The expression of microRNA 574-3p as a predictor of postoperative outcome in patients with esophageal squamous cell carcinoma

Background: Despite advances in radical esophagectomies and adjuvant therapy, the postoperative prognosis in esophageal squamous cell carcinoma (ESCC) patients remains poor. The aim of this study was to identify a molecular signature to predict postoperative favorable outcomes in patients with ESCC. Methods: As a training data set, total RNA was extracted from formalin-fixed paraffin-embedded samples of surgically removed specimens from 19 ESCC patients who underwent curative esophagectomy. The expression of microRNA (miRNA) was detected using a miRNA oligo chip on which 885 genes were mounted. As a validation data set, we obtained frozen samples of surgically resected tumors from 12 independent ESCC patients and the expression of miR-574-3p was detected by quantitative real-time PCR. Results: Our microarray analysis in the training set patients identified three miRNAs (miR-574-3p, miR-106b, and miR-1303) and five miRNAs (miR-1203, miR-1909, miR-204, miR-371-3p, miR-886-3p) which were differentially expressed between the patients with (n=14) and without (n=5) postoperative tumor relapse (p<0.01 and p<0.05, respectively). Higher expression of miR-574-3p, which showed the most significant association with non-relapse (p=0.001), was associated with favorable overall survival (p=0.016). Real-time PCR experiments on the validation set patients confirmed that higher expression of miR-574-3p was associated with non-tumor relapse (p=0.029) and better overall survival (p=0.004). Conclusions: Our results suggest that the aberrant expression of the miRNAs identified in this study plays key roles in the progression of ESCC. miR-574-3p was suggested to have a tumor suppressor effect, and thus, to be a predictor of postoperative outcome in patients with ESCC

Perforation of intramural gastric metastasis during preoperative chemotherapy in a patient with thoracic esophageal squamous cell carcinoma

AbstractIntroductionPerforation of intramural metastasis to the stomach (IMS) from esophageal cancer during chemotherapy has not been reported.Presentation of caseA 68-year-old male consulted our hospital due to appetite loss. He was diagnosed with advanced esophageal squamous cell carcinoma in the lower thoracic esophagus along with a large IMS in the upper stomach. The patient received preoperative chemotherapy of docetaxel, cisplatin, and 5-fluorouracil (DCF). During the second cycle of DCF, he had upper abdominal pain and was diagnosed with gastric perforation. Omental implantation repair for the perforation, peritoneal drainage, tube-gastrostomy, and tube-jejunostomy were performed.At 24 days after emergency surgery, he underwent thoracoscopic radical esophagectomy with total gastrectomy and reconstruction with colonic interposition. Pathological findings in the esophagus demonstrated complete replacement of the tumor by fibrosis. The gastric tumor was replaced by scar tissue with multinucleated giant cells along with a small amount of viable cancer cells. The patient was alive and healthy at 14 months after the radical operation, without tumor recurrence.DiscussionThe gastric perforation occurred due to rapid regression of the IMS which had involved the whole gastric wall before chemotherapy. Close monitoring to detect rapid tumor shrinkage during chemotherapy in patients with IMS may be warranted. A two-step operation was proposed to achieve safe curative treatment in patients with perforation of IMS during preoperative chemotherapy.ConclusionWe describe the first reported case of a patient with esophageal squamous cell carcinoma who showed perforation of IMS during preoperative chemotherapy

Thymoma-associated Graft-versus-Host Disease-like Erythroderma

We report a 40-year-old woman with recurrent thymoma associated with myasthenia gravis, in whom an unusual form of erythroderma developed. A histological examination revealed a graft-versus-host disease (GVHD)-like reaction. After high-dose steroid therapy, the metastatic thymoma lesion in the abdominal cavity was reduced in size from 9.5 × 6 × 7.5 cm to 4 × 3 × 1 cm in diameter. Nevertheless, the GVHD-like erythroderma become aggravated, her condition worsened, and the patient finally suffered from respiratory failure and died of sepsis. A GVHD-like reaction may be a rare presentation of thymoma-associated immunological disorders such as myasthenia gravis or pure red cell aplasia. Herein, we discuss the present case and review pertinent reports of thymoma cases associated with GVHD

Smart Integrated Sensor for Multiple Detections of Glucose and L-Lactate Using On-Chip Electrochemical System

Multiple sensor electrodes, a supplementary electrode, a reference electrode, and signal-processing circuits were integrated on a single chip to develop a chip-shaped electrochemical sensing system. L-lactate and glucose were measured using on-chip working electrodes modified by polyion complex to immobilize lactate oxidase and glucose oxidase, respectively. Cyclic voltammetry measurements were conducted using an on-chip potentiostat. Selective and quantitative detection of glucose and L-lactate and the interference behavior were studied. Hydrogen peroxide generated by enzymatic reactions was detected by an increase in anodic oxidation current. Reaction currents at +0.7 V versus Ag/AgCl were used to obtain calibration plots. The measured dynamic ranges for L-lactate and glucose were 0.2–1.0 mM and 2.0–8.0 mM, respectively. The sensitivities were 65 nA/mM and 15 nA/mM, respectively, using a working electrode of 0.5 mm2. The 3σ detection limit was 0.19 mM and 1.1 mM, respectively. We have achieved multiple biomaterial detections on a circuit-equipped single chip. This integrated electrochemical sensor chip could be the best candidate for realizing point-of-care testing due to its portability and potential for mass production

K-ras Mutation Targeted to Gastric Tissue Progenitor Cells Results in Chronic Inflammation, an Altered Microenvironment, and Progression to Intraepithelial

Chronic infectious diseases, such as Helicobacter pylori infection, can promote cancer in a large part through induction of chronic inflammation. Oncogenic K-ras mutation in epithelial cells activates inflammatory pathways, which could compensate for a lack of infectious stimulus. Gastric histopathology and putative progenitor markers [doublecortin and calcium/calmodulin-dependent protein kinase-like 1 (Dcamkl1) and keratin 19 (K19)] in K19-K-ras-V12 (K19-kras) transgenic mice were assessed at 3, 6, 12, and 18 months of age, in comparison with Helicobacter felis–infected wild-type littermates. Inflammation was evaluated by reverse transcription–PCR of proinflammatory cytokines, and K19-kras mice were transplanted with green fluorescent protein (GFP)–labeled bone marrow. Both H. felis infection and K-ras mutation induced upregulation of proinflammatory cytokines, expansion of Dcamkl1+ cells, and progression to oxyntic atrophy, metaplasia, hyperplasia, and high-grade dysplasia. K19-kras transgenic mice uniquely displayed mucous metaplasia as early as 3 months and progressed to high-grade dysplasia and invasive intramucosal carcinoma by 20 months. In bone marrow–transplanted K19-kras mice that progressed to dysplasia, a large proportion of stromal cells were GFP+ and bone marrow–derived, but only rare GFP+ epithelial cells were observed. GFP+ bone marrow–derived cells included leukocytes and CD45− stromal cells that expressed vimentin or α smooth muscle actin and were often found surrounding clusters of Dcamkl1+ cells at the base of gastric glands. In conclusion, the expression of mutant K-ras in K19+ gastric epithelial cells can induce chronic inflammation and promote the development of dysplasia.National Institutes of Health (U.S.) (Grant NIH 5R01 CA120979-02)National Institutes of Health (U.S.) (Grant R01 DK060694)National Institutes of Health (U.S.) (Grant U01 CA143056)National Institutes of Health (U.S.) (Grant P30 DK050306)Uehara Memorial Foundatio

ハイヨウセイ キン イシュク オ フセグ コウユビキチンカ ペプチド Cblin Cbl-b inhibitor ノ コウキノウカ

Skeletal muscle atrophy caused by unloading is characterized by both decreased responsiveness to myogenic growth factors and increased proteolysis. In our previous studies, it has been shown that ubiquitin ligase Cbl-b interacted and degraded the IGF-1 signaling intermediate IRS-1. We also reported that a peptide mimetic of tyrosin608-phosphorylated IRS-1 （DGpYMP）, named Cblin, Cbl-b inhibitor. However, Cblin may tend to be degraded by aminopeptidase in vivo. We aimed to confirm whether Cblin inhibiter muscle atrophy caused by glucocorticoids in mouse C2C12 myotubes, and effects of the modified Cblin N-terminus to prevent it from degradation. Pretreatment with Cblin significantly prevented the decrease in diameters of C2C12 myotubes treated with dexamethasone, and IRS-1 degradation, expression of atrogenes mRNA was repressed, and phosphorylation of Akt/mTOR was also protected. Moreover, the 50％ inhibitory concentration of N -myristoylated Cblin and Cblin for Cbl-b-mediated IRS-1 ubiquitination was 35μM and 120μM, respectively. In addition, N -myristoylated Cblin significantly inhibited the dexamethasone-induced reduction of myotube diameter. Taken together, these results suggest that Cblin Cblin prevented the dexamethasone induced myotube atrophy, and N -myristoyled Cblin is more effective than nonmodified Cblin in prevention of muscle atrophy

トウニョウビョウ ケア ノ リスク マネージメント

The number of diabetics has been increasing in recent years. The diabetics are under varioustreatments, including the improvement of life habit and the medication for diabetes with insulin.Our hospital set a team of diabetic care, which is composed of a diabetic specialist, certified diabeteseducators（CDEs）, nurses, dietricians and pharmacists. This team takes great care of the diabetics.For medical safety measures, the department of risk management was organized in our hospital.The department investigated the cases of Hiyari-Hatto within 1 year and 3 months, from 2005to 2006, and found that 3% of them was the diabetic case, which was caused by the nurses exceptCDEs. Therefore the department made the manual of diabetic therapy in cooperation with theCDEs. All the staffs in our hospital were educated by the seminars according to the manual. Theknowledge about the diabetic therapy proved to be mostly accurate one year after the last seminar.For the improvement of medical safety, the department of risk management helps the CDEswith holding the educational seminars by giving the informations after analyzing the cases of Hiyari-Hatto and the questionnaires following the seminars