A spatial model of tumor-host interaction: Application of chemotherapy
In this paper we consider chemotherapy in a spatial model of tumor growth. The model, which is of reaction-diffusion type, takes into account the complex interactions between the tumor and surrounding stromal cells by including densities of endothelial cells and the extra-cellular matrix. When no t...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
AIMS Press
2009-05-01
|
| Series: | Mathematical Biosciences and Engineering |
| Subjects: | |
| Online Access: | https://www.aimspress.com/article/doi/10.3934/mbe.2009.6.521 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832590203239268352 |
|---|---|
| author | Peter Hinow Philip Gerlee Lisa J. McCawley Vito Quaranta Madalina Ciobanu Shizhen Wang Jason M. Graham Bruce P. Ayati Jonathan Claridge Kristin R. Swanson Mary Loveless Alexander R. A. Anderson |
| author_facet | Peter Hinow Philip Gerlee Lisa J. McCawley Vito Quaranta Madalina Ciobanu Shizhen Wang Jason M. Graham Bruce P. Ayati Jonathan Claridge Kristin R. Swanson Mary Loveless Alexander R. A. Anderson |
| author_sort | Peter Hinow |
| collection | DOAJ |
| description | In this paper we consider chemotherapy in a spatial model of tumor growth. The model, which is of reaction-diffusion type, takes into account the complex interactions between the tumor and surrounding stromal cells by including densities of endothelial cells and the extra-cellular matrix. When no treatment is applied the model reproduces the typical dynamics of early tumor growth. The initially avascular tumor reaches a diffusion limited size of the order of millimeters and initiates angiogenesis through the release of vascular endothelial growth factor (VEGF) secreted by hypoxic cells in the core of the tumor. This stimulates endothelial cells to migrate towards the tumor and establishes a nutrient supply sufficient for sustained invasion. To this model we apply cytostatic treatment in the form of a VEGF-inhibitor, which reduces the proliferation and chemotaxis of endothelial cells. This treatment has the capability to reduce tumor mass, but more importantly, we were able to determine that inhibition of endothelial cell proliferation is the more important of the two cellular functions targeted by the drug. Further, we considered the application of a cytotoxic drug that targets proliferating tumor cells. The drug was treated as a diffusible substance entering the tissue from the blood vessels. Our results show that depending on the characteristics of the drug it can either reduce the tumor mass significantly or in fact accelerate the growth rate of the tumor. This result seems to be due to complicated interplay between the stromal and tumor cell types and highlights the importance of considering chemotherapy in a spatial context. |
| format | Article |
| id | doaj-art-9d75fd31f83641a2b2dac2ab6acc0c07 |
| institution | Kabale University |
| issn | 1551-0018 |
| language | English |
| publishDate | 2009-05-01 |
| publisher | AIMS Press |
| record_format | Article |
| series | Mathematical Biosciences and Engineering |
| spelling | doaj-art-9d75fd31f83641a2b2dac2ab6acc0c072025-01-24T01:59:54ZengAIMS PressMathematical Biosciences and Engineering1551-00182009-05-016352154610.3934/mbe.2009.6.521A spatial model of tumor-host interaction: Application of chemotherapyPeter Hinow0Philip Gerlee1Lisa J. McCawley2Vito Quaranta3Madalina Ciobanu4Shizhen Wang5Jason M. Graham6Bruce P. Ayati7Jonathan Claridge8Kristin R. Swanson9Mary Loveless10Alexander R. A. Anderson11Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455Institute for Mathematics and its Applications, University of Minnesota, 114 Lind Hall, Minneapolis, MN 55455In this paper we consider chemotherapy in a spatial model of tumor growth. The model, which is of reaction-diffusion type, takes into account the complex interactions between the tumor and surrounding stromal cells by including densities of endothelial cells and the extra-cellular matrix. When no treatment is applied the model reproduces the typical dynamics of early tumor growth. The initially avascular tumor reaches a diffusion limited size of the order of millimeters and initiates angiogenesis through the release of vascular endothelial growth factor (VEGF) secreted by hypoxic cells in the core of the tumor. This stimulates endothelial cells to migrate towards the tumor and establishes a nutrient supply sufficient for sustained invasion. To this model we apply cytostatic treatment in the form of a VEGF-inhibitor, which reduces the proliferation and chemotaxis of endothelial cells. This treatment has the capability to reduce tumor mass, but more importantly, we were able to determine that inhibition of endothelial cell proliferation is the more important of the two cellular functions targeted by the drug. Further, we considered the application of a cytotoxic drug that targets proliferating tumor cells. The drug was treated as a diffusible substance entering the tissue from the blood vessels. Our results show that depending on the characteristics of the drug it can either reduce the tumor mass significantly or in fact accelerate the growth rate of the tumor. This result seems to be due to complicated interplay between the stromal and tumor cell types and highlights the importance of considering chemotherapy in a spatial context.https://www.aimspress.com/article/doi/10.3934/mbe.2009.6.521tumor invasionanti-angiogenic therapyhypoxiachemotherapymathematical modeling. |
| spellingShingle | Peter Hinow Philip Gerlee Lisa J. McCawley Vito Quaranta Madalina Ciobanu Shizhen Wang Jason M. Graham Bruce P. Ayati Jonathan Claridge Kristin R. Swanson Mary Loveless Alexander R. A. Anderson A spatial model of tumor-host interaction: Application of chemotherapy Mathematical Biosciences and Engineering tumor invasion anti-angiogenic therapy hypoxia chemotherapy mathematical modeling. |
| title | A spatial model of tumor-host interaction: Application of chemotherapy |
| title_full | A spatial model of tumor-host interaction: Application of chemotherapy |
| title_fullStr | A spatial model of tumor-host interaction: Application of chemotherapy |
| title_full_unstemmed | A spatial model of tumor-host interaction: Application of chemotherapy |
| title_short | A spatial model of tumor-host interaction: Application of chemotherapy |
| title_sort | spatial model of tumor host interaction application of chemotherapy |
| topic | tumor invasion anti-angiogenic therapy hypoxia chemotherapy mathematical modeling. |
| url | https://www.aimspress.com/article/doi/10.3934/mbe.2009.6.521 |
| work_keys_str_mv | AT peterhinow aspatialmodeloftumorhostinteractionapplicationofchemotherapy AT philipgerlee aspatialmodeloftumorhostinteractionapplicationofchemotherapy AT lisajmccawley aspatialmodeloftumorhostinteractionapplicationofchemotherapy AT vitoquaranta aspatialmodeloftumorhostinteractionapplicationofchemotherapy AT madalinaciobanu aspatialmodeloftumorhostinteractionapplicationofchemotherapy AT shizhenwang aspatialmodeloftumorhostinteractionapplicationofchemotherapy AT jasonmgraham aspatialmodeloftumorhostinteractionapplicationofchemotherapy AT brucepayati aspatialmodeloftumorhostinteractionapplicationofchemotherapy AT jonathanclaridge aspatialmodeloftumorhostinteractionapplicationofchemotherapy AT kristinrswanson aspatialmodeloftumorhostinteractionapplicationofchemotherapy AT maryloveless aspatialmodeloftumorhostinteractionapplicationofchemotherapy AT alexanderraanderson aspatialmodeloftumorhostinteractionapplicationofchemotherapy AT peterhinow spatialmodeloftumorhostinteractionapplicationofchemotherapy AT philipgerlee spatialmodeloftumorhostinteractionapplicationofchemotherapy AT lisajmccawley spatialmodeloftumorhostinteractionapplicationofchemotherapy AT vitoquaranta spatialmodeloftumorhostinteractionapplicationofchemotherapy AT madalinaciobanu spatialmodeloftumorhostinteractionapplicationofchemotherapy AT shizhenwang spatialmodeloftumorhostinteractionapplicationofchemotherapy AT jasonmgraham spatialmodeloftumorhostinteractionapplicationofchemotherapy AT brucepayati spatialmodeloftumorhostinteractionapplicationofchemotherapy AT jonathanclaridge spatialmodeloftumorhostinteractionapplicationofchemotherapy AT kristinrswanson spatialmodeloftumorhostinteractionapplicationofchemotherapy AT maryloveless spatialmodeloftumorhostinteractionapplicationofchemotherapy AT alexanderraanderson spatialmodeloftumorhostinteractionapplicationofchemotherapy |