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- Hypoxic conditions occur in the center of tumor after tumor cells use and deplete oxygen.
- Hypoxic cells secrete signaling chemicals to induce vascularization, such as vascular epithelial growth factor (VEGF).
- This model is developed with using agentbased multicellular system simulator which is called PhysiCell .
- Cells are changing behavior according to oxygen level. After they become hypoxic, their genes are regulated.
- Our model accounts for this vascularization by increasing VEGF secretion by hypoxic cells.
- Vasculature is controlled by three mechanisms, which are grow, death, and advective flux.
- Blood supplies or uptakes metabolites from microenvironment according to blood target values.
- Tumor has a necrotic core that has nearly no oxygen.
- Cellular layering is formed as: Necrotic (purple), Hypoxic (Green), Normoxic(Red)
- VEGF concentration through tumor has ring-like distribution which is consistent with literature 3
- A small vasculature accumulation near to tumor is observed. This was an expected behavior in order to modeling equations.
National Science Foundation (Award 1720625)
National Institutes of Health (U01-CA232137-01)
Breast Cancer Research Foundation
Jayne Koskinas Ted Giovanis Foundation for Health and Policy
 PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems. Ghaffarizadeh A, Heiland R, Friedman SH, Mumenthaler SM, Macklin P. PLOS Computational Biology 14(2): e1005991. doi: 10.1371/journal.pcbi.1005991 (2018)
 xml2jupyter: Mapping parameters between XML and Jupyter widges. Heiland R, Mishler D, Zhang T, Bower E, Macklin P. bioRxiv 601211; doi: 10.1101/601211 (2019)
 Experimental and computational analyses reveal dynamics of tumor vessel cooption and optimal treatment strategies C Voutouri, N D. Kirkpatrick, E Chung, F Mpekris, J W. Baish, L L. Munn, D Fukumura, T Stylianopoulos, R K. Jain: PNAS: https://doi.org/10.1073/pnas.1818322116
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