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)

The effect of glycerol on proliferation of BHK, CHO, HBL, MCF-7, and human glioma cells was studied. Cell proliferation was significantly decreased in all the cell lines at glycerol concentrations of 2-4% in the culture medium. The inhibition was dose-dependent, complete suppression of proliferation occurring at a glycerol concentration of 4% for the MCF-7 cell line and 6-8% for the BHK, CHO and human glioma cells. Studies on [3H]thymidine incorporation correlate with the effect on cell proliferation. The viability of the cells was not significantly affected until higher concentrations of glycerol (12% +) were present. Recovery studies with BHK cells indicated that replacement of the glycerol medium with glycerol-free medium resulted in full recovery following exposure to 4% glycerol and only partial recovery (65%) of proliferation rate following exposure to 10-12% glycerol. It is concluded that glycerol, a substance that is normally present in tissues, can serve as a potent inhibitor of cell proliferation.
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PMID:Inhibition of cell proliferation by glycerol. 190 31

Although its precise function has not yet been established, galectin-1 seems to play a role in tumor progression. In this study, we investigated galectin-1 mRNA expression in human glioma specimens and glioma cell lines. Northern blot analysis showed higher galectin-1 mRNA levels in glioma tissues. The 0.7-kb galectin-1 mRNA transcript was detected, and the expression level correlated with the malignant state, from low-grade astrocytoma to glioblastoma. In several human glioma specimens, immunohistochemical examination with antiserum against a synthetic peptide corresponding to the predicted C-terminal sequence of the protein showed high levels of galectin-1 expression. To clarify the correlation between the expression of galectin-1 and the malignancy of gliomas, we examined whether expression of antisense galectin-1 would suppress tumor growth in rat 9L cells that express high levels of galectin-1. The cells were transfected with a plasmid DNA that produces antisense galectin-1 mRNA under the control of the metallothionein promoter, and stable clones expressing low levels of galectin-1 protein in comparison with control clones were isolated. Cells with low levels of galectin-1 displayed dramatic phenotypic changes in their morphology and growth properties compared with vector-transfected control 9L cells. Our data suggest that decreased expression of galectin-1 may arrest the growth of rat 9L cells.
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PMID:Expression of galectin-1 mRNA correlates with the malignant potential of human gliomas and expression of antisense galectin-1 inhibits the growth of 9 glioma cells. 1070 9

Protein (lectin)-carbohydrate interaction is supposed to be relevant for tumor cell behavior. The aims of the present work are to investigate whether galectin-1 modulates migration/invasion features in human gliomas in vitro, whether it can be detected in human gliomas immunohistochemically, and whether its expression is attributable to certain glioma subgroups with respect to invasion and prognosis. For this purpose, we quantitatively determined (by computer-assisted microscopy) the immunohistochemical expression of galectin-1 in 220 gliomas, including 151 astrocytic, 38 oligodendroglial, and 31 ependymal tumors obtained from surgical resection. We also xenografted three human glioblastoma cell lines (the H4, U87, and U373 models) into the brains of nude mice in order to characterize the in vivo galectin-1 expression pattern in relation to tumor invasion of the normal brain parenchyma. In addition, we characterized the role in vitro of galectin-1 in U373 tumor astrocyte migration and kinetics. Our data reveal expression of galectin-1 in all human glioma types with no striking differences between astrocytic, oligodendroglial, and ependymal tumors. The level of galectin-1 expression correlated with the grade in the group of astrocytic tumors only. Furthermore, immunopositivity of high-grade astrocytic tumors from patients with short-term survival periods was stronger than that of tumors from patients with long-term survivals. In human glioblastoma xenografts, galectin-1 was preferentially expressed in the more invasive parts of these xenografts. In vitro experiments revealed that galectin-1 stimulates migration of U373 astrocytes.
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PMID:Galectin-1 is highly expressed in human gliomas with relevance for modulation of invasion of tumor astrocytes into the brain parenchyma. 1124 42

Human carcinoembryonic antigen (CEA) is overexpressed in most colorectal cancers and has been widely used as a clinical marker for the management of colon cancer patients. The transcriptional regulatory elements (TREs) of CEA include two enhancer elements and a promoter in the 5'-flanking region of the CEA gene. By using these elements in different combinations to control reporter gene expression and the replication of adenovirus variants in various tumor cells, we have identified an optimal CEA regulatory cassette that tightly controls gene expression and viral replication in CEA-producing colon cancer cells. One of these variants, OV798, in which this regulatory cassette controls E1A expression, was further characterized. OV798 preferentially replicates in and kills CEA-producing colorectal cancer cell lines such as LoVo and SW1463, but its replication is attenuated by 1000-fold in the CEA-negative cell lines Colo-320DM (colon cancer), PA-1 (ovarian cancer), G361 (melanoma), U118 MG (glioma), and HBL-100 (human breast epithelial cell). The antitumor activity of OV798 was further examined in BALB/c nu/nu mice carrying s.c. human colon tumor xenografts. A single intratumoral administration of OV798 resulted in growth inhibition of human LoVo colon cancer xenografts. Six weeks after treatment, relative tumor volume decreased to 90% of baseline for the OV798 treatment group, compared to an increase to 1200% of baseline at 4 weeks for the vehicle-treated group. In vitro and in vivo characterization indicate that OV798 could be used as a therapy for human colon cancer.
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PMID:Carcinoembryonic antigen-producing cell-specific oncolytic adenovirus, OV798, for colorectal cancer therapy. 1457 65

Global protein analysis of treated and untreated glioblastoma cell lines was performed. Proteomic analysis revealed the identity of proteins that were significantly modulated by the treatment with wild-type TP53 and the cytotoxic chemotherapy SN38. In particular, galectin-1 was found to be negatively regulated by transfection with TP53 and further down-regulated by SN38. Expression level changes were confirmed by Western blot. Subsequent analysis of several high-grade glioma cell lines demonstrated very high levels of galectin-1, regardless if the cell lines contained mutant or wild-type TP53. High expression of galectin-1 in a human orthotopic murine tumor model was also detected by immunohistochemistry and revealed a consistent pattern of preferential expression in peripheral or leading tumor edges. Further examination of galectin-1 expression through microarray analysis in tumor materials from patients confirmed galectin-1 as a valuable biomarker and possible therapeutic target. These results demonstrate the utility of using proteomic approaches to interrogate and identify potential useful targets for cancer therapy by evaluating specific tumor responses, either positive or negative, to various therapies.
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PMID:Proteomic investigation of glioblastoma cell lines treated with wild-type p53 and cytotoxic chemotherapy demonstrates an association between galectin-1 and p53 expression. 1726 44

Genome-wide oligonucleotide DNA microarrays and real time RT-PCR were used to assess differential gene expression in rat glioma and hepatoma cell lines after exposure to the aryl hydrocarbon receptor (AhR) agonist 3,3',4,4',5-pentachlorobiphenyl (penta-CB). Under maximal inducing concentrations for cytochrome P450 1A1 (CYP1A1) in H4IIE rat hepatoma cells, both H4IIE and C6 rat glioma cells were exposed to sub-micromolar concentrations of penta-CB for 24h. Differential gene expression for approximately 28,000 gene probes were computationally analyzed and compared. As expected, penta-CB potently activated CYP1A1/2 transcription in liver-derived H4IIE hepatoma cells yet did not do so in brain-derived C6 glioma cells. Additionally, we show that penta-CB causes: (1) distinct patterns of gene expression between tumor cells derived from liver or brain; (2) robust transcriptional activation of select C6 glioma gene ontologies; (3) over-expression of H4IIE hepatoma genes associated with tumor progression in liver; (4) greater than 100-fold over-expression of C6 glioma genes associated with protein processing and programmed cell death and/or metastasis; (5) tissue-selective histone deacetylase inhibition in C6 glioma, but not H4IIE hepatoma cells as signaled by galectin-1 over-expression.
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PMID:The aryl hydrocarbon receptor agonist 3,3',4,4',5-pentachlorobiphenyl induces distinct patterns of gene expression between hepatoma and glioma cells: chromatin remodeling as a mechanism for selective effects. 1731 8

Galectins are evolutionarily conserved beta-galactoside-binding lectins which recognize specific glycoconjugates on the cell surface and the extracellular matrix. Accumulating evidence indicates that these proteins are involved in a variety of physiological and pathological processes including tumor growth and metastasis. Up-regulated expression of galectin-1 is a hallmark of a variety of malignant tumors. Here, we examined the expression of galectin-1 in glioma cell lines, the influence of ionizing irradiation and the intracellular and extracellular effects of this protein on tumor cell proliferation and migration. Galectin-1 was detected in both A172 and U118 glioma cells by immunoblot analysis. Ionizing irradiation induced a statistically significant up-regulation in glioma cell lines. RNA-interference-mediated silencing resulted in a significant suppression of the proliferation of the A172 cells, while the addition of recombinant galectin-1 had no effect. On the other hand, the migratory capacity of both cell lines was reduced after galectin-1 down-regulation, and up-regulated by the addition of exogenous galectin-1. Our results provide evidence of a role for galectin-1 in the regulation of glioma cell proliferation and migration. While an intracellular mechanism seemed to prevail in galectin-1-mediated regulation of tumor cell proliferation, the control of cell migration was exerted by both intracellular and extracellular mechanisms. In addition, this protein was up-regulated by ionizing radiation, indicating that the blockade of this protein should be performed before radiotherapy to avoid any undesired stimulating effects. Given the multifactorial role of galectin-1 in the regulation of tumor escape and metastasis, we conclude that targeting galectin-1 may have therapeutic benefits in the treatment of malignant glioma.
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PMID:Galectin-1 expression in human glioma cells: modulation by ionizing radiation and effects on tumor cell proliferation and migration. 1761 74

Galectins play a key role in oncogenic processes. Although several galectins are known, their relative expression at the mRNA and protein levels, the subcellular localization, and their relationship to the oncogenic manifestation remains unclear. Herein we report a comprehensive characterization of the expression of major galectins in human breast cancer (drug-sensitive MCF-7 and drug-resistant MCF-7/Adr(R)), colon cancer (HCT-116 and HT-29), and glioma (T98G) cell lines, as these cells are common model systems for studying oncogenic processes. The expected approximately 14.5 kDa galectin-1, predominantly cytosolic, was detected in the cancer and normal cell lines. Notably, two different molecular forms of galectin-1 with molecular masses of approximately 13.5 and 15 kDa were detected in T98G cells, the latter being in the extracellular medium, perhaps a result of post-translational processing. Immunocytochemistry indicated that the extracellular galectin-1 bound to the cell surface was punctated in appearance, suggesting that it was bound to specific receptors. Immunohistological studies indicated that metastasizing carcinomas express high levels of galectin-1. On the other hand, galectin-3 was readily detectable in all cancer cell lines but undetectable in normal cell lines, indicating that galectin-3 is a cancer-specific biomarker protein. Galectin-3 was a cytosolic protein but was not detected in the extracellular medium, indicating that cancer cells do not secrete this galectin. Finally, despite the RT-PCR analysis suggesting the presence of two transcripts of galectin-8 in all cancer cell lines, the corresponding approximately 36 kDa protein was only detectable in the nuclear and cytosolic fractions upon cell fractionation. Notably, a different molecular form of galectin-8 of approximately 18 kDa was immunoprecipitated from the extracellular media, suggesting that the secreted galectin-8 undergoes post-translational processing. These results highlight the expression of galectins in different molecular forms in cancers, warranting caution in interpreting the results of functional studies of individual galectins, particularly because these proteins function redundantly in cancer pathways.
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PMID:Varied expression and localization of multiple galectins in different cancer cell lines. 1828 88

Cell motility and resistance to apoptosis characterize glioblastoma (GBM) growth and malignancy. In our current work we report that galectin-1, a homodimeric adhesion molecule and carbohydrate-binding protein with affinity for beta-galactosides, is linked with cell surface expression of integrin beta1 and the process of integrin trafficking. Using immunofluorescence, depletion of galectin-1 through both stable knockdown and transient-targeted small interfering RNA (siRNA) treatment induces an intracellular accumulation of integrin-beta1 coincident with a diminution of integrin-beta1 at points of cellular adhesion at the cell membrane. Galectin-1 depletion does not alter the gene expression level of integrin-beta1. Transient galectin-1 depletion effectuates as well the perinuclear accumulation of protein kinase C epsilon (PKCepsilon) and the intermediate filament vimentin, both of which have been shown to mediate integrin recycling in motile cells. Our results argue for the involvement of galectin-1 in the PKCepsilon/vimentin-controlled trafficking of integrin-beta1. The understanding of molecular mediators such as galectin-1 and the pathways through which they drive the cell invasion so descriptive of GBM is anticipated to reveal potential therapeutic targets that promote glioma malignancy.
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PMID:Galectin-1 is implicated in the protein kinase C epsilon/vimentin-controlled trafficking of integrin-beta1 in glioblastoma cells. 1894 33

Malignant gliomas, especially glioblastomas, are associated with a dismal prognosis. Despite advances in diagnosis and treatment, glioblastoma patients still have a median survival expectancy of only 14 months. This poor prognosis can be at least partly explained by the fact that glioma cells diffusely infiltrate the brain parenchyma and exhibit decreased levels of apoptosis, and thus resistance to cytotoxic drugs. Galectins are a family of mammalian beta-galactoside-binding proteins characterized by a shared characteristic amino acid sequence. They are expressed differentially in normal vs. neoplastic tissues and are known to play important roles in several biological processes such as cell proliferation, death and migration. This review focuses on the role played by galectins, especially galectin-1 and galectin-3, in glioma biology. The involvement of these galectins in different steps of glioma malignant progression such as migration, angiogenesis or chemoresistance makes them potentially good targets for the development of new drugs to combat these malignant tumors.
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PMID:Galectins and gliomas. 1937 55


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