Abstract

an N1-S1 hepatocellular carcinoma in a rat model. Materials and Methods: 24 rats with implanted liver N1S1 tumors were divided into 4 groups: control group (n1⁄45, 1 mL normal saline, NS), bland embolization group (TAE, n1⁄44, 10 mg 50-150 micron PVA in 1 mL NS), TAE and caffeic acid group (TAEþCA, n1⁄45, 10mg PVA and 30 mg of caffeic acid in 1 mL NS), and TAE and ferulic acid group (TAEþFA, n1⁄45, 10 mg PVA and 30 mg ferulic acid in 1 mL NS). Embolization was through retrograde catheterization of the gastroduodenal artery and verified through contrast-enhanced ultrasound (CE-US). Tumor volume was measured by US before and twice a week until 4 weeks post-treatment. The repeated measures ANOVA was used to compare differences in pre-treatment tumor volume by group and over time. At 4 weeks, the rats were sacrificed and histopathologic evaluation performed. Results: There was no significant difference in the initial tumor sizes between each group. The control group showed rapid growth with a volume that was 3,000% larger compared with baseline. In the TAE group, tumor volume increased when compared to pre-treatment volume by 6.7 þ/-11.2%. Both TAEþCA and TAEþFA demonstrated a statistically significant decrease in tumor size when compared to TAE with a decrease in tumor volume by 86.8þ/-10.2% and 71.8þ/10.5%, respectively (po0.0001). Histopathogic evaluation showed marked decreases in amounts of residual tumor and inflammatory changes in the caffeic acid and ferulic acid groups when compared to the TAE group. Conclusion: Embolization with PVA and caffeic acid or ferulic acid provides a statistically significant improved tumor response compared to PVA alone in a rat N1S1 tumor model. Combination treatment through inhibition of both aerobic metabolism through embolization and inhibtion of anaerobic metabolism through lactate transport inhibition is a viable and effective treatment approach that shows great promise.

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