• 동의신경정신과학회지
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• 제18권1호
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• pp.95-110
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• 2007

Objective : The purpose of this study was to investigate molecular basis of neuroprotective effect in total ginsenosides. After H202 induced neurotoxicity, gene expression profiling of SH-SY5Y neuroblastoma cells treated by total ginsenosides is analyzed. Method : After SH-SY5Y cells were cultured, they were damaged by H202 induced oxidative stress. After twenty four hours, experimental group is treated by total ginsenosides and control group is treated by 0.9% saline. A high density cDNA microarray chip is used to analyze the gene expression profiling of SH-SY5Y cells. The Significance Analysis of Microarray method is used for identifying genes on a microarray. Results : 1. According to the results of microarray experiment, 17 genes were up-regulated, 38 genes were down-regulated. 2. Expression of OPHNl, KTANl, ATM, PRKCE, MAPKs genes associated with cell proliferation, neural growth, and the prevention of apoptosis were increased. 3. Change of EPX gene was the greatest among all genes. EPX gene associated with oxidative stress, and tumor suppressor gene ADAM11 were decreased. Conclusion : According to this study, molecular basis of neuroprotective effect of total ginsenosides is as followings: the increase of gene expression associated with cell proliferation, neuron growth, the prevention of apoptotsis and decrease of gene expression associated with oxidative stress and tumor suppressor.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.196-196
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• 2002

p16INK4a tumor suppressor gene transfer in the non-small cell lung cancer cells by transduction of recombinant adenovirus (Ad5CMV-p16) resulted in significant inhibition of cancer cell growth (Anticancer Res., 1998, 18:3257-3261). As a safety concern, we have investigated gene and protein expression after transduction of adenoviral vector (Ad5CMV-p16) in human non-small cell lung cancer (A549) cells by using microarray and 2D gel electrophoresis/ MALDI-TOF.(omitted)

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.205-209
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• 2012

Background: The inhibition of tumor cell growth without toxicity to normal cells is an important target in cancer therapy. One possible way to increase the efficacy of anticancer drugs and to decrease toxicity or side effects is to develop traditional natural products, especially from medicinal plants. Paris polyphylla Smith has shown anti-tumour effects by inhibition of tumor promotion and inducement of tumor cell apoptosis, but mechanisms are still not well understood. The present study was to explore the effect of Paris polyphylla Smith extract (PPSE) on connexin26 and growth control in human esophageal cancer ECA109 cells. Methods: The effects of PPSE on Connexin26 were examined by RT-PCR, western blot and immunofluorescence; cell growth and proliferation were examined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Results: PPSE inhibited the growth and proliferation on esophageal cancer ECA109 cells, while increasing the expression of connexin26 mRNA and protein; conversely, PPSE decreased Bcl-2 and increased Bad. Conclusion: This study firstly shows that PPSE can increase connexin26 expression at mRNA and protein level, exerting anti-tumour effects on esophageal cacner ECA109 cells via inhibiting cell proliferation and inducing cell apoptosis.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권2호
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• pp.103-109
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• 2005

In spite of the ongoing advances, standard therapies for oral cancer still has some limitations in efficacy and in ability to prolong survival rate of advanced disease and result in significant functional defect and severe cosmetic deformity. Currently gene therapy using tumor suppressor gene is considered as a potent candidate for new therapeutic approaches that can improve efficacy and reduce complications. The purpose of this research is to identify the role of adenoviral vector to transfer HCCS-1 tumor suppressor gene in oral cancer cells and to find out whether there is a possibility for it to serve in the field of gene therapy. The human SCC-25 cell line was used for transfection. To determine the efficiency of the adenovirus as a gene delivery vector cell line was transduced with LacZ gene and analysed with X-gal staining. Northern blot was performed to confirm the tranfection with HSCC-1 gene and cell viability was assessed by cell cytotoxicity assay. We had successfully construct the recombinant HSCC-1 adenovirus(Ad5CMV-HCCS-1). DNA extracted from Ad5CMV-HCCS-1 revealed HCCS-1 gene is incorporated. The transduction efficiencies were over than 50% of SCC-25 cells with a MOI of 2 and over 95% with a MOI of 50. Northern blot analysis showed that a single 0.6kb mRNA transcript was expressed in Ad5CMV-HCCS-1 transduced SCC-25 cells. There was no or very low transcription HCCS-1 mRNA in wild and Ad5CMV-LacZ transduced SCC-25 cells. Cells transduced with Ad5CMV-HCCS-1 showed significant growth inhibition. By day 6, Ad5CMV-HCCS-1 treated cell count was decreased to 30% of mock-infected cells, while that of Ad5CMV-LacZ treated cells was 90% of mock-infected cells (p<0.05). Finally, these result suggest that the Ad5CMV-HCCS-1 has potential as a gene therapy tool for oral cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6543-6546
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• 2014

MicroRNAs (miRNAs) act as critical regulators of genes involved in many biological processes. Aberrant alteration of miRNAs have been found in many cancers, including gastric cancer (GC), but the molecular mechanisms are not well understood. Herein, we investigated the role of miR-124 in GC. We found that its expression was significantly reduced in both GC tissue samples and cell lines. Forced expression of miR-124 suppressed GC cell proliferation, migration, and invasion. Furthermore, the Rho-associated protein kinase (ROCK1) was identified as a direct target of miR-124 in GC cells. Finally, silencing of ROCK1 showed similar effects as miR-124 overexpression, while supplementation of ROCK1 remarkably restored the cell growth and invasion inhibited by miR-124. Together, our data demonstrate that miR-124 acts as a tumor suppressor by targeting ROCK1, and posit miR-124 as a novel strategy for GC treatment.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.210-215
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• 2019

Colorectal cancer is one of the leading causes of cancer related death due to a poor prognosis. In this study, we investigated the effect of Gomisin G on colon cancer growth and examined the underlying mechanism of action. We found that Gomisin G significantly suppressed the viability and colony formation of LoVo cells. Gomisin G reduced the phosphorylation level of AKT implying that Gomisin G suppressed the PI3K-AKT signaling pathway. Gomisin G also induced apoptosis shown by Annexin V staining and an increased level of cleaved poly-ADP ribose polymerase (PARP) and Caspase-3 proteins. Furthermore, Gomisin G remarkably triggered the accumulation of cells at the sub-G1 phase which represents apoptotic cells. In addition, the level of cyclin D1 and phosphorylated retinoblastoma tumor suppressor protein (Rb) was also reduced by the treatment with Gomisin G thus curtailing cell cycle progression. These findings show the suppressive effect of Gomisin G by inhibiting proliferation and inducing apoptosis in LoVo cells. Taken together, these results suggest Gomisin G could be developed as a potential therapeutic compound against colon cancer.

• IMMUNE NETWORK
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• 제9권4호
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• pp.122-126
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• 2009

Transforming growth factor-$\beta$ (TGF-$\beta$) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-$\beta$ facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-$\beta$ antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-$\beta$ antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic $CD8^+$ Tcells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-$\beta$ on T cells, which are differentiated into effector T cells or newly identified tumor-supporting T cells.

• 한국환경성돌연변이발암원학회지
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• 제24권1호
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• pp.1-9
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• 2004

Three D-type cyelins (D1, D2, and D3) are expressed in G1 phase of the cell cyele and have been implicated in cell transformation and neoplasia in human and mouse. Cyclin D1 overexpression or amplification was described in various human cancers. However, there is controversy about the role of cyclin D2 in cell cyele progression and human carcinogenesis. Specially, loss of cyelin D2 is involved in a vital tumor suppressor function in normal breast tissue, and that its loss may be related to tumorigenesis. The author examined to effect over-expression of cyclin D2 on the cell proliferation, apoptosis, and cell cycle using cyclin D2 transfected stable T47D breast cancer cells to investigate whether cyclinD2 functions as a positive regulator or negative regulator in cell proliferation. Overexpression of cyclin D2 led to the suppression of cell growth in cyclin D2 transfected T47D in both in its expression level and a time dependent manner with up to 50% reduction of cell growth at 72 hours. Therefore, the authors performed the cell cycle phase analysis using the flow cytometry to investigate the effect of cyclin D2 on the cell cycle phase in cyclin D2 transfected stable T47D cells. The flow cytometry analysis revealed increased sub G0 phase in cyclin D2 transfeted cells up to 23% at 72 hours. To confirm these results induced by overexpression of cyclinD2, the apoptotic bodies were counted in control and cyclin D2 transfected T47 cells. There are markedly increases of apoptotic bodies in cyclin D2-transfected cells up to 18%. These results suggested that Cyclin D2 suppresses the cell proliferation in breast cancers cells via the induction of apotosis.

• Biomolecules & Therapeutics
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• 제30권4호
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• pp.380-388
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• 2022

Snail is implicated in tumour growth and metastasis and is up-regulated in various human tumours. Although the role of Snails in epithelial-mesenchymal transition, which is particularly important in cancer metastasis, is well known, how they regulate tumour growth is poorly described. In this study, the possible molecular mechanisms of Snail in tumour growth were explored. Baculoviral inhibitor of apoptosis protein (IAP) repeat-containing protein 3 (BIRC3), a co-activator of cell proliferation during tumourigenesis, was identified as a Snail-binding protein via a yeast two-hybrid system. Since BIRC3 is important for cell survival, the effect of BIRC3 binding partner Snail on cell survival was investigated in ovarian cancer cell lines. Results revealed that Bax expression was activated, while the expression levels of anti-apoptotic proteins were markedly decreased by small interfering RNA (siRNA) specific for Snail (siSnail). siSnail, the binding partner of siBIRC3, activated the tumour suppressor function of p53 by promoting p53 protein stability. Conversely, BIRC3 could interact with Snail, for this reason, the possibility of BIRC3 involvement in EMT was investigated. BIRC3 overexpression resulted in a decreased expression of the epithelial marker and an increased expression of the mesenchymal markers. siSnail or siBIRC3 reduced the mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. These results provide evidence that Snail promotes cell proliferation by interacting with BIRC3 and that BIRC3 might be involved in EMT via binding to Snail in ovarian cancer cells. Therefore, our results suggested the novel relevance of BIRC3, the binding partner of Snail, in ovarian cancer development.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.769-773
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• 2015

Fibulin-5 has recently been considered as a potential tumor suppressor in human cancers. Several studies have shown that it is down-regulated in a variety of tumor types and inhibits tumor growth and metastasis. This study was aimed to investigate the clinical significance of fibulin-5 in glioma and its role in cell proliferation and invasion. We found that the expression of fibulin-5 in glioma tissues was significantly lower than those in normal brain (NB) tissues. Negative expression was significantly correlated with advanced clinical stage (grade III+IV). Furthermore, Fibulin-5 negative expression was correlated with a shorter overall survival of glioma patients. Multivariate Cox repression analysis indicated that fibulin-5 was an independent factor for predicting overall survival of glioma patients. Overexpression obviously inhibited cell proliferation in U251 and U87 cells. Furthermore, it significantly reduced the number of migrating and invading glioma cells. In conclusion, impaired expression of fibulin-5 is correlated with the advanced tumor stage in glioma. Otherwise, Fibulin-5 is an independent prognostic marker for predicting overall survival of glioma patients. Mechanistically, it may function as a tumor suppressor via inhibiting cell proliferation and invasion in gliomas.