ALBERT

Description: Article APC is a well-known tumour suppressor that is frequently inactivated in colorectal cancer. Here, the authors sequence more than 1000 cancer genes in 468 colorectal cancers and show that mutation signatures can be used to classify the tumours and that multiple mutations in APC are associated with a poor prognosis. Nature Communications doi: 10.1038/ncomms11743 Authors: Michael J. Schell, Mingli Yang, Jamie K. Teer, Fang Yin Lo, Anup Madan, Domenico Coppola, Alvaro N. A. Monteiro, Michael V. Nebozhyn, Binglin Yue, Andrey Loboda, Gabriel A. Bien-Willner, Danielle M. Greenawalt, Timothy J. Yeatman

Description: MicroRNA are a series of small non-coding RNAs that have emerged as critical regulators of skeletal muscle development. Here, we concentrated on the function of miR-660 during bovine skeletal myogenesis from our previous high-throughput sequencing results, then analyzed its expression profiles and characterized related functional roles. Overexpression of miR-660 significantly attenuated myogenic differentiation of C2C12 cells, whereas miR-660 inhibition enhanced C2C12 differentiation. Dual-Luciferase Reporter Assay went for demonstrating that miR-660 directly targeted the 3'-UTR of Rho guanine nucleotide exchange factor 12(ARHGEF-12). Furthermore, we found an inverse relationship between the expression of miR-660 and ARHGEF12 in both gain- and loss-of-function studies: overexpression of miR-660 declined the mRNA and protein expressions of ARHGEF12 in C2C12 cells differentiation, however, knockdown of miR-660 had completely opposite results. Taken together, these results offered a new perspective for miR-660 in skeletal muscle differentiation. This article is protected by copyright. All rights reserved

Description: Abstract 4975 Background: Our group has developed a peptide referred to as HYD1 which binds VLA-4 integrin/CD44 containing complex and induces necrotic cell death in myeloma cells (Nair et al Mol Cancer Ther 2009, Emmons et al, Mol Cancer Ther, 2011). Furthermore, we previously demonstrated in a small subset of MM patients that HYD1 was more active in specimens obtained from relapsed/refractory patients, a finding that correlated with VLA-4 expression. The frequency of expression and prognostic significance of two key surface markers VLA4 (very late antigen 4) and CD44 in patients with MM remains poorly defined. Methods: We retrospectively reviewed records of patients with MM who had a complete flow cytometry panel (which includes assessment for CD44 and VLA4) at Moffitt Cancer Center between 1/1/2004 and 12/31/2009. CD44 and VLA4 were gated by CD138 expression and we categorized expression as negative, dim, moderate or bright. We collected demographic information, disease related characteristics (including ISS stage, cytogenetics, and baseline laboratory testing) and treatment and outcomes related data (prior therapies, response to first line therapy, follow up and vital status). Responses were per IMWG criteria and for the purpose of this study, a partial remission or better qualified as a response to therapy. High risk cytogenetics (HRC) was defined by the presence of one of the following; 17p deletion, t(4;14), t(14;16) and 13q deletion by metaphase cytogenetics. The study was approved by the IRB at the University of South Florida. Results: A four color flow cytometry panel was available for review on 101 myeloma patients including 57 males, median age at diagnosis was 60 (range 39–83) years. The percentage of ISS stage I, II and III at diagnosis was 36. 4%, 34. 8% and 28. 8% respectively and 28. 7% of the patients had HRC. At the time of the flow panel, 32 patients (31. 7%) were untreated and overall patients had a median of 3 prior therapies (range 0–11). 52 patients (51. 5%), 37 (36. 6%) and 12 (11. 9%) had no, dim or moderate CD44 expression respectively while 26 (26. 3%), 68 (68. 7%) and 5 (5. 1%) had no, dim or moderate VLA4 expression respectively. Subsequently both were sub-grouped according to presence (dim or greater) or absence of expression. A correlation between the expression of CD44 and VLA4 was noted (Fisher's exact p 〈 0. 001), 45 patients express both markers, 24 express neither markers, 28 express VLA4 but not CD44 while only 4 express CD44 and not VLA4 (p