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 composition of the free amino acid pools in various brain tumors and in normal brains obtained at surgery or at autopsy is determined with an automatic amino acid analyzer and the results statistically evaluated. The tumors have lower ratios of GABA in the pools than the normal brain; tumors with higher GABA ratios are found in those which are in close contact with and have an invasive nature to brain tissue. In gliomas, the more malignant a tumor becomes, the more different the composition in that tumor is from that in normal brain tissue. But conversely, the ratio of GABA is highest in glioblastoma. The composition of the pool in oligodendroglioma is not significantly different from that in the normal brain. Metastatic brain tumors show the highest ratios of phenylalanine, tyrosine and methionine in the pool among the tumors and the normal brain. From the viewpoint of the composition of the free amino acid pools, like from that of the histological aspects, brain tumors seem to be classified into four groups: glioma, neurinoma, meningioma and metastatic tumors.
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PMID:Composition of free amino acids in brain tumors. 54 90

Protein-tyrosine-phosphatases (PTPases, EC 3.1.3.48) play a crucial role in the regulation of protein tyrosine phosphorylation. Recently, it was found that the PTPase gene family exhibits a large variety of different functional domains associated with the PTPase catalytic domains. In this paper, we report the complete cDNA sequence of a human transmembrane PTPase, PTP zeta, isolated from fetal brain cDNA libraries. The deduced amino acid sequence of human PTP zeta is composed of a putative signal peptide of 19 amino acids, a very large extracellular domain of 1616 amino acids, a transmembrane peptide of 26 amino acids, and a cytoplasmic domain of 653 amino acids. The extracellular portion of human PTP zeta contains two striking structural features: the N-terminal 280-amino acid sequence that is homologous to carbonic anhydrases (carbonate hydro-lyase, EC 4.2.1.1), and a sequence of 1048 amino acids without a cysteine residue. While it is unlikely that the carbonic anhydrase-like domain of PTP zeta has any carbonic anhydrase activity, its three-dimensional structure may be quite similar to that of carbonic anhydrases, a structure that appears ideal for binding a small soluble ligand. The cytoplasmic portion of human PTP zeta contains two repeated PTPase-like domains, which, when expressed in Escherichia coli, had PTPase activity in vitro. Mutational analyses indicate that only the membrane-proximal PTPase domain is catalytically active. Reverse transcription-polymerase chain reaction analyses indicate that human PTP zeta is highly expressed in a glioblastoma cell line.
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PMID:A human transmembrane protein-tyrosine-phosphatase, PTP zeta, is expressed in brain and has an N-terminal receptor domain homologous to carbonic anhydrases. 132 35

Tyrosine-specific phosphorylated proteins found exclusively on the cell surface of human astrocytomas were previously identified with murine monoclonal antibodies, designated as GA-17, GB-4 and GC-3. The purpose of this study was to further characterize the antigens and investigate the relationship between them and c-kit protooncogene product. We demonstrated that the antigens had protein kinase activity. Moreover, GA-17 reacted with c-kit protein expressed on the membrane of A172 human glioblastoma cells.
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PMID:Analysis of the close relationship between human astrocytoma-specific antigens detected by murine monoclonal antibodies and c-kit proto-oncogene product. 137 Aug 80

Five radiotracers may be used for single-photon emission computed tomography (SPECT) imaging of brain tumors, namely technetium 99m pertechnetate, iodine-123 amphetamine derivatives, 99mTc-hexamethyl propylene amine oxime (HMPAO), thallium 201, and 123I alpha methyl tyrosine. Of these, pertechnetate may be considered as an "historical" procedure in brain tumors. However, there may be some equivocal cases in computed tomography or magnetic resonance imaging, where this procedure may still be used. In 1981, 123I isopropyl amphetamine was first used in brain tumors. Further studies showed, however, that IMP is not a useful tool for brain imaging in tumorous lesions. In 1986, 99mTc HMPAO appeared on the European market as a new tumor imaging agent. Some useful clinical results were obtained in patients before and after chemotherapy or radiotherapy. Thallium-201 was incidentally noted to accumulate in tumors. Using a threshold index, this agent can be used to distinguish low-versus high-grade lesions. The most promising agent for brain tumor SPECT is 123I-alpha methyl tyrosine, which shows potential to evaluate therapeutic procedures in brain tumors and may improve the differentiation between abscess and glioblastoma. The most promising aspect is the differentiation of tumor recurrences and scar tissue after brain surgery.
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PMID:Single photon emission computed tomography imaging of brain tumors. 199 25

L-3-[123I]iodo-alpha-methyltyrosine (123IMT) like tyrosine has been reported previously to have a high affinity for a transport system in the blood-brain-barrier (BBB). We examined the kinetic behavior of 124IMT in brain and plasma in two patients with glioblastoma using dynamic positron emission tomography (PET). 124IMT accumulated in brain and tumor tissue, reaching a maximum after 15 min, with a washout of 20% to 35% at 60 min postinjection. Animal experiments confirmed the accumulation of the intact tracer in murine brain, but there was no incorporation into proteins. SPECT studies with 123IMT in patients with different types of brain tumors showed increased uptake in 26 of 32 tumors. Although nonspecific uptake in tumors must be considered, the accumulation of IMT in normal brain and in some tumors with intact BBB suggests a specific uptake of IMT. As transport is the main determinant of initial amino acid uptake, 123IMT appears to be a suitable SPECT tracer of amino acid uptake although it is not incorporated into protein.
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PMID:SPECT studies of brain tumors with L-3-[123I] iodo-alpha-methyl tyrosine: comparison with PET, 124IMT and first clinical results. 215 14

We have isolated and characterized a human ROS1 cDNA from the glioblastoma cell line SW-1088. The cDNA, 8.3 kilobases long, has the potential to encode a transmembrane tyrosine-specific protein kinase with a predicted molecular mass of 259 kDa. The putative extracellular domain of ROS1 is homologous to the extracellular domain of the sevenless gene product from Drosophila. No comparable similarities in the extracellular domains were found between ROS1 and other receptor-type tyrosine kinases. Together, ROS1 and sevenless gene products define a distinct subclass of transmembrane tyrosine kinases.
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PMID:Characterization of ROS1 cDNA from a human glioblastoma cell line. 235 49

We have observed a 20- to 40-fold increase in pp60c-src tyrosyl kinase activity in human neuroblastoma cell lines over that found in either human glioblastoma cells or human fibroblasts. The level of c-src gene transcripts and pp60c-src protein synthesis in the neuroblastoma cells was not significantly increased when compared to the levels found in glioblastoma cells. Approximately one-half of the pp60c-src molecules synthesized during a 4-hr [35S]methionine or [32P]orthophosphate labeling period in neuroblastoma cells were found to migrate more slowly on NaDodSO4/polyacrylamide gels than pp60c-src molecules labeled in glioblastoma cells. Peptide and phosphoamino acid analysis of the in vivo phosphorylated c-src molecules from these two cell types revealed that pp60c-src molecules from the neuroblastoma cells possess in the amino-terminal portion of the protein at least one unique tyrosine phosphorylation site not found in pp60c-src derived from glioblastoma cells.
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PMID:Increased pp60c-src tyrosyl kinase activity in human neuroblastomas is associated with amino-terminal tyrosine phosphorylation of the src gene product. 241 74

Structural features of v-kit, the oncogene of HZ4 feline sarcoma virus, suggested that this gene arose by transduction and truncation of cellular sequences. Complementary DNA cloning of the human proto-oncogene coding for a receptor tyrosine kinase confirmed this possibility: c-kit encodes a transmembrane glycoprotein that is structurally related to the receptor for macrophage growth factor (CSF-1) and the receptor for platelet-derived growth factor. The c-kit gene is widely expressed as a single, 5-kb transcript, and it is localized to human chromosome 4 and to mouse chromosome 5. A c-kit peptide antibody permitted the identification of a 145,000 dalton c-kit gene product that is inserted in the cellular plasma membrane and is capable of self-phosphorylation on tyrosine residues in both human glioblastoma cells and transfected mouse fibroblasts. Our results suggest that p145c-kit functions as a cell surface receptor for an as yet unidentified ligand. Furthermore, carboxy- and amino-terminal truncations that occurred during the viral transduction process are likely to have generated the transformation potential of v-kit.
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PMID:Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. 244 37

Carbon-11-labeled amino acids have been successfully used to image brain tumors by PET. This study was undertaken to evaluate the potential of L-3-[123I]-iodo-alpha-methyl tyrosine (123IMT) for metabolic imaging of brain tumors. Ten patients (glioblastoma, oligodendroglioma, lymphoma, and metastases) had early and delayed brain SPECT with a rotating gamma camera after i.v.-injection of 200-300 MBq 123IMT. In nine patients the tumors showed intense uptake of the radiotracer. Tumor-to-brain tissue ratios were between 1.4 and 2.6. 123IMT shows potentials for monitoring the effects of brain tumor therapy.
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PMID:Imaging of brain tumors with L-3-[123I]iodo-alpha-methyl tyrosine and SPECT. 278 55

This report describes the preparation of polylysine-diethylene triamine pentaacetic acid (DTPA)-metal ion complexes and of iodinated polylysine derivatives and the preferential binding of these polymers to glioblastomas in culture. Synthetic polylysines (DP88 and DP299) were modified covalently either with the chelator DTPA or with 125I-Bolton Hunter reagent. The polylysine (DP88) was modified initially with fluorescein to permit fluorescence cytological studies and quantitative measurements of polylysine concentrations. The polylysines contained an average of one DTPA per 16 lysyl moieties. The polylysine-DTPA derivatives were then modified with a mixture of 153Gd and stable Gd. A copolymer (DP120) of lysine and tyrosine (4:1) was modified with 125I using chloramine T as catalyst. C6 (rat) and U87 MG (human) glioblastoma cells, in culture, bound six to seven times more polylysine-DTPA-Gd than endothelial cells from either aorta or brain. Each of the tumor cell types bound 10(8) molecules of the modified polylysine per cell when 2.5 x 10(5) cells were reacted with 50 micrograms or greater of the polylysine-DTPA-nuclide complex. The higher molecular weight polylysines delivered more radionuclide to the cells in culture. Although the tumor cells bound more [125I]polylysine and [125I]poly(lysine HBr,tyrosine) than they bound polylysyl-DTPA-Gd, the endothelial cells and the plastic culture dish also bound more of the iodinated polymers. The stoichiometry of polylysine bound per cell suggests that the sialic acid moieties on the cell surface are the primary binding sites for polylysine derivatives. Fluorescence microscopy studies revealed that the fluorescein polylysine (DP88) and the fluorescein polylysine-DTPA nuclide complex bound the tumor cells primarily at branch points along the neuritic processes, at the edge of the perikaryon and at the terminal regions of the outgrowth process. The polylysyl-DTPA-Gd can be used, with magnetic resonance imaging, to provide measurable contrast of the margin between C6 glioblastomas and normal brain in vivo in Wistar Furth rats.
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PMID:Preferential binding of radiolabeled poly-L-lysines to C6 and U87 MG glioblastomas compared with endothelial cells in vitro. 280 85


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