Takeharu Enomoto

Mitochondrial HEP27 Is a c-Myb Target Gene That Inhibits Mdm2 and Stabilizes p53

ABSTRACT The ever-expanding knowledge of the role of p53 in cellular metabolism, apoptosis, and cell cycle control has led to increasing interest in defining the stress response pathways that regulate Mdm2. In an effort to identify novel Mdm2 binding partners, we performed a large-scale immunoprecipitation of Mdm2 in the osteosarcoma U2OS cell line. One significant binding protein identified was Hep27, a member of the short-chain alcohol dehydrogenase/reductase (SDR) family of enzymes. Here, we demonstrate that the Hep27 preprotein contains an N-terminal mitochondrial targeting signal that is cleaved following mitochondrial import, resulting in mitochondrial matrix accumulation of mature Hep27. A fraction of the mitochondrial Hep27 translocates to the nucleus, where it binds to Mdm2 in the central domain, resulting in the attenuation of Mdm2-mediated p53 degradation. In addition, Hep27 is regulated at the transcriptional level by the proto-oncogene c-Myb and is required for c-Myb-induced p53 stabilization. Breast cancer gene expression analysis correlated estrogen receptor (ER) status with Hep27 expression and p53 function, providing a potential in vivo link between estrogen receptor signaling and p53 activity. Our data demonstrate a unique c-Myb-Hep27-Mdm2-p53 mitochondria-to-nucleus signaling pathway that may have functional significance for ER-positive breast cancers.

Mixed acinar-endocrine carcinoma of the pancreas with intraductal growth into the main pancreatic duct: Report of a case

The patient was a 75-year-old asymptomatic man, in whom a tumor mass in the pancreatic tail had been found 6 months earlier. Computed tomography revealed a mass 7 cm in diameter, and an enhancement with contrast medium was observed at the periphery and partially inside the mass, but not in most parts of the tumor. Endoscopic retrograde cholangiopancreatography showed a filling defect in the main pancreatic duct. A distal pancreatectomy was performed because of the possibility of a malignant tumor. The tumor consisted of a lobular invasive growth component and a component with intraductal growth into the main pancreatic duct, and histologically the tumor cells had solid acinar to partially trabecular/tubular patterns. Trypsin (an acinic cell marker) expression was widely observed, followed by the expression of chromogranin A (an endocrine cell marker) in about 30% of the tumor cells. The tumor was diagnosed as mixed acinar-endocrine carcinoma according to the WHO classification.

A rare case of concomitant huge exophytic gastrointestinal stromal tumor of the stomach and Kasabach-Merritt phenomenon

BackgroundWe report an extremely rare case of concomitant huge exophytic GIST of the stomach and Kasabach-Merritt phenomenon (KMP).Case presentationThe patient was a 67-year-old man experiencing abdominal distension since September 2006. A physical examination revealed a 25 × 30 cm hard mass that was palpable in the middle and lower left abdomen minimal intrinsic mobility and massive ascites. Since the admitted patient was diagnosed with DIC, surgery could not be performed. The patient received a platelet transfusion and the DIC was treated. Due to this treatment, the platelet count recovered to 7.0 × 104; tumor resection was performed at 16 days after admission. Laparotomy revealed a huge extraluminal tumor arising from the greater curvature of the stomach that measured 25 × 30 cm and had not ruptured into the peritoneal cavity or infiltrated other organs. Partial gastric resection was performed. The resected mass measured 25 × 25 × 20 cm. In cross section, the tumor appeared hard and homogenous with a small polycystic area. Histopathology of the resected specimen showed large spindle cell GIST with >5/50 HPF (high-power field) mitotic activity. The postoperative course was uneventful, and the coagulopathy improved rapidly.ConclusionSince the characteristic of tumor in this case was hypervascularity with bleeding and necrotic lesions, coagulopathy was thought to be caused by the trapping of platelets within a large vasculized tumor mass.

A Rare Case of Metastasis of Merkel Cell Carcinoma to the Jejunum

378 Yuta Ogura1, Takeharu Enomoto1, Shinya Mikami1, Hiroyuki Hoshino1, Akiyoshi Noda1, Osamu Saji1, Tsunehisa Matsushita1, Shinya Ishigouoka2, Masaki Yamashita2, Saeko Naruki3, Takashi Fujino3, Tetsu Fukunaga1, Takehito Otsubo1 1Division of Gastroenterological and General Surgery, 2Division of Gastroenterological Internal Medicine, 3Department of Pathology; St. Marianna University School of Medicine, Kawasaki, Japan. A Rare Case of Metastasis of Merkel Cell Carcinoma to the Jejunum JOURNAL OF CASE REPORTS 2016;6(3):378-381