6, p=0.07) and Edmondson grade 3/4 (OR 2.9, p=0.06) to correlate with S1 tumors. Predictive scores were significantly associated with S2 (p<0.001) and S3 (p<0.001) tumors in the validation set, suggesting that the histopathologic features can be used to classify HCC tumors into the 3 subclasses. Gene signatures of Hoshida HCC Subclass S1, cellular hypoxia pathway (which is known to promote lipogenesis), epithelial-mesenchymal transition,

TGF-p activation and oncoprotein YAP signaling were enriched in SH-CC (false discovery rate <0.05). Conclusions: Histopathologic features correlated well with molecular subclasses, and are accompanied with molecular pathway deregulations that potentially contribute to formation of the morphological characteristics. Selleck BYL719 Multivariable model of histopathologic features may serve as a clinical tool to predict molecular subclass of HCC, which could find more inform therapeutic decision in clinic. Disclosures: The following people have nothing to disclose: Poh Seng Tan, Anu Venkatesh, Stephen C. Ward, Claudia

Canasto-Chibuque, Anna Koh, Venugopalan Nair, Manjeet Deshmukh, Shigeki Nakagawa, Xiaochen Sun, Masahiro Kobayashi, Hiromitsu Kumada, Yujin Hoshida Background: Recent evidence suggests that some hepatocellular carcinomas (HCCs) are hierarchically organized, with a subset of cells that possess stem cell features, called cancer stem cells (CSCs). CSCs show chemoresistance to cytotoxic reagents and are MCE considered to be

critical targets for the eradication of HCC. In this study, we evaluate the effect of a novel compound, TPU0114, on cell growth and CSC features in HCC. TPU0114 is derived from a strain of Streptomyces bacteria with a low 16S rRNA gene identity with other known species. Methods: Huh1 and Huh7 cells were routinely cultured with Dulbecco’s modified eagle medium supplemented with 10% fetal bovine serum. Cell proliferation and tumorigenicity were evaluated using MTS and spheroid formation assays, respectively. Western blotting was used to evaluate the expression of phospho-NF-kB p65 and Bcl-xl. Apoptosis was assessed by Caspase 3 activation and Annexin-V staining. Fluorescence-activated cell sorting was used to evaluate the expression of the CSC markers EpCAM and CD133. Time-lapse imaging was used to monitor cell motility. 5-FU and TPU0114 were obtained from Kyowa Kirin and Bio Technical Research Industry, respectively. Results: Both TPU0114 and 5-FU suppressed the proliferation and motility of Huhl and Huh7 cells at concentrations of 1-10 μg/ml. Interestingly, 5-FU treatment (2.5 μg/ml) resulted in an enrichment of EpCAM+ CD133+ CSCs, whereas TPU0114 treatment (5 μg/ ml) showed no such effect in Huh1 or Huh7 cells. This suggests that TPU0114 may suppress the proliferation of CSCs and non-CSCs equally well. Furthermore, TPU0114 treatment reduced the spheroid-forming capacity of Huh7 cells and increased the number of Annexin-V- and activated Caspase 3-positive cells.