Considerable expectations to prevent hepatocellular carcinoma (HCC) appearance are connecte with the use of Inferon alpha (IFN alpha) in antiviral treatment of the hepatitis B or C. Several studies have reported that the incidence of HCC may b reduced after IFN therapy in patients with chronic B or C hepatitis although its real preventive efffect is still debatable. The purpose of the studies from our laboratory was to evaluate the action of IFN alpha2b on preneoplastic foci in a two-phase model of preneoplasia development in rat. We demonstrated that IFN-alpha2b administration significantly decreased both number and volume percentage of altered hepatitis foci (AHF). This reduction could be explained by an induced programmed cell death in the foci. This apoptotic effect of IFN-alpha2b on preneoplastic liver foci was mediated by the production of endogenous TGFbeta1 from hepatocytes acting by a paracrine/autocrine way. Further studies confirmed that these results were a consequence of the perturbation of the redox status induced by the IFN-2b. In conclusion, IFN-alpha2b couldenhance the proapoptotic effects of TGFbeta1, in early stages of hepatocarcinogenesis, which could be highly beneficial in cancer therapy.
[Show abstract][Hide abstract] ABSTRACT: Oxidative DNA damage by reactive oxygen species is involved in the process of liver carcinogenesis. To test the hypothesis that a remedy containing Scutellaria baicalensis Georgi (Sb) and Bupleurum scorzonerifolfium Willd (Bs) (Sb/Bs remedy) modulates hepatic neoplastic growth, BOP (N-nitrosobis(2-oxopropyl)amine)-induced liver cancers in hamsters were established.
Parameters such as survival rate, tumour area, tumour foci, 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, transforming growth factor (TGF-beta1) and tumour necrosis factor-alpha (TNF-alpha) were measured after Sb/Bs remedy treatment during BOP-induced carcinogenesis.
The results showed that the Sb/Bs remedy and its constituents Sb and Bs suppressed the tumour area in BOP-induced liver tumours. Because selenium (Sel) is toxic at a high dose (10 mg/kg), with a low survival rate (0%), the combination of Sb/Bs remedy and low-dose Sel (1 mg/kg) was found to decrease the tumour area and the number of tumour foci while increasing serum TNF-alpha and TGF-beta1, but not IL-6 levels. Besides, the Sb/Bs remedy, when combined with low-dose Sel, not only decreased the expression of 8-OHdG and increased caspase-3 expression within the glutathione S-transferase placental form-positive tumour foci but also increased tumour apoptosis in BOP-induced hamsters.
We conclude that low-dose Sel has a chemoprevention effect on BOP-induced liver tumours and such an effect was more enhanced when combined with Sb/Bs treatment.
Liver international: official journal of the International Association for the Study of the Liver 04/2008; 28(6):841-55. DOI:10.1111/j.1478-3231.2008.01698.x · 4.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the role of HO-1 in HCC progression and to study the expression of apoptotic factors represented by TNF-alpha, and Fas-L versus antiapoptotic and angiogenic factors represented by HO-1, TGF-beta, HGF, and VEGF in HCC compared to non cancerous cirrhotic liver.
Liver biopsies were taken from twelve patients with grade II HCC confined to the liver and twelve patients with non cancerous liver cirrhosis (served as control). RT-PCR of previous genes was evaluated.
HO-1, VEGF, HGF, and TNF-alpha genes were significantly increased (P<0.05) in HCC compared to control. Fas-L showed a significant decrease (P<0.05) in HCC compared to control. TGF-beta was higher in HCC than control but the difference was not statistically significant (P>0.05). HGF showed significant positive correlation with HO-1 (r=0.8217, P=0.001).
HCC is associated with increased expression of VEGF, HGF, and TGF-beta, and with suppression of Fas-L. In addition, HO-1 is highly significantly expressed in HCC. The significant positive correlation between HO-1 and HGF was first reported in Egyptian human liver biopsies, and this suggests that it may play a role in the progression of hepatocellular carcinoma.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
We describe a new rat model of biliary atresia, induced by biliary ablation with pure ethanol.
A catheter was inserted and fixed in the common bile duct of male rats. Saline or pure ethanol was injected through the catheter and the animals were monitored for 8 weeks thereafter. We measured total bilirubin (T-Bil), aspartate aminotransferase (AST), alanine transaminase (ALT), and hyaluronic acid (HA) and examined liver biopsy specimens immunohistochemically for α-smooth muscle actin staining (α-SMA) and transforming growth factor-β1 (TGF-β1).
The ethanol injection group animals were further divided into a temporary and a persistent liver dysfunction group. In the persistent group, T-Bil, AST, ALT and HA levels were significantly higher after 8 weeks in the persistent group than in the control group and the temporary group. In the ethanol injection group, α-SMA expression was prominent in the surrounding proliferative bile ducts and portal areas. The distribution of TGF-β1 was found prominently in hepatocytes in the center of nodules and in ductular epithelial cells.
This study characterizes the effects of ethanol-induced bile duct injury in rats, resulting in sclerosing cholangitis and its secondary effects. We believe that this experimental model will prove useful in the study of biliary atresia.
Surgery Today 10/2012; 43(6). DOI:10.1007/s00595-012-0379-2 · 1.53 Impact Factor
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