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)

We established and characterized two cell lines derived from glioblastoma multiforme. Both cell lines exhibited tumor cell morphology and growth kinetics and showed variable expression of glial fibrillary acidic protein (GFAP), S-100, fibronectin and vimentin. Cytofluorimetrical analysis of tumor samples showed a diploid DNA distribution, whereas permanent culture cells evolved to the hyperdiploid DNA content. Karyotype studies revealed cytogenetical abnormalities described in glial tumors including gain of chromosome 7, loss of chromosome 10 and presence of double minutes (DMs). Enhanced expression of Ha-ras and c-myc genes resulted from high p-21 and p-62 levels. The contemporary presence of TGF-alpha and EGF-Rc transcripts suggested an autocrine mechanism in the cell lines growth.
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PMID:Establishment and characterization of two cell lines derived from human glioblastoma multiforme. 132 Mar 58

Cholesterol in animals is a major structural component of cell membranes. It may therefore play a functional role in the modulation of cell osmolarity, the process of pinocytosis and the activities of membrane-associated proteins such as ionic pumps, immune responses, etc. A major relationship exists between the cell-growth processes and the cholesterol biosynthetic pathway. The cholesterol needed for new membranes may be derived either from endogenous synthesis or from exogenous sources, principally plasma low-density-lipoproteins (LDL) which enter the cells by receptor-mediated endocytosis. Both these pathways are enhanced in rapidly growing cells. Conversely, if synthesis is inhibited and no exogenous cholesterol is available, cell growth is blocked. The 3-hydroxy-3-methylglutaryl CoA (HMGCoA) reductase (the rate-limiting reaction in cholesterol biosynthesis) is the enzyme which catalyzes the conversion of HMGCoA to mevalonic acid. It has been suggested that mevalonate may play an important role in cell proliferation. All cells need at least two products synthesized from mevalonate in order to proliferate, and the only one yet identified is cholesterol. Other melavonate-derived potential candidates as cell-cycle and cell-survival products include the dolichols ubiquinone side chains, isopentenyladenosine derivatives, etc. Furthermore, it has recently been shown that membrane association appears to be an important function in mevalonate-derive modifications of several important proteins such as cellular membrane G proteins, those coded for by oncogenes (ras proteins) and lamins (nuclear proteins). In recent years the development of cholesterol-synthesis-inhibiting drugs, for lowering plasma cholesterol levels has mainly been centred on the control of HMGCoA reductase activity (vastatins). However, because mevalonic acid is the precursor of numerous metabolites, any reduction of such activity may potentiate pleiotropic effects. Vastatins are now, therefore, receiving increased attention as potential pharmacological tools for the control of abnormal cell growth in pathological situations, i.e. tumours and vascular smooth muscle cell proliferation under atherogenic conditions. In our laboratories, we have demonstrated that simvastatin can prevent arterial myocyte proliferation both in vivo and in vitro. Simvastatin can also inhibit in vitro the rate of human glioma cell growth, since it shows a strong synergistic inhibitory effect on cell proliferation when used in association with anticancer agents such as Carmustine or beta-interferon. Both simvastatin-induced cell growth inhibition and the synergy observed with these drugs can be completely reversed by incubating cells with mevalonate. This shows that the effect of simvastatin of cell proliferation is due to its specific inhibitory activity on intracellular mevalonate synthesis.
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PMID:Cholesterol and mevalonic acid modulation in cell metabolism and multiplication. 147 Nov 62

Ras (p21) proteins are involved in the control of cell growth and differentiation, but the mechanism by which they exert these effects is not yet known. Here we present evidence that c-Ha-ras (p21(Gly-12)) and its oncogenic mutant T24-ras (p21(Val-12)) selectively induce omega-conotoxin and dihydropyridine-sensitive Ca2+ currents within a few hours after introduction into the cytoplasm of neuroblastoma x glioma hybrid cells. Whereas control cells exhibited a mean Ca2+ current of 250 pA, it amounted to 730 pA in cells pretreated with ras protein. In cells loaded with p21(Gly-12), the effect occurred after 2 hours and was terminated after 8 hours. In contrast, introduction of p21(Val-12) resulted in a prolonged delay (6 hours) of the effect which lasted for more than 24 hours. When ras proteins were preactivated with the non-hydrolysable GTP analog GppNHp, the time courses of both p21(Gly-12) and p21(Val-12) effects were fast and sustained, suggesting that in intact cells (i) the GDP/GTP exchange is faster for p21(Gly-12) compared to p21(Val-12) and (ii) inactivation of p21(Gly-12) is mediated by GAP-induced GTPase activity. T-type Ca2+ currents and K+ currents were unaffected by ras proteins.
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PMID:Ras proteins activate calcium channels in neuronal cells. 165 68

Recent efforts have been directed at identifying and characterizing candidate tumor suppressor genes and the activities of oncogenes in primary brain tumors. The p53 gene mapping to region p13 of chromosome 17 has several characteristics as a tumor suppressor gene. The wild-type p53 protein, which is a transcriptional activator, may serve as a barrier to the progression of neoplastic processes, and alterations of p53 are involved in genesis of various cancers including astrocytomas. The NF1 gene, which is responsible for the susceptibility to neurofibromatosis type 1, has recently been isolated. This gene is assumed to play a role in the signal transduction pathway by interacting with the ras gene product. Recent observation revealed that the NF1 gene may regulate the neuronal differentiation, and the alteration in regulation of the NF1 transcript is potentially related to the progression of neuroectodermal tumors. Restriction fragment length polymorphism studies have also shown chromosomal losses associated with chromosome 9, 10 and 17. These losses of genetic material are suspected to involve loci near or at the p53 gene for chromosome 17, and neighboring the interferon genes on chromosome 9. Although no sublocalization of chromosome 10 deletions has been accomplished, all of these loci are thought to harbor tumor suppressor genes. Recent advances in oncogene research have focused on understanding the mechanisms of action of growth factors, growth factor receptors, and their substrates, particularly in glial oncogenesis. Fibroblast growth factor, epidermal growth factor, and their respective receptors are of particular interest. However, the ROS oncogene, which is expressed and rearranged in some glioma cell lines, may not be a critical factor in the development of gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathways of oncogenesis in primary brain tumors. 190

We have previously developed an assay to measure experimental metastatic ability of cells following intravenous injection into chorioallantoic membrane (CAM) veins of naturally immune deficient chick embryos. Here we compare metastatic properties of different cell types (ras-transformed and control NIH 3T3, LTA, and 10T1/2; melanoma; and glioma) from several species (mouse, rat, human), using chick embryos and the more commonly-used immune deficient host, nude mice. We found a good correlation between the two assays. Both hosts have advantages and disadvantages in assessing metastatic properties. We conclude that the chick embryo assay is a useful alternative host for experimental metastasis studies. This assay correlates well with and is less costly than assays using nude mice.
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PMID:Comparison of metastatic properties of a variety of mouse, rat, and human cells in assays in nude mice and chick embryos. 210 62

Sodium butyrate has been shown to inhibit the growth and induce the differentiation of F-98 rat glioma cells. In agreement with the morphological changes, we have found that mRNAs for fibronectin and collagen in these cells could be reversibly induced by butyrate. While Ki-ras mRNA levels remained relatively unchanged, mRNAs for fos and sis increased significantly during the course of butyrate induced differentiation. c-fos induction can be detected 30 min after butyrate addition, a peak level (greater than 20 fold) was reached at 2 h, with a subsequent gradual decline. c-sis induction was detectable 24 h after butyrate exposure, at which time the cells have assumed morphological transition. Interestingly, the sis mRNA induction was not reversible upon butyrate withdrawal. The sis mRNA half-life increased from 40 min in the untreated cells to 100 min in the butyrate induced cells indicating that the increase in the stability of sis mRNA contributed, at least in part, to the elevated levels of sis expression. These findings demonstrate a coordinated induction of fibronectin and collagen genes in the butyrate-treated F-98 cells. In addition, fos and sis transcripts were differentially induced; a rapid and transient induction of fos followed by an irreversible induction of sis at a later stage of differentiation.
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PMID:Induction of fos and sis proto-oncogenes and genes of the extracellular matrix proteins during butyrate induced glioma differentiation. 210 2

We found a direct correlation between increasing ras p21 protein immunopositivity and severity of human glioma using computer-assisted, digital-image processing to quantify the amount of p21 immunoreactive to the monoclonal antibody RAP-5. We determined that there was a significant difference in reactivity between glioblastoma multiformes and more-differentiated astrocytomas (experiment-wise error less than 0.05). This result confirmed the conclusions made on the same tumors using standard light microscopy and visual examination. Immunohistochemistry quantized by automated image analysis may be a useful adjunct to current histopathological strategies since it decreases assay subjectivity and variation.
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PMID:Application of automated image analysis to demonstrate the correlation between ras p21 expression and severity of gliomas. 219 8

We have cloned cDNAs encoding alpha subunits of the guanine nucleotide-binding proteins Gs, Gi, and Go and determined their nucleotide sequences. Purified preparations of Gi and Go alpha subunits (Gi alpha and Go alpha) from rat brain were completely digested with trypsin, and peptides were subjected to amino acid sequence analysis. By screening of a cDNA library from rat C6 glioma cells with a synthetic probe corresponding to a 17 amino acid sequence, a clone encoding the sequence of Go alpha was obtained. Then, the library was rescreened with a Go alpha cDNA probe to isolate several strongly or weakly hybridizing clones. cDNAs encoding the complete sequences of Gi alpha and Gs alpha were thus obtained. From nucleotide sequence analysis, the amino acid sequences of Gs alpha and Gi alpha were deduced; they contain 394 and 355 amino acid residues (including the initiator methionine), respectively. The calculated molecular weights for Gs alpha and Gi alpha were 45,663 and 40,499, respectively. The Go alpha clone encoded a sequence of 310 amino acid residues that lacked the NH2 terminus. The homology of the alpha subunits of Gs, Gi, Go, transducin, and ras-encoded protein is discussed.
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PMID:Molecular cloning and sequence determination of cDNAs for alpha subunits of the guanine nucleotide-binding proteins Gs, Gi, and Go from rat brain. 308 67

LAK are cytolytic lymphocytes with the unique capacity for killing NK-resistant fresh human tumor cells in short-term assays. LAK kill autologous as well as allogeneic tumors with complete cross-reactivity. Initial studies on the classification of LAK conclude that LAK are distinct from the classical NK and T lymphocyte systems, based on a number of criteria including surface phenotype, activation conditions, and a spectrum of susceptible target cells. LAK kill ras oncogene-transfected fibroblasts like they kill fresh tumors. As yet, the target cell determinant responsible for susceptibility to LAK lysis is unknown. Activation of LAK requires only IL 2 and is blocked by monoclonal antibodies to the IL 2 receptor. Because only IL 2 alone is sufficient for LAK activation, we have done in vitro testing to determine whether fresh PBL could be activated in the presence of tumor, as might be desirable in vivo. LAK were activated sufficiently to mediate significant destruction of fresh tumor. We also tested whether LAK could be maintained in the presence of large tumors, providing IL 2 was added. Again, results were positive, suggesting that LAK either recycle or are a self-renewing population that depend on IL 2 for continued functions. Because of these and other findings, we have initiated a clinical protocol to test whether LAK made from the PBL of patients with brain tumor could eliminate residual glioma tumor cells. Autologous LAK plus rIL 2 to maintain lytic ability are injected during surgery. Preclinical studies in a rat glioma model have shown this approach to be safe, and previous in vivo murine studies have concluded that LAK kill tumors in Winn-type lung colony formation tests (Kedar et al. 1982). Much work is needed before we can understand the LAK phenomenon and determine its usefulness in cancer therapy, as well as its inherent biologic role. We hope that this chapter will stimulate both interest and the basic research needed to realize LAK potential.
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PMID:Interleukin 2-activated cytotoxic lymphocytes in cancer therapy. 348 59

Neurofibromatosis type 1 (NF1) or von Recklinghausen neurofibomatosis, is a common heritable neurocutaneous disorder. This disorder appears to affect all races, with a prevalence estimated to be 1 in 3000. Approximately half of all cases of NF1 represent new mutations. The characteristics of NF1, which include cafe-au-lait spots, neurofibromas, Lisch nodules, optic glioma, osseous lesions, macrocephaly, short stature and mental retardation suggest that the genetic lesion affects the proper development of multiple organ systems. Within the past few years, the gene causing NF1 has been identified and the protein encoded by this gene, neurofibromin, has been the subject of detailed investigation. The NF1 gene spans over 350 kb of genomic DNA and encodes a protein product of 2818 amino acids. Neurofibromin is expressed in many different tissues. It is now known that one role of neurofibromin is as a GTPase activating protein (GAP), very likely in the same pathway of signal transduction as ras. Absence of neurofibromin in mice homozygously mutant for the NF1 gene results in profound developmental abnormalities. In mice that are heterozygous for NF1, an accelerated onset of tumor formation is observed. Combined with studies of tumors from NF1 patients showing homozygous deletions in the NF1 gene, these data suggest a role for NF1 as a "tumor suppressor". Evidence suggesting other roles played by neurofibromin, in control of proliferation in some situations and differentiation in others, is gradually bringing the previously hazy picture of this genetic disorder into sharper focus.
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PMID:Neurofibromatosis type 1: pathology, clinical features and molecular genetics. 767 Jun 56


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