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Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Chemical Engineering

Year Degree Awarded

2015

Month Degree Awarded

May

First Advisor

Neil S. Forbes

Subject Categories

Bacteriology | Biotechnology | Cancer Biology | Diagnosis | Integrative Biology | Therapeutics

Abstract

Finding and treating cancer is difficult due to limited sensitivity and specificity of current detection and treatment strategies. Many chemotherapeutic drugs are small molecules that are limited by diffusion, making it difficult to reach cancer sites requiring high doses that lead to systemic toxicity and off-target effects. Tomographic detection techniques, like PET, MRI and CT, are good at identifying macroscopic lesions in the body but are limited in their ability to detect microscopic lesions. Biomarker detection strategies are extremely sensitive and able to identify ng/ml concentrations of protein, but are poor at discriminating between healthy and disease state levels due to patient-to-patient variance, often leading to misdiagnosis. Gram negative bacteria, specifically Salmonella typhimurium and Escherichia coli, are potential anticancer agents because of their preferential accumulation and growth within tumors. This tumor specificity allows these bacteria to reduce off-target effects and it enables production of recombinant proteins directly at the tumor site. This thesis presents, three strategies for improving cancer therapy and detection using engineered bacteria.

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