Koshi Matsui

BMP-2 prevents apoptosis of the N1511 chondrocytic cell line through PI3K/Akt-mediated NF-κB activation

The signal transduction pathway by which bone morphogenetic protein-2 (BMP-2) regulates apoptosis in chondrocytes remains largely unknown. We investigated the involvement of phosphatidylinositol 3-kinase (PI3K)/Akt-mediated NF-κB activation by BMP-2 stimulation in the modulation of this antiapoptotic process in a chondrocytic cell line, N1511. BMP-2 prevented apoptosis through the inhibition of caspase-3 and -9 and an increase in Bcl-xL expression, and this antiapoptotic effect was inhibited by Noggin. Not only was NF-κB p65 activated transiently in the early phase (5–15 min) after treatment with BMP-2 but p65 at serine 536 was phosphorylated from 5 min as well. Akt was rapidly phosphorylated in response to BMP-2 treatment; however, the inhibition of PI3K by Wortmannin markedly reduced the phosphorylation of Akt by BMP-2. Wortmannin also decreased the NF-κB transcriptional activity that was up-regulated by BMP-2. Thus, BMP-2-induced NF-κB activation is mediated by PI3K/Akt signaling. Wortmannin treatment inhibited the antiapoptotic effect of BMP-2. These data indicate that BMP-2 can utilize a new signal transduction pathway in the NF-κB activation system, which plays a crucial role in the survival of the N1511 chondrocytic cell line.

Expression of GLUT-1 and GLUT‐3 in Xanthogranulomatous Cholecystitis Induced a Positive Result on 18F-FDG PET: Report of a Case

Although several reports have revealed that fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) is useful for differentiating between benign and malignant lesions in the gallbladder, the positive results of (18)F-FDG PET are not specific for malignancy because (18)F-FDG is also accumulated in inflammatory lesions. It is known that the most important pathway for (18)F-FDG to enter the cell body is mediated by the facilitative glucose transporter-1 (GLUT-1) through GLUT-3. We herein present a case of xanthogranulomatous cholecystitis (XGC) with a positive result on (18)F-FDG PET. In this case, GLUT-1 and GLUT-3 were both positively expressed in inflammatory cells at the gallbladder wall of XGC and this is the first report to reveal GLUT expression in XGC. This report reveals that surgeons should carefully consider the appropriate treatment of gallbladder tumor, even with a positive result on (18)F-FDG PET.

Prognostic significance of KLF4 expression in gastric cancer

To understand the roles of pluripotent stem cell-inducing genes in gastric cancer, the expression of Krüppel-like factor 4 (KLF4), Nanog, octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc) and sex-determining region Y-box 2 (SOX2) was examined using the newly developed gastric carcinoma tissue microarray. The associations between the immunohistochemical expression levels of the pluripotency-inducing factors and the clinicopathological data of 108 patients with gastric cancer were analyzed. No associations were identified between the expression levels of the five pluripotency-inducing factors and the tumor-node-metastasis (TNM) classification or clinicopathological characteristics of the patients. In addition, multivariate analysis revealed no association of Nanog, Oct4, SOX2 or c-Myc with the prognosis of the gastric cancer patients; however, low expression of KLF4 was determined to be an independent negative prognostic factor (P=0.0331), particularly in patients who underwent R0 resection (TNM stages 2 and 3; P=0.0048). In summary, low KLF4 expression was found to be negatively associated with overall survival, and may therefore be a useful prognostic marker in gastric cancer patients.

A patient with paroxysmal nocturnal hemoglobinuria being treated with eculizumab who underwent laparoscopic cholecystectomy: report of a case

Paroxysmal nocturnal hemoglobinuria (PNH) is acquired hemolytic anemia characterized by symptoms such as anemia and hemoglobinuria. In recent years, eculizumab as an anti-complement (C5) monoclonal antibody has been used for PNH and shown to have marked effects. We performed laparoscopic cholecystectomy in a patient with PNH being treated with eculizumab, and could avoid the risk of perioperative hemolysis and thrombosis. [Patient] The patient was a 48-year-old female who had developed PNH when she was 39 years old. At the age of 46 years, eculizumab administration was initiated once every 2 weeks. During the administration period, neither the progression of anemia nor hemoglobinuria was observed. In March 2013, gallstones were detected, and she was referred to our hospital for surgery. Eculizumab was administered 10 days before surgery, and laparoscopic cholecystectomy was performed in May 2013. After the operation, for the prevention of thrombosis, elastic stockings and a foot pump were used without anticoagulant administration. After the operation, neither the progression of anemia nor hemoglobinuria was observed. On postoperative day 5, eculizumab was administered as planned, and she showed a favorable general condition and was discharged. [Discussion] Perioperative care in PNH patients was conventionally considered to involve a high risk of developing anemia, thrombosis, or infection. However, after the advent of eculizumab, the control of the symptoms of PNH became possible in many patients. In this patient with PNH being treated with eculizumab, safe perioperative management was possible without the development of complications.

Rectal Neuroendocrine Tumor G1 with a Solitary Hepatic Metastatic Lesion

Rectal neuroendocrine tumor (NET) is a relatively rare tumor. NET is classified as G1, G2, or G3 according to the degree of mitosis or Ki-67 proliferation index, which reflect the malignant potential of the tumor, such as metastasis. Advanced cases with metastasis are indicated for chemotherapy treatment. However, the efficacy of chemotherapy is limited. Therefore, resection is considered, even in metastatic cases, if complete resection is possible. We herein report a case of small rectal NET discovered with hepatic metastasis classified as G1. The patient showed good progress with no recurrence after undergoing hepatectomy and endoscopic resection of rectal NET.

Clinicopathological significance of deoxycytidine kinase expression in esophageal squamous cell carcinoma

Deoxycytidine kinase (dCK) mediates the rate-limiting catabolic step in the activation of gemcitabine. Gemcitabine is a key drug for pancreatic and biliary tract cancer. However, gemcitabine is not widely used for esophageal squamous cell carcinoma (ESCC). In this study, we analyzed the expression of dCK in ESCC and evaluated the possibility of gemcitabine treatment for ESCC. In total, 76 ESCC patients who underwent esophagectomy between 1990 and 2008 were analyzed. dCK expression was analyzed immunohistochemically using tissue microarray and compared to the clinocopathological characteristics of the patients. Results identified 41 patients positive for dCK and 35 patients negative for dCK. A significant association was observed between dCK expression and gender (P=0.01), whereas the remaining factors were not associated with dCK expression. Prognosis of the patients with a high dCK expression was significantly worse than that of the patients with a low dCK expression (P=0.022). Furthermore, dCK expression was an independent prognostic factor regarding cause-specific prognosis (risk ratio, 2.2; P=0.031). In conclustion, the results of the present study suggested that dCK expression is a prognostic factor of the ESCC patients.

Corrigendum to “Antimicrobial susceptibility of common pathogens isolated from postoperative intra-abdominal infections in Japan” [J Infect Chemother 24 (2018) 330–340]

Yoshio Takesue a, w, , Shinya Kusachi a, , Hiroshige Mikamo a, , Junko Sato , Akira Watanabe , Hiroshi Kiyota , Satoshi Iwata , Mitsuo Kaku , Hideaki Hanaki , Yoshinobu Sumiyama c, , Yuko Kitagawa c, , Kazuhiko Nakajima , Takashi Ueda , Motoi Uchino , Toru Mizuguchi , Yoshiyasu Ambo , Masafumi Konosu , Keiichiro Ishibashi , Akihisa Matsuda , Kazuo Hase , Yasushi Harihara , Koji Okabayashi , Shiko Seki , Takuo Hara , Koshi Matsui , Yoichi Matsuo , Minako Kobayashi , Shoji Kubo , Kazuhisa Uchiyama , Junzo Shimizu , Ryohei Kawabata , Hiroki Ohge , Shinji Akagi , Masaaki Oka , Toshiro Wakatsuki , Katsunori Suzuki , Kohji Okamoto , Katsunori Yanagihara ae

Blood Supply Visualization for Reconstruction During Esophagectomy

An adequate blood supply to reconstructed organs is important for safe esophagogastric anastomosis during esophagectomy. We previously reported that the vascular network could be visualized in the gastric wall, colonic grafts, and free jejunal grafts by indocyanine green (ICG) fluorescence. ICG fluorescence could be used to select patients who do not need additional vessel anastomosis. However, anastomotic leakage was not reduced; its rate was 7.5 % (3/40). In the present study, we accumulated further patients and reviewed recent research regarding ICG fluorescence. Although the number of patients examined was increased from 40 to 70, further reductions in the rate of anastomotic leakage were not achieved. The rate of anastomotic leakage was 7.1 % (5/70). Thus, we reconfirmed that microcirculation detected by ICG fluorescence did not necessarily provide an adequate blood supply for viable anastomosis. Although blood supply as well as other conditions in patients may affect viable anastomosis, combination analyses such as ICG and laser Doppler flowmetry may improve the outcome of anastomotic leakage.

Adenocarcinoma in long-segment Barrett's esophagus 44 years after total gastrectomy.

Although Barretts esophagus may occur without gastric acid, Barretts adenocarcinoma after total gastrectomy is rare. Here, we present Barretts adenocarcinoma in long-segment Barretts esophagus after total gastrectomy. The patient was a 74-year-old male who underwent total gastrectomy 44 years ago. An endoscopic examination revealed long-segment Barretts esophagus starting 17 cm from the incisors and continuing 20 cm to esophagojejunostomy, with irregular mucosa 27–31 cm from the incisors. Pathological diagnosis of a biopsied specimen was adenocarcinoma. We performed subtotal esophagectomy with lymph node dissection in the prone position and reconstructed the esophagus with ileocolic interposition. Postoperative pathological diagnosis from a Barretts epithelial section was well differentiated adenocarcinoma. This case had the longest interval from total gastrectomy and smallest oral margin of Barretts epithelium. Our case suggested that careful surveillance is needed for patients exhibiting recurrent bile reflux following total gastrectomy.

Abstract 2720: Newly established Barrett's adenocarcinoma cell line (TYAE-1).

Although 10 esophageal adenocarcinoma cell lines have been reported, only 5 were Barrett9s adenocarcinoma cell lines. Furthermore, there was only one mouse-inoculated esophageal adenocarcinoma cell line. In this paper, we present a newly established Barrett9s esophageal adenocarcinoma cell line (TYAE-1). Material and Method: The Barrett9s esophageal adenocarcinoma cells were obtained from the resected tumor of a patient (74 years-old male). The resected tumor was confirmed as well-differentiated intraepithelial Barrett9s adenocarcinoma without lymphnode metastasis. The tumor was too small (T1a) for a primary culture, so we transplanted the tumor in the back of a nude mouse. Results: One month later, the tumor grew rapidly and was able to be re-transplanted to other mice. Up to the writing of this report, the tumor (TYAE-1m) was able to be re-transplanted 10 times every month. The histology of the transplanted tumor was slightly different from the primary tumor. The majority of the tumor was cribriform type and there were a few tubular-trabecular type cells. The expression of beta-Catenin was cytoplasmic in the cribriform part and membranous in the tubular part. Both cell types did express VEGF slightly however they did not express HER-2. We also started to perform in vitro cultures from the mice transplanted tumor and established TYAE-1c cell. TYAE-1c cells were able to be transplanted in nude mice and transplanted tumor showed the same histological features as TYAE-1m. TYAE-1m and TYAE-1c cells were sensitive to Gemcitabine treatment. On the other hand, both tumors did not show sensitivity for Docetaxel treatment. In conclusion: Although the tumor was small and had no invasive characteristics by clinicopathological examination, this tumor has aggressive behavior. This in vitro and in vivo Barrett9s adenocarcinoma model may useful for understanding the behavior of Barrett9s adenocarcinoma. Citation Format: Yutaka Shimada, Makoto Moriyama, Tomoyuki Okumura, Shinichi Sekine, Shigeaki Sawada, Koshi Matsui, Shozo Hojo, Kazuto Shibuya, Isaku Yoshioka, Toru Yoshida, Takuya Nagata, Kazuhiro Tsukada. Newly established Barrett9s adenocarcinoma cell line (TYAE-1). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2720. doi:10.1158/1538-7445.AM2013-2720