Project description:Inhibitors of Rho kinase (ROCK) are a new class of drugs with potential benefit in oncology, neurology, and fibrotic and cardiovascular diseases. ROCK inhibitors modulate many cellular functions, some of which are similar to the pleiotropic (non-lipid lowering) effects of statins, suggesting additive or synergistic properties. Studies to date have used compounds which inhibit both isoforms of ROCK, ROCK1 and ROCK2. In this study, the effect of the newly developed ROCK2 inhibitor SLx-2119 on genome-wide gene expression was compared with atorvastatin in primary human cells. Keywords: Cell type comparison, agent comparison
Project description:Keratinocytes are a targeted cells for infection of human papillomaviruses (HPV). But, there are very limited information for gene regulation of human karatinocytes by HPV infection. Y-27632, a rho-kinase inhibitor, stimulates proparation of keratinocytes. We identified genes, which are regulated by a drug for karatinocyte proparation (Y-27632). mRNA profiles of primary HEKs regulated by a rho kinase inhibitor (Y-27632, Y-drug) were generated by microarray analysis using Illumina BeadChip.
Project description:TRANSCRIPTOMIC PROFILING OF ASTROCYTES TREATED WITH THE RHO KINASE INHIBITOR FASUDIL REVEALS CYTOSKELETAL AND PRO-SURVIVAL RESPONSESTRANSFORMATION INDUCED BY THE RHO KINASE INHIBITOR FASUDIL.
Project description:Analysis of genome wide gene expression changes over a time course of 24 hours induced by the Rho kinase inhibitor Fasudil in primary mouse astrocyte cultures. Total RNA was extracted from primary astrocyte cultures prepared from mouse forebrain from 1.5 day old mice and treated with Fasudil or vehicle control for 2, 6, 12 or 24 hours.
Project description:We previously demonstrated that the lifespan of primary human keratinocytes could be extended indefinitely by culture in the presence of the Rho kinase (ROCK) inhibitor Y-27632. Here, gene expression analysis of primary human epidermal keratinocytes cells grown in the presence of Y-27632 demonstrates that ROCK inhibition primarily inhibits keratinocyte differentiation.
Project description:Analysis of genome wide gene expression changes over a time course of 24 hours induced by the Rho kinase inhibitor Fasudil in primary mouse astrocyte cultures.
Project description:The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma, given that it is aberrantly activated in almost 80% of human cutaneous melanomas (~50% BRAFV600 mutations and ~30% NRAS mutations). While targeted therapies have yielded success in BRAFV600 mutant melanoma patients, such therapies have been ineffective in NRAS mutant melanomas in part due to their cytostatic effects and primary resistance in this patient population. Here, we demonstrate that increased Rho/MRTF-pathway activation correlates with high intrinsic resistance to trametinib, a MEK inhibitor, in a panel of NRAS mutant melanoma cell lines. Combination of trametinib with the Rho/MRTF-pathway inhibitor, CCG-222740, synergistically reduced cell viability in NRAS mutant melanoma cell lines in vitro. Furthermore, the combination of CCG-222740 with trametinib induced apoptosis and reduced clonogenicity in the highly trametinib-resistant SK-Mel-147 cells. These findings suggest a role of the Rho/MRTF-pathway in high intrinsic trametinib resistance to a subset of NRAS mutant melanoma cell lines and highlights the potential of concurrently targeting the Rho/MRTF-pathway and MEK in NRAS mutant melanomas.
Project description:The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma, given that it is aberrantly activated in almost 80% of human cutaneous melanomas (~50% BRAFV600 mutations and ~30% NRAS mutations). While targeted therapies have yielded success in BRAFV600 mutant melanoma patients, such therapies have been ineffective in NRAS mutant melanomas in part due to their cytostatic effects and primary resistance in this patient population. Here, we demonstrate that increased Rho/MRTF-pathway activation correlates with high intrinsic resistance to trametinib, a MEK inhibitor, in a panel of NRAS mutant melanoma cell lines. Combination of trametinib with the Rho/MRTF-pathway inhibitor, CCG-222740, synergistically reduced cell viability in NRAS mutant melanoma cell lines in vitro. Furthermore, the combination of CCG-222740 with trametinib induced apoptosis and reduced clonogenicity in the highly trametinib-resistant SK-Mel-147 cells. These findings suggest a role of the Rho/MRTF-pathway in high intrinsic trametinib resistance to a subset of NRAS mutant melanoma cell lines and highlights the potential of concurrently targeting the Rho/MRTF-pathway and MEK in NRAS mutant melanomas.
Project description:MDA-MB-231 breast carcinoma cells were treated by non-targetting siRNA or siRNAs against EXOSC8. Subsequently, mRNAs from protrusions of the cells were quantified by RNA-seq in presence of Rho-kinase inhibitor H1152, using a filter based fractionation method.
