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)

Ribonucleic acid was isolated from a wide spectrum of central nervous system tumors to examine the expression of platelet-derived growth factors (PDGF) A and B, tumor growth factors (TGF-beta) 1 and 2, and ros messenger ribonucleic acid. Eight glioblastoma cell lines were examined as well as cell cultures from 22 tumor explants. The explants included 6 glioblastomas, 4 anaplastic astrocytomas, 5 astrocytomas, 3 ependymal tumors, 2 meningiomas, 1 medulloblastoma. and 1 ganglioglioma. For comparison, 2 nontumor glial cell cultures were included. The PDGF B-chain was expressed in 5 of 8 glioblastoma cell lines, 2 of 6 glioblastomas, and in 3 of 4 anaplastic astrocytoma explants. There was no PDGF B expression in 4 astrocytomas, 3 ependymomas of varying malignancy, in the remainder of the tumors, or in the nontumor glial cells. The PDGF A-chain was expressed in all of the tumors, with the exception of the malignant ependymoma and in both nontumor glial cell cultures. TGF-beta 1 was expressed in all of the tumors and in nontumor glial cells. The expression of TGF-beta 2 was expressed in many of the benign and malignant tumors and also in both nontumor glial cell cultures. The ros messenger ribonucleic acid was expressed in 1 of 5 glioblastoma cell lines and in 2 of 6 glioblastoma cell explants, but in none of the other tumors or in the nontumor glial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of platelet-derived growth factors, transforming growth factors, and the ros gene in a variety of primary human brain tumors. 199 89

Two different mechanisms of aggregation of heparinized human platelet-rich plasma have been identified with two tumor cell lines: In neither case are these mechanisms dependent on platelet-derived ADP. U87MG cells from a glioblastoma line of human origin caused a single irreversible wave of aggregation simultaneously with the onset of platelet secretion, and this was inhibited by heparin and hirudin but not by apyrase or phospholipase D. In contrast, Hut 20 cells from an undifferentiated tumor cell line of murine origin gave an initial reversible wave followed by a second irreversible wave, which then led to secretion. The first wave of platelet aggregation was unaffected by heparin or hirudin but was inhibited by apyrase, and the second wave was inhibited by phospholipase D. Citrate caused irreversible inhibition with either cell line, and aggregation did not occur with gel filtered platelets. These results suggest that platelet aggregation by the Hut 20 line is initially dependent on ADP released from the tumor cells, whereas aggregation induced by the U87MG line is dependent on a procoagulant activity of the tumor cell surface.
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PMID:Differing platelet aggregating effects by two tumor cell lines: absence of role for platelet-derived ADP. 733 92

The vascular system of the central nervous system is derived from capillary endothelial cells, which have invaded the early embryonic neuroectoderm. This process is called angiogenesis and is probably regulated by brain-derived factors. Vascular endothelial cell growth factor (VEGF) is an angiogenic growth factor whose expression correlates with embryonic brain angiogenesis, i.e. expression is high in the embryonic brain when angiogenesis occurs and low in the adult brain when angiogenesis is shut off under normal physiological conditions. VEGF is also a vascular permeability factor (VPF) and, therefore, its expression is also consistent with the formation of the blood-brain barrier by brain endothelial cells, i.e. capillaries are leaky in the embryonic brain but are tight in the postnatal and adult brain. Thus, VEGF/VPF may be a key factor regulating endothelial cell growth and permeability. This notion is further supported by the observation that VEGF expression is induced and strongly upregulated in human malignant glioblastoma. This tumor is characterized by vascular proliferations, vascular leakage and edema. The differentiation of blood-brain barrier endothelial cells is probably regulated by astrocytes which form foot processes apposed to the abluminal vascular basement membrane. Blood-brain barrier endothelial cells express a set of cell surface proteins that are absent from permeable capillaries. We have characterized one such novel transmembrane glycoprotein which is a new member of the immunoglobulin superfamily. This protein and the analysis of the in vitro characteristics of brain endothelial cells may help to define the molecular mechanisms that are involved in blood-brain barrier induction and permeability.
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PMID:Molecular biology of blood-brain barrier ontogenesis and function. 752 21

We have detected a tyrosine-phosphorylated 200-kDa protein in two human tumor cell lines, A1235 glioma and A172 glioblastoma. The protein is an integral plasma membrane sialoglycoprotein with tyrosine kinase activity. The interesting characteristic of this protein (gp200) is that it is recognized by a number of monoclonal and polyclonal antibodies to the 170-kDa epidermal-growth-factor (EGF) receptor; however, it lacks detectable EGF-binding activity. gp200 differs from three other EGF-receptor-related proteins, erb-B-2, erb-B-3 and erb-B-4 gene products, and hence appears to be yet another member of the EGF-receptor family of proteins. This is further strengthened by the fact that both gp200 and the EGF receptor contain a common epitope which is recognized by an anti-peptide IgG to the beta-type platelet-derived-growth-factor (PDGF) receptor. Our previous studies [Bishayee, S., Majumdar, S., Scher, C.D. & Khan, S. (1988) Mol. Cell. Biol. 8, 3696-3702] have demonstrated that this epitope in the PDGF receptor is highly susceptible to the phosphorylation state of the receptor and that such a conformational change appears to be important in biological message transmission. The expression of gp200, which appears to have tyrosine kinase activity and is immunologically related to the EGF receptor in tumor cells, suggests its possible involvement in cell growth.
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PMID:Characterization of a novel epidermal-growth-factor-receptor-related 200-kDa tyrosine kinase in tumor cells. 760 Nov 58

Localization of platelet-derived endothelial cell growth factor (PD-ECGF) in the surgical specimens of 11 human glioblastomas and 12 meningiomas was immunohistochemically examined with a polyclonal anti-PD-ECGF rabbit IgG. PD-ECGF was mainly localized in macrophages distributing around blood vessels at the peripheries of tumor tissue, especially of glioblastoma. PD-ECGF-positive macrophages were frequently accumulated in the vascular-rich stroma of glioblastoma, where occasionally expressed proliferating cell nuclear antigen-positive endothelial cells. However, few macrophages expressing PD-ECGF were scatteringly seen in meningioma. These findings suggest that PD-ECGF plays an important role in the growth of glioblastoma by affecting the stromal angiogenesis.
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PMID:[Localization of platelet-derived endothelial cell growth factor in human glioblastoma and meningioma]. 789 24

Angiogenesis, the sprouting of new blood vessels from existing vessels, occurs in many physiological and pathological processes, including embryonic development, wound healing, and tumor growth. It is required for tumor growth because new blood vessel formation is necessary for tumors to expand beyond a minimum volume. Several growth factor receptor tyrosine kinases have been implicated in angiogenesis, including receptors for epidermal, fibroblast, and platelet-derived growth factors, as well as the receptors Flk-1/KDR, Flt-1 Tek/Tie-2, and Tie-1. Endothelial cells in the vessels of tumors express Flk-1/KDR, a receptor for vascular endothelial growth factor. Flk-1 was previously shown to play a role in angiogenesis and tumor formation of s.c. xenografts of C6 glioma cells using dominant-negative methodology. We now demonstrate that Flk-1 seems to be generally involved in the growth of a wide range of solid tumors, including mammary, ovarian, and lung carcinoma, as well as glioblastoma. Furthermore, survival times in rats bearing intracerebral tumors were prolonged using the same dominant-negative methodology. The involvement of Flk-1 in a variety of tumor types suggests an important role for Flk-1 in tumor angiogenesis.
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PMID:Dominant-negative inhibition of Flk-1 suppresses the growth of many tumor types in vivo. 860 10

Epidermal growth factor (EGF) and platelet-derived growth (PDGF) are suggested to be involved in the proliferation of human gliomas. We examined the effects of these growth factors on two human malignant glioma cell lines. Treatment of the A172 glioblastoma and the Hs683 glioma cell line with EGF and PDGF resulted in the tyrosine autophosphorylation, and hence activation, of the respective growth factor receptors. In addition, both cell lines responded to EGF and PDGF with increased deoxyribonucleic acid (DNA) synthesis. Because the intrinsic protein tyrosine kinase activity of this class of growth factor receptors is indispensable for their functioning, we tested the effects of specific protein tyrosine kinase inhibitors on growth factor-induced DNA synthesis and glioma cell proliferation. Genistein inhibited both EGF- and PDGF-stimulated autophosphorylation of the receptors and induction of DNA synthesis. However, genistein seemed to be cytotoxic to the cells. The tyrphostins RG 50875 and RG 13022 dose-dependently inhibited DNA synthesis induced by EGF, PDGF, and serum. RG 13022 completely blocked the EGF- and PDGF-induced DNA synthesis at a concentration of 50 mumol/L. The tyrphostins showed no selectivity in blocking either EGF or PDGF signaling. With concentrations up to mumol/L, no cytotoxic side effects of the tyrphostins were observed. Both tyrphostins also inhibit serum-driven cell growth in a dose-dependent manner. These results support the hypothesis that activated protein tyrosine kinase receptors are involved in the proliferation of A172 and Hs683 glioma cells. Selective inhibitors of protein tyrosine kinases, therefore, might have the potential to contribute to the treatment of growth factor-dependent gliomas.
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PMID:Inhibitors of protein tyrosine phosphorylation reduce the proliferation of two human glioma cell lines. 874 58

Glioblastoma multiforme is distinguished from its less malignant astrocytoma precursors by intense angiogenesis and frequent loss of tumor suppressor genes on chromosome 10. Here we link these traits by showing that when a wild-type chromosome 10 was returned to any of three human glioblastoma cell lines U251, U87, or LG11, they lost their ability to form tumors in nude mice and switched to an antiangiogenic phenotype, as measured by the inhibition of capillary endothelial cell migration and of corneal neovascularization. This change in angiogenesis was directly due to the increased secretion of a potent inhibitor of angiogenesis, thrombospondin-1, because: (a) neutralizing thrombospondin completely relieved the inhibition; (b) the inhibitory activity of thrombospondin was not dependent on transforming growth factor beta; and (c) chromosome 10 introduction did not alter secreted inducing activity. The inducing activity was dependent on vascular endothelial cell growth factor and had an ED50 of 10 microg/ml in media conditioned by parental cells and 9-13 microg/ml in media conditioned by chromosome 10 revertants. Normal human astrocytes were also antiangiogenic due to secreted thrombospondin. The effect of chromosome 10 on thrombospondin production in vitro was reflected in patient material. Normal brain and lower grade astrocytomas known to retain chromosome 10 stained strongly for thrombospondin, but 12 of 13 glioblastomas, the majority of which lose chromosome 10, did not. These data indicate that the loss of tumor suppressors on chromosome 10 contributes to the aggressive malignancy of glioblastomas in part by releasing constraints on angiogenesis that are maintained by thrombospondin in lower grade tumors.
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PMID:Inhibition of angiogenesis in human glioblastomas by chromosome 10 induction of thrombospondin-1. 897 Nov 76

To evaluate the possible clinical intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) for malignant brain tumors, its anti-tumor activity and neurotoxicity were compared with that of 5-fluorouracil (5-FU) and 5-fluorouridine (FUrd) in vitro. FdUrd showed good tumoricidal activity against cultured mouse 203 glioma cells and rat Walker 256 carcinoma cells as well as A172 human glioblastoma cells. Daoy human medulloblastoma cells and CADO-LC4 human lung cancer cells. It also showed less toxicity for primary cultures of neurons from C57/BL6 mouse and human embryo compared to 5-FU and FUrd. Thymidine phosphorylase (TPase) and thymidine kinase (TK), key enzymes for metabolism of 5-FU derivatives, were measured in cerebrospinal fluid (CSF). TPase or TK activity was detected in the CSF of hardly any patients with malignant brain tumors including meningeal carcinomatosis. These data indicated that the CSF is a favorable site for FdUrd chemotherapy, because the rate of conversion of FdUrd injected to 5-FU would be minimal. In conclusion, FdUrd may be potentially useful for intrathecal treatment of meningeal carcinomatosis.
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PMID:[In vitro study on intrathecal application of 5-fluoro-2'-deoxyuridine (FdUrd) for meningeal dissemination of malignant tumor]. 975 55

Thymidine phosphorylase (TP) has been implicated as a potent angiogenic factor and a prognostic factor in various human solid tumors. We investigated the expression of TP in a series of human astrocytic tumors using immunohistochemistry, enzyme-linked immunosorbent assay, and reverse transcriptase/polymerase chain reaction (RT-PCR) analysis. A total of 63 astrocytic tumors [27 glioblastomas (GBM), 19 anaplastic astrocytomas (AA), 17 low-grade astrocytomas (LGA)] and 5 normal brain tissues were immunohistochemically stained with antibodies to TP, vascular endothelial growth factor (VEGF), p53, MIB-1, and factor-VIII-related antigen. They were also evaluated for the degree of apoptosis by a ApopTag kit. Ten tumors (5 GBM, 2 AA, 3 LGA) and 3 normal brain tissues were evaluated for their expression of VEGF and TP by RT-PCR analysis. TP was constantly localized in the cytoplasm of astrocytic tumor cells, less intensely in the cytoplasm of vascular endothelial cells, but not in the normal brain. Some of the TP-positive cells were of macrophage origin, but most positive cells were the tumor cells themselves. Vascular density, MIB-1 positivity, p53 positivity, VEGF expression, and the apoptotic index were significantly higher in the TP-positive tumors than in TP-negative tumors. There was a significant correlation between TP and VEGF mRNA expression. In a limited number of glioblastoma cases, the apoptotic index was significantly higher in TP-positive glioblastomas than in TP-negative glioblastomas. In human astrocytic tumors, TP was expressed in the tumor, macrophage, and endothelial cells. TP was a potent angiogenic factor closely associated with cell proliferation and tumor apoptosis.
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PMID:Expression of the angiogenic factor thymidine phosphorylase in human astrocytic tumors. 1074 8


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