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Multi-scale modeling of paracrine PDGF-driven glioma growth and invasion

Massey, Susan Christine. (2016) Multi-scale modeling of paracrine PDGF-driven glioma growth and invasion (Dissertation).

The most common primary brain tumor in adults, glioma claims thousands of lives each year. Despite efforts to improve survival rates, the standard of care has remain unchanged for more than a decade. Recent research has started to uncover the role of stromal involvement in the growth of gliomas. Consisting of the supportive cells in the tissue, these stromal cells had long been overlooked in finding strategies for treating cancers. One particular component of this stromal support of gliomas is platelet–derived growth factor (PDGF). PDGF is secreted by a number of cells in the brain, and has a number of cellular targets, including oligodendroglial progenitor cells. In animal models, upregulated PDGF signaling leads to the formation of tumors similar to human gliomas through the recruitment of oligodendroglial progenitor cells by PDGF. Central to my work is the mathematical examination of the effects of paracrine PDGF signaling on normal brain tissue and in brain tumor formation using PDE models. Model simulations show that PDGF can drive a number of outcomes in response to brain injury, and that increased PDGF signaling can speed up tumor growth and can alter the steepness of the tumor density gradient extending into adjacent normal brain tissue. Greater understanding of the contributions of PDGF in the development and growth of tumors may lead to much needed new strategies for combating glioma.

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