Metastasis consists of complex cascades and a lot of factors are involved in each step of metastasis. In recent studies, the role of epithelial-mesenchymal transition (EMT) in metastasis is suggested. EMT has a feature of epithelial cells conversing into mesenchymal cells morphologically and phenotypically, is a characteristic of malignant and metastatic cells in most cancer. The mesenchymal cells usually show more malignant phenotype, including invasion and metastasis. EMT can play an important role in metastasis of oral squamous cell carcinoma (OSCC). Although the role of Snail, slug, other transcriptional factors and E-cadherin are well known in human cancers, there are a few studies on N-cadherin and Twist expression in OSCC. The present study was aimed to analyze the expression of N-cadherin and Twist protein in OSCC from Korean patients. The immunohistochemical stain was performed using 58 primary OSCCs and 6 metastatic OSCCs, and the correlation between the expression of these proteins and clinicopathological parameters of OSCC patients was analyzed. The expression rate of high expression of N-cadherin was observed in 70.4% and Twist in 87.3% of OSCC. The expression of N-cadherin in metastatic OSCC increased than in corresponding primary OSCC (p<0.05). The spearman correlation coefficiency between N-cadherin and Twist was calculated as 0.228. The clinical factors such as lymph node metastasis and survival showed statistically significant correlation between N-cadherin expression. The expression of Twist was correlated with recurrence. In conclusion, the authors suggest that N-cadherin may play an important role in malignant behaviour of OSCC and can be considered as prognostic indicator of OSCC.

Runt-related transcription factor (RUNX) 3 is well known as a developmental regulators, as well as candidate tumor suppressor gene in human breast cancer, gastric cancer, esophageal cancer, and so on. The present study was aimed to analyze the expression of RUNX3 protein in oral squamous cell carcinoma (OSCC) from Korean patients. The immunohistochemical stain was performed with 14 normal oral mucosa (NOM) and 25 OSCCs, and statistical analysis was carried out to find out the correlation between the expression of RUNX and clinicopathological parameters of OSCC patients. In OSCC, the expression of RUNX3 protein was found to increase more than in NOM. Moreover, in the univariate correlation analysis, the gender, regional lymph node metastasis, and histopathologic differentiation of OSCC patients were positively correlated with the expression of RUNX3 (p<0.05). These results indicate that RUNX3 can play a role as an oncogene in OSCC, in contrast to some reports on RUNX3 in other human cancers. In addition, RUNX3 may be considered as new malignant biomarker of OSCC.

Cancer cells are often found in an ischemic condition due to the rapid outgrowth of their vascular supply, and these cells are expected to develop an increased potential for local invasive growth. Since the first steps are characterized by increased motility and invasiveness, expression of molecules involved in cellular adhesion to extracellular matrix (ECM) is increased in the process of cancer cell invasion and metastasis. In this work we explored the molecular characteristics and its regulatory mechanism of hypoxic oral squamous cell carcinoma (OSCC) cells. Our experiment identified that hypoxia increases α5 integrin protein levels through phosphoinositide 3-kinase (PI3K)/Akt pathway in OSCC cells.

Malignant tumor cells outgrow new blood vessel formation and tend to be in hypoxic state. Hypoxic cancer cells adapt to hypoxic conditions by transforming its characteristics. On the other hand, one of the most important features of cancer cells is that carcinoma cells loses its inherent epithelial phenotype and acquires mesenchymal characteristics, called as epithelial-mesenchymal transition(EMT). It has been already well known that EMT contributes to tumor invasion and metastasis. The present study investigated whether hypoxia play a major role in induction of phenotypic changes of oral squamous cell carcinoma(OSCC). Furthermore, the mechanism of EMT in oral squamous cell carcinoma cells by hypoxia has been clarified. To mimic hypoxic condition, cobalt chloride and desferoxamine, well-known hypoxic mimetic agents, were used. This study shows that hypoxia suppresses the expression of E-cadherin(epithelial marker) and increases vimentin and N-cadherin( mesenchymal markers) in OSCC. In addition, α5 integrin protein, which is a receptor for fibronectin and an important molecule for tumor invasion, is prominently induced by hypoxia.

Adherent cells, such as those found in epithelial tissues, must be physically associated with extracellular matrix (ECM)components to survive. Though stimulation by growth factors is an essential factor in cell survival, normal cells also requires cell adhesion to ECM proteins. The cessation of these anchorage-mediated signals seems to be a common mechanism to physiolog ically t erminate t he l ife cycle of t hese c ells b y apoptosis. This form o f cell death has been termed anoikis.In cancer, resistance to anoikis of cancer cell is important in invasion and metastasis. The present study investigated the intracellular mechanism involved in anoikis, especially in cells treated with epigallocatechin- 3-gallate(EGCG). To induce anoikis, cell culture plates were coated with 10 ㎍/ml poly-HEMA. A549 lung adenocarcinoma cells were grown in RPMI 1640 medium with/without 10% fetal bovine serum, and then cells were replated on cell culture dishes coated with poly-HEMA in the presence or absence of serum. On the other hand, EGFR inhibitor, PI3K inhibitor, and EGCG were treated to the anoikis status cells, in order to evaluate the factors of anoikis. The result revealed that growth factors or loss of adhesion can increase phosphorylate Akt. In addition, lack of cell adhesion fails to activate pro-apoptotic factors directly. Activity of Erk kinase depends on not only EGFR signaling but also cell adhesion. Akt activation is mainly affected by EGCG whereas Raf-1 activation is controlled by the presence of cell contact. In addition, EGCG increased the level of NFkB, whereas phophroylated PTEN and total PTEN were not different. In this report,increase of NFkB was correlated with Akt phosphorylation, suggesting that EGCG can protect cells from detachment–induced cell death through Akt activation and subsequent NFkB

Green tea, derived from the plant Camellia sinensis, is one of the most common beverages consumed worldwide. Epigallocatechin-3-gallate (EGCG) is the most abundant and bioactive polyphenolic constituent in green tea. Understanding how intracellular signaling pathways respond to EGCG may provide a clue to the difference of cell responses and basis for usefulness of EGCG as a chemopreventive and/or chemotherapeutic agent. In the present study, we tried to check whether EGCG could be a useful agent in chemotherapeutic treatment of oral squamous carcinoma. Furthermore, we investigated which signaling pathway is involved in biologic activities of EGCG. EGCG induced the cell death of oral squamous carcinoma cells. Furthermore, it increased phosphorylation of Akt in serum-strarved oral squamous carcinoma cells. But, initial increase of Akt activation did not affect cell survival. Activities of Raf-1 and Erk showed inconsistent response to EGCG treatment, but Erk phosphorylation is consistent with Raf-1 activity in YD 10B cells. These changes of Raf-1 and Erk activity in EGCG treated cells were different depending on cell line type. Supposedly, the difference of cell component may affect the Raf-1 and Erk reactivity to EGCG treatment. Akt activation by EGCG is independent on activities of PDK1 and PTEN, and expression of bax and bcl-2 proteins were not changed by EGCG treatment. Therefore, EGCG treatment did not induce the apoptosis of YD 10B cell. On the other hand, vascular adhesion molecule (VCAM) was decreased by EGCG treatment, so it is possible that decrease of VCAM can play certain role in survival and/or cell death in EGCG treated cells

Tumor cells under hypoxic conditions are often found due to the rapid outgrowth of their vascular supply, and,in order to survive hypoxia, these cells induce numerous signaling factors. Erk is an important kinase in cell survival, and its activity is regulated by Raf kinases through numerous growth factor receptors. The authors investigated Erk activation and Raf/Erk signaling using the hypoxia-mimetic agent, cobalt chloride (CoCl2), in oral squamous cell carcinoma (OSCC) cells. CoCl2 increases Erk phosphorylation in both a dose- and time-dependent manner. In addition, blocking the activation of epidermal growth factor receptor (EGFR) using PD168393 abolished Erk activation in response to CoCl2, suggesting that Erk phosphorylation by CoCl2 is dependent on EGFR.

In this study, the apoptotic effects of the actin disruption agent, latrunculin B(LB) have been investigated on p53 deficient chronic myeloid leukemia cell line K562. A dose-dependent decrease in K562 cell proliferation was observed after LB treatment with maximum decrease in cell proliferation being at 1.5μM where the percent inhibition was 66.53%. F-actin stained with TRITC-phalloidin was shown as a peripheral ring or appeared diffusely distributed throughout the cytoplasm in untreated cells, this actin ring was decreased following LB treatment, and even large focal actin aggregates were formed. Treatment of K562 with LB(1.5μM) generated ROS substantially. LB activated expression in a dose-dependent manner. Therefore it can be concluded that LB, depolymerising agent of actin, induces apoptosis by producing ROS and up-regulating NF-kB and COX-2 activation.

The major component of green tea is (-)-epigallocatechin-3-gallate(EGCG) which accounts for 5080% of catechin, representing 200300 mg in a brewed cup of green tea. EGCG has been known to possess growth inhibitory and pro-apoptotic effect on human cancer cell lines such as prostate, bladder and breast cancers. In contrast, several studies have suggested that EGCG could promote cell proliferation and/or survival instead of pro-apoptotic effect. Understanding how intracellular signaling pathways respond to EGCG may provide a clue to the difference of cell responses and basis for usefulness of EGCG as a chemopreventive and/or chemotherapeutic agent. To better understand the mechanisms responsible for the chemopreventive efficacy of EGCG, the authors tried to identify the key molecules that contributes to Akt activation and can inhibit this activation. In the present study, EGCG increased Akt phosphorylation, an activeform of Akt and negatively affect on direct upstream molecules of Akt including PTEN and EGFR, though Akt phosphorylation was increased.

( - ) -epigall ocatechin - 3 -ga ll ate(EGCG) 는 녹차에서 추출되는 주된 성분으로 항산화. 세포 증식 억제 및 세 포 자멸사를 유도힌다 고 알려져 있다‘ 현 재 끼지의 여러 연구에 의하띤 EGCG는 세 포 성장을 억제하고 나아가서는 apoptoS1S까지도 유발한다. 한편 일부 연구는 EGCG가 오히려 apo ptosi s를 억 제 하고， 세 포 증식을 촉진한다고 보고하고 있다. 저자들은 EGCG가 이러한 상반된 효과틀을 보이게 되 는 기전과 그에 관련된 물질들을 파악하고지 하였다， EGCG를 세포에 처리시 초기에는 세포 생존에 관여힌다고 알려진 인 산화된 Akt 단백이 증가함이 관찰되었다 그 외에도 인산화된 Erk 단백 등의 증가로 EGCG가 세포 생존을 지속시키 는 역할을 하고 있음을 알 수 있었다‘ 이러한 현상은 COS7 과 A549 세 포 에서 관찰되었으며 Hela 세포에서는 관찰되지 않아 세 포외부에서 EGCG가 결합하게 되 는 물질 혹은 세 포내 물질 등의 차이에 의해 세 포 미다 EGCG에 대한 반응이 다른 것으로 추측된다 24시간 이상 처리된 경우 ECCG가 세 포 생존에 관린된 인자들을 감소시키는 것으로 보아 EGCG에 처음에는 세 포 생존을 유도하지만 장시간 처리 시 세 포 증식 및 생존을 억제하는 물질 임 을 확인하였다.

In t his study, we tried to identify the key elements that respond to EGCG t reatment and its role in cell survival 0 1' apop tosis by EGCG. focusing on Akt pathway and Raf-MEK-ERK pathways. Cells were serum starved for 16 h and then treated with (-) -epiga llocatechin-3-gallate. To cletermine which pathway is related to effects of EGCG on cell s, the levels of phosphorylated Akt(pAkt) and Erk (pErk) were a nalyzed by immunoblotting. A549 cell s showed the increase of pAkt in response to EGCG‘ whereas Hela cells exhi bited no difference in the levels of pAkt by EGCG treatment Phos phorylation of Akt over initial basal levels became evident a fter 1 h of EGCG treatment and peaked at 3 h pErk was also increased by EGCG in Hela cells as well as in A549 cells To determine th e effect of EGCG on growth of cells‘ A549 cells were treated wi th vari 。u s concentrations of EGCG (from 10 μ M to 300 μ M) for 3 h. Cell growth was examined by MTI assay. The resulting growth curves of A549 cell s showed that EGCG promotecl cell prolifera tion in a close-dependent manner at early phase. When cells were t rea ted with EGCG for 24 h. pAkt and pErk expressions were significantly i띠1ibited ， even at 10 μ M B-raf ex pression was also clecreased in a close-dependent manner. In teresti ngly. the presence of serum weakened t his inhibitory effect of EGCG on the ex pression of survival facto rs. Our study inrucates that EGCG stimulates cell survival of A549 cells through thc PI3K/AKT pathway. though it fina lly be haves like a suppressive agent on cell su rvival

Disruption of cell - matrix attachment results in a loss of prosurvival signals and culminates in programmed cell death, referred to as anoikis , Apoptosis signal- regulating kinase 1(ASKl)/MKK5 is a ubiquitously expressed enzyme that acti vates c-Jun N-terminal kinase/stress-activated protein kinase JNK/SAPK and p38 pathways by direct site specific Ser/Thr phosphoryl ation of their respective MKKs-MKK4/MKK7 for JNK and MKK3/MKK6 for p38 kinases, The kinase activity of ASKl is stimulated by a variety of death signals, including TNF, Fas ligation, reactive oxygen species, and antineoplastic agents , The aim of this study was to investigate the relative importance of ASKl in anOlkls 1n the present study cells which lost their adhesion showed higher rate of cell death in compared to cells which maintained anchorage. 1nterestingly the res ult showed that suspended cells expressing ASK1 were more susceptible to anoikis than suspended cells having no ASK1 1n addition, cellu lar attachment seems to have significant effect on ASKl activity and p38 MAPK protein rather than serum stimulation

The production of insoluble glucan was affected by the concentration of ions and buffers in a mouth. In this study, the effects of ions and buffers on the mRNA expression of gtfB and gtfC gene of Streptococcus mutans which is an important causative agent of dental caries were investigated by Fluorescent in situ hybridization(FISH). The mRNA of gtfB and gtfC gene was normally expressed in the BHI broth containing 1 % sucrose. The gtfB and gtfC mRNA expression was increased at 0.25 mM and 4 mM of CaCl2, respectively. While the mRNA expression of two genes was inhibited at each concentration of KCl and MgCl2 when compared to the control. As for buffers, the gtfB and gtfC mRNA expression was lower than the control by the addition of sodium bicarbonate. The addition of sodium phosphate decreased the gtfB mRNA expression except for 100 mM in which the expression was increased, and the gtfC mRNA expression was similar to or lower than the control at each concentraion of sodium phosphate. The mRNA expression of the gtfB and gtfC was decreased at each concentration of potassium phosphate when compared to the control.

Gemcitabine (Gemzar, 2,2-difluorodeoxycytidine, or dFdC) is an analog of cytosine arabinoside with anti-tumor activity in a few human cancers (lung, ovary, pancreatic and breast cancers). However, the mechanism of apoptosis by this compound in carcinoma has not been fully elucidated. In the present study, we investigated that gemcitabine alone and combination with cisplatin or 5-FU are cancer toxicity using lung cancer cell line A549 by MTT, FACS analysis, and Western blot assay. Also, to confirm enhanced antitumor activity in vivo using an xenograft tumor model. The MTT assay showed higher cytotoxic effect in combination with gemcitabine-cisplatin or gemcitabine-5-FU than gemcitabine alone. FACS analysis showed that gemcitabine-cisplatin combination increased hypodiploid DNA to 70.84 %. The induction of apoptosis showed more increase in combination with gemcitabine-cisplatin or gemcitabine-5-FU than gemcitabine alone. The Western results showed higher expression of p53 and p21WAF/CIP1 protein in combination treatment with gemcitabine-cisplatin or gemcitabine-5-FU than gemcitabine treatment alone. But, Bcl-2 protein expression decreased. In vivo experiments showed that more decreased tumor size and more increased survival rate on combination with gemcitabine- cisplatin or gemcitabine-5-FU combination than gemcitabine alone. In conclusion, this study suggests that gemcitabine combined with cisplatin or 5-FU are the synergistic effect of anticancer therapy on lung cancer.

ECR PECVD법에 의해 Pt/Ti/SiO2/Si 다층 기판 위에 480˚C에서 순수한 페로브스카이트상의 PLT박막을 증착하였다. PLT 박막 증착전 ECR산소 플라즈마내에서의 Pb(DPM)2 pre-flowing처리는 Pb(DPM)2의 공급을 안정화시켜주며 박막증착초기에 Pb성분이 풍부한 분위기를 조성해 줌으로써 페로브스카이트 핵생성을 용이하게 하여 PLT박막 특성을 향상시켰다. Ti-source 유입량을 변화시킬 때 PLT박막의 증착특성, 조성, 결정상 그리고 전기적 특성을 관찰하였다. PLT박막은(100)으로 우선 배향되었으며 화학양론비가 잘 맞는 경우 높은 페로브스카이트 X-선 회절강도와 높은 유전율을 나타내었다.

The awareness of the nutrition labeling of 82 food producers and 668 government officials was assessed and compared, from May to June in 1994, to that of consumers. Compared to 82.4% of cosumers, 48.1% of producers and 47.8% of officials answered that nutrition labeling is necessary. 48% of producers expected a modest food price rise, but 70% thought food sales would not be affected with nutrition labeling. While being worried about the regulatory difficulties and the increased work load given the inadequate implementation of the current food labeling system due to insufficient personnel, 50.2% of officials wanted the new nutrition labeling system to be introduced within 1~2 years. Contrary to the general dissatisfaction with the system and the lack of confidence in it on the part of consumers, producers thought that they currently provide sufficient food information for consumers, and that consumers had much confidence in it. Producers and officials were more found worried about consumers' inadequate understanding and inactive use of the system in contrast to the widespread and welcome support on the part of consumers. But it was fully agreed by all that education and awareness is crucial for the successful implementation of nutrition labeling system.

Consumer awareness of current food labeling system and new nutrition labeling system which the government considers to adopt widely was assessed, from May to June in 1994, for 423 adults living in Seoul. Being highly conscious of food safety, they thought the current food label did not provide sufficient information. Dissatisfaction with the current system was shown higher in the female, young, or unmarried strata. The need for nutrition labeling system was widely recognized by 82% of total respondents regardless of sex, level of education, monthly income, and marital status. Although some expressed worries about proper management of the system, most of the respondents answered that the system would benefit them after all. In this connection, 59% of the respondents showed willingness to accept a price increase to be entailed by nutrition labeling. Nutrition informations that, they thought, should be covered were: calorie>minerals>cholesterol>protein>vitamins>fat>sodium. Additional labeling informations they called for were nutrient contents>RDA percentage>specific statement on reinforced or eliminated nutrients.