Dec 21, 2017
Inhibition of Endosteal Vascular Niche Remodeling Rescues Hematopoietic Stem Cell Loss in AML
D. Duarte, E. D. Hawkins, O. Akinduro, H. Ang, K. De Filippo, I. Y. Kong, M. Haltalli, N. Ruivo, L. Straszkowski, S. J. Vervoort, C. McLean, T. S. Weber, R. Khorshed, C. Pirillo, A. Wei, S. K. Ramasamy, A. P. Kusumbe, K. Duffy, R. H. Adams, L. E. Purton, L. M. Carlin, C. Lo Celso , Cell Stem Cell , DOI: 10.1016/j.stem.2017.11.006
Bone marrow vascular niches sustain hematopoietic stem cells (HSCs) and are drastically remodeled in leukemia to support pathological functions. Acute myeloid leukemia (AML) cells produce angiogenic factors, which likely contribute to this remodeling, but anti-angiogenic therapies do not improve AML patient outcomes. Using intravital microscopy, we found that AML progression...
Dec 16, 2017
Evaluation of the human relevance of the constitutive androstane receptor-mediated mode of action for rat hepatocellular tumor formation by the synthetic pyrethroid momfluorothrin
Y. Okuda, M. Kushida, H. Kikumoto, Y. Nakamura, H. Higuchi, S. Kawamura, S. M. Cohen, B. G. Lake, T. Yamada , The Journal of Toxicological Sciences , DOI: 10.2131/jts.42.773
High dietary levels of the non-genotoxic synthetic pyrethroid momfluorothrin increased the incidence of hepatocellular tumors in male and female Wistar rats. Mechanistic studies have demonstrated that the mode of action (MOA) for momfluorothrin-induced hepatocellular tumors is constitutive androstane receptor (CAR)-mediated. In the present study, to evaluate the potential human carcinogenic...
Dec 12, 2017
The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort: an important resource for translational research in soft tissue sarcoma
L. Forker, P. Gaunt, S. Sioletic, P. Shenjere, R. Potter, D. Roberts, J. Irlam, H. Valentine, D. Hughes, A. Hughes, L. Billingham, R. Grimer, B. Seddon, A. Choudhury, M. Robinson, C. M. L. West , British Journal of Cancer , DOI: 10.1038/bjc.2017.430
Background: Despite high metastasis rates, adjuvant/neoadjuvant systemic therapy for localised soft tissue sarcoma (STS) is not used routinely. Progress requires tailoring therapy to features of tumour biology, which need exploration in well-documented cohorts. Hypoxia has been linked to metastasis in STS and is targetable. This study evaluated hypoxia prognostic markers...
Dec 12, 2017
The human, F-actin-based cytoskeleton as a mutagen sensor
N. M. Clark, C. A., G. Galindo, V. K. Patel, M. L. Parry, R. J. Stoll, J. M. Yavorski, E. P. Pinkason, E. M. Johnson, C. M. Walker, J. Johnson, W. J. Sexton, D. Coppola, G. Blanck , Cancer Cell International , DOI: 10.1186/s12935-017-0488-5
Background: Forty years ago the actin cytoskeleton was determined to be disrupted in fibroblasts from persons with DNA repair-defective, hereditary colon cancer, with no clear connection between the cytoskeleton and DNA repair defects at that time. Recently, the large number of sequenced genomes has indicated that mammalian mutagenesis has a...
Dec 11, 2017
Type, Frequency, and Spatial Distribution of Immune Cell Infiltrates in CNS Germinomas: Evidence for Inflammatory and Immunosuppressive Mechanisms
P. Zapka, E. Dörner, V. Dreschmann, N. Sakamato, G. Kristiansen, G. Calaminus, C. Vokuhl, I. Leuschner, T. Pietsch , Journal of Neuropathology & Experimental Neurology , DOI: 10.1093/jnen/nlx106
Central nervous system germinomas are characterized by a massive immune cell infiltrate. We systematically characterized these immune cells in 28 germinomas by immunophenotyping and image analysis. mRNA expression was analyzed by Nanostring technology and in situ RNA hybridization. Tumor infiltrating lymphocytes (TILs) were composed of 61.8% ± 3.1% (mean ±...