Cyclic Stretch Force Induces Periodontal Ligament Cells to Secrete Exosomes That Suppress IL-1ß Production Through the Inhibition of the NF-κB Signaling Pathway in Macrophages.

In the oral mechanical environment, periodontal ligament cells (PDL cells) contribute to maintaining periodontal tissue homeostasis. Recent studies showed that exosomes, which are small vesicles secreted by various types of cells, play a pivotal role in cell-to-cell communication in biological processes. We examined the secretion of exosomes from PDL cells stimulated with cyclic stretch and their role in the inflammatory response of macrophages using the human macrophage cell line THP-1 and human primary monocytes/macrophages. We prepared supernatants from human PDL cells (PDL-sup) stimulated with cyclic stretch. The treatment of macrophages with PDL-sup, but not PDL-sup from unstimulated PDL cells, inhibited the production of IL-1ß in LPS/nigericin-stimulated macrophages. The pretreatment of PDL cells with GW4869, an inhibitor of exosome secretion, or siRNA for Rab27B, which controls exosome secretion, abrogated the inhibitory effects of PDL-sup. A transmission electron microscopy analysis demonstrated the existence of exosomes with diameters ranging between 30 and 100 nm in PDL-sup, suggesting that exosomes in PDL-sup contribute to this inhibition. An immunofluorescence microscopy analysis revealed that exosomes labeled with PKH67, a fluorescent dye, were incorporated by macrophages as early as 2 h after the addition of exosomes. Purified exosomes inhibited IL-1ß production in LPS/nigericin-stimulated macrophages and the nuclear translocation of NF-κB as well as NF-κB p65 DNA-binding activity in LPS-stimulated macrophages, suggesting that exosomes suppress IL-1ß production by inhibiting the NF-κB signaling pathway. Our results indicate that PDL cells in mechanical environments contribute to the maintenance of periodontal immune/inflammatory homeostasis by releasing exosomes.

[A case of metachronous splenic metastasis from gastric cancer].

A 76-year-old woman underwent a total gastrectomy with dissection of second group of lymph nodes for type 2 gastric cancer at the back wall of the middle stomach body. The gastric cancer was moderately differentiated adenocarcinoma, which involved the second group of lymph nodes. Tumor makers increased-the CEA level became 10.7 ng/mL and the CA19-9 level became 110 U/mL after the operation. CT scan showed a solitary splenic tumor sized about 60 mm in diameter. No other prominent metastatic lesions were demonstrated, so that a splenectomy was performed in February 2008. Histopathologically the splenic tumor was adenocarcinoma, and was diagnosed as metastasis of gastric cancer. The report which excised asynchronism spleen metastasis of a stomach cancer after the operation is very rare. She remains recurrence free 4 months later.

[Transcatheter arterial embolization for the continuous bleeding from duodenal carcinoma--a case report].

We report a case of duodenal carcinoma with continuous bleeding that was successfully treated with transcatheter arterial embolization using gelatin sponge particles. The case was a woman in her 70's who had a curative surgical resection for sigmoid colon cancer with liver and lung metastases, hepatic arterial infusion chemotherapy and radiofrequency ablation for liver metastasis in the past. She was admitted to our hospital because of liver abscess and anemia. Upper gastrointestinal endoscopy revealed active bleeding from a duodenal tumor. The biopsy of the specimens was made and showed duodenal adenocarcinoma. The patient was considered to be inoperable because of the liver abscess and transcatheter arterial embolization of an anterior superior pancreaticoduodenal artery through an inferior pancreaticoduodenal artery was performed for the continuous bleeding from duodenal carcinoma not completely treated by endoscopic hemostasis or frequent transfusion. After the tumor embolization anemia was improved and partial response was obtained by systemic chemotherapy of mFOLFOX6. Transcatheter arterial embolization for a continuous bleeding from duodenal carcinoma is a feasible and effective method as a noninvasive therapy when it is unabled to be treated by surgical resection or endoscopic therapy.

[A case of multiple superficial esophageal cancers with liver cirrhosis successfully treated by radiotherapy].

We report a case of multiple superficial esophageal cancers with liver cirrhosis successfully treated by radiotherapy. The patient was a 55-year-old man with liver cirrhosis who was under the treatment of internists at our hospital. Upper digestive tract endoscopic examination revealed multiple superficial esophageal cancers. We performed radiotherapy because pancytopenia was found in his peripheral blood data. The treatment was started on a outpatient basis, but the patient was hospitalized after sixteen treatments were finished because of hematemesis. Total irradiation was 66 Gy, and complete reduction was obtained. Eight months after the treatment, the patient shows no signs of recurrence. These results suggest that radiotherapy is an effective treatment for multiple superficial esophageal cancer.

[A case of esophageal cancer successfully treated by chemoradiotherapy after resection for multiple liver metastasis of sigmoid colon cancer].

The patient was a 56-year-old man. Colonoscopic findings showed a cancerous lesion of the sigmoid colon and we performed curative sigmoidectomy. Four months after the operation, abdominal CT scan revealed multiple metastatic lesions in the liver. We performed lateral segmentectomy and partial resection of the S4, S6, S8 segments and cannulation for hepatic arterial infusion chemotherapy. Continuous hepatic arterial infusion chemotherapy with 5-FU (1,000 mg/body/day) was performed for two weeks as a postoperative adjuvant chemotherapy. Immediately after the therapy, endoscopic examination for upper digestive tract showed a 0-lpl type cancer lesion in the middle of the thoracic esophagus. Concurrent chemoradiotherapy with low-dose FP was efficacious and a complete response was obtained. The patient has survived for nine months after the operation without any sign of recurrence. It is suggested that concurrent chemoradiotherapy an effective treatment for esophageal cancer.

[TS-1/CDDP therapy for advanced gastric cancer as neoadjuvant chemotherapy].

Five patients with inoperable advanced gastric cancer were treated with combination chemotherapy of TS-1 and cisplatin (CDDP). TS-1 of 80-120 mg/body/day was orally administered for 3 weeks followed by 2 drug-free weeks, and 60 mg/m2/day of CDDP was venally administered on Day 8. It was possible to evaluate all 5 patients for response and toxicity. Only low grade toxicities (Grade 1 or 2) of leukocytopenia, neutrocytopenia, anemia, nausea, diarrhea and stomatitis were seen. Four of 5 patients achieved a partial response, for a response rate of 80.0%. Stomach, liver, lymph node and peritoneal tumors responded to TS-1/CDDP. TS-1/CDDP therapy produces a high response in cases of gastric cancer, and it is useful as a neoadjuvant chemotherapy.

[A case of gastric cancer with paraaortic lymph node metastasis responding to TS-1/CDDP as neoadjuvant chemotherapy].

A 64-year-old male visited our hospital with complaints of epigastric pain. Computed tomography (CT) showed gastric cancer with extensive paraaortic lymph node metastasis. We decided that a curative operation was impossible, and administered the following chemotherapy. After 120 mg/day of TS-1 was orally administered for 3 weeks followed by 2 drug-free weeks with 90 mg of CDDP was administered intravenously on day 8, CT showed a 90.6% reduction in the paraaortic lymph node metastasis. No serious adverse reaction was observed. After 2 courses of this chemotherapy, surgery was performed after informed consent was obtained from the patient. Histrogical result showed PR. The patient is now healthy and no sign of recurrence has been observed. TS-1/CDDP therapy is useful for advanced gastric cancer.