Project description:4 lymphoma cell lines (DOHH2, OCILy10, TMD8 and Toledo) have been treated with DMSO, CB103, NEO02734 or OTX015. The transcriptome has been sequenced after 6hrs from the treatment. The gene expression levels have been compared in order to elucidate the differencies and similarities for the different drugs compare to DMSO (control group).
Project description:A screen of 5 anti-inflammatory compounds for their effects in explanted, cultured rat spinal cord slices. All injured (explanted) cords are cultured for 4 hrs.
Project description:A screen of 5 anti-inflammatory compounds for their effects in explanted, cultured rat spinal cord slices. All injured (explanted) cords are cultured for 4 hrs. Keywords: ordered
Project description:Rat has been treated with different compounds with the purpose of investigating toxicological mechanisms. But toxic and non-toxic compounds has been administered. 3 toxic (ANIT, DMN, NMF) 3 non-tox (Caerulein, dinitrophenol(DNP), Rosiglitazone) in 5-plicates (30 arrays in all) and 9 untreated (control), 39 samples in all. The array data was used to identify genes with biomarker potential for detecting toxic properties of compounds. Keywords: other
Project description:We report the single-cell RNA sequencing data obtained from BCL1 lymphoma-bearing mice treated with either isotype control, anti-CD20 mAb, anti-CD27 mAb or anti-CD20+anti-CD27 mAb together
Project description:The transcription factor FOXM1 is up-regulated and overexpressed in aggressive, therapy-resistant forms of hormone receptor-positive and triple negative breast cancers, and is associated with less good patient survival. FOXM1 pathway signaling is also a key driver in other aggressive cancers, including those in prostate, lung, ovary, and gastrointestinal tract. Therefore, our goal has been to identify compounds effective in suppressing FOXM1 activity and breast cancer proliferation, and displaying good potency and pharmacokinetic properties for in vivo antitumor efficacy. In this report, we describe our studies on the FOXM1 targeting activities of 1,1-diarylethylene mono- and diamine compounds and their methiodide salts in cell-free, cell-based, and in vivo assays. The compounds bind directly to FOXM1 and alter its proteolytic sensitivity, reduce the cellular level of FOXM1 protein, and suppress the proliferation of breast cancer cells. RNA-seq and gene set enrichment analyses indicate that the compounds NB-73 and NB-55 decrease the expression of FOXM1-regulated genes and suppress gene ontology processes known to be under FOXM1 regulation. Several compounds with favorable pharmacokinetic properties were studied in preclinical breast tumor models. One compound (NB-55) had good oral efficacy in suppressing the growth of FOXM1-containing breast tumors in NOD-SCID-gamma (NSG) mice, and several others (NB-73, NB-115, and NB-63) had good efficacy in tumor growth suppression by subcutaneous administration. Our findings identify and characterize a new class of compounds that effectively antagonize FOXM1 actions and tumor growth that may be suitable for further clinical evaluation in targeting aggressive breast cancers driven by FOXM1.
Project description:Identifying the Mechanism of Action (MoA) of drugs is critical for the development of new drugs, understanding their side effects, and drug repositioning. However, identifying drug MoA has been challenging and has been traditionally attempted only though large experimental setups with little success. While advances in computational power offers the opportunity to achieve this in-silico, methods to exploit existing computational resources are still in their infancy. To overcome this, we developed a novel method to identify Drug Mechanism of Action using Network Dysregulation (DeMAND). The method is based on the realization that drugs affect the protein activity of their targets, but not necessarily their mRNA expression levels. In contrast, the change in protein activity directly affects the mRNA expression levels of downstream genes. Based on this hypothesis, DeMAND identifies drug MoA by comparing gene expression profiles following drug perturbation with control samples, and computing the change in the individual interactions within a pre-determined integrated transcriptional and post-translational regulatory model (interactome). This dataset includes GEPs in 3 different B-cell lymphoma cell lines (OCI-LY3, OCI-LY7 and U2932) at 6, 12, and 24hrs. 92 FDA approved compounds were used at a concentration of IC20 at 24h. DMSO was used as control at each time-point. A total of 828 samples and 29 control samples were available for analysis. Total RNA was isolated with the RNAqueous-96 Automated Kit (Ambion) on the Janus automated liquid handling system (Perkin Elmer Inc.), quantified by NanoDrop 6000 spectrophotometer and quality checked by Agilent Bioanalyzer. 300ng of each of the samples with RIN value >7 were converted to biotinylated cRNA with the Illumina TotalPrep-96 RNA Amplification Kit (Ambion) using a standard T7-based amplification protocol and hybridized on the Human Genome U219 96-Array Plate (Affymetrix). Hybridization, washing, staining and scanning of the array plates were performed on the GeneTitan Instrument (Affymetrix) according to manufacturer’s protocols.