COX-2 immunostaining on HCC (upper left, marked with *) and adjacent liver parenchyma (lower right, marked with @).

<p>COX-2 expression is present on endothelial cells (arrows) at the interface between HCC and non-tumorous liver parenchyma. In the liver parenchyma COX-2 expression is mainly present in Kupffer cells and some inflammatory cells. Note the absence of staining in hepatocytes and tumor cells. The insert (lower right hand corner) shows COX-2 immunostaining on coloncarcinoma as a positive control.</p

Clinicopathological characteristics of the cirrhotic and noncirrhotic patient group.

1<p>α1-antitrypsin deficiency (n = 2); glycogenosis type III (n = 1); tyrosinemia (n = 2).</p

Example of representative cases analysed in this study showing Western blot of COX-2 in matched pairs of 11 noncirrhotic (upper panel) and 8 cirrhotic (lower panel) samples of HCC and tumor-adjacent liver parenchyma.

<p>(Adj: tumor-adjacent liver parenchyma; T: tumor (HCC)).</p

Plots representing relative expression of COX-2 mRNA (A), COX-2 protein (B), miR-16 (C), miR-21 (D) and miR-101 (E) in in normal liver, HCC tumor tissue (T) and tumor-adjacent parenchyma (Ad) in noncirrhotic and in cirrhotic liver.

<p>Median values and 25^th–75^th percentiles are shown. P-values: *<0.05; **<0.01; ***<0.001.</p

Biliary parameters during intravenous taurocholic acid (TCA) administration.

<p>Biliary bile flow (A), bile salt concentration (B), bile salt secretion rate (C) and relationship between bile salt secretion rate and bile flow (D) in Cftr knockout mice (<i>Cftr</i>^<i>—/</i>) and control littermates (<i>Cftr</i>^<i>+/+</i>) during intravenous infusion with TCA in stepwise increasing dosage of. The gray symbols in (D) represent baseline values before the start of TCA infusion. Data are presented as means ± SEM of N = 5–7 mice per group. There was no significant difference between <i>Cftr</i>^<i>-/-</i> and <i>Cftr</i>^<i>+/+</i> mice, at any of the individual time points, for bile flow, bile salt concentration and bile salt secretion rate (regression lines:. <i>Cftr</i>^<i>-/-</i>: y = 0.0044x + 7.9 vs. <i>Cftr</i>^<i>+/+</i>: y = 0.0037x + 6.0).</p

Liver histology of Cftr knockout mice (Cftr^-/-) and controls, fed a control diet or a cholic acid (CA) containing diet for 3 weeks.

<p>Liver histology (magnification 40x) of <i>Cftr</i> knockout mice (<i>Cftr</i>^<i>-/-</i>) and control littermates (<i>Cftr</i>^<i>+/+</i>) after a control or 0.5%-CA containing diet for three weeks. Liver slices with HE staining (panels: A-D), or Ki67 staining on HE staining background (panels: E-H). The white arrows, pointing at Ki67 positive cells indicate active cell proliferation in parenchymal and portal areas.</p

Body and liver weights in Cftr knockout, ΔF508 Cftr and control mice, fed a control diet or a cholic acid (CA) containing diet for 3 weeks.

<p>Body weight (A, B), absolute liver weight (C,D) and relative liver weight reported as a percentage of the body weight (E, F) in <i>Cftr</i> knockout mice (<i>Cftr</i>^<i>-/-</i>, panels A. C and E) or ΔF508 <i>Cftr</i> mice (<i>Cftr</i>^tm1EUR, panels B, D and F) and their respective control littermates (<i>Cftr</i>^<i>+/+</i>), after a control or 0.5%-CA (wt/wt) chow diet for three weeks. Data are presented as means ± SEM of N = 5–7 mice per group. *P-value<0.05.</p

Liver histology in Cftr knockout mice (Cftr^-/-) and controls, fed a control diet or a cholic acid (CA) containing diet for 3 weeks or for 3 months.

<p>Histological evaluation of liver parenchymal inflammation (A), parenchymal Ki67 activity (B), portal inflammation (C), and portal Ki67 activity (D), in Cftr knockout mice (<i>Cftr</i>^<i>-/-</i>) and control littermates (<i>Cftr</i>^<i>+/+</i>) after a control diet, a 0.5%-CA (wt/wt) chow diet for three weeks, or a 0.5%-CA (wt/wt) chow diet for three months. Histology was scored in a blinded and semi-quantitative fashion using an ordinal scale (0: absent; 1: sporadic; 2: regular; 3: frequent). All results are presented individually per mouse; the horizontal black line represents the median of N = 5–7 mice per group. *P-value<0.05.</p

Biliary parameters and bile composition of Cftr knockout mice (Cftr^-/-) and controls, fed a control diet or a cholic acid (CA) containing diet for 3 weeks.

<p>Biliary bile flow (A), bile salt concentration (B), bile salt secretion rate (C), phospholipid concentration (D), phospholipid-to-bile salt ratio (E), serum ALT levels (F), percent contribution to total biliary bile salts of cholate, deoxycholate and others (chenodeoxycholate, ursodeoxcholate, α-muricholate and β-muricholate) (G), and, Heuman index of biliary bile salts representing the hydrophobicity (H), in Cft<i>r</i> knockout mice (<i>Cftr</i>^<i>-/-</i>) and control littermates (<i>Cftr</i>^<i>+/+</i>) after a control or 0.5%-CA (wt/wt) chow diet for three weeks. Data are presented as means ± SEM or percentage (panel G) of N = 5–7 mice per group. *P-value<0.05.</p

Parameters of hepatocellular secretory function of DCD livers that were preserved by either 4 h of oxygenated HMP or SCS and subsequently reperfused for 2 <b>h by normothermic </b><i>ex vivo</i> sanguineous perfusion.

<p><i>Panel A</i>: Evolution of bile production in the HMP and SCS group. <i>Panel B and C</i>: Biliary concentration of bile salts and phospholipids, respectively. <i>Panel D</i>: Bile salt toxicity, as represented by the ratio of biliary bile salt and phospholipid concentrations. There were no statistically significant differences between the groups. <i>Panel E–F</i>: Relative mRNA expression of the main hepatocellular bile transporters BSEP (bile salt export pump; Abcb11) and MDR3 (multidrug resistance protein 3, Abcb4) after 2 h of <i>ex vivo</i> sanguineous reperfusion of DCD livers that were preserved by either 4 h of oxygenated HMP or SCS. There were no significant differences between the two groups.</p