Project description:Human Fetal pulmonary Fibroblasts (CCL153) were treated by PMA, IL1, TGFbeta and TNFalpha for 24 hours and compared for microRNA expression with control cells.
Project description:The usage of IGF1 and FGF2 instead of EGF and p38 inhibitor during human intestinal organoid culture enables to preserve differentiated cell populations. We analyzed gene expression of human small intestinal organoids cultured with either IGF1/FGF2 or EGF/p38i.
Project description:Comprehensive in vitro expression profiling of small chemical compound inhibitors of TGFbR1 kinase activity. Additional file E-MTAB-265.additonal.1.zip contains excel file with Taqman data validating the array normalization method
Project description:To explore the broader impact of kinase inhibitors on breast cancer cells, SKBR3/HER2+ cells were treated with two small molecule drugs, i.e., Lapatinib (10 uM) - a Tyr kinase inhibitor, and Ipatasertib (1 uM) - a Ser/Thr kinase inhibitor. Serum-starved cells (24 h) were exposed for 36 h to Lapatinib/EGF or a combination of Lapatinib/Ipatasertib/EGF. EGF - only stimulated cells were used as control. The EGF concentration was 10 nM throughout all experiments. Proteomic profiles of nuclear and cytoplasmic cell fractions of treated vs non-treated cells were generated by nano-LC-MS/MS using an Orbitrap QE instrument.
Project description:We profiles the effects of six protein phosphatase inhibitors on EGF-dependent phosphoproteome dynamics. The cells were treated with 20 nM EGF for 8 or 20 min with or without 15 min pre-treatment of one of the phosphatase inhibitors (100 nM or 1 M; Raphin1 acetate, sanguinarine chloride, KY-226, SHP099, NSC95397, or BCI). We further focused on sanguinarine chloride, and Hela cells were treated with 20 nM EGF for 3, 8, or 20min with or without 15 min pre-treatment of sanguinarine (5, 50, or 500 nM). We also examined combination of sanguinarine chloride (500 nM) and BIRB796 (500 nM), a p38-kinase inhibitor.
Project description:Ventoclax-based combinations are a new standard of care for patients with acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy, but not all patients respond to these treatments, and those who do may relapse. MDM2 inhibitors are promising therapeutics for treating TP53 wild-type tumors, including most de novo AML cases, but clinical trials have shown modest and variable clinical activity. Functional genomic data suggest that venetoclax and the MDM2 inhibitor, idasanutlin, may be ineffective against monocytic leukemia (FAB M4/M5) or leukemia cells with a high immune signature. We hypothesize upregulated myeloid transcription factors and enrichment of certain environmental cues that confer intrinsic and extrinsic drug resistance to these cells. We show that monocytic leukemia cells express a high level of CEBPB and CEBPB overexpression confers drug resistance to a broad range of BH3 mimetics, venetoclax combinations, and MDM2 inhibitors by downregulating CASP3, CASP6, BCL2, and p53 pathway targets, while upregulating MCL1, BCL2A1, and the NFKB/IL1/TNFA pathway. Moreover, leukemia monocytes can extrinsically protect leukemia blasts from venetoclax and MDM2 inhibition by secreting elevated IL1 and TNFA, which drive myelo/monocytic differentiation and upregulate inflammatory cytokines and receptors, including IL1/TNFA pathway in an autoregulatory loop. Remarkably, IL1A/IL1B and TNFA uniquely upregulate CEBPB expression in M4/M5 cells and protect them from apoptosis induced by venetoclax and MDM2 inhibitors. Conversely, TNFA treatment enhances extrinsic apoptosis in M0/M1 leukemia cells. Inhibitors of IRAK or MAPK14 (p38), which block IL1/TNFA signaling, showed synergistic cytotoxicity in M4/M5 AML when combined with venetoclax and idasanutlin. In summary, we described a targetable, positive feedback loop between CEBPB and IL1/TNFA in monocytic leukemia that drives intrinsic and extrinsic drug resistance to BCL2 and MDM2 inhibitors, offering promising therapeutic strategies to enhance treatment efficacy for monocytic leukemia.
Project description:The efficacy of the epidermal growth factor receptor (EGFR) inhibitors have been demonstrated in patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC) and colorectal cancer (CRC). Dermatological reactions can cause significant physical and psycho-social discomfort to patients. In the present study, the investigators evaluated the effect of epidermal growth factor (EGF) ointment on EGFR inhibitor-related skin side effects (ERSEs).
| 2177761 | ecrin-mdr-crc
Project description:Downstream targets of METTL3 small molecule inhibitors