FRIDAY, February 16, 2007
Time: 1:00 PM
ED 210

Title: Mathematical Study of Brain Tumor Therapies and Initiation of Brain Tumor Stem Cells

Jianjun Paul Tian
Mathematical Biosciences Institute
Ohio State University

Glioma is the most serious malignant brain tumor. In order to improve the efficacy of therapies, it is important to understand its progression with therapies and its genesis. In this talk, I will first present our effort in understanding of glioma progression with different therapies in terms of mathematical models. The first model is about virotherapy of glioma, which is a free boundary problem with five nonlinear partial differential equations. Virotherapy is a promising treatment for malignant solid tumors, and it is now in animal experimental stage. In order to treat human glioma by virotherapy, it is critical to understand all factors involved in the therapy. Our model finds an important factor of the therapy, burst size of virus, and the effect of immunosuppression drug cyclophosphamide in animal experiments. The model prediction has been verified by experimental results. The second model is about radiotherapy plus chemotherapy after surgical resection, which is a two-component free boundary problem. After surgery, the tumor progression depends on the degree of resection and radiation, and a particular drug. We use human data to estimate parameter values, and the model can predict the mean survival times of patients who undergo different protocols of treatments. The third part of the talk is about initiation of brain tumor stem cells. This work is ongoing, and our focus now is on two molecular signals SHH and GABA in subventricular zone niche of adult neural stem cells. Hopefully, we can "reconcile" the "contradiction" that GABA has inhibitory effect both on stem cell proliferation and on the velocity of cells moving within the niche and that of speed of migration, and we can test hypothesis that stem cells will become cancer stem cells once they leave niche signal control.