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)

Supranutrition dietary levels of the element selenium (Se) that have been shown to reduce or retard tumor development resulting from transplantation. The rat placental form of glutathione-S-transferase (GST-p) has been reported to be a good marker for pre-neoplastic or neoplastic lesions. Four groups of rats with glioma were exposed to Se-free, 0.05, 2.0, and 4.0 ppm sodium selenite GST-p was investigated. Normal brain tissue did not differ significantly in all groups. In contrast, GST-p in tumor was significantly higher in Se-free and 4.0-ppm groups compared to 0.5- and 2.0-ppm groups. The concentration of Se in normal brain tissue did not differ significantly in Se-supplement groups. By contrast, Se in tumors was significantly higher in the 0.5- and 2.0-ppm groups compared to the Se-free and 4.0-ppm groups. Mean group survival at 30 d after treatment was determined and compared with previous dietary Se. Survival was significantly longer in the 0.5- and 2.0-ppm groups than in the Se-free and 4.0-ppm groups. The 2.0-ppm group had enhanced survival, similar to the 0.5-ppm group. The Se-free and 4.0-ppm groups might have no protection against carcinogenesis.
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PMID:The decrement of carcinogenesis by dietary selenium and expression of placental form of glutathione-S-transferase in rat glioma. 928 62

To investigate a possible association between G-proteins and presenilin-1 (PS-1), a series of glutathione S-transferase-fusion proteins containing portions of PS-1 were prepared and used in vitro in binding experiments with tissue and recombinant G-proteins. The results demonstrate that the 39 C-terminal amino acids of PS-1 selectively bind the brain G-protein, Go. Addition of guanosine 5'-3-O-(thio)triphosphate promoted Go dissociation from PS-1, indicating that this domain mimics the function of G-protein-coupling domains found in receptors. The 39-amino acid synthetic polypeptide activated Go in a magnesium ion-dependent manner. Physical interaction of full-length PS-1 and Go was also demonstrated. Following transfection of Goalpha and N-terminally FLAG-tagged PS-1 in COS-7 cells, Go was immunoprecipitated by FLAG antibodies. In addition, endogenous PS-1 and Goalpha were colocalized immunocytochemically in human glioma cell lines. The results indicate that PS-1 regulates Go activities in living cells.
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PMID:Regulation of brain G-protein go by Alzheimer's disease gene presenilin-1. 963 88

pICln is a ubiquitous cellular protein that has been proposed to be a volume-sensitive Cl- channel or a channel regulator. Detailed biochemical, cellular and molecular characterization of pICln is required to understand its function. Our goal in the present investigation was to define further the biochemical properties of pICln and the proteins that associate with it. Immunoprecipitation of pICln from 32P-orthophosphoric acid-labeled C6 glioma cells revealed that the protein is phosphorylated constitutively, primarily on serine residues. Protein kinase activity was detected in pICln immunoprecipitates, revealing that a constitutively active protein kinase co-precipitates with pICln. A specific association between pICln and a protein kinase was also observed in affinity assays using a recombinant GST-pICln fusion protein. The pICln-associated kinase displayed broad substrate specificity and was inhibited in a concentration-dependent manner by heparin, zinc and 5,6-dichloro-1-beta-D-ribofuranosylbenose (DRB). These characteristics resembled those of casein kinase I and II. The pICln-associated kinase was not recognized, however, by antibodies against these two enzymes. Association of the kinase with pICln was disrupted by increasing concentrations of NaCl in the washing buffer, suggesting that electrostatic interactions are involved in kinase binding. Mutagenesis experiments corroborated this observation. Truncation of pICln demonstrated that two highly charged clusters of acidic amino acid residues are both necessary and sufficient for kinase binding. Phosphopeptide mapping demonstrated that pICln contains at least two phosphorylated serine residues that are located on trypsin cleavage fragments rich in acidic amino acid residues. We propose that the kinase or a kinase binding protein binds to acidic amino acids located between D101 and Y156 and phosphorylates nearby serine residues.
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PMID:Characterization of pICln phosphorylation state and a pICln-associated protein kinase. 965 71

The glutathione S-transferase (GST)-pi gene is overexpressed in many human cancers and preneoplastic lesions and is associated with failure of cancer chemotherapy and poor patient survival. Although GST-pi overexpression in tumors of the central nervous system has been observed, the prognostic and/or clinical relevance of this overexpression has, to date, not been investigated. In this study, we analyzed the level of GST-pi expression and its subcellular localization in 61 primary gliomas and correlated the results with tumor histology, patient age, and patient survival. We observed a strong positive correlation between the level of GST-pi expression and tumor grade and between the presence of GST-pi in glioma cell nuclei and patient age. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves showed the level of GST-pi expression and its nuclear localization to be inversely correlated with patient survival. Relative risk for death of patients with high versus low tumor GST-pi expression was 3.2 (P = 0.0069) by univariate analysis and 2.6 (P = 0.036) by multivariate analysis. The relative risk of death associated with the presence of nuclear GST-pi in glioma cells was 3.9 (P = 0.0001) by univariate analysis and 4.4 (P < 0.0001) by multivariate analysis. These data indicate that high GST-pi expression in tumor cells and the presence of the GST-pi protein in tumor cell nuclei are associated with clinically more aggressive gliomas and are strong predictors of poor patient survival.
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PMID:Prognostic significance of glutathione S-transferase pi expression and subcellular localization in human gliomas. 981 22

During aerobic metabolism, a small amount of partially reduced oxygen is produced, yielding reactive oxygen species (ROS). Peroxisomes and mitochondria are major contributors to cellular ROS production, which is normally balanced by consumption by antioxidants. The fatty acid analogue tetradecylthioacetic acid (TTA) promotes mitochondrial and peroxisomal proliferation, and may induce oxidative stress and change the growth potential of cancer cells. In the present study, we found that TTA reduced [(3)H]thymidine incorporation in the glioma cell lines BT4Cn (rat), D54Mg (human), and GaMg (human) in a dose- and time-dependent manner. The 50% inhibitory TTA doses were approximately 125 microM for BT4Cn and D54Mg cells and 40 microM for GaMg cells after 4 days. alpha-Tochopherol counteracted this inhibition in GaMg cells. TTA enhanced the oxidation of [1-(14)C]palmitic acid, which could be explained by stimulation of enzymes involved in peroxisomal (fatty acyl-CoA oxidase) and/or mitochondrial (carnitine palmitoyltransferase) fatty acid oxidation. The glutathione content and the activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase were differentially affected. Increased malondialdehyde (MDA) production was seen in TTA-treated GaMg and D54Mg cells, but not in BT4Cn cells, in vitro. In BT4Cn tumor tissue from TTA-treated rats, MDA was increased while the alpha-tocopherol content tended to decrease. TTA increased the level of cytosolic cytochrome c in BT4Cn cells, which suggests induction of apoptotic cascades. Although several mechanisms are likely to be involved in the TTA-mediated effects on growth, we propose that modulation of cellular redox conditions caused by changes in fatty acid metabolism may be of vital importance.
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PMID:Growth reduction in glioma cells after treatment with tetradecylthioacetic acid: changes in fatty acid metabolism and oxidative status. 1126 48

PTEN/MMAC1 (phosphatase and tensin homolog/mutated in multiple advanced cancers 1) is a tumor suppressor gene, the inactivation of which is an important step in the progression of gliomas to end-stage glioblastoma multiforme. We examined the distribution of PTEN protein in 49 primary human gliomas by immunocytochemistry using polyclonal antibodies that we raised against PTEN-glutathione S-transferase fusion proteins expressed in Escherichia coli. The study group consisted of 6 low-grade astrocytomas, 7 anaplastic astrocytomas, 21 glioblastomas multiforme, 4 low-grade oligodendrogliomas, 6 malignant oligodendrogliomas, and 5 malignant mixed oligoastrocytomas. For each tumor, we determined the percentage of tumor cells showing PTEN immunoreactivity in the most cellular regions of the tumor specimen. In both astrocytomas and oligodendrogliomas, there was an inverse relationship between the percentage of PTEN+ cells and malignancy grade, consistent with a role for PTEN as a tumor suppressor gene, the expression of which declines during glioma progression. In nonneoplastic tissue, PTEN was expressed in human fetal brain at 16, 23, and 27 weeks' gestation, but not in adult brain, indicating that PTEN is developmentally regulated in the CNS. In 21 glioblastomas multiforme, we correlated PTEN protein expression with PTEN gene sequence. Although PTEN-mutant tumors showed significantly diminished PTEN protein expression compared with wild-type cases, suppressed expression of PTEN is more prevalent than predicted from mutation frequencies.
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PMID:Immunocytochemical mapping of the phosphatase and tensin homolog (PTEN/MMAC1) tumor suppressor protein in human gliomas. 1130 23

We have produced a polyclonal antibody that specifically recognizes cGMP-binding cGMP-specific phosphodiesterase (PDE5). The antibody was raised in rabbit using as immunogen a fusion protein, in which glutathione S-transferase was coupled to a 171 amino acid polypeptide of the N-terminal region of bovine PDE5. The antibody is able to immunoprecipitate PDE5 activity from mouse tissues and neuroblastoma extracts while it has no effect on all other PDE isoforms present in the extracts. PDE5 activity recovered in the immunoprecipitates retains its sensitivity to specific inhibitors such as zaprinast (IC(50)=0.6 microM) and sildenafil (IC(50)=3.5 nM). Bands of the expected molecular mass were revealed when solubilized immunoprecipitates were analysed in Western blots. The antibody selectively stained cerebellar Purkinje neurones, which are known to express high levels of PDE5 mRNA. Western blot analysis of mouse tissues revealed the highest expression signal in mouse lung, followed by heart and cerebellum, while a lower signal was evident in brain, kidney and a very low signal was present in the liver. In the hybrid neuroblastoma-glioma NG108-15 cells the antibody revealed a high PDE5 induction after dibutyryl-cAMP treatment.
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PMID:Expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in mouse tissues and cell lines using an antibody against the enzyme amino-terminal domain. 1138 65

The relationship between the degree of the expression of Cu/Zn SOD, GST-pi and bcl-2 in the initial and recurrent tumor tissue after radiotherapy and/or chemotherapy and the cellular heterogeneity obtained from DNA content by image cytometry was investigated. Subjects were 7 patients who had glial tumors which were surgically removed at onset and removed a second time at recurrence. Radiotherapy and chemotherapy were also administered after initial resection. Immunoreactivity for copper/zinc super oxide dismutase (Cu/Zn SOD), GST (glutathione-S-transferase)-pi, and bcl-2 were evaluated from routinely prepared tissue blocks. Tumors were classified into two groups by cytometric analysis of DNA ploidy in the G2M cell cycle phase. One tumor group consisted of single clonal cells in both the initial and recurrent tumors and the other group consisted of tumors with polyclonal cells in the initial and recurrent tumor. In this study, one patient (case 3) with single clonal cell glioblastoma at recurrence did not show high Cu/Zn SOD activity after radiotherapy and chemotherapy but showed a short survival time after recurrence. In three patients (cases 1, 2, 3) with single clonal-cell glioblastoma, the recurrent tumor cells showed high GST-pi immunoreactivity and survival time was short after recurrence. Tumor cells in two patients (cases 5, 7) with single clonal cell anaplastic glioma at recurrence, showed high GST-pi immunoreactivity and had a short survival time after recurrence. In three single clonal glioblastomas (cases 1, 2, 3), the recurrent tumor showed the increased bcl-2 immunoreactivity and showed a short survival time after recurrence. In two patients (case 5, 7) with single clonal cell anaplastic glioma at recurrence, tumor cells showed a high bcl-2 immunoreactivity and these patients showed a short survival time after recurrence. Although the number of subjects is very small, our study shows that the immunoreactivity of bcl-2 and GST-pi in malignant gliomas may be very important factors in radio- and chemosensitivity, and shows that GST-pi is induced by radiation and anti-cancer drugs.
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PMID:Expression of enzymes and oncogene induced after radiotherapy and/or chemotherapy in patients with brain tumors. 1143 58

Drug resistance, which often occurs during chemotherapy, is still a great obstacle to the success of human malignancy treatment. Among many possible mechanisms of drug resistance (biological, biochemical, kinetic or pharmacological), both typical and atypical multidrug-resistance (MDR) have been extensively studied. We picked up MDR-1, MXR, MRP1, MRP2, TopoII alpha, MGMT, and GST-pi as drug-resistant gene, based on experimental data and previous reports. Expression of these genes were measured in 14 malignant glioma specimens by reverse transcription polymerase chain reaction assay. We chose anticancer drugs for each patient, based on results of drug resistant gene expression to acquire good response to drugs. Though our follow-up periods are not long enough to analyze the results of our chemotherapy, 78% (7/9) of our glioma patients who were treated with our chemotherapy are free from tumor progression. The assays, which measure the expression of drug resistant genes, are necessary to allow rapid detection of the drug-sensitivity to chemotherapy in malignant glioma patients.
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PMID:[Chemotherapy for gliomas based on the expression levels of drug resistant genes]. 1151 3

Cyclophilin D (CyPD) is thought to sensitize opening of the mitochondrial permeability transition pore (mPTP) based on the findings that cyclosporin A (CsA), a pseudo-CyPD substrate, hyperpolarizes the mitochondrial membrane potential (DeltaPsi) and inhibits apoptosis. We provide evidence that contrasts with this model. Using live cell imaging and two photon microscopy, we report that overexpression of CyPD desensitizes HEK293 and rat glioma C6 cells to apoptotic stimuli. By site-directed mutagenesis of CyPD that compromises peptidyl-prolyl cis-trans isomerase (PPIase) activity, we demonstrate that the mechanism involved in this protective effect requires PPIase activity. Furthermore, we show that, under resting conditions, DeltaPsi is hyperpolarized in CyPD wild type-overexpressing cells but not in cells overexpressing mutant forms of CyPD that lack PPIase activity. Finally, in glutathione S-transferase (GST) pull-down assays, we demonstrate that CyPD binding to the adenine nucleotide translocator (ANT), which is considered to be the core component of the mPTP, is not affected by the loss of PPIase activity. Collectively, our data suggest that CyPD should be viewed as a cell survival-signaling molecule and indicate a protective role of CyPD against apoptosis that is mediated by one or more targets other than the ANT.
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PMID:Mitochondrial targeted cyclophilin D protects cells from cell death by peptidyl prolyl isomerization. 1207 16


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