Cross-sectional and longitudinal evaluation of liver volume and total liver fat burden in adults with nonalcoholic steatohepatitis

PURPOSE: To explore the cross-sectional and longitudinal relationships between fractional liver fat content, liver volume, and total liver fat burden. METHODS: In 43 adults with non-alcoholic steatohepatitis participating in a clinical trial, liver volume was estimated by segmentation of magnitude-based low-flip-angle multiecho GRE images. The liver mean proton density fat fraction (PDFF) was calculated. The total liver fat index (TLFI) was estimated as the product of liver mean PDFF and liver volume. Linear regression analyses were performed. RESULTS: Cross-sectional analyses revealed statistically significant relationships between TLFI and liver mean PDFF (R(2) = 0.740 baseline/0.791 follow-up, P < 0.001 baseline/P < 0.001 follow-up), and between TLFI and liver volume (R(2) = 0.352/0.452, P < 0.001/< 0.001). Longitudinal analyses revealed statistically significant relationships between liver volume change and liver mean PDFF change (R(2) = 0.556, P < 0.001), between TLFI change and liver mean PDFF change (R(2) = 0.920, P < 0.001), and between TLFI change and liver volume change (R(2) = 0.735, P < 0.001). CONCLUSION: Liver segmentation in combination with MRI-based PDFF estimation may be used to monitor liver volume, liver mean PDFF, and TLFI in a clinical trial

Targeting EZH2-mediated methylation of H3K27 inhibits proliferation and migration of Synovial Sarcoma in vitro

Synovial sarcoma is an aggressive soft tissue sarcoma genetically defined by the fusion oncogene SS18-SSX. It is hypothesized that either SS18-SSX disrupts SWI/SNF complex inhibition of the polycomb complex 2 (PRC2) methyltransferase Enhancer of Zeste Homologue 2 (EZH2), or that SS18-SSX is able to directly recruit PRC2 to aberrantly silence target genes. This is of potential therapeutic value as several EZH2 small molecule inhibitors are entering early phase clinical trials. In this study, we first confirmed EZH2 expression in the 76% of human synovial sarcoma samples. We subsequently investigated EZH2 as a therapeutic target in synovial sarcoma in vitro. Knockdown of EZH2 by shRNA or siRNA resulted in inhibition of cell growth and migration across a series of synovial sarcoma cell lines. The EZH2 selective small-molecule inhibitor EPZ005687 similarly suppressed cell proliferation and migration. These data support the hypothesis that targeting EZH2 may be a promising therapeutic strategy in the treatment of synovial sarcoma; clinical trials are initiating enrollment currently