mirConnX is a user-friendly web interface for inferring, displaying and parsing mRNA and microRNA (miRNA) gene regulatory networks. mirConnX combines sequence information with gene expression data analysis to create a disease-specific, genome-wide regulatory network. A prior, static network has been constructed for all human and mouse genes. It consists of computationally predicted transcription factor (TF)-gene associations and miRNA target predictions. The prior network is supplemented with known interactions from the literature. Dynamic TF- and miRNA-gene associations are inferred from user-provided expression data using an association measure of choice. The static and dynamic networks are then combined using an integration function with user-specified weights. Visualization of the network and subsequent analysis are provided via a very responsive graphic user interface. Two organisms are currently supported: Homo sapiens and Mus musculus. The intuitive user interface and large database make mirConnX a useful tool for clinical scientists for hypothesis generation and explorations. mirConnX is freely available for academic use at http://www.benoslab.pitt.edu/mirconnx.

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AlphaVbeta3 (alphavbeta3) is an important molecule for tumor-induced angiogenesis and is upregulated in metastatic melanoma (MM). We proposed to study the mechanism of action of etaracizumab, a monoclonal antibody targeting alphavbeta3, in MM. Patients with MM and biopsiable tumor were treated with etaracizumab in 3 dose cohorts starting from 8 mg/kg. Tumor saturation by etaracizumab using LM609 immunohistochemical staining of tumor sections was the primary endpoint. Subsequent dose cohorts were defined based on the tumor saturation by etaracizumab. Secondary end points were analysis of clinical benefit and changes from baseline of several tumor and peripheral blood biomarkers. Eighteen patients were enrolled at 3 dose levels. Etaracizumab showed better melanoma cell saturation at the 8mg/kg and 1 mg/kg dose compared with the 4 mg/kg dose and better vascular endothelial cell saturation at 8 mg/kg compared with lower dose groups. Etaracizumab demonstrated an acceptable safety profile. The optimal biologic dose out of those selected for investigation was 8 mg/kg. Patients treated at the highest dose may have had better clinical benefit secondary to suppression of the activated immediate downstream effector of alphavbeta3 signaling, FAK, in melanoma cells, but this alone did not ultimately affect melanoma cell proliferation or apoptosis. No apparent antiangiogenic or immunomodulatory effects of etaracizumab were noted.

Background: Time-lapse microscopic imaging provides a powerful approach for following changes in cell phenotype over time. Visible responses of whole cells can yield insight into functional changes that underlie physiological processes in health and disease. For example, features of cell motility accompany molecular changes that are central to the immune response, to carcinogenesis and metastasis, to wound healing and tissue regeneration, and to the myriad developmental processes that generate an organism. Previously reported image processing methods for motility analysis required custom viewing devices and manual interactions that may introduce bias, that slow throughput, and that constrain the scope of experiments in terms of the number of treatment variables, time period of observation, replication and statistical options. Here we describe a fully automated system in which images are acquired 24/7 from 384 well plates and are automatically processed to yield high-content motility and morphological data.