BME PhD Prospectus Defense - Kristie Charoen

Starts:
9:00 am on Thursday, May 23, 2013
Ends:
11:00 am on Thursday, May 23, 2013
Location:
44 Cummington St, Room 203
Title: “An in vitro Tumor Model for Probing Cancer Behavior”

Committee:
Chair, Advisor: Professor Mark Grinstaff
Professor Muhammad Zaman
Professor Michael Smith
Dr. Yolanda Colson

Abstract:
Despite the wealth of research focused on cancer, it is often performed in one of two models. There is the standard monolayer of cells, used as the testing ground for new drug delivery methods and novel drug candidates. It lacks the three dimensional nature of a tumor and any stromal content. The second model is the animal model, which differs in size and anatomy to the human, but remains the more physiological setting. However the high cost associated remains a prohibitive barrier. The objective of this thesis is to create a more physiologically relevant model of a tumor for applications in cancer biology and drug delivery. A model developed in the 1960s, encourages the aggregation of cells into a multicellular tumor-like structure called a spheroid. My preliminary research has adapted this protocol to place a spheroid into a collagen gel. The spheroid then demonstrates a number of physiological hallmarks of a tumor such as a proliferating ring of cells, necrotic core and mass transport issues. The collagen acts as a matrix for the spheroid, and allows cell ingrowth. This model can be of interest in two different areas. In terms of cancer biology, it can be used to simulate mechanical perturbations found in resection and look at tumor response. From the drug delivery perspective, it is a viable model to test the efficacy of a system in addressing challenges such as transport, uptake and diffusion. Therefore to establish this as a viable model there are three aims:
Aim 1. Create a system to model and probe a tumor. Incorporate stromal elements such collagen, fibrin and fibroblasts. Characterize the growth of the system. Demonstrate qualitative and quantitative methods to probe it such as flow cytometry, live/dead assays and mRNA expression.
Aim 2. Model a resection and determine at the effect upon gene expression via microarray. Quantify cell ingrowth.
Aim 3. Test the efficacy of multiple drug delivery methods such as expansile nanoparticles, polymeric nanoparticles, cast films and electrospun meshes. Conduct studies in parallel with a 2D monolayer to establish differences between models.