Isolated hepatic perfusion (IHP) with melphalan is used for patients with nonresectable metastases confined to the liver. To improve the efficacy of IHP and to reduce the toxicity to the liver, reversion (retrograde perfusion) of the bloodstream through the liver in a rat model was studied. For liver tumor induction male WAG/Rij rats were inoculated with CC531 cells, a colorectal tumor cell lin...

imatinib is an orally administered tyrosine kinase inhibitor which inhibits the bcr-abl protein-tyrosine kinase with high selectivity. imatinib is rapidly absorbed from the gut, after oral intake and has an almost absolute bioavailability of 98%. the metabolism of imatinib is mediated by the cytochrome p450 (cyp) isoenzymes in the liver and gut wall. cgp74588 is a major active metabolite of ima...

SOME malignancies of the extremities can be treated by hyperthermic isolated limb chemotherapy. This procedure involves arterial and venous cannulation of the affected limb and isolated perfusion using a bypass pump. When a steady state is reached, the blood is warmed and oxygenated, and a chemotherapeutic agent (e.g., melphalan) is added and circulated in the limb for up to 1 h. Because the li...

Since in the usual perfusion of isolated rat liver via the portal vein an insulin-dependent increase of hepatic glucose uptake could not be demonstrated, the possibility was considered that hepatic glucose uptake might not be a function of the absolute concentration of this substrate but of its concentration gradient between the portal vein and the hepatic artery. Therefore a new method was est...

Stem cell‑derived hepatocyte precursor cells represent a promising model for clinical transplantation to diseased livers, as well as for establishment of in vitro systems for drug metabolism and toxicology studies. The present study aimed to establish a new method of induction of hepatocyte differentiation using various factors and evaluate the effect of different partial hepatectomies and the ...

We had prepared earlier a prokaryotic-expressed tumor necrosis factor-alpha (TNF-[alpha]) mutant that exhibited a higher antitumor activity and a lower systemic toxicity compared with that of wild-type TNF-[alpha] in both syngeneic murine tumor models and human tumor xenografts models. For its clinical use as an antitumor agent, we evaluated repeated-dose toxicity, anaphylaxis, genetic toxicity...