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)

Little progress has been made in the treatment outcome of patients with glioblastoma in the past 10 to 15 years, despite an aggressive multimodality regimen using surgery, radiation, and chemotherapy. New approaches, particularly molecular strategies, have become the clinicians' and scientists' hope for the future in brain-tumor therapy. Several molecular approaches have been shown to have in vitro and in vivo activities against brain tumor cells. These include the use of retroviral and adenoviral vectors, herpes simplex viruses, antisense vectors, and antisense oligonucleotides. Preclinical studies with the retroviral vector have already been extended to a clinical trial, clearly demonstrating the clinical potential of these molecular approaches.
Curr Opin Neurol 1994 Dec
PMID:New approaches to molecular therapy of brain tumors. 786 80

Topoisomerase I (topo I) gene expression and cell sensitivity to camptothecin were investigated in seven human cancer cell lines not selected in vitro for drug resistance. The cell lines were of different tumor origin, and included two ovarian carcinomas (A2780 and IGROV-1), a cervix squamous cell carcinoma (A431), an osteosarcoma (U2-OS), a glioblastoma (GBM) and two different clones of a malignant melanoma (665/2/60 and 665/2/21). Topo I gene expression was evaluated by Northern blotting analysis and cell sensitivity to camptothecin was determined using the colony-forming assay after a 1 h exposure to the drug. A wide range of drug sensitivity levels was found among the examined cell lines. Cell doubling times and distribution in cell cycle phases were not correlated with camptothecin cytotoxicity. In particular, the percent of untreated cells in S phase was not predictive of the drug sensitivity. No correlation was found between level of topo I gene expression and cell response to camptothecin. These results indicate that the level of topo I expression is not the only critical determinant of cell sensitivity to camptothecin in unselected human cancer cell lines. Therefore, topo I gene expression may not be a useful predictive parameter of tumor response.
Anticancer Drugs 1994 Dec
PMID:Topoisomerase I gene expression and cell sensitivity to camptothecin in human cell lines of different tumor types. 788 2

The monocyte chemotactic protein-1 (MCP-1) is a 76 amino acid protein that specifically attracts monocytes. The expression of MCP-1 gene can be induced by lipopolysaccharides (LPS), phorbol esters (TPA) and several cytokines. However, how they regulate MCP-1 gene expression is not known. We tested whether the two putative TPA-responsive elements (TREs) and one kappa B enhancer-like region found in the MCP-1 promoter region, are involved in this regulation of MCP-1 gene expression. The 5' untranslated region of MCP-1 gene was linked to chloramphenicol acetyl transferase (CAT) reporter gene and transfected into human glioblastoma cells in which endogenous MCP gene expression was found to be stimulated by TPA and tumor necrosis factor-alpha (TNF-alpha). The 128 bp 5'-flanking region containing one TRE was adequate for basal promoter activity but the presence of both TREs in the MCP-1 promoter region were needed to give TPA responsive enhancement (2.5 fold) of expression of the marker gene. Mutations in either of the TRE's could abolish the TPA induction of CAT expression. Replacement of the kappa B enhancer-like element with a TRE-like sequence caused a 10-fold enhancement of CAT expression by TPA treatment. Random mutation of kappa B enhancer-like element did not affect CAT expression or its TPA induction. None of the MCP promoter constructs showed significant increase in CAT expression by treatment with tumor necrosis factor-alpha (TNF-alpha). This result suggested that the TNF regulation of MCP-1 gene involves other parts of the gene besides the proximal 5' flanking region.
Mol Cell Biochem 1994 Dec 21
PMID:Functional role of the cis-acting elements in human monocyte chemotactic protein-1 gene in the regulation of its expression by phorbol ester in human glioblastoma cells. 789 69

The activity of IMP dehydrogenase (EC 1.2.1.14), the key enzyme of de novo guanylate biosynthesis, was shown to be increased in tumor cells. Tiazofurin (TR), a potent and specific inhibitor of this enzyme, proved to be effective in the treatment of refractory granulocytic leukemia in blast crisis. We examined the effects of tiazofurin as a single agent and in combination with hypoxanthine and allopurinol in six different neuroectodermal tumor cell lines, the STA-BT-3 and 146-18 human glioblastoma cell lines, the SK-N-SH, LA-N-1 and LA-N-5 human neuroblastoma cell lines, and the STA-ET-1 Ewing tumor cell line. Tiazofurin inhibited tumor cell growth with IC50 values between 2.2 microM (LA-N-1 cell line) and 550 microM (LA-N-5 cells) and caused a significant decrease of intracellular GTP pools (GTP concentrations decreased to 39-79% of control). Incorporation of [8-14C]guanine into GTP pools was determined as a measure of guanylate salvage activity; incubation with 100 microM hypoxanthine caused a 62-96% inhibition of the salvage pathway. Incubation with tiazofurin (100 microM) and hypoxanthine (100 microM) synergistically inhibited tumor cell growth, and the addition of allopurinol (100 microM) strengthened these effects. Therefore, this drug combination, inhibiting guanylate de novo and salvage pathways, may prove useful in the treatment of human neuroectodermal tumors.
Biochem Pharmacol 1993 Dec 03
PMID:Synergistic action of tiazofurin with hypoxanthine and allopurinol in human neuroectodermal tumor cell lines. 790 33

The poor prognosis of human malignant gliomas is due to their invasion and recurrence, the molecular mechanisms of which remain poorly characterized. We have accumulated substantial evidence implicating the cysteine protease cathepsin B in human glioma malignancy. Increases in cathepsin B expression were observed throughout progression. In primary brain tumor tissue, transcript abundance (Northern blot analysis) increased in low-grade astrocytoma to high-grade glioblastoma from 3- to 6-fold, respectively, above normal brain levels. This increase correlated with increases in protein abundance (from + to ) as measured by immunohistochemistry. Furthermore, in glioblastoma cell lines increases in transcript abundance (ranging from 3- to 12-fold) were accompanied by increases in enzyme activity (44-133 nmol/min x mg protein). Altered subcellular localization was observed both immunohistochemically and by indirect immunofluorescence confocal microscopy and was found to correlate with increased grade. In addition, this increase in cathepsin B expression and altered subcellular localization correlated with histomorphological invasion and clinical evidence of invasion as detected by magnetic resonance imaging. These data support the hypothesis that cathepsin B plays a role in human glioma progression and invasion.
Cancer Res 1994 Dec 01
PMID:Cathepsin B expression and localization in glioma progression and invasion. 795 39

The authors describe the clinical behavior of eight patients with cerebral astrocytomas, in whom computerized tomography (CT) or magnetic resonance (MR) imaging of the brain was characterized by diffuse bilateral cerebral hemisphere tissue density abnormalities and minimal focal mass effect. Five patients were newly diagnosed, and three others had been treated for focal low-grade astrocytoma. Histological diagnoses included anaplastic astrocytoma (three patients), low-grade astrocytoma (three patients), glioblastoma (one patient), and gliosis with later development of glioblastoma (one patient). In five patients, brain tumor was not suspected from the neuroimaging studies, the findings of which were mistaken for radiation leukoencephalopathy, vasogenic edema, or multiple sclerosis. Serial CT scans or MR images undertaken over intervals of 3 to 184 weeks showed progression of abnormal tissue densities in seven patients and multifocal contrast-enhancing masses developed on CT scan in two patients. An autopsy in each of four patients showed diffuse cerebral infiltration by astrocytoma. It is concluded that neuroimaging studies in some patients with diffusely infiltrating cerebral astrocytoma are atypical for neoplasm and can be mistaken for other diseases, especially those that predominantly affect cerebral hemisphere white matter.
J Neurosurg 1994 Dec
PMID:Diffuse bilateral cerebral astrocytomas with atypical neuroimaging studies. 796 10

Data on biodistribution and pharmacokinetics of Na2B12H11SH are few and lack in standardization. This study comprises a uniform series of 10 patients with glioblastoma administered Na2B12H11SH i.v. 24 h before surgery at a dose level used in earlier therapeutical trials (75 mg/kg body weight). Boron concentrations in tumor, normal brain, peritumoral edematous brain, blood, and urine were determined by inductively coupled plasma-atomic emission spectroscopy 24 h after Na2B12H11SH administration; boron uptake in tumor (mean, 12.2 micrograms/g) was sufficiently selective compared to concentrations in normal and edematous brain (1.2 and 2.3 micrograms/g, respectively). Mean concentration ratio of tumor:blood was slightly above unity. Boron concentration in blood decreased according to an open two-compartment model, mean excretion in urine over 24 h was 81.9%. The only side effect was an inconstant facial flush. Among efforts aiming at an optimized treatment protocol a dose escalation study seems to be justified.
Cancer Res 1994 Dec 15
PMID:Boron neutron capture therapy: boron biodistribution and pharmacokinetics of Na2B12H11SH in patients with glioblastoma. 798 20

We have used molecular genetic methods to examine the status of cell cycle-inhibitory genes in human brain tumors. We found that p16 and a neighboring gene, p15, were often homozygously deleted in glioblastoma multiformes but not in medulloblastomas or ependymomas. The deletions occurred in both primary tumors and their derived xenografts, but no intragenic mutations in either of the two genes were found. The p15 gene was expressed in a more widespread pattern in normal tissues than p16, but the products of both genes had similar capacities to bind to cyclin D-dependent kinases 4 and 6. These data suggest that the target of deletion in glioblastoma multiforme includes both p15 and p16 genes. The reason that homozygous deletions, rather than intragenic mutations, are so common in these tumors may be that deletion is a more efficient mechanism for simultaneous inactivation of both genes.
Cancer Res 1994 Dec 15
PMID:Deletion of p16 and p15 genes in brain tumors. 798 28

There are three types of interferons (IFN), alpha, beta and gamma. IFN-alpha is produced in the leukocytes infected with virus, while IFN-beta is from fibroblasts infected with virus. IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen or non-sensitized lymphocytes with mitogens. It is believed that IFN-alpha and beta originated from the same ancestral gene, whereas IFN-gamma did not. IFN has not only an antiviral activity, but also various kinds of biological activities including cell growth inhibition, immunosuppressive effects, enhancement of macrophage, natural killer (NK) cell, killer (K) cell and neutrophil functions, and cell differentiation-inducing activity. IFN also shows the antitumor activity resulting from the integration of the above-mentioned biological activities. IFN is also deeply involved in the pathogenesis of various diseases, e.g., collagen diseases such as SLE and rheumatoid arthritis, insulin-dependent diabetes mellitus, fulminant hepatitis, severe pancreatitis, nephritis, multiple sclerosis, allergic diseases, and atherosclerosis. At present, IFN is clinically used in therapy against virus infections such as hepatitis B and C, and for malignancies such as renal cell carcinoma, multiple myeloma, malignant melanoma, glioblastoma, skin cancers, malignant lymphoma and chronic myelogenous leukemia.
Gan To Kagaku Ryoho 1994 Dec
PMID:[Interferon-alpha, beta, gamma]. 799 28

A 9-year, 6-month-old boy presented with peripheral-type multiple cranial nerve palsy due to extensive cerebrospinal fluid (CSF) dissemination of intracranial glioblastoma multiforme. Tissue obtained from biopsy did not stain for glial fibrillary acidic protein (GFAP). The relationship between GFAP-negative tumor cells and extensive CSF dissemination agreed with recent reports. Magnetic resonance imaging with gadolinium-DPTA enhancement clearly depicted not only the cranial meningeal dissemination but also spinal metastasis. Magnetic resonance imaging showed undoubted usefulness in demonstrating disseminated glioblastoma.
Childs Nerv Syst 1993 Dec
PMID:A case of cerebral glioblastoma with extensive cerebrospinal fluid dissemination: diagnostic value of immunohistochemical examination and MR imaging. 812 77


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