Patient-derived xenograft (PDX) models in basic and translational breast cancer research

Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational preclinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and "Triple-negative" (TNBC)). Many of these models are well-characterized with respect to genomic, transcriptomic, and proteomic features, metastatic behavior, and treatment response to a variety of standard-of-care and experimental therapeutics. These stably transplantable PDX lines are generally available for dissemination to laboratories conducting translational research, and contact information for each collection is provided. This review summarizes current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward "credentialing" of PDX models as surrogates to represent individual patients for use in preclinical and co-clinical translational research. In addition, this review highlights important unresolved questions, as well as current limitations, that have hampered more efficient generation of PDX lines and more rapid adoption of PDX use in translational breast cancer research

Relationship Between Trade, Investment and Environment: A Review of Issues

The inter-linkage between economic openness and environmental repercussions is a widely researched area. The current study contributes in the existing pool of research by conducting a cross-country empirical analysis for the year 2008 by exploring the interrelationship between openness indicators (trade and investment) and environmental performance of a country. For this purpose, the analysis separately considers export orientation, import orientation, FDI inwardness and FDI outwardness of the countries in different variations of the proposed empirical model. The regression results do not provide strong support to the Pollution Haven Hypothesis (PHH). The findings also confirm a relationship between socio-economic and socio-political factors in a country and its environmental performance

SOUTHEASTERN MINNESOTA FARM MANAGEMENT ASSOCIATION 1983 ANNUAL REPORT

Farm Management,

SOUTHWESTERN MINNESOTA FARM MANAGEMENT ASSOCIATION 1983 ANNUAL REPORT

Farm Management,

Modulatory profiling identifies mechanisms of small molecule-induced cell death

Cell death is a complex process that plays a vital role in development, homeostasis, and disease. Our understanding of and ability to control cell death is impeded by an incomplete characterization of the full range of cell death processes that occur in mammalian systems, especially in response to exogenous perturbations. We present here a general approach to address this problem, which we call modulatory profiling. Modulatory profiles are composed of the changes in potency and efficacy of lethal compounds produced by a second cell death-modulating agent in human cell lines. We show that compounds with the same characterized mechanism of action have similar modulatory profiles. Furthermore, clustering of modulatory profiles revealed relationships not evident when clustering lethal compounds based on gene expression profiles alone. Finally, modulatory profiling of compounds correctly predicted three previously uncharacterized compounds to be microtubule-destabilizing agents, classified numerous compounds that act nonspecifically, and identified compounds that cause cell death through a mechanism that is morphologically and biochemically distinct from previously established ones

Data from: Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis

Exchange of extracellular cystine for intracellular glutamate by the antiporter system xc− is implicated in numerous pathologies. Pharmacological agents that inhibit system xc− activity with high potency have long been sought, but have remained elusive. In this study, we report that the small molecule erastin is a potent, selective inhibitor of system xc−. RNA sequencing revealed that inhibition of cystine–glutamate exchange leads to activation of an ER stress response and upregulation of CHAC1, providing a pharmacodynamic marker for system xc− inhibition. We also found that the clinically approved anti-cancer drug sorafenib, but not other kinase inhibitors, inhibits system xc− function and can trigger ER stress and ferroptosis. In an analysis of hospital records and adverse event reports, we found that patients treated with sorafenib exhibited unique metabolic and phenotypic alterations compared to patients treated with other kinase-inhibiting drugs. Finally, using a genetic approach, we identified new genes dramatically upregulated in cells resistant to ferroptosis

Data Package 2

FPKM expression values from RNA-seq using parental DU-145 prostate cancer cells and clonal cell lines derived from the parental line with resistance to erastin-induced ferroptosis. Sample nomenclature is as follows: "2.5E-2" means this resistant line was produced using a selective pressure of 2.5uM Erastin, and was the second clone evaluated at that concentration. The column titles map to one parental and five resistant clonal lines tested: DU-145 (parental, sensitive), 2.5E-1, 2.5E-2, 2.5E-3, 2.5E-5, and 2.6E-23 (all resistant). Fold changes were calculated using the ratio of each resistant line/parental (column directly to the right of each resistant line). Average fold changes (resistant/parental, column M) and average ΔFPKM (resistant - parental, column N) for each gene across all resistant lines were calculated. For these experiments, only genes with FPKM > 0.1 in the DU-145 condition and FPKM ≥ 1 for all other conditions were evaluated