Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of a brain tumor alters regional cerebral blood flow, oxygen consumption, and glucose utilization in adjacent and remote brain tissue, but its effect on brain neurotransmitter levels is unclear. In the present report, the levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in tumor tissue and gray and white matter obtained from cats with induced brain tumors were measured. Glioma cells (9L) were xenotransplanted into the central white matter of the right hemisphere, and 15 d later the brains were frozen in vivo. Samples of tumor, parietal (peritumor), temporal, and frontal gray and white matter were divided for analysis of water content and quantification of amines and their metabolites. The water content of white matter, but not gray matter, adjacent to the tumor was increased. Neurotransmitter amine and metabolite levels were much lower in the tumor than in brain tissue. In gray matter adjacent to the tumor, concentrations of DA and its metabolites HVA and DOPAC were significantly decreased from control, whereas 5-HIAA was increased. The NA, DA, HVA, and DOPAC levels were decreased in temporal gray matter, whereas all amine and metabolite levels were unchanged in frontal gray matter. These results indicate that altered neurotransmitter metabolism is one of the effects of the presence of a brain tumor.
Mol Chem Neuropathol 1989 Apr
PMID:Regional monoamine and metabolite levels in a feline brain tumor model. 274 38

The SV40(cT) mutant encodes a large tumor antigen (cT-ag) that is defective for transport from the cell cytoplasm into the nucleus. This mutant is able to transform established cell lines at near wild-type virus efficiencies, but has a markedly decreased ability to transform primary cells and to induce tumors in newborn hamsters (R. E. Lanford, C. Wong, and J. S. Butel, 1985, Mol. Cell. Biol. 5, 1043-1050). To explore the biology of transport-defective T-ag in vivo, transgenic mice carrying the cT-ag gene were produced. Five of eight founder animals died early in life of choroid plexus tumors (mean age +/- SE, 52 +/- 11.0 days); renal and thymic lesions were also observed. Mice of an SV40(cT) transgenic line regularly succumb to brain tumors (mean age, 81 +/- 1.2 days). SV40 T-ag is expressed in the tumor cells and is retained in the cytoplasm. The observation that SV40(cT) is equivalent to wild-type virus at tumor induction in transgenic mice emphasizes the probable importance of extranuclear forms of SV40 T-ag in brain tumor formation. This study also indicates that in vitro cell transformation assays may not always be accurate reflections of the oncogenic potential of a transforming gene in vivo, because of the different cell types involved.
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PMID:Tumorigenesis in transgenic mice by a nuclear transport-defective SV40 large T-antigen gene. 282 Jan 26

c-myc is overexpressed in glioblastoma multiforme, the most common form of brain tumor. To find a suitable target for in vivo antisense therapy of gliomas, we investigated the biological effects on the human glioma cell line, U87MG, of antisense oligonucleotides targeted against the translation start site of c-myc mRNA. Parameters examined included c-myc protein level, cell proliferation, and cell adhesion to substratum. Oligonucleotides were administered by electroporation as capped phosphorothioates. Antisense oligomers caused a reduction in c-myc protein expression, loss of cell adhesion to plastic, and complete growth inhibition. Various control sequences, including sense, scrambled, and three-base mismatched oligomers, were also tested. Some of the controls retained a dG quartet found in the antisense sequence. Reduction in c-myc protein and cell growth and loss of cell adhesion were specific to the antisense sequence. Surprisingly, fully thioated antisense and scrambled sequences, either containing or lacking a dG quartet, were equally inhibitory to both cell growth and adhesion. Loss of cell adhesion was observed with only phosphorothioate-containing oligomers, not with either their phosphodiester or nuclease-resistant PA congeners, and was completely reversed when cells were plated onto fibronectin. These results demonstrate that a commonly used c-myc antisense oligomer also displays dramatic, sequence- but not antisense-specific effects on cell proliferation and cellular adhesion, depending on the backbone.
Mol Pharmacol 1995 Oct
PMID:Contribution of sequence and phosphorothioate content to inhibition of cell growth and adhesion caused by c-myc antisense oligomers. 747 2

The effects of various Ca2+ channel agonists and antagonists on tumor cell growth were investigated using U-373 MG human astrocytoma and SK-N-MC human neuroblastoma cell lines. Classical Ca2+ channel antagonists, verapamil, nifedipine, and diltiazem, and inorganic Ca2+ channel antagonists, Ni2+ and Co2+, inhibited growth of these tumor cells in a dose-dependent manner. Except Ni2+, these Ca2+ channel antagonists did not induce a significant cytotoxicity, suggesting that the growth-inhibitory effects of these drugs may be the result of the influence on the proliferative signaling mechanisms of these tumor cells. In contrast, Bay K-8644, a Ca2+ channel agonist, neither enhanced the growth of tumor cells nor increased intracellular Ca2+ concentration, indicating that voltage-sensitive Ca2+ channels may not be involved in tumor cell proliferation. Moreover, growth-inhibitory concentrations of Ca2+ channel antagonists significantly blocked agonist (carbachol or serum)-induced intracellular Ca2+ mobilization, which was monitored using Fura-2 fluorescence technique. These results suggest that the inhibition of the growth of human brain tumor cells induced by Ca2+ channel antagonists may not be the result of interaction with Ca2+ channels, but may be the result of the interference with agonist-induced intracellular Ca2+ mobilization, which is an important proliferative signaling mechanism.
Mol Chem Neuropathol 1994 Jun
PMID:Inhibition of cell growth and intracellular Ca2+ mobilization in human brain tumor cells by Ca2+ channel antagonists. 752 51

Changes in CD44 transcripts have been previously found to be associated with metastasis in animal models. The purpose of this study was to investigate CD44V changes in four well established high grade human brain tumor cell lines, known to possess prominent invasive behavior. In Northern blot analysis, CD44S and CD44V were expressed strongly in three high-grade glioblastoma multiforme cell lines (GBM 8401, GBM 8909, GBM 8804) and one malignant meningioma cell line (IOMM). By RT-PCR and blot hybridization, three variant transcripts (650 bps, 850 bps, and 1,000 bps) were detected in GBM 8804 and two isoform transcripts (650 bps, 850 bps) were recognized in GBM 8401 and 8909. Further, in a malignant meningioma cell line (IOMM), only one weak isoform (650 bps) was detected. However, by Northern blot analysis, neither CD44S or CD44V could be expressed in normal brain and meningeal tissue. These results indicate that discrete CD44 mRNA splice variants are expressed in high grade glial cell tumors and malignant meningioma and suggest a possible role in the invasion of malignant brain tumors.
Biochem Mol Biol Int 1994 Jul
PMID:Selective expression of CD44 messenger RNA splice variants in four high grade human brain tumour cell lines. 752 22

Gliomas, the most common form of intrinsic brain tumor, are characterized by diffuse local invasion of the normal brain structures, irrespective of their histological grade of malignancy; a feature that is a major obstacle to successful therapy. They generally infiltrate the central nervous system (CNS) as individual tumor cells several centimeters beyond the macroscopic tumor margin and consequently often recur, after subtotal surgical resection. Factors involved in the control of both their proliferation and invasiveness are poorly documented. In this work, the role of gangliosides on proliferation of both human fetal human brain cells and five cell lines derived from human gliomas with different grades of malignancy was investigated. In addition, 8 microns-porosity polycarbonate filters were used to study cell motility. In addition, these filters were coated with the reconstituted extracellular matrix (ECM) composite, Matrigel, to assess invasiveness. The results presented show that gangliosides generally exert a proliferation inhibitory effect on fetal brain cells and glioma cell lines in vitro and play an important role in promoting glioma cell motility and invasiveness. The molecular mechanisms involved in the action of gangliosides may prove useful in identifying new targets for an anti-invasion therapy.
Mol Chem Neuropathol
PMID:Gangliosides modulate proliferation, migration, and invasiveness of human brain tumor cells in vitro. 763 17

We studied whether pretreatment of U-251 MG human brain tumor cells with the polyamine analog 1,19-bis-(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) affected the cytotoxicity of the topoisomerase II inhibitor etoposide. We found that BE-4-4-4-4 protected cells from the cytotoxic effects of etoposide. Possible mechanisms for this protection may be related to enhanced DNA-nuclear matrix association in analog-treated cells.
Cell Mol Biol (Noisy-le-grand) 1994 Nov
PMID:Pretreatment with the polyamine analog 1,19-bis-(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) inhibits etoposide cytotoxicity in U-251 MG (NCI) human brain tumor cells. 784 64

Ganglioside composition was examined in an experimental mouse brain tumor growing as a solid tumor in vivo and as a cultured cell line in vitro. Gangliosides were also studied in the solid tumor rederived from the cultured tumor cell line. Although GM3-NeuAc was the major ganglioside in both the solid tumor and cultured tumor cells, several gangliosides expressed in the solid tumors (e.g., GM2-NeuGc, GM1, and GM1b) were not expressed in the cultured tumor cells. These gangliosides, however, are major components of mouse macrophages. Furthermore, significant amounts of gangliosides containing N-glycolylneuraminic acid (NeuGc) were found in the solid tumor growing in vivo, but only trace amounts were present in the cultured tumor cells. NeuGc is a common ganglioside sialic acid in mouse nonneural cells, whereas N-acetylneuraminic (NeuAc) is the predominant sialic acid in mouse brain. The trace amounts of NeuGc in the cultured cells are attributed to contamination from the fetal bovine serum. Radiolabeling of the cultured tumor cell gangliosides with [14C]galactose revealed that GM3-NeuAc was the only ganglioside synthesized by the tumor cells. The results suggest that nontumor-infiltrating cells, e.g., macrophages, lymphocytes, and endothelial cells, may contribute significantly to the total ganglioside composition of solid tumors growing in vivo.
Mol Chem Neuropathol
PMID:Influence of growth environment on the ganglioside composition of an experimental mouse brain tumor. 808 38

Malignant astrocytoma is the most common primary human brain tumor. Most astrocytomas express a combination of platelet-derived growth factor (PDGF) and PDGF receptor which could close an autocrine loop. It is not known whether these autocrine loops contribute to the transformed phenotype of astrocytoma cells or are incidental to that phenotype. Here we show that dominant-negative mutants of the PDGF ligand break the autocrine loop and revert the phenotype of BALB/c 3T3 cells transformed by the PDGF-A or PDGF-B (c-sis) gene. Then, we show that these mutants are selective in that they do not alter the phenotype of 3T3 cells transformed by an activated Ha-ras or v-src gene or by simian virus 40. Finally, we show that these mutants revert the transformed phenotype of two independent human astrocytoma cell lines. They have no effect on the growth of human medulloblastoma, bladder carcinoma, or colon carcinoma cell lines. These observations are consistent with the view that PDGF autocrine loops contribute to the transformed phenotype of at least some human astrocytomas.
Mol Cell Biol 1993 Dec
PMID:Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells. 824 42

Using a combination of polymerase chain reaction and single-strand conformation polymorphism techniques (PCR-SSCP) we have analyzed 78 brain tumor samples (70 primary and 8 metastatic) for the presence of mutations in the conserved regions of the Tp53 (tumor p53) gene. We have found that only two groups, gliomas (exclusively in astrocytomas) and metastases, displayed Tp53 mutations. Three of eight (37.5%) metastases showed a mutant Tp53 allele accompanied by loss of the normal one. In contrast, the frequency of Tp53 mutations in the primary brain tumors examined was lower (5.7%). Although we have examined different types of primary brain tumors, Tp53 mutations were exclusively observed in both, low and high-grade astrocytomas (four of 24). The Tp53 mutations detected in astrocytic tumors appear to be correlated with the malignancy grade. The low-grade astrocytomas were heterozygous for the mutation, whereas the high-grade astrocytomas had affected the two Tp53 alleles, suggesting a two-steps model for inactivation of the p53 gene in astrocytomas. Thus, single p53 mutation seems to occur in initial stages of astrocytoma tumorigenesis; the later lost of the remaining wild-type allele appears associated with the progression towards a more malignant stage.
Hum Mol Genet 1993 Oct
PMID:Timing of p53 mutations during astrocytoma tumorigenesis. 826 22


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