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Multiscale modeling of tumor growth and angiogenesis: Evaluation of tumor-targeted therapy
The dynamics of tumor growth and associated events cover multiple time and spatial scales, generally including extracellular, cellular and intracellular modifications. The main goal of this study is to model the biological and physical behavior of tumor evolution in presence of normal healthy tissue...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259971/ https://www.ncbi.nlm.nih.gov/pubmed/34161319 http://dx.doi.org/10.1371/journal.pcbi.1009081 |
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author | Jafari Nivlouei, Sahar Soltani, M. Carvalho, João Travasso, Rui Salimpour, Mohammad Reza Shirani, Ebrahim |
author_facet | Jafari Nivlouei, Sahar Soltani, M. Carvalho, João Travasso, Rui Salimpour, Mohammad Reza Shirani, Ebrahim |
author_sort | Jafari Nivlouei, Sahar |
collection | PubMed |
description | The dynamics of tumor growth and associated events cover multiple time and spatial scales, generally including extracellular, cellular and intracellular modifications. The main goal of this study is to model the biological and physical behavior of tumor evolution in presence of normal healthy tissue, considering a variety of events involved in the process. These include hyper and hypoactivation of signaling pathways during tumor growth, vessels’ growth, intratumoral vascularization and competition of cancer cells with healthy host tissue. The work addresses two distinctive phases in tumor development—the avascular and vascular phases—and in each stage two cases are considered—with and without normal healthy cells. The tumor growth rate increases considerably as closed vessel loops (anastomoses) form around the tumor cells resulting from tumor induced vascularization. When taking into account the host tissue around the tumor, the results show that competition between normal cells and cancer cells leads to the formation of a hypoxic tumor core within a relatively short period of time. Moreover, a dense intratumoral vascular network is formed throughout the entire lesion as a sign of a high malignancy grade, which is consistent with reported experimental data for several types of solid carcinomas. In comparison with other mathematical models of tumor development, in this work we introduce a multiscale simulation that models the cellular interactions and cell behavior as a consequence of the activation of oncogenes and deactivation of gene signaling pathways within each cell. Simulating a therapy that blocks relevant signaling pathways results in the prevention of further tumor growth and leads to an expressive decrease in its size (82% in the simulation). |
format | Online Article Text |
id | pubmed-8259971 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-82599712021-07-19 Multiscale modeling of tumor growth and angiogenesis: Evaluation of tumor-targeted therapy Jafari Nivlouei, Sahar Soltani, M. Carvalho, João Travasso, Rui Salimpour, Mohammad Reza Shirani, Ebrahim PLoS Comput Biol Research Article The dynamics of tumor growth and associated events cover multiple time and spatial scales, generally including extracellular, cellular and intracellular modifications. The main goal of this study is to model the biological and physical behavior of tumor evolution in presence of normal healthy tissue, considering a variety of events involved in the process. These include hyper and hypoactivation of signaling pathways during tumor growth, vessels’ growth, intratumoral vascularization and competition of cancer cells with healthy host tissue. The work addresses two distinctive phases in tumor development—the avascular and vascular phases—and in each stage two cases are considered—with and without normal healthy cells. The tumor growth rate increases considerably as closed vessel loops (anastomoses) form around the tumor cells resulting from tumor induced vascularization. When taking into account the host tissue around the tumor, the results show that competition between normal cells and cancer cells leads to the formation of a hypoxic tumor core within a relatively short period of time. Moreover, a dense intratumoral vascular network is formed throughout the entire lesion as a sign of a high malignancy grade, which is consistent with reported experimental data for several types of solid carcinomas. In comparison with other mathematical models of tumor development, in this work we introduce a multiscale simulation that models the cellular interactions and cell behavior as a consequence of the activation of oncogenes and deactivation of gene signaling pathways within each cell. Simulating a therapy that blocks relevant signaling pathways results in the prevention of further tumor growth and leads to an expressive decrease in its size (82% in the simulation). Public Library of Science 2021-06-23 /pmc/articles/PMC8259971/ /pubmed/34161319 http://dx.doi.org/10.1371/journal.pcbi.1009081 Text en © 2021 Jafari Nivlouei et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Jafari Nivlouei, Sahar Soltani, M. Carvalho, João Travasso, Rui Salimpour, Mohammad Reza Shirani, Ebrahim Multiscale modeling of tumor growth and angiogenesis: Evaluation of tumor-targeted therapy |
title | Multiscale modeling of tumor growth and angiogenesis: Evaluation of tumor-targeted therapy |
title_full | Multiscale modeling of tumor growth and angiogenesis: Evaluation of tumor-targeted therapy |
title_fullStr | Multiscale modeling of tumor growth and angiogenesis: Evaluation of tumor-targeted therapy |
title_full_unstemmed | Multiscale modeling of tumor growth and angiogenesis: Evaluation of tumor-targeted therapy |
title_short | Multiscale modeling of tumor growth and angiogenesis: Evaluation of tumor-targeted therapy |
title_sort | multiscale modeling of tumor growth and angiogenesis: evaluation of tumor-targeted therapy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259971/ https://www.ncbi.nlm.nih.gov/pubmed/34161319 http://dx.doi.org/10.1371/journal.pcbi.1009081 |
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