Methods: Hepatocytes in six high-grade DNs of two cases with HBV-related liver cirrhosis were separated by laser microdissection. Genomic DNA of the separated DNs was extracted with commercial kit. By using the Roche NimbleGen 720K array, array CGH was carried out for analysis of genomic profile changes in the high-grade DNs. The loci with genomic imbalance observed most frequently in DNs were further analyzed the frequency in 83 cases of HCC by using conventional assays such as differential PCR and realtime quantitative PCR. Results: array-CGH analysis revealed that the most genomic imbalances in the high-grade Akt inhibitor DNs are genomic losses of small segments,

with loss of heterozygosity (LOH) at 5q13.2 and 8p23.1 observed most frequently. LOH at 5q13.2 has not been reported frequently observed in HCC and the detection of 5q13.2 in 83 cases of HCC showed 36.1% of HCCs with LOH at 5q13.2, where a series of functional important genes harbored such as general transcription factor IIH subunit 2 (GTF2H2), a gene involved in the development of breast cancer reported previously. LOH at 8p23.1 has already been reported frequently observed in HCC by other studies, and the detection of 8p23.1 Selleckchem GSK3235025 in 83 cases of HCC showed the frequency of LOH at D8S1130 and D8S503 were 61.29% and 68.4%

respectively, similar as the previous studies. Conclusion: LOH at 5q13.2 and 8p23.1 in the dysplastic hepatocytes of cirrhotic liver are common events in hepatocel-lular carcinoma. Chromosome abnormalities maybe occur and accumulate in preneoplastic lesions of liver cirrhosis. Disclosures: The following people have nothing to disclose: Zhang Zhao, Guang-Yong Chen, Jiang Long, Jian Huang Background: Sorafenib is the only systemic therapy approved for advanced hepatocellular 上海皓元 carcinoma (HCC). Sorafenib is a VEGFR, p38MAPK and B/C-RAF tyrosine kinase inhibitor. While mutations in KRAS or BRAF are very rare in HCC, sorafenib’s efficacy has been attributed in

part to inhibition of cell proliferation through blockade of the MAPK pathway. However, the benefits remain limited, presumably due to complex and yet unclear resistance mechanisms that promote treatment evasion. Methods: We used a panel of human and and murine HCC cell lines for in vitro studies. For in vivo studies, we used carcinogen-induced (CCL4/EtOH), GEMM (Ad5CMVCre injection in MST1−/−MST2-/F mice), and orthotopic human xenograft models in mice. Tumor growth was monitored by high-frequency ultrasound. Mice were treated with sorafenib (oral gavage, 50 mg/kg/day) and ERK activation was inhibited with selumetinib (oral gavage 50 mg/kg/b.i.d.). Results: In vitro assays showed variable cytotoxicity of sorafenib in human and murine HCC cell lines. We examined whether HCC sensitivity correlated with MAPK activity. At baseline, the activation of p38MAPK, but not ERK phosphorylation was detectable in the cell lines tested.