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Isolated liver perfusion permits administration of high doses of chemotherapeutic agents. Comparison with hepatic artery infusion

Thorlacius, Henrik LU ; Larmark, Mona LU ; Randell, M; Hultberg, Björn LU and Jeppsson, Bengt LU (2001) In European Surgical Research 33(5-6). p.342-347
Abstract
Tumor cells are dependent on glutamine metabolism and acivicin, which is a selective glutamine antagonist, has been shown to effectively retard tumor growth in several malignancies. However, systemic treatment with acivicin is associated with significant side effects. The purpose of the present study was to examine whether use of an in vivo isolated liver perfusion model may allow administration of lethal doses of acivicin and compare it to regional infusion of acivicin in the hepatic artery. Five days after tumor inoculation, acivicin was administered by an isolated liver perfusion model or by regional infusion via the hepatic artery. It was found that regional infusion of acivicin (5 and 10 mg/kg) via the hepatic artery caused systemic... (More)
Tumor cells are dependent on glutamine metabolism and acivicin, which is a selective glutamine antagonist, has been shown to effectively retard tumor growth in several malignancies. However, systemic treatment with acivicin is associated with significant side effects. The purpose of the present study was to examine whether use of an in vivo isolated liver perfusion model may allow administration of lethal doses of acivicin and compare it to regional infusion of acivicin in the hepatic artery. Five days after tumor inoculation, acivicin was administered by an isolated liver perfusion model or by regional infusion via the hepatic artery. It was found that regional infusion of acivicin (5 and 10 mg/kg) via the hepatic artery caused systemic illness and diarrhea, and all animals in this group died within 3 days. In contrast, we observed no signs of systemic illness, diarrhea or hepatocellular injury in rats receiving isolated liver perfusion with or without acivicin (10 mg/kg) administration. Noteworthy, we found that isolated perfusion with acivicin reduced the glutamine content in liver tumors by 39% compared to perfusion with control medium. In line with this, it was found that isolated perfusion with acivicin (10 mg/kg) inhibited tumor growth in the liver. Taken together, this study suggests that application of the isolated liver perfusion model avoids the toxic and lethal effects of high doses of chemotherapy, herein acivicin, and may provide a useful approach to treat liver tumors in vivo. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Local perfusion, Acivicin, Glutamine, Liver, Tumor
in
European Surgical Research
volume
33
issue
5-6
pages
342 - 347
publisher
Karger
external identifiers
  • pmid:11805394
  • scopus:0035704311
ISSN
0014-312X
DOI
language
English
LU publication?
yes
id
d7d83a90-ee52-47c3-9b12-6ac547ae629c (old id 1122494)
date added to LUP
2008-07-16 10:19:07
date last changed
2018-05-29 09:37:30
@article{d7d83a90-ee52-47c3-9b12-6ac547ae629c,
  abstract     = {Tumor cells are dependent on glutamine metabolism and acivicin, which is a selective glutamine antagonist, has been shown to effectively retard tumor growth in several malignancies. However, systemic treatment with acivicin is associated with significant side effects. The purpose of the present study was to examine whether use of an in vivo isolated liver perfusion model may allow administration of lethal doses of acivicin and compare it to regional infusion of acivicin in the hepatic artery. Five days after tumor inoculation, acivicin was administered by an isolated liver perfusion model or by regional infusion via the hepatic artery. It was found that regional infusion of acivicin (5 and 10 mg/kg) via the hepatic artery caused systemic illness and diarrhea, and all animals in this group died within 3 days. In contrast, we observed no signs of systemic illness, diarrhea or hepatocellular injury in rats receiving isolated liver perfusion with or without acivicin (10 mg/kg) administration. Noteworthy, we found that isolated perfusion with acivicin reduced the glutamine content in liver tumors by 39% compared to perfusion with control medium. In line with this, it was found that isolated perfusion with acivicin (10 mg/kg) inhibited tumor growth in the liver. Taken together, this study suggests that application of the isolated liver perfusion model avoids the toxic and lethal effects of high doses of chemotherapy, herein acivicin, and may provide a useful approach to treat liver tumors in vivo.},
  author       = {Thorlacius, Henrik and Larmark, Mona and Randell, M and Hultberg, Björn and Jeppsson, Bengt},
  issn         = {0014-312X},
  keyword      = {Local perfusion,Acivicin,Glutamine,Liver,Tumor},
  language     = {eng},
  number       = {5-6},
  pages        = {342--347},
  publisher    = {Karger},
  series       = {European Surgical Research},
  title        = {Isolated liver perfusion permits administration of high doses of chemotherapeutic agents. Comparison with hepatic artery infusion},
  url          = {http://dx.doi.org/},
  volume       = {33},
  year         = {2001},
}