Jun 21, 2017
WNT antagonists exhibit unique combinatorial antitumor activity with taxanes by potentiating mitotic cell death
M. M. Fischer, B. Cancilla, V. P. Yeung, F. Cattaruzza, C. Chartier, C. L. Murriel, J. Cain, R. Tam, C.-Y. Cheng, J. W. Evans, G. O’Young, X. Song, J. Lewicki, A. M. Kapoun, A. Gurney, W.-C. Yen, T. Hoey , Sciences Advances , DOI: 10.1126/sciadv.1700090
The WNT pathway mediates intercellular signaling that regulates cell fate in both normal development and cancer. It is widely appreciated that the WNT pathway is frequently dysregulated in human cancers through a variety of genetic and epigenetic mechanisms. Targets in the WNT pathway are being extensively pursued for the development...
Jun 20, 2017
Antitumor activity of indenoisoquinoline inhibitors of topoisomerase 1 (TOP1) via apoptosis and autophagocytosis pathways in animal models.
R. J. Kinders, A. B. Dull, D. Wilsker, A. LeBlanc, C. Mazcko, M. G. Hollingshead, R. E. Parchment, J. H. Doroshow , Journal of Clinical Oncology , DOI: 10.1200/JCO.2017.35.15_suppl.11588
Background: We performed pharmacodynamic biomarker analysis for response to a panel of three indenoisoquinolines (LMP776, LMP400 and NSC706744, J. Med. Chem. 49:7740, 2006) that have demonstrated anti-tumor activity in dogs. In preclinical xenograft models treated with indenoisoquinolines, we observed that gH2AX was not a useful biomarker for the biological activity...
Jun 19, 2017
Learning size adaptive local maxima selection for robust nuclei detection in histopathology images
N. Brieu, G. Schmidt , 2017 IEEE 14th International Symposium on Biomedical Imaging (ISBI 2017) , DOI: 10.1109/ISBI.2017.7950670
The detection of cells and nuclei is a crucial step for the automatic analysis of digital pathology slides and as such for the quantification of the phenotypic information contained in tissue sections. This task is however challenging because of high variability in size, shape and textural appearance of the objects...
Jun 12, 2017
Elimination of large tumors in mice by mRNA-encoded bispecific antibodies
C. R. Stadler, H. Bähr-Mahmud, L. Celik, B. Hebich, A. S. Roth, R. P. Roth, K. Karikó, Ö. Türeci, U. Sahin , nature medicine , DOI: 10.1038/nm.4356
The potential of bispecific T cell–engaging antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro–transcribed pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding...
Jun 12, 2017
MerTK as a therapeutic target in glioblastoma
J. Wu, L. N. Frady, R. E. Bash, S. M. Cohen, A. N. Schorzman, Y.-T. Su, D. M. Irvin, W. C. Zamboni, X. Wang, S. V. Frye M. G. Ewend, E. P. Sulman, M. R. Gilbert, H. S. Earp C. R. Miller , Neuro-Oncology , DOI: 10.1093/neuonc/nox111
Background: Glioma-associated macrophages and microglia (GAMs) are components of the glioblastoma (GBM) microenvironment that express MerTK, a receptor tyrosine kinase that triggers efferocytosis and can suppress innate immune responses. The aim of the study was to define MerTK as a therapeutic target using an orally bioavailable inhibitor, UNC2025.Methods: We examined...