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Notch signaling is an area of great interest in oncology. RO4929097 is a potent and selective inhibitor of gamma-secretase, producing inhibitory activity of Notch signaling in tumor cells. The RO4929097 IC50 in cell-free and cellular assays is in the low nanomolar range with >100-fold selectivity with respect to 75 other proteins of various types(More)
Interferons (IFNs) direct innate and acquired immune responses and, accordingly, are used therapeutically to treat a number of diseases, yet the diverse effects they elicit are not fully understood. Here, we identified the promyelocytic leukemia zinc finger (PLZF) protein as a previously unrecognized component of the IFN response. IFN stimulated an(More)
The transcriptional repressor PLZF was identified by its translocation with retinoic acid receptor alpha in t(11;17) acute promyelocytic leukemia (APL). Ectopic expression of PLZF leads to cell cycle arrest and growth suppression, while disruption of normal PLZF function is implicated in the development of APL. To clarify the function of PLZF in cell growth(More)
PURPOSE To understand the changes in gene expression in polycythemia vera (PV) progenitor cells and their relationship to JAK2V617F. EXPERIMENTAL DESIGN Messenger RNA isolated from CD34(+) cells from nine PV patients and normal controls was profiled using Affymetrix arrays. Gene expression change mediated by JAK2V617F was determined by profiling CD34(+)(More)
PURPOSE To explore the role of TWEAK in tumor growth and antitumor immune response and the activity and mechanism of RG7212, an antagonistic anti-TWEAK antibody, in tumor models. EXPERIMENTAL DESIGN TWEAK-induced signaling and gene expression were explored in tumor cell lines and inhibition of these effects and antitumor efficacy with RG7212 treatment was(More)
The Wilms tumor gene (WT1) is mutated or deleted in patients with heredofamilial syndromes associated with the development of Wilms tumors, but is infrequently mutated in sporadic Wilms tumors. By comparing the microarray profiles of syndromic versus sporadic Wilms tumors and WT1-inducible Saos-2 osteosarcoma cells, we identified interferon-inducible(More)
A genomics-based approach to identify pharmacodynamic biomarkers was used for a cyclin-dependent kinase inhibitory drug. R547 is a potent cyclin-dependent kinase inhibitor with a potent antiproliferative effect at pharmacologically relevant doses and is currently in phase I clinical trials. Using preclinical data derived from microarray experiments, we(More)
An 18-year-old woman was evaluated because of primary amenorrhea and hypogonadism. Chromosome analysis from peripheral blood lymphocytes revealed a nonmosaic 46,X,+mar constitution. The marker was shown to be a rearranged Y chromosome consisting of an inverted duplication of the long arm: rea(Y)(qter-q11::q11-qter). Deletion mapping analysis with Y-specific(More)
In its role as a tumor suppressor, WT1 transactivates several genes that are regulators of cell growth and differentiation pathways. For instance, WT1 induces the expression of the cell cycle regulator p21, the growth-regulating glycoprotein amphiregulin, the proapoptotic gene Bak, and the Ras/mitogen-activated protein kinase (MAPK) inhibitor Sprouty1.(More)
Polycythemia vera (PV), essential thrombocythemia and primary myelofibrosis, are myeloproliferative neoplasms (MPNs) with distinct clinical features and are associated with the JAK2V617F mutation. To identify genomic anomalies involved in the pathogenesis of these disorders, we profiled 87 MPN patients using Affymetrix 250K single-nucleotide polymorphism(More)