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BACKGROUND Techniques enabling targeted re-sequencing of the protein coding sequences of the human genome on next generation sequencing instruments are of great interest. We conducted a systematic comparison of the solution-based exome capture kits provided by Agilent and Roche NimbleGen. A control DNA sample was captured with all four capture methods and(More)
Histone deacetylase (HDAC) inhibitors are promising antitumor agents, but they have not been extensively explored in B-cell lymphomas. Many of these lymphomas have the t(14;18) translocation, which results in increased bcl-2 expression and resistance to apoptosis. In this study, we examined the effects of two structurally different HDAC inhibitors,(More)
Large granular lymphocytic (LGL) leukemia is characterized by clonal expansion of cytotoxic T cells or natural killer cells. Recently, somatic mutations in the signal transducer and activator of transcription 3 (STAT3) gene were discovered in 28% to 40% of LGL leukemia patients. By exome and transcriptome sequencing of 2 STAT3 mutation-negative LGL leukemia(More)
UNLABELLED We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one patient at a time. ISM is based on (i) molecular profiling and ex vivo drug sensitivity and resistance testing (DSRT) of patients' cancer cells to 187 oncology drugs, (ii) clinical implementation of therapies predicted to be effective, and (iii)(More)
Solid tumors express a range of factors required to sustain their growth and promote their dissemination. Among these are vascular endothelial growth factor-A (VEGF-A), the key angiogenic stimulant, and VEGF-C, a primary mediator of lymphangiogenesis. Small molecule tyrosine kinase inhibitors offer the potential to inhibit more than one kinase and impede(More)
We developed a systematic algorithmic solution for quantitative drug sensitivity scoring (DSS), based on continuous modeling and integration of multiple dose-response relationships in high-throughput compound testing studies. Mathematical model estimation and continuous interpolation makes the scoring approach robust against sources of technical variability(More)
We developed a quality assurance (QA) tool, namely microarray outlier filter (MOF), and have applied it to our microarray datasets for the identification of problematic arrays. Our approach is based on the comparison of the arrays using the correlation coefficient and the number of outlier spots generated on each array to reveal outlier arrays. For a human(More)
In previous work, we undertook a comparison of cells from three highly malignant in vitro epithelial lines with cells from three lines showing little or no evidence of tumorigenicity, to see if consistent structural perturbations were present. Cells from highly malignant lines showed common anomalies in the organization of the lamellar cytoplasm. The(More)
A synergistic interaction of Bcl-2 and c-Myc plays a role in lymphomagenesis in mice and in some patients as well. Progression of follicular lymphoma to a more aggressive lymphoma is seen in the majority of patients, and approximately 10% of the transformed lymphomas have a translocation of c-myc in addition to the translocation of bcl-2 found in the(More)
Advanced tumors are often immunosuppressive. Intratu-moral administration of adenovirus activates Toll-like receptor signalling leading to production of pro-inflamma-tory cytokines and activation of the innate immune system. Oncolytic adenovirus causes immunogenic cancer cell death and creates a danger signal at tumors, thus undermining immunological(More)