• BMB Reports
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• v.36 no.1
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• pp.82-94
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• 2003

Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-${\kappa}B$ binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-${\kappa}B$ binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-$\gamma$, RANTES, TNF-$\alpha$, TNFR p75, IL-$1{\beta}$ in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric/cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1779-1782
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• 2012

Background & Objectives: In patients with gastric cancer, the most frequently reported family history of cancer also involves the stomach. The aim of this study was to assess the presence of gastric precancerous lesions in first-degree relatives of patients with gastric cancer and to compare the obtained results with those of individuals with no such family history. Methods: Between 2007 and 2009, 503 consecutive persons more than 30 years old were enrolled in the study covering siblings, parents or children of patients with confirmed adenocarcinoma of stomach. The control group was made up of 592 patients who were synchronously undergoing upper gastrointestinal endoscopy for evaluation of dyspepsia without gastric cancer or any family history. All subjects were endoscopically examined. Results: The overall prevalence of Helicobacter pylori was 77.7% in the cancer relatives and in 75.7% in the control group. Chronic gastritis was found in 90.4% vs. 81.1% (P<0.001). Regarding histological findings, 37(7.4%) of the study group had atrophy vs. 12(1.7%) in the control group (P<0.001), while no difference was observed for intestinal metaplasia (20.3%vs. 21.6%, P=0.58). Dysplasia were shown in 4% of cancer relatives but only 0.4% of the control group (P<0.001). There was no gender specificity. Conclusions: Findings of our study point to great importance of screening in relatives of gastric cancer patients in Iran.

• Korean Journal of Veterinary Research
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• v.54 no.3
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• pp.171-177
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• 2014

Garlic and mugwort have long been used in traditional medicine to prevent various diseases. Several in vitro studies have reported protective efficacies of garlic and mugwort in cases of gastric cancer. In the present study, we investigated the cancer preventive effects of garlic and mugwort mixture extract (GME) in a Helicobacter (H.) pylori-associated gastric carcinogenesis mouse model. To induce gastric cancer, C57BL/6 mice were treated with N-methyl-N-nitrosourea and H. pylori. Various concentrations of GME (0, 100, 500, and 1,000 ppm) were then fed to the mice for 38 weeks, after which the tumor tissues were examined for histopathology, mucin histochemistry and ${\beta}$-catenin. The incidence of gastric tumors was significantly lower in the highest dose GME-treated mice (46.7%) than control mice (85.7%) (p < 0.05). The multiplicity and size of tumors were also significantly reduced by GME feeding in a dose-dependent manner (p < 0.01). Furthermore, GME suppressed the H. pylori-associated chronic inflammation measured by histologic grading of H. pylori density, chronic gastritis, glandular atrophy and intestinal metaplasia in non-tumorous gastric mucosae. Our data suggest that GME suppresses gastric tumorigenesis via suppression of H. pylori-associated chronic inflammation.

• Parasites, Hosts and Diseases
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• v.41 no.1
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• pp.63-67
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• 2003

A 69-year-old Korean man was admitted to emergency room with complaints of abdominal pain, vomiting, and diarrhea, Laboratory tests revealed eosinophilia, anemia, hypoproteinemia, and hyponatremia. The gastric mucosa showed whitish mottled and slightly elevated lesions on the body angle of antrum. Microscopically, chronic gastritis with incomplete intestinal metaplasia was observed. Many adult worms, larvae, and eggs in cross sections were located in the crypts. Furthermore, the filariform larvae of Strongyloides stercoralis with a notched tail were detected through the culture.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3437-3441
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• 2012

Background: Oncogenic Bmi-1 (B-lymphoma Moloney murine leukemia virus insertion region-1) belongs to the Polycomb-group (PcG) family of proteins and plays an important role in the regulation of proliferation, senescence, cell cycle and apoptosis, chromosome stability, activation of gene transcription. Methods: To clarify the roles of Bmi-1 in tumourigenesis and progression of gastric carcinomas, it was examined by immunohistochemistry (IHC) and real-time RT-PCR in gastric carcinomas, dysplasia, intestinal metaplasia (IM), and gastritis with a comparison of its expression with clinicopathological parameters of carcinomas. Results: There was gradually increased Bmi-1 protein expression from gastritis, IM, dyplasia to carcinoma (p<0.001). Bmi-1 expression was positively linked to tumor size, depth of invasion, lymph node metastasis and worse prognosis of carcinomas (p<0.001), but not to age or sex of carcinoma patients (p>0.05). There was higher Bmi-1 protein expression in intestinal-type carcinomas than diffuse-type ones (p<0.001). At mRNA level, Bmi-1 protein expression was increased from gastritis, IM, dysplasia and carcinoma (p<0.001). Bmi-1 overexpression was observed in gastric carcinoma with larger diameter, deeper invasion, lymph node metastasis, and intestinal-type carcinoma (p<0.05). Conclusion: These findings indicate that up-regulated Bmi-1 expression is positively linked to pathogenesis, growth, invasion, metastasis and differentiation of gastric carcinomas. It was considered as a promising marker to indicate the aggressive behaviors and prognosis of gastric carcinomas.

• Journal of Yeungnam Medical Science
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• v.5 no.2
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• pp.189-193
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• 1988

Adenosquamous carcinoma of stomach is a mixed glandular-epidermoid tumor where both components are neoplastic. Its incidence is extremely rare. The five theories on the origin of squamous components are 1) island of ectopic squamous epithelium in the gastric mucosa, 2) squamous metaplasia of gastric epithelium, 3) squamous differentiation in a preexisting adenocarcinoma, 4) endothelial cell differentiated toward squamous elements, and 5) totipotential undifferentiated cells of the gastric mucosa. We experienced three cases of adenosquamous carcinoma. Case 1 was a 71-year-old female patient. ; an ulcerative lesion was present in the pylorus, measuring 5cm in diameter. Case 2 was a 57-year-old male patient. ; an ulcerative lesion is present in the pylorus, measuring 6 em in diameter. Case 3 was a 58-year-old female patient. ; an ulcerative lesion was present in the body and fundus, measuring 10cm in diameter. Microscopic examination revealed a mixed malignant squamous and adenomatous component.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2555-2558
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• 2016

Background: Gastric cancer is the second most common gastrointestinal cancer and is still associated with significant morbidity and mortality due to late presentation and diagnosis at advanced stages. Studies have reported that a variable proportion of gastric cancer is positive for the human epidermal growth factor receptor 2 (HER2) and patients with HER2 positive (HER2 +ve) lesions can benefit from targeted therapy. This study was conducted to assess the prevalence of HER2 +ve gastric cancers in Brunei Darussalam, a developing Southeast Asian nation. Materials and Methods: Patients were identified from the Department of Pathology registry and retrospectively reviewed. HER2 expression was assessed by immunohistochemistry and only those staining 3+were considered positive. Results: Our study included 103 cases (66 males and 37 females) with a mean age of $65.1{\pm}14.8$ years old. There were 14 cases positive for HER2 (10 males and 4 females) giving a prevalence of 13.6%. The HER2 +ve cases were significantly older ($70.6{\pm}19.3$ years old) than the negative cases ($64.2{\pm}13.8$, p=0.041) and had significantly more advanced disease (stages 3 and 4, p=0.026). There were no significant differences in gender distribution, presence of intestinal metaplasia, EBV status, Helicobacter pylori status, tumor location (proximal vs. distal) and degree of tumor differentiation (all p values >0.05). Conclusions: Our study showed that 13.6% of our gastric cancers are positive for HER2, the affected patients being older and having more advanced disease at diagnosis.

• Clinical Endoscopy
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• v.51 no.6
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• pp.513-526
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• 2018

White light imaging (WLI) may not reveal early upper gastrointestinal cancers. Linked color imaging (LCI) produces bright images in the distant view and is performed for the same screening indications as WLI. LCI and blue laser imaging (BLI) provide excellent visibility of gastric cancers in high color contrast with respect to the surrounding tissue. The characteristic purple and green color of metaplasias on LCI and BLI, respectively, serve to increase the contrast while visualizing gastric cancers regardless of a history of Helicobacter pylori eradication. LCI facilitates color-based recognition of early gastric cancers of all morphological types, including flat lesions or those in an H. pylori-negative normal background mucosa as well as the diagnosis of inflamed mucosae including erosions. LCI reveals changes in mucosal color before the appearance of morphological changes in various gastric lesions. BLI is superior to LCI in the detection of early esophageal cancers and abnormal findings of microstructure and microvasculature in close-up views of upper gastrointestinal cancers. Excellent images can also be obtained with transnasal endoscopy. Using a combination of these modalities allows one to obtain images useful for establishing a diagnosis. It is important to observe esophageal cancers (brown) using BLI and gastric cancers (orange) surrounded by intestinal metaplasia (purple) and duodenal cancers (orange) by LCI.

• Journal of Gastric Cancer
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• v.1 no.1
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• pp.4-9
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• 2001

Purpose: The trefoil factor family 1 (TFF1) has a protective effect against gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs or ethanol. In addition, a TFF1 knockout mouse model has exhibited circumferential adenomas with high-grade dysplasia, of which $30\%$ progressed into frankly invasive carcinomas. We tried to determine whether the expression pattern of the TFF1 could be involved in the development of sporadic gastric carcinomas. Materials and Methods: We examined TFF1 expression in a series of 43 sporadic gastric carcinomas and 18 gastric adenomas by immunohistochemistry. Results: Strong positive TFF1 staining was identified primarily in the normal gastric mucosa, mainly in the cytoplasm of the superficial and foveolar epithelium. We found TFF1 expression in $55.8\%$ (24 out of 43) of the gastric carcinomas and in $16.7\%$ (3 out of 18) of the gastric adenomas. Statistically, TFF1 immunoreactivity was significantly higher in diffuse-type ($82.4\%$) than in intestinal-type ($38.5\%$) carcinomas(p=0.0058, Fisher's exact test). Conclusion: Our findings provide sufficient evidence that the expression of TFF1 in gastric cancer may simply disclose gastric-type differentiation of neoplastic cells and provide further support for the existence of at least two pathways of malignant transformation of the gastric mucosa: one via intestinal metaplasia and adenomatous dysplasia, leading to glandular carcinomas with intestinal-type differentiation, and the other via hyperplastic changes or de novo changes, leading to diffuse carcinomas and to a subset of glandular carcinomas displaying gastric-type differentiation.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.917-921
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• 2016

However, the incidence of gastric cancer (GC) has been decreased in past decades; GC is the second cause of cancer related death in the world. Evidence has illustrated that several factors including Helicobacter pylori (H. pylori) infection, host genetics, and environmental factors (smoking and particularly diet) may play a crucial role in gastric carcinogenesis. It has been demonstrated that high consumption of fresh fruits, vegetables, high level of selenium and zinc in drinking water, sufficient iron, and cholesterol protect against GC, while; smoked, pickled, and preserved foods in salt, and nitrites increase the risk of GC. Epidemiological studies have also proved that H. pylori infection and a high salt diet could independently induce atrophic gastritis and intestinal metaplasia. Recently, studies have been demonstrated that dietary factors directly influence H. pylori virulence. The use of appropriate diet could reduce levels of H. pylori colonization or virulence and prevent or delay development of peptic ulcers or gastric carcinoma. This is attractive from a number of perspectives including those of cost, treatment tolerability, and cultural acceptability. This review will describe new insights into the pathogenesis of H. pylori in relation to environmental factors, especially dietary, not only to find the developed means for preventing and treating GC, but also for understanding the role of chronic inflammation in the development of other malignancies.