Vertical Inhibition of the RAF-MEK-ERK Cascade Induces Myogenic Differentiation, Apoptosis, and Tumor Regression in Mutant Rhabdomyosarcoma.

Oncogenic RAS signaling is an attractive target for fusion-negative rhabdomyosarcoma (FN-RMS). Our study validates the role of the ERK MAPK effector pathway in mediating RAS dependency in a panel of mutant RMS cells and correlates efficacy of the MEK inhibitor trametinib with pharmacodynamics of ERK activity. A screen is used to identify trametinib-sensitizing targets, and combinations are evaluated in cells and tumor xenografts.

Bevacizumab therapy normalizes the pathological intraocular environment beyond neutralizing VEGF.

Purpose: Vascular endothelial growth factor (VEGF) plays a key role in neovascularization by stimulating the proliferation and migration of vascular endothelial cells. The anti-VEGF therapy bevacizumab acts by binding to VEGF and preventing its effects. However, this linear interaction represents only a partial view of the pathobiology of neovascular diseases and the anti-VEGF treatment.

Multiplex immunoassay analysis of biomarkers in clinically accessible quantities of human aqueous humor.

Purpose: Aqueous humor is intimately related to the cells of the anterior and posterior chambers, which affect its composition. Aqueous analysis provides useful information regarding physiological and pathophysiological processes in the eye. Human aqueous samples are typically less than 100 microl, limiting the usefulness of the analysis with traditional Enzyme-Linked immunoSorbant Assay (ELISA) techniques.

Isolation and characterization of mAMSA-hypersensitive mutants. Cytotoxicity of Top2 covalent complexes containing DNA single strand breaks.

Topoisomerase II (Top2) is the primary target for active anti-cancer agents. We developed an efficient approach for identifying hypersensitive Top2 mutants and isolated a panel of mutants in yeast Top2 conferring hypersensitivity to the intercalator N-[4-(9-acridinylamino)-3-methoxyphenyl]methanesulphonanilide (mAMSA). Some mutants conferred hypersensitivity to etoposide as well as mAMSA, whereas other mutants exhibited hypersensitivity only to mAMSA.

Comparing the use of Affymetrix to spotted oligonucleotide microarrays using two retinal pigment epithelium cell lines.

Purpose: The present study was designed to compare the results obtained from two different microarray platforms: spotted cDNAs using a two-color system (Clontech, Atlas Glass Human 3.8) and the Affymetrix platform. We evaluated the internal consistency within each of the platforms, and compared the results across the two platforms.