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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent findings implicate macrophages and some of their secreted products, especially tumor necrosis factor (TNF), as tumor promoters. Inhibitors of these inflammatory components are currently regarded as potential therapeutic tools to block tumor progression. Here, we show that infiltrating macrophages represented a significant population of nonneoplastic cells within malignant gliomas, in which they were the exclusive producers of TNF. Contrary to the reported pro-oncogenic effects of TNF in other types of solid tumors, glioma-bearing mice deficient in TNF developed larger tumors and had reduced survival compared with their wild-type controls. Histologic examinations revealed that glioma volume was negatively correlated with the number of macrophages and small cavities called microcysts. Overall, our results support the concept that macrophages alter brain tumor development through a TNF-dependent process that culminates in the formation of microcysts. This raises the question of whether anti-inflammatory drugs, such as those commonly administrated to patients with brain cancer, could interfere with antitumor mechanisms.
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PMID:Tumor necrosis factor reduces brain tumor growth by enhancing macrophage recruitment and microcyst formation. 1586 93

Whether viruses or immunologic factors might cause or prevent human brain cancer is of interest. Statistically significant inverse associations of adult glioma with history of chickenpox and immunoglobulin G antibodies to varicella-zoster virus have been reported. The authors evaluate associations of immunoglobulin G antibodies to varicella-zoster virus and three other herpesviruses among 229 adults with glioma and 289 controls in the San Francisco Bay Area Adult Glioma Study (1997-2000). Cases were less likely than controls to report a history of chickenpox (for self-reported cases vs. controls: the age-, gender-, and ethnicity-adjusted odds ratio = 0.59, 95% confidence interval: 0.40, 0.86), and they also had lower levels of immunoglobulin G to varicella-zoster virus (for being in the highest quartile vs. the lowest quartile: the age-, gender-, and ethnicity-adjusted odds ratio = 0.41, 95% confidence interval: 0.24, 0.70). The inverse association with anti-varicella-zoster virus immunoglobulin G was most marked for glioblastoma multiforme cases versus controls and was only somewhat attenuated by excluding subjects taking high-dose steroids and other medications. Cases and controls did not differ notably for positivity to three other herpesviruses, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus. Cohort studies may help to clarify the nature of the association between immunity to and/or clinical manifestations of varicella-zoster virus and glioblastoma.
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PMID:History of chickenpox and shingles and prevalence of antibodies to varicella-zoster virus and three other herpesviruses among adults with glioma and controls. 1587 Jan 57

The etiology of brain cancer is not well understood. We conducted a population-based case-control study among 112 white women in Nebraska who were newly diagnosed with glioma between July 1988 and June 1993, and 215 controls, to identify risk factors for this disease. A 1.7-fold increased risk of glioma was observed for women who ever used hair coloring products (95% confidence interval (CI) = 1.0-2.9, 62 cases), and a 2.4-fold risk for those who used permanent hair coloring products (odds ratio (OR) = 2.4, 95% CI = 1.3-4.5, 39 cases). For women with the most aggressive form of glioma, glioblastoma multiforme, risk increased with duration of exposure to 4.9 (95% CI = 1.6-15.7, 10 cases) after 21 or more years of permanent hair coloring use. Higher risks were observed with earlier age at first use, but we did not see an exposure-response pattern with frequency of use of permanent dyes. No association was observed with use of non-permanent (sometimes called temporary or semi-permanent) hair coloring products. These suggestive findings need confirmation in future studies with larger sample sizes, fewer proxy respondents, and the ability to evaluate the effect of changes in formulations over time.
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PMID:Hair dyes and risk of glioma among Nebraska women. 1613 96

Angiostatin, a well-characterized angiostatic agent, is a proteolytic cleavage product of human plasminogen encompassing the first four kringle structures. The fifth kringle domain (K5) of human plasminogen is distinct from angiostatin and has been shown, on its own, to act as a potent endothelial cell inhibitor. We propose that tumor-targeted K5 cDNA expression may act as an effective therapeutic intervention as part of a cancer gene therapy strategy. In this study, we provide evidence that eukaryotically expressed His-tagged human K5 cDNA (hK5His) is exported extracellularly and maintains predicted disulfide bridging conformation in solution. Functionally, hK5His protein produced by retrovirally engineered human U87MG glioma cells suppresses in vitro migration of both human umbilical vein endothelial cells and human macrophages. Subcutaneous implantation of Matrigel-embedded hK5His-producing glioma cells in nonobese diabetic/severe combined immunodeficient mice reveals that hK5His induces a marked reduction in blood vessel formation and significantly suppresses the recruitment of tumor-infiltrating CD45+ Mac3+ Gr1- macrophages. Therapeutically, we show in a nude mouse orthotopic brain cancer model that tumor-targeted K5 expression is capable of effectively suppressing glioma growth and promotes significant long-term survival (>120 days) of test animals. These data suggest that plasminogen K5 acts as a novel two-pronged anticancer agent, mediating its inhibitory effect via its action on host-derived endothelial cells and tumor-associated macrophages, resulting in a potent, clinically relevant antitumor effect.
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PMID:Plasminogen kringle 5-engineered glioma cells block migration of tumor-associated macrophages and suppress tumor vascularization and progression. 1616 13

This work reports a novel computational method based on augmented cell-graphs (ACG), which are constructed from low-magnification tissue images for the mathematical diagnosis of brain cancer (malignant glioma). An ACG is a simple, undirected, weighted and complete graph in which a node represents a cell cluster and an edge between a pair of nodes defines a binary relationship between them. Both the nodes and the edges of an ACG are assigned weights to capture more information about the topology of the tissue. In this work, the experiments are conducted on a dataset that is comprised of 646 human brain biopsy samples from 60 different patients. It is shown that the ACG approach yields sensitivity of 97.53% and specificities of 93.33 and 98.15% (for the inflamed and healthy, respectively) at the tissue level in glioma diagnosis.
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PMID:Augmented cell-graphs for automated cancer diagnosis. 1620 28

KS Biomedix (formerly Avicenna Medica; now a subsidiary of the Xenova group) and Nycomed, together with Japanese licensee Sosei and Chinese licensee PharmaEngine, are developing TransMID, a transferrin-mediated diphtheria toxin delivery system for the potential treatment of adult, recurrent, inoperable, high-grade glioma (as TransMID-107R). It is also under investigation for other forms of brain cancer, including early brain cancer (as TransMID-107N), metastatic brain cancer (as TransMID-107M) and pediatric brain cancer (as TransMID-107P). TransMID is currently undergoing phase III clinical trials.
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PMID:Technology evaluation: TransMID, KS Biomedix/Nycomed/Sosei/PharmaEngine. 1624 84

Malignant gliomas comprise a small percentage of all cancers, but continue to cause disproportionate levels of morbidity and mortality. Despite decades of intensive effort from many disciplines--surgery, radiation oncology and medicine--they remain refractory to cure and, in most cases, even to prolonged treatment response. Comprehensive multidisciplinary treatment is well recognized as the optimal approach. While continued advances and refinement in both surgical and radiotherapy-based techniques are certain, medical therapies are expanding at a much more rapid rate. This is due, in large part, to an understanding of the molecular events that underlie cancer pathogenesis and improved laboratory techniques to manufacture and study molecules that influence this process. This review will focus on medical therapies in the treatment of malignant glioma, never losing sight of their place as one of several therapeutic modalities used to confront brain cancer.
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PMID:Chemotherapy for malignant glioma. 1627 64

Polysorbate 80 (Tween 80) has been widely used as an emulsifier with excellent effects in nanoparticles technology for biomedical applications. This work was thus triggered to synthesize poly(lactide)/Tween 80 copolymers with various copolymer blend ratio, which were synthesized by ring-opening polymerization and characterized by 1H NMR and TGA. Nanoparticles of poly(lactide)/Tween 80 copolymers were prepared by the dialysis method without surfactants/emulsifiers involved. Paclitaxel was chosen as a prototype anticancer drug due to its excellent therapeutic effects against a wide spectrum of cancers. The drug-loaded nanoparticles of poly(lactide)/Tween 80 copolymers were then characterized by various state-of-the-art techniques, including laser light scattering for particles size and size distribution, field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) for surface morphology; laser Doppler anemometry for zeta potential; differential scanning calorimetry (DSC) for the physical status of the drug encapsulated in the polymeric matrix; X-ray photoelectron spectrometer (XPS) for surface chemistry; high performance liquid chromatography (HPLC) for drug encapsulation efficiency; and in vitro drug release kinetics. HT-29 cells and Glioma C6 cells were used as an in vitro model of the GI barrier for oral chemotherapy and a brain cancer model to evaluate in vitro cytotoxicity of the paclitaxel-loaded nanoparticles. The viability of C6 cells was decreased from 37.4 +/- 4.0% for poly(D,L-lactide-co-glycolic acid) (PLGA) nanoparticles to 17.8 +/- 4.2% for PLA-Tween 80-10 and 12.0 +/- 5.4% for PLA-Tween 80-20 copolymer nanoparticles, which was comparable with that for Taxol at the same 50 microg/mL drug concentration.
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PMID:In vitro investigation on poly(lactide)-Tween 80 copolymer nanoparticles fabricated by dialysis method for chemotherapy. 1660 31

Human gliomas are the most common primary central nervous system neoplasm, and they are a complex, heterogeneous, and difficult disease to treat. In the past two decades, advances in molecular biology have revolutionized our understanding of the mechanism by which these neoplasms are initiated and progress. While surgery, radiation therapy, and chemotherapy have roles to play in the treatment of patients with gliomas; these therapies are self-limited because of the intrinsic resistance of glioma cells to therapy, and the diffusely infiltrating nature of the lesions. It is now known that malignant gliomas arise from a number of well-characterized genetic alterations and activations of oncogenes and inactivation of tumor suppressor genes. These genetic alterations disrupt critical cell cycle, growth factor activation, apoptotic, cell motility, and invasion pathways that lead to phenotypic changes and neoplastic transformation. Research in each of these fields has uncovered potential therapeutic targets that look promising for disease control. Gliomas can now be modeled with fidelity and reproducibility using several transgenic and knockout strategies. Transgenic mouse models are facilitating the testing of various therapeutic strategies in vivo. Finally, the recognition of the putative brain tumor stem cell, the tumor initiating cell in brain cancer, provides an enticing target through which we could eliminate the source of the brain tumor with increased efficacy and less toxicity to normal tissues. In this review, we provide an up-to-date discussion of the many of key technologies and tools that are being used in molecular biology to advance our understanding of the biological behavior of human malignant gliomas.
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PMID:Molecular biology of human gliomas. 1670 Jun 15

The National Institute for Occupational Safety and Health evaluated farm pesticide exposure and glioma risk in a study that included 457 glioma cases and 648 population-based controls, all adult men (18-80 yr old) and nonmetropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin. Multiple logistic regressions were used to control for farm residence, age, age group, education, and exposure to other pesticides. No associations were found between glioma and 12 specific pesticides. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) and found reduced glioma risk for insecticides (OR = 0.53, CI = 0.37-0.77), fumigants (OR = 0.57, CI = 0.34-0.95), and organochlorines (OR = 0.66, CI = 0.47-0.94). In analyses excluding proxy respondents (47% of cases) most CIs included 1.0. No positive association of farm pesticide exposure and glioma was found. Other farm exposures may explain the excess brain cancer risk seen in previous studies.
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PMID:Gliomas and farm pesticide exposure in men: the upper midwest health study. 1678 73


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