• Journal of Gastric Cancer
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• v.20 no.1
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• pp.95-105
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• 2020

Purpose: Gastric cancer is a highly metastatic malignant tumor, often characterized by chemoresistance and high mortality. In the present study, we aimed to investigate the role of B-cell lymphoma 3 (Bcl-3) protein on cell migration and chemosensitivity of gastric cancer. Materials and Methods: The gastric cancer cell lines, AGS and NCI-N87, were used for the in vitro studies and the in vivo studies were performed using BALB/c nude mice. Western blotting, wound healing assay, Cell Counting Kit-8 assay, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to evaluate the role of Bcl-3 in gastric cancer. Results: We found that the protein expression of hypoxia (HYP)-inducible factor-1α and Bcl-3 were markedly upregulated under hypoxic conditions in both AGS and NCI-N87 cells in a time-dependent manner. Interestingly, small interfering RNA-mediated knockdown of Bcl-3 expression affected the migration and chemosensitivity of the gastric cancer cells. AGS and NCI-N87 cells transfected with si-RNA-Bcl-3 (si-Bcl-3) showed significantly reduced migratory ability and increased chemosensitivity to oxaliplatin, 5-fluorouracil, and irinotecan. In addition, si-Bcl-3 restored the autophagy induced by HYP. Further, the protective role of si-Bcl-3 on the gastric cancer cells could be reversed by the autophagy inducer, rapamycin. Importantly, the in vivo xenograft tumor experiments showed similar results. Conclusions: Our present study reveals that Bcl-3 knockdown inhibits cell migration and chemoresistance of gastric cancer cells through restoring HYP-induced autophagy.

• The Korean Journal of Cytopathology
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• v.17 no.1
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• pp.51-55
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• 2006

The plasmacytoid variant is an extremely rare form of urothelial carcinoma in which the malignant cells resemble those of plasmacytoma. We report the cytologic features of 3 cases of this disorder. All 3 patients were male and presented with painless macroscopic hematuria. The voided urine cytology revealed a few scattered clusters of tumor cells in a bloody background. Each tumor cell had an abundant amount of cytoplasm that was clear or densely stained and characterized by eccentrically located nuclei. A histological examination of tissue obtained from a radical cystectomy confirmed the cytologic diagnosis in each 3 case, revealing a diffusely infiltrating tumor composed of round, noncohesive tumor cells demonstrating a high nuclear grade. These cells had infiltrated the tunica propria in 2 cases, but were limited to the submucosa in 1 case. The tumor cells were plasmacytoid in appearance, each demonstrating an eccentric nucleus and dense cytoplasm, as seen in the cytologic findings. All of the tumors were immunoreactive for pancytokeratin, CK7, CK20; negative for epithelial membrane antigen (EMA), leukocyte common antigen (LCA), kappa, lambda, and CD79a. Thus, it is important to consider the plasmacytoid variant of urothelial carcinoma in addition to plasmacytoma or lymphoma as a diagnosis when encountering plasmacytoid tumor cells in a voided urine sample.

• Journal of Pharmacopuncture
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• v.18 no.1
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• pp.19-26
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• 2015

Objectives: Quercetin, a flavonoid compound, has been reported to induce apoptosis in cancer cells, but its anti-inflammatory effects, which are also closely linked with apoptosis, if any, on non-small-cell lung cancer (NSCLC) have not so far been critically examined. In this study, we tried to determine if quercetin had any demonstrable anti-inflammatory potential, which also could significantly contribute to inducing apoptosis in a NSCLC cell line, A549. Methods: In this context, several assays, including cytotoxicity, flow cytometry and fluorimetry, were done. Gene expression was analyzed by using a western blot analysis. Results: Results revealed that quercetin could induce apoptosis in A549 cells through mitochondrial depolarization by causing an imbalance in B-cell lymphoma 2/Bcl2 Antagonist X (Bcl2/Bax) ratio and by down-regulating the interleukine-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway. An analysis of the data revealed that quercetin could block nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) activity at early hours, which might cause a down-regulation of the IL-6 titer, and the IL-6 expression, in turn, could inhibit p-STAT3 expression. Down-regulation of both the STAT3 and the NF-${\kappa}B$ expressions might, therefore, cause down-regulation of Bcl2 activity because both are major upstream effectors of Bcl2. Alteration in Bcl2 responses might result in an imbalance in the Bcl2/Bax ratio, which could ultimately bring about mitochondria mediated apoptosis in A549 cells. Conclusion: Overall, the finding of this study indicates that a quercetin induced anti-inflammatory pathway in A549 cells appeared to make a significant contribution towards induction of apoptosis in NSCLC and, thus, may have a therapeutic use such as a strong apoptosis inducer in cancer cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.2
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• pp.189-194
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• 2011

Nardostachys chinensis (N. Chinensis) belonging to the family Valerianaceae have been used in traditional medicine to elicit stomachic and sedative effects. The present study investigated the effects of water extract of N. Chinensis in human lymphoma U937 cells. The proliferation of U937 cells was decreased by N. Chinensis. Anti-proliferative effect of N. Chinensis on U937 cells was associated with G0/G1 phase arrest, which was mediated by regulating the expression of p21 and p27 protein. In addition, the levels of CDK2, CDK4, CDK6, Cyclin D3, and Cyclin A were decreased, but Cyclin D1, Cyclin D2 and Cyclin E were essentially undetectable. N. Chinensis induced the differentiation of U937 as shown by increased expression of differentiation surface antigen CD11b, but not CD14. Taken together, these results demonstrated that N. Chinensis potently inhibits the proliferation of U937 cells via the G0/G1 phase cell cycle arrest in association with p21 and p27, and induces granulocytic differentiation.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.6
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• pp.95-103
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• 2019

Periodontal inflammation, a major kind of periodontal diseases, is characterized to bleed, pain, and teeth loss, and it is resulted from oxidative stress. Membrane-free stem cell extract could avoid the immunogencity rejection by removal of cell membrane. In the present study, we investigated the protective effect of membrane-free stem cell extract from oxidative stress-induced periodontal inflammation in human periodontal ligament fibroblasts (HPLF). In the cell viability measurement, membrane-free stem cell extract showed significant increase of cell viability, compared with the $H_2O_2$-treated control group. To further investigation of molecular mechanisms, we measured inflammation and apoptosis related protein expressions. Membrane-free stem cell extract attenuated inflammation-related protein expressions such as nuclear factor kappa light chain enhancer of activated B cells, inducible nitric oxide synthase, and interleukin-6. In addition, the treatment of membrane-free stem cell extract decreased apoptotic protein expressions such as cleaved caspase-9, -3, poly (ADP-ribose) polymerase, and B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 ratio in the $H_2O_2$-treated HPLF cells. In conclusion, membrane-free stem cell extract exhibited anti-oxidative stress effects by regulation of inflammation and apoptosis in HPLF, suggesting that it could be used as the treatment agents for periodontal inflammatory disease.

• The Korean Journal of Cytopathology
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• v.9 no.1
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• pp.21-28
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• 1998

Cytologic evaluation of cerebrospinal fluid(CSF) is an effective tool in diagnosing many disorders involving the central nervous system(CNS). CSF examination has been found to be of particular value in the diagnosis of metastatic carcinoma, lymphomatous or leukemic involvement of CNS and certain primary CNS tumors. As a survey of metastatic tumors to CSF and an evaluation of the preparation techniques increasing cellular yield in our laboratory, 713 CSF specimens examined between July 1995 and April 1997(1 year 10 months), were reviewed. There were 75 positive and 5 suspicious cases, the latter have had no evidence of tumors clinically. Primary tumors of 75 positive cases were classified as follows; 4(5.3%) as primary brain tumors, 40(53.3%) as secondary carcinomas, 13(17.3%) as leukemias, and 18 (24.0%) as lymphomas. The most common primary site of metastatic carcinomas was the lung in 17 cases(42.5%) followed by the stomach in 13(32.5%), breast in 8 (20.0%), and unknown primary in 2(5.0%). Four primary brain tumors were 3 cerebellar medulloblastomas and a supratentorial primitive neuroectodermal tumor (PNET). All 40 metastatic carcinomas were adenocarcinoma presented as single cells or cell clusters. Although signet ring cells were frequent in the cases of gastric primary cancers, no significant cytologic differences according to the primary site were observed. The cytologic features of leukemia and lymphoma were characterized by hypercellular smears presenting as individual atypical cells with increased N/C ratio, presence of nucleoli, and nuclear protrusions. In medulloblastomas and PNET, the principal cytologic findings were small undifferentiated cells arranged singly or in loose clusters with occasional rosettoid features. This study suggests that the CSF cytology is useful in the diagnosis of malignancy, especially metastatic extracranial tumors and the diagnostic accuracy can be improved by increasing cellular yield using cytocentrifuge.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.4
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• pp.10-19
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• 2010

Methods: Intravenous administration of Platycodon grandiflorum was performed 2 days before tumor inoculation, then mice were killed 14 days after tumor inoculation, then number of tumor colonies were counted. Methanol extracts of Platycodon grandiflorum was added to colon26-M3.1 carcinoma cells, L5178Y-R lymphoma cells and Hela cells, and then cell growth was counted. To observe the immunomodulating effects of Platycodon grandiflorum, production of IL-6, IL-10, IL-12 and TNF-$\alpha$ were measured with ELISA assay and the cell growth of macrophage were also counted. Furthermore, antimetastatic experiment after depletion NK cells by injection of anti-asialo GM1 serum was also administered. Results: Intravenous administration of Platycodon grandiflorum significantly inhibited metastasis of colon26-M3.1 carcinoma cells. In an in vitro cytotoxicity analysis, Platycodon grandiflorum affected tumor cell growth above specific concentration. As compared with control, the production of IL-6, IL-10, IL-12 and TNF-$\alpha$ were incresed. And depletion NK cell completly abolished the inhibitory effect of metastasis. Conclusion: Platycodon grandiflorum appears to have considerable activity on immunomodulating effects and inhibit the metastasis of tumor. Further evaluation is needed for settling this.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.490-496
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• 2017

Imatinib resistance has become a major clinical problem for chronic myeloid leukemia. The aim of the present study was to investigate the involvement of MEG3, a lncRNA, in imatinib resistance and demonstrate its underlying mechanisms. RNAs were extracted from CML patients' peripheral blood cells and human leukemic K562 cells, and the expression of MEG3 was measured by RT-qPCR. Cell proliferation and cell apoptosis were evaluated. Western blotting was used to measure the protein expression of several multidrug resistant transporters. Luciferase reporter assay was performed to determine the binding between MEG3 and miR-21. Our results showed that MEG3 was significantly decreased in imatinib-resistant CML patients and imatinib-resistant K562 cells. Overexpression of MEG3 in imatinib-resistant K562 cells markedly decreased cell proliferation, increased cell apoptosis, reversed imatinib resistance, and reduced the expression of MRP1, MDR1, and ABCG2. Interestingly, MEG3 binds to miR-21. MEG3 and miR-21 were negatively correlated in CML patients. In addition, miR-21 mimics reversed the phenotype of MEG3-overexpression in imatinib-resistant K562 cells. Taken together, MEG3 is involved in imatinib resistance in CML and possibly contributes to imatinib resistance through regulating miR-21, and subsequent cell proliferation, apoptosis and expression of multidrug resistant transporters.

• Journal of Korean Neurosurgical Society
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• v.49 no.1
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• pp.13-19
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• 2011

Objective: The purpose of this study is to investigate the combined effects of ginkgo biloba extract, ginkgolide A and B and aspirin on SK-N-MC, human neuroblastoma cell viability and mRNA expression of growth associated protein43 (GAP43), Microtubule-associated protein 2 (MAP2), B-cell lymphoma2 (Bcl2) and protein53 (p53) gene in hypoxia and reperfusion condition. Methods: SK-N-MC cells were cultured with Dulbecco's Modified Eagle's Medium (DMEM) media in $37^{\circ}C$, 5% $CO_2$ incubator. The cells were cultured for 8 hours in non-glucose media and hypoxic condition and for 12 hours in normal media and $O_2$ concentration. Cell survival rate was measured with Cell Counting Kit-8 (CCK-8) reagent assay. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to estimate mRNA levels of GAP43, MAP2, Bcl2, and p53 genes. Results: The ginkgolide A and B increased viable cell number decreased in hypoxic and reperfused condition. The co-treatment of ginkgolide B with aspirin also increased the number of viable cells, however, there was no additive effect. Although there was no increase of mRNA expression of GAP43, MAP2, and Bcl2 in SK-N-MC cells with individual treatment of ginkgolide A, B or aspirin in hypoxic and reperfused condition, the co-treatment of ginkgolide A or B with aspirin significantly increased GAP43 and Bcl2 mRNA levels. In MAP2, only the co-treatment of ginkgolide A and aspirin showed increasing effect. The mRNA expression of p53 had no change in all treating conditions. Conclusion: This study suggests that the combined treatments of Ginkgo biloba extracts and aspirin increase the regeneration of neuroblastoma cells injured by hypoxia and reperfusion.

• The Korea Journal of Herbology
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• v.36 no.1
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• pp.41-49
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• 2021

Objective : Citrus unshiu peel (Citri Unshius Pericarpium) has been prescribed to suppress coughing and phlegm in Korean medicine. In this study, the effect of ethanol extract of Citrus unshiu peel (CEE) on apoptosis was investigated using cadmium chloride (CdCl2) treated HepG2 cells. Methods : CEE was prepared by extracting 300 g of Citri Unshius Pericarpium in 3 L of ethanol for 72 h. Apoptosis was determined by the TUNEL assay. The mitochondrial membrane potential (MMP) was monitored using the membrane-permeable fluorescent dye Rh123. The expression level of each protein was monitored by Western blot analysis. Results : CEE protected HepG2 cells from apoptosis as determined by the TUNEL assay. A decrease in MMP was observed in cells exposed to cadmium, indicating that mitochondria are involved in the induction of apoptosis. However, CEE recovered the reduction in MMP caused by cadmium. In addition, decreased expression of B-cell lymphoma 2 (Bcl-2), procaspase, and poly(ADP-ribose) polymerase (PARP) by cadmium was increased by CEE. The anti-apoptotic effect of CEE was found to be associated with inhibition of JNK and p38 phosphorylation when examining the expression of phosphorylated MAPK by Western blot. Conclusion : This study showed that CEE exerted anti-apoptotic effects in cadmium-induced HepG2 cells by inhibiting the reduction of MMP and changes in the expression level of apoptotic proteins. These results suggest the potential for CEE to be used for heavy metal-induced liver damage.