Results Pigs and surgery A total of twelve pigs survived the six week experiment, four PHx, four sham operated and four control animals. Pigs that died due to the extensive surgery
were CB-839 replaced: five pigs subject to PHx died, one due to ulcerative gastritis five days post PHx, and one due to blood loss, two days post PHx. Three pigs were terminated, one due to acute pericarditis eight days post PHx, one due to bile-leakage eight days post PHx, and one due to ingestion of foreign Selleck KPT 330 materials resulting in occlusion of the oesophagus, 23 days post PHx. One pig subjected to sham operation died due to acute peroperative heart failure during anaesthesia 24 days after primary surgery. All post mortem QNZ clinical trial examinations were performed by an independent official veterinarian at the National Veterinary Institute in Tromsø, Norway. Weight and volume of liver at termination By the end of the sixth week, the liver had fully regenerated in all PHx pigs. In control animals, the liver constituted 2.33% of total body mass, in sham animals the liver constituted 2.48% and in resected animals 2.78% of total body mass. Blood sample analysis We found a significant increase in albumin levels in the sham group at six
weeks post PHx. Bilirubin was under the detection level (2.2 mmol/l) for all animals at all time points except in one animal at three weeks with a value of 49 mmol/l. International Normalized Ratio (INR) was less than 1.1 for all animals at all time points. There were no significant time, group or time*group interaction for these analyses. No significant changes in Interleukin-1 (IL-1), Interleukin-10 enough (IL-10), Tumor necrosis factor-α
(TNF-α) or TGF-β were found. An increase in serum levels of Interleukin-6 (IL-6) was observed in resection group (not significant). Microarray analysis General trends By analysing contrasts between resection, sham and control groups using a false discovery rate (FDR) = 0.20, we found a total of 609 genes differentially expressed (362 genes by comparing control and sham, 215 genes by comparing control and resection, and 32 by comparing sham and resection pigs). Overall, more genes were found associated with the regulation of cell cycle and apoptosis in the liver remnants after PHx compared to livers in the control group. All differentially expressed genes regulating cell cycle and apoptosis are presented in Table 1. Table 1 Genes proposed to regulate cell cycle and apoptosis with specific functions according to Ace View[46] Resection Group Up-regulated Down-regulated Function 3-0 weeks PRKRA (0.8) Negative regulator of cell proliferation GSK3A (0.3) Negative regulator of cell proliferation IGFBP7 (0.9) Regulation of cell proliferation TIA1 (−1.8) Inducer of apoptosis 6-0 weeks ZNF490 (2.