• Journal of Gastric Cancer
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• v.11 no.2
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• pp.69-77
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• 2011

Purpose: In an effort to examine the clinicopathological characteristics of GC and the status of its surgical treatment, the Korean Gastric Cancer Association (KGCA) conducted a nationwide survey targeting surgically-treated gastric cancer patients in 2009. Materials and Methods: A standardized electrical case report was sent to every member institution of the KGCA via E-mail with detailed instructions regarding the survey data. Completed data forms were retrieved from each institution and analyzed by the KGCA information committee. Results: Data on 14,658 patients was collected from 59 institutions. The mean patient age was $59.2{\pm}11.9$ years with a male to female ratio of 2.05 : 1. Lower third cancer (56.0%) was the most common among all gastric cancers. The histological type revealed poorly differentiated adenocarcinoma (34.1%) to be the most common, and the Lauren classification revealed the intestinal type (50.0%) to be the most prevalent. Curative surgery was performed in 92.4% of patients with laparoscopic surgery in 25.8% of patients. A Billroth I reconstruction was performed most frequently after a distal gastrectomy (63.4% of distal gastrectomy). T1 cancers accounted for 57.6% of all cases, and 62.6% of patients showed no lymph node metastasis. Compared to previous reports, it was found that patients are becoming older, laparoscopic surgery is being performed increasingly, and the proportion of T1 cancer is increasing with time. Conclusions: This survey presented the clinicopathological characteristics and current status of the surgical treatment of gastric cancer in Korea. This survey is expected aid research studies as well as planning and evaluation programs targeting cancer control.

• 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.

• Biomedical Science Letters
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• v.23 no.3
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• pp.230-237
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• 2017

Changes in the activity of alkaline phosphatase (ALP) isoenzymes and isoforms in human serum have a major diagnostic value, therefore the regulation of ALP activities is a valuable target for therapeutic interventions. To assess the pharmacological activity of retinoids, i.e., all-trans retinoic acid and 13-cis retinoic acid, their tissue-specific inhibitory effect on human serum ALP activity was elucidated by chemical inhibition methods, heat-sensitive inactivation, and wheat-germ lectin precipitation test. Retinoids showed significant inhibition of the total ALP activity in human serum at a concentration of 5 mM. All-trans retinoic acid (5 mM) and 13-cis retinoic acid (5 mM) inhibited ALP activities by up to 12% and 15%, respectively, compared to that by guanidine hydrochloride (200 mM). L-phenylalanine (100 mM) and urea (30 mM) had no further inhibitory effect on ALP activities in human serum pretreated with retinoids (5 mM). Retinoids significantly inhibited ALP activities by up to 20% compared with that of tetramisole (30 mM). The ALP activities in retinoid-pretreated serum remained unchanged after the heat inactivation process. These results suggest that retinoids are inhibitors of the intestinal ALP isoenzyme. Remarkably, retinoids revealed potent inhibitory activities against ALP in wheat-germ lectin precipitant serum, indicating that they also function as inhibitors of the bone ALP isoform. The results show that retinoids inhibit the specific tissue-derived human serum ALP activities, moreover, the inhibitory effect of retinoids against bone ALP activity suggests their clinical utility as monitoring and prevention of metastasis of bone cancer.

• 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.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.692-698
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• 2019

Background: Breast cancer is a severe disease and the second leading cause of cancer death in women worldwide. To surmount this, various diagnosis and treatment options for breast cancer have been developed. One of the most effective strategies for cancer treatment is to induce apoptosis using naturally occurring compounds. Compound K (CK) is a ginseng saponin metabolite generated by human intestinal bacteria. CK has been studied for its cardioprotective, antiinflammatory, and liver-protective effects; however, the role of CK in breast cancer is not fully understood. Methods: To investigate the anticancer effects of CK in SKBR3 and MDA-MB-231 cells, cell viability assays and flow cytometry analysis were used. In addition, the direct targets of CK anticancer activity were identified using immunoblotting analysis and overexpression experiments. Invasion, migration, and clonogenic assays were carried out to determine the effects of CK on cancer metastasis. Results: CK-induced cell apoptosis in SKBR3 cells as determined through 3-(4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assays, propidium iodide (PI) and annexin V staining, and morphological changes. CK increased the cleaved forms of caspase-7, caspase-8, and caspase-9, whereas the expression of Bcl-2 was reduced by CK. In assays probing the cell survival pathway, CK activated only AKT1 and not AKT2. Moreover, CK inhibited breast cancer cell invasion, migration, and colony formation. Through regulation of AKT1 activity, CK exerts anticancer effects by inducing apoptosis. Conclusion: Our results suggest that CK could be used as a therapeutic compound for breast cancer.

• Molecules and Cells
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• v.46 no.8
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• pp.476-485
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• 2023

Gastric cancer stem-like cells (GCSCs) possess stem cell properties, such as self-renewal and tumorigenicity, which are known to induce high chemoresistance and metastasis. These characteristics of GCSCs are further enhanced by autophagy, worsening the prognosis of patients. Currently, the mechanisms involved in the induction of stemness in GCSCs during autophagy remain unclear. In this study, we compared the cellular responses of GCSCs with those of gastric cancer intestinal cells (GCICs) whose stemness is not induced by autophagy. In response to glucose starvation, the levels of β-catenin and stemness-related genes were upregulated in GCSCs, while the levels of β-catenin declined in GCICs. The pattern of deubiquitinase ubiquitin C-terminal hydrolase-L3 (UCH-L3) expression in GCSCs and GCICs was similar to that of β-catenin expression depending on glucose deprivation. We also observed that inhibition of UCH-L3 activity reduced β-catenin protein levels. The interaction between UCH-L3 and β-catenin proteins was confirmed, and it reduced the ubiquitination of β-catenin. Our results suggest that UCH-L3 induces the stabilization of β-catenin, which is required to promote stemness during autophagy activation. Also, UCH-L3 expression was regulated by c-Fos, and the levels of c-Fos increased in response to autophagy activation. In summary, our findings suggest that the inhibition of UCH-L3 during nutrient deprivation could suppress stress resistance of GCSCs and increase the survival rates of gastric cancer patients.

• Advances in nano research
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• v.15 no.5
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• pp.451-466
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• 2023

Gastrointestinal cancer (GC) is a prevalent malignant tumor of the digestive system that poses a severe health risk to humans. Due to the specific organ structure of the gastrointestinal system, both endoscopic and MRI diagnoses of GIC have limited sensitivity. The primary factors influencing curative efficacy in GIC patients are drug inefficacy and high recurrence rates in surgical and pharmacological therapy. Due to its unique optical features, good biocompatibility, surface effects, and small size effects, nanotechnology is a developing and advanced area of study for the detection and treatment of cancer. Because of its deep location and complex surgery, diagnosing and treating gastrointestinal cancer is very difficult. The early diagnosis and urgent treatment of gastrointestinal illness are enabled by nanotechnology. As diagnostic and therapeutic tools, nanoparticles directly target tumor cells, allowing their detection and removal. XGBoost was used as a classification method known for achieving numerous winning solutions in data analysis competitions, to capture nonlinear relations among many input variables and outcomes using the boosting approach to machine learning. The research sample included 300 GC patients, comprising 190 males (72.2% of the sample) and 110 women (27.8%). Using convolutional neural networks (CNN) and artificial neural networks (ANN)-EXtreme Gradient Boosting (XGBoost), the patients mean± SD age was 50.42 ± 13.06. High-risk behaviors (P = 0.070), age at diagnosis (P = 0.037), distant metastasis (P = 0.004), and tumor stage (P = 0.015) were shown to have a statistically significant link with GC patient survival. AUC was 0.92, sensitivity was 81.5%, specificity was 90.5%, and accuracy was 84.7 when analyzing stomach picture.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.1
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• pp.26-34
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• 2009

Purpose: The purpose of this study was to find out what clinicopathologic or immunohistochemical parameter that may affect FDG uptake of primary tumor in PET/CT scan of the gastric carcinoma patient. Materials and Methods: Eighty-nine patients with stomach cancer who underwent pre-operative FDG PET/CT scans were included. In cases with perceptible FDG uptake in primary tumor, the maximum standardized uptake value (SUVmax) was calculated. The clinicopathologic results such as depth of invasion (T stage), tumor size, lymph node metastasis, tumor differentiation and Lauren's classification and immunohistochemical markers such as Ki-67 index, expression of p53, EGFR, Cathepsin D, c-erb-B2 and COX-2 were reviewed. Results: Nineteen out of 89 gastric carcinomas showed imperceptible FDG uptake on PET/CT images. In cases with perceptible FDG uptake in primary tumor, SUVmax was significantly higher in T2, T3 and T4 tumors than T1 tumors ($5.8{\pm}3.1$ vs. $3.7{\pm}2.1$, p=0.002). SUVmax of large tumors (above or equal to 3 cm) was also significantly higher than SUVmax of small ones (less than 3 cm) ($5.7{\pm}3.2$ vs. $3.7{\pm}2.0$, p=0.002). The intestinal types of gastric carcinomas according to Lauren showed higher FDG uptake compared to the non-intestinal types ($5.4{\pm}2.8$ vs. $3.7{\pm}1.3$, p=0.003). SUVmax between p53 positive group and negative group was significantly different ($6.0{\pm}2.8$ vs. $4.4{\pm}3.0$, p=0.035). No significant difference was found in presence of LN metastasis, tumor differentiation, Ki-67 index, and expression of EGFR, Cathepsin D, c-erb-B2 and COX-2. Conclusion: T stage of gastric carcinoma influenced the detectability of gastric cancer on FDG PET PET/CT scan. When gastric carcinoma was perceptible on PET/CT scan, T stage, size of primary tumor, Lauren's classification and p53 expression were related to degree of FDG uptake in primary tumor.

• Journal of Gastric Cancer
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• v.6 no.4
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• pp.214-220
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• 2006

Purpose: p53 is one of the most commonly mutated genes in human tumors. The aim of this study was to analyze p53 mutation in gastric cancer and its correlations with the clinicopathologic variables to clarify the usefulness of p53 mutation as a prognostic factor. Materials and Methods: Specimens from 331 patients with gastric cancer who underwent a gastrectomy between March 1999 and April 2001 at the Kyungpook National University Hospital were used. p53 gene mutations were assessed by using a polymerase chain-reaction single-strand conformation polymorphism (PCR-SSCP) analysis. The correlations between p53 gene mutation and clinocopathologic parameters were analyzed. Results: p53 mutations were found in 66 (19.9%) tumors. Among those 66 cases, mutations were seen in 23 tumors at axon 5, in 8 at exon 6, in 21 at exon 7, and in 17 at exon 8. Two mutations were shown in 3 tumors. Thiriy-six (23.1%) of 156 intestinal-type tumors and 19 (13.1%) of 145 diffuse-type tumors showed p53 gene mutation (P=0.007). The frequency of p53 gene mutation didn't show any significant differences according to age, sex, stage, location, or gross type. Exon 5 mutations showed more frequently in intestinal-type tumors than in diffuse-type tumors (9.7% vs. 2.8%, P=0.024), and p53 mutation were more frequent in lymph nodes metastasis group than lymph nodes non-metastasis group with statistical significance (25.0% vs 15.6%, P=0.034). The five-year survival rate showed no statistically significant difference with p53 mutation (P=0.704). Conclusion: p53 mutations assessed by PCR-SSCP had little value as a prognostic factor after gastrectomy in patients with gastric cancer.

• Radiation Oncology Journal
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• v.3 no.2
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• pp.103-111
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• 1985

The early carcinoma of the uterine cervix may be treated by either radical surgery or radical radiotherapy according to the patient's characteristics, and the survival is high with either treatment. But, because of the size of the lesion, metastasis to lymph nodes, and vascular space invasion by tumor have all been shown to influence recurrence and survival, postoperative radiotherapy may be considered as their histopathologic finding after radical surgery. However, there are still debates on the increasing survival rates with postoperative radiotherapy. Two hundreds and three patients with carcinoma of the uterine cervix who were treated with postoperative radiotherapy from February 1979 to September 1982 in the Department of Therapeutic Radiology, Seoul National University were analyzed and following results were obtained. 3-year actuarial survival rate and 3-year disease free sruvival rate were $83.4\%\;and\;73.4\%$ respectively and 3-year actuarial survival rates by stages were $90.7\%$ for IB, $69.6\%$ for IIA, and $85.2\%$ for IIB. 3-year disease free survival rates by stage IB, IIA, IIB were $79.8\%,\;07.8\%,\;68.3\%$ respectively. The overall failure rate was $25.1\%(51/203)$; local recurrence rate was $8.4\%$, distant metastasis rate was $14.3\%$ and simultaneous local recurrence and distant metastasis was $2.4\%$. Failure rates by stages were $19.8\%$ (18/19) for IB, $29.1\%$ (16/55) for IIA and $29.8\%$ (17/57) for IIB. The overall acute complication rate was $57.6\%$; tolerable cases was $50.2\%$ and severe cases was $7.4\%$. Late complication rate was $7.9\%$ and the major late complication were intestinal obstruction. aggravated urinary symptom, radiation cystitis in order of frequency.