Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An analysis of more than 18,000 primary central nervous system (CNS) tumors revealed only 18 cases (0.01%) in which dropped spinal metastases had caused the presenting symptoms. This group included 11 males and 7 females in whom there was no history of surgical intervention or irradiation. Primitive neuroectodermal tumors ( PNET , medulloblastoma), comprised the largest group (11 patients) followed by high-grade astrocytomas (anaplastic and glioblastoma) (5 patients). One case each of germinoma and ependymoma were also identified. The clinicopathologic data of these cases, and a brief review of the literature are presented.
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PMID:Spinal metastases. A rare mode of presentation of brain tumors. 632 8

A survey of in vitro cytotoxic effects of camptothecin in human epitheliod sarcoma, colon, breast and ovarian carcinomas, glioblastoma, and neuroblastoma (PNET) cell lines, was done. We chose the MTT assay to measure survival and observed that 24 h exposures to camptothecin caused consistently greater toxicity than 1 h exposures. The LD50 for camptothecin was in the 12.5-25 ng/ml range. There was a 10-fold range of growth rates measured by OD after 5 days exposure and varied expression of MDR1 in these cell lines--none of which could be correlated with tumor sensitivity to drug. The most sensitive cell lines were colon and glioblastoma, and the most resistance were ovarian, breast and epithelioid sarcoma.
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PMID:Camptothecin cytotoxic effects in vitro: dependency on exposure duration and dose. 757 68

Neuronal thread protein is a novel 21-kDa protein that accumulates in brains with Alzheimer's disease and exhibits developmentally associated changes in the level of expression. Recently, we discovered that primary human primitive neuroectodermal tumor (PNETs), malignant astrocytomas, and several human PNET and glioblastoma cell lines also express thread protein immunoreactivity. However, in addition to the 21-kDa species, there are approximately 17- and approximately 14-kDa thread protein-immunoreactive molecules expressed in both PNET and glioblastoma cell lines and a fourth approximately 8-kDa thread protein detected in glioblastoma cell lines. Metabolic labeling studies demonstrated that the 21-kDa thread proteins are phosphorylated, whereas the approximately 17-, approximately 14-, and approximately 8-kDa thread proteins are not. Glycosylated residues were not detected in either the PNET- or glioblastoma-derived thread proteins. Using a panel of monoclonal antibodies, we observed differences between PNET and glioblastoma cells suggesting that the thread proteins expressed in neuronal and glial cells are distinct. The levels of thread protein immunoreactivity in both PNET and glial cells were highest during the log phase of cell growth and lowest in serum-starved, nonproliferating cultures. The findings suggest that there are several distinct neuronal and glial derived thread proteins expressed in the central nervous system and that their levels of expression may be modulated with cell growth.
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PMID:Characterization of thread proteins expressed in neuroectodermal tumors. 768 27

The toxicity and therapeutic effect of the ventriculolumber perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl-1-1(2-chloroethyl)-1-nitros our ea hydrochloride (ACNU) against subarachnoid dissemination of gliomas were studied. Twenty-one patients (6 patients with anaplastic glioma, 7 with glioblastoma and 8 with medulloblastoma or PNET) received ventriculolumber perfusion of ACNU when they were diagnosed as having subarachnoid dissemination. The course of perfusion and cumulative dose of ACNU was 10 times and 95 mg on average, respectively. Most of the patients received systemic chemotherapy in combination with perfusion therapy and some patients with radiotherapy. Response rate was 17% and median survival time after the diagnosis of dissemination was 12 months for anaplastic gliomas, 29% and 12 months for glioblastoma, and 88% and over 25 months for medulloblastoma and PNET. The ventriculolumber perfusion of ACNU was performed for prophylactic purpose in 7 patients with high risk at the early postoperative period in combination with conventional adjuvant therapy. The course of perfusion and cumulative dose of ACNU was 2.3 times and 21 mg on average, respectively. One patient developed subarachnoid dissemination and died 22 months after surgery. Other 6 patients survived without dissemination on median over 29 months after surgery. Side effects encountered were headache in 4 patients, nausea and vomiting in 5, a convulsion in 2, right facial weakness in 1, fecal incontinence in 3 and meningitis in 2. They were all temporary except for facial weakness occurred in one patient. These data suggest that the ventriculolumber perfusion of ACNU is a safe and useful in the treatment and prophylaxis against the subarachnoid dissemination of gliomas.
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PMID:Ventriculolumber perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)-methyl]-1-(2-chloroethyl-1-nitrosou rea hydrochloride for subarachnoid dissemination of gliomas. 969 73

More than half of the children and adolescents with malignant brain tumors will relapse following initial therapy. Irrespective of the therapeutic modalities the prognosis of patients with recurrent or metastatic brain tumors is still poor. New strategies such as high dose chemotherapy (HDCT) with autologous blood stem cell transplantation (ABSCT) offer the possibility to improve the longterm prognosis of these patients. Following conventional chemotherapy with carboplatin/etoposide and after achieving complete or partial remission (CR or PR) 10 patients aged from 3.2 to 25.5 years (median, 10.3 years) with refractory or recurrent malignant brain tumors (anaplastic astrocytoma/glioblastoma, n = 2; medulloblastoma/PNET, n = 6; ependymoma, n = 1; plexus carcinoma, n = 1) received in a pilot study one course of HDCT with ABSCT. The consolidation regimen consisted of thiotepa (400-600mg/m2/d, i.v. 6 h, d-9), carboplatin and etoposide (500mg/m2/d, CVI 24h, d-8 to d-5, respectively) and was followed by the retransfusion of autologous blood stem cells on day 0. Before starting HDCT 6 patients showed CR and 4 patients had PR or stable disease (SD). Following the HDCT 3 of the 4 patients with residual tumor had CR or PR. 6 patients have remained in continuous CR or SD 8 to 41 months (median 17.2 months) after the HDCT. 2 patients relapsed 8.5 and 9.5 months after HDCT and died from progressive disease. Two patients died therapy-related from systemic aspergillosis and were not evaluable for response. Hematological recovery with an absolute neutrophile count of > 0.5 x 10(9)/l and a platelet count of > 30 x 10(9)/l was reached on days +11 (median; range, +9 to +14) and +16 (median; range, +6 to +47), respectively. The main nonhematological toxic effects were infections, severe mucositis, and hyperbilirubinemia. Although the long-term efficacy of HDCT with ABSCT is still not evaluable and the toxicity of this regimen is high, a multicenter phase II trial seems to be justified in view of the poor prognosis of recurrent or refractory brain tumors in children and adolescents.
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PMID:[High dose chemotherapy with thiotepa, carboplatin, VP16 and autologous stem cell transplantation in treatment of malignant brain tumors with poor prognosis. Results of a mono-center pilot study]. 974 61

Ten children (6 girls and 4 boys) who completed a protocol in which their localized brain tumors were successfully treated without cranial irradiation were referred for neuropsychological assessment. At the time of testing, they were disease free without any neuroaxis dissemination or leptomeningeal disease. Tumor types included pineoblastoma, glioblastoma, ependymoma, PNET and medulloblastoma. They had a mean age of 5 years and 8 months (SD = 1.86; range = 2.1-8.9 years) and were an average of 37.8 months post bone marrow transplant (SD = 16.42; range = 14-58 months). Neuropsychological data from this study reveal that the mean scores for this nonradiated group of children were within the average range for the following domains: academic achievement tests of reading, spelling and mathematics, verbal and visual memory, visual-motor integration, social-emotional and behavioral functioning. Furthermore, this group of children were performing within the low average range of overall Intelligence, as well as both verbal IQ/verbal reasoning and performance IQ/abstract visual reasoning. On tasks of fine motor dexterity, this group was within the low average range when using their dominant hand; however, they performed within the borderline range when using their non-dominant hand. Of note, this group of children demonstrated significant deficits within the borderline to impaired ranges on language tasks of expressive picture naming and receptive picture vocabulary.
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PMID:Pilot neuropsychological findings from a treatment regimen consisting of intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors. 984 Mar 84

The human erythrocyte GLUT-1 is a transmembrane protein which facilitates transport of glucose in the cell in an energy-independent fashion. Neuroectodermal stem cells show strong membrane immunoreactivitry with this marker at early developmental stages in rodents. Membranous expression by undifferentiated neuroectodermal cells gradually decreases while GLUT-1 becomes confined to the endothelial cells, when these acquire blood-brain barrier function. We thus sought to determine whether GLUT-1 expression was limited to embryonal neoplasms of the central nervous system (CNS) which are presumably derived from developmentally arrested neuroectodermal stem cells. Archival material of 40 primary CNS neoplasms were examined for immunoreactivity with anti-GLUT-1. This included both non-embryonal neoplasms (18 astrocytic tumours, one ependymoma and three oligodendroglioma) and embryonal neoplasms (12 cerebellar medulloblastomas, four supratentorial PNETs and two atypical teratoid/rhabdoid tumours (AT/RhT)). In addition, cell lines and nude mice xenografts derived from both undifferentiated and differentiated tumours were assessed for GLUT-1 immunoreactivity by both immunohistochemistry and Western blotting. All embryonal tumours, MBs and PNET xenografts consistently showed GLUT-1 membrane staining. Non-embryonal neoplasms were negative except for vascular staining. Membrane protein fraction of embryonal tumours cell lines immunoreacted by immunoblot with GLUT-1, whereas the glioblastoma cell line was negative. Expression of GLUT-1 supports the stem cell nature of the cells of origin of MBs, supratentorial PNET and AT/RhTs. As a result, GLUT-1 is a useful marker to define the embryonal nature of CNS neoplasms.
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PMID:Membranous expression of glucose transporter-1 protein (GLUT-1) in embryonal neoplasms of the central nervous system. 1073 70

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been implicated in the immense invasive potential and neovascularization of primary brain tumors. We investigated the gene expression profiles of MMPs 1, 2, 3, 7, 9, 12, 13, 14, 16 and of TIMPs 1, 2, 3, and 4 in various primary brain tumors (astrocytoma WHO grade I-III, glioblastoma, PNET, ependymoma III and oligoastrocytoma II) using novel RNase protection assay probe sets. In addition, we determined the level and cellular source of gelatinolytic activity and localized gelatinase B and TIMP-1 RNA. Distinct expression patterns of the MMP and TIMP genes were found in the various brain tumors tested. While the WHO grade I and II tumors had MT1/MT3 ratios below 1, the malignant (grade III and IV) tumors had ratios above 1. Strong expression of TIMP-1 RNA was observed in all malignant tumors and in grade I pilocytic astrocytomas and localized to the walls of neovessels. Quantitative analysis of enzymatic activity in the soluble fraction of protein extracts revealed that in most tumors gelatinases remained in the inactive pro-form. In situ zymography revealed net gelatinolytic activity in neurons of normal brain and in tumor cells and vessel walls of all tumors tested. Immunohistochemistry demonstrated that gelatinase B was localized to vessel walls, to neutrophils in areas of hemorrhage, and in glioblastomas to macrophages. Together these data demonstrate that the different primary brain tumors show distinct regulation of MMP and TIMP genes. The localization of the soluble gelatinase B indicates an association with neovascularization, whereas membrane-bound MMPs may account for the invasive potential of the glial tumor cells.
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PMID:Distinct expression patterns and levels of enzymatic activity of matrix metalloproteinases and their inhibitors in primary brain tumors. 1139 36

Since 1998, we have introduced a mixed epithermal- and thermal neutron beam for boron neutron capture therapy (BNCT) to improve the neutron beam distribution. Sixteen patients with malignant glioma (glioblastoma, n = 14; anaplastic ependymoma, n = 1; PNET, n = 1) were treated by BNCT in Japan. Of these, 9 died; 3 due to cerebrospinal fluid (CSF) dissemination, 1 each of tumor invasion, meningitis, pneumonia, and unknown causes, and 2 patients died of local recurrence or radiation necrosis. The current postmortem study is comprised of 3 patients with glioblastoma who were treated with BNCT employing an epithermal neutron beam and sodium borocaptate (BSH: Na2B12H11SH). None of the patients manifested local regrowth at the primary site. However, in 2 patients there was CSF dissemination; tumor cells were recognized throughout the subarachnoid space. In the other patient, tumor cells had massively invaded the ipsilateral- and contralateral hemisphere and brain stem from the bottom of the tumor cavity via the corpus callosum and cerebral peduncle. Our findings indicate that BNCT can achieve local control of glioblastoma at the primary site. However, to further improve the clinical outcome after BNCT, steps must be taken to prevent CSF dissemination.
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PMID:Histopathological findings in autopsied glioblastoma patients treated by mixed neutron beam BNCT. 1517 18

Doublecortin (DCX) is required for neuroblastic migration during the development of the cerebral cortex. DCX is a microtubule-associated protein that plays a role in cellular motility. These facts led us to hypothesize that DCX is increased in invasive brain tumors. DCX expression was assessed in 69 paraffin-embedded brain tumors of neuroepithelial origin. In addition, mouse brain sections of the subventricular zone and dentate gyrus were used as positive controls for immunostaining, and specificity of antibody staining was demonstrated by peptide neutralization. DCX was highly expressed in both high-grade invasive tumors (glioblastoma, n=11; anaplastic astrocytoma/oligoastrocytoma, n=7; and medulloblastoma/PNET, n=6) and low-grade invasive tumors (oligodendroglioma, n=3; and astrocytoma/oligoastrocytoma, n=5). However, DCX was less intensely expressed in the circumscribed group of tumors (pilocytic astrocytoma, n=6; ependymoma/subependymoma, n=7; dysembryoplastic neuroepithelial tumor, n=4; ganglioglioma, n=2; meningioma, n=9; and schwannoma, n=9). By the Cochran-Mantel-Haenszel statistical test, the circumscribed group was significantly different from both the high-grade invasive group (P<0.0001) and the low-grade invasive group (P<0.0001). We conclude that DCX is preferentially expressed in invasive brain tumors. In addition, DCX immunostaining was stronger at the margin of the tumor than at the center. For a subset of these tumors, we also detected DCX mRNA and protein by Northern and Western blotting. DCX mRNA and protein was detected in glioma cell lines by Northern blotting, immunofluorescence microscopy and Western blotting. Collectively, the immunohistochemistry, Western blots and Northern blots conclusively demonstrate expression of DCX by human brain tumors.
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PMID:Doublecortin is preferentially expressed in invasive human brain tumors. 1619 16


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