[Show abstract][Hide abstract] ABSTRACT: Small bowel tumors are very rare and generally malignant. As a result of the anatomical location and nonspecific manifestations of small bowel tumors, they are very difficult to diagnose. Balloon-assisted enteroscopy is a relatively noninvasive method compared to surgical resection, and allows for real-time observation, tissue confirmation with biopsy, and interventional procedures. Here, we report the case of a 69-year-old woman with a small bowel metastatic carcinoma observed with double balloon enteroscopy (DBE). She had a history of multiple cancers including ovarian cancer, bladder cancer, and breast cancer. The antegrade DBE procedure was performed before surgery for biopsy tissue confirmation. The patient underwent small bowel resection, and the final diagnosis was the same as that determined by preoperative biopsy. The final diagnosis was metastatic small bowel cancer originating from a cancer of the breast. This is the first detailed report of the preoperative diagnosis of small intestinal metastatic breast cancer by DBE.
[Show abstract][Hide abstract] ABSTRACT: SH2-containing protein tyrosine phosphatase 1 (SHP1) is an important negative regulator in cytokine-mediated signal transduction and cell cycling. Recent studies have demonstrated that SHP1 promoter methylation is frequently observed in gastric adenocarcinoma tissues. In this in vitro study, we attempted to reveal promoter hypermethylation and to investigate effects of SHP1 in gastric carcinoma cell lines. We observed that both gene and protein expression of SHP1 were negative in 8 of 10 gastric cancer cell lines (SNU-1, SNU-5, SNU-16, SNU-638, SNU-719, MKN-28, MKN-45, AGS). Methylation-specific PCR (MSP) showed a methylation-specific band only in the 10 gastric cancer lines. Bisulfite pyrosequencing in AGS, MKN-28, and SNU-719 cells indicated that methylation frequency was as high as 94.4, 92.6, and 94.5 %, respectively, in the three cell lines. Treatment of SNU-719, MKN-28, and AGS cells with 5-Aza-2'-deoxycytidine (5-Aza-dc) led to re-expression of SHP1 in these cells. Introduction of exogenous SHP1 in SNU-719 and MKN-28 cells by transient transfection substantially downregulated protein expression of constitutive phosphor-Janus kinase 2 (JAK2) (tyrosine 1007/1008) and phosphor-signal transducers and activators of transcription 3 (STAT3) (tyrosine 705), which in turn decreased expression of STAT3 target genes including those encoding cyclin D1, MMP-9, VEGF-1, and survivin. Induction of SHP1 significantly inhibited cell proliferation, migration and invasion in SNU-719 and MKN-28 cells. Taken together, epigenetic silencing of SHP1 is frequently caused by promoter hypermethylation in gastric carcinoma cells. Overexpression of SHP1 downregulates the JAK2/STAT3 pathway to modulate various target genes and inhibit cell proliferation, migration, and invasion in gastric cancer cells.
[Show abstract][Hide abstract] ABSTRACT: Background/aims:
Astaxanthin is a carotenoid pigment that has antioxidant, antitumoral, and anti-inflammatory properties. In this in vitro study, we investigated the mechanism of anticancer effects of astaxanthin in gastric carcinoma cell lines.
The human gastric adenocarcinoma cell lines AGS, KATO-III, MKN-45, and SNU-1 were treated with various concentrations of astaxanthin. A cell viability test, cell cycle analysis, and immunoblotting were performed.
The viability of each cancer cell line was suppressed by astaxanthin in a dose-dependent manner with significantly decreased proliferation in KATO-III and SNU-1 cells. Astaxanthin increased the number of cells in the G0/G1 phase but reduced the proportion of S phase KATO-III and SNU-1 cells. Phosphorylated extracellular signal-regulated kinase (ERK) was decreased in an inverse dose-dependent correlation with astaxanthin concentration, and the expression of p27(kip-1) increased the KATO-III and SNU-1 cell lines in an astaxanthin dose-dependent manner.
Astaxanthin inhibits proliferation by interrupting cell cycle progression in KATO-III and SNU-1 gastric cancer cells. This may be caused by the inhibition of the phosphorylation of ERK and the enhanced expression of p27(kip-1).
Gut and Liver 10/2015; DOI:10.5009/gnl15208 · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Esophagopleural fistula (EPF) is a rare condition that is usually accompanied by severe infection and life-threatening morbidity. Here, we report the successful treatment of an EPF by closing an esophageal orifice using the over-the-scope-clip (OTSC) system without postprocedural complications. A 41-year-old man had serious thoracic and abdominal trauma due to a traffic accident. Computed tomography revealed findings suggestive of esophageal rupture due to Boerhaave syndrome. An emergent explorative operation was performed for primary repair with the insertion of a vacuum-assisted closure device. A postoperative upper gastrointestinal series revealed an EPF tract connecting the left pleural space and distal esophagus. We performed an endoscopic procedure using the "traumatic-type"OTSC to seal the EPF, and the esophageal orifice was completely healed 2 weeks postoperatively. The OTSC system might represent a safe and feasible modality for the treatment of EPF.
[Show abstract][Hide abstract] ABSTRACT: A recent study reported that plumbagin downregulated the activity of Janus kinase 2 (JAK2)‑signal transducer and activator of transcription 3 (STAT3) pathway to show various antitumor effects in multiple myeloma cells. We aimed in this in vitro study to demonstrate the inhibition of JAK2/STAT3 pathway by plumbagin through inducing SH2‑containing protein tyrosine phosphatase 1 (SHP1) expression in the MKN‑28 gastric cancer cell line. We performed western blot analysis to measure SHP1, phospho‑JAK2/STAT3 level, and observed that plumbagin induced SHP1 expression and simultaneously downregulated phospho‑JAK2/STAT3 in MKN‑28 cells, with negative SHP1 expression. This effect was consistent when JAK2/STAT3 signaling was activated by interleukin‑6 (IL‑6), and ameliorated when cells were treated with prevanadate, a protein tyrosin phosphatase inhibitor. Furthermore, plumbagin significantly reduced gene expression of cyclin D1, vascular endothelial growth factor (VEGF)‑1, Bcl‑xL, survivin and matrix metalloproteinase‑9 (MMP‑9), known target products of STAT3 activation in gastric cancinogenesis by reverse transcription‑polymerase chain reaction (RT‑PCR). Several functional studies such as water soluble tetrazolium salt‑1 (WST‑1) assay, wound closure assay, Matrigel invasion assay and Annexin V assay were also performed, and we validated the functional effect of plumbagin for inhibition of cell proliferation, migration and invasion, and induction of apoptosis. Collectively, our findings suggest that plumbagin is a potential regulator of cellular growth, migration, invasion and apoptosis by inhibiting both constitutive and inducible STAT3 activity through induction of SHP1 in gastric cancer cells.
International Journal of Oncology 03/2015; 46(6). DOI:10.3892/ijo.2015.2935 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatolithiasis is a well-known risk factor of cholangiocarcinoma. Despite advances in diagnostic modalities, diagnosing cholangiocarcinoma in patients with hepatolithiasis still challenging and there are not enough reports on the incidence of cholangiocarcinoma in patient with hepatolithiasis after treatment. We aimed to evaluate the incidence and clinical characteristics of cholangiocarcinoma in patients with hepatolithiasis who underwent liver resection or non-resection.
Among a total of 257 patients who received treatment for hepatolithiasis, 236 patients were eligible for analysis. Exclusion criteria were follow-up period less than 9 months, preoperative diagnosis of cholangiocarcinoma, occurrence of cholangiocarcinoma within 1 year after treatment. Completeness of stone clearance was defined when there was no intrahepatic duct stone during whole follow-up period. A retrospective study was done to analyze the patients' characteristics, the results and complications of the procedure, and the long-term outcomes for these patients. Kaplan-Meier method and cox proportional regression were used for statistical analysis.
95 patients underwent hepatic resection (resection group) and 144 patients did not (non-resection group). Complete stone clearance was 71 % (67/95) in resection group and 41 % (58/141) in non-resection group (p < 0.001). The incidence of cholangiocarcinoma was 6.8 % (16/236) during follow-up period (mean 41 ± 41 months). Cholangiocarcinoma occurred 6.3 % (6/95) and 7.1 % (10/141) in resection and non-resection group, respectively. There was no significant difference in survival between two groups (p = 0.254). In analysis of according to completeness of stone clearance regardless of treatment modality, cholangiocarcinoma incidence was higher in patients with residual stone (10.4 %) than complete stone removal (3.3 %) (p = 0.263). On multivariate analysis, none of the factors (age, gender, CA19-9, stone location, bile duct stenosis, liver atrophy, stone recurrence, residual stone, and hepatic resection) showed relationship with the incidence of cholangiocarcinoma.
Hepatic resection for hepatolithiasis is considered to have a limited value in preventing cholangiocarcinoma and the patients should be carefully followed even after hepatic resection. A combination of different treatment modalities is necessary to decrease the residual stone and improve the outcome of the patients with hepatolithiasis.
World Journal of Surgery 02/2015; 39(6). DOI:10.1007/s00268-015-2965-0 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effects of butein on inflammatory cytokines, matrix metalloproteinase-9 (MMP-9), and colitis in interleukin (IL)-10(-/-) mice.
To synchronize colitis, 8- to 10-wk-old IL-10(-/-) mice were fed pellet-chow containing piroxicam for 2 wk. Subsequently, phosphate-buffered saline or butein (1 mg/kg per day, ip) was injected for 4 wk. Histologic scores, inflammatory cytokines, MMP-9 and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) expressions were analyzed in IL-10(-/-) mice and in Colo 205 cells.
Butein reduced the colonic inflammatory score by > 50%. Expression levels of IL-6, IL-1β, interferon (IFN)-γ and MMP-9 were decreased in the colons of mice exposed to butein, whereas other inflammatory cytokines (IL-17A, IL-21 and IL-22) were unchanged. Immunohistochemical staining for pSTAT3 and MMP-9 was significantly decreased in the butein-treated groups compared with the controls. Butein inhibited IL-6-induced activation of STAT3 in Colo 205 cells.
Butein ameliorated colitis in IL-10(-/-) mice by regulating IL-6/STAT3 and MMP-9 activation.
[Show abstract][Hide abstract] ABSTRACT: Most of subepithelial tumor (SET) in stomach is incidentally found during esophagogastroduodenoscpic examination. Even small gastric SETs less than 2.0 cm might have malignant potential, thus ambiguous cases should be removed and pathologically confirmed for optimal diagnosis and treatment. As endoscopic techniques are developed, endoscopic removal of gastric SETs has been reported increasingly. The endoscopic procedures for resection of gastric SETs include classic methods such as snare polypectomy or incisional enucleation, and more progressive and standard technique such as endoscopic submucosal dissection. For gastric SETs originated from deeper layer including muscularis mucosa, novel procedures such as endoscopic submucosal tunnel dissection and endoscopic full-thickness resection (EFTR) are now being introduced, and cooperation with laparoscopic approach such as laparoscopy- assisted EFTR might be an alternative option to overcome shortcomings of endoscopic procedures only and ensure more safe and complete resection.
[Show abstract][Hide abstract] ABSTRACT: There has been no study on the efficacy of lafutidine for patients with reflux esophagitis in Korea.
To evaluate the efficacy of a new-generation histamine-2 receptor antagonist, lafutidine, in comparison with famotidine in patients with reflux esophagitis.
This was a randomized, double-blind, non-inferiority trial enrolling patients with erosive esophagitis. The efficacy and safety of 20 mg lafutidine (treatment group) were compared with those of 40 mg famotidine (control group) and 20 mg omeprazole (reference group). The primary endpoint was the complete healing rates of reflux esophagitis on endoscopy after 8 weeks of treatment. The non-inferiority margin was assumed to be -15 %.
The healing rates of reflux esophagitis on endoscopy after 8 weeks of treatment were 70.14 % (101/144) in the lafutidine, 63.45 % (92/145) in the famotidine, and 85.71 % (126/147) in the omeprazole group. The difference in healing rates between the lafutidine and famotidine groups was 6.69 % (95 % confidence interval = [-4.14 to 17.52]). In addition, lafutidine was superior to famotidine in clinical improvement (53.73 % vs. 39.55 %, P = 0.0200).
Lafutidine was non-inferior to famotidine in healing of reflux esophagitis. Lafutidine, however, was superior to famotidine in terms of symptom relief of reflux esophagitis.
[Show abstract][Hide abstract] ABSTRACT: Methylation rates of the Ras association domain family 1A gene (RASSF1A) have been variously reported as between 7.5 and 66.7% in gastric carcinoma tissues. The role of this gene in gastric cancer also remains to be fully elucidated. The present study aimed to investigate whether promoter hypermethylation of RASSF1A occurs in gastric adenocarcinoma tissues and gastric cancer cell lines, and to determine the effects of RASSF1A in gastric carcinoma cell lines. The results showed a methylation‑specific band only in SNU‑719, MKN28 and AGS human gastric cancer cells (indicating full methylation), none of which exhibited RASSF1A expression. By contrast, SNU‑16, MKN‑45 and KATO‑III human gastric carcinoma cells exhibited methylation as well as unmethylation‑specific bands (indicating partial methylation), and all displayed positive or weakly positive expression of RASSF1A. Bisulfite sequencing in AGS and SNU‑719 cells revealed that virtually all CpG sites were densely methylated. When SNU‑719, MKN‑28 and AGS cells were treated with the demethylating agent 5‑aza‑2'‑deoxycytidine, RASSF1A gene expression was restored and the methylation‑specific polymerase chain reaction pattern was altered in all three cell lines. Transfection of a plasmid expressing RASSF1A into AGS and SNU‑719 cells significantly inhibited cell proliferation. Exogenous RASSF1A also reduced the expression of cyclin D1 and phospho‑retinoblastoma protein, and increased that of p27 as demonstrated by western blot analysis. Furthermore, RASSF1A expression was significantly reduced (P=0.048) and the methylation rate was elevated in gastric adenocarcinoma tissues, compared with those in adjacent healthy intestinal metaplasia (34.6 vs. 66.7%, P=0.029). The present study indicated that epigenetic silencing of RASSF1A is frequently caused by promoter hypermethylation in gastric cancer cell lines as well as in gastric adenocarcinoma tissues, which may contribute to gastric carcinogenesis.
Molecular Medicine Reports 12/2014; 11(4). DOI:10.3892/mmr.2014.3055 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) is a widely used diagnostic marker for hepatocellular carcinoma (HCC). We evaluated the correlation between alcoholic liver disease (ALD) and serum PIVKA-II levels in chronic liver disease (CLD) patients.
We retrospectively reviewed the medical records of 2,528 CLD patients without HCC. Among these patients, 76 exhibited serum high PIVKA-II levels of >125 mAU/mL (group 1). We categorized 76 control patients matched by age, sex, and the presence of liver cirrhosis from the remaining patients who were negative for serum PIVKA-II (group 2).
Group 1 revealed increased antibiotic usage (23.7% vs 2.6%, p<0.001) and incidence of ALD (60.5% vs 14.5%, p<0.001) as well as elevated aspartate aminotransferase (52.5 IU/L vs 30.5 IU/L, p=0.025) and γ glutamyl transpeptidase (67.5 IU/L vs 36.5 IU/L, p=0.005) levels compared with group 2. Further, group 1 was significantly associated with a worse Child-Pugh class than group 2. In the multivariate analysis, ALD (odds ratio [OR], 7.151; p<0.001) and antibiotic usage (OR, 5.846; p<0.001) were significantly associated with positive PIVKA-II levels.
Our study suggests that ALD and antibiotics usage may be confounding factors when interpreting high serum PIVKA-II levels in patients without HCC. Therefore, serum PIVKA-II levels in patients with ALD or in patients administered antibiotics should be interpreted with caution. (Gut Liver, Published online December 5, 2014).
Gut and liver 12/2014; 9(2). DOI:10.5009/gnl14047 · 1.81 Impact Factor