• Journal of Gastric Cancer
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• v.3 no.2
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• pp.88-92
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• 2003

Purpose: Mounting evidence suggests that alterations of Akt/protein kinase B (PKB) play an important role in tumorigenesis. Phosphorylated Akt regulates many of the key effector molecules involved in apoptosis, angiogenesis, and cell-cycle progression during tumorigenesis. The expression of phosphorylated Akt has been described in some human malignancies, but not in primary human gastric cancer. The purpose of this study was to explore the expression status of phosphorylated Akt protein in gastric carcinomas. Materials and Methods: In the current study, we analyzed the expression of phosphorylated Akt protein in 60 advanced gastric adenocarcinomas by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the phosphorylated Akt in 42 ($70\%$) of the 60 cancers. Normal gastric mucosal cells showed no or weak expression of phosphorylated Akt protein. Conclusion: Taken together, these results indicate that Akt is frequently activated in gastric adenocarcinoma cells and suggest that phosphorylayed Akt may play a role in the development of human gastric adenocarcinomas.

• Korean Journal of Medicinal Crop Science
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• v.18 no.3
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• pp.135-142
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• 2010

Low quality fresh ginseng was fermented by Pheliuus linteus mycelium at $22^{\circ}C$ for 30 days, then extracted by water solvent at $100^{\circ}C$ for 180 min. On human normal cell lines (HEK293), cytotoxicity was about 10% lower in adding extracts of the fermentation ginseng than that from low quality ginseng. The fermented extracts also inhibited the growth of several human cancer cells. Among them, respectively, digestive organs related cancer cells, such as human stomach adenocarcnioma and human epithelial adenocarcinoma were most effectively inhibited up to 85% and 90%, respectively. Then, selectivities were in the ranges of 3 to 5, compared to 2 to 3 from low quality fresh ginseng. Generally, fermented ginseng extract showed higher anticancer activities as well as higher DPPH radical sacavening activity, possibly due to high contents of total phenolic components as 6.96 mg/g. It was very interesting that the fermented ginseng contained very higher contents of ginsenoside-Rc+$Rb_2$, compared to others in low quality fresh ginseng because of partition digestion of mycelium growth. The results can tell that low quality fresh ginseng can be utilized by the fermentation with Pheliuus linteus mycelium.

• Journal of Microbiology and Biotechnology
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• v.31 no.10
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• pp.1358-1365
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• 2021

To clarify the role of long intergenic nonprotein-coding RNA 1232 (LINC01232) in the progression of gastric cancer and the potential mechanism, we analyzed the expression of LINC01232 in TCGA database using the GEPIA online tool, and the LINC01232 level in gastric cancer cell lines was detected by quantitative real time-polymerase chain reaction (qRT-PCR) as well. Cell proliferation assay, colony formation assay, transwell assay and tumor formation experiment in nude mice were conducted to observe the biological behavior changes of gastric cancer cells through the influence of LINC01232 knockdown. LncATLAS database and subcellular isolation assay were used for subcellular distribution of LINC01232 in gastric cancer cells. The interaction among LINC01232, zeste homolog 2 (EZH2) and kruppel-like factor 2 (KLF2) was clarified by RNA-protein interaction prediction (RPISeq), RNA immunoprecipitation (RIP), qRT-PCR and chromatin immunoprecipitation (ChIP) assay. Rescue experiments were further conducted to elucidate the biological function of LINC01232/KLF2 axis in the progression of gastric cancer. LINC01232 was upregulated in stomach adenocarcinoma (STAD) tissues and gastric cancer lines. LINC01232 knockdown inhibited the proliferative capacities of gastric cancer cells in vitro, and impaired in vivo tumorigenicity. LINC01232 was mainly distributed in the cell nucleus where it epigenetically repressed KLF2 expression via binding to the enhancer of EZH2, which was capable of binding to promoter regions of KLF2 to induce histone H3 lysine 27 trimethylation (H3K27me3). LINC01232 exerts oncogenic activities in gastric cancer via inhibition of KLF2, and therefore, the knockdown of KLF2 could reverse the regulatory effect of LINC01232 in the proliferative ability of gastric cancer cells.

• Journal of Gastric Cancer
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• v.19 no.1
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• pp.62-71
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• 2019

Purpose: The laparoscopic transhiatal approach (LA) for adenocarcinoma of the esophagogastric junction (AEJ) is advantageous since it allows better visualization of the surgical field than the open approach (OA). We compared the surgical outcomes of the 2 approaches. Materials and Methods: We analyzed 108 patients with AEJ who underwent transhiatal distal esophagectomy and gastrectomy with curative intent between 2003 and 2015. Surgical outcomes were reviewed using electronic medical records. Results: The LA and OA were performed in 37 and 71 patients, respectively. Compared to the OA, the LA was associated with significantly shorter duration of postoperative hospital stay (9 vs. 11 days, P=0.001), shorter proximal resection margins (3 vs. 7 mm, P=0.004), and extended operative times (240 vs. 191 min, P=0.001). No significant difference was observed between the LA and OA for intraoperative blood loss (100 vs. 100 mL, P=0.392) or surgical morbidity rate ($grade{\geq}II$) for complications (8.1% vs. 23.9%, P=0.080). Two cases of anastomotic leakage occurred in the OA group. The number of harvested lymph nodes was not significantly different between the LA and OA groups (54 vs. 51, P=0.889). The 5-year overall and 3-year relapse-free survival rates were 81.8% and 50.7% (P=0.024) and 77.3% and 46.4% (P=0.009) for the LA and OA groups, respectively. Multivariable analyses revealed no independent factors associated with overall survival. Conclusions: The LA is feasible and safe with short- and long-term oncologic outcomes similar to those of the OA.

• Journal of Gastric Cancer
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• v.18 no.4
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• pp.400-408
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• 2018

Purpose: This study aimed to evaluate immediate outcomes and clinical courses of patients with early gastric carcinoma with lymphoid stroma (GCLS) who underwent endoscopic resection. Materials and Methods: We retrospectively reviewed the medical records of 40 patients (mean age, 56.9 years; 90.0% male) who underwent endoscopic resection and were pathologically diagnosed with GCLS confined to the mucosa or to the submucosa between March 1998 and December 2017. Results: Forty GCLS lesions in 40 patients were treated using endoscopic resection. Only 4 (10%) patients received diagnosis of GCLS before endoscopic resection. Fourteen (35.0%) lesions were intramucosal cancers and 26 (65.0%) exhibited submucosal invasion. En bloc resection (97.5%) was achieved for all lesions except one, with no significant complications. The complete resection rate was 85.0% (34 of 40 lesions). After endoscopic resection, 17 patients were referred for surgery and underwent gastrectomy with lymph node (LN) dissection because of deep submucosal invasion (n=16) and misclassification as undifferentiated cancer (n=1). No LN metastasis was determined in the specimens obtained during surgery. During a mean follow-up period of 49.7 months for 23 patients without surgical treatment, no regional LN enlargements, distant metastases, or gastric cancer-related deaths were found, although 1 metachronous lesion (undifferentiated adenocarcinoma, follow-up duration: 7 months) was observed. Conclusions: In patients with early GCLS, endoscopic resection is technically feasible and has favorable clinical outcomes. Therefore, endoscopic resection might represent an alternative treatment modality in patients with early GCLS with a low likelihood of LN metastasis.

• Korean Journal of Clinical Oncology
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• v.14 no.2
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• pp.120-127
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• 2018

Purpose: The purpose of this study was to determine the immunologic role of lymph node (LN) and stage migration by assessing LN count and metastatic LN count. Methods: A total of 2,117 patients with gastric adenocarcinoma located in the body and antrum who underwent distal/subtotal gastrectomy with D2 LN dissection between January 1, 1998 and December 31, 2008 were enrolled. LN count and number of metastases were determined in the N1 tier (area of D1 dissection) and N2 tier (area of D2 dissection). The lower and upper quartiles of LN counts in the same pN stage were grouped to compare the prognosis and LN positivity according to the LN tier. Results: Stage migration from N1 tier to N2 tier occurred in 3.2% of cases. The 5-year disease-specific survival rates of the upper and lower LN count groups within the N1 tier were 91.0% and 86.7% (P=0.01), respectively. LN positivity in the N2 tier of the lower LN count group was higher than that of the upper LN count group (14.1% vs. 8.2%, P<0.01). Stage migration in the N2 tier of the lower LN count group was also higher than that of the upper LN count group (4.6% vs. 1.8%, P<0.01). Conclusion: The lower LN count group had a decreased survival rate compared to that of the upper LN count group, suggesting that perigastric LN has an immunological defense role in weakening the disseminating power of metastatic tumor cells, as indicated by the LN count.

• Journal of Gastric Cancer
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• v.20 no.4
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• pp.385-394
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• 2020

Purpose: Patients with gastric cancer who receive neoadjuvant therapy are staged before treatment (cStage) and after treatment (ypStage). We aimed to compare the prognostic reliability of cStage and ypStage, alone and in combination. Materials and Methods: Data for all patients who received neoadjuvant therapy followed by surgery for gastric adenocarcinoma from 2004 to 2015 were extracted from the National Cancer Database. Kaplan-Meier (KM)curves were used to model overall survival based on cStage alone, ypStage alone, cStage stratified by ypStage, and ypStage stratified by cStage. P-values were generated to summarize the differences in KM curves. The discriminatory power of survival prediction was examined using Harrell's C-statistics. Results: We included 8,977 patients in the analysis. As expected, increasing cStage and ypStage were associated with worse survival. The discriminatory prognostic power provided by cStage was poor (C-statistic 0.548), while that provided by ypStage was moderate (C-statistic 0.634). Within each cStage, the addition of ypStage information significantly altered the prognosis (P<0.0001 within cStages I-IV). However, for each ypStage, the addition of cStage information generally did not alter the prognosis (P=0.2874, 0.027, 0.061, 0.049, and 0.007 within ypStages 0-IV, respectively). The discriminatory prognostic power provided by the combination of cStage and ypStage was similar to that of ypStage alone (C-statistic 0.636 vs. 0.634). Conclusions: The cStage is unreliable for prognosis, and ypStage is moderately reliable. Combining cStage and ypStage does not improve the discriminatory prognostic power provided by ypStage alone. A ypStage-based prognosis is minimally affected by the initial cStage.

• Journal of Gastric Cancer
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• v.21 no.1
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• pp.49-62
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• 2021

Purpose: This study aimed to investigate the prognostic value of lymph node ratio (LNR) in patients with locally advanced gastric cancer who received neoadjuvant chemotherapy. Materials and Methods: We retrospectively enrolled gastric cancer patients treated with neoadjuvant chemotherapy and curative surgery at the First Affiliated Hospital of Zhejiang University from 2004 to 2015 as the study cohort. Patients with the same inclusion criteria treated in 2016-2017 were enrolled as the validation cohort. Kaplan-Meier curves were assessed using the log-rank test to analyze the differences in overall survival (OS). Multivariate survival analysis was performed using the Cox proportional hazards model. The areas under the receiver operating characteristic curve of ypN and LNR categories for predicting the actual 3-year OS were compared. Results: A total of 265 patients were included in the proposal cohort. The median number of retrieved lymph nodes (rLNs) was 32. The number of positive lymph nodes (pLNs) increased as rLN increased (P=0.037), but the LNR remained relatively constant (P=0.462). The LNR was categorized into 4 groups according to the prognosis: ypNr0, node-negative with rLN>25; ypNr1, node-negative with rLN≤25 or 00.3. In the validation cohort of 43 enrolled patients, there was a clear distinction in OS that significantly (P<0.001) varied depending on the LNR values and LNR was the only independent prognostic factor in multivariate analysis (P<0.001). Conclusions: LNR was an independent prognostic factor for survival of patients with gastric cancer after preoperative chemotherapy and might be an alternative predictor for ypN stage.

• Journal of Digestive Cancer Research
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• v.3 no.1
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• pp.39-41
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• 2015

We report a case of long term survival on trastuzumab based treatment. A 51-year-old man with dyspepsia received esophagogastroduodenoscopy on another hospital and was transferred for further evaluation under the impression of advanced gastric cancer, Borrmann type III, antrum, lesser curvature. After further studies in our hospital, the patient was diagnosed with advanced gastric cancer, adenocarcinoma, moderately differentiated with pancreas invasion and lymph node metastasis. Though he was recommended with chemotherapy, he refused and left for oriental herbal medicine. After 4 months, the patient was admitted through emergency room for hematemesis. Diagnosed with gastric outlet obstruction due to gastric cancer in the antrum, he underwent the placement of pyloric metal stent insertion. Immunohistochemical staining showed HER2-positive finding, and he was treated with palliative chemotherapy of trastuzumab, capecitabine, and cisplatin, 16 times during 11 months. The patient showed neutropenia after the therapy, so cisplatin was left out, and he received combination chemotherapy of trastuzumab and capecitabine, 34 times during 25 months. Response evaluation showed no remarkable change in extent of primary stomach cancer, lymph node metastasis, and regression of metastasis site, and the patient is continuing chemotherapy.

• Clinical Endoscopy
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• v.55 no.6
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• pp.767-774
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• 2022

Background/Aims: Few studies have compared the performances of endoscopic knives. This study aimed to compare the therapeutic outcomes of a novel core knife and the conventional IT knife 2 for endoscopic submucosal dissection (ESD) of gastric mucosal lesions. Methods: This prospective, non-inferiority trial included patients diagnosed with gastric adenoma or early-stage adenocarcinoma at Keimyung University Dongsan Hospital between June and November 2020. The patients were randomly assigned to either the core knife or the IT knife 2 group. The operators and assistants scored the knives' grip convenience and cutting abilities. Results: A total of 39 patients were enrolled (core knife group, 20 patients; IT knife 2 group, 19 patients). There were no significant between-group differences in operator-assessed grip convenience (9.600 vs. 9.526, p=0.753), cutting ability (9.600 vs. 9.105, p=0.158), or assistant-assessed grip convenience (9.500 vs. 9.368, p=0.574). Conclusions: The core knife achieved therapeutic outcomes that were comparable to those of the IT knife 2 for ESD of gastric mucosal lesions.