• Journal of Gastric Cancer
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• v.1 no.1
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• pp.10-16
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• 2001

Purpose: The p53 protein is a tumor supressor gene, and its mutation is associated with biologic aggressiveness. CD44v6, one of the CD44 family, is a cell surface glycoprotein that plays a role in cancer invasion and metastasis. Vascular endothelial growth factor (VEGF) is another recently identified growth factor with significant angiogenic properties. The purpose of this study was to investigate p53, CD44v6, and VEGF expressions to determine whether degree of expression was related to pathological parameters such as Lauren's classification, depth of invasion, and lymph node metastasis. Materials and Methods: Immunohistochemical stains of p53, CD44v6, and VEGF in formalin-fixed paraffin-embedded tissue sections of 125 gastric adenocarcinomas were done. Results: The overall expression rates of p53, CD44v6, and VEGF were $54.4\%$ (68/125), $36.8\%$ (46/125), and $48.0\%$ (60/125), respectively. The p53, not CD44v6 and VEGF was higher in intestinal-type gastric carcinomas by Lauren's classification. The expressions of p53, CD44v6, and VEGF were statistically correlated with depth of tumor invasion. The expression of CD44v6 was higher in the lymph node metastatic group than in the negative group. The p53 expression was significantly associated with VEGF expression. Conclusions: These data suggest that the expressions of p53, CD44v6, and VEGF are biologically related to malignancy. The p53 and CD44v6 expressions are independent; however, p53 gene mutation is one of the contributing factors to VEGF expression in gastric adenocarcinoma.

• Journal of the Korean Crystal Growth and Crystal Technology
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• v.22 no.1
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• pp.36-41
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• 2012

We have been performed on $Co^{60}$ ${\gamma}$-ray irradiation of South Sea cultured pearls, with the absorbed dose of 0.1~100 kGy at room temperature. In addition, it was investigated electron paramagnetic resonance (EPR) and amino acid analysis (AAA) for detection of Gamma irradiated South Sea cultured pearls. It was observed that the irradiated South Sea cultured pearls revealed additional free radical peak such as $CO_2^-$, at a g-factor of $2.001{\pm}0.002$ in EPR spectra. From the amino acid analysis (AAA), it was shown that some of amino acid in the protein of the nacre destroyed after ${\gamma}$-ray; glutamic acid residue by 11.43 %, alanine by 3.11 %, and histidine by 43.75 %. It was useful to detect the irradiated South Sea cultured pearls by EPR measurement in our study.

• Journal of Periodontal and Implant Science
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• v.25 no.2
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• pp.239-251
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• 1995

The selective migration, attachment and proliferation of periodontal ligament cells are the desired goal of periodontal regeneration therapy. Fibronectin is well known for an attachment protein for dentin surface. Also, Fibroblast growth factor (FGF) is well known to enhance the periodontal regeneration. The purpose of this study was to evaluation the effect of fibronection and FGF on the attachment rate and the cellular activity. Human gingival fibroblast and periodontal ligament cells were cultured from the teeth extracted for non-periodontal reson. Cultured human gingival fibroblast and periodontal ligament cells in vitro were treated with fibronectin and FGF a various dosage and culture times. Cellular activity was examined by MTT assay. The results of this study was demonstrated that cell attachment rate of experimental group was under the control value at 1st, 2nd, 3rd incubation day. But, at 3rd incubation day, attchment value tended to return to the control value. In case of fibronectin alone application, cellular activity was decreased than that of control at 1st, 2nd incubation day. But 3rd day, cellular activity was returned to the control value. The activity of gingival fibroblast in FGF alone application was decreased thatn that of control at each incubation day. But activity of periodontal cell group was increased cell activities at 2nd, 3rd day. Additionally cellular activity of fibronectin & FGF combined application on gingival fibroblast group was similar to control value at incubation day. But activity of periodontal ligament cell group was increased at 2nd, 3rd day compared with control group.This study demonstrated that combined application of fibronectin & FGF induced the selective chemotaxis for periodontal ligament cell in vitro.

• BMB Reports
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• v.49 no.4
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• pp.220-225
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• 2016

Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signalregulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a role in cancer cell survival; thus, regulation of ERK1/2 activation may improve the efficacy of cancer therapies that target ERK signaling.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3471-3476
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• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6219-6225
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• 2014

Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6391-6395
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• 2014

Overexpression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQP expression. In this study, we demonstrated that EGF (epidermal growth factor) induces SiHa cells migration and AQP8 expression. Wound healing results showed that cell migration was increased by 2.79-1.50-fold at 24h and 48h after EGF treatment. AQP8 expression was significantly increased (3.33-fold) at 48h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035, blocked EGF-induced AQP8 expression and cell migration and AQP8 expression was decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa. Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/Erk (extracellular signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF-treated) to 0.43-fold (U0126-treated). Immunofluorescence microscopy further confirmed the results. Collectively, our findings show that EGF induces AQP8 expression and cell migration in human cervical cancer SiHa cells via the EGFR/Erk1/2 signal transduction pathway.

• BMB Reports
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• v.34 no.4
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• pp.385-389
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• 2001

Insulin-like growth factor binding protein-1 (IGFBP-1) appears to be an important modular of the insulin growth factor (IGF) bioactivity in metabolic disease and chronic hypoxia. Treatment of desferrioxamine (Dfo), cobalt, or nickel in HepG2 cells stimulated the expression of IGFBP1 mRNA as hypoxia. However, the presence of ferric ammonium citrate (FAC) in the 1% $O_2$ decreased the upregulation of the IGFBP-1 mRNA expression. In addition, actinomycin D and cycloheximide abolished the increase in the expression of IGFBP-1 mRNA that was induced by Dfo and transition metals (cobalt and nickel). To obtain further information about the putative oxygen sensor, we postulate that putative heme proteins, responsible for the oxygen-sensing process in HepG2 cells, should be sensitive to hypoada. The mechanism of these upregulations of the IGFBP-1 mRNA expression by Dfo and transition metals was investigated by treatment with 2 mM of 4,6-dioxoheptanoic acid (DHA), an inhibitor of heme biosynthesis. The results showed that 1% $O_2$-, Dfo-, cobalt-, or nickel induced IGFBP-1 mRNA expressions in HepG2 cells were all markedly inhibited when the heme synthesis was blocked by DHA. We suggest that the IGFBP-1 mRNA expression in the HepG2 cell is regulated by 1% $O_2$, Dfo, cobalt, or nickel, implicating the involvement of the putative heme-containing oxygensensing molecule.

• Nutrition Research and Practice
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• v.10 no.3
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• pp.259-264
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• 2016

BACKGROUND/OBJECTIVES: Stromal cell-derived growth factor 1 (SDF-1), also known as chemokine ligand 12, and chemokine receptor type 4 are involved in cancer cell migration. Compound K (CK), a metabolite of protopanaxadiol-type ginsenoside by gut microbiota, is reported to have therapeutic potential in cancer therapy. However, the inhibitory effect of CK on SDF-1 pathway-induced migration of glioma has not yet been established. MATERIALS/METHODS: Cytotoxicity of CK in C6 glioma cells was determined using an EZ-Cytox cell viability assay kit. Cell migration was tested using the wound healing and Boyden chamber assay. Phosphorylation levels of protein kinase C $(PKC){\alpha}$ and extracellular signal-regulated kinase (ERK) were measured by western blot assay, and matrix metallopeptidases (MMP) were measured by gelatin-zymography analysis. RESULTS: CK significantly reduced the phosphorylation of $PKC{\alpha}$ and ERK1/2, expression of MMP9 and MMP2, and inhibited the migration of C6 glioma cells under SDF-1-stimulated conditions. CONCLUSIONS: CK is a cell migration inhibitor that inhibits C6 glioma cell migration by regulating its downstream signaling molecules including $PKC{\alpha}$, ERK1/2, and MMPs.

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.9-17
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• 2004

Objective : Mesangial cell proliferation and excessive accumulation of extracellular matrix (ECM) proteins is the common pathologic feature of glomerulosclerosis, and platelet-derived growth factor (PDGF) BB-chain, transforming growth factor betal $(TGF-{\beta}1)$, cyclin dependent kinases (CDK) and CDK inhibitors mediated in these pathophysiological processes. Bupleurum falcatum which is one of the most widely used components in traditional oriental medicines, has multiple pharmacological effects, such as antipyretic, analgesic, immune modulating, anti-inflammatory, anti-allergic, anti-thrombotic, anti-atherosclerotic, and antitussive effects. Methods : In this study, we evaluated the influence of Bupleurum falcatum on mesangial cell proliferation, DNA synthesis and expression of PDGF-BB chain, $TGF-{\beta}1$, CDKI, CDK2, CDK4, p21 and p27 in fetal bovine serum (FBS)-activated human mesangial cell. Results : Bupleurum falcatum reduced the mesangial cell proliferation and DNA synthesis more than control and captopril. And in the ELISA analysis of $TGF-{\beta}1$, and RT-PCR of PDGF-BB chain, CDK1, CDK2, CDK4, p21, and p27, Bupleurum falcatum inhibited the expression of $TGF-{\beta}1$ protein and PDGF-BB, CDK1, CDK2 gene and promoted that of p21 gene in a dose-dependent manner in comparing with control and captopril. Conclusions: These results suggest that Bupleurum falcatum may inhibit the mesangial cell proliferation and DNA synthesis by regulation of PDGF-BB and $TGF-{\beta}1$ expressions, and by modulation of CDK1, CDK2 and p21 expression.