• Journal of Life Science
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• v.9 no.2
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• pp.24-33
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• 1999

The gastrointestinal tract of three Percida, Lateolabrax japonicus, Epinephelus septemfasciatus and Mugil cephalus, was investigated immunocytochemically for the occurrence of somatostatin-. seotonin-, gastrin-, pancreatic polypeptide(PP)-, cholecystokinin-8(CCK-8)- and glucagon-immunoreactive cells. In Lateolabrax japonicus and Epinephelus septemfasciatus, five endorcrine cell types, such as somatostatin-, serotonin-, gastrin-, PP- and CCk-8-immunoreactive cells were demonstrated. In Mugil cephalus, however, six endocrine cell types, such as somatostatin-, serotnin-gastrin-, PP-, CCK-8- and glucagon-immunoreactive cells were detected. Somatostatin- and serotonin-immunoreactive cells were detected in the gastric mucosa of all species. Glucagon-immunoreactive cells were found only in the gastric mucoas of Mugil cephalus. In the pyloric caeca, PP-and CCK-8-immnuoreactive cells fo all species. gastrin-immunoreactive cells of Epinephelus septemfasciatus and Mugil cephalus, and serotonin-immunoreactive cells of Epinephelus septemfasciatus were demonstrated. In the intestinal mucosa of all species, gastrin-, PP- and CCK-8-immunoreactive cells were detected, and in the intestinal mucosa of Epinephelus septemfasciatus serotonin-immunoreactive cells were also detected. The frequency of these immunoreactive cells differs from each portion of the gastrointestinal tract of all species.

• Journal of Gastric Cancer
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• v.20 no.2
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• pp.139-151
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• 2020

Purpose: Globally, there is a high incidence of gastric cancer (GC). Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is reported to play a vital role in several human malignancies. However, there is limited understanding of the role of LETM1 in GC. This study aims to investigate the effects of LETM1 on proliferation, migration, and invasion of GC cells. Materials and Methods: The expression levels of LETM1 in the normal gastric mucosal epithelial cells (GES-1) and GC cells were analyzed by quantitative real-time polymerase chain reaction and western blotting. CCK-8, wound healing, and Transwell invasion assays were performed to evaluate the effect of LETM1 knockdown or overexpression on the proliferation, migration, and invasion of the GC cells, respectively. Additionally, the effect of LETM1 knockdown or overexpression on GC cell apoptosis was determined by flow cytometry. Furthermore, the effect of LETM1 knockdown or overexpression on the expression levels of PI3K/Akt signaling pathway-related proteins was evaluated by western blotting. Results: The GC cells exhibited markedly higher mRNA and protein expression levels of LETM1 than the GES-1 cells. Additionally, the knockdown of LETM1 remarkably suppressed the GC cell proliferation, migration, and invasion, and promoted the apoptosis of GC cells, which were reversed upon LETM1 overexpression. Furthermore, the western blotting analysis indicated that LETM1 facilitates GC progression via the PI3K/Akt signaling pathway. Conclusions: LETM1 acts as an oncogenic gene to promote GC cell proliferation, migration, and invasion via the PI3K/Akt signaling pathway. Therefore, LETM1 may be a potential target for GC diagnosis and treatment.

• The Korean Journal of Zoology
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• v.17 no.2
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• pp.69-80
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• 1974

The mucosubstances in the gastrointestinal mucous secreting cells of Rana rugosa were detected histochmeically during pre-hibernating, hibernating, post-hibernating and active phases. The results of the observation were as follows: 1. The mucosubstances in the gastrointestinal mucous secreting cells of active frog were strongly PAS-active in stomach, PAS-active and alcianophilic at pH 2.5 in small intestine and alcianophilic at pH 2.5 in large intestine. 2. The PAS-active mucosubstances in the gastric surface epithelial cells were increased remarkably during hibernation. 3. The alcianophilic mucosubstances at both pH 2.5 and pH 1.0 were decreased remarkably in the goblet cells of small intestine during hibernation, but a little PAS-active ones were increased. 4. The alcianophilic mucosubstances at pH 2.5 were decreased remarkably and a lttle PAS-active ones also were done in the goblet cells of large intestine during hibernation. 5. The increases of the contained quantity of mucosubstances in the gastric surface epithelial cells during hibernationi may have theeffects of preventing cohesions of gastric mucosae and suppressing activities of gastric acid and enzymes. The mucosubstances neutral acidity in the intestine during hibernation may be secreted, because of acidity being done near neutrality in its lumen, due to remarkable decrease of intestinal juices and gastric acids.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2425-2430
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• 2015

Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. EHZ2 is involved in drug resistance and is overexpressed in drug-resistant cancer cell lines. In this study, we investigated the effects of EHZ2 on cisplatin -resistance in A549/DDP and AGS/DDP cells. EHZ2 mRNA and protein were found to be significantly overexpressed in A549/DDP and AGS/DDP cells, compared to parental cells. EHZ2 siRNA successfully silenced EHZ2 mRNA and protein expression. Proliferation was inhibited and drug resistance to cisplatin was improved. Flow cytometry showed that silencing of EHZ2 arrested A549/DDP and AGS/DDP cells in the G0/G1 phase, increasing apoptosis, rh-123 fluorescence intensity and caspase-3/8 activities. Silencing of EHZ2 also significantly reduced the mRNA and protein expression levels of cyclin D1 and MDR1,while up-regulating p15, p21, p27 and miR-218 in A549/DPP cells. Furthermore, silencing of EHZ2 also significantly increased the expression level of tumor suppressor factor miR-218. We also found down-regulating EHZ2 expression increased methylation in A549/DDP and AGS/DDP cells. This study demonstrates that drug resistance can be effectively reversed in human cisplatin-resistant lung and gastric cancer cells through delivery of siRNAs targeting EHZ2.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4271-4274
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• 2014

The epithelial to mesenchymal transition (EMT) is a key step during embryonic morphogenesis and plays an important role in drug resistance and metastasis in diverse solid tumors. We previously reported that 48 h treatment of anti-cancer drug doxorubicin could induce EMT in human gastric cancer BGC-823 cells. However, the long term effects of this transient drug treatment were unknown. In this study we found that after 48 h treatment with $0.1{\mu}g/ml$ doxorubicin, most cells died during next week, while a minor population of cells survived and formed colonies. We propagated the surviving cells in drug free medium and found that these long term cultured drug survival cells (abbreviated as ltDSCs) retained a mesenchymal-like cell morphology, and expressed high levels of EMT-related molecules such as vimentin, twist and ${\beta}$-catenin. The expression of chromatin reprogramming factors, Oct4 and c-myc, were also higher in ltDSCs than parental cells. We further demonstrated that the protein level of p300 was upregulated in ltDSCs, and inhibition of p300 by siRNA suppressed the expression of vimentin. Moreover, the ltDSCs had higher colony forming ability and were more drug resistant when compared to parental cells. Our results suggested that an epigenetic mechanism is involved in the EMT of ltDSCs.

• Journal of Gastric Cancer
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• v.3 no.4
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• pp.186-190
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• 2003

Purpose: The balance between cell proliferation and apoptosis is crucial for homeostatic maintenance in a cell population. Decreased apoptosis or uncontrolled proliferation can lead to cancer. The Fas receptor signal through a cytoplasmic death domain is very important in the apoptotic pathway. To identify the effect of the death domain of the Fas gene in the development and/or progression of gastric cancer, we examined the apoptotic potential of five known Fas mutants detected in gastric cancers. Materials and Methods: A wild-type Fas gene was cloned with cDNA from normal liver tissue and full length Fas was sequenced. Mutants of the gene were generated with sitedirected mutagenesis by using the wild-type gene and specific primers. Wild- and mutant-type genes were transfected to HEK293 cells. Forty-eight hours after transfection the cells were stained with DAPI and cell death was counted under fluorescent microscopy. Results: In wild-type Fas-transfected cells, the percentage of apoptotic cells was $85.9\pm3.6\%$, and significant cell death and classic morphologic signs of apoptosis were observed. However, the percentages of apoptotic cells transfected with N239D, E240G, D244V, and R263H of tumor-derived mutant Fas were $29.5\pm2.08\%,\;28.5\pm3.34\%,\;25.225\pm2.06\%,\;and\;36.625\pm4.49\%$, respectively. Conclusion: These results suggest that inactivation of Fas caused by mutations in the death domain of the Fas gene may be one of the possible escape mechanisms against Fas-mediated apoptosis and that inactivating mutation of the Fas may contribute to the development or progression of gastric cancers.

• 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.

• Journal of Gastric Cancer
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• v.1 no.4
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• pp.202-209
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• 2001

Purpose: When cancer cels invade the stroma, they should be dissociated from the adjacent cells at first. E-cadherin and $\beta-catenin$ constitute an important protein complex associated with cellular adhesion, development, and differentiation, especially in epithelial cells. The role of E-cadherin and $\beta-catenin$ in gastric carcinogenesis were studied. Materials and Methods: The expression of E-cadherin and $\beta-catenin$ in gastric adenocarcinomas by using immunohistochemical staining and the mutation by using polymerase chain reaction- single stranded conformation polymorphism (PCR-SSCP) and sequencing were performed in 40 adenocarcinomas and 5 dysplasia of stomach. Thirteen cases, which had lymph node metastasis, were also included for immunohistochemical staining. Results: Inappropriate cytoplasmic and/or nuclear expression of a E-cadherin-$\beta-catenin$ complex was more frequent in poorly differentiated, diffuse type signet ring cell carcinomas than in well-differentiated, intestinal type adenocarcinomas (P<0.05). However, the expression was not related with clinical stage or lymph node metastasis. Mutation of E-cadherin was detected in 4 cases by using PCR-SSCP, whereas mutation of $\beta-catenin$ was detected in 2 cases. Conclusion: E-cadherin and $\beta-catenin$ seem to be important in gastric carcinogenesis, especially in poorly differentiated diffuse type.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.270-276
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• 2008

In this study we investigated the effects of Magnolia Bark (MB) extract and its constituents, such as honokiol and magnolol, on gastritis in rats and the growth of human gastric cancer cells. The MB extract, honokiol, and magnolol showed the acid-neutralizing capacities, the antioxidant activities, and the inhibitory effect on the growth of Helicobacter pylori (H. pylori.) at the dose of $50\;{\mu}g/ml$ and over, which is equivalent to that of ampicillin ($100\;{\mu}g/ml$). Honokiol and magnolol had no significant cytotoxicity to human gastric caner cells (AGS and SNU638). However, the MB extract had cytotoxic activity against AGS gastric cancer cell. The MB extract, honokiol, and magnolol significantly inhibited HCI-ethanol-induced gastric lesions without clear change of mucus content. In pylorus ligated rats, honokiol significantly decreased the volume of gastric secretion and gastric acid output, and increased the pH. Magnolol increased the mucus content to almost the same as the control group at oral doses of 50 mg/kg. Therefore, we could guess that antigastritic action of honokiol and magnolol may be associated with the antioxidant activities, acid-neutralizing capacities, inhibition of secretion in gastric acid, and anti-H. pylori action. From these results, we could suggest that MB extract and its constituents, such as honokiol and magnolol, may be useful for the treatment and/or protection of gastritis.

• 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.