Breeze : an integrated quality control and data analysis application for high-throughput drug screening

High-throughput screening (HTS) enables systematic testing of thousands of chemical compounds for potential use as investigational and therapeutic agents. HTS experiments are often conducted in multi-well plates that inherently bear technical and experimental sources of error. Thus, HTS data processing requires the use of robust quality control procedures before analysis and interpretation. Here, we have implemented an open-source analysis application, Breeze, an integrated quality control and data analysis application for HTS data. Furthermore, Breeze enables a reliable way to identify individual drug sensitivity and resistance patterns in cell lines or patient-derived samples for functional precision medicine applications. The Breeze application provides a complete solution for data quality assessment, dose-response curve fitting and quantification of the drug responses along with interactive visualization of the results.Peer reviewe

Effective elimination of adult B-lineage acute lymphoblastic leukemia by disulfiram/copper complex in vitro and in vivo in patient-derived xenograft models

Disulfiram (DS), a clinically used drug to control alcoholism, has displayed promising anti-cancer activity against a wide range of tumors. Here, we demonstrated that DS/copper (Cu) complex effectively eliminated adult B-ALL cells in vitro and in vivo in patient-derived xenograft (PDX) humanized mouse models, reflected by inhibition of cell proliferation, induction of apoptosis, suppression of colony formation, and reduction of PDX tumor growth, while sparing normal peripheral blood mononuclear cells. Mechanistically, these events were associated with disruption of mitochondrial membrane potential and down-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-xL. Further analysis on B-ALL patients’ clinical characteristics revealed that the ex vivo efficacy of DS/Cu in primary samples was significantly correlated to p16 gene deletion and peripheral blood WBC counts at diagnosis, while age, LDH level, extramedullary infiltration, status post intensive induction therapy, immune phenotype, risk category, and Ph chromosome had no effect. Together, these findings indicate that disulfiram, particularly when administrated in combination with copper, might represent a potential repurposing agent for treatment of adult B-ALL patients, including those clinically characterized by one or more adverse prognostic factors

Breeze: an integrated quality control and data analysis application for high-throughput drug screening

High-throughput screening (HTS) enables systematic testing of thousands of chemical compounds for potential use as investigational and therapeutic agents. HTS experiments are often conducted in multi-well plates that inherently bear technical and experimental sources of error. Thus, HTS data processing requires the use of robust quality control procedures before analysis and interpretation. Here, we have implemented an open-source analysis application, Breeze, an integrated quality control and data analysis application for HTS data. Furthermore, Breeze enables a reliable way to identify individual drug sensitivity and resistance patterns in cell lines or patient-derived samples for functional precision medicine applications. The Breeze application provides a complete solution for data quality assessment, dose-response curve fitting and quantification of the drug responses along with interactive visualization of the results

LE MYELOME A IGE (ETUDE CRITIQUE A PARTIR DE DEUX OBSERVATIONS PERSONNELLES)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Pendidikan Kaum Tertindas

xliii, 220 hlm.; 21 c

Relative weight of local and global properties depends on both the position of local elements and the saliency of global form

International audienceLove, Rouder, and Wisniewski (1999) and Ripoll and Marty (2005) showed that subjects could process global properties very quickly in a same/different task on abstract visual scenes for which the conspicuity of local and global properties had been controlled. In this new experiment, two important new factors were manipulated: saliency of the global pattern and location of local similarity. The results showed that the saliency of the global form as well as the location of local similarity determines the strength of global and local effects. Global effects continue to manifest themselves even when the extraction of the global form is difficult. Finally, the whole pattern of results suggests that local and global processing proceeds simultaneously and involves two attentional systems whose spatial characteristics are very different