Nov 15, 2013
Hypoxic Activation of the PERK/eIF2α Arm of the Unfolded Protein Response Promotes Metastasis through Induction of LAMP3
H. Mujcic, A. Nagelkerke, K. M.A. Rouschop, S. Chung, N. Chaudary, P. N. Span, B. Clarke, M. Milosevic, J. Sykes, R. P. Hill, M. Koritzinsky, B. G. Wouters , Clinical Cancer Research , DOI: 10.1158/1078-0432.CCR-13-0526
Purpose: Conditions of poor oxygenation (hypoxia) are present in many human tumors, including cervix cancer, and are associated with increased risk of metastasis and poor prognosis. Hypoxia is a potent activator of the PERK/eIF2α signaling pathway, a component of the unfolded protein response (UPR) and an important mediator of hypoxia...
Oct 30, 2013
Unimolecular Dual Incretins Maximize Metabolic Benefits in Rodents, Monkeys, and Humans
B. Finan, T. Ma, N. Ottaway, T. D. Müller, K. M. Habegger, K. M. Heppner, H. Kirchner, J. Holland, J. Hembree, C. Raver, S. H. Lockie, D. L. Smiley, V. Gelfanov, B. Yang, S. Hofmann, D. Bruemmer, D. J. Drucker, P. T. Pfluger, D. Perez-Tilve, J. Gidda, L. Vignati, L. Zhang, J. B. Hauptman, M. Lau, M. Brecheisen, S. Uhles, W. Riboulet, E. Hainaut, E. Sebokova, K. Conde-Knape, A. Konkar, R. D. DiMarchi, M. H. Tschöp , Science Translational Medicine , DOI: 10.1126/scitranslmed.3007218
We report the discovery and translational therapeutic efficacy of a peptide with potent, balanced co-agonism at both of the receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This unimolecular dual incretin is derived from an intermixed sequence of GLP-1 and GIP, and demonstrated enhanced antihyperglycemic...
Oct 29, 2013
Human tissue in systems medicine
P. D. Caie, K. Schuur, A. Oniscu, P. Mullen, P. A. Reynolds, D. J. Harrison , The FEBS Journal , DOI: 10.1111/febs.12550
Histopathology, the examination of an architecturally artefactual, two-dimensional and static image remains a potent tool allowing diagnosis and empirical expectation of prognosis. Considerable optimism exists that the advent of molecular genetic testing and other biomarker strategies will improve or even replace this ancient technology. A number of biomarkers already add...
Oct 8, 2013
p53 accumulation is a strong predictor of recurrence in estrogen receptor-positive breast cancer patients treated with aromatase inhibitors
M. Yamamoto, M. Hosoda, K. Nakano, S. Jia, K. C. Hatanaka, E. Takakuwa, Y. Hatanaka, Y. Matsuno, H. Yamashita , Cancer Science , DOI: 10.1111/cas.12302
Aromatase inhibitors have played a central role in endocrine therapy for estrogen receptor (ER)-positive breast cancer in postmenopausal women. However, factorspredictive of the efficacy of aromatase inhibitors, and prognostic factors, both for early and late recurrence in women treated with adjuvant aromatase inhibitors have not been identified. Whole genome analysis...
Sep 15, 2013
Short telomeres are frequent in hereditary breast tumors and are associated with high tumor grade
B. Martinez-Delgado, M. Gallardo, M. Tanic, K. Yanowsky, L. Inglada-Perez, A. Barroso, M. Rodriguez-Pinilla, M. Cañamero, M. A. Blasco, J. Benitez , Breast Cancer Research and Treatment , DOI: 10.1007/s10549-013-2696-6
Telomere shortening is a common event involved in malignant transformation. Critically short telomeres may trigger chromosomal aberrations and produce genomic instability leading to cancer development. Therefore, telomere shortening is a frequent molecular alteration in early stages of many epithelial tumors and in breast cancer correlates with stage and prognosis. A...