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Depolymerization and polymerization of the actin filament are indispensable in eukaryotes. The DNase I binding loop (D-loop), which forms part of the interface between the subunits in the actin filament, is an intrinsically disordered loop with a large degree of conformational freedom. Introduction of the double mutation G42A/G46A to the D-loop of the beta cytoskeletal mammalian actin restricted D-loop conformational freedom, whereas changes to the critical concentration were not large, and no major structural changes were observed. Polymerization and depolymerization rates at both ends of the filament were reduced, and cofilin binding was inhibited by the double mutation. These results indicate that the two glycines at the tip of the D-loop are important for actin dynamics, most likely by contributing to the large degree of conformational freedom.

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This report describes a patient with a gastrointestinal stromal tumor (GIST) of the rectum who developed an erythematous drug eruption and abnormal hepatic function due to imatinib mesilate but was able to continue treatment after desensitization. The patient is a 92-year-old man with a rectal GIST, 94 mm in size. As surgical resection was considered difficult, he was treated medically with imatinib mesilate at a dose of 200 mg/day, half the recommended adult dose. On Day 13 of treatment, a grade 3 drug eruption developed, and abnormal liver function tests were also noted. As the tumor was found to be KIT positive and was thus expected to respond to imatinib, he requested and underwent desensitization to imatinib mesilate. During desensitization therapy, he received imatinib mesilate four times a day at incremental doses, starting at 1 μg, and finished the 10-day course with no adverse drug reactions. A simple suspension method was used to prepare low-dose solutions to reduce the risk of exposure of healthcare professionals to the drug. The trough plasma concentration of imatinib three days after the end of desensitization was 1,560 ng/mL, which is higher than the minimum effective concentration of 1,100 ng/mL. Pharmacists played an important role in preparing dosing solutions, taking the physicochemical properties and biological toxicity of the drug into account in order to achieve the target plasma concentration. Close collaboration with pharmacists is essential to ensure successful desensitization.