Abstract. We investigated the effects of brefeldin A and ilimaquinone, inhibitors of membrane trafficking, using serotonin transporter (SERT)-expressing COS-7 cells. Both drugs significantly inhibited the serotonin uptake activity of SERT and caused SERT to be retained in the endoplasmic reticulum (ER), indicating that membrane trafficking is an important factor for SERT functional regulation. In agreement with previous reports, a C-terminal-deletion mutant of SERT (SERTΔCT) mostly localized to the ER and completely lacked serotonin uptake activity. To further elucidate the role of the C-terminus of SERT, we investigated whether overexpression of FLAG-tagged SERT C-terminus (FLAG-SERT-CT) affected the serotonin uptake activity and glycosylation of SERT. Interestingly, when concomitantly expressed with full-length FLAG-SERT in COS-7 cells, FLAG-SERT-CT increased the serotonin uptake activity and mature glycosylation of FLAG-SERT. These results indicate that the C-terminal region of SERT plays a crucial role in the functional regulation of SERT via membrane trafficking and glycosylation. In addition, proteasome inhibitors induced apparent ER stress, significantly decreased the serotonin uptake activity and mature glycosylation of SERT and caused SERT to be localized to the ER, suggesting that SERT function would be attenuated via membrane trafficking in pathological states that trigger ER stress.

We present the case of a 40-year-old man with previously treated thymic carcinoma, complaining of gradually worsening back pain. Computed tomography scans of the chest showed multiple pleural disseminated nodules with a pleural effusion in the right thorax. The patient was treated with carboplatin on day 1 plus nab-paclitaxel on day 1 and 8 in cycles repeated every 4 weeks. Objective tumor shrinkage was observed after 4 cycles of this regimen. In addition, the elevated serum cytokeratin 19 fragment level decreased, and the patient's back pain was relieved without any analgesics. Although he experienced grade 4 neutropenia and granulocyte colony-stimulating factor (G-CSF) injection, the severity of thrombocytopenia and nonhematological toxicities such as reversible neuropathy did not exceed grade 1 during the treatment. To our knowledge, this is the first report to demonstrate the efficacy of combination chemotherapy consisting of carboplatin and nab-paclitaxel against thymic carcinoma. This case report suggests that nab-paclitaxel in combination with carboplatin can be a favorable chemotherapy regimen for advanced thymic carcinoma.

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