High grade serous ovarian cancer (HGSOC) is the most common and aggressive ovarian cancer subtype with the worst clinical outcome due to intrinsic or acquired drug resistance. Standard treatment involves platinum compounds. Cancer development and chemoresistance is often associated with an increase in histone deacetylase (HDAC) activity. The purpose of this study was to examine the potential of HDAC inhibitors (HDACi) to increase platinum potency in HGSOC. Four HGSOC cell lines with different cisplatin sensitivity were treated with combinations of cisplatin and entinostat (class I HDACi), panobinostat (pan-HDACi), or nexturastat A (class IIb HDACi), respectively. Inhibition of class I HDACs by entinostat turned out superior in increasing cisplatin potency than pan-HDAC inhibition in cell viability assays (MTT), apoptosis induction (subG1), and caspase 3/7 activation. Entinostat was synergistic with cisplatin in all cell lines in MTT and caspase activation assays. MTT assays gave combination indices (CI values) < 0.9 indicating synergism. The effect of HDAC inhibitors could be attributed to the upregulation of pro-apoptotic genes (CDNK1A, APAF1, PUMA, BAK1) and downregulation of survivin. In conclusion, the combination of entinostat and cisplatin is synergistic in HGSOC and could be an effective strategy for the treatment of aggressive ovarian cancer.
Cake-cutting is a playful name for the fair division of a heterogeneous, divisible good among agents, a well-studied problem at the intersection of mathematics, economics, and artificial intelligence. The cake-cutting literature is rich and edifying. However, different model assumptions are made in its many papers, in particular regarding the set of allowed pieces of cake that are to be distributed among the agents and regarding the agents' valuation functions by which they measure these pieces. We survey the commonly used definitions in the cake-cutting literature, highlight their strengths and weaknesses, and make some recommendations on what definitions could be most reasonably used when looking through the lens of measure theory.
Frei et al. [6] showed that the problem to decide whether a graph is stable with respect to some graph parameter under adding or removing either edges or vertices is Θ P 2 -complete. They studied the common graph parameters α (independence number), β (vertex cover number), ω (clique number), and χ (chromatic number) for certain variants of the stability problem. We follow their approach and provide a large number of polynomial-time algorithms solving these problems for special graph classes, namely for graphs without edges, complete graphs, paths, trees, forests, bipartite graphs, and co-graphs.
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