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- Type of Document: M.Sc. Thesis
- Language: Farsi
- Document No: 54616 (08)
- University: Sharif University of Technology
- Department: Mechanical Engineering
- Advisor(s): Firoozabadi, Bahar; Mozafari, Ali Asghar
- Abstract:
- Search for effective methods for treating cancer requires a deep understanding of the tumor microenvironment and its role in cancerous tumor growth and progression. Mathematical modeling methods, which have fewer limitations than experimental methods for examining the microcirculation of cancer in detail, are suggested to answer many questions about the behavior and dynamics of cancerous tumors. In the present study, a multi-scale mathematical model of the three-dimensional tumor microenvironment, including molecular, cellular, and tissue scales, is presented. In this model, important aspects of tumor microenvironmental dynamics including tumor growth, angiogenesis, cancer metabolism, and cellular signals are considered. The governing equations for modeling tumor microenvironment are divided into two categories, which are: Discrete cell equations to determine cell dynamics, and continuous environment equations to determine the distribution of biochemical and mechanical factors in the microenvironment of cancer. The discrete-continuous dual hybrid method has been used to simultaneously solve the governing equations and a program has been developed to implement it using MATLAB coding. The simulation results show that the cancerous tumor grows in three different stages: avascular growth, angiogenesis, and vascular growth. Tumor progression has been simulated under the influence of abnormal conditions commonly encountered by cancer patients, including biochemical disorders of the blood, changes in blood pressure, and the phenomenon of desmoplasia. The simulation results showed that hyperoxemia and hyperglycemia, chemotherapy-induced hypertension, and desmoplasia, increase tumor growth rate by up to 95% for hyperoxemia, 50% for hyperglycemia, 12% for hypertension, and 75% for desmoplasia. In order to study the cancer response to chemotherapy, the simulated tumor is applied as a computational model for the administration of various chemotherapy approaches including anti-cancer therapy, concurrent and neoadjuvant combination therapies with anti-cancer and antiangiogenic drugs are considered. In this study, the effect of diabetes (hyperglycemia) was considered as the most important secondary disorder for cancer patients on the effectiveness of treatment. The results showed that chemotherapy combined with anti-angiogenesis improved treatment by 17% and 25% for non-diabetic and diabetic conditions, respectively, reduced drug accumulation in healthy tissue by up to 80%, and improved drug delivery to tumor tissue, up to four times. As such, neoadjuvant combination therapy, especially for a diabetic cancer patient, provides better therapeutic results and drug delivery accuracy, with an increase of up to about three times compared to concurrent combination therapy. The present mathematical model with the ability to simulate experimental observations of tumor progression and its response to treatment can be used as an accurate computational tool to find effective treatment strategies. In addition to chemotherapy simulation, the tumor response to other anti-cancer methods such as immunotherapy, radiotherapy and their combination can be simulated using the proposed model
- Keywords:
- Tumor Microenvironment ; Angiogenesis ; Tumor Growth ; Interstitial Fluid ; Growth Factor ; Anticancer Drugs ; Anti-Angiogenic Drug
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