Chie Takasu, Chiharu Nakasu, Yu Saitou, Yuji Morine, Tetsuya Ikemoto, Shin-ichiro Yamada, Hiroki Teraoku and Mitsuo Shimada : Mechanism of Lenvatinib Resistance via Exosomal miRNA-132/Nrf2 Axis in Hepatocellular Carcinoma., Annals of Gastroenterological Surgery, 10, 1, 178-186, 2025.
(Summary)
Lenvatinib is a multiple receptor tyrosine kinase inhibitor and a first-line targeted therapy for hepatocellular carcinoma (HCC). However, its efficacy is insufficient because of acquired resistance. We investigated the role of exosomal miRNA exchange between resistant cancer cells and naive cancer cells in the development of lenvatinib resistance. We generated lenvatinib-resistant (LVT-res) Huh7 and PLC cell lines. We first analyzed the miRNA expression profiles of Nrf2 in cancer using three public datasets and then investigated exosomal miRNA expressions. Exosomal miRNA-132 was found to be elevated in resistant cells compared with parental cells. The parental cells were cocultured with LVT-res cultured conditioned medium as recipient cells. We then compared the characteristics in parental cancer cells, resistant cells, and recipient cells. The proliferation and migration rates of recipient cells were significantly increased compared with the parental cells. Recipient cells also showed chemoresistance. The PTEN/GSK3β/Nrf2 signaling pathway was significantly upregulated in recipient cells compared with the parental cells. Inhibition of exosomal miRNA-132 reduced the malignant potential of recipient cells, chemoresistance, cell proliferation, and migration rates. Furthermore, the PTEN/GSK3β/Nrf2 signaling pathway was downregulated in recipient cells with inhibition of exosomal miRNA-132. Our study provides new findings on the role of the miRNA-132/Nrf2 axis in LVT-res cancer cells. This might be a potential therapeutic target in HCC chemoresistance.
Masaaki Nishi, Chie Takasu, Yuuma Wada, Takuya Tokunaga, Hideya Kashihara, Daichi Ishikawa, Toshiaki Yoshimoto, Chiharu Nakasu and Mitsuo Shimada : Surgical Technique of Robotic Distal Gastrectomy for Gastric Cancer Using the Hinotori Surgical System, Surgical Laparoscopy, Endoscopy & Percutaneous Techniques, 35, 3, e1369, 2025.
(Summary)
The da Vinci Surgical System (Intuitive Surgical) currently dominates robotic gastrectomy for gastric cancer. The hinotori Surgical Robot System (Medicaroid Corporation) is a newly developed, Japan-made surgical assist robot. This study aimed to introduce the initial experience of robotic gastrectomy using the hinotori and discuss key techniques and challenges. This single-center retrospective study involved 10 eligible patients who underwent curative robotic distal gastrectomy using the hinotori for primary Stage I to III gastric cancer. Short-term surgical outcomes were evaluated. Lymph node dissection was mainly performed using the conventional double bipolar technique, left-handed double bipolar technique, or laparoscopic coagulation shears from the assist port. No patients developed intraoperative complications, and all procedures were successfully completed without conversion to open or laparoscopic surgery. All patients achieved R0 resection. The median operation time was 275 minutes (range, 252 to 336 min), and the estimated blood loss was 5 mL (range, 3 to 20 mL). The drain amylase content on postoperative day 1 was 220.5 IU/L (range, 66 to 1207 IU/L). The median number of retrieved lymph nodes was 29.5 (range, 11 to 58). No patients developed postoperative Clavien-Dindo grade ≥IIIa complications, and there was no mortality. Robotic gastrectomy using the hinotori shows potential benefits for gastric cancer. Further studies are needed to validate these advantages.
(Keyword)
gastric cancer / hinotori / minimally invasive surgery / robotic gastrectomy