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)

Gliomas in the form of astrocytomas, anaplastic astrocytomas and glioblastomas are the most common brain tumors in humans. Early detection of these cancers is crucial for successful treatment. Proteomics promises the discovery of biomarkers and tumor markers for early detection and diagnosis. In the current study, a differential gel electrophoresis technology coupled with matrix-assisted laser desorption/ionization-time of flight and liquid chromatography-tandem mass spectroscopy was used to investigate tumor-specific changes in the proteome of human brain cancer. Fifty human brain tissues comprising varying diagnostic groups (non-tumor, grade I, grade II, grade III and grade IV) were run in duplicate together with an internal pool sample on each gel. The proteins of interest were automatically picked, in-gel digested and mass spectrometry fingerprinted. Two hundred and eleven protein spots were identified successfully and were collapsed into 91 unique proteins. Approximately 20 of those 91 unique proteins had, to our knowledge, not been reported previously as differentially expressed in human brain cancer. Alb protein, peroxiredoxin 4 and SH3 domain-binding glutamic acid-rich-like protein 3 were upregulated in glioblastoma multiform versus non-tumor tissues. However, aldolase C fructose-biphosphate, creatine kinase, B chain dihydrolipoyl dehydrogenase, enolase 2, fumarate hydratase, HSP60, lactoylglutathione lyase, lucine aminopeptidase, Mu-crystallin homolog, NADH-UO 24, neurofilament triplet L protein, septin 2, stathmin and vacuolar ATP synthase subunit E were downregulated in glioblastoma multiform compared with non-tumor tissues. These differentially expressed proteins provided novel information on the differences existing between normal brain and gliomas, and thus might prove to be useful molecular indicators of diagnostic or prognostic value.
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PMID:Biomarker discovery: a proteomic approach for brain cancer profiling. 1723 37

Recent studies have identified stem cells in brain cancer. However, their relationship to normal CNS progenitors, including dependence on common lineage-restricted pathways, is unclear. We observe expression of the CNS-restricted transcription factor, OLIG2, in human glioma stem and progenitor cells reminiscent of type C transit-amplifying cells in germinal zones of the adult brain. Olig2 function is required for proliferation of neural progenitors and for glioma formation in a genetically relevant murine model. Moreover, we show p21(WAF1/CIP1), a tumor suppressor and inhibitor of stem cell proliferation, is directly repressed by OLIG2 in neural progenitors and gliomas. Our findings identify an Olig2-regulated lineage-restricted pathway critical for proliferation of normal and tumorigenic CNS stem cells.
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PMID:Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma. 1729 53

We report a novel computational method based on graph evolution process to model the malignancy of brain cancer called glioma. In this work, we analyze the phases that a graph passes through during its evolution and demonstrate strong relation between the malignancy of cancer and the phase of its graph. From the photomicrographs of tissues, which are diagnosed as normal, low-grade cancerous and high-grade cancerous, we construct cell-graphs based on the locations of cells; we probabilistically generate an edge between every pair of cells depending on the Euclidean distance between them. For a cell-graph, we extract connectivity information including the properties of its connected components in order to analyze the phase of the cell-graph. Working with brain tissue samples surgically removed from 12 patients, we demonstrate that cell-graphs generated for different tissue types evolve differently and that they exhibit different phase properties, which distinguish a tissue type from another.
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PMID:Mathematical modeling of the malignancy of cancer using graph evolution. 1746 76

Although relatively rare, malignant glioma (MG) is frequently used for testing novel cancer treatments. However, human MG trials have often been initiated on the basis of preclinical models that involve numerous discontinuities with the human disease. Below, we discuss various limitations of the mainstay model used in MG preclinical research, the murine orthotopic xenograft. After discussing alternative model systems like transgenic mouse models and canine xenografts, we argue that companion animals with spontaneous brain cancers offer a scientifically and ethically attractive system for preclinical testing of novel MG interventions. Ethical advantages and practical challenges of companion animal brain cancer trials are briefly discussed.
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PMID:Faithful companions: a proposal for neurooncology trials in pet dogs. 1751 Mar 77

Malignant gliomas are a debilitating class of brain tumors that are resistant to radiation and chemotherapeutic drugs, contributing to the poor prognosis associated with these tumors. Over-expression of transcription factors such as NFkappaB and AP-1 contribute to the enhanced glioma survival, radioresistance, and chemoresistance. Curcumin, which may inhibit these pathways, was therefore investigated for a potential therapeutic role in glioma. The effect of curcumin on glioma survival was investigated in human (T98G, U87MG, and T67) and rat (C6) glioma cell lines. The ability of curcumin to overcome glioma cell radioresistance and chemoresistance was also explored. Curcumin reduced cell survival in a p53- and caspase-independent manner, an effect correlated with the inhibition of AP-1 and NFkappaB signaling pathways via prevention of constitutive JNK and Akt activation. Curcumin-sensitized glioma cells to several clinically utilized chemotherapeutic agents (cisplatin, etoposide, camptothecin, and doxorubicin) and radiation, effects correlated with reduced expression of bcl-2 and IAP family members as well as DNA repair enzymes (MGMT, DNA-PK, Ku70, Ku80, and ERCC-1). These findings support a role for curcumin as an adjunct to traditional chemotherapy and radiation in the treatment of brain cancer.
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PMID:Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFkappaB transcription factors. 1759 14

There is a pressing need for new therapeutic, diagnostic, and drug delivery approaches for treating brain cancers. Nanotechnology offers a new method for targeted brain cancer therapy and could play a major role in gene and drug delivery. The goals of our study were to visualize in vitro ingestion, cytotoxicity, and loading capacity of Multi-Walled Carbon Nanotubes (MWCNTs) in microglia. Furthermore, we investigated internalization differences between microglia and glioma cells. BV2 microglia and GL261 glioma cells were incubated with MWCNTs, which were synthesized through catalytic chemical vapor deposition technique. Real-time RT-PCR, cell proliferation analysis, siRNA and DNA loading, electron microscopy, and flow cytometry were performed. We demonstrated that MWCNTs do not result in proliferative or cytokine changes in vitro, are capable of carrying DNA and siRNA and are internalized at higher levels in phagocytic cells as compared to tumor cells. This study suggests MWCNTs could be used as a novel, non-toxic, and biodegradable nano-vehicles for targeted therapy in brain cancers. Further studies are needed to demonstrate the full capacity of MWCNTs as nanovectors.
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PMID:Internalization of MWCNTs by microglia: possible application in immunotherapy of brain tumors. 1760 50

We have previously shown that six propolins, A-F, could be isolated from Taiwanese propolis (TP) and that they exerted a broad spectrum of biological activities. Recently, we isolated a seventh compound, propolin G. Its chemical structure has been identified by NMR and fast atom bombardment-mass spectrometry spectra and was found to be identical to a known compound, nymphaeol C. We used high-performance liquid chromatography to determine the relative contents of propolins C, D, F, and G in TP collected in various seasons and regions and found them to be relatively higher in TPs collected from May to July than from September to October. In our present study, we were interested in the various biological activities of TP extract as well as in propolin G as a pure compound. We found that propolin G could efficiently induce apoptosis in brain cancer cell lines (glioma and glioblastoma). The apoptosis might have been through a mitochondrial- and caspase-dependent pathway. This result demonstrated that the TP collection season was more an important factor than the geographical region. Propolis has been suggested to possess a potent antioxidant activity. We further evaluated the antioxidant property of propolin G using DPPH (1,2-diphenyl-2-picryhydrazyl). Our results indicate that propolin G does possess free radical scavenging activity. We also evaluated the neuroprotective action of propolin G, TP, and BP (Brazilian propolis) extracts against oxidative stress in rat primary cortical neurons. Our data demonstrate that propolin G and TP extracts have a marked neuroprotective effect that is greater than BP extract. In conclusion, the isolation and characterization of propolin G from TP have demonstrated for the first time that this compound is a potent inducer of apoptosis in brain cancer cells and that this compound and TP extract exhibit a protective effect against oxidative stress in rat cortical neurons.
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PMID:Propolin G, a prenylflavanone, isolated from Taiwanese propolis, induces caspase-dependent apoptosis in brain cancer cells. 1768 31

Glioma is a highly invasive, rapidly spreading form of brain cancer that is resistant to surgical and medical treatment. The recent progresses made in intracellular and ion channels of glioma cells provide a potential new approach for biochemical therapy of brain tumor. In this paper, we reviewed clinical data on chemotherapy by temozolomide and results from new studies on voltage-gated potassium channels, large-conductance Ca(2+)-activated K(+) channels, volume-activated chloride channels, glioma-specific chloride channel and their modulators. These new findings may represent future directions for brain tumor studies and treatment.
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PMID:Potential biochemical therapy of glioma cancer. 1770 67

Treatment of brain cancer is limited in part by inefficient intracellular delivery of drugs and DNA for chemotherapy and gene therapy, respectively. This study tested the hypothesis that ultrasound may be used to enhance intracellular delivery and efficacy of chemotherapeutics and genes in glioma cells in vitro. First, suitable ultrasound conditions were identified by measuring intracellular uptake of calcein and viability of GS 9L rat gliosarcoma cells after a range of different ultrasound exposures. We selected sonication at 10 J/cm2, which achieved intracellular delivery of approximately 10(6) molecules/cell. Next, glial cells were sonicated with varying concentrations of model chemotherapeutics: BCNU and bleomycin. For both drugs, cytotoxicity was increased in a synergistic manner when accompanied by ultrasound exposure. Finally, expression of a plasmid DNA encoding a GFP reporter was increased up to 30-fold when exposed to ultrasound. Altogether, these findings suggest that ultrasound may be useful to increase the efficacy of chemotherapy and gene therapy of glioma cells.
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PMID:Ultrasound-enhanced chemotherapy and gene delivery for glioma cells. 1787 33

Glioblastoma multiforme is the most severe form of brain cancer. First line therapy includes the methylating agent temozolomide and/or the chloroethylating nitrosoureas [1-(2-chloroethyl)-1-nitrosourea; CNU] nimustine [1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea; ACNU], carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea; BCNU], or lomustine [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; CCNU]. The mechanism of cell death after CNU treatment is largely unknown. Here we show that ACNU and BCNU induce apoptosis in U87MG [p53 wild-type (p53wt)] and U138MG [p53 mutant (p53mt)] glioma cells. However, contrary to what we observed previously for temozolomide, chloroethylating drugs are more toxic for p53-mutated glioma cells and induce both apoptosis and necrosis. Inactivation of p53 by pifithrin-alpha or siRNA down-regulation sensitized p53wt but not p53mt glioma cells to ACNU and BCNU. ACNU and BCNU provoke the formation of DNA double-strand breaks (DSB) in glioma cells that precede the onset of apoptosis and necrosis. Although these DSBs are repaired in p53wt cells, they accumulate in p53mt cells. Therefore, functional p53 seems to stimulate the repair of CNU-induced cross-links and/or DSBs generated from CNU-induced lesions. Expression analysis revealed an up-regulation of xpc and ddb2 mRNA in response to ACNU in U87MG but not U138MG cells, indicating p53 regulates a pathway that involves these DNA repair proteins. ACNU-induced apoptosis in p53wt glioma cells is executed via both the extrinsic and intrinsic apoptotic pathway, whereas in p53mt glioma cells, the mitochondrial pathway becomes activated. The data suggest that p53 has opposing effects in gliomas treated with methylating or chloroethylating agents and, therefore, the p53 status should be taken into account when deciding which therapeutic drug to use.
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PMID:Differential sensitivity of malignant glioma cells to methylating and chloroethylating anticancer drugs: p53 determines the switch by regulating xpc, ddb2, and DNA double-strand breaks. 1808 19


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