[Postoperative Gastric Metastasis from Needle Tract Seeding after Using of EUS-FNA for Pancreatic Body Cancer-A Case Report].

A 67-year-old woman with a pancreatic cancer diagnosed by endoscopic ultrasound with fine needle aspiration(EUS- FNA)was underwent distal pancreatectomy. Two years and 10 months after the operation, a computed tomography scan revealed a tumor in the posterior wall of the lower body of the stomach. Upper gastrointestinal endoscopy showed a 15 mm-sized submucosal tumor on the posterior wall of the angular region, and its biopsy showed tubular adenocarcinoma that it was resembling the resected pancreatic cancer. Needle tract seeding(NTS)of the pancreatic cancer to the gastric wall was suspected. After 5 courses of chemotherapy with gemcitabine and nab-paclitaxel, the tumor shrank and there were no other signs of metastasis, we performed distal gastrectomy. The pathological findings of the resected specimen showed a tubular adenocarcinoma, consistent with the primary pancreatic tumor. We finally diagnosed as the NTS of the pancreatic cancer to the gastric wall. In the case of EUS-FNA for the body or tail tumor of pancreas, it should be paid attention to the recurrence due to NTS because the surgical resection does not include the needle tract site.

[Surgical Resection of the Lymph Node Metastasis after Liver Resection for Hepatocellular Carcinoma].

A 76-year-old man had undergone right lobectomy after transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC)in segment 5/6 of the liver. He had undergone TACE for intrahepatic recurrence in segment 1 eight months after the operation. Abdominal CT revealed intrahepatic recurrence in segment 2 and segment 3 and a hepatic portal lymph node swelling 13 months after the operation, he underwent TACE and radiofrequency ablation for intrahepatic lesions. There was neither intrahepatic recurrences nor new extrahepatic lesions, and the hepatic portal lymph node resection was performed. He was discharged on postoperative day 8, and there has been no subsequent recurrence over 42 months after initial treatment. The lymph node metastasis of HCC is rare and systemic chemotherapy such as molecular targeted argent is the standard treatment, but its prognosis is poor. When a patient has a resectable metastasis with controlled intrahepatic lesions, lymph node resection appears to be an effective option.

Cellular signaling and gene expression profiles evoked by a bivalent macrocyclic peptide that serves as an artificial MET receptor agonist.

Non-native ligands for growth factor receptors that are generated by chemical synthesis are applicable to therapeutics. However, non-native ligands often regulate cellular signaling and biological responses in a different manner than native ligands. Generation of surrogate ligands comparable to native ligands is a challenging need. Here we investigated changes in signal transduction and gene expression evoked by a bivalent macrocyclic peptide (aMD5-PEG11) capable of high-affinity binding to the MET/hepatocyte growth factor (HGF) receptor. Binding of aMD5-PEG11 to the MET extracellular region was abolished by deletion of the IPT3-IPT4 domain, indicating the involvement of IPT3-IPT4 in the binding of aMD5-PEG11 to the MET receptor. aMD5-PEG11 induced dimerization and activation of the MET receptor and promoted cell migration that was comparable to induction of these activities by HGF. Signal activation profiles indicated that aMD5-PEG11 induced phosphorylation of intracellular signaling molecules, with a similar intensity and time dependency as HGF. In 3-D culture, aMD5-PEG11 as well as HGF induced epithelial tubulogenesis and up-regulated the same sets of functionally classified genes involved in multicellular organism development. Thus, a non-native surrogate ligand that consisted of a bivalent macrocyclic peptide can serve as an artificial MET receptor agonist that functionally substitutes for the native ligand, HGF.

Selection-based discovery of macrocyclic peptides for the next generation therapeutics.

Naturally occurring macrocyclic peptides represent a unique class of compounds that exhibit various biological activities ranging from antibiotics to immunosuppressant. Although the discovery of such macrocyclic peptides had relied on their isolation from living organisms, recent advances in ribosomal peptide synthesis and in display techniques made it possible to use artificially generated macrocyclic peptide libraries for selection of ligands for biologically relevant proteins. In this review, we discuss the technologies and their applications for the discovery of peptide ligands.