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:Major efforts are underway to identify agents that can potentiate effects of immune checkpoint inhibition. Here, we show that ascorbic acid (AA) treatment caused genome wide demethylation and enhanced expression of endogenous retroviral elements in lymphoma cells. AA also increased 5-hydroxymethylcytosine (5hmC) levels of CD8+ T cells and enhanced their cytotoxic activity in a lymphoma co-culture system. High-dose AA treatment synergized with anti-PD1 therapy in a syngeneic lymphoma mouse model, resulting in marked inhibition of tumor growth compared with either agent alone. Analysis of the intra-tumoral epigenome revealed increased 5hmC with AA treatment, consistent with in vitro findings. Analysis of the tumor immune microenvironment revealed that AA strikingly increased intra-tumoral infiltration of CD8+ T cells and macrophages, suggesting enhanced tumor immune recognition. The combination treatment markedly enhanced intra-tumoral infiltration of macrophages and CD8+ T lymphocytes, granzyme B production by cytotoxic cells (cytotoxic T cells and Natural Killer cells), and IL-12 production by antigen presenting cells compared with single agent anti-PD1. These data indicate that AA potentiates anti-PD1 checkpoint inhibition through synergistic mechanisms. The study provides compelling rationale for testing combinations of AA and anti-PD1 agents in lymphoma patients as well as in pre-clinical models of other malignancies.