Date of Award

Summer 2021

Document Type

Open Access Thesis

Department

Biomedical Science

First Advisor

Traci Testerman

Abstract

Pseudomyxoma peritonei is a devastating gastrointestinal disease characterized by the production of mucinous ascites within the peritoneal cavity. Historically, this condition is discovered in the advanced state due to the lack of adequate screening tests and typically presents as an enlarged abdomen and with symptoms of gastrointestinal distress. Treatment for this disease is a combination of cytoreductive surgery and heated intraperitoneal perfusion chemotherapy, but a successful operation does not guarantee full remission of this malignancy. This study focuses on 3 untested variants of PMP cancer, and 2 mucinous colorectal adenocarcinomas that had invaded into the peritoneal cavity. Clinical presentation of the mucinous colorectal adenocarcinomas with peritoneal invasion resembles PMP cancer. Tumor biopsies were obtained through Mercy Medical Center in Baltimore, Maryland. These cancers underwent 2 growth experiments to obtain both the doubling rate and to explore ex vivo whether or not each unique proliferative rate impacted chemotherapy agent sensitivities. Four common colorectal cancer chemotherapies were examined and their interactions analyzed alongside 5 cancers. LD50 was calculated for each unique interaction between the chemotherapy agent and the cancers, and this LD50 was compared to clinically relevant plasma concentrations for the agent established through literature searches. The results dictate that Mitomycin C and 5-Fluorouracil were the most effective solitary chemotherapy agents. Oxaliplatin therapy showed some sensitivity, but the required concentration to achieve a 50% reduction in ATP values lay beyond normal plasma concentration parameters. Irinotecan therapy yielded little sensitivity, showing that Irinotecan was unable to inhibit normal cellular growth even at peak tested concentrations. We decided to modestly explore multi-drug interactions after the disappointing Irinotecan results, combining 5-Fluorouracil and Irinotecan to create a more robust Irinotecan data pool. Results from the combination therapy were more promising, with each cancer showing sensitivity to the treatment. However, calculated LD50 for the Irinotecan concentrations in the multidrug therapy were in excess of clinical accepted plasma concentrations. Multi-drug therapy shows promise in the treatment of these specific cancers, and future experimentation should expand to include other common combination therapies.

Rights

© 2021, Raymond Kennith Bogdon

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