• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.273-280
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• 2005

Purpose: Cyclin G2 has been reported to be a negative cell-cycle regulator in various cancer tissues. However, the pattern of cyclin G2 expression in gastric cancer is relatively unknown. We investigated the expression of cyclin G2 in gastric cancer tissues and evaluated the clinical significance of its expression. Materials and Methods: Well-preserved gastric cancer tissues were consecutively obtained from 172 patients who underwent gastric cancer operations at Samsung Medical Center between November 1994 and December 1997. Cyclin G2 expression in the tissues was examined immunohistochemically, and the clinicopathological features and prognostic significance according to the expression were analyzed. Results: Of the 172 gastric cancer tissues, cyclin G2 expression was positive in 43 tissues (25.0%). According to the stage, cyclin G2 expression was lower in more advanced stages (P<0.001). Negative expression of cyclin G2 was positively correlated with more advanced depth of tumor invasion (P<0.05), presence of lymph-node metastasis (P<0.05) and presence of lymphatic invasion (P<0.05). The prognosis of the cyclin G2(+) group was significantly better than that of the cyclin G2(-) group (P<0.001). Multivariate analysis revealed that T stage, lymph-node metastasis, distant metastasis, and lymphatic invasion were independent prognostic factors, but the expression of cyclin G2 was not. Conclusion: Cyclin G2 was expressed in 25% of the gastric cancer tissues, and negative expression of cyclin G2 was associated with more advanced tumor progression. Cyclin G2 may be a negative cell-cycle regulator in gastric cancer, and further studies are necessary to elucidate its exact role in the mechanism of carcinogenesis.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.473-479
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• 2005

Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.3
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• pp.418-427
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• 2003

Conjugated linoleic acid (CLA) is the mixture of positional and geometric isomers of linoleic acid (LA, C18:2 $\omega$6), which is found abundantly in dairy products and meats. This study was peformed to investigate the anticarcinogenic effect of CLA in MCF-7 breast cancer cells. MCF-7 cell were treated with LA and CLA at the various concentrations of 15, 30, 60, 120 UM each. After incubation for 48 and 72 hours, cell proliferation, fatty acids incorporation into cell, peroxidation and activities of antioxidant enzymes were measured. Postaglandin E$_2$ (PGE$_2$) and thromboxane $A_2$ (TXA$_2$) were measured for the eicosanoids metabolism. There was no cell growth differences in both of LA and CLA treated MCF-7 cells at 48 hr incubation. Compared to LA, cell growth was decreased by CLA treatment according to increasing concentration at longer incubation times, respectively (p<0.05). Both of LA and CLA was incorporated into the cellular lipids 22~54% higher than in control but LA incorporation was not so linear as CLA according to concentration. Arachidonic acid (C20:4, $\omega$6) was synthesized after treatment of LA but did not in CLA, respectively. The lipid peroxide concentration in LA 120 $\mu$M group increased as 1.7 times as that in CLA 120 $\mu$M treated. The activities of antioxidant enzymes such as glutathione peroxidase and glutathione reductase were increased by the supplementation with CLA 120 $\mu$M at 72 hr incubation (p<0.001) compared to LA, otherwise activity of superoxide dismutase was not different in both. PGE$_2$ and TXA$_2$ levels were lower in condition of CLA treatments according to lower levels of arachidonic acids than those in LA treated group, respectively. Overall, the dietary CLA might change the MCF-7 cell growth by the changes of cell composition, production of lipid peroxide, activities of antioxidant enzymes and eicosanoid synthesis compared to dietary LA.

• Journal of the Korean Applied Science and Technology
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• v.37 no.1
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• pp.102-113
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• 2020

In this study, anti-arthritic effect of the mixed extract of radiation mutant Perilla frutescens var. crispa and Atractylodes macrophala koidz was investigated. Cell viability was determined by MTT assay in RAW 264.7 cells. The anti-inflammatory effect of mixed extracts was determined through measurement of the levels of reactive oxygen species (ROS) and nitric oxide (NO), release of inflammatory cytokines and expression of NF-κB, COX-2 and iNOS in LPS-induced RAW 264.7 cells after treatment of mixed extracts (5, 10, 25 ㎍/㎖). We showed that the mixed extracts was not toxic in the dose of 5, 10, 25 ug/ml, and significantly inhibited production of nitric oxide and ROS, cytokines including IL-1β, IL-6, TNF-α, and inflammatory proteins including NF-κB, COX-2 and iNOS in LPS-induced RAW 264.7 cells. Moreover, the mixed extract inhibited the type II collagen induced arthritis in DBA mice in the dose of 66.5 and 133mg/kg/day. Therefore, we suggest that mixed extract of radiation mutant Perilla frutescens var. crispa and Atractylodes macrophala koidz can be developed as a raw material for health functional food and therapeutics to treat the inflammatory arthritis.

• Radiation Oncology Journal
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• v.18 no.1
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• pp.51-58
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• 2000

Purpose :The effect of PTK inhibitors (herbimycin A and genistein) on the induction of radiation-induced apoptosis in Ph-positive KS62 leukemia cell line was investigated. Materials and Methods :K562 cells in exponential growth phase were irradiated with a linear accelerator at room temperature. For 6 MV X-ray irradiation and drug treatment, cultures were initiated at 2×106 cells/mL. The cells were irradiated with 10 Gy. Stock solutions of herbimycin A and genistein were prepared in dimethyl sulphoxide (DMSO). After incubation at 37$^{\circ}C$ for 0$\~$48 h, the extent of apoptosis was determined using agarose gel electrophoresis and TUNEL assay. The progression of cells through the cell cycle after irradiation and drug treatment was also determined with flow cytometry. Western blot analysis was used to monitor bel-2, bel-X$_{L}$ and bax protein levels. Results :Treatment with 10 Gy X-irradiation did not result in the induction of apoptosis. The HMA alone (500 nM) also failed to induce apoptosis. By contrast, incubation of K562 cells with HMA after irradiation resulted in a substantial induction of nuclear condensation and fragmentation by agarose gel electro-phoresis and TUNEL assay. Genistein failed to enhance the ability of X-irradiation to induce DNA fragmentation. Enhancement of apoptosis by HMA was not attributable to downregulation of the bel-2 or bel-X$_{L}$ anti-apoptotic proteins. When the cells were irradiated and maintained with HMA, the percentage of cells in G2/M phase decreased to 30$\~$40$\%$ at 48 h. On the other hand, cells exposed to 10 Gy X-irradiation alone or maintained with genistein did not show marked cell cycle redistribution. Conclusion : We have shown that nanomolar concentrations of the PTK inhibitor HMA synergize with X-irradiation in inducing the apoptosis in Ph (+) K562 leukemia cell line. While, genistein, a PTK inhibitor which is not selective for p210$^{bcr/abl}$ failed to enhance the radiation induced apoptosis in KS62 cells. It is unlikely that the ability of HMA to enhance apoptosis in K562 cells is attributable to bel-2 family. It is plausible that the relationship between cell cycle delays and cell death is essential for drug development based on molecular targeting designed to modify radiation-induced apoptosis.

• Journal of Life Science
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• v.27 no.10
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• pp.1199-1206
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• 2017

The lymphotoxin ${\beta}$ receptor ($LT{\beta}R$), a member of the tumor necrosis factor receptor family, plays an important role in lymphoid tissue's architecture and organogenesis. We found that $LT{\beta}R$ stimulation induced changes in stress fibers (SFs) in fibroblastic reticular cells (FRCs). MLCK and ROCK play critical roles in the regulation of SF formation in cells. The present study was performed to investigate the antifibrotic effects on SF regulation of $LT{\beta}R$ signaling, with a focus on MLCK inhibition. The effect of $LT{\beta}R$ on the SF change was analyzed using immunoblot and fluorescence assays and agonistic $anti-LT{\beta}R$ antibody-treated FRCs. In addition, we checked the level of Rho-guanosine diphosphate (GDP)/guanosine triphosphate (GTP) exchange activity with FRC lysate. Phospho-ezrin proteins acting as membrane-cytoskeleton linkers completely de-phosphorylated in agonistic $anti-LT{\beta}R$ antibody-treated FRCs. The actin bundles rearranged into SFs, where phospho-myosin light chain (p-MLC) co-localized in FRCs. ML7-treated FRCs completely blocked SFs and showed retraction and shrinkage processes comparable to those observed in agonistic $anti-LT{\beta}R$ antibody-treated cells. Inhibition of ROCK activity induced changes in the actin cytoskeleton organization; however, some SFs remained in the cells, while they were completely disrupted by MLCK inhibition with ML7. We showed that the phosphorylation of MLC was completely abolished with $LT{\beta}R$ stimulation in FRCs. When $LT{\beta}R$ was stimulated with the agonistic $anti-LT{\beta}R$ antibody, the Rho-GDP/GTP exchange activity was reduced, however, the activity was not completely abolished. Collectively, the results illustrated that MLCK was potently responsible for the SF regulation triggered via $LT{\beta}R$ signaling in FRCs.

• Journal of Life Science
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• v.18 no.1
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• pp.120-128
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• 2008

The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/ Apo1L is a cytokine that activates apoptosis through cell surface death receptors. TRAIL has sparked growing interest in oncology due to its reported ability to selectively trigger cancer cell death. Euphorbiae humifusae Wind has been used in traditional Oriental medicine as a folk remedy used for the treatment of cancer. However, the mechanism responsible for the anticancer effects of E. humifusae not clearly understood. Here, we show that treatment with subtoxic doses of water extract of E. humifusae (WEEH) in combination with TRAIL induces apoptosis in TRAIL-resistant human gastric carcinoma AGS cells. Combined treatment with WEEH and TRAIL induced chromatin condensation and sub-G1 phase DNA content. These indicators of apoptosis were correlated with the induction of caspase activity that resulted in the cleavage of poly (ADP-ribose) polymerase. Combined treatment also triggered the loss of mitochondrial membrane potential. Furthermore, co-treatment with WEEH and TRAIL down-regulated the protein levels of the anti-apoptotic proteins such as Bcl-2, Bcl-xL, XIAP and cIAP-1. Although more study will be needed to examine the detailed mechanisms, this combined treatment may offer an attractive strategy for safely treating gastric adenocarcinomas and the results provide important new insights into the possible molecular mechanisms of the anticancer activity of E. humifusae.

• Journal of Life Science
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• v.23 no.3
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• pp.389-398
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• 2013

Platycodin D is a major constituent of triterpene saponins, which is found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. Several pharmacological effects of this compound have been reported recently, such as anti-inflammation, immunogenicity, anti-adipogenesis, lowered cholesterol, and anti-cancer activity. However, the mechanism by which this action occurs is poorly understood. In this study, we found that platycodin D greatly increased the potential of the anti-proliferative effect in various cancer cell lines. Our data revealed that platycodin D treatment resulted in a time- and concentration-response growth inhibition of U937 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, chromatin condensation, and the accumulation of cells in the sub-G1 phase. Apoptosis induction of U937 cells by platycodin D correlated with an increase in the Bax/Bcl-2 ratio and caused the down-regulation of IAP family members. In addition, platycodin D treatment resulted in proteolytic activation of caspase-3, the concomitant degradation of poly(ADP-ribose) polymerases, and the collapse of the mitochondria membrane potential (${\Delta}{\Psi}_m$). However, the cytotoxic effects induced by platycodin D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrated the important role that caspase-3 played in the observed cytotoxic effect. These findings suggest that platycodin D may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells. These findings also provided important new insights into possible molecular mechanisms of the anti-cancer activity of platycodin D.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.9
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• pp.1333-1339
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• 2011

After mulberry (Morus alba) leaves were fermented with Hericium erinaceum mycelium by solid-state culture to enhance physiological activity, fermented mulberry leaves (MA-HE) was extracted by hot-water (MA-HEHW) and ethanol (MA-HE-E). MA-HE-HW showed enhanced mitogenic and intestinal immune system modulating activities (1.41 and 1.52 fold of saline control, respectively) compared to hot-water extracts of non-fermented mulberry leaves (MA-HW) and H. erinaceum mycelium (HE-HW) at $100\;{\mu}g$/mL. Meanwhile, when we tested the inhibitory effects of extracts on nitric oxide (NO), tumor necrosis factor (TNF)-${\alpha}$, and interleukin (IL)-$1{\beta}$ and IL-6 production, MA-HE-E significantly inhibited these pro-inflammatory mediators in LPS-stimulated RAW 264.7 cells (45.1, 41.3, 70.2, and 55.7% inhibition of LPS control at $1,000\;{\mu}g$/mL). In addition, MA-HE-HW and MA-HE-E did not show any cytotoxicity on RAW 264.7 cells at $1,000\;{\mu}g$/mL whereas HE-E and MA-E indicated cytotoxicity (80.1 and 30.7% cell viability of saline control). These results suggest that mulberry leaves fermented with H. erinaceum by solid-state culture might have enhanced immunomodulatory and anti-inflammatory effects compared to non-fermented mulberry leaves, resulting in ingredients biotransformed for fermentation with H. erinaceum mycelium.

• Tuberculosis and Respiratory Diseases
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• v.55 no.4
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• pp.370-377
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• 2003

Background : Pneumocystis carinii pneumonia (PCP) is one of the most common cause of infection in patients with HIV infection. Recently, the incidence of PCP have been increasing in immunocompromised hosts without HIV infection. We compared the clinical characteristics of PCP between HIV infected and non-infected persons. Patients and Methods : We retrospectively reviewed the charts of 25 patients diagnosed as PCP from 1996 to 2002. Age, sex, underlying conditions, use of immunosuppressants, clinical courses, laboratory findings, treatment and prognosis were compared between HIV infected and non-infected persons. Results : Twenty-five patients with PCP were identified. 16 were HIV infected, and 9 were HIV non-infected. The mean age of overall patients was $43.4{\pm}13.2$ years. Underlying conditions in HIV non-infected persons were hematologic malignancy (7 cases), solid organ transplant (1 case), and autoimmune disease (1 case). Seven cases (77.8%) of HIV non-infected persons had a history of steroid use. Mean duration of symptoms was longer in HIV infected persons than in HIV non-infected persons, but it was not statistically significant. PaO2 was lower in HIV infected persons ($61.2{\pm}16.9$ mmHg vs. $65.4{\pm}15.4$), but it was not statistically significant. Chest X ray showed typical ground glass opacity in 12 cases (75%) of HIV infected persons and in 4 cases (44.4%) of HIV non-infected persons. Twelve cases (75%) of HIV infected persons were treated with steroid, as were 6 cases (66.7%) of HIV non-infected persons. Ventilator care was needed in 6 cases (37.5%) of HIV infected persons and in 2 cases (22.2%) of HIV non-infected persons. Mortality of HIV infected persons was 50%, and that of HIV non-infected persons was 11.1%. Conclusions : PCP showed some different clinical characteristics between HIV infected and non-infected persons. Prospective studies regarding the risk factors of PCP, prophylaxis, treatment and prognosis in HIV infected and non-infected persons are warranted.