Nov 13, 2017
Inhibition of TRF1 Telomere Protein Impairs Tumor Initiation and Progression in Glioblastoma Mouse Models and Patient-Derived Xenografts
L. Bejarano, A. J. Schuhmacher, M. Méndez, D. Megías, C. Blanco-Aparicio, S. Martínez, J. Pastor, M. Squatrito, M. A. Blasco , Cancer Cell , DOI: 10.1016/j.ccell.2017.10.006
Glioblastoma multiforme (GBM) is a deadly and common brain tumor. Poor prognosis is linked to high proliferation and cell heterogeneity, including glioma stem cells (GSCs). Telomere genes are frequently mutated. The telomere binding protein TRF1 is essential for telomere protection, and for adult and pluripotent stem cells. Here, we find...
Nov 6, 2017
Mesenchymal stem cells seeded on a human amniotic membrane improve liver regeneration and mouse survival after extended hepatectomy.
A. Despeyroux, C. Duret, C. Gondeau, E. Perez-Gracia, L. Chuttoo, H. de Boussac, P. Briolotti, C. Bony, D. Noël, C. Jorgensen, D. Larrey, M. Daujat-Chavanieu, A. Herrero , Journal of Tissue Engineering and Regenerative Medicine , DOI: 10.1002/term.2607
Liver failure remains the leading cause of post-operative mortality after hepatectomy. This study investigated the effect of treatment with allogenic mesenchymal stem cells (MSCs) on survival and liver regeneration 48 hr and 7 days after 80% hepatectomy in C57Bl/6 mice. To optimize their biodistribution, MSCs were grown on acellular human amniotic membranes...
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...