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| HAL : inria-00440447, version 1 |
| PubMed : 19615383 |
| DOI : 10.1016/j.jtbi.2009.06.026 |
| Voir la fiche détaillée |  BibTeX,EndNote,... |
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| Journal of Theoretical Biology 260, 4 (2009) 545-62 |
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| A pharmacologically based multiscale mathematical model of angiogenesis and its use in investigating the efficacy of a new cancer treatment strategy. |
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| Frédérique Billy 1Benjamin Ribba 2, 3 |
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| (21/10/2009) |
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| Tumor angiogenesis is the process by which new blood vessels are formed and enhance the oxygenation and growth of tumors. As angiogenesis is recognized as being a critical event in cancer development, considerable efforts have been made to identify inhibitors of this process. Cytostatic treatments that target the molecular events of the angiogenesis process have been developed, and have met with some success. However, it is usually difficult to preclinically assess the effectiveness of targeted therapies, and apparently promising compounds sometimes fail in clinical trials. We have developed a multiscale mathematical model of angiogenesis and tumor growth. At the molecular level, the model focuses on molecular competition between pro- and anti-angiogenic substances modeled on the basis of pharmacological laws. At the tissue scale, the model uses partial differential equations to describe the spatio-temporal changes in cancer cells during three stages of the cell cycle, as well as those of the endothelial cells that constitute the blood vessel walls. This model is used to qualitatively assess how efficient endostatin gene therapy is. Endostatin is an anti-angiogenic endogenous substance. The gene therapy entails overexpressing endostatin in the tumor and in the surrounding tissue. Simulations show that there is a critical treatment dose below which increasing the duration of treatment leads to a loss of efficacy. This theoretical model may be useful to evaluate the efficacy of therapies targeting angiogenesis, and could therefore contribute to designing prospective clinical trials. |
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| 1 : | Laboratoire d'Etudes Aérodynamiques (LEA) |
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ENSMA – CNRS : UMR6609 – Université de Poitiers |
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| 2 : | Laboratoire de Biométrie et Biologie Evolutive (LBBE) |
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Université Claude Bernard - Lyon I – CNRS : UMR5558 – INRIA |
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| 3 : | NUMED (ENS Lyon / UCB Lyon / Inria Grenoble Rhône-Alpes) |
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Université Claude Bernard - Lyon I – INRIA – École Normale Supérieure - Lyon – CNRS : UMR5669 – Unité de Mathématiques Pures et Appliquées |
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| 4 : | Institut de Mathématiques de Bordeaux (IMB) |
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CNRS : UMR5251 – Université Sciences et Technologies - Bordeaux I – Université Victor Segalen - Bordeaux II |
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| 5 : | MC2 (INRIA Bordeaux - Sud-Ouest) |
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INRIA – Université Sciences et Technologies - Bordeaux I – Université Victor Segalen - Bordeaux II – CNRS : UMR |
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| 6 : | Laboratoire de Mathématiques (LAMA) |
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CNRS : UMR5127 – Université de Savoie |
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| Domaine | : | Sciences du Vivant/Cancer Informatique/Modélisation et simulation |
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| Lien vers le texte intégral |
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| http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=19615383 |
| inria-00440447, version 1 | |
| http://hal.inria.fr/inria-00440447 | |
| oai:hal.inria.fr:inria-00440447 | |
| Contributeur : Olivier Saut | |
| Soumis le : Jeudi 10 Décembre 2009, 18:39:20 | |
| Dernière modification le : Mardi 22 Janvier 2013, 16:27:39 | |
