Limits...
The antitumor effect and hepatotoxicity of a hexokinase II inhibitor 3-bromopyruvate: in vivo investigation of intraarterial administration in a rabbit VX2 hepatoma model.

Jae HJ, Chung JW, Park HS, Lee MJ, Lee KC, Kim HC, Yoon JH, Chung H, Park JH - Korean J Radiol (2009 Nov-Dec)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center and Clinical Research Institute, Seoul National University Hospital, Korea.

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.

Show MeSH

Related in: MedlinePlus

Biochemical analysis of liver enzymes; mean values of liver enzymes in each group. Line graph shows that aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels tended to transiently increase at one day after intraarterial administration and they decreased to levels close to normal at seven days. Levels of AST and ALT of high dose 3-BrPA group and Lipiodol-doxorubicin emulsion group were significantly elevated as compared to those levels of control group at one day, whereas those levels of low dose 3-BrPA group did not show statistically significant difference as compared with those levels of control group. There was also no significant difference between both AST and ALT enzyme levels of high dose 3-BrPA group and those of Lipiodol-doxorubicin emulsion group.A. AST levels.B. ALT levels.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2770822&req=5

Figure 4: Biochemical analysis of liver enzymes; mean values of liver enzymes in each group. Line graph shows that aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels tended to transiently increase at one day after intraarterial administration and they decreased to levels close to normal at seven days. Levels of AST and ALT of high dose 3-BrPA group and Lipiodol-doxorubicin emulsion group were significantly elevated as compared to those levels of control group at one day, whereas those levels of low dose 3-BrPA group did not show statistically significant difference as compared with those levels of control group. There was also no significant difference between both AST and ALT enzyme levels of high dose 3-BrPA group and those of Lipiodol-doxorubicin emulsion group.A. AST levels.B. ALT levels.

Mentions: Figure 4 shows the plasma (AST) level and the plasma level (ALT) before and at 1, 2 and 7 days after intraarterial administration. For both AST and ALT, the enzyme levels were elevated at the first day and then they decreased to levels close to normal at seven days after intraarterial administration. The levels of AST and ALT in the high dose 3-BrPA group and the Lipiodol-doxorubicin emulsion group were significantly elevated compared to those levels of the control group at one day (Kruskal-Wallis test, p < 0.05), whereas those levels of the low dose 3-BrPA group did not show a statistically significant difference compared with those levels of the control group (p > 0.05). There was also no significant difference between both the AST and ALT enzyme levels of the high dose 3-BrPA group and those levels of the Lipiodol-doxorubicin emulsion group (p > 0.05).


The antitumor effect and hepatotoxicity of a hexokinase II inhibitor 3-bromopyruvate: in vivo investigation of intraarterial administration in a rabbit VX2 hepatoma model.

Jae HJ, Chung JW, Park HS, Lee MJ, Lee KC, Kim HC, Yoon JH, Chung H, Park JH - Korean J Radiol (2009 Nov-Dec)

Biochemical analysis of liver enzymes; mean values of liver enzymes in each group. Line graph shows that aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels tended to transiently increase at one day after intraarterial administration and they decreased to levels close to normal at seven days. Levels of AST and ALT of high dose 3-BrPA group and Lipiodol-doxorubicin emulsion group were significantly elevated as compared to those levels of control group at one day, whereas those levels of low dose 3-BrPA group did not show statistically significant difference as compared with those levels of control group. There was also no significant difference between both AST and ALT enzyme levels of high dose 3-BrPA group and those of Lipiodol-doxorubicin emulsion group.A. AST levels.B. ALT levels.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2770822&req=5

Figure 4: Biochemical analysis of liver enzymes; mean values of liver enzymes in each group. Line graph shows that aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels tended to transiently increase at one day after intraarterial administration and they decreased to levels close to normal at seven days. Levels of AST and ALT of high dose 3-BrPA group and Lipiodol-doxorubicin emulsion group were significantly elevated as compared to those levels of control group at one day, whereas those levels of low dose 3-BrPA group did not show statistically significant difference as compared with those levels of control group. There was also no significant difference between both AST and ALT enzyme levels of high dose 3-BrPA group and those of Lipiodol-doxorubicin emulsion group.A. AST levels.B. ALT levels.
Mentions: Figure 4 shows the plasma (AST) level and the plasma level (ALT) before and at 1, 2 and 7 days after intraarterial administration. For both AST and ALT, the enzyme levels were elevated at the first day and then they decreased to levels close to normal at seven days after intraarterial administration. The levels of AST and ALT in the high dose 3-BrPA group and the Lipiodol-doxorubicin emulsion group were significantly elevated compared to those levels of the control group at one day (Kruskal-Wallis test, p < 0.05), whereas those levels of the low dose 3-BrPA group did not show a statistically significant difference compared with those levels of the control group (p > 0.05). There was also no significant difference between both the AST and ALT enzyme levels of the high dose 3-BrPA group and those levels of the Lipiodol-doxorubicin emulsion group (p > 0.05).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center and Clinical Research Institute, Seoul National University Hospital, Korea.

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.

Show MeSH
Related in: MedlinePlus