SAR103168: a tyrosine kinase inhibitor with therapeutic potential in myeloid leukemias.

SAR103168, a tyrosine kinase inhibitor of the pyrido [2,3-d] pyridimidine subclass, inhibited the kinase activities of the entire Src kinase family, Abl kinase, angiogenic receptor kinases (vascular endothelial growth factor receptor [VEGFR] 1 and 2), Tie2, platelet derived growth factor (PDGF), fibroblast growth factor receptor (FGFR) 1 and 3, and epidermal growth factor receptor (EGFR). SAR103168 was a potent Src inhibitor, with 50% inhibitory concentration (IC50) = 0.65 ± 0.

Evaluating translocation gene fusions by SNP array data.

Somatic cell genetic alterations are a hallmark of tumor development and progression. Although various technologies have been developed and utilized to identify genetic aberrations, identifying genetic translocations at the chromosomal level is still a challenging task. High density SNP microarrays are useful to measure DNA copy number variation (CNV) across the genome.

Segmental duplications containing tandem repeated genes encoding putative deubiquitinating enzymes.

Both inter- and intra-chromosomal segmental duplications are known occurred in human genome during evolution. Few cases of such segments involving functional genes have been reported. While searching for the human orthologs of murine hematopoietic deubiquitinating enzymes (DUBs), we identified four clusters of DUB-like genes on chromosome 4p15 and chromosome 8p22-23 that are over 90% identical to each other at the DNA level.

Human T helper (Th) cell lineage commitment is not directly linked to the secretion of IFN-gamma or IL-4: characterization of Th cells isolated by FACS based on IFN-gamma and IL-4 secretion.

Upon activation in vitro, only a fraction of the bulk human T helper cell cultures secret the hallmark Th1/2 cytokines (IFN-gamma for Th1 and IL-4 for Th2, respectively). It is uncertain whether these IFN-gamma-/IL-4- cells are differentiated Th1 or Th2 cells. Here, we have characterized live IFN-gamma+, IL-4+ and IFN-gamma-/IL-4- cells isolated from Th cell cultures treated under Th1 or Th2 polarizing conditions by employing affinity matrix capture technology.

Prediction of IFN-gamma regulated gene transcription.

IFN-gamma, a cytokine promoting cell-mediated immunity and antiviral effects, regulates the expression of a large set of genes involved in the immune response. Based on logistic regression, an in silico model for predicting IFN-gamma regulated transcription has been developed by scoring the transcription factor binding sites on the putative promoters of regulated versus not regulated genes derived from the microarray data of IFN-gamma treated human macrophages. The model effectively discriminates the transcription factor binding sites that confer responsiveness to IFN-gamma from those that do not.

Genome-wide prediction and analysis of function-specific transcription factor binding sites.

DNA-binding transcription factors play a central role in transcription regulation, and the annotation of transcription-factor binding sites in upstream regions of human genes is essential for building a genome-wide regulatory network. We describe methodology to accurately predict the transcription-factor binding sites in the proximal-promoter region of function-specific genes. In order to increase the accuracy of transcription factor binding-site prediction, we rely on recent genome sequence data, known transcription factor binding-site matrices, and Gene Ontology biological-function-based gene classification.

Comparing gene discovery from Affymetrix GeneChip microarrays and Clontech PCR-select cDNA subtraction: a case study.

Background: Several high throughput technologies have been employed to identify differentially regulated genes that may be molecular targets for drug discovery. Here we compared the sets of differentially regulated genes discovered using two experimental approaches: a subtracted suppressive hybridization (SSH) cDNA library methodology and Affymetrix GeneChip technology. In this "case study" we explored the transcriptional pattern changes during the in vitro differentiation of human monocytes to myeloid dendritic cells (DC), and evaluated the potential for novel gene discovery using the SSH methodology.