[Show abstract][Hide abstract]ABSTRACT: Signaling pathways of gastric carcinogenesis and gastric cancer progression are being avidly studied to seek optimal treatment of gastric cancer. Among them, hepatocyte growth factor (HGF)/c-MET, phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathways have been widely investigated. Their aberrant expression or mutation has been significantly associated with advanced stage or poor prognosis of gastric cancer. Recently, aberrations of immune checkpoints including programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) have been suggested as an important step in the formation of a microenvironment favorable for gastric cancer. Accomplishments in basic research have led to the development of novel agents targeting these signaling pathways. However, phase ? studies of selective anti-HGF/c-MET antibodies and mTOR inhibitor failed to show significant benefits in terms of overall survival and progression-free survival. Few agents directly targeting STAT3 have been developed. However, this target is still critical issue in terms of chemoresistance, and SH2-containing protein tyrosine phosphatase 1 might be a significant link to effectively inhibit STAT3 activity. Inhibition of PD-1/ PD-L1 showed durable efficacy in phase ? studies, and phase ? evaluation is warranted. Therapeutic strategy to concurrently inhibit multiple tyrosine kinases is a reasonable option, however, lapatinib needs to be further evaluated to identify good responders. Regorafenib has shown promising effectiveness in prolonging progression-free survival in a phase ? study. In this topic highlight, we review the biologic roles and outcomes of clinical studies targeting these signaling pathways.
Article · May 2016 · World Journal of Gastroenterology
[Show abstract][Hide abstract]ABSTRACT: Aim:
To ascertain whether the Prague circumferential (C) length and maximal (M) length criteria for grading the extent of Barrett's esophagus can be applied prior to its widespread application in South Korea.
Two hundred and thirteen consecutive cases with endoscopic columnar-lined esophagus (CLE) were included and classified according to the Prague C and M criteria.
Of 213 cases with CLE, the distribution of maximum CLE lengths was: 0.5-0.9 cm in 99 cases (46.5%); 1.0-1.4 cm in 63 cases (29.6%); 1.5-1.9 cm in 15 cases (7.0%); 2.0-2.4 cm in 14 cases (6.6%); 2.5-2.9 cm in 1 case (0.5%); and 7.0 cm in 1 case (0.5%). Twenty cases (9.4%) had columnar islands alone. Two hundred and eight cases (97.7%) lacked the circumferential CLE component (C0Mx). Columnar islands were found in 70 cases (32.9%), of which 20 cases (9.4%) had columnar islands alone.
In regions where most CLE patients display short or ultrashort tongue-like appearance, more detailed descriptions of CLE's in < 1.0 cm lengths and columnar islands, as well as avoidance of repeating the prefix "C0" need to be considered in parallel with the widespread application of the Prague system in South Korea.
[Show abstract][Hide abstract]ABSTRACT: Melanocytic nevus is the benign proliferation of melanocytes. The most common location of melanocytic nevus is the skin of the extremities; however, there are few case reports of melanocytic nevus at the rectal mucosa. No prior case of malignant melanoma from melanocytic nevus at the rectal mucosa has been reported; therefore, it is unclear whether resection should be performed or close observation is sufficient. However, the potential malignant transformation of melanocytic nevus should be considered, including melanocytic nevus on the rectum. Melanocytic nevus of the skin can be removed by surgical excision; however, due to rare incidence on the mucosa of the gastrointestinal tract, the optimal treatment for rectal melanocytic nevus remains controversial. Here, we report the first case of melanocytic nevus on the rectal mucosa that was removed by endoscopic submucosal dissection. This case report provides useful information about the optimal management of rectal melanocytic nevus.
[Show abstract][Hide abstract]ABSTRACT: Background and aim:
The aim of this study was to compare HOXB7 expression level between gastric cancer and non-cancerous gastric tissues. Additionally, the functional effects of HOXB7, including its pro-migration or invasion and anti-apoptosis roles, were evaluated in gastric cancer cells.
Both gene and protein expression levels of HOXB7 were examined in gastric cancer cell lines, and HOXB7 expression was compared between primary or metastatic gastric cancer tissues and chronic gastritis or intestinal metaplasia tissues. Functional studies included a wound healing assay, a Matrigel invasion assay, and an Annexin-V assay, and Akt/PTEN activity was measured by western blotting.
Both gene and protein expression levels of HOXB7 could be clearly detected in various gastric cancer cell lines except MKN-28 cell. HOXB7 expression was significantly higher in primary or metastatic gastric cancer tissues than in chronic gastritis or intestinal metaplasia tissues. HOXB7 knockdown led to inhibition of cell invasion and migration, had an apoptotic effect, downregulated phosphor-Akt, and upregulated PTEN in AGS and SNU-638 cells. Reinforced expression of HOXB7 caused the opposite effects in MKN-28 and MKN-45 cells.
Our study suggests that HOXB7 has an oncogenic role in gastric cancer, which might be related to the modulation of Akt/PTEN activity to induce cell migration/invasion and anti-apoptotic effects. This article is protected by copyright. All rights reserved.
Article · Mar 2016 · Journal of Gastroenterology and Hepatology
[Show abstract][Hide abstract]ABSTRACT: Health-related quality of life (HRQOL) is an important outcome indicator for chronic disease, and particularly in the absence of biological markers for illness, such as with irritable bowel syndrome (IBS). The aims of this study were to develop and evaluate a new IBS-specific HRQOL instrument (IBS-HR-QOL).
This methodological study comprised three steps: conceptualization of the IBS-HR-QOL, item extraction and establishment of content validity, and psychometric evaluation of the instrument with 267 IBS patients recruited from four university hospitals.
The content validity of the developed IBS-HR-QOL was assessed by 11 experts. Exploratory and confirmatory factor analyses yielded four factors. The criterion and convergent validities of the IBS-HR-QOL were demonstrated using the Short Form-36 and the Hospital Anxiety and Depression Scale, respectively. Known-groups validity was demonstrated using a symptom-severity scale. The internal consistency reliability and test-retest reliability were satisfactory, with a Cronbach’s alpha and intraclass correlation coefficient of 0.93 and 0.88, respectively.
The IBS-HR-QOL comprises a total of 16 items. The IBS-HR-QOL demonstrated good psychometric properties. This instrument is easily comprehensible and short, rendering it feasible for use in clinical practice and research.
Full-text Article · Feb 2016 · Health and Quality of Life Outcomes
[Show abstract][Hide abstract]ABSTRACT: Aims:
Pancreatic cystic neoplasms (PCN) with malignant potential are thought to be less aggressive than ordinary ductal adenocarcinoma, even in the setting of malignant transformation. Therefore, deciding whether or not to carry out surgery is very difficult, especially in elderly and asymptomatic patients, because of the high risk of perioperative morbidities. The aim of the present study was to examine clinical outcomes of PCN patients aged 65 years or older.
This retrospective analysis included patients with incidentally detected PCN with follow-up durations >1 year. Patients diagnosed with obvious simple cysts, pseudocysts or pancreatic cancer and patients with a history of pancreatic disease were excluded from the study.
The present study included 201 patients (older group 104 patients ≥65 years; younger group 97 patients <65 years). Surgical resections were carried out for 27 patients in the older group and 41 patients in the younger group. There were 133 patients who were followed up without surgery (mean follow-up duration 41 months). Postoperative morbidity occurred in 22.2% of the patients in the older group and 21.9% of the patients in the younger group. Malignancy occurred in one patient in the older group and in two patients in the younger group. The PCN diameter increased in 20 patients during follow up: 16.9% of the older group and 12.5% of the younger group.
The malignancy rate was very low in incidental PCN patients irrespective of age. Follow-up observation without surgery appears to be a safe option in older patients with morbidity. Geriatr Gerontol Int 2016; ●●: ●●-●●.
Article · Feb 2016 · Geriatrics & Gerontology International
[Show abstract][Hide abstract]ABSTRACT: Objectives:
We evaluated the value of carbohydrate antigen 19-9 (CA 19-9) as a pancreatic cancer (PC) screening tool in an asymptomatic new-onset diabetic patients.
Medical records of asymptomatic patients newly diagnosed with diabetes mellitus (DM) were reviewed retrospectively at our hospital from January 2004 to January 2013.
In total, 2363 asymptomatic diabetic patients with CA 19-9 measurements were enrolled. Of them, 68 (2.9%) were diagnosed with PC. In the 1719 patients who had CA 19-9 measured within 1 year after the DM diagnosis, a total of 51 (3.0 %) patients developed PC and the odds ratio (OR) of PC according to higher CA 19-9 than normal upper limit, 37 IU/mL was 5.57 (P < 0.001). In 248 patients checked CA 19-9 between 1 and 2 years after DM diagnosis, PC was detected in 9 (3.6%) cases and OR of high CA 19-9 was 4.51 (P = 0.019). However, beyond 2 years, the OR for PC showed no statistical significance. The patients with high CA 19-9 levels tended to have more advanced-stage disease.
Early check-up of CA 19-9 could be a useful marker for screening for PC in asymptomatic patients with new-onset DM in the first 2 years.
[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).