1), maxilla (n = 1), and diploe (n = 1). At the time of diagnosis, six patients had distant metastases; all of these patients died, with an average survival of 8.8 months. Radiologic workup included standard radiographs, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy. The radiographic appearance of these tumors was not specific for differentiation of PNETs from other types of bone and soft tissue tumors. The typical appearance resembled large non-calcified, soft tissue masses with cystic or necrotic areas. Heterogeneous enhancement with intravenous contrast agents was evident on CT, as was an intermediate signal intensity on Tl-weighted images and hyperintense signal on T2-weighted and STIR sequences. After gadolinium administration, variable enhancement was seen. MRI and CT were useful in predicting resectability, in detecting distant metastases, and in the evaluation of response to treatment. Surgery was performed in all cases, either for definitive diagnosis or for therapy. All patients received combined chemotherapy and radiotherapy and five patients received autologous bone marrow transplantation. Clinical follow-up was obtained over a mean period of 3 years (range 1 day to 6 years). Prognosis was poor with a median survival of 3.4 years. Our experience in 17 patients with peripheral neuroectodermal tumors indicates that although their radiologic features are non-specific, they should be included in differential diagnosis of soft tissue tumors of aggressive behavior, especially in a young age group. CT and MRI are useful in delineating the extent and resectability of tumor and in monotoring treatment.

Adolescent↗
PubMed1994

Primitive neuroectodermal tumor of the orbit.

A 10-year-old girl developed a lump in the lateral aspect of the right eyebrow over a 3-week period. Computed tomography and magnetic resonance imaging revealed a soft-tissue mass in the superolateral aspect of the right orbit associated with zygo-maticofrontal bone erosion and hyperostosis. An incisional biopsy specimen was studied using light microscopy, immunohistochemical staining, and electron microscopy, resulting in a diagnosis of peripheral primitive neuroectodermal tumor. The results of an extensive evaluation for systemic involvement were negative. The patient was subsequently treated with chemotherapy and radiation therapy. Primary primitive neuroectodermal tumor of the orbit is rare. The differential diagnosis and the diagnostic features of this entity are discussed herein.

Child↗
PubMed1996

Neuroectodermal antigens persist in benign and malignant salivary gland tumor cultures.

OBJECTIVE: To determine whether a heterogeneous collection of salivary gland tumors shared common antigenic characteristics and growth patterns in tissue culture. DESIGN: Cell cultures were derived from benign and malignant salivary gland neoplasms, cultured conservatively, and serially analyzed for epithelial, myoepithelial, and neuroectodermal antigens. SUBJECTS: Nineteen samples reflecting the spectrum of salivary tumor pathologic characteristics were established in tissue culture. Most were derived from benign pleomorphic adenomas, and several were from carcinomas, including carcinoma ex pleomorphic adenoma, and mucoepidermoid and adenoid cystic carcinoma. RESULTS: All cultures were epithelial as determined by morphologic and antigenic examination, using antibodies for cytokeratin. The phenotype of cells derived from benign tumors, especially the pleomorphic adenomas, resembled those in the original neoplasm. Those from carcinomas were similar, with less differentiated characteristics. Manipulation of growth conditions altered the phenotypes shown in culture. Some cultures contained cells expressing vascular smooth-muscle actin and glial fibrillary acidic protein or nestin. CONCLUSIONS: This model cell system containing proliferative cells from several tumor types is consistent with a stem-cell theory of salivary gland tumor origin. Our data were not consistent with the bicellular or multicellular theory. We hypothesize a neuroectodermal origin for this group of apparently heterogeneous tumors. These cultured cells will be valuable for in-depth investigation of the loss of proliferation controls in benign and malignant tumors of the salivary gland.

Antibodies, Monoclonal↗
PubMed2000

Outcome for children with supratentorial primitive neuroectodermal tumors treated with surgery, radiation, and chemotherapy.

BACKGROUND: The outcome of a child with a primitive neuroectodermal tumors arising supratentorially (SPNET) is not well characterized and may differ from the outcome of a patient with a histologically similar cerebellar tumor (medulloblastoma [MB]). Recently, 5-year progression free survival rates as high as 80% have been reported for children with MB treated with craniospinal radiation (CRT) and chemotherapy including cisplatin, lomustine (CCNU), and vincristine (VCR). METHODS: The authors reviewed the outcome of 22 consecutive patients age 3 years and older (mean age, 10 years; range, 3-18 years) with SPNET who were treated at the study institutions between 1981 and 1996. Tumor location included was 13 pineal, 6 cortical, and 3 thalamic or suprasellar. Five patients had disease dissemination at diagnosis. All patients underwent surgery and staging, followed by CRT and chemotherapy with cisplatin, CCNU, and VCR. RESULTS: Of the 22 patients, 13 had developed disease progression and 10 had died at the time of last follow-up. Overall progression free survival (PFS) was 47% +/- 11% at 3 years and 37% +/- 11% at 5 years. There was a significant difference in PFS between patients with localized disease versus those with disseminated disease (P = 0.04). There was no statistical association between tumor location and survival. Although not significant (P = 0.21), there was a trend toward better survival of those patients with complete or near-complete resection compared with those with partial resection or biopsy. CONCLUSIONS: The results of the current study demonstrate that the outcome for children with SPNET treated with radiation and chemotherapy appears worse than for children with MB treated with identical therapy. This suggests that there may be biologic differences between supratentorial and infratentorial primitive neuroectodermal tumors, thus requiring refinements in treatment.

Adolescent↗
PubMed1992

Sinonasal primitive neuroectodermal tumor arising in a long-term survivor of heritable unilateral retinoblastoma.

BACKGROUND: Patients who survive retinoblastoma (RB) are at risk for having second nonocular tumors, usually osteosarcomas, which often are fatal. Such patients almost always have bilateral RB. METHODS: This article reports a woman who, at the age of 1 year had been cured of a unilateral RB by radiation therapy and enucleation. Eighteen years later, she had a sinonasal small cell tumor that rapidly recurred and proved fatal 2 months after surgical debulking. The tumor was studied by immunohistochemistry and electron microscopic (EM) examination. RESULTS: It showed diffuse neuron-specific enolase staining, focal weak staining for chromogranin, synaptophysin, and Leu-7 monoclonal antibodies in paraffin-embedded, B5-fixed tissue (Great Lakes Diagnostics, Troy, MI). EM study showed an undifferentiated primitive neuroectodermal tumor with many polyribosomes, simple cell junctions, few microtubules, and rare dense core granules. CONCLUSIONS: The combined immunohistochemical, ultrastructural, and clinical features of the tumor were interpreted as a sinonasal primitive neuroectodermal tumor with early neuronal differentiation. The tumor was pathologically indistinguishable from poorly differentiated olfactory neuroblastoma (ONB) and Ewing sarcoma.

Chromogranins↗
PubMed2003

Malignant peripheral primitive neuroectodermal tumor-peripheral neuroepithelioma of the head and neck: a clinicopathologic study of five cases and review of the literature.

BACKGROUND: The term primitive neuroectodermal tumor (PNET) encompasses a number of neoplasms of common neuroectodermal origin, but of variable clinical, histopathologic, ultrastructural, and molecular characteristics. Here, we focus on one particular member of the PNET family, the malignant peripheral PNET (pPNET) or peripheral neuroepithelioma of head and neck. METHODS: Five patients diagnosed with malignant pPNET-peripheral neuroepithelioma of head and neck were included in the study. All existing literature was reviewed. RESULTS: The diagnosis of malignant pPNET-peripheral neuroepithelioma of the head and neck was confirmed in all five cases. All patients are alive after treatment with a combination of therapeutic modalities; only one patient had metastatic disease develop. A literature review revealed another 38 reported cases. CONCLUSIONS: Malignant pPNET-peripheral neuroepithelioma should be included in the differential diagnosis of small, round, blue cell tumors of head and neck. A combination of multiple diagnostic modalities is essential for correct diagnosis, and multimodality treatment offers the best outcome.

12E7 Antigen↗
PubMed2003

Involvement of p53 in specific anti-neuroectodermal tumor activity of aloe-emodin.

Previously, we have identified aloe-emodin (AE) as a new type of anticancer agent, with activity that is based on apoptotic cell death promoted by a neuroectodermal tumor-specific drug uptake. We attempt to clarify the intracellular target of AE and the apoptosis-signaling pathway activated by AE in neuroblastoma cell lines. Two-photon excitation microscopy and spectroscopic titrations documented that AE is highly concentrated in susceptible cells and binds to DNA. One of the most important mediators of apoptotic response to genotoxic stimuli, such as anticancer agents, is the p53 tumor suppressor gene. To evaluate the role played by p53 in AE-induced apoptosis a p53 mutant cell line, which lacks transcriptional activity of p53 targeted genes, was tested. AE displayed a reduced growth inhibitory and pro-apoptotic activity in p53 mutant cells (SK-N-BE(2c)) with respect to the p53 wild-type line (SJ-N-KP). This effect was not caused by a reduced drug uptake in the mutant neuroblastoma cell line but was related to a different apoptotic cell phenotype. Whereas SJ-N-KP cells were susceptible to a p53 transcription-dependent pathway of apoptosis, SK-N-BE(2c) cells underwent apoptosis with up-regulation of p53 expression but not of p53-target genes. After AE treatment p53 translocates to the mitochondria inter-membrane space in both neuroblastoma cell lines. Due to its high accumulation in neuroectodermal tumor cells AE could also kill tumor cells harboring p53 mutant genes. This property would further contribute to AE specific anti-tumor activity and might be exploitable in the clinic.

Anthraquinones↗
PubMed1982

Congenital primitive neuroectodermal tumor (neuroepithelioma) of the chest wall.

Primitive neuroectodermal tumor (neuroepithelioma) is a relatively common central nervous system tumor in children. Those arising from a peripheral nerve are extremely rare in childhood. There is only one reported case in 6-year-old where the tumor arose from the sciatic nerve. A case of neuroectodermal tumor of the chest wall, arising from the intercostal nerve, in a newborn is presented. The tumor metastasized to the brain. Prominent Homer-Wright rosettes, with central eosinophilic fibrillar substance similar to that seen in neuroepithelioma of the central nervous system, were present in the primary tumor and brain metastases. Ultrastructure, as revealed by transmission electron microscopy, is also described.

Brain Neoplasms↗
PubMed1993

Modulation of POMC expression in human neuroectodermal cells.

Neuroblastoma cell lines have been reported to contain two proopiomelanocortin (POMC) mRNA transcripts. We have now shown by immunocytochemistry and radioimmunoassay (RIA) that a number of neuroectodermally derived cell lines contain immunoreactive beta-endorphin although cell concentrations were not characteristic of any tumour type. To explore further the functional significance of beta-endorphin expression, we analysed neuroblastoma cell lines having intermediate (I), substrate adherent (S) and neuronal (N) phenotypes. No differences in cell beta-endorphin content were detected. However, the expression of POMC mRNA and of immunoreactive beta-endorphin was reduced within a few hours of treatment of these cell lines with retinoic acid. Culture of the cell lines in the presence of beta-endorphin resulted in small but significant increases in growth. Although the POMC gene is in the same chromosomal segment as N-myc, which is normally amplified in neuroblastoma, no corresponding amplification of POMC could be demonstrated. The data suggest that POMC gene products may contribute to the autocrine/paracrine growth of neuroectodermal tumours.

Cell Line↗
PubMed1995

Growth-inhibiting effect of intratumoral recombinant human tumor necrosis factor on an experimental model of primitive neuroectodermal tumor.

The effect of intratumoral administration of recombinant human tumor necrosis factor on an experimental model of primitive neuroectodermal neoplasia was studied. A clear inhibition of tumor growth was achieved by immunotherapy that consisted in intralesion injections of 100 micrograms of tumor necrosis factor daily, the first three days of each week, for a period of four weeks. At this time, tumor size was 2.21 +/- 0.66 cm2 (mean +/- standard deviation) in the treated group, versus 7.62 +/- 0.43 cm2 in the control group. These data support previous studies on the influence of tumor necrosis factor on the development of ethyl-nitrosourea-induced tumors, and suggest the potential usefulness of this cytokine in human primitive neuroectodermal neoplasms.

Animals↗