Gliomas is one of the most devastating diseases as they are difficult to treat and with high mortality. The authors conducted a comprehensive review on gliomas with a focus on cellular pathways that mediate tumor proliferation and invasion as well as current therapies on gliomas.
Treated glioblastoma patients survive from 6 to 14 months. In the first part of this review, we describe glioma origins, cancer stem cells and the genomic alterations that generate dysregulated cell division, with enhanced proliferation and diverse response to radiation and chemotherapy. We review the pathways that mediate tumour cell proliferation, neo-angiogenesis, tumor cell invasion, as well as necrotic and apoptotic cell death. Then, we examine the ability of gliomas to evade and suppress the host immune system, exhibited at the levels of antigen recognition and immune activation, limiting the effective signaling between glioma and host immune cells.
The second part of the review presents current therapies and their drawbacks. This is followed by a summary of the work of our laboratory during the past 20 years, on oligosaccharide and glycosphingolipid inhibitors of astroblast and astrocytoma division. Neurostatins, the O-acetylated forms of gangliosides GD1b and GT1b naturally present in mammalian brain, are cytostatic for normal astroblasts, but cytotoxic for rat C6 glioma cells and human astrocytoma grades III and IV, with ID50 values ranging from 200 to 450 nM. The inhibitors do not affect neurons or fibroblasts up to concentrations of 4 µM or higher.
At least four different neurostatin-activated, cell-mediated antitumoral processes, lead to tumor destruction: (i) inhibition of tumor neovascularization; (ii) activation of microglia; (iii) activation of natural killer (NK) cells; (iv) activation of cytotoxic lymphocytes (CTL). The enhanced antigenicity of neurostatin-treated glioma cells, could be related to their increased expression of connexin 43. Because neurostatins and their analogues show specific activity and no toxicity for normal cells, a clinical trial would be the logical next step.
PDF (9.62 MB PDF FORMAT)
RIS citation (ENDNOTE, REFERENCE MANAGER, PROCITE, REFWORKS)
BibTex citation (BIBDESK, LATEX)
I have been very pleased with the attention and dedication provided to my paper. It was very well organized and informative and all the information that I needed during the process of publication was readily available. The review process was quick and I am very satisfied with the service provided by Libertas. Thank you for your service.
All authors are surveyed after their articles are published. Authors are asked to rate their experience in a variety of areas, and their responses help us to monitor our performance. Presented here are their responses in some key areas. No 'poor' or 'very poor' responses were received; these are represented in the 'other' category.See Our Results
Copyright © 2013 Libertas Academica Ltd (except open access articles and accompanying metadata and supplementary files.)