Nov 2, 2017
Nonsteroidal Anti-Inflammatory Drug-Induced Leaky Gut Modeled Using Polarized Monolayers of Primary Human Intestinal Epithelial Cells
A. P. Bhatt, D. B. Gunasekara, J. Speer, M. I. Reed, A. N. Peña, B. R. Midkiff, S. T. Magness, S. J. Bultman, N. L. Allbritton, M. R. Redinbo , ACS Infectious Diseases , DOI: 10.1021/acsinfecdis.7b00139
The intestinal epithelium provides a critical barrier that separates the gut microbiota from host tissues. Nonsteroidal anti-inflammatory drugs (NSAIDs) are efficacious analgesics and antipyretics and are among the most frequently used drugs worldwide. In addition to gastric damage, NSAIDs are toxic to the intestinal epithelium, causing erosions, perforations, and longitudinal...
Nov 2, 2017
Modulation of telomere protection by the PI3K/AKT pathway
M. Méndez-Pertuz, P. Martínez, C. Blanco-Aparicio, E. Gómez-Casero, A. B. García, J. Martínez-Torrecuadrada, M. Palafox, J. Cortés, V. Serra, J. Pastor, M. A. Blasco , nature communications , DOI: 10.1038/s41467-017-01329-2
Telomeres and the insulin/PI3K pathway are considered hallmarks of aging and cancer. Here, we describe a role for PI3K/AKT in the regulation of TRF1, an essential component of the shelterin complex. PI3K and AKT chemical inhibitors reduce TRF1 telomeric foci and lead to increased telomeric DNA damage and fragility. We...
Oct 30, 2017
Akt inhibition improves long‐term tumour control following radiotherapy by altering the microenvironment
E. J. Searle, B. A. Telfer, D. Mukherjee, D. M. Forster, B. R. Davies, K. J. Williams, I. J. Stratford, T. M. Illidge , EMBO Mol Med , DOI: 10.15252/emmm.201707767
Radiotherapy is an important anti‐cancer treatment, but tumour recurrence remains a significant clinical problem. In an effort to improve outcomes further, targeted anti‐cancer drugs are being tested in combination with radiotherapy. Here, we have studied the effects of Akt inhibition with AZD5363. AZD5363 administered as an adjuvant after radiotherapy to...
Oct 28, 2017
Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program
F. Cardoso, J. M. S. Bartlett, L. Slaets, C. H. M. van Deurzen, E. van Leeuwen-Stok, P. Porter, B. Linderholm, I. Hedenfalk, C Schröder, J. Martens, J. Bayani, C. van Asperen M. Murray, C. Hudis, L. Middleton, J. Vermeij, K. Punie, J. Fraser, M. Nowaczyk, I. T. Rubio, S. Aebi, C. Kelly, K. J. Ruddy, E. Winer, C Nilsson, L. Dal Lago, L. Korde, K. Benstead, O. Bogler, T. Goulioti, A. Peric, S. Litière, K. C. Aalders, C. Poncet, K. Tryfonidis, S. H. Giordano , Annals of Oncology , DOI: 10.1093/annonc/mdx651
Background: Male breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period.Methods: Patients with follow-up and tumor samples,...
Oct 24, 2017
A CD3-bispecific molecule targeting P-cadherin demonstrates T cell-mediated regression of established solid tumors in mice
T. S. Fisher, A. T. Hooper, J. Lucas, T. H. Clark, A. K. Rohner, B. Peano, M. W. Elliott, K. Tsaparikos, H. Wang, J. Golas, M. Gavriil, N. Haddish-Berhane, L. Tchistiakova, H.-P. Gerber, A. R. Root, C. May , Cancer Immunology, Immunotherapy , DOI: 10.1007/s00262-017-2081-0
Strong evidence exists supporting the important role T cells play in the immune response against tumors. Still, the ability to initiate tumor-specific immune responses remains a challenge. Recent clinical trials suggest that bispecific antibody-mediated retargeted T cells are a promising therapeutic approach to eliminate hematopoietic tumors. However, this approach has...