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)

ESR spectroscopy revealed that high molecular weight natural substances, such as protein-bound polysaccharide PSK, alkali-lignin and lignin sulfonate, significantly enhanced the ascorbyl radical intensity derived from sodium ascorbate or ascorbic acid in culture medium. Enhancement of the ascorbyl radical intensity was coupled with rapid degradation of ascorbate. These substances synergistically enhanced the ascorbate-induced cytotoxicity against human leukemic and glioblastoma cell lines. These data suggest the possible role of the ascorbyl radical in cytotoxicity induction.
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PMID:Enhancement of radical intensity and cytotoxic activity of ascorbate by PSK and lignins. 891 16

ESR spectroscopy revealed that the radical intensity of sodium ascorbate and ascorbic acid was significantly higher under hyperthermic conditions. The enhancement of ascorbyl radical intensity was coupled with the accelerated degradation of ascorbate and cytotoxicity induction against human leukemic and glioblastoma cell lines. Sodium ascorbate produced higher ascorbyl radical intensity and more potent cytotoxicity, as compared with ascorbic acid. These data demonstrate that ascorbic acid does not inhibit, but rather stimulates the cytotoxic action of hyperthermia. The combination of hyperthermia and ascorbate treatment might produce higher antitumor activity.
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PMID:Enhancement of radical intensity and cytotoxic activity of ascorbate by hyperthermia. 891 17

A panel of eight human pancreatic tumour cell lines displayed high intrinsic radioresistance, with mean inactivation doses between 2.4 and 6.5 Gy, similar to those reported for melanoma and glioblastoma. The radiosensitising potency of sodium nitroprusside, a bioreductive nitric oxide donor, was assessed in a model of metabolism-induced hypoxia in a cell micropellet. Sodium nitroprusside at 0.1 mM revealed a radiosensitising effect with an overall enhancement ratio of 1.9 compared with 2.5 for oxygen. Radiosensitising activity correlated with the enhancement of single-strand DNA breakage caused by radiation. In suspensions with cell densities of between 3% and 30% (v/v), the half-life of sodium nitroprusside decreased from 31 to 3.2 min, suggesting a value of around 1 min for micropellets. Despite this variation, the radiosensitising activity was similar in micropellets and in diluted cell suspensions. S-nitroso-L-glutathione was found to possess radiosensitising activity, consistent with a possible role of natural thiols in the storing of radiobiologically active nitric oxide adducts derived from sodium nitroprusside. As measured by a nitric oxide-specific microsensor, activation of sodium nitroprusside occurred by bioreduction, whereas S-nitroso-L-glutathione showed substantial spontaneous decomposition. Both agents appear to exert radiosensitising action through nitric oxide as its scavenging by carboxy phenyltetramethylimidazolineoxyl N-oxide (carboxy-PTI0) and oxyhaemoglobin resulted in attenuated radiosensitisation. Sodium nitroprusside was at least 10-fold more potent than etanidazole, a 2-nitroimidazole used as a reference. Our data suggest that sodium nitroprusside, a drug currently used for the treatment of hypertension, is a potential tumour radioresponse modifier.
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PMID:Intrinsic radiosensitivity of human pancreatic tumour cells and the radiosensitising potency of the nitric oxide donor sodium nitroprusside. 895 86

We studied the electrophysiological properties of cells from human glioblastomas obtained after surgery. The membrane currents were compared in cells of acute tissue slices and primary cultures using the whole cell mode of the patch-clamp technique. Very strikingly, in about a third of the tumor cells in situ and in vitro, depolarizing voltage steps elicited large, tetrodotoxin-sensitive inward currents with a threshold of about -30 mV, indicating the presence of voltage-gated sodium channels. In addition, three types of potassium currents, a delayed rectifying, an A-type, and an inward rectifying, were observed. Such a set of voltage-gated channels is characteristic for neurons. Indeed, in these glioblastoma cells, depolarizing current pulses in the current clamp mode were able to generate action potentials with properties similar to those observed in neurons. We interpret this finding as the ability of glioblastoma cells to acquire neuronlike properties but retain some glial features, since they still express markers typical for astrocytes and their precursors. The role of sodium channels in glioblastoma cells is unclear at this moment and needs further investigation. Our findings, however, imply that the tumor tissue can be intrinsically excitable and that neoplastic glial cells themselves may be an etiologic factor for epileptic seizures.
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PMID:Action potential-generating cells in human glioblastomas. 905 38

Cytotoxic activity of sodium ascorbate against a human glioblastoma T98G cell line was concentration-dependently inhibited by serum in the RPMI1640 medium. The inhibitory effect of sera from pancreatic or stomach cancer patients was significantly higher than that of fetal bovine serum (FBS), with or without heat-inactivation. The cytotoxic activity of sodium ascorbate almost completely disappeared in 60-80% of patient sera. ESR spectroscopy revealed that both patient sera and FBS increased the ascorbyl radical intensity, but to significantly lower extents, as compared with that attained by RPMI1640 medium. The present study suggests the importance of re-evaluating the efficacy of not only ascorbate but also other chemotherapeutic drugs under more physiological conditions.
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PMID:Inhibition of cytotoxic activity of ascorbate by human cancer patient sera. 906 88

Various metal ions were investigated for their ability to modify the radical intensity and cytotoxic activity of sodium ascorbate or ascorbic acid. The addition of metal ions, such as Cu+, Cu2+, Fe2+, Zn2+, Mn2+ and Fe3+, dose-dependently enhanced the ascorbyl radical intensity whereas Na+, K+, Ca2+ and Mg2+ were totally inactive. The enhancement of ascorbyl radical intensity by metal ions was tightly coupled with the accelerated degradation of ascorbate. Addition of either serum or albumin significantly reduced the stimulation effect of Cu2+, and almost completely eliminated that of Fe3+ and Zn2+. The noncytotoxic concentration of Cu2+ significantly enhanced the cytotoxicity of ascorbate against cultured human glioblastoma T98G cell line. The present data suggest the possible role of metal ions in the regulation of the biological activity of ascorbate.
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PMID:Effect of metal ions on radical intensity and cytotoxic activity of ascorbate. 913 59

In order to test whether ascorbyl radical can directly induce apoptotic cell death, it was produced by the reaction of sodium L-ascorbate with L-ascorbate oxidase. Sodium L-ascorbate induced cytotoxicity against both human glioblastoma and promyelocytic leukemic cell lines. The addition of ascorbate oxidase significantly enhanced both degradation and radical generation of ascorbate, but completely eliminated its cytotoxic activity against both of these cells. These data demonstrate that the ascorbyl radical is not the sole determinant of apoptosis induction.
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PMID:Effect of ascorbate oxidase on radical intensity and cytotoxic activity of ascorbate. 913 65

We investigated the effect of deferoxamine mesylate (DFO), an iron chelator, to test whether ascorbate-induced cytotoxicity is due to iron-catalyzed oxidation. Exposing human promyelocytic leukemic HL-60 cells to either sodium ascorbate or ascorbic acid for 1 h resulted in the progressive production of apoptotic cells characterized by cell shrinkage, as well as nuclear and internucleosomal DNA fragmentation. The addition of micromolar to millimolar concentrations of DFO during the 1-h exposure did not inhibit, but rather enhanced the ascorbate-induced apoptosis in both regular and serum-free RPMI1640 medium. However, a higher concentration of serum significantly inhibited the ascorbate-induced cytotoxicity. In contrast, the cytotoxic activity of ascorbate against T98G human glioblastoma cells was enhanced or reduced by micromolar and millimolar concentrations of DFO, respectively. Ascorbate significantly increased the oxidation potential in the culture medium, and the pro-oxidant action of ascorbate was further augmented by the presence of the cells. DFO did not significantly affect the ascorbyl radical intensity and only slightly reduced the ascorbate-elevated oxidation potential. These data demonstrated that ascorbate can induce cytotoxicity even in iron-deficient medium.
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PMID:Effect on an iron-chelator on ascorbate-induced cytotoxicity. 919 88

A primary histopathological feature of Alzheimer's disease is the accumulation of beta-amyloid (A beta) in the brain of afflicted individuals. However, A beta is produced continuously as a soluble protein in healthy individuals where it is detected in serum and CSF, suggesting the existence of cellular clearance mechanisms that normally prevent its accumulation and aggregation. Here, we demonstrate that A beta forms stable complexes with activated alpha2-macroglobulin (alpha2M*), a physiological ligand for the low-density lipoprotein receptor-related protein (LRP) that is abundantly expressed in the CNS. These alpha2M*/125I-A beta complexes are immunoreactive with both anti-A beta and anti-alpha2M IgG and are stable under various pH conditions, sodium dodecyl sulfate, reducing agents, and boiling. We demonstrate that alpha2M*/125I-A beta complexes can be degraded by glioblastoma cells and fibroblasts via LRP, because degradation is partially inhibited by receptor-associated protein (RAP), an antagonist of ligand interactions with LRP. In contrast, the degradation of free 125I-A beta is not inhibited by RAP and thus must be mediated via an LRP-independent pathway. These results suggest that LRP can function as a clearance receptor for A beta via a physiological ligand.
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PMID:Alpha2-macroglobulin complexes with and mediates the endocytosis of beta-amyloid peptide via cell surface low-density lipoprotein receptor-related protein. 934 34

The human lung adenocarcinoma cell line A-427 is significantly more sensitive to cytotoxic lipid peroxidation products of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) than the human lung adenocarcinoma cell line SK-LU-1, and the glioblastoma cell lines A-172 and U-87 MG. The cytotoxic effect as well as lipid peroxidation were abolished by vitamin E. The differential sensitivities of the cell lines were not correlated to the levels of lipid peroxidation products (measured as the end product malondialdehyde), indicating differences in sensitivities to products of lipid peroxidation. The high sensitivity of A-427 is apparently due to a low level of selenium-dependent glutathione peroxidase (GSH-Px), because pretreatment with sodium selenite (250 nM) increased the GSH-Px activity 3- to 4-fold and protected the cells almost completely against the growth inhibitory effect of DHA. Furthermore, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) a seleno-organic GSH-Px mimic, suppressed the cytotoxic action of DHA to A-427 in a dose dependent manner. Northern analysis demonstrated that pretreatment with sodium selenite (250 nM) was accompanied by an increased level of GSH-Px mRNA (1.8-fold) in A-427 cells, while the level remained unchanged under the same conditions in DHA/EPA-resistant A-172 cells. In addition, the level of selenophosphate synthetase mRNA (SelD), a key intermediate in tRNA(Sec) formation, increased 1.2- to 1.7-fold in A-427 and A-172 cells after pretreatment with sodium selenite. These results indicate that upregulation of GSH-Px activity by sodium selenite in the EPA/DHA sensitive cell line A-427 may be due to an increase in mRNAs for GSH-Px and a precursor important for formation of tRNA(Sec) which is required for incorporation of selenocysteine in GSH-Px during translation. These results demonstrate an important role for GSH-Px in the cellular defence against cytotoxic lipid peroxidation products. Furthermore, measurement of GSH-Px activities in tumour cells may be one useful biochemical predictor for their sensitivities to polyunsaturated fatty acids.
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PMID:Evidence that changes in Se-glutathione peroxidase levels affect the sensitivity of human tumour cell lines to n-3 fatty acids. 936 97


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