Project description:Human islets were treated with IL-1b and IFN-g for 24h, digested with trypsin, multiplexed with TMT-10, fractionated by high pH reverse-phase chromatography and analyzed by tandem LC-MS/MS.
Project description:EndoC-betaH1 cells were treated with IL-1b and IFN-g for 48h, digested with trypsin, multiplexed with TMT-10, fractionated by high pH reverse-phase chromatography and analyzed by tandem LC-MS/MS.
Project description:This phase 1b, single-center, double-blind study evaluated safety, efficacy, and effect on molecular profiles of a topical Janus kinase/spleen tyrosine kinase (JAK/Syk) inhibitor, cerdulatinib gel 0.37%, in ten adults with mild-to-moderate atopic dermatitis (AD).
Project description:The mTOR-allosteric inhibitor, RAD001, in combination with a PI3K/mTOR ATP-site competitive inhibitor, BEZ235, causes gene reprogramming, autophagy and tumor regression, in a mouse model approximating human HCC with poor prognosis, leading to an investigator Phase 1B-2 clinical trial.
Project description:Small activating RNAs (saRNAs), are short double-stranded RNAs designed to upregulate transcription of target genes. By this virtue, they can be used to restore expression of genes frequently silenced in cancer. AW1-51 (also referred to as CEBPA-51), the first saRNA therapeutic to enter clinical evaluation, has demonstrated biological activity and safety in Phase II trials for hepatocellular carcinoma, both as monotherapy and in combination with sorafenib, and in Phase 1a/1b in combination with pembrolizumab for patients with advanced solid tumors. It targets the master regulator CCAAT enhancer-binding protein alpha (CEBPA), abnormally silenced by DNA methylation in a wide range of hematological and not hematological malignancies. However, the molecular events enabling this mechanism are only partially elucidated. In this study, we uncovered the molecular basis for AW1-51-induced transcriptional reactivation of CEBPA demonstrating that by directly promoting DNA demethylation of CEBPA promoter restores CEBPA expression, protein synthesis, and consequently cell differentiation. These findings unveil AW1-51 as a prototype for RNA-based precision medicine enabling conditional expression of CEBPA in diseases characterized by aberrant gene silencing and extending its potential therapeutic impact beyond cancer.
Project description:Small activating RNAs (saRNAs), are short double-stranded RNAs designed to upregulate transcription of target genes. By this virtue, they can be used to restore expression of genes frequently silenced in cancer. AW1-51 (also referred to as CEBPA-51), the first saRNA therapeutic to enter clinical evaluation, has demonstrated biological activity and safety in Phase II trials for hepatocellular carcinoma, both as monotherapy and in combination with sorafenib, and in Phase 1a/1b in combination with pembrolizumab for patients with advanced solid tumors. It targets the master regulator CCAAT enhancer-binding protein alpha (CEBPA), abnormally silenced by DNA methylation in a wide range of hematological and not hematological malignancies. However, the molecular events enabling this mechanism are only partially elucidated. In this study, we uncovered the molecular basis for AW1-51-induced transcriptional reactivation of CEBPA demonstrating that by directly promoting DNA demethylation of CEBPA promoter restores CEBPA expression, protein synthesis, and consequently cell differentiation. These findings unveil AW1-51 as a prototype for RNA-based precision medicine enabling conditional expression of CEBPA in diseases characterized by aberrant gene silencing and extending its potential therapeutic impact beyond cancer.
Project description:Using specimens from a phase 1b trial of the RV144 regimen in HIV-1-uninfected South Africans (HVTN 097), we profiled innate responses to the first ALVAC-HIV immunization. PBMC transcriptional responses peaked 1 day post-vaccination. Type I and II interferon signaling pathways were activated, as were innate pathways critical for adaptive immune priming.
2021-03-17 | GSE164366 | GEO
Project description:Genomics sequencing evaluation of Bacillus macrobrachium rosenbergii mr-1B as a microbial agent