Further hypoxia determined a significant decrease of PPF on hOSTs demonstrating that, in this in vitro model of osteoblastic niche, cellular and physical parameters combine to inhibit HSC maturation within the osteoblastic niche (Figure 3D).
In lung, ovarian, prostate, and pancreatic tumor xenograft studies, FASN inhibition and paclitaxel or docetaxel combine to inhibit xenograft tumor growth with significantly enhanced anti-tumor activity.
Together, these studies indicate that environmental agents including oxidative stress and diet combine to inhibit T-cell DNA methylation, and that the epigenetically modified cells cause lupus-like autoimmunity in genetically predisposed people and mice.
Tyrosine kinase inhibitors could be combined to simultaneously inhibit multiple-linked signaling pathways.
The ability of the combined treatment to inhibit lipid peroxidation was also evaluated in NCTC 2544 and HaCaT cells by assessing MDA production, either in basal conditions or after a treatment with two different prooxidant agents with different specificity of action, as follows: AAPH (25 mM) and t-BOOH (0.25 mM).
In line with the ability of the combined treatment to inhibit the production of IL-6 and MCP-1, it reduced the phosphorylation of I κB α) in HaCaT cells, both in the presence and in the absence of TNF- α.
Two of the six p63 isoforms contain an extended C-terminus with two distinct regulatory elements that combine to auto-inhibit TAp63 α and impart a dominant-negative ability to ΔNp63 α.
A detailed understanding of each of the existing extracellular proteases, including their expression pattern during physiological and pathological events, and their preferred substrates, will provide an opportunity to combine drugs to inhibit extracellular proteases that can substitute for each other, thus obtaining the complete inhibition of the targeted process.
Crucially, within the separate two families, A. fumigatus chitinases possess highly conserved active sites [22,23], suggesting that it may be possible to generate separate pan- AfChiA x and pan- AfChiB x inhibitors that could be combined to investigate the phenotype of inhibiting all 17 chitinases concurrently.
