Most gastrointestinal stromal tumours (GISTs) are caused by constitutively active mutations in Kit tyrosine kinase. The drug imatinib, a specific Kit inhibitor, improves the prognosis of metastatic GIST patients, but these patients become resistant to the drug by acquiring secondary mutations in the Kit kinase domain. We recently reported that a Kit mutant causes oncogenic signals only on the Golgi apparatus in GISTs. In this study, we show that in GIST, 2-methylcoprophilinamide (M-COPA, also known as "AMF-26"), an inhibitor of biosynthetic protein trafficking from the endoplasmic reticulum (ER) to the Golgi, suppresses Kit autophosphorylation at Y703/Y721/Y730/Y936, resulting in blockade of oncogenic signalling. Results of our M-COPA treatment assay show that Kit Y703/Y730/Y936 in the ER are dephosphorylated by protein tyrosine phosphatases (PTPs), thus the ER-retained Kit is unable to activate downstream molecules. ER-localized Kit Y721 is not phosphorylated, but not due to PTPs. Importantly, M-COPA can inhibit the activation of the Kit kinase domain mutant, resulting in suppression of imatinib-resistant GIST proliferation. Our study demonstrates that Kit autophosphorylation is spatio-temporally regulated and may offer a new strategy for treating imatinib-resistant GISTs.

Foot care nursing is attracting attention as a medically effective treatment for the foot lesions caused by such problems as diabetes or aging. In this study, we experimentally examined how aromatherapy affects human brain functions during foot care nursing using near-infrared spectroscopy (NIRS). 11 subjects received both foot care nursing massages and aroma oil massages. We analyzed the changes in their oxygenated hemoglobin (oxy-Hb) concentrations based on their brain activity by t-tests, and the t-test results showed significant differences between two kinds of massages in both the somatosensory and prefrontal association areas. The oxy-Hb concentration in both massages with and without aroma oil also showed a tendency to decrease with time. Our questionnaire results showed that our subjects felt more comfortable and relaxed while receiving foot care nursing with aroma oils. These results suggest that aroma oil massages are an effective foot care nursing tool and that foot care nursing is a medically effective treatment.

The first total synthesis of (+)-tanzawaic acid B, a natural polyketide bearing a pentadienoic ester and octalin moiety, has been accomplished. The synthetic improvement from previous synthetic conditions facilitated our gram-scale synthesis of the chiral octalin that possesses seven stereogenic centers and that is the core skeleton of almost all of the tanzawaic acid family.

The first total synthesis of (–)-merrillianin (1), which is a natural sesquiterpene with a tri- fused structure having a cyclopentane ring and five- and seven-membered lactone parts, is demonstrated. This asymmetric total synthesis enabled the absolute stereo structure determination of naturally occurring (–)-1.

The first total synthesis of (–)-merrillianin (1), which is a natural sesquiterpene with a tri- fused structure having a cyclopentane ring and five- and seven-membered lactone parts, is demonstrated. This asymmetric total synthesis enabled the absolute stereo structure determination of naturally occurring (–)-1.