Identification of potential small-molecule protein-protein inhibitors of cancer metastasis by 3D epitope-based computational screening.

In cancer cells exposed to extracellular pressure or shear stress, AKT1-FAK interaction drives focal adhesion kinase (FAK) phosphorylation, leading to force-activated cancer cell adhesion and metastasis. Blocking the AKT1-FAK interaction is therefore an attractive target for cancer therapy, avoiding the side effects of global FAK inhibition. Starting with our previous identification of a short FAK peptide that binds AKT1, we identified a series of small-molecule inhibitor candidates using a novel approach for inhibiting protein-protein interactions. Using a 3D structural fragment of the FAK peptide as the query, millions of drug-like, commercially available molecules were screened to identify a subset mimicking the volume and chemistry of the FAK fragment to test for their ability to block pressure-sensitive FAK phosphorylation by AKT1. Two compounds reduced the stimulation of FAK phosphorylation in response to extracellular pressure in human SW620 colon cancer cells without affecting basal FAK phosphorylation. Thus, using a 3D protein interaction epitope as a novel query for ligand-based virtual screening can successfully identify small-molecules that show promise in modulating cancer cell adhesion and metastasis.

[Analysis of non-confraternity sports accidents in the surgical department of a former district hospital during the period of 2 years]. / Sportunfallerhebung der Nicht-BG-Fälle einer chirurgischen Abteilung eines ehemaligen Kreiskrankenhauses uber den Zeitraum von zwei Jahren.

This epidemiological study analyses all n = 1,659 outpatient and inpatient non-confraternity sports accidents treated during a 2-year period in a former district hospital. The largest share with 40.6% is soccer, followed by cycling (15%), general fitness sports (7.6%), outdoor sports (6.5%), winter sports (5.5%), and riding (5.2%). Soccer injuries rise steadily until the age of 30. Of 86 horse riding accidents a total of 68 involved women, but only 18 men (ratio 8 : 2). 53% of the horse riding accidents among women concern the age group between 10 and 20 years. 70.6% (79%) of the athletes under (over) 20 years were male, 29.4% (21%) female (p < 0.05). Topographically the lower extremities represent the most affected body region in all sports (runners 84.4%, soccer players 60.2%). Most accidents occur on a Sunday. The most common diagnosis is contusion, most commonly in martial arts (60.8%), followed by horse riding (51%). There is an astonishing dominance of soccer accidents given the fact that this study records all athletes, not just club athletes, unlike insurance studies. Important preventive measures would be a comprehensive biological training prophylaxis and the provision of communication of age-specific accident prevention proposals for the mainly affected sports.

[Analysis of sports injuries covered by German occupational accident insurance associations at a former district hospital over a period of six years]. / Analyse der berufsgenossenschaftlichen Sportunfälle eines ehemaligen Kreis- krankenhauses uber den Zeitraum von sechs Jahren.

An epidemiological analysis was carried out of 1,126 sports injuries covered by German occupational accident insurance at a small regional hospital over a period of six years, of which 86.6% were allotted to the sport at schools. The types of sport most frequently involved were general fitness sports (n = 486), soccer (n = 137), volleyball (n = 126), gymnastics (n = 125) and basketball (n = 121). In the general fitness sports (n = 228 women/girls, n = 258 men/boys), bruising injuries dominated (47%), followed by sprains (29%), mostly involving the upper extremities (53%). In soccer injuries (proportion of woman = 15%), bruising and injuries to the lower extremities ranked first. Falls (33%) and sprains (31%) were the most common gymnastics injuries. Injuries to the upper extremities were most common in volleyball and basketball with 72% and 68% respectively. The distribution of these sports injuries more or less mirrors the distribution of sports disciplines at schools and institutions like the Federal Border Police. Sporting activity here should include preventive elements such a proprioceptive training.