Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between chromatin structure and endonuclease sensitivity was investigated. The cells used in this study were a) human myelogenous leukemic cell lines (HL-60, ML-I, U-937, THP-I) (Group I), which produced internucleosomal DNA cleavage, and b) human T-cell leukemia (MOLT-4), erythroleukemia (K562), glioblastoma (T98G, U87MG) and glioma (KG-1-C) cell lines (Group II), which produced no internucleosomal DNA cleavage, upon treatment with various apoptosis-inducing agents. When the nuclei, isolated from these cells were digested with micrococcal nuclease, chromatin DNA was cleaved into oligonucleosomal units. Although sensitivity to micrococcal nuclease considerably differed from cell to cell, Group I cells were generally more sensitive to micrococcal nuclease digestion than Group II cells. Similar sensitivity to DNase I was observed in both groups of cells. Acid-urea polyacrylamide gel electrophoresis of histone fractions from control and apoptosing HL-60 cells (induced either by hydrogen peroxide or UV irradiation) revealed no significant change in the relative composition of five major histones, indicating the absence of selective degradation of histone HI, but rather the nonspecific degradation of many nuclear proteins. These data suggest a difference in a chromatin structure between Group I and II cells, which might result in the selective production of internucleosomal DNA cleavage only in Group I cells.
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PMID:Chromatin structure and endonuclease sensitivity in human leukemic cell lines. 870 41

Analytical parameters known to be important for the separation of DNA by capillary electrophoresis, including gel polymer concentration, electrical field strength and temperature, were investigated and optimized for the analysis of RNA molecules from 100 to 2000 bases. Denaturation, essential to obtain uniform and identifiable peaks, was accomplished by heating the sample in 80% formamide prior to electrophoresis and the presence of 2-8 M urea in the electrophoresis buffer. Efficient separations were obtained over a wide range of electrical field strengths and temperatures using the gel polymer hydroxypropylmethylcellulose (HPMC) as separation matrix. Low HPMC concentrations (< 0.3%) were suited for the separation of high molecular mass RNA (> 1000 bases) whereas higher HPMC concentrations were required for optimal separation of low molecular mass RNA. An optimized system was applicable for the separation of the predominating RNA populations (small RNA of 60-300 bases (as a group of unseparated peaks), 18S and 28S rRNA) in total RNA from a human glioma cell line. This is the first systematic investigation of electrophoresis of higher molecular mass RNA in capillaries, and motivates further studies to transfer electrophoresis of RNA to the capillary format.
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PMID:Analysis of RNA by capillary electrophoresis. 890 69

The amino terminus of mouse epidermal growth factor (mEGF) was coupled directly to the aldehyde end of dextran through a reductive amination procedure. The highest coupling efficiency was approximately 80% and could be reached after approximately 24 h of reaction time at pH 8. Gel filtration on Sephadex G-50 Fine removed free mEGF from the conjugate. Preparative polyacrylamide gel electrophoresis was used to separate the conjugate from excess noncharged dextran. The conjugate bound specifically to the EGF receptor on cultured glioma cells as shown in displacement tests with free mEGF. The conjugate was stable in the pH interval 4-9, in 2 M sodium chloride, in 7 M urea, and in human serum and could still bind to the EGF receptor after such treatments. The conjugates are candidates for targeted nuclide therapy.
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PMID:Preparation and purification of an end to end coupled mEGF-dextran conjugate. 940 68

The purpose of this study was to characterize the effects of sodium 4-phenylbutyrate (phenylbutyrate) on the proliferation, morphology, migration and invasiveness of malignant glioma cells in vitro. Phenylbutyrate is a novel differentiating and cytotoxic compound used clinically with low toxicity in the treatment of beta-thalassemia, sickle cell anemia and urea cycle disorders. Preliminary clinical trials testing phenylbutyrate as an anti-cancer agent have included patients with malignant glioma. However, little information is available regarding the effects of phenylbutyrate on glioma cells, particularly with respect to the expression of genes important in the pathogenesis of glial malignancy. In experiments reported here, glioma cell lines and explant cells from a tumor patient were exposed to 2, 4 and 8 mM phenylbutyrate and compared to untreated control cells. The effect on cellular proliferation was assessed using cell counts and DNA flow cytometry. Changes in morphology were evaluated using vimentin staining. Scratch and Matrigel assays were performed to assess changes in cellular migration and invasiveness. Finally, Northern blot analysis was used to study c-myc and urokinase expression. Phenylbutyrate was found to have dose-dependent inhibitory effects on glioma cell proliferation, morphology, migration, invasiveness and c-myc and urokinase expression. Mean growth-inhibitory (IC50) phenylbutyrate concentrations ranged from 0.5 mM for T98G cells to 5.0 mM for explant cells. Phenylbutyrate treatment reduced % S phase cells, increased % G0/G1 cells, and produced morphologic changes consistent with induction of differentiation. 24 hours of treatment with 4 mM phenylbutyrate resulted in a 50% reduction in migration and invasiveness. Northern blots showed a decrease in urokinase and c-myc expression at non-cytotoxic doses. We conclude that phenylbutyrate is a promising candidate compound for treating patients with malignant glioma.
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PMID:Inhibitory effects of phenylbutyrate on the proliferation, morphology, migration and invasiveness of malignant glioma cells. 952 87

Methylmercury (MeHg) specifically depolymerizes microtubules and inhibits cell proliferation in mouse glioma cells. The effect of microtubule depolymerization by MeHg on tubulin synthesis was studied. Tubulin synthesis analyzed by two-dimensional electrophoresis using [35S]methionine as a tracer was markedly inhibited in mouse glioma cells exposed to 5 x 10(-6)M MeHg for 3 hr, which completely depolymerized microtubules. Under this condition, density of the protein bands other than tubulin in autoradiogram remained unchanged on gradient urea-polyacrylamide gels. Furthermore, the decrease in tubulin mRNA level was relevant to that in tubulin synthesis, although actin mRNA levels remained unchanged. In addition, specific transcription rates of beta-tubulin genes appeared to be unaffected under the same experimental condition as above. Thus, it is concluded that the disruption of microtubules by MeHg resulted in the inhibition of the synthesis of tubulin itself through autoregulatory repression in post-transcriptional processes as in the case of colchicine treatment.
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PMID:Methylmercury-induced microtubule depolymerization leads to inhibition of tubulin synthesis. 992 40

Previously it has been shown that persistent activation of the stimulatory adenylyl cyclase pathway with cholera toxin (CT) downregulates the Gs alpha polypeptide (80%) in a cAMP-independent manner in C6 glioma cells (Shah, 1997). This study was conducted to examine the short and long term effects of CT on the regulation of pertussis toxin-sensitive and -insensitive G proteins and their transcripts in C6 glioma cells. Treatment of C6 cells with CT (100 ng/ml) up to 16 h had no effect on either Gi or Gq/11 alpha proteins. However, prolonged exposure (24-48 h) caused increased expression of Gi (20-30%) and Gq/11 alpha proteins (40%). Urea gradient gels, which can separate Gq alpha and G11 alpha proteins, revealed that prolonged CT treatment increased the expression of both of these G proteins. The CT-mediated enhanced expression of Gq alpha and G11 alpha proteins was accompanied by increased mRNA levels of these proteins as determined by RT/PCR. Cyclic-AMP elevating agents like forskolin (10 microM) and db-cAMP (1 mM) mimicked the effect of CT on Gi but not Gq/11 alpha proteins. These studies show long term cAMP-dependent regulation of Gi and cAMP-independent expression of Gq/11 alpha proteins in C6 glioma cells.
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PMID:Cholera toxin mediated regulation of the expression of Gq alpha and G11 alpha GTP binding proteins. 1041 Mar 8

Recombinant forms of the neurotrophic factor pigment epithelium-derived factor (PEDF) activate metabolism of RAW macrophage cells while simultaneously inhibiting their proliferation. The recombinant forms (rPEDF) acted with EC(50)s of 0.1-1 nM while full-length native bovine PEDF was inactive. Urea, which is the buffer used to extract recombinant PEDF, stimulated RAW cell proliferation, the first report of an effect of urea on non-kidney cells. PEDF acted within 12 h and its effects persisted up to 72 h with continuous exposure. Although rPEDF had no direct action on glioma cell lines, it increased the amount of a soluble factor released by RAW cells which was capable of blocking glioma cell division. Thus PEDF may function as a neuroimmune modulator, affecting both neural and immune system cells.
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PMID:Recombinant forms of the neurotrophic factor pigment epithelium-derived factor activate cellular metabolism and inhibit proliferation of the RAW macrophage cell line. 1060 19

The INK4a-ARF locus encodes 2 separate proteins through differential splicing of alternative first exons to produce p16INK4a (exon 1alpha) and p14ARF (exon 1beta) products in human cells. The p16INK4a protein inhibits the cyclin D-dependent kinases (CDK) that control the phosphorylation of the Rb protein and cell proliferation. The p14ARF gene product can complex with and sequester the MDM2 protein within the nucleus, thus modulating the activity of the p53 protein. Loss of p16INK4a expression would disrupt the retinoblastoma (Rb)/p16INK4a/cyclin D-dependent kinase (CDK4) pathway, whereas loss of p14ARF expression would inactivate both the Rb and p53/ MDM2/p14ARF pathways through MDM2, which can complex with either Rb or p53. Loss of the p16INK4a gene on 9p21 has been documented in a wide range of human tumors, including one third of glioblastomas. However, in tumors showing homozygous loss of exon 2 of the p16INK4a gene, loss of exon 1beta of the p14ARF gene has not been established. In this study, we have assessed deletion of the p14ARF gene in 29 pediatric and 107 adult high-grade astrocytomas and 9 glioma cell lines, using multiplex PCR analysis for exon 1beta. We found homozygous deletions for exon 1alpha and exon 1beta in 3 of 29 (10%) of the pediatric cases (2 grade III, 1 grade IV), 25 of 107 (23%) of the adult cases (6 grade III and 19 grade IV), and 8 of 9 (89%) of the glioma cell lines. Therefore, loss of the INK4a-ARF locus in high-grade astrocytomas may contribute to the highly malignant behavior and treatment resistance of these tumors through elimination of multiple checkpoint cell cycle control proteins.
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PMID:Incidence of p14ARF gene deletion in high-grade adult and pediatric astrocytomas. 1066 22

Epidemiological studies suggest that some familial aggregations of glioma may be due to inherited predisposition. Many genes involved in familial cancers are frequently altered in the corresponding sporadic forms. We have investigated several genes known to be altered in sporadic gliomas for their potential contribution to familial glioma. Fifteen glioma patients with a family history of brain tumors were identified through the Mayo Clinic Department of Neurology (nine diffuse astrocytomas, two oligodendrogliomas, two mixed oligoastrocytomas, one pilocytic astrocytoma, and one pineal glioma). Eleven of the propositi had one or more first degree relative with a glioma. Lymphocyte DNA was derived from each of the patients and analyzed by polymerase chain reaction (PCR) and direct sequencing of the PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 genes. In addition, fluorescence in situ hybridization (FISH) was performed on EBV-transformed lymphocytes from each affected individual to detect germline copy number of the p16(INK4A)/p14(ARF) tumor suppressor region. A p53 germline point mutation was identified in one family with some findings of Li-Fraumeni syndrome, and a hemizygous germline deletion of the p16(INK4A)/p14(ARF) tumor suppressor region was demonstrated by FISH in a family with history of both astrocytoma and melanoma. Thus, whereas germ-line mutations of PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 are not common events in familial glioma, outside of familial cancer syndromes, point mutations of p53 and hemizygous deletions and other rearrangements of the p16(INK4A)/p14(ARF) tumor suppressor region may account for a subset of familial glioma cases. Collectively, these data lend genetic support to the heritable nature of some cases of glioma.
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PMID:Investigation of germline PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 alterations in familial glioma. 1079 39

Normal human fibroblasts have been shown to undergo a p16(Ink4a)-associated senescence-like growth arrest in response to sustained activation of the Ras/Raf/MEK/ERK pathway. We noted a similar p16(Ink4a)-associated, senescence-like arrest in normal human astrocytes in response to expression of a conditional form of Raf-1. While HPV16 E7-mediated functional inactivation of the p16(Ink4a)/pRb pathway in astrocytes blocked the p16(Ink4a)-associated growth arrest in response to activation of Raf-1, it also revealed a second p21(Cip1)-associated, senescence-associated, beta-galactosidase-independent growth arrest pathway. Importantly, the p21(Cip1)-associated pathway was present not only in normal astrocytes but also in p53-, p14(ARF)-, and p16(Ink4a)/pRb-deficient high grade glioma cells that lacked the p16(Ink4a)-dependent arrest mechanism. These results suggest that normal human cells have redundant arrest pathways, which can be activated by Raf-1, and that even tumors that have dismantled p16(Ink4a)-dependent growth arrest pathways are potentially regulated by a second p21(Cip1)-dependent growth arrest pathway.
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PMID:Dual growth arrest pathways in astrocytes and astrocytic tumors in response to Raf-1 activation. 1127 20


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