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Triple-negative breast cancer cell lines treated with mebedazole (an FDA-approved anti-parasitic).

ABSTRACT: The main purpose of this project is to identify gene expression changes between treated triple negative breast cancer cells (w/ MBZ) vs. non-treated cells (w/o MBZ). We have submitted two different cell ilnes, and those overlapping pathways will be important to elucidate the mechansim of MBZ. Cell Lines = SM or MD Drug treatment = 0M or 1M

ORGANISM(S): Homo sapiens

PROVIDER: GSE190845 | GEO | 2022/02/28

REPOSITORIES: GEO

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Breast cancer cell lines treated with mebedazole (an FDA-approved anti-parasitic) under 20% or 1% oxygen conditions.

Project description:The main purpose of this project is to identify gene expression changes between treated breast cancer cells (w/ MBZ) vs. non-treated cells (w/o MBZ) under normal (20% O2) or hypoxic (1% O2) conditions. Preliminary analysis using iclue revealed that MBZ might behave similarly to HIF inhbitors so we hypothesize that MBZ might repress HIF-response under hypoxia. We have submitted three different cell lines: SUM159 (SM), MDA-MB-231 (MDA) and MCF7; MBZ treatment: 0uM of MBZ (0M or 0); 1uM MBZ (1M or 1); Oxygen conditions: 1% O2 - hypoxia (H); 20% O2 - normoxia (N).

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Repurposing FDA-approved drugs for the treatment of malignant peripheral nerve sheath tumors

Project description:Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas developed from Schwann cell lineage. They account for up to 10% of all soft tissue sarcomas. Although there is an unmet need for new therapeutic agents for MPNSTs, to date there have been few transcriptomic analyses of this tumor type. We studied FDA approved drugs for MPNST treatment and compared their transcriptomic changes in cell lines before and after treatment. We demonstrated that Fludarabine treated NF1 MPNST cells exhibited altered signaling pathways such as the upregulation of the Wnt/Ca+ pathway and downregulation of the hedgehog and hypoxia signaling pathways in the Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA) analysis. The combined Colchicine and Fludarabine treatment enhanced the cytotoxicity of sporadic MPNST cells through altered signaling pathways, including increased Wnt/β-catenin pathway and others. The transcriptomic analysis comparing NF1/sporadic MPNST cells and normal Schwann cells indicated that NF1 MPNST cells had more splicing events, fewer single nucleotide variants, and induced RNA expression than sporadic MPNST cells. In summary, we identified a transcriptomic differences between MPNSTs and Schwann cells, between sporadic MPNST cells and NF1 MPNST cells, and between drug treated MPNST cells and vehicle treated cells.

2023-10-21 | GSE159896 | GEO

Triple-negative breast cancer cell lines treated with mebedazole (an FDA-approved anti-parasitic).

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Evaluation of a Pooling Chemoproteomics Strategy with an FDA-approved Drug Library

Project description:Chemoproteomics is a key platform for characterizing the mode of action (MoA) for compounds, especially for targeted protein degraders such as proteolysis targeting chimerics (PROTACs) and molecular glues. With deep proteome coverage, multiplexed tandem mass tag-mass spectrometry (TMT-MS) can tackle up to 18 samples in a single experiment. Here, we present a pooling strategy to further enhance the throughput, and apply the strategy to an FDA-approved drug library (95 best-in-class compounds). The TMT-MS-based pooling strategy was evaluated in the following steps. First, we demonstrated the capability of TMT-MS by analyzing over 15,000 unique proteins (>12,000 gene products) in HEK293 cells treated with five PROTACs (two BRD/BET degraders and three degraders for FAK, ALK, and BTK kinases). We then introduced a rationalized pooling strategy to separate structurally similar compounds in different pools, and identified the proteomic response to 14 pools from the drug library. Finally, we validated the proteomic response from one pool by re-profiling the cells under individual drug treatment with sufficient replicates. Interestingly, numerous proteins were found to change upon drug treatment, including AMD1, ODC1, PRKX, PRKY, EXO1, AEN and LRRC58 by 7-Hydroxystaurosporine; C6orf64, HMGCR and RRM2 by Sorafenib; SYS1 and ALAS1 by Venetoclax; and ATF3, CLK1 and CLK4 by Palbocilib. Thus, the pooling chemoproteomics screening provides an efficient method for dissecting the molecular targets of compound libraries.

2023-03-11 | PXD033780 | Pride

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Identification of FDA-Approved Drugs that Induce Heart Regeneration in Mammals

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