• Yonsei Medical Journal
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• 제59권9호
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• pp.1041-1048
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• 2018

Purpose: Heat shock factor 1 (HSF1) is a key regulator of the heat shock response and plays an important role in various cancers. However, the role of HSF1 in gastric cancer is still unknown. The present study evaluated the function of HSF1 and related mechanisms in gastric cancer. Materials and Methods: The expression levels of HSF1 in normal and gastric cancer tissues were compared using cDNA microarray data from the NCBI Gene Expression Omnibus (GEO) dataset. The proliferation of gastric cancer cells was analyzed using the WST assay. Transwell migration and invasion assays were used to evaluate the migration and invasion abilities of gastric cancer cells. Protein levels of HSF1 were analyzed using immunohistochemical staining of tissue microarrays from patients with gastric cancer. Results: HSF1 expression was significantly higher in gastric cancer tissue than in normal tissue. Knockdown of HSF1 reduced the proliferation, migration, and invasion of gastric cancer cells, while HSF1 overexpression promoted proliferation, migration, and invasion of gastric cancer cells. Furthermore, HSF1 promoted the proliferation of gastric cancer cells in vivo. In Kaplan-Meier analysis, high levels of HSF1 were associated with poor prognosis for patients with gastric cancer (p=0.028). Conclusion: HSF1 may be closely associated with the proliferation and motility of gastric cancer cells and poor prognosis of patients with gastric cancer. Accordingly, HSF1 could serve as a prognostic marker for gastric cancer.

• Journal of Gastric Cancer
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• 제12권3호
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• pp.140-148
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• 2012

Purpose: Among cell adhesion molecules, serum levels of intercellular adhesion molecule-1 and E-selectin are known to be correlated with the metastatic potential of gastric cancer. In the present study, the authors investigated the expression of intercellular adhesion molecule-1 and E-selectin in gastric cancer tissues and cultured gastric cancer cells, and examined their clinical value in gastric cancer. Materials and Methods: The protein was extracted from gastric cancer tissues and cultured gastric cancer cells (MKN-28 and Kato-III) and the expression of intercellular adhesion molecule-1 and E-selectin was examined by western blotting. The clinical significance of intercellular adhesion molecule-1 and E-selectin was explored, using immunohistochemical staining of specimens from 157 gastric cancer patients. Results: In western blot analysis, the expressions of intercellular adhesion molecule-1 in gastric cancer tissues and cultured gastric cancer cells were increased, however, E-selectin in gastric cancer tissues and cells were not increased. Among 157 gastric cancer patients, 79 patients (50%) were intercellular adhesion molecule-1 positive and had larger tumor size, an increased depth of tumor invasion, lymph node metastasis and perineural invasion. The intercellular adhesion molecule-1 positive group showed a higher incidence of tumor recurrence (40.5%), and a poorer 3-year survival than the negative group (54.9 vs. 85.9%, respectively). Conclusions: Intercellular adhesion molecule-1 is overexpressed in gastric cancer tissues and cultured gastric cancer cells, whereas E-selectin is not overexpressed. Increased expression of intercellular adhesion molecule-1 in gastric cancer could be related to the aggressive nature of the tumor, and has a poor prognostic effect on gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.781-784
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• 2012

The aim of this study was to evaluate the effect of the adenovirus-mediated double suicide gene (CD/TK) for selective killing of gastric cancer cells. Gastric cancer cells SCG7901 and normal gastric epithelial cell lines were infected by adenoviruses Ad-survivin/GFP and Ad-survivin/CD/TK. GFP expression and CD-TK were detected by fluorescence microscopy and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. After treatment of the infected cells with the pro-drugs ganciclovir (GCV) and/or 5-FC, the cell growth status was evaluated by methyl thiazolyl tetrazolium assay. Cell cycle changes were detected using flow cytometry. In nude mice bearing human gastric cancer, the recombinant adenovirus vector was injected directly into the tumor followed by an intraperitoneal injection of GCV and/or 5-FC. The subsequent tumor growth was then observed. The GFP gene driven by survivin could be expressed within the gastric cancer line SCG7901, but not in normal gastric epithelial cells. RT-PCR demonstrated the presence of the CD/TK gene product in the infected SCG7901 cells, but not in the infected normal gastric epithelial cells. The infected gastric cancer SCG7901, but not the gastric cells, was highly sensitive to the pro-drugs. The CD/TK fusion gene system showed significantly greater efficiency than either of the single suicide genes in killing the target cells (P<0.01). Treatment of the infected cells with the pro-drugs resulted in increased cell percentage in G0-Gl phase and decreased percentage in S phase. In nude mice bearing SCG7901 cells, treatment with the double suicide gene system significantly inhibited tumor growth, showing much stronger effects than either of the single suicide genes (P<0.01). The adenovirus-mediated CD/TK double suicide gene driven by survivin promoter combined with GCV an 5-FC treatment could be an effective therapy against experimental gastric cancer with much greater efficacy than the single suicide gene CD/TK combined with GCV or 5-FC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4607-4610
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• 2013

The aim of this study was evaluated the prevalence of Treg cells in peripheral blood in patients with gastric cancer, and investigate the effect of gastric cancer cells on their differentiation. ELISA was employed to assess the concentrations of TGF-${\beta}$ and IL-10 in gastric cancer patients' serum. Then, mouse gastric cancer cells were co-cultured with T lymphocytes or T lymphocytes + anti-TGF-${\beta}$. Flow cytometric analysis and RT-PCR were then performed to detect Treg cells and TGF-${\beta}$ and IL-10 expression in gastric cancer cells. Our data showed that the expression of TGF-${\beta}$ and IL-10 in the patients with gastric cancer was increased compared to the case with healthy donors. The population of Treg cells and the expression levels of TGF-${\beta}$ and IL-10 in the co-culture group were much higher than in the control group (18.6% vs 9.5%) (P<0.05). Moreover, the population of Treg cells and the expression levels of TGF-${\beta}$ and IL-10 in the co-culture systerm were clearly decreased after addition of anti-TGF-${\beta}$ (7.7% vs 19.6%) (P<0.01). In conclusion, gastric cancer cells may induce Treg cell differentiation through TGF-${\beta}$, and further promote immunosuppression.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2263-2267
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• 2012

Objective: MicroRNAs (miRNAs) play important roles in carcinogenesis. The aim of the present study was to explore the effects of miR-181b on gastric cancer. Methods: The expression level of miR-181b was quantified by qRT-PCR. MTT, flow cytometry and matrigel invasion assays were used to test proliferation, apoptosis and invasion of miR-181b stable transfected gastric cancer cells. Results: miR-181b was aberrantly overexpressed in gastric cancer cells and primary gastric cancer tissues. Further experiments demonstrated inducible expression of miR-181b by Helicobacter pylori treatment. Cell proliferation, migration and invasion in the gastric cancer cells were significantly increased after miR-181b transfection and apoptotic cells were also increased. Furthermore, overexpression of miR-181b downregulated the protein level of tissue inhibitor of metalloproteinase 3 (TIMP3). Conclusion: The upregulation of miR-181b may play an important role in the progress of gastric cancer and miR-181b maybe a potential molecular target for anticancer therapeutics of gastric cancer.

• Journal of Microbiology and Biotechnology
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• 제13권3호
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• pp.394-399
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• 2003

The in vitro cytotoxic effects of newly synthesized copper (II) glycinate complex were investigated in two gastric cancer cell lines of SNU484 and SNU638 cells. The complex inhibited the growth and decreased the viability of both gastric cancer cells in a dose-dependent manner. Gastric cancer tells treated with the complex exhibited the features of apoptosis, as demonstrated by fragmentation of chromosomal DNA, activation of caspase-3-like enzyme, and cleavage of poly［ADP-ribose］ polymerase (PARP). With the treatment of copper (II) glycinate complex, the active form of caspase-3 was observed in SNU484 cells, but not in SNU638 cells, indicating that an alternative pathway of apoptosis might have been triggered in SNU638 cells. In conclusion, copper (II) glycinate complex induces apoptosis of SNU484 and SNU638 gastric cancer cells, and it is suggested that novel copper (II) glycinate complex is highly active against human gastric cancer cells.

• Journal of Digestive Cancer Research
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• 제6권1호
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• pp.6-10
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• 2018

The importance of signal transducer and activator of transcription 3 (STAT3) signaling in gastric carcinogenesis was firmly evaluated in the previous studies. Fully activated STAT3 induces various target genes involving tumor invasion and epithelial-mesenchymal transition (EMT), and mediates interaction between cancer cells and microenvironmental immune cells. Thus, suppression of STAT3 activity is an important issue for inhibition of gastric carcinogenesis and invasion. Unfortunately, data from clinical studies of direct inhibitor targeting STAT3 have been disappointing. SH2-containing protein tyrosine phosphatase 1 (SHP-1) effectively dephosphorylates and inhibits STAT3 activity, which has not been extensively studied gastric cancer research field. However, by summarizing recent data, it is evident that protein and gene expression of SHP-1 are minimal in gastric cancer cells, and induction of SHP-1 effectively downregulates phosphorylated STAT3 and inhibits cellular invasion in gastric cancer cells. Several SHP-1 inducers have been investigated in the experimental studies, including proton pump inhibitor, arsenic trioxide, and other natural compounds. Taken together, we suggest that modulation of SHP-1/STAT3 signaling axis may present a new way for treatment of gastric cancer, and development of effective SHP-1 inducer may be an important task in the future search field of gastric cancer.

• Journal of Gastric Cancer
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• 제18권4호
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• pp.356-367
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• 2018

Purpose: Kallikrein (KLK) proteases are hormone-like signaling molecules with critical functions in different cancers. This study investigated the expression of KLK6 in gastric cancer and its potential role in the growth, migration, and invasion of gastric cancer cells. Materials and Methods: In this study, we compared protein levels of KLK6, vascular endothelial growth factor (VEGF), and matrix metallopeptidase (MMP) 9 in normal gastric epithelial and gastric cancer cell lines by western blot. Fluorescence-activated cell sorting was employed to sort 2 clones of SGC-7901 cells with distinct KLK6 expression, namely, KLK6-high ($KLK6^{high}$) and KLK6-low ($KLK6^{low}$), which were then expanded. Lastly, immunohistochemical analysis was performed to investigate KLK6 expression in gastric cancer patients. Results: The expression levels of KLK6, VEGF, and MMP 9, were significantly higher in the gastric cancer cell lines SGC-7901, BGC-823, MKN-28, and MGC-803 than in the normal gastric epithelial cell line GES-1. Compared to $KLK6^{low}$ cells, $KLK6^{high}$ cells showed enhanced viability, colony-forming ability, migration, and invasion potential in vitro. Importantly, immunohistochemical analysis of a human gastric cancer tissue cohort revealed that the staining for KLK6, VEGF, and MMP9 was markedly stronger in the cancerous tissues than in the adjacent normal tissues. KLK6 expression also correlated with that of VEGF and MMP9 expression, as well as several key clinicopathological parameters. Conclusions: Together, these results suggest an important role for KLK6 in human gastric cancer progression.

• Molecules and Cells
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• 제41권6호
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• pp.591-602
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• 2018

Gastric cancer is the fifth most common type of malignancy worldwide, and the survival rate of patients with advanced-stage gastric cancer is low, even after receiving chemotherapy. Here, we validated neurotensin receptor 1 (NTSR1) as a potential therapeutic target in gastric cancer. We compared NTSR1 expression levels in sixty different gastric cancer-tissue samples and cells, as well as in other cancer cells (lung, breast, pancreatic, and colon), by assessing NTSR1 expression via semi-quantitative real-time reverse transcription polymerase chain reaction, immunocytochemistry and western blot. Following neurotensin (NT) treatment, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) and further determined the effects on cell migration and invasion via wound-healing and transwell assays. Our results revealed that NTSR1 mRNA levels were higher in gastric cancer tissues than non-cancerous tissues. Both of NTSR1 mRNA levels and expression were higher in gastric cancer cell lines relative to levels observed in other cancer-cell lines. Moreover, NT treatment induced MMP-9 expression and activity in all cancer cell lines, which was significantly decreased following treatment with the NTSR1 antagonist SR48692 or small-interfering RNA targeting NTSR1. Furthermore, NT-mediated metastases was confirmed by observing epithelial-mesenchymal transition markers SNAIL and E-cadherin in gastric cancer cells. NT-mediated invasion and migration of gastric cancer cells were reduced by NTSR1 depletion through the Erk signaling. These findings strongly suggested that NTR1 constitutes a potential therapeutic target for the inhibition of gastric cancer invasion and metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2839-2843
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• 2013

Objective: To investigate the effects of miR-106b on malignant characteristics of gastric cancer cells, and explore possible mechanisms. Methods: Expression of miR-106b, p21 and E2F was determined by real-time PCR. Transfection with miR-106b mimics was conducted, and gastric cancer cells with miR-106b overexpression were obtained. Cells transfected with mimic mutants and those without transfection served as negative and blank controls, respectively. Flow cytometry and transwell assays were adopted to detect the effects of miR-106b overexpression on cell cycle, migration and invasion of gastric cancer cells. Results:. The expression of miR- 106b in gastric cancer cells was significantly higher than that in normal gastric mucosa cells. Furthermore, the expression level of miR-106b rose according to the degree of malignacy among the three GC cell strains (MKN- 45 > SGC-7901 > MKN-28). Overexpression of miR-106b shortened the G0/G1 phase and accelerated cell cycle progression, while reducing p21 and E2F5, without any significant effects on the capacity for migration and invasion of gastric cancer cells. Conclusions: miR-106b may promote cell cycling of gastric cancer cells through regulation of p21 and E2F5 target gene expression.