Jan 3, 2018
Palbociclib synergizes with BRAF and MEK inhibitors in treatment naïve melanoma but not after the development of BRAF inhibitor resistance
C. A. Martin, C. Cullinane, L. Kirby, S. Abuhammad, E. J. Lelliott, K. Waldeck, R. J. Young, N. Brajanovski, D. P. Cameron, R. Walker, E. Sanij, G. Poortinga, R. D. Hannan, R. B. Pearson, R. J. Hicks, G. A. McArthur, K. E. Sheppard , International Journal of Cancer , DOI: 10.1002/ijc.31220
Increased CDK4 activity occurs in the majority of melanomas and CDK4/6 inhibitors in combination with BRAF and MEK inhibitors are currently in clinical trials for the treatment of melanoma. We hypothesize that the timing of the addition of CDK4/6 inhibitors to the current BRAF and MEK inhibitor regime will impact...
Dec 21, 2017
Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1
M. Cifdaloz, L. Osterloh, O. Graña, E. Riveiro-Falkenbach, P. Ximénez-Embún, J. Muñoz, C. Tejedo, T. G. Calvo, P. Karras, D. Olmeda, B. Miñana, G. Gómez-López, E. Cañon, E. Eyras, H. Guo, F. Kappes, P. L. Ortiz-Romero, J. L. Rodríguez-Peralto, D. Megías, J. Valcárcel, M. S. Soengas , nature communications , DOI:10.1038/s41467-017-02353-y
Melanomas are well-known for their altered mRNA expression profiles. Yet, the specific contribution of mRNA binding proteins (mRBPs) to melanoma development remains unclear. Here we identify a cluster of melanoma-enriched genes under the control of CUGBP Elav-like family member 1 (CELF1). CELF1 was discovered with a distinct prognostic value in...
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 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 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 ±...