abstract: Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer
type worldwide, accounts for more than 630,000 new cases and 350,000 deaths
annually. Drug-resistance and tumor recurrence are the most challenging problems
in head and neck cancer treatment. It is hypothesized that a very small fraction
of stem-like cells within HNSCC tumor, called cancer stem cells (CSCs), is
responsible for tumor initiation, progression, resistance and recurrence. It has also
been shown that IL-6 secreted by head and neck tumor-associated endothelial cells
(ECs) enhances the survival, self-renewal and tumorigenic potential of head and
neck CSCs. In this study we will use a mathematical multi-scale model which operates
at the intracellular, molecular, and tissue level to investigate the impacts of
EC-secreted IL-6 signaling on the crosstalk between tumor cells and ECs during
tumor growth. This model will be calibrated by using the experimental in vivo
data.
Eventually the model will be modified to explore the responses of head and neck
cancer cells to combination therapy involving Tocilizumab (an anti-IL-6R antibody)
and Cisplatin (the most frequently used chemotherapy for head and neck
cancer). The model will be able to predict the final proportion of CSCs in response
to endothelial cell-secreted IL-6 and drug therapies. The model will be validated
by directly comparing the experimental treatment data and the model predictions.
This could potentially provide a condition under which we could control enlargement
of the head and neck CSC pool and tumor recurrence. It may also suggest
the best bounds for Cisplatin and/or Tocilizumab dose and frequency to be tested
in the clinical trial. / Dissertation/Thesis / Doctoral Dissertation Applied Mathematics for the Life and Social Sciences 2017
| Identifer | oai:union.ndltd.org:asu.edu/item:45568 |
| Date | January 2017 |
| Contributors | Nazari, Fereshteh (Author), Jackson, Trachette L. (Advisor), Jackson, Trachette L. (Committee member), Castillo-Chavez, Carlos (Committee member), Towers, Sherry (Committee member), Kang, Yun (Committee member), Arizona State University (Publisher) |
| Source Sets | Arizona State University |
| Language | English |
| Detected Language | English |
| Type | Doctoral Dissertation |
| Format | 199 pages |
| Rights | http://rightsstatements.org/vocab/InC/1.0/, All Rights Reserved |
Page generated in 0.0157 seconds