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...

Full description

Bibliographic Details
Main Authors: Ekaterina Guzev, Suchita Suryakant Jadhav, Eleonora Ela Hezkiy, Michael Y. Sherman, Michael A. Firer, Svetlana Bunimovich-Mendrazitsky
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/15/2325
_version_ 1797442509310263296
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.
first_indexed 2024-03-09T12:42:52Z
format Article
id doaj.art-7797f6065d634a97a377899707ec1521
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-09T12:42:52Z
publishDate 2022-07-01
publisher MDPI AG
record_format Article
series Cells
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
work_keys_str_mv AT ekaterinaguzev validationofamathematicalmodeldescribingthedynamicsofchemotherapyforchroniclymphocyticleukemiainvivo
AT suchitasuryakantjadhav validationofamathematicalmodeldescribingthedynamicsofchemotherapyforchroniclymphocyticleukemiainvivo
AT eleonoraelahezkiy validationofamathematicalmodeldescribingthedynamicsofchemotherapyforchroniclymphocyticleukemiainvivo
AT michaelysherman validationofamathematicalmodeldescribingthedynamicsofchemotherapyforchroniclymphocyticleukemiainvivo
AT michaelafirer validationofamathematicalmodeldescribingthedynamicsofchemotherapyforchroniclymphocyticleukemiainvivo
AT svetlanabunimovichmendrazitsky validationofamathematicalmodeldescribingthedynamicsofchemotherapyforchroniclymphocyticleukemiainvivo