• Journal of Gastric Cancer
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• v.14 no.3
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• pp.147-155
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• 2014

Homeostatic imbalance between cell proliferation and death in gastric mucosal epithelia may lead to gastritis and gastric cancer. Despite abundant gastrokine 1 (GKN1) expression in the normal stomach, the loss of GKN1 expression is frequently detected in gastric mucosa infected with Helicobacter pylori, as well as in intestinal metaplasia and gastric cancer tissues, suggesting that GKN1 plays an important role in gastric mucosal defense, and the gene functions as a gastric tumor suppressor. In the stomach, GKN1 is involved in gastric mucosal inflammation by regulating cytokine production, the nuclear factor-${\kappa}B$ signaling pathway, and cyclooxygenase-2 expression. GKN1 also inhibits the carcinogenic potential of H. pylori protein CagA by binding to it, and up-regulates antioxidant enzymes. In addition, GKN1 reduces cell viability, proliferation, and colony formation by inhibiting cell cycle progression and epigenetic modification by down-regulating the expression levels of DNMT1 and EZH2, and DNMT1 activity, and inducing apoptosis through the death receptor-dependent pathway. Furthermore, GKN1 also inhibits gastric cancer cell invasion and metastasis via coordinated regulation of epithelial mesenchymal transition-related protein expression, reactive oxygen species production, and PI3K/Akt signaling pathway activation. Although the modes of action of GKN1 have not been clearly described, recent limited evidence suggests that GKN1 acts as a gastricspecific tumor suppressor. This review aims to discuss, comment, and summarize the recent progress in the understanding of the role of GKN1 in gastric cancer development and progression.

• Journal of Gastric Cancer
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• v.14 no.4
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• pp.238-245
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• 2014

Purpose: Gastric cancer often occurs in the elderly but is uncommon in young individuals. Whether young patients have different clinical behaviors and outcomes from those of older patients remain unclear. Materials and Methods: We identified 1,366 cases of newly diagnosed noncardia gastric adenocarcinoma from the Kaiser Permanente Northern California Cancer Registry between 2000 and 2010. We then compared the clinicopathological features and survival among the different age groups. Results: The male : female ratio differed significantly between the younger and older patient groups (0.84 in age <50 years vs. 1.52>60 years, P<0.01). More younger patients were Hispanic (54% patients <40 years vs. 19% patients ${\geq}70$ years, P<0.0001), while more older patients were Caucasian (49% patients ${\geq}70$ years vs. 15% patients <40 years; P<0.0001). The diffuse/mixed histological type was more prevalent in younger patients (70% patients <40 years vs. 27% patients ${\geq}70$ years; P<0.0001), whereas the intestinal type was more frequent in older patients (71% in patients ${\geq}70$ years vs. 30% in patients <40 years; P<0.0001). Poorly differentiated adenocarcinoma was more common in the younger patients (80% in patients <40 years vs. 60% in patients ${\geq}70$ years; P=0.016). Survival rates at 1, 2, and 5 years gradually declined with increasing age (overall P=0.0002). Conclusions: Young patients with gastric cancer had more aggressive disease but higher overall survival rates than older patients. Younger Hispanic patients and older Caucasian patients were more likely to be diagnosed with gastric cancer. These differences may be due to biological predisposition and/or environmental exposure.

• Radiation Oncology Journal
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• v.29 no.4
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• pp.252-259
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• 2011

Purpose: To evaluate retrospectively the survival outcome, patterns of failure, and complications in patients treated with postoperative chemoradiotherapy (CRT) in advanced gastric cancer. Materials and Methods: Between January 2000 and December 2006, 80 patients with advanced gastric cancer who received postoperative concurrent CRT were included. Pathological staging was IB-II in 9%, IIIA in 38%, IIIB in 33%, and IV in 21%. Radiotherapy consisted of 45 Gy of radiation. Concurrent chemotherapy consisted of a continuous intravenous infusion of 5-fluorouracil and leucovorin on the first 4 days and last 3 days of radiotherapy. Results: The median follow-up period was 48 months (range, 3 to 83 months). The 5-year overall survival, disease-free survival, and locoregional recurrence-free survivals were 62%, 59%, and 80%, respectively. In the multivariate analysis, significant factors for disease-free survival were T stage (hazard ratio [HR], 0.278; P = 0.038), lymph node dissection extent (HR, 0.201; P = 0.002). and maintenance oral chemotherapy (HR, 2.964; P = 0.004). Locoregional recurrence and distant metastasis occurred in 5 (6%) and 18 (23%) patients, respectively. Mixed failure occurred in 10 (16%) patients. Grade 3 leukopenia and thrombocytopenia were observed in 4 (5%) and one (1%) patient, respectively. Grade 3 nausea and vomiting developed in 8 (10%) patients. Intestinal obstruction developed in one (1%). Conclusion: The survival outcome of the postoperative CRT in advanced gastric cancer was similar to those reported previously. Our postoperative CRT regimen seems to be a safe and effective method, reducing locoregional failure without severe treatment toxicity in advanced gastric cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4839-4842
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• 2013

Aims and Background: To improve understanding of the relationship between schistosome-related enteropathy and colorectal carcinoma with particular focus on endoscopic findings and clinicopathological characteristics of colonic schistosomiasis. Materials and Methods: All cases of intestinal schistosomiasis diagnosed at West China Hospital, Chengdu, China, between October 2006 and October 2012 were included in this study. A total of 179 cases of colonic schistosomiasis diagnosed through colonoscopy and pathological examinations were collected for analysis and the demographics, symptoms, endoscopic findings and clinicopathological characteristics were retrospectively evaluated. Results: Of the 179 colonic schistosomiasis patients, 32 combined with colorectal cancer (CRC) were found, between the ages of 44 and 85 years (24 males, 75%). These 32 lesions were classified as 12 endophytic/ulcerative (37.5%), 10 exophytic/fungating (31.2%), 4 annular (12.5%), 3 giant polypus (9.4%), and 3 IIc (superficial depressed type) (9.4%). The segments of rectum and sigmoid colon were involved in 19 patients (59.4%) and 6 patients (18.8%), respectively. The histopathologic types were classified as follows: 30 welldifferentiated adenocarcinomas, one mucinous adenocarcinoma and one poorly differentiated adenocarcinoma. The pathological findings suggest colorectal malignancy with deposited schistosome ova. Conclusions: Chronic schistosomal infestation has a probable etiological role in promoting genesis of colorectal neoplasms.

• Journal of Gastric Cancer
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• v.10 no.4
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• pp.149-154
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• 2010

Purpose: Replication error is an important mechanism in carcinogenesis. The microsatellite instability (MSI-H) of colorectal cancers is associated with the development of multiple cancers. The influence of MSI-H on the development of multiple gastric cancers in sporadic gastric cancer patients has not been defined. This study was performed to reveal the association between the clinicopathologic features and MSI in sporadic gastric cancers. Materials and Methods: Between July 2004 and March 2009, the clinicopathologic characteristics, including MSI status, were evaluated in 128 consecutive patients with sporadic gastric cancers. None of the patients had hereditary non-polyposis colorectal cancer of familial gastric cancer. The markers that were recommended by the NCI to determine the MSI status for colorectal cancers were used Results: MSI-H cancers were found in 10.9% of the patients (14/128). Synchronous gastric cancers were shown in 4 patients (3.1%). Synchronous cancers were found in 2 of 14 patients with MSI-H gastric cancer (14.3%) and 2 of 114 patients with MSS gastric cancer (1.8%; P=0.059, Fisher's exact test). Among the patients with synchronous cancer 50% (2/4) had MSI-H cancer, but 9.7% of the patients (12/124) without synchronous cancer had MSI-H cancer. MSI-H (RR, 24.7; 95% CI, 1.5~398.9; P=0.024) was related with to synchronous gastric cancer, but age, gender, family history, histologic type, location, gross morphology, size, and stage were not related to synchronous gastric cancer. Conclusions: MSI is associated with the intestinal-type gastric cancer and the presence of multiple gastric cancers in patients with sporadic gastric cancer. Special attention to the presence of synchronous and the development of metachronous multiple cancer in patients with MSI-H gastric cancer is needed.

• Journal of Gastric Cancer
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• v.16 no.1
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• pp.21-27
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• 2016

Purpose: Transducer-like enhancer of split 1 (TLE1) is a member of the Groucho/TLE family of transcriptional co-repressors that regulate the transcriptional activity of numerous genes. TLE1 is involved in the tumorigenesis of various tumors. We investigated the prognostic significance of TLE1 expression and its association with clinicopathological parameters in gastric cancer (GC) patients. Materials and Methods: Immunohistochemical analysis of six tissue microarrays was performed to examine TLE1 expression using 291 surgically resected GC specimens from the Soonchunhyang University Cheonan Hospital between July 2006 and December 2009. Results: In the non-neoplastic gastric mucosa, TLE1 expression was negative. In GC, 121 patients (41.6%) were positive for TLE1. The expression of TLE1 was significantly associated with male gender (P=0.021), less frequent lymphatic (P=0.017) or perineural invasion (P=0.029), intestinal type according to the Lauren classification (P=0.024), good histologic grade (P<0.001), early pathologic T-stage (P=0.012), and early American Joint Committee on Cancer stage (P=0.022). In the Kaplan-Meier analysis, the TLE1 expression was significantly associated with longer disease-free (P=0.022) and overall (P=0.001) survival rates. Conclusions: We suggested that TLE1 expression is a good prognostic indicator in GCs.

• Journal of Digestive Cancer Research
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• v.11 no.3
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• pp.165-170
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• 2023

Gastric cancer is histologically classified into two types. One is the intestinal and diffuse type according to Lauren's classification, and the other is the differentiated and undifferentiated type based on Nakamura's classification. In 2007, Japanese groups proposed a new type of well-differentiated gastric adenocarcinoma in the gastric fundic glands with distinct endoscopic and clinicopathologic features. This is gastric adenocarcinoma of the fundic-gland type (GA-FG), a rare variant of gastric cancer. In a 2012 Korean study, of 6,000 cases of gastric cancer tissues, only three cases of GA-FG were identified. GA-FG is usually located in the upper third of the stomach and not known to be associated with the Helicobacter pylori infection. We herein report a case of GA-FG diagnosed in a 63-year-old man. A gastric polyp was incidentally detected during an upper endoscopy screening while conducting a health check-up, and he was diagnosed with GA-FG after an endoscopic mucosal resection (EMR) was conducted for diagnostic and therapeutic purposes. Our case suggests that for both diagnostic and therapeutic purposes, EMR may be beneficial in case of gastric polyps with suspected GA-FG.

• Journal of Gastric Cancer
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• v.17 no.1
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• pp.52-62
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• 2017

Purpose: The Trastuzumab for gastric cancer (GC) trial identified human epidermal growth factor receptor 2 (HER2) as a predictor of successful treatment with trastuzumab (HER2 receptor targeting agent) among patients with advanced/metastatic GC. To date, the prevalence of HER2 overexpression in the Korean population is unknown. The present study aimed to assess the incidence of HER2 positivity among GC and gastroesophageal (GE) junction cancer samples and the relationship between HER2 overexpression and clinicopathological characteristics in Korean patients. Materials and Methods: Tumor samples collected from 1,695 patients with histologically proven GC or GE junction enrolled at 14 different hospitals in Korea were examined. After gathering clinicopathological data of all patients, HER2 status was assessed by immunohistochemistry (IHC) at each hospital, and IHC 2+ cases were subjected to silver-enhanced in situ hybridization at 3 central laboratories. Results: A total of 182 specimens tested positive for HER2, whereas 1,505 tested negative. Therefore, the overall HER2-positive rate in this study was 10.8% (95% confidence interval=9.3%-12.3%). The HER2-positive rate was higher among intestinal-type cases (17.6%) than among other types, and was higher among patients older than 70 years and 50 years of age, compared to other age groups. Conclusions: Our evaluation of the HER2 positivity rate (10.8%) among Korean patients with GC and GE junction indicated the necessity of epidemiological data when conducting studies related to HER2 expression in GC and GE junction.

• Journal of Gastric Cancer
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• v.10 no.4
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• pp.212-218
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• 2010

Purpose: The aim of this study was to determine proportions of upper third gastric cancer (UTG) among all gastric cancers and analyze clinicopathological features of the disease. Materials and Methods: The medical records of 12,300 patients who underwent gastric surgery between 1986 and 2006 at Seoul National University Hospital (SNUH) were retrospectively reviewed. Clinicopathological features of 1,260 patients with UTG and 9,929 patients with middle or lower third gastric cancer (MLG) were compared, and annual proportions of UTG were evaluated. Results: The proportion of patients with UTG rapidly increased from 2.6% in 1986 to 12.5% in 1992. However, linear regression analysis showed that the rate of increase was reduced (0.21%/year) after 1992 (12.5% to 14.2% from 1992 to 2006). Compared with the MLG group, the UTG group had a lower proportion of (22.3% vs. 39.7%, P<0.001) and a greater proportion of stage III/IV disease (39.4% vs. 31.7%, P<0.001). The UTG group also had larger tumors than the MLG group in stages I/II and III (3.5 cm/5.3 cm/6.5 cm vs. 3.2 cm/5.0 cm/5.8 cm, P=0.020/0.028 /<0.001), a higher proportion of undifferentiated cancer (63.1% vs. 53.7%, P<0.001), and less intestinal Lauren's type (38.8% vs. 47.4%, P<0.001). The 5-year survival rate of the UTG group was significantly lower than that of the MLG group in stages I/II and III (85.6%/63.1%/34.2% vs. 91.6%/ 69.2%/44.7%, P<0.001/0.028/0.006). Conclusions: The proportion of UTGs has increased over the last two decades at SNUH, but the rate of increase has been greatly reduced since 1992. The UTG group showed a poorer prognosis compared with the MLG group in stages I/II and III.

• Journal of Digestive Cancer Reports
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• v.8 no.2
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• pp.81-90
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• 2020

We performed a comprehensive meta-analysis on whether Helicobacter pylori (H. pylori) eradication can prevent gastric cancer in individuals with precancerous lesions (chronic atrophic gastritis, intestinal metaplasia, and dysplasia). The studies evaluating the effect of H. pylori eradication on gastric cancer were searched from PubMed, KoreaMed, EMBASE, and Cochrane Library. Subgroup analyses by precancerous lesions, regions and follow-up time were performed. Six randomized clinical trials were included. In the overall population, H. pylori eradication significantly decreased the risk of gastric cancer (risk ratio [RR]=0.56; 95% confidence interval [CI]: 0.41-0.77, p<0.01). Eradication therapy significantly reduced the risk of gastric cancer in Asian and group who followed up more than 10 years (RR=0.51; 95% CI: 0.35-0.73, p<0.01; I²=0%, p=0.46). However, subgroup analysis according to the precancerous lesions did not show any significant results (p>0.05). In the general population especially in Asian population, H. pylori eradication can reduce the risk of gastric cancer. The effect of the eradication treatment is remarkable upon the long-term follow-up. In contrast, there is insufficient evidence whether the eradication should be recommended for the individuals with precancerous lesions.