Feb 11, 2013
LKB1 Inactivation Dictates Therapeutic Response of Non-Small Cell Lung Cancer to the Metabolism Drug Phenformin
D. B. Shackelford, E. Abt, L. Gerken, D. S. Vasquez, A. Seki, M. Leblanc, L. Wei, M. C. Fishbein, J. Czernin, P. S. Mischel, R. J. Shaw , Cancer Cell , DOI: 10.1016/j.ccr.2012.12.008
The LKB1 (also called STK11) tumor suppressor is mutationally inactivated in ∼20% of non-small cell lung cancers (NSCLC). LKB1 is the major upstream kinase activating the energy-sensing kinase AMPK, making LKB1-deficient cells unable to appropriately sense metabolic stress. We tested the therapeutic potential of metabolic drugs in NSCLC and identified...
Feb 6, 2013
Enhanced proteolytic clearance of plasma aβ by peripherally administered neprilysin does not result in reduced levels of brain aβ in mice
Walker JR, Pacoma R, Watson J, Ou W, Alves J, Mason DE, Peters EC, Urbina HD, Welzel G, Althage A, Liu B, Tuntland T, Jacobson LH, Harris JL, Schumacher AM , J Neurosci , Volume 33, Issue 6, pp. 2547-64
Accumulation of β-amyloid (Aβ) in the brain is believed to contribute to the pathology of Alzheimer's Disease (AD). Aβ levels are controlled by the production of Aβ from amyloid precursor protein, degradation by proteases, and peripheral clearance. In this study we sought to determine whether enhancing clearance of plasma Aβ...
Jan 8, 2013
Automated Quantitative RNA in Situ Hybridization for Resolution of Equivocal and Heterogeneous ERBB2 (HER2) Status in Invasive Breast Carcinoma
Z. Wang, B. P. Portier, A. M. Gruver, S. Bui, H. Wang, N. Su, H.-T. Vo, X.-J. Ma, Y. Luo, G. T. Budd, R. R. Tubbs , The Journal of Molecular Diagnostics , DOI: 10.1016/j.jmoldx.2012.10.003
Patient management based on HER2 status in breast carcinoma is an archetypical example of personalized medicine but remains hampered by equivocal testing and intratumoral heterogeneity. We developed a fully automated, quantitative, bright-field in situ hybridization technique (RNAscope), applied it to quantify single-cell HER2 mRNA levels in 132 invasive breast carcinomas,...
Jan 3, 2013
Acidity generated by the tumor microenvironment drives local invasion
Estrella V, Chen T, Lloyd M, Wojtkowiak J, Cornnell HH, Ibrahim-Hashim A, Bailey K, Balagurunathan Y, Rothberg JM, Sloane BF, Johnson J, Gatenby RA, Gillies RJ , Cancer Res , DOI: 10.1158/0008-5472.CAN-12-2796
The pH of solid tumors is acidic due to increased fermentative metabolism and poor perfusion. It has been hypothesized that acid pH promotes local invasive growth and metastasis. The hypothesis that acid mediates invasion proposes that H+ diffuses from the proximal tumor microenvironment into adjacent normal tissues where it causes...
Jan 1, 2013
Protein tyrosine phosphatase 1B restrains mammary alveologenesis and secretory differentiation
Milani ES, Brinkhaus H, Dueggeli R, Klebba I, Mueller U, Stadler M, Kohler H, Smalley MJ, Bentires-Alj M , Development , Volume 140, pp. 117-125
Tyrosine phosphorylation plays a fundamental role in mammary gland development. However, the role of specific tyrosine phosphatases in controlling mammary cell fate remains ill defined. We have identified protein tyrosine phosphatase 1B (PTP1B) as an essential regulator of alveologenesis and lactogenesis. PTP1B depletion increased the number of luminal mammary progenitors...