Author ORCID Identifier
https://orcid.org/0009-0006-7109-8342
Date Available
8-1-2026
Year of Publication
2025
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy (PhD)
College
Medicine
Department/School/Program
Clinical and Translational Science
Faculty
Joseph Kim
Abstract
Cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC) is a treatment used for primary peritoneal malignancy or metastases, including colon cancer. We aimed to explore the effects of hyperthermia and/or mitomycin C (MMC) on mismatch repair (MMR) proteins and heat shock proteins (hsps) and the potential for post-HIPEC treatment with pembrolizumab treatment. Colon cancer cells were treated with hyperthermia and/or MMC for 90 minutes. Subcellular fractionation and immunofluorescent imaging were performed to identify protein abundance and localization of MSH2, MLH1, hsp70, and hsp27. Proteomics analysis was performed for HT29 cells. HT29 cells and patient-derived organoids (PDOs) underwent simulated HIPEC and treatment with pembrolizumab. We found that MMC alone and in combination with hyperthermia increased levels of MSH2, hsp27, and hsp70 and across multiple cell lines, with variable localization depending on the protein of interest. In HT29 cells treated with MMC, we found an increase in positive regulators of programmed cell death at normothermia compared to hyperthermia. Hyperthermia did not increase the cytotoxicity of MMC in colon cancer cells or PDOs. Further work is needed to examine the relationships of MMR proteins and hsps and potential therapeutic impact, as well as assessing the utility of hyperthermia with intraperitoneal MMC for colon cancer.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2025.294
Funding Information
This research was supported by a National Institutes of Health grant (no. R03CA267326) in 2023, a National Institutes of Health training grant (no. 5T32CA160003-12) and a University of Kentucky Department of Behavioral Science pilot grant in 2024.
Recommended Citation
Reagan, Anna M., "Impact of hyperthermia and Mitomycin C on heat shock proteins, mismatch repair proteins, and cytotoxicity in colon cancer" (2025). Theses and Dissertations--Clinical and Translational Science. 24.
https://uknowledge.uky.edu/cts_etds/24
