POSTER PRESENTATIONS RAS-dependent AKT signaling in RPK;Pdk1lox/lox mice revealed lower levels of hepatocyte proliferation in comparison to RPK mice and possibly impaired tumor formation in vivo. Conclusions: The RPK mouse model is a tool to investigate critical mechanisms in liver carcinogenesis to mimic activated RAS signaling found in many human hepatocellular and cholangiocarcinomas. Combination of MEK and PI3K/AKT inhibitors synergistically inhibited cell growth and survival in vitro. Furthermore, our data indicate that RAS driven AKT activation might be involved in tumor development in our in vivo model. Future studies will focus on the role of individual RAS effector pathways in tumor initiation, differentiation and metastasis development in vivo. THU-114 Hepatic tumour burden is reduced by endogenous overexpression of chemerin-157 E.M. Haberl1, R. Pohl1, L. Rein-Fischboeck1, T.S. Weiss2, C. Buechler1. 1 Internal Medicine I; 2University Children Hospital (KUNO), University Hospital Regensburg, Regensburg, Germany E-mail:
[email protected] Background and Aims: Hepatocellular carcinoma (HCC) is one of the most deadly malignancies and in many cases arises as a consequence of chronic liver diseases caused by viral infections, alcohol abuse and non-alcoholic fatty liver disease (NAFLD). The chemokine chemerin is produced by hepatocytes and reduced levels in human HCC tissues are associated with a worse prognosis. The chemoattractant activity of chemerin is suggested to contribute to the recruitment of immune cells which protects from tumour development and progression. Our aim was to increase active hepatic chemerin protein via adenoassociated virus 8 (AAV8) and to investigate its effect on HCC development in mice. Methods: Two week old C3H/HeNRj mice were injected with Diethylnitrosamine (DEN) to induce HCC. After six months mice were infected with 1012 AAV8 particles to achieve a liver specific overexpression of active chemerin (Chemerin-157). Afterwards, we examined the effect of increased Chemerin-157 expression on HCC development. Therefore, tumour number was quantified and the expression of endogenous chemerin in tumourous tissue compared to healthy liver tissue was analyzed. Results: DEN/AAV8-Chemerin-157-injected mice showed no differences in body and liver weight compared to the respective control infected mice. Serum chemerin levels tended to be higher in AAV8Chemerin-157-injected mice, while hepatic chemerin level was increased three times compared to the AAV8-control-injected mice. The quantification of single tumours in the liver showed, that thereby hepatic tumour burden was reduced by about 30%. Chemerin protein level in tumourous tissue of AAV8-control-injected mice was increased two-fold compared to healthy liver, while the level in tumourous tissue of AAV8-Chemerin-157-injected mice was similar to healthy liver. Analysis of tissues of 21 HCC patients by immunoblot showed higher chemerin expression in the tumour. Therefore, similar to human HCC, endogenous chemerin protein was increased upon cancer development. Conclusions: Increased hepatic Chemerin-157-expression limits growth of HCC. THU-115 Preclinical evaluation of polyethylenimine-mediated RNA interference of Polo-Like Kinase 1 gene for ultrasound imageguided treatment of hepatocellular carcinoma E. Heuillard1,2, G.B. About3, M. Goncalves1,2, F. Gosse1,2, V. Lindner4, T. Sorg3, R. Memeo2,4, Y. Herault3, P. Erbacher5, P. Pessaux2,4, T.F. Baumert2,4, E. Robinet1,2. 1IHU Strasbourg; 2U1110, INSERM; 3Mouse Clinical Institute; 4Strasbourg University Hospital; 5PolyPlus Transfection, Strasbourg, France E-mail:
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Background and Aims: Hepatocellular carcinoma (HCC) is the second cause of cancer death worldwide. Indeed, due to limited treatments options (surgical resection, liver transplantation, radiofrequency ablation or chemotherapy with Sorafenib), the 5-year overall survival rate is
