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AG488 as a therapy against gliomas

High-grade gliomas such as glioblastomas (GBM) present a deadly prognosis following diagnosis and very few effective treatment options. Here, we investigate if the small molecule AG488 can be an effective therapy against GBM with both anti-angiogenic as well as an anti-microtubule inhibiting modalit...

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Autores principales: Ziegler, Jadith, Bastian, Anja, Lerner, Megan, Bailey-Downs, Lora, Saunders, Debra, Smith, Nataliya, Sutton, Jake, Battiste, James D., Ihnat, Michael A., Gangjee, Aleem, Towner, Rheal A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641093/
https://www.ncbi.nlm.nih.gov/pubmed/29069750
http://dx.doi.org/10.18632/oncotarget.18284
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author Ziegler, Jadith
Bastian, Anja
Lerner, Megan
Bailey-Downs, Lora
Saunders, Debra
Smith, Nataliya
Sutton, Jake
Battiste, James D.
Ihnat, Michael A.
Gangjee, Aleem
Towner, Rheal A.
author_facet Ziegler, Jadith
Bastian, Anja
Lerner, Megan
Bailey-Downs, Lora
Saunders, Debra
Smith, Nataliya
Sutton, Jake
Battiste, James D.
Ihnat, Michael A.
Gangjee, Aleem
Towner, Rheal A.
author_sort Ziegler, Jadith
collection PubMed
description High-grade gliomas such as glioblastomas (GBM) present a deadly prognosis following diagnosis and very few effective treatment options. Here, we investigate if the small molecule AG488 can be an effective therapy against GBM with both anti-angiogenic as well as an anti-microtubule inhibiting modalities, using a human G55 glioma xenograft model in nude mice. From in vitro studies, we report that AG488 incubation reduced cell viability in G55 and HMEC-1 cells more so than TMZ treatment, and AG488 treatment also decreased cell viability in normal astrocytes, but not as much as for G55 cells (p<0.0001). In vivo investigations indicated that AG488 therapy helped reduce tumor volumes (p<0.0001), prolong survival (p<0.01), increase tumor perfusion (p<0.01), and decrease microvessel density (MVD) (p<0.05), compared to untreated mice or mice treated with non-specific IgG, in the G55 xenograft model. Additionally, AG488 did not induce apoptosis in normal mouse brain tissue. Animal survival and tumor volume changes for AG488 were comparable to TMZ or anti-VEGF therapies, however AG488 was found to be more effective in decreasing tumor-related vascularity (perfusion and MVD). AG488 is a potential novel therapy against high-grade gliomas.
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spelling pubmed-56410932017-10-24 AG488 as a therapy against gliomas Ziegler, Jadith Bastian, Anja Lerner, Megan Bailey-Downs, Lora Saunders, Debra Smith, Nataliya Sutton, Jake Battiste, James D. Ihnat, Michael A. Gangjee, Aleem Towner, Rheal A. Oncotarget Research Paper High-grade gliomas such as glioblastomas (GBM) present a deadly prognosis following diagnosis and very few effective treatment options. Here, we investigate if the small molecule AG488 can be an effective therapy against GBM with both anti-angiogenic as well as an anti-microtubule inhibiting modalities, using a human G55 glioma xenograft model in nude mice. From in vitro studies, we report that AG488 incubation reduced cell viability in G55 and HMEC-1 cells more so than TMZ treatment, and AG488 treatment also decreased cell viability in normal astrocytes, but not as much as for G55 cells (p<0.0001). In vivo investigations indicated that AG488 therapy helped reduce tumor volumes (p<0.0001), prolong survival (p<0.01), increase tumor perfusion (p<0.01), and decrease microvessel density (MVD) (p<0.05), compared to untreated mice or mice treated with non-specific IgG, in the G55 xenograft model. Additionally, AG488 did not induce apoptosis in normal mouse brain tissue. Animal survival and tumor volume changes for AG488 were comparable to TMZ or anti-VEGF therapies, however AG488 was found to be more effective in decreasing tumor-related vascularity (perfusion and MVD). AG488 is a potential novel therapy against high-grade gliomas. Impact Journals LLC 2017-05-30 /pmc/articles/PMC5641093/ /pubmed/29069750 http://dx.doi.org/10.18632/oncotarget.18284 Text en Copyright: © 2017 Ziegler et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Ziegler, Jadith
Bastian, Anja
Lerner, Megan
Bailey-Downs, Lora
Saunders, Debra
Smith, Nataliya
Sutton, Jake
Battiste, James D.
Ihnat, Michael A.
Gangjee, Aleem
Towner, Rheal A.
AG488 as a therapy against gliomas
title AG488 as a therapy against gliomas
title_full AG488 as a therapy against gliomas
title_fullStr AG488 as a therapy against gliomas
title_full_unstemmed AG488 as a therapy against gliomas
title_short AG488 as a therapy against gliomas
title_sort ag488 as a therapy against gliomas
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641093/
https://www.ncbi.nlm.nih.gov/pubmed/29069750
http://dx.doi.org/10.18632/oncotarget.18284
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