[Effects of angiogenesis inhibitor TNP-470 to suppress the recurrence in the liver remnant after partial hepatectomy for liver metastases in rabbits].
We investigated the effects of an angiogenesis inhibitor, TNP-470, in suppressing the recurrence in the liver remnant after partial hepatectomy for VX2 liver metastases model of rabbits. After inoculation of 1 x 10(6) VX2 tumor cells via the portal vein, the medial lobe of the liver was resected. Then, TNP-470 (7 mg/body/day) was infused (Group 1), or distilled water (Group 2), continuously via the mesenteric vein for a week. The control group received only infused distilled water via the mesenteric vein. Fourteen days after the tumor inoculation, there were 66.0 +/- 20.2 (mean +/- SD) metastatic colonies on the liver surface of control group, against 23.3 +/- 24.0 and 123.7 +/- 47.9 colonies in Group 1 and Group 2, respectively. There were significant differences between control group and Group 2, and between Group 1 and Group 2. We consider that the liver regeneration following hepatectomy might provoke tumor growth of occult metastases in the liver remnants. TNP-470 suppressed these growth by its anti-neovascular activity. And this effect reduced the number of metastatic colonies. Fourteen days after hepatectomy, the weights of the liver were no different among 3 groups. The BrdU Labeling Index was also no different between Group 1 and Group 2. TNP-470 did not suppress the regeneration of the liver remnant. We consider that the systemic side effects of TNP-470 might be made minimal, because this agent affects only on endothelial cells. These results suggest that the angiogenesis inhibitor TNP-470 is beneficial to suppress hepatic recurrence after partial hepatectomy for liver metastases without suppression of liver regeneration.
Mugitani
T
T
1st Dept. of Surgery, Kyoto Prefectural University of Medicine.
Taniguchi
H
H
Koishi
Y
Y
Masuyama
M
M
Tanaka
H
H
Koyama
H
H
Hoshima
M
M
Miyata
K
K
Takahashi
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D003510:Cyclohexanes; D006498:Hepatectomy; D008113:Liver Neoplasms / Q000098:blood supply* / Q000503:physiopathology / Q000556:secondary; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011817:Rabbits; D012717:Sesquiterpenes / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol