• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.397-405
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• 2017

MDL-12330A is a widely used adenylyl cyclase (AC) inhibitor that blocks AC/cAMP signaling. In this study, we demonstrated a novel antitumor activity of this drug in gastric carcinoma (GC) cell lines. In these GC cells, MDL-12330A reduced cell viability and induced cell death in a concentration-dependent manner. At a moderate concentration (${\sim}20{\mu}M$), MDL-12330A mainly induced apoptotic death whereas at concentrations greater than $20{\mu}M$, it increased non-apoptotic cell death. The induction of apoptosis was at least partially regulated by CHOP-mediated DR5 upregulation, as detected by immunoblotting and gene interference assays. More importantly, low concentrations of MDL-12330A effectively enhanced recombinant human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (rhTRAIL)-induced apoptosis and clonogenicity in these gastric cancer cells. This study demonstrates a possible role of MDL-12330A as a potential sensitizer to TRAIL, and suggests a novel therapeutic strategy targeting gastric cancer cells.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.223-230
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• 2007

Several methods have been used in the detection of Helicobacter pylori (H. pylori) which was believed to be a pathogenic organism causing chronic gastritis, benign peptic ulcer, gastric carcinoma or malignant lymphoma. Even though several methods were introduced for detection of H. pylori in stomach, there were controversies in their sensitivities and specificities. This experiment were designed to study the comparative analysis of staining methods (hematoxylin and eosin (H&E), Giemsa, Warthin-Starry and immunohistochemical stain) to dectect H. pylori in the gastric mucosa. The results were as follows. Average density score of H. pylori classified by Genta were 2.29 in Warthin-Starry stain, 2.19 in Giemsa stain, 1.34 in immunohistochemical stain and 0.98 in H&E stain. By comparison between inflammatory degree by Sydney system and result of Warthin-Starry stain, the detection rate and densities of H. pylori were increased from mild (61.5% and 0.8), moderate (90.4 and 2.1), and severe (100% and 3.2). From the above findings, Warthin-Starry stain is useful method for detection of H. pylori in gastric mucosa.

• Journal of Digestive Cancer Research
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• v.10 no.1
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• pp.22-30
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• 2022

Immune checkpoint inhibition has been established as a new treatment option for various types of carcinoma, and many clinical trials are being actively conducted as a treatment for advanced or metastatic gastric cancer, either as a monotherapy with an immune checkpoint inhibitor or as a combination therapy with standard chemotherapy. In the CheckMate-649 clinical trial to confirm the efficacy of the combination of nivolumab and chemotherapy (FP) in advanced gastric cancer and gastroesophageal junction cancer, nivolumab group showed improvement in overall survival in programmed death ligand 1-positive cancer patients compared with placebo group. Also, the combination therapy of pembrolizumab, trastuzumab and chemotherapy (FP) in first-line treatment was tested through the KEYNOTE-811 trial. The pembrolizumab group showed 22.7% of improvement in objective response rate compared with placebo group. Accordingly, the combination of nivolumab/pembrolizumab with standard chemotherapy was approved for the first-line treatment. In KEYNOTE-059 trials for patients with progressive disease after at least two lines of chemotherapy, pembrolizumab monotherapy showed improvement in objective response rate and overall survival, and the use of pembrolizumab was approved for the third-line or more treatment. In this article, we review the result of clinical trials related to immune checkpoint inhibitors that have been recently introduced in the treatment of gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4711-4716
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• 2014

Introduction: Adiponectin (ApN) is a complement C1q-related protein, mainly secreted from adipose tissue, that signals through ApN receptor1 (Adipo-R1) and ApN receptor 2 (Adipo-R2). Low serum ApN concentrations are associated with obesity-related malignancies. However, there are very few studies on any prognostic role of ApN receptors in gastric cancer. Objectives: The aim of this study is to investigate the relationship between AdipoR1/R2 expression and early/advanced stage gastric cancer in terms of clinicopathologic characteristics and survival. Materials and Methods: Eighteen patients with early and 39 with advanced stage gastric cancer who underwent surgical gastric resection were included in this study. Results: Adipo-R1 expression was low in 2 of the 18 patients with early stage gastric cancer (11.1%), while 4 had low Adipo-R2 expression (22.2%). In those with advanced stage gastric cancer, 7 of 39 had low Adipo-R1 expression (17.9%) and 16 had low Adipo-R2 expression (41%). Adipo-R2 expression was significantly higher (p=0.011) in moderately differentiated tumors when compared to well-differentiated tumors. While there was nearly a statistically significant relationship between TNM stage (T, tumor size; N, regional lymph node; M, whether distant metastases exist) and Adipo-R2 expression (p=0.054), there was no relationship between Adipo-R1/-R2 expression with tumor stage and survival. Conclusion: Adipo-R1/-R2 expression has no prognostic significance of in early/advanced stage gastric cancer.

• Journal of Gastric Cancer
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• v.3 no.2
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• pp.75-79
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• 2003

Purpose: Evidence exists that dysregulation of apoptosis is involved in the pathogenesis of cancer development. The Bcl-$x_{L}$/Bcl-2-associated death promoter (BAD), a member of the Bcl-2 family, is a critical regulatory component of the intrinsic cell-death pathway that exerts its pro-apoptotic effect upon heterodimerization with anti-apoptotic proteins Bcl-2 and Bcl-$X_{L}$. Expression of the BAD protein has been reported in several cancer types, but not in stomach cancer. The aim of this study was to explore the expression status of the BAD protein in gastric carcinomas. Materials and Methods: In the current study, we analyzed the expression of the BAD protein in 60 advanced gastric adenocarcinomas by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the BAD protein in 57 ($95\%$) of the 60 cancers. Normal gastric mucosal cells showed weaker expressions of the BAD protein than gastric carcinomas. Conclusion: Taken together, these results suggest that stomach cancer cells in vivo may need BAD protein expression for apoptosis. Also, the higher expression of the BAD protein in stomach cancer cells than in normal gastric mucosal cells suggests that apoptosis might be easily triggered in susceptible stomach cancer cells, thereby producing selective pressure to make more apoptosis-resistant cells during tumor development.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2765-2769
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• 2013

Background: A close association between patterns identified by magnifying narrow-band imaging (M-NBI) and histological type has been described. M-NBI patterns were also recently reported to be related to the mucin phenotype; however, detials remain unclear. Materials and Methods: We investigated the cellular differentiation of gastric cancer lesions, along with their mucosal distribution observed by M-NBI. Ninety-seven depressed-type early gastric cancer lesions (74 differentiated and 23 undifferentiated adenocarcinomas) were visualized by M-NBI. Findings were divided into 4 patterns based on abnormal microvascular architecture: a chain loop pattern (CLP), a fine network pattern (FNP), a corkscrew pattern (CSP), and an unclassified pattern. Mucin phenotypes were judged as gastric (G-type), intestinal (I-type), mixed gastric and intestinal (M-type), and null (N-type) based on 4 markers (MAC5AC, MUC6, MUC2, and CD10). The relationship of each pattern of microvascular architecture with organoid differentiation indicated by cancer cell differentiation and its distribution in each histological type of early gastric cancer was investigated. Results: All CLP and FNP lesions were differentiated. The cancer cell distribution showed organoid differentiation in 84.2% (16/19) and 61.1% (22/36) of the two types of lesions, respectively, and there was a significant difference from the unclassified pattern with organoid differentiation (p<0.001). Almost all (94.7%; 18/19) CSP lesions were undifferentiated, and organoid differentiation was observed in 72.2% (13/18). There was a significant difference from the unclassified pattern with organoid differentiation (p<0.05). Conclusions: Cellular differentiation and distribution are associated with microvascular architecture observed by M-NBI.

• Journal of Digestive Cancer Research
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• v.10 no.1
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• pp.1-8
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• 2022

The incidence of gastric neuroendocrine tumors (NET) has been increased with the improvement of endoscopy accessibility. The World Health Organization classified NET of low (G1), intermediate (G2), high (G3) grade and neuroendocrine carcinoma with poor differentiation by mitotic count and Ki-67 labeling index. Gastric NET are divided into three subtypes based on the pathophysiology, and treatment is determined according to the subtype and prognostic factors of tumor. For diagnosis, endoscopy with biopsy, endoscopic ultrasonography, abdominal pelvis computed tomography, and serum gastrin level measure are required. In general, type 3, size > 2 cm, deep submucosal infiltration, high histological grade, lymphovascular invasion and metastasis are poor prognostic factors. Type 1 or 2 without these factors are treated by endoscopic resection, and other tumors needs surgery. Endoscopic resection of early type 3 or type 1 and 2 tumors with poor prognostic factors still remains a challenge.

• Microbiology and Biotechnology Letters
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• v.23 no.5
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• pp.599-601
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• 1995

A cytotoxic compound, MCHS-4, was isolated from the mycelium of Streptomyces T70 and identified as manumycin A. The compound showed significant cytotoxicity against human gastric carcinoma cell line, SNU-1 and human hepatocellular cell line, SNU-354.

• Journal of Gastric Cancer
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• v.1 no.4
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• pp.215-220
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• 2001

Purpose: The aim of the study was to obtain data on the anatomic and histologic distributions, the clinical features, and the treatment results for patients with primary gastric non-Hodgkin's lymphoma. Materials and Methods: One hundred thirty-two patients who were treated at 8 university hospitals and 2 general hospitals between January 1991 and December 2000 were enrolled to evaluate clinico-pathologic features. Results: The lower one-third of the stomach was the most frequent site ($42\%$), and the most frequent chief complaint was epigastric pain ($54\%$). Gastric resection was performed in 114 cases. Pathologic findings of preoperative endoscopic biopsy specimens from the 114 patients that underwent surgery were a gastric lymphoma in 94 cases ($82\%$), a carcinoma in 15 cases ($13\%$), an ulcer in 4 cases ($4\%$), and a gastrointestinal stromal tumor in 1 case ($1\%$). The stage distributions by Musshoff's criteria were 71 cases ($54\%$) of stage IE, 36 cases ($27\%$) of stage $II_{1}E$, 8 cases ($6\%$) of stage $II_{2}E$, 2 cases ($2\%$) of stage IIIE, and 15 cases ($11\%$) of stage IVE. Histologic gradings by the Working Formulation in were 31 cases ($23\%$) of low grade, 96 cases ($73\%$) of intermediate grade, and 5 cases ($4\%$) of high grade. Chemotherapy-related complications occurred in 25 cases ($22\%$) while operation-related complications occurred in 6 cases ($5\%$). Seventeen patients ($13\%$) only underwent surgery, 19 ($14\%$) had chemotherapy (CTx) and/or radiotherapy (RTx) only, and 96 patients ($73\%$) received surgery and CTx and/or RTx. No substantial differences in survival were found in relation to the different histologic grades and different treatments. The five-year survival was $85\%$ in stage I or II and $47\%$ in stage III or IV (P=0.0000). Conclusion: Pathologic stage appears to be the single most important prognostic indicator. Survival differences according to treatment modalities were not statistically significant. However, the low number of patients treated with various approaches over a long period precludes a firm conclusion.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1797-1802
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• 2013

Background: The aim of this study was to assess clinical factors associated with Helicobacter pylori positivity and to evaluate the incidence of gastric carcinoma in first-degree family members of infected patients. A total of 580 patients (mean age:$38{\pm}17$) with gastrointestinal complaints underwent C-14 urea breath test (UBT). Patients were grouped as: Group-1, untreated patients (n:384); and Group-2, patients who previously treated with eradication triple therapy (n:196). C-14 UBT was performed 1-2 months after the completion of eradication therapy. Associations of H pylori positivity with age, gender, ABO and Rhesus groups, smoking, dietary habits, and history of gastric cancer in first-degree family members were evaluated. The frequency of H pylori positivity was significantly higher in group-1 (58%) compared to group-2 (20%), p=0.001. There were no correlations between H pylori positivity and age, gender, ABO groups, Rhesus subgroups, smoking and dietary habits in both patient groups. The frequency of gastric cancer in family members was significantly higher in patients with H pylori infection among group-1, compared to infected patients among group-2 (56% vs. 28.6% respectively, p=0.03). We observed a significant association between H pylori positivity and the presence of gastric cancer in first-degree relatives of group-1 patients. Our results provide some confirmation of the presence of a link between gastric cancer development and H pylori. C-14 UBT is a sensitive, reliable and a widely recommended test for the detection of H pylori infection and recurrence. We suggest that detection and eradication of H pylori may contribute to a reduced risk of gastric cancer in the family members of infected patients.