Medicine and Health Sciences Commons^™

Activation Of Signal Transduction Pathways During Hepatic Oncogenesis., W Chung, M Kim, S De La Monte, L Longato, R Carlson, B L. Slagle, X Dong, J R. Wands

Faculty Publications

BACKGROUND AND AIMS: Understanding the molecular pathogenesis of hepatocellular carcinoma (HCC) is essential to identify therapeutic targets. A hepatitis B virus (HBV) related double transgenic murine model was developed. METHODS: Liver specific expression of HBV X protein (HBx) and insulin receptor substrate 1 (IRS1) was achieved and transgenic mice were followed from birth to age 21 months. Liver and tumor tissue were assessed for histologic changes as well as activation of signal transduction pathways by qRT-PCR and multiplex ELISA protein assays. RESULTS: Overexpression of HBx and IRS1 stimulates liver cell proliferation in the double transgenic mice. Only the male mice …

Dissecting The Roles Of Trim24 In Regulation Of Hepatic Lipid Metabolism And Inflammation, Lindsey C. Minter

Dissertations & Theses (Open Access)

DISSECTING THE ROLES OF TRIM24 IN REGULATION OF HEPATIC LIPID

METABOLISM AND INFLAMMATION

Lindsey Cauthen Minter, B.S., B.A.

Advisory Professor: Michelle C. Barton, Ph.D.

In this dissertation, I report the characterization of a new mouse model that recapitulates development of hepatocellular carcinoma (HCC) following spontaneous hepatic lipid accumulation, inflammation, and damage of liver tissue, due to complete loss of Trim24 expression. In human HCC and other cancers, TRIM24 expression is aberrantly high, while deletion of TRIM24 in the mouse has been shown to act as a liver specific tumor suppressor. The hypothesis tested here was that TRIM24, the E3 ubiquitin …

Mapping The Human Vasculature By In Vivo Phage Display, Julianna Bronk

Dissertations & Theses (Open Access)

In vivo phage display screenings by intravenous injection of a random phage-displayed peptide library allow for the selection of peptides that localize to specific vascular beds. At the University of Texas MD Anderson Cancer Center, we have had the opportunity to perform phage display screenings in cancer patients in order to select for cancer specific targets directly in humans. These targets serve to define biochemical diversity of endothelial cell surfaces and can be validated and explored towards the design of vascular-targeted pharmacology. In the most recent patient screen, samples were recovered from hepatocellular carcinoma (HCC) as well as 26 additional …

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

Dissertations & Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …