PDE based geometry model for BCG immunotherapy of bladder cancer

Lazebnik, Teddy; Aaroni, Niva; Bunimovich‐Mendrazitsky, Svetlana

doi:10.1016/j.biosystems.2020.104319

Cited by 16 publications

(11 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From the spatial point of view, we adopt the mesh obtained by [ 44 ] for the outer layer of the bladder. Following the assumption presented by [ 27 ], we copied the same mesh for the inner layer such that the average Euclidean distance (

) between the outer and inner layers is constant and is equal to

. In addition, based on the model proposed by [ 45 ], we used eight cell layers of the urothelium with a depth of 40 cells.…”

Section: Model Definitionmentioning

confidence: 99%

“…In a similar manner, Ref. [ 27 ] further extended the model proposed by [ 24 ] by introducing more detailed biological dynamics based on the biological description proposed by [ 19 ], increasing the number of cell populations from four to 10. The authors showed that the extended model provides a more realistic treatment protocol prediction compared to that of the same model without spatial dynamics.…”

Section: Introduction and Related Workmentioning

confidence: 99%

See 1 more Smart Citation

Cell-Level Spatio-Temporal Model for a Bacillus Calmette–Guérin-Based Immunotherapy Treatment Protocol of Superficial Bladder Cancer

Lazebnik

2022

Cells

Self Cite

View full text Add to dashboard Cite

Bladder cancer is one of the most widespread types of cancer. Multiple treatments for non-invasive, superficial bladder cancer have been proposed over the last several decades with a weekly Bacillus Calmette–Guérin immunotherapy-based therapy protocol, which is considered the gold standard today. Nonetheless, due to the complexity of the interactions between the immune system, healthy cells, and cancer cells in the bladder’s microenvironment, clinical outcomes vary significantly among patients. Mathematical models are shown to be effective in predicting the treatment outcome based on the patient’s clinical condition at the beginning of the treatment. Even so, these models still have large errors for long-term treatments and patients that they do not fit. In this work, we utilize modern mathematical tools and propose a novel cell-level spatio-temporal mathematical model that takes into consideration the cell–cell and cell–environment interactions occurring in a realistic bladder’s geometric configuration in order to reduce these errors. We implement the model using the agent-based simulation approach, showing the impacts of different cancer tumor sizes and locations at the beginning of the treatment on the clinical outcomes for today’s gold-standard treatment protocol. In addition, we propose a genetic-algorithm-based approach to finding a successful and time-optimal treatment protocol for a given patient’s initial condition. Our results show that the current standard treatment protocol can be modified to produce cancer-free equilibrium for deeper cancer cells in the urothelium if the cancer cells’ spatial distribution is known, resulting in a greater success rate.

show abstract

) between the outer and inner layers is constant and is equal to

. In addition, based on the model proposed by [ 45 ], we used eight cell layers of the urothelium with a depth of 40 cells.…”

Section: Model Definitionmentioning

confidence: 99%

Section: Introduction and Related Workmentioning

confidence: 99%

Cell-Level Spatio-Temporal Model for a Bacillus Calmette–Guérin-Based Immunotherapy Treatment Protocol of Superficial Bladder Cancer

Lazebnik

2022

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

“…Using Equations ( 1)-( 3), we could numerically simulate the effect of Cyt or Ibr on A20 mCherry cells by substituting necessary parameters with the values from the Table 1. Fourth-order adaptive step Runge-Kutta integration applied with the ODE45 subroutine of MATLAB [21] was used to carry out computer simulations. The finite-distance analysis error of the proposed model is presented in Appendix B.…”

Section: Validation Of the In Vitro A20 Mcherry Cell Drug Cytotoxicit...mentioning

confidence: 99%

Differential Response to Cytotoxic Drugs Explains the Dynamics of Leukemic Cell Death: Insights from Experiments and Mathematical Modeling

Guzev

Bunimovich‐Mendrazitsky

Firer

2022

Symmetry

Self Cite

View full text Add to dashboard Cite

This study presents a framework whereby cancer chemotherapy could be improved through collaboration between mathematicians and experimentalists. Following on from our recently published model, we use A20 murine leukemic cells transfected with monomeric red fluorescent proteins cells (mCherry) to compare the simulated and experimental cytotoxicity of two Federal Drug Administration (FDA)-approved anticancer drugs, Cytarabine (Cyt) and Ibrutinib (Ibr) in an in vitro model system of Chronic Lymphocytic Leukemia (CLL). Maximum growth inhibition with Cyt (95%) was reached at an 8-fold lower drug concentration (6.25 μM) than for Ibr (97%, 50 μM). For the proposed ordinary differential equations (ODE) model, a multistep strategy was used to estimate the parameters relevant to the analysis of in vitro experiments testing the effects of different drug concentrations. The simulation results demonstrate that our model correctly predicts the effects of drugs on leukemic cells. To assess the closeness of the fit between the simulations and experimental data, RMSEs for both drugs were calculated (both RMSEs < 0.1). The numerical solutions of the model show a symmetrical dynamical evolution for two drugs with different modes of action. Simulations of the combinatorial effect of Cyt and Ibr showed that their synergism enhanced the cytotoxic effect by 40%. We suggest that this model could predict a more personalized drug dose based on the growth rate of an individual’s cancer cells.

show abstract

“…In order to find the most relevant patient-specific regimen, one can further analyze the image of the model (e.g., Eq. (8)) by solving the ODE and to produce a function T ( b, τ b , N ) → {0, 1} when the source space contained in ℝ 3 and the image space is exactly {0, 1} [47]. The parameters ( b, τ b , N ) are used as the source space since they define the BCG-based treatment protocol.…”

Section: Numerical Simulationsmentioning

confidence: 99%

Clinically Relevant Mathematical Model for the BCG-based Treatment Of Type 1 Diabetes

Lazebnik

Bunimovich‐Mendrazitsky

Kiselyov³

2021

Preprint

Self Cite

View full text Add to dashboard Cite

This work introduces a model of immunotherapy treatment, namely the Bacillus Calmette-Guerin (BCG) vaccine, of type 1 diabetes (T1D). The model takes into consideration a clinically relevant interaction network between multiple immune cells and compartments. A set of ordinary differential equations (ODEs) is introduced to capture the connectivity between these variables and clinical presentation of the disease. Four subsets of the T1D patients and healthy controls that exhibit normal and high-level glucose consumption are evaluated. The results that obtained for mice, suggest that BCG treatment of the T1D patients that follow healthy eating habits normalizes glucose to levels observed in non-diabetic controls. Furthermore, glucose consumption profoundly influences disease progression. The stable equilibrium state with constant glucose levels is not attainable without repeated BCG treatment. This outcome suggests that immunotherapy may modulate molecular and cellular manifestations of the disease but it does not eliminate T1D. Of note, our data indicate that the BCG immunotherapy treatment may benefit healthy controls on a high-glucose diet. One may speculate the preventive BCG treatment to provide long-term health benefits in this specific cohort.

show abstract

PDE based geometry model for BCG immunotherapy of bladder cancer

Cited by 16 publications

References 67 publications

Cell-Level Spatio-Temporal Model for a Bacillus Calmette–Guérin-Based Immunotherapy Treatment Protocol of Superficial Bladder Cancer

Cell-Level Spatio-Temporal Model for a Bacillus Calmette–Guérin-Based Immunotherapy Treatment Protocol of Superficial Bladder Cancer

Differential Response to Cytotoxic Drugs Explains the Dynamics of Leukemic Cell Death: Insights from Experiments and Mathematical Modeling

Clinically Relevant Mathematical Model for the BCG-based Treatment Of Type 1 Diabetes

Contact Info

Product

Resources

About