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The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model

Cited 24 time in Web of Science Cited 29 time in Scopus
Authors
Jae, Hwan Jun; Chung, Jin Wook; Park, Hee Sun; Lee, Min Jong; Kim, Hyo-Cheol; Chung, Hesson; Park, Jae Hyung; Yoon, Jung Hwan; Lee, Ki Chang
Issue Date
2009-12
Publisher
KOREAN RADIOLOGICAL SOC
Citation
KOREAN JOURNAL OF RADIOLOGY; Vol.10 6; 596-603
Keywords
Hepatocellular carcinoma3-BromopyruvateVX2 carcinomaIntraarterial chemotherapyHexokinase II inhibitor
Abstract
Objective: The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. Materials and Methods: This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. Results: The tumor necrosis rate was significantly higher in the high dose group (93% +/- 7.6 [mean +/- SD]) than that in the control group (48% +/- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +/- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +/- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Conclusion: Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method.
ISSN
1229-6929
Language
English
URI
http://hdl.handle.net/10371/78118
DOI
https://doi.org/10.3348/kjr.2009.10.6.596
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College of Medicine/School of Medicine (의과대학/대학원)Radiology (영상의학전공)Journal Papers (저널논문_영상의학전공)
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