Date of Award

8-1-2013

Document Type

Campus Access Thesis

Degree Name

Master of Science (MS)

Department

Physics, Applied

First Advisor

Jonathan Celli

Second Advisor

Bala Sndaram

Third Advisor

Steven Arnason

Abstract

Photodynamic therapy (PDT) is a laser-based treatment currently in clinical and preclinical evaluation for several forms of human cancer. In particular, ongoing clinical studies suggest that PDT is safe and effective for treating locally advanced pancreatic cancer, a lethal disease for which new treatments are urgently needed. Motivated simultaneously by the need to explore combinations with systemic chemotherapy for advanced metastatic disease and evidence that PDT may interact synergistically with platinum-based chemotherapy agents, this thesis examines combinations of PDT with oxaliplatin chemotherapy. The latter is a potent agent that is increasingly used for treatment of pancreatic cancer as part of a multidrug combination with the noted drawbacks of significant toxicity and adverse events. Here, using in vitro 3D pancreatic tumor models, a systematic evaluation of dose, sequence and schedule in PDT and oxaliplatin combinations is reported, showing that specific combinations achieve enhanced tumoricidal efficacy and delayed regrowth relative to the additive combination of both treatments. Results are obtained by quantitative processing of fluorescence image data to analyze response in many treatment conditions simultaneously in 3D tumor models. The findings reported in this thesis could be potentially important in revealing a new strategy to achieve improved treatment response with lower doses of oxaliplatin and less adverse impact on healthy tissues. Aspects of the methodology development itself, which is described herein, could also be used in future studies to accelerate the pace of screening PDT-chemotherapy combinations in 3D cancer models.

Comments

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