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Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions
Glioblastoma multiforme (GBM) causes significant neurological morbidity and short survival times. Brain invasion by GBM is associated with poor prognosis. Recent clinical trials of bevacizumab in newly-diagnosed GBM found no beneficial effects on overall survival times; however, the baseline health-...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266618/ https://www.ncbi.nlm.nih.gov/pubmed/25506702 http://dx.doi.org/10.1371/journal.pone.0115018 |
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author | Scribner, Elizabeth Saut, Olivier Province, Paula Bag, Asim Colin, Thierry Fathallah-Shaykh, Hassan M. |
author_facet | Scribner, Elizabeth Saut, Olivier Province, Paula Bag, Asim Colin, Thierry Fathallah-Shaykh, Hassan M. |
author_sort | Scribner, Elizabeth |
collection | PubMed |
description | Glioblastoma multiforme (GBM) causes significant neurological morbidity and short survival times. Brain invasion by GBM is associated with poor prognosis. Recent clinical trials of bevacizumab in newly-diagnosed GBM found no beneficial effects on overall survival times; however, the baseline health-related quality of life and performance status were maintained longer in the bevacizumab group and the glucocorticoid requirement was lower. Here, we construct a clinical-scale model of GBM whose predictions uncover a new pattern of recurrence in 11/70 bevacizumab-treated patients. The findings support an exception to the Folkman hypothesis: GBM grows in the absence of angiogenesis by a cycle of proliferation and brain invasion that expands necrosis. Furthermore, necrosis is positively correlated with brain invasion in 26 newly-diagnosed GBM. The unintuitive results explain the unusual clinical effects of bevacizumab and suggest new hypotheses on the dynamic clinical effects of migration by active transport, a mechanism of hypoxia-driven brain invasion. |
format | Online Article Text |
id | pubmed-4266618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42666182014-12-26 Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions Scribner, Elizabeth Saut, Olivier Province, Paula Bag, Asim Colin, Thierry Fathallah-Shaykh, Hassan M. PLoS One Research Article Glioblastoma multiforme (GBM) causes significant neurological morbidity and short survival times. Brain invasion by GBM is associated with poor prognosis. Recent clinical trials of bevacizumab in newly-diagnosed GBM found no beneficial effects on overall survival times; however, the baseline health-related quality of life and performance status were maintained longer in the bevacizumab group and the glucocorticoid requirement was lower. Here, we construct a clinical-scale model of GBM whose predictions uncover a new pattern of recurrence in 11/70 bevacizumab-treated patients. The findings support an exception to the Folkman hypothesis: GBM grows in the absence of angiogenesis by a cycle of proliferation and brain invasion that expands necrosis. Furthermore, necrosis is positively correlated with brain invasion in 26 newly-diagnosed GBM. The unintuitive results explain the unusual clinical effects of bevacizumab and suggest new hypotheses on the dynamic clinical effects of migration by active transport, a mechanism of hypoxia-driven brain invasion. Public Library of Science 2014-12-15 /pmc/articles/PMC4266618/ /pubmed/25506702 http://dx.doi.org/10.1371/journal.pone.0115018 Text en © 2014 Scribner et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Scribner, Elizabeth Saut, Olivier Province, Paula Bag, Asim Colin, Thierry Fathallah-Shaykh, Hassan M. Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions |
title | Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions |
title_full | Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions |
title_fullStr | Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions |
title_full_unstemmed | Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions |
title_short | Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions |
title_sort | effects of anti-angiogenesis on glioblastoma growth and migration: model to clinical predictions |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266618/ https://www.ncbi.nlm.nih.gov/pubmed/25506702 http://dx.doi.org/10.1371/journal.pone.0115018 |
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