Transcription Factor Sp1 Is Involved in Expressional Regulation of Coxsackie and Adenovirus Receptor in Cancer Cells

Coxsackie and adenovirus receptor (CAR) was first known as a virus receptor. Recently, it is also known to have tumor suppressive activity such as inhibition of cell proliferation, migration, and invasion. It is important to understand how CAR expression can be regulated in cancers. Based on an existence of putative Sp1 binding site within CAR promoter, we investigated whether indeed Sp1 is involved in the regulation of CAR expression. We observed that deletion or mutation of Sp1 binding motif (−503/−498) prominently impaired the Sp1 binding affinity and activity of CAR promoter. Histone deacetylase inhibitor (TSA) treatment enhanced recruitment of Sp1 to the CAR promoter in ChIP assay. Meanwhile, Sp1 binding inhibitor suppressed the recruitment. Exogenous expression of wild-type Sp1 increased CAR expression in CAR-negative cells; meanwhile, dominant negative Sp1 decreased the CAR expression in CAR-positive cells. These results indicate that Sp1 is involved in regulation of CAR expression

C-kit-negative Extragastrointestinal Stromal Tumor Originating in the Mesentery Misdiagnosed as an Ovarian Tumor before Surgery

Gastrointestinal stromal tumors (GISTs) are rare digestive system malignancies with extragastrointestinal stromal tumors (EGISTs) being even less. Diagnosing GISTs usually requires the identification of c-kit (CD117) expression by immunohistochemical staining. A 53-year-old woman complaining of dyspepsia was referred for the evaluation of a 1.5-cm extrinsic compression at the greater curvature of the proximal antrum. EUS revealed a multiseptated mass with positive Doppler findings. Abdominal CT showed that she harbored a large, 20-cm mass in her abdominal cavity, most likely arising from the right ovary. Surgery revealed a hypervascular tumor arising from the mesentery and attached to the gastric lesser curvature. Pathological examination revealed negativity for c-kit, but positivity for the protein “Discovered on GIST-1” (DOG1), confirming the EGIST diagnosis. Herein, we report this rare case of a c-kit-negative EGIST originating in the mesentery, which was diagnosed based on staining for DOG1

Clinical Experiences of Cardiac Myxoma

Although cardiac myxoma is rare, it is the most common primary cardiac tumor. Seventy-four cases of cardiac myxoma that were surgically treated in our center between August 1980 and February 2005 were retrospectively reviewed. The mean patient age was 50.4 ± 15.0 (range 7-80) years, and 53 patients (71.6%) were female. The most common preoperative symptom, occurring in 44 patients, was dyspnea. The interval from onset of symptoms to surgery was 9 months. Seventy cases were located in the left atrium, 3 in the right atrium and 1 in the right ventricle. The myxoma in the right ventricle could not be resected completely, due to severe infiltration. Cardiopulmonary bypass and aortic cross clamp times were 100.4 ± 37.1 and 64.8 ± 29.8 minutes, respectively. There were no hospital deaths, and 7 patients suffered from postoperative complications including atrial fibrillation in 2 cases. During the follow up period (mean 105.7 ± 73.6 months), there was no tumor recurrence and 6 late deaths that were not related to the underlying tumor. There was no evidence of tumor growth in the cases with incomplete resection during the 14-month follow-up. In conclusion, in this study there was no recurrence of tumors after complete resection and surgical resection is considered to be the curative method of treatment for cardiac myxoma

GASTROPROTECTIVE EFFECTS OF LEEJUNG-TANG, AN ORIENTAL TRADITIONAL HERBAL FORMULA, ON ETHANOL-INDUCED ACUTE GASTRIC INJURY IN RATS

Leejung-tang (LJT, Rechu-to in Japanese and Lizhong-tang in Chinese) is an oriental traditional traditional herbal formula. LJT has been used for treatment of gastrointestinal disorders in Korea, Japan, and China for a long time. In present study, we investigated the protective effects of LJT against absolute ethanol induced gastric injuries. Rats in the control group were given PBS orally (5 mL/kg body weight) as the vehicle, and the absolute-ethanol group (EtOH group) received absolute ethanol (5 mL/kg body weight) by oral gavage. Rats in the positive control group were given omeprazole orally (50 mg/kg body weight) 2 h prior to the administration of absolute ethanol. The treatment groups received LJT (400 mg/kg body weight) 2 h prior to absolute ethanol administration. All rats were sacrificed 1 h after receiving the ethanol treatment. The stomach was excised for macroscopic examination and biochemical analysis. The administration of LJT protected gastric mucosa against ethanol-induced acute gastric injury, including hemorrhage and hyperemia. LJT reduced the increase in lipid peroxidation in ethanol-induced acute gastric lesions. LJT increased GSH content and activities of the antioxidant enzymes, catalase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase. These results indicate that LJT protects gastric mucosa against ethanol-induced acute gastric injury by increasing their antioxidant content. We suggest that LJT can be developed as an effective drug for the treatment of acute gastric injury

Detecting the Recurrence of Gastric Cancer after Curative Resection: Comparison of FDG PET/CT and Contrast-Enhanced Abdominal CT

The purpose of this study was to evaluate the value of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) for detecting the recurrence of gastric cancer. We performed a retrospective review of 139 consecutive patients who underwent PET/CT and contrast-enhanced abdominal CT (CECT) for surveillance of gastric cancer after curative resection. Recurrence of gastric cancer was validated by histopathologic examination for local recurrence or serial imaging study follow-up with at least 1 yr interval for recurrence of distant metastasis form. Twenty-eight patients (20.1%) were confirmed as recurrence. On the patient based analysis, there was no statistically significant difference in the sensitivity, specificity and accuracy of PET/CT (53.6%, 84.7%, and 78.4%, respectively) and those of CECT (64.3%, 86.5%, and 82.0%, respectively) for detecting tumor recurrence except in detection of peritoneal carcinomatosis. Among 36 recurrent lesions, 8 lesions (22.2%) were detected only on PET/CT, and 10 lesions (27.8%) only on CECT. PET/CT had detected secondary malignancy in 8 patients. PET/CT is as accurate as CECT in detection of gastric cancer recurrence after curative resection, excepting detection of peritoneal carcinomatosis. Moreover, additional PET/CT on CECT could improve detection rate of tumor recurrence and provide other critical information such as unexpected secondary malignancy

4-O-Carboxymethylascochlorin Inhibits Expression Levels of on Inflammation-Related Cytokines and Matrix Metalloproteinase-9 Through NF–κB/MAPK/TLR4 Signaling Pathway in LPS-Activated RAW264.7 Cells

Toll-like receptor 4 (TLR4) and matrix metalloproteinase-9 (MMP-9) are known to play important roles in inflammatory diseases such as arteriosclerosis and plaque instability. The purpose of this study was to perform the effect of 4-O-carboxymethylascochlorin (AS-6) on MMP-9 expression in lipopolysaccharide (LPS)-induced murine macrophages and signaling pathway involved in its anti-inflammatory effect. Effect of AS-6 on MAPK/NF-κB/TLR4 signaling pathway in LPS-activated murine macrophages was examined using ELISA, Western blotting, reverse transcription polymerase chain reaction (RT-PCR) and fluorescence immunoassay. MMP-9 enzyme activity was examined by gelatin zymography. AS-6 significantly suppressed MMP-9 and MAPK/NF-κB expression levels in LPS-stimulated murine macrophages. Expression levels of inducible nitric oxide synthase (iNOS), COX2, MMP-9, JNK, ERK, p38 phosphorylation, and NF-κB stimulated by LPS were also decreased by AS-6. Moreover, AS-6 suppressed TLR4 expression and dysregulated LPS-induced activators of transcription signaling pathway. The results of this study showed that AS-6 can inhibit LPS-stimulated inflammatory response by suppressing TLR4/MAPK/NF-κB signals, suggesting that AS-6 can be used to induce the stability of atherosclerotic plaque and prevent inflammatory diseases in an in vitro model

Modeling of endothelial cell dysfunction using human induced pluripotent stem cells derived from patients with end-stage renal disease

Background Endothelial cell (EC) dysfunction is a frequent feature in patients with end-stage renal disease (ESRD). The aim of this study was to generate human induced pluripotent stem cells, differentiate ECs (hiPSC-ECs) from patients with ESRD, and appraise the usefulness of hiPSC-ECs as a model to investigate EC dysfunction. Methods We generated hiPSCs using peripheral blood mononuclear cells (PBMCs) isolated from three patients with ESRD and three healthy controls (HCs). Next, we differentiated hiPSC-ECs using the generated hiPSCs and assessed the expression of endothelial markers by immunofluorescence. The differentiation efficacy, EC dysfunction, and molecular signatures of EC-related genes based on microarray analysis were compared between the ESRD and HC groups. Results In both groups, hiPSCs and hiPSC-ECs were successfully obtained based on induced pluripotent stem cell or EC marker expression in immunofluorescence and flow cytometry. However, the efficiency of differentiation of ECs from hiPSCs was lower in the ESRD-hiPSCs than in the HC-hiPSCs. In addition, unlike HC-hiPSC-ECs, ESRD-hiPSC-ECs failed to form interconnecting branching point networks in an in vitro tube formation assay. During microarray analysis, transcripts associated with oxidative stress and inflammation were upregulated and transcripts associated with vascular development and basement membrane extracellular matrix components were downregulated in ESRD-hiPSC-ECs relative to in HC-hiPSC-ECs. Conclusion ESRD-hiPSC-ECs showed a greater level of EC dysfunction than HC-hiPSC-ECs did based on functional assay results and molecular profiles. hiPSC-ECs may be used as a disease model to investigate the pathophysiology of EC dysfunction in ESRD