• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.260-265
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• 2005

Purpose: The protein kinase Chk1 is required for cell cycle arrest in response to DNA damage and is shown to play an important role in the G2/M checkpoint. The aim of this study was to investigate the relationship between microsatellite instability and frameshift mutation of the Chk1 gene in gastric cancers. Materials and Methods: The microsatellite instability was analyzed in 95 primary gastric carcinomas by using microdissection and 6 microsatellite markers. We also peformed single strand conformational polymorphism and sequencing to detect frameshift mutation of the Chk1 gene. Results: We found positive microsatellite instability in 19 (20%) of the 95 gastric cancers, 13 high- and 6 low-frequency microsatellite instability cases. The frameshift mutation of Chk1, which resulted in a truncated Chk1 protein, was detected in two high-frequency microsatellite instability cases. Conclusion: These data suggest that the microsatellite instability may contribute to the development of gastric carcinomas through inactivation of Chk1.

• Journal of Gastric Cancer
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• v.22 no.3
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• pp.169-183
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• 2022

Gastric cancer is prevalent in Korea and ranked as the third most common cancer in 2019, followed by lung and thyroid cancers. The National Cancer Screening Program (NCSP) for gastric cancer has been implemented in adults aged ≥ 40 since 1999 and involves endoscopic screening every 2 years. The beneficial effects of the current NCSP on early cancer detection, cost-effectiveness, and mortality reduction are evident. However, the screening program results in a large socioeconomic burden and the consumption of medical resources, as it focuses solely on secondary prevention (early detection) rather than primary prevention of cancer. Helicobacter pylori is defined as a group I carcinogen by the International Agency for Research on Cancer. Hence, its eradication has been suggested as an important primary gastric cancer prevention strategy. Well-designed randomized controlled trials involving high-risk groups (post-endoscopic resection of early gastric cancer and family history of gastric cancer) and long-term follow-up studies in the general population have provided high-quality evidence regarding the effects of H. pylori eradication on gastric cancer prevention. In this review, we discussed the evidences for a possible modification of the current gastric cancer secondary prevention strategy by introducing primary prevention through H. pylori eradication. Areas for future research to optimize primary prevention strategies were also suggested.

• Journal of Gastric Cancer
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• v.20 no.4
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• pp.345-354
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• 2020

Early detection of gastric cancer is crucial because the survival rate can be improved through curative treatment. Although surgery and gastrectomy with lymph node dissection remain as the gold standard for curative treatment, early gastric cancer (EGC) with negligible risk of lymph node metastasis can be treated with endoscopic resection (ER), such as endoscopic submucosal dissection. Among gastric cancers, undifferentiated-type cancer is distinguished from differentiated-type cancer in various aspects in terms of clinical features and pathophysiology. The undifferentiated-type cancer is also known to be associated with an aggressive behavior and a poor prognosis. Therefore, the indication of ER for undifferentiated EGC is limited compared with differentiated-type. Recent studies have reported that ER for undifferentiated EGC is safe and shows favorable short- and long-term outcomes. However, it is necessary to understand the details of the research results and to selectively accept them. In this review, we aimed to evaluate the current practice guidelines and the short-term and long-term outcomes of ER for undifferentiated type EGC.

• Journal of Digestive Cancer Research
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• v.8 no.2
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• pp.77-80
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• 2020

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. The increased expression of cyclooxygenase (COX)-2 has been implicated in the development and progression of gastric cancers. A number of recent studies have been published evaluating the chemopreventive effect of aspirin and non steroidal anti inflammatory drungs (NSAIDs) against gastric cancer. Aspirin and NSAIDs use may reduce the risk of gastric cancer incidence and death, whereas other studies have reported contradictory results. Therefore, further study should be needed to clarify the role of aspirin and NSAIDs in the chemoprevention of gastric cancer.

• Journal of Gastric Cancer
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• v.20 no.3
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• pp.233-244
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• 2020

Purpose: For unresectable or initially metastatic gastric cancer, conversion surgery (CVS), after systemic chemotherapy, has received attention as a treatment strategy. This study evaluated the prognostic value of ypTNM stage and the oncologic outcomes in patients receiving CVS. Materials and Methods: A retrospective review of clinicopathologic findings and oncologic outcomes of 116 patients who underwent CVS with curative intent, after combination chemotherapy, between January 2000 and December 2015, has been reported here. Results: Twenty-six patients (22.4%) underwent combined resection of another organ and 12 patients received para-aortic lymphadenectomy (10.3%). Pathologic complete remission (CR) was confirmed in 11 cases (9.5%). The median overall survival (OS) and disease-free survival (DFS) times were 35.0 and 21.3 months, respectively. In multivariate analysis, ypTNM stage was the sole independent prognostic factor for DFS (P=0.042). Tumors invading an adjacent organ or involving distant lymph nodes showed better survival than those with peritoneal seeding or solid organ metastasis (P=0.084). Kaplan-Meier curves showed that the 3-year OS rate of patients with pathologic CR and those with CR of the primary tumor but residual node metastasis was 81.8% and 80.0%, respectively. OS was 65.8% for stage 1 patients, 49.8% for those at stage 2, and 36.3% for those at stage 3. Conclusions: The ypTNM staging is a significant prognostic factor in patients who underwent CVS for localized unresectable or stage IV gastric cancers. Patients with locally advanced but unresectable lesions or with tumors with distant nodal metastasis may be good candidates for CVS.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6335-6338
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• 2015

Background: Cancers have dysfunctional redox regulation resulting in production of reactive oxygen species (ROS), damaging DNA, RNA and free NTPs, and causing the accumulation of oxidative nucleic acids in cytoplasm. The major types are 8-oxo-7,8-dihydroguanine(8-oxoGsn) in RNA and 8-oxo-7,8-dihydro-2' deoxyguanosine(8-oxodGsn) in Mt-DNA. The MTH1 protein sanitizes oxidized nucleotide pools from NTPs to monophosphates, preventing the occurrence of transversion mutations. This study concerned cytoplasmic 8-oxodGsn/Gsn and MTH1 expression in gastric cancer and para-cancer tissues and elucidated roles of nucleic-acid oxidation and anti-oxidation. Materials and Methods: A polymer HRP detection system was used to detect 8-oxo-Gsn/dGsn and MTH1 expression in 51 gastric cancer and para-cancer tissue samples. Analyses of patient clinical and pathological data were also performed. Results: The expression of MTH1 and the 8-oxo-dGsn/Gsn ratio were significantly higher in cancer tissues than para-cancer tissues (P<0.05). Cytoplasmic 8-oxo-Gsn and MTH1 were both found to positively correlate (P<0.05) with tumor differentiation, while no significant associations were found with gender, age, invasion depth, lymph node metastasis and clinical stage (P>0.05). Conclusions: We found 8-oxo-dGsn/Gsn and MTH1 are both highly expressed in gastric cancer tissues, especially in well differentiated lesions. In addition, oxidated mtDNA is prevalently expressed in gastric cancers, while 8-oxo-Gsn expression in cytoplasmic RNA is a bit lower, but more selectively.

• Journal of Gastric Cancer
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• v.6 no.2
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• pp.84-90
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• 2006

Purpose: The macroscopic findings of tumors are not always identical with the microscopic findings. This study investigated the oncologic implications of macroscopic serosal invasion in advanced gastric cancer to find out how to improve the accuracy for the depth of invasion assessed by the surgeon during an operation. Materials and Methods: The medical records of 789 patients with advanced gastric cancer who underwent a gastrectomy at Kyungpook National University Hospital between 1995 and 1999 were reviewed. The prognoses and the recurrence patterns were analyzed according to macroscopic serosal invasion and microscopic serosal invasion, and the clinico-pathological factors of cT3/ss cancers were compared with those of cT3/se cancers. Results: Difference of survival rates according to macroscopic serosal invasion and microscopic serosal invasion revealed statistically significant. Recurrence rates were similar in patients with macroscopic and microscopic serosal invasion (42.2% and 41.4%, respectively). Peritoneal recurrence rates were also similar (19.8% and 21.9%, respectively). The sensitivity and the specificity of macroscopic assessment of serosal invasion were 70.3% and 77.8%, respectively, On univariate and multivariate analyses, Borrmann type I/II cancers and the absence of distant metastases revealed the risk factors for overestimating of serosal invasion. Conclusion: Macroscopic serosal invasion assessed by a surgeon intraoperatively can be used to give a prognosis and to predict the recurrence pattern precisely, although there is a risk for overestimation when the tumor is a Borrmann type I/II cancer or the tumor has no distant metastases. (J Korean Gastric Cancer Assoc 2006;6:84-90)

• Journal of Gastric Cancer
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• v.21 no.3
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• pp.221-235
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• 2021

Purpose: The Korean Gastric Cancer Association (KGCA) has been conducting nationwide surveys on patients with surgically treated gastric cancer, every 5 years, since 1995. This study details the results of the survey conducted in 2019. Materials and Methods: This survey was conducted from March to December 2020 using a standardized case report form, which was sent to every member of the KGCA via e-mail. We collected data on 54 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. We compared the results of the 2019 survey with previous surveys. Results: Data of 14,076 cases were collected from 68 institutions. The mean patient age was 62.9 years and the proportion of patients who were aged ≥71 years increased from 9.1% in 1995 to 28.8% in 2019. The proportion of upper-third tumors steadily increased from 11.2% in 1995 to 20.9% in 2019 and that of early gastric cancer increased from 57.7% in 2009 to 63.6% in 2019. Regarding operative procedures, a total laparoscopic approach was used in more than half of the cases (55.1%) in 2019. The most common anastomotic method was the Billroth II procedure (45.0%) after distal gastrectomy and double tract reconstruction (81.2%) after proximal gastrectomy in 2019. The postoperative mortality rate was 1.0%, and the overall postoperative complication rate was 14.5%. Conclusions: The results of the 2019 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for gastric cancer research in the future.

• Journal of Gastric Cancer
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• v.24 no.1
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• pp.4-28
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• 2024

Liquid biopsy, a minimally invasive procedure that causes minimal pain and complication risks to patients, has been extensively studied for cancer diagnosis and treatment. Moreover, it facilitates comprehensive quantification and serial assessment of the whole-body tumor burden. Several biosources obtained through liquid biopsy have been studied as important biomarkers for establishing early diagnosis, monitoring minimal residual disease, and predicting the prognosis and response to treatment in patients with cancer. Although the clinical application of liquid biopsy in gastric cancer is not as robust as that in other cancers, biomarker studies using liquid biopsy are being actively conducted in patients with gastric cancer. Herein, we aimed to review the role of various biosources that can be obtained from patients with gastric cancer through liquid biopsies, such as blood, saliva, gastric juice, urine, stool, peritoneal lavage fluid, and ascites, by dividing them into cellular and acellular components. In addition, we reviewed previous studies on the diagnostic, prognostic, and predictive biomarkers for gastric cancer using liquid biopsy and discussed the limitations of liquid biopsy and the challenges to overcome these limitations in patients with gastric cancer.

• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.19-24
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• 2006

Mothers against decapentaplegic homolog 4 (SMAD4) is a tumor suppressor gene associated with gastrointestinal carcinogenesis. The aim of the present study was to characterize more precisely its role in the development and progression of human gastric carcinoma. In this study, using tissue microarray analysis of 283 gastric cancers and related lesions, we found loss of SMAD4 protein expression in the cytoplasm (36/114, 32%) and in the nucleus (46/114, 40%) of gastric cancer cells. The loss of nuclear SMAD4 expression in primary tumors correlated significantly with poor survival, and was an independent prognostic marker in multivariate analysis. We also found a substantial decrease in SMAD4 expression at both the RNA and protein level in several human gastric carcinoma cell lines. To identify the genetic and/or epigenetic mechanisms of altered SMAD4 expression in gastric carcinoma, loss of heterozygosity (LOH), promoter hypermethylation, and exon mutations were examined. We found that LOH (20/70, 29%) and promoter hypermethylation (4/73, 5%) were associated with the loss of SMAD4 expression. SMAD4 protein levels wore also affected in certain gastric carcinoma cell lines following incubation with Mc132, a proteasome inhibitor. Taken together, our results indicate that the loss of SMAD4, especially loss of nuclear SMAD4 expression, is involved in gastric cancer progression. The loss of SMAD4 in gastric carcinomas is due to several mechanisms, including LOH, hypermethylation, and proteasome degradation.