Validation of a Mathematical Model Describing the Dynamics of Chemotherapy for Chronic Lymphocytic Leukemia In Vivo
In recent years, mathematical models have developed into an important tool for cancer research, combining quantitative analysis and natural processes. We have focused on Chronic Lymphocytic Leukemia (CLL), since it is one of the most common adult leukemias, which remains incurable. As the first step...
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MDPI AG
2022-07-01
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author | Ekaterina Guzev Suchita Suryakant Jadhav Eleonora Ela Hezkiy Michael Y. Sherman Michael A. Firer Svetlana Bunimovich-Mendrazitsky |
author_facet | Ekaterina Guzev Suchita Suryakant Jadhav Eleonora Ela Hezkiy Michael Y. Sherman Michael A. Firer Svetlana Bunimovich-Mendrazitsky |
author_sort | Ekaterina Guzev |
collection | DOAJ |
description | In recent years, mathematical models have developed into an important tool for cancer research, combining quantitative analysis and natural processes. We have focused on Chronic Lymphocytic Leukemia (CLL), since it is one of the most common adult leukemias, which remains incurable. As the first step toward the mathematical prediction of in vivo drug efficacy, we first found that logistic growth best described the proliferation of fluorescently labeled murine A20 leukemic cells injected in immunocompetent Balb/c mice. Then, we tested the cytotoxic efficacy of Ibrutinib (Ibr) and Cytarabine (Cyt) in A20-bearing mice. The results afforded calculation of the killing rate of the A20 cells as a function of therapy. The experimental data were compared with the simulation model to validate the latter’s applicability. On the basis of these results, we developed a new ordinary differential equations (ODEs) model and provided its sensitivity and stability analysis. There was excellent accordance between numerical simulations of the model and results from in vivo experiments. We found that simulations of our model could predict that the combination of Cyt and Ibr would lead to approximately 95% killing of A20 cells. In its current format, the model can be used as a tool for mathematical prediction of in vivo drug efficacy, and could form the basis of software for prediction of personalized chemotherapy. |
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format | Article |
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issn | 2073-4409 |
language | English |
last_indexed | 2024-03-09T12:42:52Z |
publishDate | 2022-07-01 |
publisher | MDPI AG |
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spelling | doaj.art-7797f6065d634a97a377899707ec15212023-11-30T22:15:50ZengMDPI AGCells2073-44092022-07-011115232510.3390/cells11152325Validation of a Mathematical Model Describing the Dynamics of Chemotherapy for Chronic Lymphocytic Leukemia In VivoEkaterina Guzev0Suchita Suryakant Jadhav1Eleonora Ela Hezkiy2Michael Y. Sherman3Michael A. Firer4Svetlana Bunimovich-Mendrazitsky5Department of Mathematics, Ariel University, Ariel 4070000, IsraelDepartment of Chemical Engineering, Ariel University, Ariel 4070000, IsraelDepartment of Molecular Biology, Ariel University, Ariel 407000, IsraelDepartment of Molecular Biology, Ariel University, Ariel 407000, IsraelDepartment of Chemical Engineering, Ariel University, Ariel 4070000, IsraelDepartment of Mathematics, Ariel University, Ariel 4070000, IsraelIn recent years, mathematical models have developed into an important tool for cancer research, combining quantitative analysis and natural processes. We have focused on Chronic Lymphocytic Leukemia (CLL), since it is one of the most common adult leukemias, which remains incurable. As the first step toward the mathematical prediction of in vivo drug efficacy, we first found that logistic growth best described the proliferation of fluorescently labeled murine A20 leukemic cells injected in immunocompetent Balb/c mice. Then, we tested the cytotoxic efficacy of Ibrutinib (Ibr) and Cytarabine (Cyt) in A20-bearing mice. The results afforded calculation of the killing rate of the A20 cells as a function of therapy. The experimental data were compared with the simulation model to validate the latter’s applicability. On the basis of these results, we developed a new ordinary differential equations (ODEs) model and provided its sensitivity and stability analysis. There was excellent accordance between numerical simulations of the model and results from in vivo experiments. We found that simulations of our model could predict that the combination of Cyt and Ibr would lead to approximately 95% killing of A20 cells. In its current format, the model can be used as a tool for mathematical prediction of in vivo drug efficacy, and could form the basis of software for prediction of personalized chemotherapy.https://www.mdpi.com/2073-4409/11/15/2325A20 cellscytotoxicity ratein vivo experimentslogistic cancer growth ratemathematical modelpersonalized chemotherapy |
spellingShingle | Ekaterina Guzev Suchita Suryakant Jadhav Eleonora Ela Hezkiy Michael Y. Sherman Michael A. Firer Svetlana Bunimovich-Mendrazitsky Validation of a Mathematical Model Describing the Dynamics of Chemotherapy for Chronic Lymphocytic Leukemia In Vivo Cells A20 cells cytotoxicity rate in vivo experiments logistic cancer growth rate mathematical model personalized chemotherapy |
title | Validation of a Mathematical Model Describing the Dynamics of Chemotherapy for Chronic Lymphocytic Leukemia In Vivo |
title_full | Validation of a Mathematical Model Describing the Dynamics of Chemotherapy for Chronic Lymphocytic Leukemia In Vivo |
title_fullStr | Validation of a Mathematical Model Describing the Dynamics of Chemotherapy for Chronic Lymphocytic Leukemia In Vivo |
title_full_unstemmed | Validation of a Mathematical Model Describing the Dynamics of Chemotherapy for Chronic Lymphocytic Leukemia In Vivo |
title_short | Validation of a Mathematical Model Describing the Dynamics of Chemotherapy for Chronic Lymphocytic Leukemia In Vivo |
title_sort | validation of a mathematical model describing the dynamics of chemotherapy for chronic lymphocytic leukemia in vivo |
topic | A20 cells cytotoxicity rate in vivo experiments logistic cancer growth rate mathematical model personalized chemotherapy |
url | https://www.mdpi.com/2073-4409/11/15/2325 |
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