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      Galectins and Gliomas

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          Abstract

          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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          Most cited references124

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          Drug resistance and the solid tumor microenvironment.

          Resistance of human tumors to anticancer drugs is most often ascribed to gene mutations, gene amplification, or epigenetic changes that influence the uptake, metabolism, or export of drugs from single cells. Another important yet little-appreciated cause of anticancer drug resistance is the limited ability of drugs to penetrate tumor tissue and to reach all of the tumor cells in a potentially lethal concentration. To reach all viable cells in the tumor, anticancer drugs must be delivered efficiently through the tumor vasculature, cross the vessel wall, and traverse the tumor tissue. In addition, heterogeneity within the tumor microenvironment leads to marked gradients in the rate of cell proliferation and to regions of hypoxia and acidity, all of which can influence the sensitivity of the tumor cells to drug treatment. In this review, we describe how the tumor microenvironment may be involved in the resistance of solid tumors to chemotherapy and discuss potential strategies to improve the effectiveness of drug treatment by modifying factors relating to the tumor microenvironment.
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            Galectins as modulators of tumour progression.

            Galectins are a family of animal lectins with diverse biological activities. They function both extracellularly, by interacting with cell-surface and extracellular matrix glycoproteins and glycolipids, and intracellularly, by interacting with cytoplasmic and nuclear proteins to modulate signalling pathways. Current research indicates that galectins have important roles in cancer; they contribute to neoplastic transformation, tumour cell survival, angiogenesis and tumour metastasis. They can modulate the immune and inflammatory responses and might have a key role helping tumours to escape immune surveillance. How do the different members of the Galectin family contribute to these diverse aspects of tumour biology?
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              Diffuse glioma growth: a guerilla war

              In contrast to almost all other brain tumors, diffuse gliomas infiltrate extensively in the neuropil. This growth pattern is a major factor in therapeutic failure. Diffuse infiltrative glioma cells show some similarities with guerilla warriors. Histopathologically, the tumor cells tend to invade individually or in small groups in between the dense network of neuronal and glial cell processes. Meanwhile, in large areas of diffuse gliomas the tumor cells abuse pre-existent “supply lines” for oxygen and nutrients rather than constructing their own. Radiological visualization of the invasive front of diffuse gliomas is difficult. Although the knowledge about migration of (tumor)cells is rapidly increasing, the exact molecular mechanisms underlying infiltration of glioma cells in the neuropil have not yet been elucidated. As the efficacy of conventional methods to fight diffuse infiltrative glioma cells is limited, a more targeted (“search & destroy”) tactic may be needed for these tumors. Hopefully, the study of original human glioma tissue and of genotypically and phenotypically relevant glioma models will soon provide information about the Achilles heel of diffuse infiltrative glioma cells that can be used for more effective therapeutic strategies.
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                Author and article information

                Journal
                Brain Pathol
                bpa
                Brain Pathology (Zurich, Switzerland)
                Blackwell Publishing Ltd
                1015-6305
                1750-3639
                January 2010
                : 20
                : 1
                : 17-27
                Affiliations
                [1 ]simpleLaboratory of Toxicology; Institute of Pharmacy; Université Libre de Bruxelles (ULB) Brussels, Belgium
                [2 ]simpleDepartment of Neurosurgery; Erasme University Hospital; Université Libre de Bruxelles (ULB) Brussels, Belgium
                Author notes
                Robert Kiss, PhD, Laboratory of Toxicology, Institute of Pharmacy, Univesité Libre de Bruxelles (ULB), Campus de la Plaine CP205/1—Boulevard du Triomphe, 1050 Brussels, Belgium (E-mail: rkiss@ 123456ulb.ac.be )

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                Article
                10.1111/j.1750-3639.2009.00270.x
                2805916
                19371355
                3cfd4d59-de57-4c10-ab02-f64c3b6bb5c7
                Journal Compilation © 2010 International Society of Neuropathology

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                History
                : 04 October 2008
                : 30 December 2008
                Categories
                Review Articles

                Pathology
                glioma,resistance,angiogenesis,galectin,migration
                Pathology
                glioma, resistance, angiogenesis, galectin, migration

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