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)

Recent improvements in the understanding of brain tumor biology have opened the door to a number of rational therapeutic strategies targeting distinct oncogenic pathways. The successful translation of such "designer drugs" to clinical application depends heavily on effective and expeditious screening methods in relevant disease models. By recapitulating both the underlying genetics and the characteristic tumor-stroma microenvironment of brain cancer, genetically engineered mouse models (GEMMs) may offer distinct advantages over cell culture and xenograft systems in the preclinical testing of promising therapies. This review focuses on recently developed GEMMs for both glioma and medulloblastoma, and discusses their potential use in preclinical trials. Examples showcasing the use of GEMMs in the testing of molecularly targeted therapeutics are given, and relevant topics, such as stem cell biology, in vivo imaging technology and radiotherapy, are also addressed.
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PMID:Genetically engineered mouse models of brain cancer and the promise of preclinical testing. 1907 78

MicroRNAs (miRNAs) are non-protein-coding RNAs that function as post-transcriptional gene regulators. Recent evidence has shown that miRNA plays a pivotal role in the development of many cancers including glioma, a lethal brain cancer. We have recently compared the miRNA expression profiles between normal brain and glioma tissues from Chinese patients by miRNA microarray and identified a panel of differentially expressed miRNAs. Here, we studied the function of one miRNA, miR-15b, in glioma carcinogenesis and elucidated its downstream targets. Over-expression of miR-15b resulted in cell cycle arrest at G0/G1 phase while suppression of miR-15b expression resulted in a decrease of cell populations in G0/G1 and a corresponding increase of cell populations in S phase. We further showed that CCNE1 (encoding cyclin E1) is one of the downstream targets of miR-15b. Taken together, our findings indicate that miR-15b regulates cell cycle progression in glioma cells by targeting cell cycle-related molecules.
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PMID:MicroRNA-15b regulates cell cycle progression by targeting cyclins in glioma cells. 1913 80

Glioblastoma (GBM) is a highly lethal primary brain cancer with hallmark features of diffuse invasion, intense apoptosis resistance and florid necrosis, robust angiogenesis, and an immature profile with developmental plasticity. In the course of assessing the developmental consequences of central nervous system (CNS)-specific deletion of p53 and Pten, we observed a penetrant acute-onset malignant glioma phenotype with striking clinical, pathological, and molecular resemblance to primary GBM in humans. This primary, as opposed to secondary, GBM presentation in the mouse prompted genetic analysis of human primary GBM samples that revealed combined p53 and Pten mutations as the most common tumor suppressor defects in primary GBM. On the mechanistic level, the "multiforme" histopathological presentation and immature differentiation marker profile of the murine tumors motivated transcriptomic promoter-binding element and functional studies of neural stem cells (NSCs), which revealed that dual, but not singular, inactivation of p53 and Pten promotes cellular c-Myc activation. This increased c-Myc activity is associated not only with impaired differentiation, enhanced self-renewal capacity of NSCs, and tumor-initiating cells (TICs), but also with maintenance of TIC tumorigenic potential. Together, these murine studies have provided a highly faithful model of primary GBM, revealed a common tumor suppressor mutational pattern in human disease, and established c-Myc as a key component of p53 and Pten cooperative actions in the regulation of normal and malignant stem/progenitor cell differentiation, self-renewal, and tumorigenic potential.
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PMID:Pten and p53 converge on c-Myc to control differentiation, self-renewal, and transformation of normal and neoplastic stem cells in glioblastoma. 1915 Sep 64

O-[(18)F]Fluoromethyl-D-tyrosine (D-[(18)F]FMT) has been reported as a potential tumor-detecting agent for positron emission tomography (PET). However, the reason why D-[(18)F]FMT is better than L-[(18)F]FMT is unclear. To clarify this point, we examined the mechanism of their transport and their suitability for tumor detection. The stereo-selective uptake and release of enantiomerically pure D- and L-[(18)F]FMT by rat C6 glioma cells and human cervix adenocarcinoma HeLa cells were examined. The results of a competitive inhibition study using various amino acids and a selective inhibitor for transport system L suggested that D-[(18)F]FMT, as well as L-[(18)F]FMT, was transported via system L, the large neutral amino acid transporter, possibly via LAT1. The in vivo distribution of both [(18)F]FMT and [(18)F]FDG in tumor-bearing mice and rats was imaged with a high-resolution small-animal PET system. In vivo PET imaging of D-[(18)F]FMT in mouse xenograft and rat allograft tumor models showed high contrast with a low background, especially in the abdominal and brain region. The results of our in vitro and in vivo studies indicate that L-[(18)F]FMT and D-[(18)F]FMT are specifically taken up by tumor cells via system L. D-[(18)F]FMT, however, provides a better tumor-to-background contrast with a tumor/background (contralateral region) ratio of 2.741 vs. 1.878 with the L-isomer, whose difference appears to be caused by a difference in the influence of extracellular amino acids on the uptake and excretion of these two isomers in various organs. Therefore, D-[(18)F]FMT would be a more powerful tool as a tumor-detecting agent for PET, especially for the imaging of a brain cancer and an abdominal cancer.
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PMID:Evaluation of O-[(18)F]fluoromethyl-D-tyrosine as a radiotracer for tumor imaging with positron emission tomography. 1932 75

Some studies of brain cancer have found an excess risk for farmers. The National Institute for Occupational Safety and Health previously found no increased glioma risk for ever (vs. never) being exposed to pesticides on a farm among 798 cases and 1,175 population-based controls (adult (ages 18-80 years) nonmetropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin). For this analysis (1995-1998), 288 cases and 474 controls (or their proxies) who had lived on farms at age 18 years or after were asked about exposure to crops, livestock, and farm tasks. Logistic regression was used to calculate odds ratios adjusted for age, age group, sex, state, and education. Never immediately washing up (adjusted odds ratio (OR) = 3.08, 95% confidence interval (CI): 1.78, 5.34) or changing clothes (OR = 2.84, 95% CI: 1.04, 7.78) after applying pesticides was associated with increased glioma risk. Living on a farm on which corn, oats, soybeans, or hogs were raised was associated with decreased risk (corn-OR = 0.37, 95% CI: 0.20, 0.69; oats-OR = 0.63, 95% CI: 0.40, 1.00; soybeans-OR = 0.69, 95% CI: 0.48, 0.98; hogs-OR = 0.63, 95% CI: 0.43, 0.93). Negative associations may be due to chance or a "healthy farmer" effect. Farmers' increased risk of glioma may be due to work practices, other activities, or an inverse association with allergies (reported by other investigators).
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PMID:Exposure to farm crops, livestock, and farm tasks and risk of glioma: the Upper Midwest Health Study. 1940 43

Tetrazolium violet (TV), a tetrazolium salt, was synthesized as a novel and potent anticancer agent with a broad spectrum of anticancer activity against many cancer cells. A previous study showed that tetrazolium violet inhibited cell growth, and induced cell cycle arrest and apoptosis in C6 Rat glioma cells. It also showed that treatment of cells with TV for 24 h resulted in a dramatic up-regulation of p53, and an increase in the activity of caspase-3, accompanied with a significant increase of Bax/Bcl-2 ratio. In this study, we further investigated which Fas/FasL and caspase were activated by TV during the apoptosis. Annexin-V-propidium iodide (PI) binding assay and nucleosome ELISA assay further indicated that TV induced a typical apoptosis, in a time-dose-dependent manner. The data showed that the activity of Fas/FasL and caspase-8 and -9 were significantly enhanced by the compound, which suggested that TV might be used as a Fas/FasL and caspases promoter to initiate brain cancer cell apoptosis.
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PMID:Tetrazolium violet induces apoptosis via caspases-8, -9 activation and Fas/FasL up-regulation in rat C6 glioma cells. 1940 76

Cancer stem cells (CSCs) are a minute sub-population of self-renewing, immortal cells, which can be responsible for chemoresistance observed in the treatment of cancer. CSCs are similar to cancer cells requiring telomerase activity or alternative mechanisms for their proliferation and regeneration. This study explored the correlation between CD133 (stem cell marker) and telomerase expression using CD133+ cells isolated from the glioma GOS-3 cell line with magnetic affinity cell sorting (MACS). GOS-3 CD133+ showed a transcription downregulation of hTERT ( approximately 100-fold decrease) compared with CD133- cells. In order to further substantiate the novel finding, serum deprivation was adopted to enrich CD133 expression in GOS-3 cells. A pronounced upregulation of cd133 and downregulation of telomerase expression were produced as a consequence of decreasing serum supplement levels in GOS-3 cells. These findings showed for the first time that telomerase is downregulated in brain cancer stem cells compared to cancer cells.
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PMID:Telomerase downregulation in cancer brain stem cell. 1943 Aug 94

Glioblastoma multiforme is the most common form of primary brain cancer. In the past decade, virotherapy of tumors has gained credence, particularly in glioma management, as these tumors are not completely resectable and tend to micro-metastasize. Adenoviral vectors have an advantage over other viral vectors in that they are relatively non-toxic and do not integrate in the genome. However, the lack of coxsackie and adenovirus receptors on surface of gliomas provides for inefficient transduction of wild-type adenoviral vectors in these tumors. By targeting receptors that are overexpressed in gliomas, modified adenoviral constructs have been shown to efficiently infect glioma cells. In addition, by taking advantage of tumor-specific promoter elements, oncolytic adenoviral vectors offer the promise of selective tumor-specific replication. This dual targeting strategy has enabled specificity in both laboratory and pre-clinical settings. This review examines current trends in adenoviral virotherapy of gliomas, with an emphasis on targeting modalities and future clinical applications.
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PMID:Adenoviral virotherapy for malignant brain tumors. 1945 8

This study has developed a chitosan-based delivery system to locally administer ellagic acid for brain cancer treatment. We fabricated chitosan/ellagic acid composite films with various concentrations of ellagic acid. In vitro release study was performed by using a UV spectrophotometer, and enzymatic degradation rate was determined by analyzing the increased free amino groups. Viability of brain cancer cells (human U87 glioblastomas and rat C6 glioma cells) was measured via direct and indirect cell culture on the films by MTS assay. Caspase-3 activation, Western blot for p53, and anti-angiogenesis assays were also examined. In the in vivo study, GFP-tagged rat C6 glioma cells were implanted subcutaneously at the right flank region of nude mice and treatments were initiated by implanting the films subcutaneously. Tumor growth was evaluated by measuring tumor volume using a caliper, an ultrasound machine, and an optical imaging system. The chitosan/ellagic acid composite films were enzymatically degradable and exhibited a sustained slow release of ellagic acid. These materials could inhibit the cancer cell growth in an ellagic acid concentration-dependent manner by inducing apoptosis of cancer cells as well as suppressing angiogenesis. These materials also significantly suppressed tumor tissue growth in vivo.
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PMID:The inhibition of glioma growth in vitro and in vivo by a chitosan/ellagic acid composite biomaterial. 1950 95

Glioblastoma is the most common and the most aggressive type of brain cancer. The median survival time from the time of diagnosis is approximately one year. Invasion of glioma cells from the core tumor into the surrounding brain tissue is a major reason for treatment failure: these migrating cells are not eliminated in surgical resection and cause tumor recurrence. Variations are seen in number of invading cells, and in the extent and patterns of migration. Cells can migrate diffusely and can also be seen as clusters of cells distinct from the main tumor mass. This kind of clustering is also evident in vitro using 3D spheroid models of glioma invasion. This has been reported for U87 cells stably expressing the constitutively active EGFRVIII mutant receptor, often seen expressed in glioblastoma. In this case the cells migrate as clusters rather than as single cells migrating in a radial pattern seen in control wild type U87 cells. Several models have been suggested to explain the different modes of migration, but none of them, so far, has explored the important role of cell-cell adhesion. The present paper develops a mathematical model which includes the role of adhesion and provides an explanation for the various patterns of cell migration. It is shown that, depending on adhesion, haptotactic, and chemotactic parameters, the migration patterns exhibit a gradual shift from branching to dispersion, as has been reported experimentally.
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PMID:A mathematical model for pattern formation of glioma cells outside the tumor spheroid core. 1959 56


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