Project description:To elucidate the molecular mechanisms of HDAC1-3 inhibitors in inhibiting M-MDSCs, RNA-seq analysis of M-MDSCs and PMN-MDSCs isolated from Hepa 1-6 tumor-bearing mice treated with MS-275 or CXD101 were performed.
Project description:To elucidate the molecular mechanisms of HDAC1-3 inhibitors in inhibiting M-MDSCs, ATAC-seq analysis of M-MDSCs isolated from Hepa 1-6 tumor-bearing mice treated with MS-275 or CXD101 were performed.
Project description:Phase I trial to study the effectiveness of combining MS-275 with isotretinoin in treating patients who have metastatic or advanced solid tumors or lymphomas. MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Isotretinoin may help cancer cells develop into normal cells. MS-275 may increase the effectiveness of isotretinoin by making cancer cells more sensitive to the drug. MS-275 and isotretinoin may also stop the growth of solid tumors or lymphomas by stopping blood flow to the cancer. Combining MS-275 with isotretinoin may kill more cancer cells
Project description:RATIONALE: MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth.
PURPOSE: This phase I trial is studying the side effects and best dose of MS-275 in treating patients with advanced solid tumors or lymphoma.
Project description:This study describes transcriptome profiling of mouse ES cells treated with MS-275. We included RNA-Seq of ds_cDNA synthesized from double poly(A) selected mRNA RNA-Seq profiling on mouse ES cells treated with MS-275
Project description:BACKGROUND: Ulcerative colitis (UC) is a common chronic inflammatory bowel disease without curative treatment. METHODS: We conducted gene set enrichment analysis to explore potential therapeutic agent for UC. Human colon tissue samples were collected to test H3 acetylation in UC. Both in vivo and in vitro colitis models were constructed to verify the role and mechanism of H3 acetylation modification in UC. Intestine-specific vitamin D receptor (VDR)-/- mice and VD (vitamin D)-deficient diet-fed mice were used to explore downstream molecular mechanism accordingly. RESULTS: According to the Connectivity Map database, MS-275 (class I histone deacetylase inhibitor) was the top-ranked agent, indicating potential importance of histone acetylation in the pathogenesis of UC. We then found that histone H3 acetylation was significantly decreased in the colon epithelium of UC patients and negatively associated with disease severity. MS-275 treatment inhibited histone H3 deacetylation, and subsequently attenuated nuclear factor kappa B (NF-?B)-induced inflammation, reduced cellular apoptosis, maintained epithelial barrier function, and thereby reduced colitis activity in a mouse model of colitis. We also identified VDR to be a downstream effector of MS-275. The curative effect of MS-275 on colitis was abolished in VDR-/- mice and in VD-deficient diet-fed mice and VDR directly targeted p65. In UC patients, histone H3 acetylation, VDR and zonulin-1 expression showed similar downregulation patterns and were negatively associated with disease severity. CONCLUSION: We demonstrate that MS-275 inhibits histone deacetylation and alleviates colitis by ameliorating inflammation, reducing apoptosis and maintaining intestinal epithelial barrier via VDR, providing new strategies for UC treatment.
Project description:This study describes transcriptome profiling of mouse ES cells treated with MS-275. We included RNA-Seq of ds_cDNA synthesized from double poly(A) selected mRNA
