Vanderbilt University

About: Vanderbilt University is a education organization based out in Nashville, Tennessee, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 45066 authors who have published 106528 publications receiving 5435039 citations. The organization is also known as: Vandy.

The matrix-degrading metalloproteinases.

Abstract: The matrix-degrading metalloproteinases are an intriguing family of enzymes that have evolved to digest specific extracellular matrix components. The expression of these enzymes is very highly regulated and can be controlled transcriptionally by a number of growth factors, tumor promoters, oncogenes, and hormones. It is suggested that the coordinated regulation of matrix metalloproteinases and their inhibitors by these agents modify the integrity of the extracellular matrix. These modifications may, at least in part, be responsible for mediating the effects of these factors on complex physiological processes.

Initial invasive or conservative strategy for stable coronary disease.

Abstract: Background Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical ther...

RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)

Abstract: Activated RAS promotes dimerization of members of the RAF kinase family. ATP-competitive RAF inhibitors activate ERK signalling by transactivating RAF dimers. In melanomas with mutant BRAF(V600E), levels of RAS activation are low and these drugs bind to BRAF(V600E) monomers and inhibit their activity. This tumour-specific inhibition of ERK signalling results in a broad therapeutic index and RAF inhibitors have remarkable clinical activity in patients with melanomas that harbour mutant BRAF(V600E). However, resistance invariably develops. Here, we identify a new resistance mechanism. We find that a subset of cells resistant to vemurafenib (PLX4032, RG7204) express a 61-kDa variant form of BRAF(V600E), p61BRAF(V600E), which lacks exons 4-8, a region that encompasses the RAS-binding domain. p61BRAF(V600E) shows enhanced dimerization in cells with low levels of RAS activation, as compared to full-length BRAF(V600E). In cells in which p61BRAF(V600E) is expressed endogenously or ectopically, ERK signalling is resistant to the RAF inhibitor. Moreover, a mutation that abolishes the dimerization of p61BRAF(V600E) restores its sensitivity to vemurafenib. Finally, we identified BRAF(V600E) splicing variants lacking the RAS-binding domain in the tumours of six of nineteen patients with acquired resistance to vemurafenib. These data support the model that inhibition of ERK signalling by RAF inhibitors is dependent on levels of RAS-GTP too low to support RAF dimerization and identify a novel mechanism of acquired resistance in patients: expression of splicing isoforms of BRAF(V600E) that dimerize in a RAS-independent manner.

A meta-analysis of writing instruction for adolescent students.

Abstract: There is considerable concern that the majority of adolescents do not develop the competence in writing they need to be successful in school, the workplace, or their personal lives. A common explanation for why youngsters do not write well is that schools do not do a good job of teaching this complex skill. In an effort to identify effective instructional practices for teaching writing to adolescents, the authors conducted a meta-analysis of the writing intervention literature (Grades 4-12), focusing their efforts on experimental and quasi-experimental studies. They located 123 documents that yielded 154 effect sizes for quality of writing. The authors calculated an average weighted effect size (presented in parentheses) for the following 11 interventions: strategy instruction (0.82), summarization (0.82), peer assistance (0.75), setting product goals (0.70), word processing (0.55), sentence combining (0.50), inquiry (0.32), prewriting activities (0.32), process writing approach (0.32), study of models (0.25), grammar instruction (- 0.32).