Numerical Simulation Of Blood Perfusion And Drug Delivery During "Normalization Window" Of Solid Tumor By Anti-angiogenesis Therapy

Tumor, especially the malignant tumor has become one of the most serious diseases that could cause death. Currently, anti-angiogenesis therapy has become a hot topic in the study of tumor treatment. Clinical trials have confirmed that anti-angiogenesis therapy can normalize tumors'abnormal micro vascular and microenvironment. Besides, it can improve the transport of chemical drugs and the sensitivity of tumor cells to radiation therapies. Therefore, it is important to study the tumor hemodynamics and drug transport during the normalization window. It could be able to offer theoretical guidance for making reasonable combination therapeutic schedule of tumor treatment.Main work of the dissertation1. Research on the effect of microenvironment on tumor blood perfusion under anti-angiogenesis therapyWe focus on the effect of changing microenvironment (including permeability, hydraulic conductivity, oncotic pressure, surface area to volume ratio and tumor radius) due to anti-angiogenesis therapy on the blood perfusion of solid tumors. We build a mathematical model and simulate the blood perfusion of the tumor during the "normalization window". Then, we simulate the interstitial pressure of tumor blood perfusion under anti-angiogenesis therapy with difference iterative method. The results show that the interstitial pressure in the tumor tissue domain decreases while the pressure gradient increases during the normalization window. Besides the retrain of tumor-induced angiogenesis, the therapy changes the hemodynamic parameters of the vascular wall which normalizes the hemodynamic environment of tumor tissue and is propitious to transportation of other drugs.2. Numerical simulation of drug delivery during the normalization window under anti-angiogenesis therapy We use the tumor microvascular network generated by former work to simulate drug delivery during the normalization window, while with the non-normalization window for comparison. The results show that the tumor interstitial fluid pressure decreases, while the pressure gradient increases. It makes the chemical drugs more efficient to transport to target tumor cells.3. The influence of "normalization window" to drug deliveryThe effect of the lasting time as well as the bounds of "normalization window" on the drug delivery is studied. This work can provide a reference for making the best treatment.Innovations of the study1. According to the experimental data, we did the numerical simulation of the blood perfusion during the "normalization window" with the anti-angioenic treatment of solid tumors. Besides, the effect of the kinetic parameters of solid tumors' microenvironment on the hemodynamics is studied. It can provide the theoretical reference for clinical trials to relief the interstitial fluid pressure.2. The drug delivery of the tumor during the "normalization window" is also studied. The results show that the improvement of microenvironment and the decrease of the interstitial fluid pressure improve the efficiency of drug delivery within the tumor.3. The influence of the "normalization window" on the drug delivery is of concern. The bounds and the precise mechanism are still not clear medically. The study may provide a reference for clinical research.The study above has not been reported.