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Angiogenesis and radiological tumor growth in patients with glioblastoma

BACKGROUND: The preoperative growth of human glioblastomas (GBMs) has been shown to vary among patients. In animal studies, angiogenesis has been linked to hypoxia and faster growth of GBM, however, its relation to the growth of human GBMs is sparsely studied. We have therefore aimed to look for ass...

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Autores principales: Mikkelsen, Vilde Elisabeth, Stensjøen, Anne Line, Granli, Unn Sophie, Berntsen, Erik Magnus, Salvesen, Øyvind, Solheim, Ole, Torp, Sverre Helge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122710/
https://www.ncbi.nlm.nih.gov/pubmed/30176826
http://dx.doi.org/10.1186/s12885-018-4768-9
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author Mikkelsen, Vilde Elisabeth
Stensjøen, Anne Line
Granli, Unn Sophie
Berntsen, Erik Magnus
Salvesen, Øyvind
Solheim, Ole
Torp, Sverre Helge
author_facet Mikkelsen, Vilde Elisabeth
Stensjøen, Anne Line
Granli, Unn Sophie
Berntsen, Erik Magnus
Salvesen, Øyvind
Solheim, Ole
Torp, Sverre Helge
author_sort Mikkelsen, Vilde Elisabeth
collection PubMed
description BACKGROUND: The preoperative growth of human glioblastomas (GBMs) has been shown to vary among patients. In animal studies, angiogenesis has been linked to hypoxia and faster growth of GBM, however, its relation to the growth of human GBMs is sparsely studied. We have therefore aimed to look for associations between radiological speed of growth and microvessel density (MVD) counts of the endothelial markers vWF (Factor VIII related antigen) and CD105 (endoglin). METHODS: Preoperative growth was estimated from segmented tumor volumes of two preoperative T1-weighted postcontrast magnetic resonance imaging scans taken ≥14 days apart in patients with newly diagnosed GBMs. A Gompertzian growth curve was computed from the volume data and separated the patients into two groups of either faster or slower tumor growth than expected. MVD counts of the immunohistochemical markers von Willebrand factor (vWF) (a pan-endothelial marker) and CD105 (a marker of proliferating endothelial cells) were assessed for associations with fast-growing tumors using Mann-Whitney U tests and a multivariable binary logistic regression analysis. RESULTS: We found that only CD105-MVD was significantly associated with faster growth in a univariable analysis (p = 0.049). However, CD105-MVD was no longer significant when corrected for the presence of thromboses and high cellular density in a multivariable model, where the latter features were significant independent predictors of faster growth with respective odds ratios 4.2 (95% confidence interval, 1.2, 14.3), p = 0.021 and 2.6 (95% confidence interval, 1.0, 6.5), p = 0.048. CONCLUSIONS: MVDs of neither endothelial marker were independently associated with faster growth, suggesting angiogenesis-independent processes contribute to faster glioblastoma growth. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4768-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-61227102018-09-10 Angiogenesis and radiological tumor growth in patients with glioblastoma Mikkelsen, Vilde Elisabeth Stensjøen, Anne Line Granli, Unn Sophie Berntsen, Erik Magnus Salvesen, Øyvind Solheim, Ole Torp, Sverre Helge BMC Cancer Research Article BACKGROUND: The preoperative growth of human glioblastomas (GBMs) has been shown to vary among patients. In animal studies, angiogenesis has been linked to hypoxia and faster growth of GBM, however, its relation to the growth of human GBMs is sparsely studied. We have therefore aimed to look for associations between radiological speed of growth and microvessel density (MVD) counts of the endothelial markers vWF (Factor VIII related antigen) and CD105 (endoglin). METHODS: Preoperative growth was estimated from segmented tumor volumes of two preoperative T1-weighted postcontrast magnetic resonance imaging scans taken ≥14 days apart in patients with newly diagnosed GBMs. A Gompertzian growth curve was computed from the volume data and separated the patients into two groups of either faster or slower tumor growth than expected. MVD counts of the immunohistochemical markers von Willebrand factor (vWF) (a pan-endothelial marker) and CD105 (a marker of proliferating endothelial cells) were assessed for associations with fast-growing tumors using Mann-Whitney U tests and a multivariable binary logistic regression analysis. RESULTS: We found that only CD105-MVD was significantly associated with faster growth in a univariable analysis (p = 0.049). However, CD105-MVD was no longer significant when corrected for the presence of thromboses and high cellular density in a multivariable model, where the latter features were significant independent predictors of faster growth with respective odds ratios 4.2 (95% confidence interval, 1.2, 14.3), p = 0.021 and 2.6 (95% confidence interval, 1.0, 6.5), p = 0.048. CONCLUSIONS: MVDs of neither endothelial marker were independently associated with faster growth, suggesting angiogenesis-independent processes contribute to faster glioblastoma growth. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4768-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-09-03 /pmc/articles/PMC6122710/ /pubmed/30176826 http://dx.doi.org/10.1186/s12885-018-4768-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Mikkelsen, Vilde Elisabeth
Stensjøen, Anne Line
Granli, Unn Sophie
Berntsen, Erik Magnus
Salvesen, Øyvind
Solheim, Ole
Torp, Sverre Helge
Angiogenesis and radiological tumor growth in patients with glioblastoma
title Angiogenesis and radiological tumor growth in patients with glioblastoma
title_full Angiogenesis and radiological tumor growth in patients with glioblastoma
title_fullStr Angiogenesis and radiological tumor growth in patients with glioblastoma
title_full_unstemmed Angiogenesis and radiological tumor growth in patients with glioblastoma
title_short Angiogenesis and radiological tumor growth in patients with glioblastoma
title_sort angiogenesis and radiological tumor growth in patients with glioblastoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122710/
https://www.ncbi.nlm.nih.gov/pubmed/30176826
http://dx.doi.org/10.1186/s12885-018-4768-9
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