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      • NMR Analyses of the Conformational Transition of theAntibacterial Peptide Sarcotoxin IA Interacting with Lipid A

        Maho Yagi-Utsumi,Pornthip Boonsri,Yoshiki Yamaguchi,Koichi Kato 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1

        Glycolipids offer recognition sites of a variety of proteins such as antibodies and microbial toxins, thereby playing physiological and pathological roles on cell membrane surfaces.Therefore, these glycolipid-protein interaction systems could be potential therapeutic targets for various diseases, including bacterial infections and neurodegenerative disorders [1]. To elucidate the underlying mechanisms of molecular recognition between glycolipids and proteins, we investigatedthe interaction between sarcotoxin IA and lipid Aas a model system to characterize conformational transitions and intermolecular interactions of the membrane-binding peptides promoted on glycolipids. Lipid A is a major component of the outer membrane of Gram-negative bacteria and can be a recognition target in the innate immune system. This molecule can also serve as targets of sarcotoxin IA, which is a 39-residue cecropin-type antibacterial peptide from Sarcophaga peregrina. In order to obtain structural information at atomic level, we expressed sarcotoxin IA peptides in Escherichia coli to achieve 13C- and15N-labeling for detailed NMR analyses. We observed NMR spectral changes of sarcotoxin IA upon interacting with lipid A, which was embeded in micelles composed of dodecylphosphocholine. Our spectroscopic data revealed that the N-terminal segment of sarcotoxin IA was converted from random- coil to an amphiphilic α-helix upon specific binging to lipid A. By inspecting chemical shift perturbation data, we successfully identified key lysine residues involved in interaction with lipid A and consequent antibacterial activity.

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        Implications of Liver-Directed Therapy for Postoperative Hepatic Metastasis from Esophageal Cancer

        Masayuki Urabe,Koichi Yagi,Shinichiro Shiomi,Tetsuro Toriumi,Yasuhiro Okumura,Yasuyuki Seto 대한심장혈관흉부외과학회 2022 Journal of Chest Surgery (J Chest Surg) Vol.55 No.5

        Background: Distant recurrence of esophageal cancer (EC), even after radical resection, is common, and the most frequent site of EC metastasis is the liver. However, a multidisciplinary treatment strategy for postoperative liver metastasis (LM) from EC has yet to be established; in particular, the role of liver-directed therapy (LDT) remains uncertain. We investigated the clinicopathological features and outcomes of patients undergoing post-esophagectomy LM with versus without LDT to explore its therapeutic implications. Methods: Among 624 consecutive patients undergoing R0/R1 esophagectomy for EC, 30 were identified in whom LM had developed as the initial recurrence. Their characteristics were retrospectively reviewed. Results: Six of the 30 subjects underwent LDT for metachronous LM. Five of those 6 also received systemic chemotherapy. A comparison between the 6 LDT and 24 non-LDT cases revealed no significant differences in major clinicopathological and operative factors, except for concurrent metastasis to extrahepatic organs (1/6 vs. 15/24, p=0.044). Twenty-nine of the 30 patients died during the study period, whereas 1 who had received multimodal treatment with LDT remained alive more than 200 months after multiple LM had been detected. Kaplan-Meier analysis for survival after LM demonstrated significantly prolonged survival in LDT cases compared to non-LDT cases treated with systemic chemotherapy alone (p=0.014). Even when the analysis was limited to patients without extrahepatic metastasis, this significant prognostic advantage of LDT was maintained (p=0.047). Conclusion: Multimodal treatment combined with LDT might be beneficial for patients with metachronous LM from EC and should therefore be considered a potential treatment option.

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