Citations

Accurate quantification of subtle wrist motion changes resulting from ligament injuries is crucial for diagnosis and prescription of the most effective interventions for preventing progression to osteoarthritis. Current imaging techniques are unable to detect injuries reliably and are static in nature, thereby capturing bone position information rather than motion which is indicative of ligament injury. A recently developed technique, 4D (three dimensions + time) computed tomography (CT) enables three-dimensional volume sequences to be obtained during wrist motion. The next step in successful clinical implementation of the tool is quantification and validation of imaging biomarkers obtained from the four-dimensional computed tomography (4DCT) image sequences. Measures of bone motion and joint proximities are obtained by: segmenting bone volumes in each frame of the dynamic sequence, registering their positions relative to a known static posture, and generating surface polygonal meshes from which minimum distance (proximity) measures can be quantified. Method accuracy was assessed during in vitro simulated wrist movement by comparing a fiducial bead-based determination of bone orientation to a bone-based approach. The reported errors for the 4DCT technique were: 0.00–0.68 deg in rotation; 0.02–0.30 mm in translation. Results are on the order of the reported accuracy of other image-based kinematic techniques.

Abstract The Polycomb repressive complex 2 (PRC2) is important for maintenance of stem cell pluripotency and suppression of cell differentiation by promoting histone H3 lysine 27 trimethylation (H3K27me3) and transcriptional repression of differentiation regulatory genes. Here we show that the tumor suppressor protein BRCA1 interacts with EZH2 and other components of PRC2 in mouse embryonic stem (ES) and human breast cancer cells. The BRCA1-binding region in EZH2 overlaps with the non-coding RNA (ncRNA)-binding domain, and BRCA1 expression inhibits the binding of EZH2 to the HOTAIR ncRNA. Decreased expression of BRCA1 causes EZH2 re-targeting genome wide and elevates H3K27me3 levels at PRC2 target loci in both mouse ES and human breast cancer cells. BRCA1 deficiency blocks ES cell differentiation and enhances breast cancer migration and invasion in an EZH2-dependent manner. These results reveal that BRCA1 is a key negative modulator of PRC2 and that loss of BRCA1 inhibits ES cell differentiation and enhances cancer aggressive phenotypes via augmented PRC2 function. Citation Format: Xianzhou Zeng, Shuai Chen, Lan Wang, Haojie Huang. BRCA1 is a negative modulator of the PRC2 complex. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5358. doi:10.1158/1538-7445.AM2013-5358