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Query: UMLS:C0027651 (tumor)
685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA fingerprints were generated by the oligonucleotide probe (GTG)5 from surgically removed tissue and/or primary cell culture of 36 intracranial tumors (31 gliomas, 1 medulloblastoma, 4 metastatic carcinomas) and compared with the constitutional banding pattern obtained from the peripheral blood leukocytes of each patient. A multitude of somatic changes was detected and found to reflect the chromosome alterations identified by parallel karyotype analysis. Gain and/or loss of bands or significant band intensity shifts could be demonstrated in the fingerprints of more than 80% of the tumors investigated. This included a highly amplified fingerprint fragment in five independent gliomas (four of them had double minutes, dmin) which appeared not individual- but tumor-specific (2.4 kilobases, kb, after HaeIII digestion). Rehybridization with the oligonucleotide probes (GT)8 and (GATA)4, respectively, revealed additional amplified fingerprint fragments in the tumor DNA of these patients. While a (ca/gt)n fragment (2.6 kb. HaeIII) was also found to be amplified in all five cases, one band detected with (GATA)4 (1.4 kb, HaeIII) represented a unique feature for one of these tumors only. Amplification of the epidermal growth factor receptor (EGFR) gene via Southern blot hybridization was revealed only in those tumors showing the amplified DNA fingerprint fragments as well. Thus in many gliomas the amplification unit harbors two simple repetitive DNA fingerprint loci, (cac/gtg)n and (ca/gt)n, in addition to the EGFR gene.
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PMID:Coamplification of simple repetitive DNA fingerprint fragments and the EGFR gene in human gliomas. 167 8

A case of cerebellar medulloblastoma with clusters of mature ganglion cells and glial cells is described. The patient, a 15-year-old girl, underwent three operations followed each time by radiation and chemotherapy during the four-year clinical course. Histologically, the ganglion cells were clearly identifiable by their abundant eosinophilic cytoplasm, round nuclei with prominent nucleoli, tigroid granules, and argyrophilic fibrils and axons. Immunohistochemically, the cells were NSE- and NF-positive, and ultrastructurally they contained abundant tubules and filaments, neurosecretory granules and well developed rough endoplasmic reticulum. There were many cells transitional in appearance between primitive cells and mature ganglion cells. The tumor also had many mature yet atypical astrocytes and oligodendrocytes. The exact mechanism of the extensive neuronal and glial maturation of medulloblastoma cells is unclear, but the repetitive surgical interventions, radiation and chemotherapy might have had certain cytostatic effects on rapidly dividing medulloblastoma cells, giving them a chance to mature into postmitotic cells with potential for neuronal and glial differentiation.
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PMID:Ganglioglial differentiation in medulloblastoma. 169 Apr 97

Granulocyte colony-stimulating factor (G-CSF) was previously shown to be produced constitutively by malignant epithelial cells and by monocytes/macrophages, fibroblasts and endothelial cells following stimulation. In this study we investigated the ability of medulloblastoma cells, representing malignant embryonal neuroectodermal cells, to produce G-CSF. Conditioned medium was freshly prepared from unstimulated explanted tumor tissue from two patients with medulloblastoma as well as from the medulloblastoma cell lines TE-671 and DAOY, and as controls normal glial cells. Following 72 hours of culture at a density of 5 x 10(5) cells/ml in RPMI 1640 with 10% FCS, the supernatants were harvested and tested for the presence of G-CSF in (1) the CFU-GM asay, (2) proliferation assay using the G-CSF dependent cell line NFS-60, and (3) Western blot analysis using an anti-G-CSF monoclonal antibody. Biological active and immunological detectable G-CSF was secreted by the medulloblastoma cell line DAOY and by one of the explanted tumor biopsies. The cell line TE-671 as well as normal glial cells did not produce G-CSF under identical culture conditions. We conclude that in addition to previously described sources of G-CSF, neuroectodermally derived medulloblastoma cells are also able to produce G-CSF constitutively. The G-CSF production was increased after stimulation with IL-1 alpha or TNF alpha. The role of G-CSF in neuroectodermal tissues remains to be further investigated.
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PMID:Medulloblastoma cells constitutively produce granulocyte colony-stimulating factor. 169 36

The TE 671 medulloblastoma cell line was induced by phorbol-12-myristate-13-acetate (PMA) to resemble neuronal cells by both morphological and immunohistochemical criteria. Five days following PMA treatment at a concentration of 10 ng/ml, the cells acquired long cellular processes and cell growth was markedly inhibited. Immunohistochemically, PMA-treated cells stained intensely for neuron-specific enolase and were positive for neurofilaments. Northern blot analysis revealed that PMA induced the transcript for acidic fibroblast growth factor. Our data suggest that the TE 671 cell may be useful not only in the study of acidic fibroblast growth factor regulation but also as a model for embryonic tumor cell differentiation.
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PMID:Phorbol ester induces morphological changes and acidic fibroblast growth factor RNA expression in the RD/TE 671 cell line. 170 2

Primitive neuroectodermal tumors (PNET) represent a family of undifferentiated neural neoplasms which predominantly occur in children. PNETs are likely to originate from precursor cells and exhibit a marked potential for neuronal, glial and ependymal differentiation. A prominent example is the medulloblastoma of the cerebellum. In a model system using a novel transgenic CNS transplantation model, we have introduced a combination of ras and myc oncogenes into cell suspensions from fetal forebrain (E14) and postnatal cerebellum (P2) of the rat. Oncogene transfer into fetal forebrain grafts resulted in a high incidence of anaplastic neural tumors predominantly derived from glial precursors. Cell lines established from these neoplasms expressed high levels of both oncogenes. In a second experiment, the ras/myc vector was introduced into cell suspensions from neonatal cerebellum. The transformed cells were cultured for 3 weeks. Following stereotaxic transplantation, tumors of a similar morphology were observed. However, one animal developed a neoplasm with features of a cerebellar medulloblastoma. A cell line which exhibits a marked capacity for neurite extension and synaptogenesis was established from this tumor. Since these cells neither express ras nor myc, an insertion mutagenesis event appears to be responsible. Experiments to characterize this mutation are in progress. Our results indicate a potent transforming effect of ras and myc on neural precursor cells in vivo.
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PMID:[Induction of primitive neuroectodermal tumors by oncogene complementation]. 170 33

Medulloblastoma is one of the most common malignant brain tumors in childhood. These cells are immature bipotential cells that could differentiate into both neuronal and glial cells. The authors established two human medulloblastoma cell lines. One was derived from a 2-year-old girl with cerebellar tumor (designated as ONS-76) and another was from a 9-year-old girl with metastatic tumor in the right frontal lobe (ONS-81). Immunohistochemical studies showed that both cell lines possessed 145 and 200 kDa neurofilament proteins and neuron-specific enolase, without glial fibrillary acidic protein and S-100 protein. It was shown that interferon gamma could enhance or induce the expression of the major histocompatibility complex (MHC) antigens which play a major role in immune response. Also shown for the first time was the expression of MHC class II antigens on human medulloblastoma (ONS-76 and 81) with neuronal differentiation.
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PMID:[Expression of major histocompatibility complex on human medulloblastoma cells]. 170 54

An experimental model of meningeal dissemination was developed by intracisternal inoculation of human medulloblastoma (ONS-76) cells into nude mice. All mice died within 65 days after inoculation of 1 x 10(7) tumor cells. The median survival time was 56 days. Clinical signs and histological findings were similar to those in medulloblastoma patients with meningeal dissemination. Immunohistochemical studies showed that ONS-76 cells in the subarachnoid space expressed major histocompatibility complex (MHC) class I antigens until 20 days after inoculation. After 30 days, expression of MHC class I antigens decreased and cells began to proliferate rapidly. Expression of MHC class I antigens on tumor cells may result in effective recognition by the host immune system.
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PMID:Murine model of leptomeningeal dissemination using human medulloblastoma cells. 172 23

The poor prognosis associated with central nervous system (CNS) malignancy has led investigators to seek new, innovative treatment modalities. Immunotoxins, carrier molecules linked to toxic agents, combine high specificity for tumor-associated antigens with extreme potency. The rationale for both the development of these compounds and for their application to CNS neoplasia is explained. This report discusses the design and construction of immunoconjugates, using toxins that differ in their mechanism of action bound to ligands directed against various antigens. A comparison is made between the in vitro efficacy of standard chemotherapy and immunotoxins in glioblastoma- and medulloblastoma-derived cell lines. A review is included of the results of experiments in animals with leptomeningeal neoplasia, where prolongation of survival following intrathecal administration of immunotoxins has been reported. The obstacles encountered in clinical trials with other types of cancer are addressed and approaches to optimize the use of these novel agents in the context of treating malignant disease of the CNS are suggested.
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PMID:Immunotoxins and central nervous system neoplasia. 172 47

Of 29 consecutive children treated for malignant primary tumors of the central nervous system (CNS) at this institution, postoperative examination showed radiographic or cytologic evidence of neuraxis dissemination in 10 (34%). Given the historically poor results in disseminated CNS tumors treated with surgery and radiation therapy alone, these ten patients were treated prospectively with an investigational Phase II protocol consisting of preirradiation cisplatin (90 mg/m2 on day 1) and etoposide (150 mg/m2 on days 3 and 4). The diagnoses included medulloblastoma (n = 4), malignant glioma (n = 3), cerebral primitive neuroectodermal tumor (n = 1), pineoblastoma (n = 1), and mixed glioma of the brainstem (n = 1). Postoperative neuraxis scanning with computed tomography, magnetic resonance imaging, or spinal myelography showed measurable intracranial or spinal metastases in all children. The cerebrospinal fluid (CSF) cytologic examination was positive for tumor cells in five. The best responses, based on serial imaging of neuraxis metastases, included two complete responses, four partial responses, and three stable disease states. One patient had progressive disease at the primary site despite stable disease in the spine; progressive neuraxis disease was documented in only one patient during chemotherapy. Clearance of tumor cells from the CSF was documented in three patients. The adverse effects of chemotherapy, consisting of transient myelosuppression and mild ototoxicity, were minimal. Reversible neurologic deterioration occurred in two patients; one patient became acutely quadriplegic after a prolonged convulsive seizure without radiographic evidence of tumor progression.
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PMID:Neuraxis dissemination in pediatric brain tumors. Response to preirradiation chemotherapy. 173 73

Six well characterized human medulloblastoma cell lines (D283 Med, Daoy, D341 Med, D384 Med, D425 Med, and D458 Med) were examined for the expression of O6-methylguanine-DNA methyltransferase (MGMT) by activity and Western and Northern blot analysis. High levels of MGMT activity were present in D283 Med, Daoy, D341 Med, and D384 Med (1.36, 0.80, 1.68, and 1.62 pmol/mg of protein, respectively), but negligible MGMT activity was detected in D425 Med and D458 Med (0.06 and 0.05 pmol/mg of protein, respectively), which were derived separately at different times from the same patient. The presence of MGMT protein and its transcript was demonstrated in D283 Med, Daoy, D341 Med, and D384 Med, but both the protein and the mRNA were undetectable in D425 Med and D458 Med. Nevertheless, all six cell lines contained an apparently unaltered MGMT gene, as determined by Southern blot analysis. The absence of MGMT activity in D425 Med and D458 Med is likely due to the absence of the protein, resulting from a lack of transcription of the MGMT gene. The varying levels of expression of MGMT in medulloblastoma cells found in this study should provide a molecular basis for drug design and selection in chemotherapy of this tumor.
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PMID:Expression of O6-methylguanine-DNA methyltransferase in six human medulloblastoma cell lines. 173 73


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