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Pemetrexed and gemcitabine as combination therapy for the treatment of Group3 medulloblastoma

ABSTRACT: We devised a high-throughput, cell-based assay to identify novel therapeutic compounds to treat Group3 medulloblastoma (G3 MB). Mouse G3 MBs, grown as neurospheres, were screened against a library of approximately 7,000 compounds including FDA-approved drugs. We identified two FDA-approved drugs, pemetrexed and gemcitabine that preferentially inhibited tumor proliferation in vitro compared to control neurospheres, and substantially inhibited tumor proliferation in vivo. When combined, the two drugs significantly increased survival

ORGANISM(S): Mus musculus

PROVIDER: GSE46406 | GEO | 2014/04/15

SECONDARY ACCESSION(S): PRJNA200287

REPOSITORIES: GEO

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Pemetrexed and gemcitabine as combination therapy for the treatment of Group3 medulloblastoma

Project description:We devised a high-throughput, cell-based assay to identify novel therapeutic compounds to treat Group3 medulloblastoma (G3 MB). Mouse G3 MBs, grown as neurospheres, were screened against a library of approximately 7,000 compounds including FDA-approved drugs. We identified two FDA-approved drugs, pemetrexed and gemcitabine that preferentially inhibited tumor proliferation in vitro compared to control neurospheres, and substantially inhibited tumor proliferation in vivo. When combined, the two drugs significantly increased survival P7 Trp53-/-, Cdkn2c-/- neurospheres and MYC mouse cells were compared treated and untreated with drugs pemetrexed+gemcitabine

2014-04-15 | E-GEOD-46406 | biostudies-arrayexpress

A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor

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Machine Learning Identifies Candidates for Drug Repurposing in Alzheimer's Disease

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Targeting Group3 Medulloblastoma by the anti-PRUNE-1 and anti-LSD1- KDM1A molecules augments their potential therapeutic value.

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Pemetrexed and gemcitabine as combination therapy for the treatment of Group3 medulloblastoma.

Project description: Not available

| S-EPMC3994669 | biostudies-literature

In vivo electroporation-based conditional oncogenic activation implicates multiple distinct cellular origins for Group3 medulloblastoma

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polyA+ RNA expression profiles of Drosophila melanogaster male and female brains after treatment with Sodium salicylate, Chlorpromazine, or Trifluoperazine2HCl

Project description:To explore some of the sex differential responses to drug treatment, we exposed 3 day post-eclosion virgin Drosophila melanogaster (genotype DGRP-900, FlyBase line ID: FBst0028261) to 3 FDA approved drugs and characterized transcript abundance among male and female brains after 24 hours of drug exposure. The 3 tested drugs are water-soluble group N (Nervous system) compounds according to The Anatomical Therapeutic Chemical (ATC) classification system. Two (Chlorpromazine and Trifluoperazine2HCl) are primarily used to treat psychotic disorders, while the third (Sodium salicylate) is used as an analgesic and antipyretic. Following drug treatment, we dissected fly brains, isolated polyA+ RNA and performed high-throughput RNA-Seq analysis. We conducted quantification and statistical analysis of gene expression difference between tested drugs, sexes and their interaction.

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Gene expression data from DMD patient hiPSC-derived myoblasts treated with fenofibrate, ginsenoside Rd or DMSO

Project description:Drug development costs a significant amount of time and resources for new pharmaceutical drugs. However, the progress has been limited for orphan diseases such as Duchenne muscular dystrophy (DMD). By using human induced pluripotent stem cells (hiPSCs), here we show an exemplary drug screening campaign and the identification of two potential drugs effective in a DMD mouse model. We developed a DMD-hiPSC screening platform utilizing high-content imaging to identify hit compounds that enhance myogenic fusion abilities of patient-specific myoblasts. Among 1524 compounds (Johns Hopkins Clinical Compound library), two hit compounds restored in vitro fusion defects of DMD patient hiPSC-derived myoblasts. Transcriptional profiling revealed that the function of two hit compounds, ginsenoside Rd (natural product, ginseng extract) and fenofibrate (FDA-approved drug), are associated with FLT3 signaling and TGF-β signaling, respectively. The preclinical tests in mdx mice show that the treatment of the two hit compounds can ameliorate the skeletal muscle and behavioral phenotypes caused by DYSTROPHIN deficiency, suggesting therapeutic potential of these two compounds. Our study demonstrates the feasibility of early-stage drug development for rare diseases using symptom-relevant cells derived from patient-specific hiPSCs.

2020-05-09 | GSE121023 | GEO

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