Systematic evaluation of scoring methods for Ki67 as a surrogate for 21-gene recurrence score.

Although Ki67 labeling index is a potential predictive marker for chemotherapy benefit, its clinical utility has been limited by the lack of a standard scoring method resulting in poor interobserver reproducibility. Especially, there is no consensus on the use of average versus hotspot score for reporting. In order to determine the best method for Ki67 scoring and validate manual scoring method proposed by the International Ki67 Working Group (IKWG), we systematically compared average versus hotspot score in 240 cases with a public domain image analysis program QuPath.

Discovery of 5-Phenoxy-2-aminopyridine Derivatives as Potent and Selective Irreversible Inhibitors of Bruton's Tyrosine Kinase.

As a member of the tyrosine protein kinase Tec (TEC) family, Bruton's tyrosine kinase (BTK) is considered a promising therapeutic target due to its crucial roles in the B cell receptor (BCR) signaling pathway. Although many types of BTK inhibitors have been reported, there is an unmet need to achieve selective BTK inhibitors to reduce side effects. To obtain BTK selectivity and efficacy, we designed a novel series of type II BTK inhibitors which can occupy the allosteric pocket induced by the DFG-out conformation and introduced an electrophilic warhead for targeting Cys481.

Inhibitory effect of α-amyrin acetate isolated from Fraxinus rhynchophylla on Th17 polarization.

Background: T helper 17 (Th17) cells, which are differentiated from CD4 T cells, drive inflammation, leading to autoimmune diseases such as psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Therefore, inhibiting Th17 polarization could be a therapeutic target for inflammatory diseases.

Purpose: We investigated the inhibitory effect of Fraxinus rhynchophylla (Oleaceae) on Th17 differentiation and found its active component.