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)

The expression of the genes in the human HOX2 locus has been studied during differentiation of two human neuroblastoma (SH-SY5Y and Kelly), a human glioblastoma (251-MG), and the murine F9 embryonal carcinoma cell lines. Cells were differentiated with retinoic acid (RA), or with RA together with dibutyral cyclic AMP (db-cAMP) and nerve growth factor (NGF) in order to assess the changes in the expression patterns of these homeobox genes during neuronal differentiation. We show that the genes of the HOX2 locus are expressed in a complex transcription pattern that varies with cell type. The two uninduced neuroblastoma cell lines show a similar pattern of expression for a number of HOX2 genes although the levels of expression are different for individual cell lines. The embryonal carcinoma cell line F9 expresses low levels of several HOX2 genes which is restricted to the 5' region of the HOX2 cluster. The glioblastoma cell line, 251-MG expresses almost all of the genes of the HOX2 locus. Differentiation of these cells modulates the expression of the HOX2 genes in a manner that is dependent upon the cell type as well as the differentiation factor. Differentiation affects both the level of HOX2 gene expression and the distribution of transcript sizes. In conclusion, our analysis reveals a complex pattern of expression for the genes of the HOX2 locus in neuronal and glial cells and suggests that the cell-specific expression of these genes may be correlated with the phenotypic differences that are observed between different neuronal and glial cell populations within the nervous system.
Differentiation 1992 Sep
PMID:Modulation of HOX2 gene expression following differentiation of neuronal cell lines. 136 Apr 33

The presence of homocysteate and homocysteine sulfinate was demonstrated in extracts prepared from cultures of rat cortical and cerebellar astrocytes as well as from C6 glioblastoma cells by o-phthalaldehyde derivatization and subsequent HPLC analysis. Homocysteate-like immunoreactivity was found in cultured cortical astrocytes by postembedding immunocytochemistry at the level of light microscopy. These findings support the notion of a glial localization of the excitatory transmitter candidate homocysteate.
Neurosci Lett 1992 Sep 28
PMID:Homocysteate and homocysteine sulfinate, excitatory transmitter candidates present in rat astroglial cultures. 136 Oct 45

A human glioblastoma cell line was found to express in vitro mRNA transcripts specific for insulin-like growth factor-II (IGF-II) and growth-hormone releasing-hormone (GHRH). In the absence of gross morphological changes, retinoic acid reduced the growth rate without major change of IGF-II mRNA expression, while alpha-difluoromethylornithine produced a complete growth arrest and a sharp decrease of IGF-II mRNA expression. Both reagents increased the expression of GHRH mRNA. Also in this glioblastoma cell line, like other neuroectodermal tumours, IGF-II mRNA is expressed independently from GHRH and seems to be parallel to growth rate.
Neurosci Lett 1992 Sep 14
PMID:IGF-II mRNA expression in LI human glioblastoma cell line parallels cell growth. 143 9

Antiproliferative cytokine secretion by lymphokine-activated killer (LAK) cells during coculture with glioblastoma cell lines, autologous glioma cells, and nongliomatous tumor cell lines (Daudi and K562 cells) was assessed, as was the antiproliferative activity of the culture supernatants against the T98G (glioblastoma) cell line. A neutralization test using agents against interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), and lymphotoxin (LT) showed that antiproliferative activity was due to IFN-gamma, but not to TNF or LT. Nongliomatous tumor cells stimulated LAK cells to secrete cytokines, but gliomatous tumor cells did not. It was found that there is a discrepancy between the LAK cell capability to lyse malignant glioma cells and the ability to secrete cytokines. This may be due to the factors secreted by glioblastoma cells.
J Neurosurg 1992 Sep
PMID:Antiproliferative cytokines secreted by lymphokine-activated killer cells stimulated with tumor cells. 150 88

Human cell-free extracts were used to detect activities specifically incising O6-methylguanine (m6G) paired with C or T in DNA. A 45-bp double-stranded DNA containing one m6G across from a T (m6G:T) was the test substrate. Extracts from glioblastoma cell lines A172 and A1235 (lacking the m6G-specific repair protein m6G-DNA methyltransferase, MGMT) and colon carcinoma cell line HT29, containing MGMT, showed incision activities specific for the T strand of m6G:T [and G:T, as reported previously by Wiebauer and Jiricny (1989)] substrates, but did not cleave m6G:C (or G:C) substrates. Competition experiments showed that the activity was similar to, if not identical with, the activity in human cells that incises G:T mismatches. The incision sites were similar to those recognized by human G:T- or G:A-specific mismatch enzymes, i.e., the phosphodiester bonds both 3' and 5' to the poorly matched T, suggesting the glycolytic removal of the poorly matched T followed by backbone incisions by class I or II AP endonucleases. Three experiments in which MGMT was inactivated showed that the m6G:T incision activity was not simply due to a two-step mechanisms in which MGMT would first mediate conversion of the m6G:T substrate to a G:T substrate which would serve as a substrate for G:T incision. Extracts from HT29 contained a DNA-binding factor, possibly DNA sequence-specific, that inhibited incision of the m6G:T (but not the G:T) substrate, that was removed by the addition of synthetic DNA to the reaction.
Biochemistry 1992 Sep 01
PMID:Incision at O6-methylguanine:thymine mispairs in DNA by extracts of human cells. 151 Sep 86

Transforming growth factor-beta 1 (TGF-beta 1) has been found to occur as latent high molecular weight complexes, with or without an associated component denoted latent TGF-beta 1-binding protein (LTBP). We show here that a human glioblastoma cell line (U-1240 MG) secretes all isoforms of TGF-beta s found in mammalian cells (TGF-beta 1, -beta 2, and -beta 3). Approximately 26% of the secreted TGF-beta is in an active form. Latent TGF-beta s were partially purified from medium conditioned by the U-1240 MG cell line using anion exchange chromatography. Analysis of the different fractions by immunoblotting using antisera against precursor parts of the different TGF-beta isoforms, and against LTBP, revealed that not only TGF-beta 1 but also other isoforms of TGF-beta may occur in high molecular weight forms containing LTBP. In addition, each one of the TGF-beta isoforms occurred in smaller forms not containing LTBP. Interestingly, each of the TGF-beta isoforms was also seen in complexes of about 210 kDa containing associated component(s) distinct from LTBP. These results indicate that each of the different isoforms of TGF-beta is synthesized and secreted by this glioblastoma cell line in several different high molecular weight latent forms; the biological importance of the various latent TGF-beta complexes is discussed.
J Biol Chem 1992 Sep 25
PMID:Transforming growth factor-beta 1, -beta 2, and -beta 3 secreted by a human glioblastoma cell line. Identification of small and different forms of large latent complexes. 152 69

Monoclonal antibodies to the transferrin receptor or to the T cell antigen, CD5, were chemically linked to mammalian RNase A and found to specifically inhibit protein synthesis in antigen-positive cells. Antibody-mediated specificity of these cytotoxic ribonuclease chimeras (CRCs) was demonstrated in three ways. 1) Toxicity was due to the chemical linkage of RNase to antibody, as the individual components added separately or in combination did not inhibit protein synthesis; 2) the anti-transferrin receptor CRCs inhibited protein synthesis in those cells expressing the human transferrin receptor (K562, U251, Jurkat cells) but had no detectable toxicity to cells lacking the human transferrin receptor (Vero or NIH 3T3 cells); 3) free antibody to either the human transferrin receptor (454A12 or 5E-9) or to the T cell antigen, CD5 (T101), blocked the cytotoxicity of the respective CRC. Two CRC species, designated P1 and P2, that differed in size and stoichiometry of RNase A to antibody, were purified by size-exclusion high performance liquid chromatography. The higher molecular weight P1 conjugate had an IC50 of 20-30 nM, whereas the P2 conjugate had a higher IC50 of 300-500 nM. Bioactivity could be reversibly increased more than 10-fold by freezing. The cytotoxicity of the CRCs was examined in vivo in a solid tumor animal model. Intratumoral injections of an anti-transferrin receptor CRC into established U251 human glioblastoma tumors grown in the flanks of nude mice prevented tumor growth, whereas RNase A mixed with antibody was ineffective. CRCs, therefore, express cytotoxicity in vitro and in vivo. Mammalian nucleases coupled to antibodies may be utilized as cell type-selective cytotoxins and have potential as pharmacologic reagents. The systemic toxicity and immunogenicity observed with mammalian derived cytotoxins may be significantly less than that of the currently employed plant- and bacterial-derived immunotoxins.
J Biol Chem 1992 Sep 25
PMID:Cytotoxic ribonuclease chimeras. Targeted tumoricidal activity in vitro and in vivo. 152 74

Expression of major heat shock and stress-induced protein, HSP70, is known to be under complex regulation in tumor cells. In this study, we investigated the alternations of cytokinetics and HSP70 expression by hyperthermia in the in vitro experimental systems, using two rat glioma cell lines, two human glioblastoma cell lines and rat glioblast cells. For hyperthermal treatment the flasks were placed in water baths warmed up at 41 -45 degrees C for 15 min. To determine the effect of hyperthermia on the cell cycle progression, the changes in the DNA distribution of the cell population were studied by flow cytometry (FCM). The levels of HSP70 protein were determined by immunoblot analysis. The relationship between cell cycle and HSP70 expression was investigated by FCM using PI and FITC-labelled HSP70 double staining technique. These results were as follows: 1) Compared with the control, hyperthermic treatment at 42 degrees C or 44 degrees C caused both 354A and T98G cells to accumulate in S phase 18 hours after treatment and G2/M phase after 6-18 hours. 2) Hyperthermic treatment at 42 degrees C caused C6 cells to accumulate in S phase 6 hours after treatment, whereas heat treatment at 44 degrees C caused C6 cells to accumulate in S phase after 18 hours and G2/M phase after 6 hours. 3) A172 cells were accumulated only in G2/M phase by hyperthermia. 4) Glioblast cells did not show the alterations of cytokinetics by heat treatment remarkably. 5) HSP70 protein synthesis were enhanced under hyperthermic conditions in all type of cells, whether primary glioblast or permanent glioma cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)
No To Shinkei 1991 Sep
PMID:[Alterations in cytokinetics and heat shock protein (70 kDa) expression of glial cell by hyperthermia]. 174 92

Since previous published studies of astrocytomas have shown alterations in the short arm of chromosome 17, and this chromosomal location is that which encodes the p53 protein, we used a monoclonal antibody and immunocytochemistry to detect this protein in a series of brain biopsies. The normal p53 protein has a short half-life and is not detectable using this method. Expression of an altered p53 protein was detected in 29 of 71 brain biopsies, but only in those that showed astrocytic features. p53 expression was detected in 20/32 glioblastomas, 5/12 anaplastic astrocytomas, and 3/5 mixed anaplastic oligo-astrocytomas, but only in astrocytic cells. It could not be detected in any other histologic types of primary brain neoplasms, either benign or malignant. The protein was detected in only 1/11 biopsies interpreted as showing gliosis, but this was in a patient who had previously had a resection for glioblastoma, and may have represented unrecognized infiltrating astrocytoma cells. The p53 protein was also expressed in the nuclei of the two human astrocytoma cell lines examined, U251MG and D54MG. These results are in general agreement with previous detailed chromosomal analyses that have found loss of heterozygosity in up to 60% of malignant astrocytic gliomas.
Mod Pathol 1991 Sep
PMID:Immunocytochemical detection of p53 in human gliomas. 175 78

Interleukin 1 (IL-1) is a multifunctional cytokine produced by numerous cell types, including cells of the central nervous system (CNS). In the CNS, IL-1 produced by glia is thought to support trophic functions after brain injury. However, little is known about whether the IL-1 receptor (IL-1R) is expressed in brain cells and how these receptors might be regulated. Analysis of IL-1R expression in the human glioblastoma cell line U-87 MG indicated the presence of a specific, saturable, and high-affinity (dissociation constant = 104 +/- 14 pM) binding site, which was of moderately high density (1,228 +/- 156 sites/cell). Incubation of U-87 MG cells with cortisol or dexamethasone for as little as 6 h resulted in an upregulation of IL-1R expression, which could be blocked by coincubation with cycloheximide or actinomycin D. IL-1 beta downregulated the expression of its own binding site. Upregulation of the IL-1R by glucocorticoids (GCs) appeared to be coupled to the release of interleukin 6 (IL-6), since IL-1 was significantly more potent in inducing IL-6 release in U-87 cells that were preincubated in the presence of GCs compared with cells incubated in the absence of GCs. These results suggest that IL-1 acts on glial cells via a high-affinity receptor and indicate that GCs may amplify or prolong the actions of IL-1 in the CNS.
Am J Physiol 1991 Sep
PMID:Glucocorticoid upregulation of interleukin 1 receptor expression in a glioblastoma cell line. 183 63


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