Cargando…

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-...

Descripción completa

Detalles Bibliográficos
Autores principales: Scribner, Elizabeth, Saut, Olivier, Province, Paula, Bag, Asim, Colin, Thierry, Fathallah-Shaykh, Hassan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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
_version_ 1782349035115380736
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
work_keys_str_mv AT scribnerelizabeth effectsofantiangiogenesisonglioblastomagrowthandmigrationmodeltoclinicalpredictions
AT sautolivier effectsofantiangiogenesisonglioblastomagrowthandmigrationmodeltoclinicalpredictions
AT provincepaula effectsofantiangiogenesisonglioblastomagrowthandmigrationmodeltoclinicalpredictions
AT bagasim effectsofantiangiogenesisonglioblastomagrowthandmigrationmodeltoclinicalpredictions
AT colinthierry effectsofantiangiogenesisonglioblastomagrowthandmigrationmodeltoclinicalpredictions
AT fathallahshaykhhassanm effectsofantiangiogenesisonglioblastomagrowthandmigrationmodeltoclinicalpredictions