• BMB Reports
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• v.46 no.1
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• pp.25-30
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• 2013

Gap junctions and their structural proteins, connexins (Cxs), have been implicated in carcinogenesis. To explore the involvement of Cx32 in gastric carcinogenesis, immunochemical analysis of Cx32 and proliferation marker Ki67 using tissue-microarrayed human gastric cancer and normal tissues was performed. In addition, after Cx32 overexpression in the human gastric cancer cell line AGS, cell proliferation, cell cycle analyses, and $p21^{Cip1}$ and $p27^{Kip1}$ expression levels were examined by bromodeoxyuridine assay, flow cytometry, real-time RT-PCR, and western blotting. Immunohistochemical study noted a strong inverse correlation between Cx32 and Ki67 expression pattern as well as their location. In vitro, overexpression of Cx32 in AGS cells inhibited cell proliferation significantly. $G^1$ arrest, up-regulation of cell cycle-regulatory proteins $p21^{Cip1}$ and $p27^{Kip1}$ was also found at both mRNA and protein levels. Taken together, Cx32 plays some roles in gastric cancer development by inhibiting gastric cancer cell proliferation through cell cycle arrest and cell cycle regulatory proteins.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.487-492
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• 2011

In our previous study, we investigated Chenopodium album Linne (CAL) ethanol extract and its fractions on anti-gastritic actions using the HCl/ethanol and indomethacin induced gastric lesion model and Helicobacter pylori (H. pylori). Based on the results, butanol fraction was most effective among fractions obtained from CAL. This study aims to elucidate the mechanisms of butanol fraction, and betaine as a constituent of the butanol fraction, on gastritis and anti-gastric cancer cell growth. First, we examined antioxidant properties using hydrogen peroxide and superoxide radical, and we found that butanol fraction and betaine may be good antioxidants. Second, cytotoxicity was assessed by measuring cell viability and 4,6-diamidino-2-phenylinodole dihydrochloride (DAPI) staining of human gastric cancer cells (AGS cells). We also examined the relationship between the cytotoxicity and intracellular $Ca^{2+}$ signaling mechanism. The butanol fraction demonstrated cell viability 71.49% at the concentration of 100 ${\mu}g/ml$ and increased intracellular $Ca^{2+}$ concentration in a dose dependent manner. Finally, we observed the mucus content as a defensive factor and gastric secretion as an aggressive factor, and found that the mucus content noticeably increased when treated with butanol fraction and betaine and gastric secretion decreased when treated with betaine in vivo study. From these results, we suggest that CAL butanol fraction and betaine may have protective effects on gastritis.

• Journal of Gastric Cancer
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• v.12 no.2
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• pp.73-80
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• 2012

Purpose: The specific aim of this study is to unravel a DNA copy number alterations, and to search for novel genes that are associated with the development of Korean gastric cancer. Materials and Methods: We investigated a DNA copy number changes in 23 gastric adenocarcinomas by array-comparative genomic hybridization and quantitative real-time polymerase chain reaction analyses. Besides, the expression of UQCRFS1, which shows amplification in array-CGH, was examined in 186 gastric cancer tissues by an immunohistochemistry, and in 9 gastric cancer cell lines, as well as 24 gastric cancer tissues by immunoblotting. Results: We found common gains at 48 different loci, and a common loss at 19 different loci. Amplification of UQCRFS1 gene at 19q12 was found in 5 (21.7%) of the 23 gastric cancers in an array-comparative genomic hybridization and DNA copy number were increased in 5 (20.0%) out of the 25 gastric cancer in quantitative real-time polymerase chain reaction. In immunohistochemistry, the overexpression of the protein was detected in 105 (56.5%) out of the 186 gastric cancer tissues. Statistically, there was no significant relationship between the overexpression of UQCRFS1 and clinicopathologic parameters (P>0.05). In parallel, the overexpression of UQCRFS1 protein was confirmed in 6 (66.7%) of the 9 gastric cancer cell lines, and 12 (50.0%) of the 24 gastric cancer tissues by immunoblotting. Conclusions: These results suggest that the overexpression of UQCRFS1 gene may contribute to the development and/or progression of gastric cancer, and further supported that mitochondrial change may serve as a potential cancer biomarker.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.295-305
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• 2017

Purpose: We previously found that the histone methyltransferase suppressor of variegation, enhancer of zeste, trithorax and myeloid-nervy-deformed epidermal autoregulatory factor-1 domain-containing protein 3 (SMYD3) is a potential independent predictive factor or prognostic factor for overall survival in gastric cancer patients, but its roles seem to differ from those in other cancers. Therefore, in this study, the detailed functions of SMYD3 in cell proliferation and migration in gastric cancer were examined. Materials and Methods: SMYD3 was overexpressed or suppressed by transfection with an expression plasmid or siRNA, and a wound healing migration assay and Transwell assay were performed to detect the migration and invasion ability of gastric cancer cells. Additionally, an MTT assay and clonogenic assay were performed to evaluate cell proliferation, and a cell cycle analysis was performed by propidium iodide staining. Furthermore, the expression of genes implicated in the ataxia telangiectasia mutated (ATM) pathway and proteins involved in cell cycle regulation were detected by polymerase chain reaction and western blot analyses. Results: Compared with control cells, gastric cancer cells transfected with si-SMYD3 showed lower migration and invasion abilities (P<0.05), and the absence of SMYD3 halted cells in G2/M phase and activated the ATM pathway. Furthermore, the opposite patterns were observed when SMYD3 was elevated in normal gastric cells. Conclusions: To the best of our knowledge, this study provides the first evidence that the absence of SMYD3 could inhibit the migration, invasion, and proliferation of gastric cancer cells and halt cells in G2/M phase via the ATM-CHK2/p53-Cdc25C pathway. These findings indicated that SMYD3 plays crucial roles in the proliferation, migration, and invasion of gastric cancer cells and may be a useful therapeutic target in human gastric carcinomas.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8215-8219
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• 2014

CD133 is one of the most important stem cell markers in solid cancers and Ki-67 is a marker that reflects cell proliferation. The relationships between the expression of CD133 and Ki-67 and prognosis in gastric carcinoma are unknown and need exploring. We examined 50 gastric cancer patients retrospectively in the Radiation Oncology Department of the Faculty of Medicine, Gazi University. CD133 and Ki-67 expression was examined using immunohistochemical staining. The survival rate in patients with CD133 positive expression was significantly worse than that in the patients with negative expression (p=0.04). Expression of CD133 had a positive correlation with that of Ki-67 (r=0.350; p=0.014). Multivariate analysis revealed that the expression of CD133 was an independent prognostic factor in gastric cancer (p=0.02). Conclusion, expression of CD133 may be a useful prognostic marker in gastric cancer.

• Journal of Gastric Cancer
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• v.24 no.1
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• pp.69-88
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• 2024

This review comprehensively examines the diverse spectrum of gastric cancers, focusing on unusual or uncommon histology that presents significant diagnostic and therapeutic challenges. While the predominant form, tubular adenocarcinoma, is well-characterized, this review focuses on lesser-known variants, including papillary adenocarcinoma, micropapillary carcinoma, adenosquamous carcinoma, squamous cell carcinoma (SCC), hepatoid adenocarcinoma, gastric choriocarcinoma, gastric carcinoma with lymphoid stroma, carcinosarcoma, gastroblastoma, parietal cell carcinoma, oncocytic adenocarcinoma, Paneth cell carcinoma, gastric adenocarcinoma of the fundic gland type, undifferentiated carcinoma, and extremely well-differentiated adenocarcinoma. Although these diseases have different nomenclatures characterized by distinct histopathological features, these phenotypes often overlap, making it difficult to draw clear boundaries. Furthermore, the number of cases was limited, and the unique histopathological nature and potential pathogenic mechanisms were not well defined. This review highlights the importance of understanding these rare variants for accurate diagnosis, effective treatment planning, and improving patient outcomes. This review emphasizes the need for ongoing research and case studies to enhance our knowledge of these uncommon forms of gastric cancer, which will ultimately contribute to more effective treatments and better prognostic assessments. This review aimed to broaden the pathological narrative by acknowledging and addressing the intricacies of all cancer types, regardless of their rarity, to advance patient care and improve prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5463-5468
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• 2014

MicroRNAs might act as oncogenes or tumor suppressors in cancer. Recent studies have shown that miR-421 is up-regulated in human gastric cancer. Here, we found that miR-421 was over-expressed in gastric cancer tissues and cell lines. Bioinformatics analysis predicted that the caspase-3 gene was a target of miR-421. Caspase-3 was negatively regulated by miR-421 at the post-transcriptional level. Bax and Bcl-2 were also regulated by miR-421. Moreover, tumor necrosis factor receptor-I and -II, death receptors in the apoptosis pathway, were up-regulated by miR-421. The over-expression of miR-421 promoted gastric cancer cell growth and inhibited apoptosis of the BGC-823 gastric cancer cell line. These observations indicate that miR-421 acts as a tumor promoter by targeting the caspase-3 gene and preventing apoptosis of gastric cancer cells through inhibition of caspase-3 expression. These findings contribute to our understanding of the functions of miR-421 in gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1781-1787
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• 2015

Background: miRNAs are relatively recently discovered cancer biomarkers which have important implications for cancer early diagnosis, treatment and estimation of prognosis. Here we focussed on expression of mir-196a-5p in gastric cancer tissues and cell lines so as to analyse its significance for clinicopathologic characteristics and generate enriched KEGG pathways clustered by target genes for exploring its potential roles as a biomarker in gastric cancer. Materials and Methods: The expression of mir-196a-5p in poorly, moderate and well differentiated gastric cancer cell lines compared with GES-1 was detected by RT-qPCR, and the expression of mir-196a-5p in gastric cancer tissues comparing with adjacent non cancer tissues of 58 cases were also assessed by RT-qPCR. Subsequently, an analysis of clinical significance of mir-196a-5p in gastric cancer and enriched KEGG pathways was executed based on the miRWalk prediction database combined with bioinformatics tools DAVID 6.7 and Mirfocus 3.0. Results: RT-qPCR showed that mir-196a-5p was up-regulated in 6 poorly and moderate differentiated gastric cancer cell lines SGC-7901, MKN-45, MKN-28, MGC-803, BGC-823, HGC-27 compared with GES-1, but down-regulated in the highly differentiated gastric cancer cell line AGS. Clinical data indicated mir-196a-5p to beup-regulated in gastric cancer tissues (47/58). Overexpression of mir-196a-5p was associated with more extensive degree of lymph node metastasis and clinical stage (P < 0.05; x2 test). Enriched KEGG pathway analyses of predicted and validated targets in miRWalk combined with DAVID 6.7 and Mirfocus 3.0 showed that the targeted genes regulated by mir-196a-5p were involved in malignancy associated biology. Conclusions: Overexpression of mir-196a-5p is associated with lymph node metastasis and clinical stage, and enriched KEGG pathway analyses showed that targeted genes regulated by mir-196a-5p may contribute to tumorgenesis, suggesting roles as an oncogenic miRNA biomarker in gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.835-840
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• 2013

Accumulating evidence has shown that microRNAs are involved in cancer development and progression. However, it remains unknown about the potential role of miR-19a in the pathogenesis of gastric cancer. Here, we report that suppressor of cytokine signaling 1 (SOCS1) is a novel target of miR-19a in gastric cancer cells and that miR-19a expression is inversely correlated with SOCS1 expression in gastric cancer cells and a subset of gastric cancer tissues. Ectopic expression of miR-19a dramatically promoted proliferation and tumorigenicity of gastric cancer cells both in vitro and in vivo. Moreover, we showed that silencing of SOCS1 promoted cell growth and colony formation resembling that of miR-19a overexpression, whereas re-introduction of SOCS1 (without the 3'-UTR) attenuated the pro-tumorigenic functions. Taken together, our findings suggest that the SOCS1 gene is a direct target of miR-19a, which functions as an oncogenic miRNA in gastric cancer by repressing the expression of tumor suppressor SOCS1.

• Journal of Gastric Cancer
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• v.14 no.3
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• pp.211-214
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• 2014

We report our experience of a concurrent robot assisted distal gastrectomy and partial nephrectomy for synchronous early gastric cancer and renal cell carcinoma. A 55-year-old female patient was diagnosed with early gastric cancer on screening endoscopy. Abdominal computed tomography showed an incidental right renal cell carcinoma. Robot assisted distal gastrectomy was performed, followed by partial nephrectomy. The final pathological examination showed signet ring cell carcinoma within the lamina propria and renal cell carcinoma with negative resection margins. The patient showed no evidence of recurrence at 6-months. A robot-assisted combined operation could be a treatment option for early stages of synchronous malignancies.