1,721,082 research outputs found
Epigenetic regulators: Polycomb-miRNA circuits in cancer
Full text linkPolycomb group (PcG) proteins belong to a family of epigenetic modifiers and play a key role in dynamic control of their target genes. Several reports have found that aberrations in PcG-microRNA (miRNA) interplay in various cancer types often associated with poor clinical prognosis. This review discusses important PcG-miRNA molecular networks which act as critical interfaces between chromatin remodeling, and transcriptional and post-transcriptional regulation of their target genes in cancer. Moreover, here are discussed several compounds influencing the activity of PcG proteins entered in clinical arena for the treatment of solid tumors, multiple myeloma and B lymphomas, thus highlighting the therapeutic potential of targeting this protein family
New insights in the transcriptional activity and coregulator molecules in the arterial wall
No full textNew trends in anti-atherosclerotic agents
No full textNew approaches to atherosclerosis-related diseases include novel uses of proven treatments and development of innovative agents. Several commonly used cardiovascular drugs such as dihydropyridine calcium antagonists, ACE inhibitors containing the sulphydryl group, or highly lipophilic beta-blockers have some anti-atherosclerotic activities. Moreover, new clinical trials suggesting that additional reduction of low-density lipoprotein cholesterol levels with statin therapy results in additional benefit in coronary heart disease prevention. Notably, new cholesterol transport or bile acid transport inhibitors have been found to produce significant reductions in intestinal cholesterol absorption and experimental atherosclerosis. Inhibitors of acyl coenzyme A:cholesterol acyltransferase, which can reduce cholesterol storage in macrophages and in arterial lesions, have also been developed. Finally, newer therapeutical strategies against atherogenesis may include the use of antioxidants and cholestyramine during pregnancy or the development of metalloproteinase inhibitors
CXCR4 inhibitors: tumor vasculature and therapeutic challenges
Full text linkCXCL12, also known as SDF-1, is the single natural ligand for chemokine receptors CXCR4 and CXCR7. CXCL12 has angiogenic properties in normal endothelial tissue and is involved in the outgrowth and metastasis of CXCR4 expressing tumors. Recent investigations have indicated that CXCL12 levels increase after chemo- and anti- VEGF therapy, favouring recurrences. The blockade of CXCL12/CXCR4 axis has emerged as a potential additional or alternative target for neo-adjuvant treatments. We have reviewed recent patent applications between 2008 and 2011 in tumor angiogenesis and the most clinical data supporting the potential use of anti-CXCR4 agents in this field. Among these, AMD3100, also known as Plerixaform (Mozobil® by Genzyme), is approved for stem cell mobilisation in patients with leukaemia, while BKT140 (Emory University), POL6326 (Polyphor Ag) and TG-0054 (ChemoCentryx) are currently in clinical trials in combination with chemotherapy for multiple myeloma and leukaemia. The aptamer Nox-A12 (Noxxon) is in trials for chronic lymphatic leukaemia treatment. MSX-122 (Metastatix) is in Phase I trials for solid tumor treatment, while CXCR7-specific inhibitor CCX2066 (ChemoCentryx) is still in preclinical studies. We have also considered other strategies, such RNA interference and miRNA, which could be tested for solid tumor adjuvant therapy
Glycoxidation of low-density lipoprotein promotes multiple apoptotic pathways and NFkappaB activation in human coronary cells
No full textApoptosis of arterial cells induced by oxidized low-density lipoprotein (oxLDL) is thought to contribute to the progression of vascular dysfunction and atherogenesis. It is well established that diabetes mellitus is accompanied by both glycosylation and oxidation LDL, but the biological effects of these modified lipoproteins are poorly understood. We demonstrate here that glycosylated oxLDL (glc-oxLDL) promotes apoptotic signaling in human coronary smooth muscle cells. This was associated by a decrease of the antiapoptotic protein Bcl-2, an increase of the pro-apoptotic protein Bax, and activation of caspase 3. Glc-oxLDL also activated NFK: B and decreased IK: B, these effects were more pronounced than those achieved with oxLDL. Our study shows that glc-oxLDL influences a broad cascade of signaling transduction pathways, which may not only result in apoptosis, but also could affect NFkappaB in human coronary cells. This cascade of events may influence the evolution of atherogenesis and vascular complications in diabetic patients
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