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Background Reactive oxygen species modulator-1 (Romo1) is a novel protein that has been reported to be crucial for cancer cell proliferation and invasion. However, its clinical implications in colorectal cancer patients are not well-known. For the first time, we investigated the association between Romo1 and the clinical outcomes of colorectal cancer patients. Study We examined Romo1 expression in resected tumor tissues immunohistochemically and assessed it with histological scores. We conducted survival analyses for patients who had curative resection (n = 190) in accordance with clinical parameters including level of Romo1 expression, and we examined the association between Romo1 expression and cell invasion using Matrigel invasion assay in colorectal cancer cells. Results We observed significantly longer mean disease-free survival in the low Romo1 group compared with the high Romo1 group (161 vs 127.6 months, p = 0.035), and the median overall survival of the low Romo1 group was significantly longer than that of the high Romo1 group (196.9 vs 171.3 months, p = 0.036). Cell invasiveness decreased in the Romo1 knockdown colorectal cancer cells in contrast to the controlled cells. Romo1 overexpression in tumor tissue was associated with a high lymph node ratio between the metastatic and examined lymph nodes (p = 0.025). Conclusions Romo1 overexpression in tumor tissue was significantly associated with survival in curatively resected colorectal cancer patients, suggesting Romo1 expression as a potential adverse prognostic marker. Increased Romo1 expression was found to be associated with high lymph node ratio. Cancer invasiveness appeared to be a key reason for the poor survival related to highly expressed Romo1.

Visceral larva migrans (VLM) syndrome is a clinical manifestation of systemic organ involvement by Toxocara species. VLM with involvement of the bladder and liver is a rare finding. A 62-year-old woman presented with diffuse bladder wall thickening and multiple liver masses with peripheral eosinophilia and urinary symptoms. We considered malignancy or eosinophilic cystitis through clinical manifestations and imaging findings. However, no suspicious malignant lesions were observed on cystoscopy and liver mass biopsy revealed the presence of eosinophilic necrotizing granuloma without malignant cells. Anti-Toxocara antibodies were detected by western blotting and the patient was diagnosed with VLM syndrome. After taking prednisolone, urinary symptoms disappeared. On abdominal CT scan taken after three months, the size of multiple liver masses and bladder wall thickening had decreased. VLM syndrome should be suspected in patients with an atypical imaging pattern and peripheral eosinophilia.

Human cases of echinostomiasis have been sporadically diagnosed by extracting worms in the endoscopy in Korea and Japan. Most of these were caused by Echinostoma hortense infection. However, in the present study, we detected 2 live worms of Echinostoma cinetorchis in the ascending colon of a Korean man (68-year old) admitted to the Gyeongsang National University Hospital with complaint of intermittent right lower quadrant abdominal pain for 5 days. Under colonoscopy, 1 worm was found attached on the edematous and hyperemic mucosal surface of the proximal ascending colon and the other was detected on the mid-ascending colon. Both worms were removed from the mucosal surface with a grasping forceps, and morphologically identified as E. cinetorchis by the characteristic head crown with total 37 collar spines including 5 end-group ones on both sides, disappearance of testes, and eggs of 108×60 µm with abopercular wrinkles. The infection source of this case seems to be the raw frogs eaten 2 months ago. This is the first case of endoscopy-diagnosed E. cinetorchis infection in Korea.

Background: The efficacy of second-line chemotherapy (CT2) after the failure of first-line chemotherapy (CT1) for advanced biliary tract cancer (BTC) has not been established. We investigated the favorable prognostic factors for CT2 to determine which patients could be expected to benefit from CT2. Methods: From a total of 168 patients who were treated with chemotherapy at our institution between January 2003 and December 2012, we retrospectively reviewed 50 patients who received CT2. Patients were treated with various chemotherapeutic combinations as CT1 and CT2. Results: The median overall survival (OS) of patients who received and CT2 was 10.2 and 5.5 months, respectively. Good performance status (PS), a serum albumin level >3.5 g/dl and metastasis to only 1 organ were independent prognostic factors that affected the OS of the patients who received CT2. Patients who had only 1 metastastic organ, a good PS and a serum albumin level >3.5 g/dl at the beginning of CT2 demonstrated prolonged survival compared to patients who did not exhibit these 3 factors (9.5 vs. 4.3 months, p < 0.005). Conclusions: CT2 should be considered for patients with advanced BTC, especially for those who have only 1 metastatic organ and remain in generally good medical condition after the failure of CT1.

Purpose Peritoneal carcinomatosis in gastric cancer (GC) patients results in extremely poor prognosis. Malignant ascites samples are the most appropriate biological material to use to evaluate biomarkers for peritoneal carcinomatosis. This study identified exosomal MicroRNAs (miRNAs) differently expressed between benign liver cirrhosis-associated ascites (LC-ascites) and malignant gastric cancer-associated ascites (GC-ascites), and validated their role as diagnostic biomarkers for GC-ascites. Materials and Methods Total RNA was extracted from exosomes isolated from 165 ascites samples (73 LC-ascites and 92 GC-ascites). Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n=22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were performed to validate the expression levels of selected exosomal miRNAs in the training (n=70) and validation (n=73) cohorts. Furthermore, carcinoembryonic antigen (CEA) levels were determined in ascites samples. Results The miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly downregulated in the GC-ascites samples compared to the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC]=0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved by the combined analysis of miR-181b-5p and CEA (AUC=0.981 and 0.946 for the training and validation cohorts, respectively). Conclusions We identified exosomal miRNAs capable of distinguishing between non-malignant and GC-ascites, showing that the combined use of miR-181b-5p and CEA could improve diagnosis.

Aims We investigated the effect of the multi-herbal medicine, WSY-1075 in an animal model of hydrochloric acid (HCl)-induced cystitis. Methods Rats were randomly assigned to three groups: sham-operated (control), HCl-induced only (HC), and HC treated with WSY-1075 (HC + WT). Oral administration of either distilled water (control, HC) or WSY-1075 (400 mg/kg) was continued for 4 weeks. In HC and HC + WT groups, cystitis was induced with 0.4 M HCl beginning on the 22nd day. Rats in each group underwent cystometrography, and bladders were examined for evidence of inflammation and oxidative stress. Results Treatment with WSY-1075 decreased the frequency of urination and reduced inflammation of the bladder tissue in a rat model of HCl-induced cystitis. Compared with the control group, the HC group showed severe chronic inflammatory and fibrosis signs, and the inflammatory grades significantly decreased following WSY-1075 treatment in the HC-WT group. The HC + WT group showed a markedly decreased expression of pro-inflammatory cytokines compared to the HC group. The level of malondialdehyde was significantly greater in the HC group compared to the control group, and it was significantly reduced in the treated (HC + WT) group. The levels of superoxide dismutase increased in the HC + WT group, which confirmed the anti-oxidant effect of WSY-1075. Conclusions We suggest that reduction of oxidative stress may play a role in this anti-inflammatory effect. Neurourol. Urodynam. 34:86–91, 2015. © 2013 Wiley Periodicals, Inc.

Summary Objectives This study was performed to measure the burden of disease from premature death and disability for chronic diseases in Korea in 2007. Study design Chronic diseases were defined using the WHO definitions. Disability-adjusted life years (DALY) were used to analyse insurance claim data. Methods This was a population-based study and included the total population of Korea. DALYs were used to analyse insurance claim data. Years of life lost (YLL) and years lost to disability (YLD) were measured in terms of incidence rate and number of deaths. DALYs were aggregated to YLL and YLD. To ensure code validity, only patients who had visited a tertiary hospital or a clinic three or more times for the same disease were included. Results Cerebrovascular disease was the leading contributor to the chronic disease burden, with a value of 907.4, followed by diabetes mellitus (899), ischaemic heart disease (710), cirrhosis of the liver (616.5), chronic obstructive pulmonary disease (512.9), asthma (503.1), hypertensive heart disease (407.5), stomach cancer (356) and peptic ulcer disease (292.5). As these results demonstrate, the highest ranked diseases were cardio-cerebrovascular or related diseases, as well as the fact that hypertension, diabetes mellitus and related complications, which are associated diseases, have became increasingly severe problems. And the rural areas have a higher burden of disease than metropolitan cities. According to difference in social status, Medicaid 2 group has more burden of disease than other groups. Conclusions It has been possible to present evidence regarding the burden of diseases and the relatively high risk of cardio-cerebrovascular disease. If the various types of cancer were combined and then the calculating tool applied, the burden would likely be greater than that of cardio-cerebrovascular disease. However, based on DALY, ischaemic heart disease demonstrated a remarkable increase compared to the rate in the previous study based on 2002 data. Underprivileged people in particular have been struggling – with chronic diseases.

Objectives : This study was to evaluate the anti-inflammatory and anti-pruritic effects of WSY-1075 composited with Corni Fructus, Angelica gigantis Radix, Lycii Fructus, Ginseng Radix, Cervi parvum Cornu and Cinnamomi Cortex in rat peritoneal mast cells (RPMCs) and scratching mouse model. Methods : WSY-1075 was prepared by extracting with 30% ethanol. In the present study, we investigated the effect of WSY-1075 on the production of tumor necrosis factor- (TNF-), interleukin- (IL-) and histamine in rat peritoneal mast cells (RPMCs) activated with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187, and on the scratching behavior in mice treated with pruriogens. Results : WSY-1075 was not cytotoxic effect in used all concentration. PMA plus A23187 treatment significantly increased TNF-, IL- and IL-6 production compared with media control in RPMCs. However, TNF-, and IL-6 production increased by PMA plus A23187 treatment were significantly inhibited by WSY-1075 (200 and 400 ). WSY-1075 also inhibited the histamine release from RPMCs stimulated by compound 48/80, which promotes histamine release. Moreover, WSY-1075 administration had an inhibitory effects on the scratching behavior induced by pruritogen (compound 48/80, histamine, serotonin and substence P) in ICR mice. Conclusion : These results suggest that WSY-1075 administration (200 mg/kg or 400 mg/kg) has the anti-inflammatory and anti-pruritic effects on the activated rat peritoneal mast cell and mouse pruritus. WSY-1075 has a potential use as a composition of medicinal plants for treatment against inflammation- and pruritus-related disease.

Objectives : This study was performed to assess the ameliorative effects of Gagam-GongJin-dan (WSY-1075) composited with Corni Fructus, Angelica gigantis Radix, Lycii Fructus, Ginseng Radix, Cervi parvum Cornu and Cinnamomi Cortex in contact dermatitis animal model. Methods : WSY-1075 was orally administrated the various concentrations (50-400 mg/kg, body weight/day) with one time per day for 10 days from 4 days after DNFB sensitization. We investigated ameliorative effects of WST-1075 on the scratching behavior, skin clinical serverity and inflammatory mediators in 2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis mice. Results : The orally administration of WSY-1075 (400 mg/kg) inhibited the scratching behavior induced by sensitization and challenge with DNFB. WSY-1075 (200 mg/kg or 400 mg/kg) administration also reduced the skin damage, inflammatory mediators, mast cell infiltration induced by DNFB. Moreover, WSY-1075 (above 200 mg/kg) administration inhibited the serum levels of IgE and IL-4 in DNFB-induced contact dermatitis mice.

Objective : The purpose of this study was to investigate the synergistic effect of Angelicae gigantis Radix (AG) and Lycii fructus (LF) ethanol extracts on skin-whitening effects. Method : LFAG extracts were prepared by extracting with 80% ethanol. The efficacy of LFAG was judged by measurement of cell viability, tyrosinase activity, melanin production, tyrosinase and microphthalmiaassociated transcription factor (MITF) expression in B16F10 murine melanoma cells by lipopolysaccharides (LPS) treatment . Results : Each extract (LF or AG) inhibited the tyrosinase activity in a dose-dependent manner. The co-treatment of LFAG extracts (25 μg/mL LF plus 25 μg/mL AG) markedly suppressed the LPS-induced cellular tyrosine activity, melanin production, tyrosinase and MMP-1 expression in B16F10 murine melanoma cells. These suppressive effects were synergistically increased by their combination.

Objectives : To develop a natural antioxidant and anti-hemolytic agents, we investigated the effects of ethanol extracts of Carpesii Fructus and Farfarae Flos. Methods : Aerial parts of Carpesii Fructus and Farfarae Flos were extracted with 80% ethanol. Antioxidant activity of Carpesii Fructus or Farfarae Flos extract was evaluated by employing three different assays, i.e., 1,1-diphenyl-2-picryl hydrazyl (DPPH), 2,2`-azino-bis (3-ethylbenzthiazoline-6-suphonic acid) diammonium (ABTS) scavenging and reducing power activities. Also, anti-hemolytic activity of Carpesii Fructus or Farfarae Flos extract was determined using [2,2`-azobis (2-methylpropionamidine) dihydrochloride (AAPH)]-induced hemolysis, glutathione (GSH) depletion and malondialdehyde (MDA) formation in normal rat red blood cells (RBC) or plasma. Results : The extracts obtained from Carpesii Fructus and Farfarae Flos dose-dependently increased the scavenging activity on DPPH- or ABTS-induced radicals and the reducing power activities. Carpesii Fructus and Farfarae Flos were similar to the scavenging activity and the reducing power of butylated hydroxy anisole effect at high concentration (). RBC oxidative hemolysis and plasma MDA formation induced by AAPH were significantly suppressed by the extracts of Carpesii Fructus and Farfarae Flos in a dose-dependent manner. Also, Carpesii Fructus and Farfarae Flos extracts prevented the depletion of cystosolic antioxidant GSH in RBCs. Carpesii Fructus generally had better than the free radical scavenging activity, the reducing power and anti-hemolytic effects of Farfarae Flos. Conclusions : These results suggest that Carpesii Fructus and Farfarae Flos may have value as the potential antioxidant and anti-hemolytic medicinal plant.

Background/Aims: The aim of this study was to investigate the mortality, bleed ing control rate, and their associated predictors in patients treated with Seng staken-Blakemore (SB) tube for uncontrolled variceal hemorrhage associated with hemodynamic instability or failure of endoscopic treatment. Methods: The clinical data of 66 consecutive patients with uncontrolled variceal hemorrhage treated with SB tube at Gyeongsang National University Hospital from October 2010 to October 2015 were retrospectively analyzed. Results: The overall success rate of initial hemostasis with SB tube was 75.8%, and the independent factors associated with hemostasis were non-intubated state before SB tube (odds ratio, 8.50; p = 0.007) and Child-Pugh score < 11 (odds ratio, 15.65; p = 0.022). Rebleeding rate after successful initial hemostasis with SB tube was 22.0%, and esophageal rupture occurred in 6.1%. Mortality within 30 days was 42.4%, and the related independent factors with mortality were failure of ini tial hemostasis with SB tube (hazard ratio, 6.24; p < 0.001) and endotracheal intu bation before SB tube (hazard ratio, 2.81; p = 0.018). Conclusions: Since the era of endoscopic band ligation, SB tube might be a ben eficial option as a temporary salvage treatment for uncontrolled variceal hemor rhage. However, rescue therapy had a high incidence of fatal complication and rebleeding.

Objectives: This study investigated the etiology of acute viral hepatitis and compared the clinical features of hepatitis E virus (HEV) infections with those of other acute viral hepatitis infections in Korea. Methods: This study included 2,357 consecutive patients who were diagnosed with acute hepatitis, based on acute illness with jaundice or elevated alanine aminotransferase levels (>100 IU/L), between January 2007 and January 2016. Acute viral infections were observed in 23 (19.8%) patients with HEV, 49 (42.2%) patients with hepatitis A virus, 28 (24.1%) patients with hepatitis B virus, and 16 (13.8%) patients with hepatitis C virus. Results: The incidence of acute HEV infection was higher among older patients (median age: 49 years) and male patients (69.6%), and was associated with the consumption of undercooked or uncooked meat (43.5%). Half of the acute HEV infections involved underlying liver disease, such as alcoholic liver disease, chronic hepatitis B, common bile duct stones, and autoimmune hepatitis. Two HEV-infected patients were diagnosed with Guillain-Barré syndrome, although no patients developed fulminant hepatitis. Conclusion: Our findings indicate that HEV infection in Korea is frequently transmitted through the consumption of raw meat and may cause acute or chronic liver disease.

Background Although elevated levels of lactoferrin provide a biomarker for inflammatory bowel diseases and colorectal cancer, the clinical significance of these elevated levels in ascitic fluid of patients with ascites caused by liver cirrhosis is limited. The aims of our study were to investigate the usefulness of ascitic fluid lactoferrin levels for the diagnosis of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and to evaluate the association between lactoferrin levels and the development of hepatocellular carcinoma (HCC). Methods A total of 102 patients with ascites caused by cirrhosis were consecutively enrolled into the study, from December 2008 to December 2011. Ascitic fluid lactoferrin levels were quantified using a human lactoferrin enzyme-linked immunosorbent assay kit. Results The median ascitic fluid lactoferrin levels were significantly higher in patients with SBP than in those without SBP (112.7 ng/mL vs. 0.6 ng/mL; p

Gastric cancer and colorectal cancer are the leading cause of cancer mortality and have a dismal prognosis. The introduction of biological agents to treat these cancers has resulted in improved outcomes, and combination chemotherapy with targeted agents and conventional chemotherapeutic agents is regarded as standard therapy. Additional newly clarified mechanisms of oncogenesis and resistance to targeted agents require the development of new biologic agents. Aberrantly activation of the inositide signaling pathway by a loss of function PTEN mutation or gain of function mutation/amplification of PIK3CA is an oncogenic mechanism in gastric cancer and colorectal cancer. Clinical trials with biologic agents that target the inositide signaling pathway are being performed to further improve treatment outcomes of patients with advanced gastric cancer and metastatic colorectal cancer (CRC). In this review we summarize the inositide signaling pathway and introduce targeted agents that inhibit abnormal activation of this signaling pathway and clinical trials currently being performed in patients with advanced or metastatic gastric cancer and metastatic CRC using molecular target agents.

Hepatitis C virus (HCV) genotype 3 infection is very rare in high-income Asia Pacific. The aim of our retrospective observational study was to evaluate the incidence, clinical features, and treatment outcomes of patients with a genotype 3 HCV infection in the Gyeongnam Province of Korea. Ninety-eight consecutive patients diagnosed with a genotype 3 HCV infection at Gyeongsang National University Hospital, between January 2005 and December 2014, were enrolled into the study. Relevant characteristics of the study group included: 80.6% men, mean age of 41.8 years, and including 69 patients with chronic hepatitis, 25 with liver cirrhosis, and 4 with hepatocellular carcinoma (HCC). Risk factors for HCV infection, sustained virologic response rate, development of HCC, and mortality in patients with genotype 3 were retrospectively analyzed. Among all patients diagnosed with a HCV infection during the study period, the prevalence of genotype 3 was 7.3%. The incidence of genotype 3 was higher in young patients with a risk factor of IVDU (54.0%) and tattooing (62.3%). Among 45 treatment-naive genotype 3 patients, sustained virologic response was achieved with a combination of pegylated-interferon alpha and ribavirin in 75.6%. The cumulative 5-year incidence of HCC was 13.6%, and 8.9% for overall mortality. Liver cirrhosis at enrollment was an independent risk factor for HCC development. This is the first study to elucidate the clinical features and outcomes among the patients with HCV genotype 3 infection in Korea. Further prospective studies are needed to investigate transmission routes and outcomes for HCV genotype 3 infections.

Background The risk of anti-tuberculosis (TB) drug-induced liver injury (DILI) in patients with chronic viral hepatitis (CVH) is not clear. The aim of this study was to investigate incidence and risk factors associated with TB DILI in CVH and non-CVH patients. Methods Retrospectively, a total of 128 CVH patients who received anti-TB medication from January 2005 to February 2014 were reviewed. Among these, 83 patients had hepatitis B virus (HBV), 41 patients had hepatitis C virus (HCV) and 4 patients were dual hepatitis B and hepatitis C virus co-infected (HBV + HCV) with 251 non-CVH patients who received anti-TB medication selected as the controls. There were no human immunodeficiency virus co-infected patients. Risk factors for DILI were analyzed using cox regression analysis. Results The incidence of DILI was significantly higher in the HCV group (13/41 [31.7 %], p

Background EUS-guided radiofrequency ablation (EUS-RFA) could be used as an adjunct and effective alternative mode of treatment for unresectable locally advanced and nonmetastatic pancreatic adenocarcinoma. However, its translation into clinical practice has been restricted because of limited data and high procedure-related risk. Objective To evaluate the feasibility, efficacy, and safety of EUS-RFA in the normal porcine pancreas. Design Prospective, endoscopic, experimental study in a porcine model. Setting Tertiary-care referral center animal laboratory. Patients Animal study. Intervention EUS-RFA of the pancreas was attempted on 10 adult mini pigs. An 18-gauge endoscopic RFA electrode was used to puncture the body and tail of the pancreas, with an output power of 50 W for 5 minutes. Main Outcome Measurements The feasibility, efficacy, and safety of EUS-RFA. Results A spherical necrotic lesion surrounded by fibrous tissue localized in the pancreatic parenchyma was observed on histopathologic examination. The mean diameter of the ablated tissue was 23.0 ± 6.9 mm. No major procedure-related complications were noted, and all pigs survived without any distress behavioral pattern for 7 days until autopsy. Limitations Small sample size with short-term observation and the lack of evaluation of the head of the pancreas. Conclusion EUS-RFA of the pancreatic body and tail was feasible, effective, and relatively safe in a porcine model. More animal studies to assess damage to adjacent organs are required before human trials can be conducted.

Objective : This study aimed to compare the difference between Angelica decursiva, Peucedanum praeruptorum and Anthriscus sylvestris which have been used as herbal medicine, Jeonho (Angelicae Decursivae Radix) in Korea and provided the evidence to exclude A. sylvestris not to use as Joenho. Methods : The similarities of original medicinal herb with samples from local market were evaluated including morphological appearance and chromatographic fingerprint. In addition, relation between original medicinal herb and local samples were analyzed using statistical clustering methods. Results : A. decursiva, P. praeruptorum and A. sylvestris represented different morphological appearances and chromatographic fingerprint. Several samples from China exhibited similar morphological and chromatographic appearance with A. decursiva or P. praeruptorum. Eleven samples from Korea showed identical similarity to A. sylvestris. Conclusions : Since A. sylvestris represented obvious differences compared to A. decursiva and P. praeruptorum, it is required not to use A. sylvestris as medicinal herb, Jeonho. Additionally, exact identification and quality control must be applied to A. decursiva or P. praeruptorum from China in order to maintain therapeutical efficacy.

Objective：Myeongganbo (MGB) composited with Hovenia Semen, Puerariae Radi x and Dioscoreae Rhizoma is the prescription for protection of liver function. The purpose of this study was to investigate the effects of MGB extract against acetaminophen (APAP)-induced liver injury in mice.Methods：MGB extract was prepared by extracting with hot distilled water . The extract was freeze-dried following filtration through vacuum distillation system. Mice f asted for overnight were orally administrated with or without MGB extract of different doses (25-200 mg/kg/day). After 30 min, APAP was orally applied with a single dose (400 mg/kg). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in plasmas of mice. Glutathione (GSH), glutathion e peroxidase GSH-px), cyclooxygenase-2 (COX-2) activity and tumor necrosis factor-α (TNF-α) level were investigated in liver homogenates. Liver sections were stained with haematoxylin & eosin, anti-TNF-α and anti-mouse COX-2 antibodies. Results：APAP treatment remarkably increased AST and ALT activities in p lasma but inhibited GSH and GSH-px levels in liver homogenates. Also, liver injury was significantly accelerated by APAP treatment. Furthermore, APAP remarkably elevated COX-2 activity and TNF-α levels in liver homogenates. However, administration of MGB extract was able to counteract these effects. Histological studies provided supportive evidence for biochemical and molecular analysisConclusions：These results suggest that MGB extract has potent hepatoprotective effect against APAP-induced liver injury, these properties may contribute to liver disease care.Key words：Myeongganbo；acetaminophen；hepatoprotection；cyclooxygenase-2；tumor necrosis factor-α

Background/Aims Complementary medicines, including herbal preparations and nutritional supplements, are widely used without prescriptions. As a result, there has been growing interest in the risk of hepatotoxicity with these agents. It is difficult to determine causal relationships between these herbal preparations and hepatotoxicity. We report on 25 patients diagnosed with toxic hepatitis following ingestion of Polygonum multiflorum Thunb. Methods Twenty-five patients (median age, 48 years [24 to 65 years]; M:F=18:7) with suspected P. multiflorum Thunb-induced liver injury were admitted to our hospital between 2007 and 2009. We analyzed clinical and histological data, including the types and the duration of P. multiflorum Thunb intake and the duration of hospital care. We also determined the type of liver injury using the R ratio (serum activity of ALT/serum activity of ALP). Results The types of complementary medicine used included tea (n=16), liquor (n=5), tea and liquor (n=2), powder (n=1), and honeyed pudding (n=1). The most common presenting sign was jaundice (76%), and 18 patients (72%) had evidence of hepatocellular liver injury. Histological findings were consistent with acute hepatitis in all cases (n=10) for which liver biopsy was performed. Twenty-three patients (91.6%) recovered with conservative management, 1 patient (4%) had a liver transplant, and 1 patient (4%) died of hepatic failure. Conclusions In our cases, we found that P. multiflorum Thunb could be hepatotoxic and could lead to severe drug-induced liver injury, and even death.

Background Recently, placement of fully covered self-expandable metal stents (FCSEMSs) has been proposed as an alternative treatment for the management of benign biliary strictures. However, the major limitations of FCSEMSs are frequent migration and removal complications. Objective We conducted this study to compare the antimigration effects, complication rates, and short-term efficacy of 2 FCSEMSs with either an anchoring flap (AF) or a flared end (FE) at the proximal end of the stent. Design A multicenter, prospective comparative pilot study. Setting Two tertiary referral centers. Patients A total of 43 patients with benign biliary stricture who were candidates for placement of FCSEMSs were assigned to the AF (n = 22) or the FE group (n = 21). Interventions Predefined duration of placement and removal of FCSEMSs. Results After a median period of placement of 6 months (interquartile range 4-6), no patients in the AF group and 33% of patients (7 of 21, 1 in proximal and 6 in distal) in the FE group had stent migration ( P = .004). The removal rate of the FCSEMSs was 100% in both groups (per protocol, n=22 in the AF group and n=17 in the FE group). Immediate improvement of biliary stricture was 91% (20/22, per protocol) in the AF group and 88% (15/17, per protocol) in the FE group. All stents were removed without difficulty. Limitations Short-term follow-up after the removal of FCSEMSs. Conclusions With regard to the antimigration effect of FCSEMSs for benign biliary stricture, the AF design may be superior to the FE. For up to 6 months, both FCSEMSs can be endoscopically removed without complications. (Clinical trial registration number: NCT00945516.)

Expression of hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) is known to play an important role in cancer progression in various cancer cell lines. Although genipin, a constituent of Gardenia fruit, has shown to have anti-tumor activity, its role in suppression of HIF-1 protein and downstream genes has yet to be clarified. We examined the effect of genipin on intracellular level of HIF-1α and extracellular level of VEGF proteins using colon cancer cell line HCT116. We observed genipin suppressed accumulation of HIF-1α under hypoxia in various cancer cell lines including HCT116. We found out suppressed accumulation of HIF-1α occurred through modulation of protein degradation. Genipin was also observed to suppress expression of VEGF and invasion of colon cancer cells through blocking of the ERK signaling pathway. Taken together, our results provide a new insight into the potential role of genipin in suppressing cancer progression of colon cancer cells. Citation Format: Dae-Hee Lee, Sang-Choul Oh, Suk-young Lee, Hong Jun Kim. Genipin inhibits invasion and migration of colon cancer cells by suppression of HIF1α accumulation and VEGF expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2061.

Genipin, a major component of Gardenia jasminoides Ellis fruit, has been shown to inhibit the growth of gastric, prostate, and breast cancers. However, the anti-proliferative activity of genipin in colorectal cancer (CRC) has not been characterized. Herein, we demonstrated that genipin inhibits the proliferation of CRC cells and that genipin suppressed the Hedgehog pathway. Further investigation showed that p53 and NOXA protein levels were increased during inhibition of Hedgehog pathway-mediated apoptosis in CRC cells. We also showed that p53 modulated the expression of NOXA during genipin-induced apoptosis, and suppression via SMO also played a role in this process. Subsequently, GLI1 was ubiquitinated by the E3 ligase PCAF. In a xenograft tumor model, genipin suppressed tumor growth, which was also associated with Hedgehog inactivation. Taken together, these results suggest that genipin induces apoptosis through the Hedgehog signaling pathway by suppressing p53. These findings reveal a novel regulatory mechanism involving Hedgehog/p53/NOXA signaling in the modulation of CRC cell apoptosis and tumor-forming defects.

7,9,2′,4′-Tetrahydroxy-8-isopentenyl-5-methoxychalcone (THIPMC), isolated from the roots of Sophora flavescens Ait., was found to be active against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), either alone or in combination with ampicillin (AM) or gentamicin (GM), vis checkerboard assay. Minimum inhibitory concentrations ranged from 1 to 8 μg/mL for THIPMC, from 128 to 1024 μg/mL for AM, and from 128 to 512 μg/ mL for GM, respectively. The combinations of THIPMC plus AM or GM yielded a fractional inhibitory concentration index ranging from 0.188 to 0.375 μg/mL, thereby indicating a synergistic effect. These findings suggest that THIPMC alone or in combination with antibiotics against MRSA might be useful for controlling MRSA infections. However, VRE infection was only effectively treated by THIPMC alone.

Methanol extracts of the root of Dipsacus asper Wall (Dipsacaceae) were found to exhibit apoptosis-inducing activities in U937 (human monocyte-like histiocytic) cells. Investigation of the active n-BuOH fraction led to the isolation of akebia saponin D (ASD). Structure was established by spectroscopic methods. Treatment of U937 cells with ASD induced apoptosis in a dose dependent manner. ASD exerted strong cytotoxicity against human and murine leukemia cells. It is significantly increased the subG1 cell population and expression of p53 and Bax gene. And also ASD enhanced NO production from RAW264.7 macrophage cells. Taken together, these results strongly indicate that ASD may exert apoptosis-inducing activity via induction of apoptosis through activation chiefly via the nitric oxide and apoptosis-related p53 and Bax gene expression. These data provide scientific evidence that Dipsacus asper Wall can be useful as a chemopreventive agent.

In this paper, we describe an implementation of small mobile robot that can be used at research and application of mobile sensor networking. This robot that will constitute the sensor network, as a platform of multi-robot system for each to be used as sensor node, has to satisfy restrictions in many aspects in order to perform sensing, communication protocol, and application algorithms. First, the platform must be designed with a robust structure and low power consumption since its maintenance after deployment is difficult. Second, it must have flexibility and modularity to be used effectively in any structure so that it can be used in various applications. Third, it must support the technique of wireless network for ubiquitous computing environment. At last, to let many nodes be scattered, it must be cost-effective and small. Considering the above restrictions of the mobile platform for sensor network, we designed and implemented robots control the current of actuator by using additional circuit for power efficiency. And we chose MSP430 as MCU, CC2420 as RF transceiver, and etc, that have the strength in the aspect of power. For flexibility and modularity, the platform has expansion ports. The results of experiments are described to show that this robot can act as sensor node by RF communication process with Zigbee standard protocol, execute the navigation process with simple obstacle avoidance and the moving action with RSSI(Received Signal Strength Indicator), operate at low-power, and be made with approx. $100.

Primary malignant pericardial mesothelioma (PMPM) is a rare tumor with poor prognosis. Surgery is the treatment of choice, but numerous cases are inoperable. For the treatment of inoperable or metastatic cases, systemic chemotherapy is required. However, a standard chemotherapeutic regimen for the treatment of pericardial mesothelioma has not yet been established. Chemotherapy involving pemetrexed and cisplatin has been actively used in the treatment of pleural or peritoneal mesothelioma, and may be considered for the treatment of PMPM. The present study reports the case of a patient with PMPM with lung metastasis who demonstrated a positive response to treatment with pemetrexed and cisplatin followed by pemetrexed maintenance chemotherapy, leading to prolonged progression-free survival for 21 months.

Catalpol is an effective component of rehmannia root and known to possess various pharmacological properties. The present study was aimed at investigating the potential effects of catalpol on the lifespan and stress tolerance usingC. elegansmodel system. Herein, catalpol showed potent lifespan extension of wild-type nematode under normal culture condition. In addition, survival rate of catalpol-fed nematodes was significantly elevated compared to untreated control under heat and oxidative stress but not under hyperosmolality conditions. We also found that elevated antioxidant enzyme activities and expressions of stress resistance proteins were attributed to catalpol-mediated increased stress tolerance of nematode. We further investigated whether catalpol’s longevity effect is related to aging-related factors including reproduction, food intake, and growth. Interestingly, catalpol exposure could attenuate pharyngeal pumping rate, indicating that catalpol may induce dietary restriction of nematode. Moreover, locomotory ability of aged nematode was significantly improved by catalpol treatment, while lipofuscin levels were attenuated, suggesting that catalpol may affect age-associated changes of nematode. Our mechanistic studies revealed thatmek-1, daf-2, age-1, daf-16, andskn-1are involved in catalpol-mediated longevity. These results indicate that catalpol extends lifespan and increases stress tolerance ofC. elegansvia DAF-16/FOXO and SKN-1/Nrf activation dependent on insulin/IGF signaling and JNK signaling.

Although chemotherapy is widely recommended for patients with metastatic biliary tract cancer, the natural course of these patients, especially those with good performance status who are indicated for chemotherapy, is not known.We retrospectively reviewed patients with metastatic or locally advanced biliary cancer who were diagnosed at six cancer centers. Patients were eligible if they had good performance (ECOG 0-2) and no history of any treatment for cancer. The primary objective was to evaluate the survival time of patients with advanced biliary cancer with good performance who were untreated.Of the 1677 patients, 204 met the inclusion criteria. The median age and overall survival were 72.0 years and 7.1 months. Overall survival (months) by location was 4.7 for intrahepatic, 9.7 for extrahepatic, 4.4 for gallbladder and 11.2 for ampulla of vater cancer. In subgroup analysis, overall survival of locally advanced biliary cancer was 13.8 months and that of patients with normal carcinoembryonic antigen/carbohydrate antigen 19-9 was 10.6 months. In multivariate analysis, variables that were associated with poor prognosis were metastatic biliary cancer [hazard ratio 2.19 (P = 0.001)], high baseline carcinoembryonic antigen level (defined as4.0 ng/ml) [hazard ratio 1.51 (P = 0.024)] and high baseline carbohydrate antigen 19-9 level (defined as100 U/ml) [hazard ratio 1.93 (P = 0.001)].Advanced biliary tract cancer with good performance status showed modest survival without any treatment. Furthermore, subgroup analysis showed that patients with normal carbohydrate antigen 19-9 or carcinoembryonic antigen level or locally advanced status had favorable survival. Further studies comparing the outcome of chemotherapy with that of best supportive care in patients with unresectable biliary tract cancer are warranted.

Preauricular sinuses are common congenital malformations that usually occur at the anterior margin of the ascending limb of the helix. There are rare cases in which the location of the preauricular sinus is posterior to the tragus, and the direction of the sinus tract is toward the posterior. This variant type of preauricular sinus is called, 'postauricular sinus'. Postauricular sinus is uncommon. Thus, diagnosis and treatment may be delayed due to its location of its opening and atypical clinical symptoms. Typical treatment is a single stage operation through bidirectional skin incision. However, we found out that according to the length and invasion depth of the sinus tract, there was an option between unidirectional and bidirectional skin incisions that we may choose from.

Reactive oxygen species modulator 1 (Romo1) is a novel protein that has been reported to be crucial for cancer cell proliferation and invasion. However, its clinical implications in colorectal cancer (CRC) patients are not well-known. For the first time, we investigated the association between Romo1 and the clinical outcomes of CRC patients. We examined Romo1 expression in resected tumor tissues immunohistochemically and assessed it with histological scores. We conducted survival analyses for patients who had curative resection (n=190) in accordance with clinical parameters including level of Romo1 expression, and we examined the association between Romo1 expression and cell invasion using Matrigel invasion assay in CRC cell lines. We observed significantly longer mean disease-free survival (DFS) in the low Romo1 group compared with the high Romo1 group (161 vs 127.6 months, p=0.035), and the median overall survival (OS) of the low Romo1 group was significantly longer than that of the high Romo1 group (196.9 vs 171.3 months, p=0.036). Cell invasiveness decreased in the Romo1 knockdown CRC cells in contrast to the controlled cells. Romo1 overexpression in tumor tissue was associated with a high lymph node ratio (LNR) between the metastatic and examined lymph nodes (p=0.025). Romo1 overexpression in tumor tissue was significantly associated with survival in curatively resected CRC patients, suggesting Romo1 expression as a potential adverse prognostic marker. Increased Romo1 expression was found to be associated with high LNR. Cancer invasiveness appeared to be a key reason for the poor survival related to highly expressed Romo1. Citation Format: Min Jee Jo, Hong Jun Kim, Suk-Young Lee, Dae-Hee Lee, Sang Cheul Oh. Reactive oxygen species modulator 1 (Romo1) predicts unfavorable prognosis in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2254. doi:10.1158/1538-7445.AM2017-2254

Supplemental Digital Content is available in the text, The appropriate α-fetoprotein (AFP) level to confirm hepatocellular carcinoma (HCC) could be 100 ng/mL; however, the clinical significance of falsely elevated AFP in patients without HCC has not been fully studied. We investigated the clinical features and outcome of patients without HCC but with high AFP levels (100 ng/mL), especially with chronic hepatitis B (CHB) or C (CHC). The sample included 124 consecutive patients with CHB (n = 97) or CHC (n = 27), with AFP levels >100 ng/mL and without HCC at baseline. Multivariate Cox proportional regression analysis was performed to determine the factors associated with AFP normalization and HCC development. During the mean 52-month follow-up, the proportion of patients with CHB with AFP normalization (90.7%) was significantly higher than the proportion of patients with CHC (59.3%, P 100 ng/mL). With either CHB or CHC, persistent AFP elevation (>12 months), regardless of antiviral treatment, might be an important marker of HCC development.

Post-gastrectomy anastomosis site obstruction is a relatively rare complication after a subtotal gastrectomy. We present a case of a 75-year-old man who underwent a truncal vagotomy, omental patch, gastrojejunostomy, and Braun anastomosis for duodenal ulcer perforation and a gastric outlet obstruction. Following the 10(th) postoperative day, the patient complained of abdominal discomfort and vomiting. We diagnosed post-gastrectomy anastomosis site obstruction by an upper gastrointestinal series and an upper endoscopic examination. We inserted a self-expandable metallic stent (SEMS) at the anastomosis site. The stent was fully expanded after deployment. On the day following the stent insertion, the patient began to eat, and his abdominal discomfort was resolved. This paper describes the successful management of post-gastrectomy anastomosis site obstruction with temporary placement of a SEMS.

An ectopic opening of the common bile duct (CBD) into the duodenal bulb is a very rare congenital anomaly of the biliary system, which may cause recurrent duodenal ulcer or biliary diseases such as choledocholithiasis and cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP) plays a major role in the diagnosis of this anomaly. We report two such cases: one in a 61-year-old man and the other in a 57-year-old man. In the first case, this anomaly caused acute cholangitis with multiple CBD stones, which were successfully treated by ERCP. In the second case, abdominal computed tomography showed pneumobilia, which was further evaluated using ERCP. Besides, this patient was diagnosed with an ectopic opening of the CBD associated with gallbladder cancer. We report these unusual cases and review the relevant medical literature.

We investigated the effect of the multi-herbal medicine, WSY-1075 in an animal model of hydrochloric acid (HCl)-induced cystitis.Rats were randomly assigned to three groups: sham-operated (control), HCl-induced only (HC), and HC treated with WSY-1075 (HC + WT). Oral administration of either distilled water (control, HC) or WSY-1075 (400 mg/kg) was continued for 4 weeks. In HC and HC + WT groups, cystitis was induced with 0.4 M HCl beginning on the 22nd day. Rats in each group underwent cystometrography, and bladders were examined for evidence of inflammation and oxidative stress.Treatment with WSY-1075 decreased the frequency of urination and reduced inflammation of the bladder tissue in a rat model of HCl-induced cystitis. Compared with the control group, the HC group showed severe chronic inflammatory and fibrosis signs, and the inflammatory grades significantly decreased following WSY-1075 treatment in the HC-WT group. The HC + WT group showed a markedly decreased expression of pro-inflammatory cytokines compared to the HC group. The level of malondialdehyde was significantly greater in the HC group compared to the control group, and it was significantly reduced in the treated (HC + WT) group. The levels of superoxide dismutase increased in the HC + WT group, which confirmed the anti-oxidant effect of WSY-1075.We suggest that reduction of oxidative stress may play a role in this anti-inflammatory effect.

Recent studies proved that an inactivation of RUNX3 (runt-related transcription factor-3) expression is highly associated with lymph node metastasis and poor prognosis in various cancer types. However, the mechanism of RUNX3-mediated suppression of tumor metastasis remains unclear. Herein, we aimed to clarify the effect of RUNX3 on metastasis and angiogenesis in colorectal cancer (CRC). First, we found that the reduction of expression of RUNX3 in CRC tissues when compared with tumor adjacent normal colon tissues, as indicated by reduced RUNX3 staining, was significantly correlated with TNM stage. Second, we demonstrated that RUNX3 overexpression inhibited CRC cell migration and invasion resulting from the elevated upregulation of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) expression. In contrast, the knockdown of RUNX3 reduced the inhibition of migration and invasion of CRC cells. Last, Vascular endothelial growth factor(VEGF) is an inducer of angiogenesis and lymphangiogenesis. We found that restoration of RUNX3 decreased vascular endothelial growth factor (VEGF) secretion and suppressed endothelial cell growth and tube formation in CRC cells. Taken together, our data demonstrated that RUNX3 may provide insights into the development of RUNX3 for CRC metastasis diagnostics and therapeutics. Citation Format: Bo Ram Kim, Jung Lim Kim, Yoo Jin Na, Seong Hye Park, Sun Il Lee, Sanghee Kang, Sung Yup Joung, Suk Young Lee, Hong-Jun Kim, Dae-Hee Lee, Byung-Wook Min, Sang Cheul Oh. RUNX3 inhibits metastasis and angiogenesis in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1617.

Recent studies have reported that metformin is an anti-diabetic drug, and is the potential a promising anti-cancer agent. The purpose of this study is to evaluate whether metformin effectively sensitize human colorectal cancer (CRC) cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Metformin alone did not induce apoptosis, but significantly potentiated TRAIL-induced apoptosis in CRC cells. CRC cells treated with metformin and TRAIL activated the intrinsic and extrinsic pathways of caspase activation. To elucidate the underlying mechanism, we found that metformin significantly reduced the protein levels of Mcl-1 (Myeloid cell leukemia 1) in CRC cells, and overexpression of Mcl-1 attenuated the cell death by metformin alone, or in combination with TRAIL. Further experiments revealed that metformin did not affect the mRNA level, but proteasomal degradation and protein stability of Mcl-1. The metformin-induced degradation of Mcl-1 required the E3 ligase Mule, which is responsible for the polyubiquitination of Mcl-1. Taken together, our study is the first report indicating that metformin enhances TRAIL-induced apoptosis through the degradation of Mcl-1 by the proteasome machinery. Citation Format: Seong Hye Park, Dae-Hee Lee, Jung Lim Kim, Sun Il Lee, Bo Ram Kim, Yoo Jin Na, Suk Young Lee, Hong-Jun Kim, Sung Yup Joung, Sanghee Kang, Sang Cheul Oh. Metformin enhances TRAIL-induced apoptosis by Mcl-1 degradation via Mule in colorectal cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3497.

Activation of sonic hedgehog (Shh) signaling has been involved in progression of various cancers. Cyclopamine uses as effective treatment for cancers in which hedgehog signaling is overexpressed. In this study, we elucidated that cyclopamine sensitizes to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in gastric cancer cells. Single treatment with cyclopamine or TRAIL could not induce significant cytotoxicity in gastric cancer cells. However, combination treatment of TRAIL with cyclopamine effectively led to caspase dependent apoptosis. We found that cyclopamine increased ER (Endoplasmic Reticulum) stress level in gastric cancer cells, and using ER stress inhibitor attenuated the cell death by cyclopamine. As further underlying mechanism, induction of ER stress by cyclopamine caused upregulation of JNK (c-Jun N-terminal kinases) protein, and then accumulation of p53 protein. We conducted experiment using p53 wild-type and p53-mutated gastric cancer cells, and this of particular importance since p53 wild-type gastric cancer cells had more significant efficacy than p53-mutated cells by cyclopamine. Accumulation of p53 increased DR5 protein. Taken together, we showed that cyclopamine sensitizes to TRAIL-induced apoptosis in gastric cancer cells. Citation Format: Yoo Jin Na, Dae-Hee Lee, Jung Lim Kim, Bo Ram Kim, Seong Hye Park, Byung-Wook Min, Sun Il Lee, SangHee Kang, Sung Yup Joung, Suk Young Lee, Hong-Jun Kim, Sang Cheul Oh. Cyclopamine enhances TRAIL-induced apoptosis by induction of DR5 via ER stress in gastric cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3512.

We encountered an indigenous case of intestinal capillariasis with protein-losing enteropathy in the Republic of Korea. A 37-year-old man, residing in Sacheon-si, Gyeongsangnam-do, admitted to the Gyeongsang National University Hospital (GNUH) due to long-lasting diarrhea, abdominal pain, anasarca, and weight loss. He recalled that he frequently ate raw fish, especially the common blackish goby (Acanthogobius flavimanus) and has never been abroad. Under the suspicion of protein-losing enteropathy, he received various kinds of medical examinations, and was diagnosed as intestinal capillariasis based on characteristic sectional findings of nematode worms in the biopsied small intestine. Adults, juvenile worms, and eggs were also detected in the diarrheic stools collected before and after medication. The clinical symptoms became much better after treatment with albendazole 400 mg daily for 3 days, and all findings were in normal range in laboratory examinations performed after 1 month. The present study is the 6th Korean case of intestinal capillariasis and the 3rd indigenous one in the Republic of Korea.

BACKGROUND/AIMS Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is a well-established diagnostic technique for examining various organs of the gastrointestinal tract and pancreas, but little is known about its use in the diagnostic work-up of GB lesions. The objective of this retrospective study was to evaluate the efficacy of EUS-FNA of GB lesions. METHODOLOGY Twenty-eight patients who underwent EUS-FNA for evaluation of GB lesions were enrolled. The pathological results and complications were assessed. RESULTS EUS-FNA of GB was performed in 13 patients and that of enlarged lymph nodes was done in 18. Of the 13 GB lesions sampled by EUS-FNA, 10 were diagnosed as malignant and 3 were negative for malignant cells. Of the latter 3, two were false negatives for malignancy. All 14 metastatic lymphadenopathy cases were diagnosed with EUS-FNA of lymph nodes. EUS-FNA could differentiate adenocarcinomas and other malignant diseases. Cholecystitis occurred in one patient after EUS-FNA of the GB. CONCLUSIONS EUS-FNA is a feasible, safe and reliable method for obtaining samples from GB lesions. EUS-FNA of lymph nodes is complementary to EUS-FNA of the GB and provides nodal stage as well as histological diagnosis.

Purpose Imatinib mesylate is a powerful tyrosine kinase inhibitor that specifically targets BCR-ABL, KIT, and PDGFR kinases and is used in treatment of chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GIST), and other cancers. Although imatinib has not yet been used in gastric cancer, we verified that high-dose imatinib leads gastric cancer cell lines to apoptosis via down regulation of Akt phosphorylation in previous study. This study was undertaken to evaluate the in vitro effect of low-dose imatinib in inhibition of invasion and migration of gastric cancer cells and to define molecular mechanism underlying these effects. Methods This study was to determine the expression of PDGFR molecules in gastric cancer cells (four human gastric cancer cell lines; AGS, MKN28, MKN45, and SNU638) by semi-quantitative polimerase chain reaction (PCR). The effects of low-dose imatinib (≤20uM.ml) on cell viability were examined using MTT assay. The effects of imatinib and PDGF-BB on cell motility and cell invasion were studied using wound healing assay and matrigel invasion assay respectively. Results The results showed expression of PDGFR in all four gastric cancer cells. We measured the sensitivity of gastric cancer cell line (AGS, MKN28, MKN45, SNU638) to imatinib using MTT assay. Cell viability of low-dose imatinib treated cell was not decreased. However, cell migration and invasion was decreased with low-dose imatinib. When PDGF-BB was added, cell motility and invasion were activated. However, when both PDGF-BB and imatinib were added, that activation was not shown. Conclusion In conclusion, low-dose imatinib mesylate inhibits PDGF-BB mediated cell migration and invasion not decreasing cell viability. The results suggest that imatinib mesylate may be useful in the treatment of gastric cancer. Citation Format: Hong Jun Kim, Suk Young Lee, Sang Cheul Oh, Jun Suk Kim, Jung Lim Kim, Bo Ram Kim, Yoo Jin Na. Low-dose imatinib mesylate suppressed PDGF-BB mediated motility and invasion of gastric cancer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C35.

Asan Medical Center, University of Ulsan College of Medicine, Seoul, KoreaBackground/Aims: Histologically confirmed metastatic pancreatic cancers are infrequent. The aim of this study was to analyze clinical, therapeutic and prognostic features of pancreatic metastases.Methods: We retrospectively evaluated stage of primary malignancies, interval between diagnosis of primary tumors and detection of pancreatic metastases, treatment for metastases to the pancreas, survival rate, and prognostic factors in 31 patients with pancreatic metastases.Results: The mean age at the time of primary cancer diagnosis was 52.4±13.2 years. Primary cancers were renal cell carcinoma (n=16), non-small cell lung cancer (n=6), small cell lung cancer (n=3), colorectal carcinoma (n=2), osteosarcoma (n=1), gastric carcinoma (n=1), malignant melanoma (n=1), and thymic carcinoma (n=1). Pancreatic metastases were synchronous in six cases and metachronous in twenty five cases, with median interval time of 40.8 months (range 3-186) between the diagnosis of primary tumor and detection of pancreatic metastases. The median survival after the detection of the metastases was 16 months. In multivariate analysis, non-renal cell carcinoma as primary malignancy and positive symptom related to pancreatic metastases were associated with poor prognosis (hazard ratio [HR], 8.33; 95% CI, 2.1-33; p=0.003, and HR, 4.02; 95% CI, 1.27-12.7; p=0.018).Conclusions: Metastatic tumors to the pancreas have to be kept in mind when a patient with pancreatic mass has a history of other malignancy, even if treated several years before. In the absence of widely metastatic disease, aggressive diagnostic and therapeutic approach may offer the chance of long-term survival in selected patients. (Korean J Gastroenterol 2011;57:358-364)Key Words: Pancreatic metastasis; Carcinoma, renal cell; Survival