GLI1::FOXO4-rearranged kidney tumors: a potentially distinct renal subtype within the spectrum of GLI1-altered tumors?

Pathogenic alterations, namely, fusions and amplifications, of the GLI1 gene have been identified in various mesenchymal tumors, including pericytoma with t(7;12), plexiform fibromyxoma, gastroblastoma, and other malignant mesenchymal neoplasms arising in the soft tissues, as well as in various visceral organs. However, only three cases of GLI1-rearranged renal tumors have been reported to date, comprising two low-grade spindle cell tumors with GLI1::FOXO4 fusion along with one GLI1-rearranged case with an unknown fusion partner. In this study, we analyzed three cases with GLI1::FOXO4 fusion and overlapping morphology.

Isoform-Selective Enzyme Inhibitors by Exploring Pocket Size According to the Lock-and-Key Principle.

In the design of high-affinity and enzyme isoform-selective inhibitors, we applied an approach of augmenting the substituents attached to the benzenesulfonamide scaffold in three ways, namely, substitutions at the 3,5- or 2,4,6-positions or expansion of the condensed ring system. The increased size of the substituents determined the spatial limitations of the active sites of the 12 catalytically active human carbonic anhydrase (CA) isoforms until no binding was observed because of the inability of the compounds to fit in the active site. This approach led to the discovery of high-affinity and high-selectivity compounds for the anticancer target CA IX and antiobesity target CA VB.

[Analysis of kinetics of the combined inhibition of cholinesterases].

In the paper the analysis of the possible kinetic schemes is performed for the process of the combined inhibition of cholinesterases. It is shown that the considered schemes result in the identical experimental dependencies of the inhibition constants from the concentration of the inhibitor. Based on the analysis of about 200 experiments a linear dependence was found between logarithms of constants describing the reversible and irreversible action of the inhibitor.