Troglitazone Inhibits Matrix Metalloproteinase-9 Expression and Invasion of Breast Cancer Cell through a Peroxisome Proliferator-Activated Receptor γ-Dependent Mechanism / 한국유방암학회지

PURPOSE: Peroxisome proliferator-activated receptor γ (PPARγ) is involved in the pathology of numerous diseases including atherosclerosis, diabetes, obesity, and cancer. Matrix metalloproteinases (MMPs) play a significant role in tissue remodeling related to various processes such as morphogenesis, angiogenesis, tissue repair, invasion, and metastasis. We investigated the effects of PPARγ on MMP expression and invasion in breast cancer cells. METHODS: MCF-7 cells were cultured and then cell viability was monitored in an MTT assay. Western blotting, gelatin zymography, real-time polymerase chain reaction, and luciferase assays were performed to investigate the effect of the synthetic PPARγ ligand troglitazone on MMP expression. Transcription factor DNA binding was analyzed by electrophoretic mobility shift assay. A Matrigel invasion assay was used to assess the effects of troglitazone on MCF-7 cells. RESULTS: Troglitazone did not affect MCF-7 cell viability. 12-O-tetradecanoylphorbol-13-acetate (TPA) induced MMP-9 expression and invasion in MCF-7 cell. However, these effects were decreased by troglitazone. TPA increased nuclear factor κB and activator protein-1 DNA binding, while troglitazone inhibited these effects. The selective PPARγ antagonist GW9662 reversed MMP-9 inhibition by troglitazone in TPA-treated MCF-7 cells. CONCLUSION: Troglitazone inhibited nuclear factor κB and activator protein-1-mediated MMP-9 expression and invasion of MCF-7 cells through a PPARγ-dependent mechanism.

The Association between Dehydroepiandrosterone Sulfate (DHEA-S) and Bone Mineral Density in Korean Men and Women

BACKGROUND: The relationship between dehydroepiandrosterone sulfate (DHEA-S) and bone mineral density (BMD) is controversial. And findings of most studies that have investigated this relationship are restricted to postmenopausal women. In this study, we investigated the relationship between serum DHEA-S and BMD in both men and women. METHODS: This cross-sectional study evaluated a total of 294 healthy Korean participants through a medical examination program. And a subgroup of 154 participants was subjected to a longitudinal analysis. We measured BMD by dual energy X-ray absorptiometry and assayed DHEA-S by a chemiluminescent immunoassay. RESULTS: We evaluated the association between serum DHEA-S concentration and BMD at the femur trochanter after adjusting for cofounders such as age, body mass index, lifestyle factors, serum cortisol level, serum insulin-like growth factor 1 (IGF-1) level, and sex. Through our longitudinal study, we found that the changes in BMD at the total spine, at the femur neck, and at the femur trochanter were all smaller in the ΔDHEA-S 0 group. CONCLUSIONS: We found that there was a positive correlation between serum DHEA-S and femur BMD, which suggests that controlling serum DHEA-S levels may retard age-related BMD reduction in Koreans.

Silibinin Enhances Ultraviolet B-Induced Apoptosis in MCF-7 Human Breast Cancer Cells / 한국유방암학회지

PURPOSE: Chemotherapies for breast cancer generally have strong cellular cytotoxicity and severe side effects. Thus, significant emphasis has been placed on combinations of naturally occurring chemopreventive agents. Silibinin is a major bioactive flavonolignan extracted from milk thistle with chemopreventive activity in various organs including the skin, prostate, and breast. However, the mechanism underlying the inhibitory action of silibinin in breast cancer has not been completely elucidated. Therefore, we investigated the effect of silibinin in MCF-7 human breast cancer cells and determined whether silibinin enhances ultraviolet (UV) B-induced apoptosis. METHODS: The effects of silibinin on MCF-7 cell viability were determined using the MTT assay. The effect of silibinin on PARP cleavage, as the hallmark of apoptotic cell death, and p53 protein expression in MCF-7 cells was analyzed using Western blot. The effect of silibinin on UVB-induced apoptosis in MCF-7 cells was analyzed by flow cytometry. RESULTS: A dose- and time-dependent reduction in viability was observed in MCF-7 cells treated with silibinin. Silibinin strongly induced apoptotic cell death in MCF-7 cells, and induction of apoptosis was associated with increased p53 expression. Moreover, silibinin enhanced UVB-induced apoptosis in MCF-7 cells. CONCLUSION: Silibinin induced a loss of cell viability and apoptotic cell death in MCF-7 cells. Furthermore, the combination of silibinin and UVB resulted in an additive effect on apoptosis in MCF-7 cells. These results suggest that silibinin might be an important supplemental agent for treating patients with breast cancer.

Characterization of a Novel Monoclonal Antibody (27H2) Recognizing Human CD34 Class III Epitope

BACKGROUND: Monoclonal antibodies (mAbs) recognizing Class III epitope of CD34 are essential for flow cytometric diagnosis of leukemia. METHODS: 27H2 mAb was developed from a mouse alternatively immunized with human acute leukemia cell lines, KG1 and Molm-1. Using flow cytometric analysis of various leukemic cell lines and peripheral blood, immunohistochemical study of frozen tonsil, we characterized 27H2 mAb. Antigen immunoprecipitated with 27H2 mAb immunobloted with anti-CD34 mAb. A case of bone marrow sample of acute lymphoblastic leukemia (ALL) patient was obtained at CBNU Hospital. For epitope identification enzyme treatment with neuraminidase and O-sialoglycoprotein endopeptidase (OSGE) and blocking assay with known classIII mAb (HPCA-2) were done. RESULTS: Only KG1 and Molm-1 revealed positive immunoreactivity. Immunohistochemical staining disclosed strong membranous immunoreactivity on high endothelial venules. Antigen immunoprecipitated by 27H2 mAb showed approximately 100 kDa sized band immunoblotted with anti-CD34 under non-reducing conditions. Epitope recognized by 27H2 mAb disclosed resistancy to both neuraminidase and OSGE treatment and completely blocked with known class III mAb preincubation. CD34 positive leukemic cells in BM of pre B cell ALL patient detected by FITC-conjugated 27H2 and HPCA-2 were identified with similar sensitivity. CONCLUSION: A novel murine mAb recognizing class III epitope of human CD34 with high affinity, which is useful for flow cytometric diagnosis of leukemia, was developed.

A Study on the Policy Making Process of the Mental Health Act (1995) in Korea : A Comparative Analysis of Two Different Legislation Periods / 신경정신의학

The purpose of this paper is to produce a policy decision making model most appropriate for formulating mental health policy in Korea. This research will also illuminate the legislation process and make accurate predictions about the revision process of the Mental Health Act. Using the Allison Models, we analyzed the legislation process of for the Korean Mental Health Act from the 1980s to 1995, which was largely divided into two periods. We applied the three types of model to each of these two periods. The results of the comparative analysis show that the process of the Mental Health Act enactment can be explained through by each of the three types of Allison models and that there is no dominant model. However, the analysis shows that, compared with the 'Rational Actor' model, the 'Organizational Behavior' model and the 'Governmental Politics' model are better able to explain the decision making process compared to the 'Rational Actor' model.

Cordycepin inhibits UVB-induced matrix metalloproteinase expression by suppressing the NF-kappa B pathway in human dermal fibroblasts

Cordycepin (3'-deoxyadenosine) has been shown to exhibit many pharmacological activities, including anti-cancer, anti-inflammatory, and anti-infection activities. However, the anti-skin photoaging effects of cordycepin have not yet been reported. In the present study, we investigated the inhibitory effects of cordycepin on matrix metalloproteinase-1 (MMP-1) and -3 expressions of the human dermal fibroblast cells. Western blot analysis and real-time PCR revealed cordycepin inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB strongly activated NF-kappa B activity, which was determined by I kappa B alpha degradation, nuclear localization of p50 and p65 subunit, and NF-kappa B binding activity. However, UVB-induced NF-kappa B activation and MMP expression were completely blocked by cordycepin pretreatment. These findings suggest that cordycepin could prevent UVB-induced MMPs expressions through inhibition of NF-kappa B activation. In conclusion, cordycepin might be used as a potential agent for the prevention and treatment of skin photoaging.

Low-density lipoprotein protects Vibrio vulnificus-induced lethality through blocking lipopolysaccharide action

Lipoprotein plays a role in the host defense against bacterial infection, and its serum level has been demonstrated to be an important prognosis factor of survival. We have previously demonstrated that LDL directly inactivates the hemolytic activity of Vibrio vulnificus cytolysin (VVC) in vitro. The object of this study was therefore to examine whether the LDL-mediated inactivation of VVC leads to protection against lethal infection of V. vulnificus in vivo, using wild and VVC-deficient V. vulnificus strains. Unexpectedly, we found that LDL protects mouse lethality induced by VVC-deficient as well as wild V. vulnificus strain. We also demonstrated that LDL blocks V. vulnificus LPS-induced lethality in mice. These results suggest that LDL preferentially act on endotoxin rather than exotoxin in the protection against V. vulnificus-induced mice lethality.

TNF-alpha upregulates PTEN via NF-kappaB signaling pathways in human leukemic cells

TNF-alpha plays a variety of biological functions such as apoptosis, inflammation and immunity. PTEN also has various cellular function including cell growth, proliferation, migration and differentiation. Thus, possible relationships between the two molecules are suggested. TNF-alpha has been known to downregulate PTEN via NF-kappaB pathway in the human colon cell line, HT-29. However, here we show the opposite finding that TNF-alpha upregulates PTEN via activation of NF-kappaB in human leukemic cells. TNF-alpha increased PTEN expression at HL-60 cells in a time- and dose-dependent manner, but the response was abolished by disruption of NF-kappaB with p65 anisense phosphorothioate oligonucleotide or pyrrolidine dithiocarbamate. We found that TNF-alpha activated the NF-kappaB pathways, evidenced by the translocation of p65 to the nucleus in TNF-alpha-treated cells. We conclude that TNF-alpha induces upregulation of PTEN expression through NF-kappaB activation in human leukemic cells.

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha

Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.

Norovirus Outbreak after a School Trip among Girls' High School Students

Norovirus is one of the common causative agents of viral gastroenteritis in developed countries. A large outbreak of gastroenteritis occurred among girls' high school students in Cheongju city, Chungbuk province, who had attended a school trip to Cheju island from 19 to 21 May 2003. One hundred and ninety six students were consistent with case definition and attack rate was 54.9%. The epidemic curve was characteristic of a point-source outbreak. The frequency of diarrhea was 1 to 6 times (76.8%) and the duration of diarrhea was within two days (85.1%) in most cases. The most common symptom with diarrhea was abdominal pain followed by headache, tenesmus, febrile sense, chill and vomiting. The following bacterial organisms, Salmonella spp, Shigella spp, Vibrio spp, Staphylococcus aureus, and E coli O157 were examined in 196 stool specimens, but no suspicious organism was detected. In virological examinations, Norovirus was dectected in 3 out of 25 stool specimens from the sick students. Among the 22 stool specimens of the food handlers during the school trip, both bacterial and virological examinations were all negative. Among the 13 environmental specimens, the groundwater of the hotel, where the students had stayed during their school trip, was contaminated with general bacteria and E. Coli. However, we could not detect Norovirus in the groundwater of the hotel. We concluded that Norovirus might be a possible cause of this outbreak, and the water supply of the hotel might be a probable source of this outbreak.

Age-related decline in expression of calnexin

Aging is accompanied by the changes in the cells that decrease their capacity to respond to various forms of stress. Cells are known to respond to stresses through expression of stress- response proteins, heat-shock proteins composed of molecular chaperones. Recent studies suggest that chaperone level and stress-induced chaperone expression could decrease with aging. The aim of the present study is to identify chaperones that show a significant change in protein expression with aging. We used an in vitro aging model system of human diploid fibroblasts (HDF). Proteome analysis of HDF showed that endoplasmic reticulum (ER) chaperone, calnexin, significantly decreased with aging. Oxidative stress-induced expression of calnexin also attenuated in old HDF compared to young cells. These findings suggest calnexin decreases with aging and might contribute to a cytoprotection in a variety of human age-related diseases.

Clinicopathologic Study of Remnant Gastric Cancer

PURPOSE: Remnant gastric cancer (RGC) is usually diagnosed at an advanced stage, and consequently the prognosis is poor. This retrospective study was performed to evaluate the clinicopathological characteristics and prognosis of RGC. METHODS: A total of 39 patients, with RGC, were diagnosed after a partial gastrectomy, at the Dept. of Surgery, Korea University College of Medicine between September 1983 and December 2000 (7 for benign gastric diseases, the B group and 32 for gastric carcinoma, the M group). The clinicopathological features and 5-year survival rates were investigated for the two groups. RESULTS: The average age was 54.1+/-10.1, and a male predominance was shown. The latency period between the initial surgeries were 35.3+/-25.3 and 142.0+/-71.9 months for groups M and B, respectively. 21 (66%) of the tumors were located in the anastomosis site in the M group, with 4 (57.1%) in the non-anastomosis site in the B group. Significant differences were seen in the latency period and tumor location between the two groups. According to the operation method, RGC mainly developed in the non-anastomosis site in patients having undergone the Billroth I method, whereas it developed in the anastomosis site in cases having undergone the Billroth II method (P=0.047). The overall 5 year survival rate was 42.8%, 71.4% in the B group and 37.2% in the M group. CONCLUSION: There were differences in the latency periods and locations between the benign and malignant groups, and the prognosis with the remnant gastric cancer was no different from that of primary gastric cancer. These results suggest that the early detection of gastric cancer in the remnant stomach, by periodical follow up, is important.

Prognostic Value of Natural Killer Cell and Dendritic Cell Infiltration in Gastric Cancer

PURPOSE: Natural killer cells (NKC) and dendritic cells(DC) have non-specific cytotoxic effect against various tumor such as breast cancer, colorectal cancer and lung cancer. However, the relationsjip between the infiltration of these cells and the prognosis of gastric cancer has not yet been elucidated. Therefore the aim of this study is to assess the prognostic impact of NKC and DC infiltration in gastric cancer patient. METHODS: Ninety-seven patients who had undergone a gastrectomy (radical subtotal gastrectomy or radical total gastrectomy) at Yonsei Wonju Christian Hospital between Jan. 1995 and Dec. 1995 were enrolled in the study. Immunohistochemical staining was performed for evaluation of NKC infiltration with CD57 antibody and of DC infiltration with S-100 protein. In DC, the number of S-100 protein positive DC was graded as either low dendritic cell infiltration(0 to 20) or high dendritic cell infiltration (over 20 cells) under high power microscopy (x400 HPF). In NKC, a total of 25 areas containing pericancerous tissue were selected for determining the number of NKC infiltration, after which patients were classified as either low NKC infiltraion (0 to 25) or high NKC infiltration (over 25 cells). The Kaplan-Meier method was used to obtain survival curve and multivariated analysis were performed using Cox regression model. RESULTS: The 5-year survival rate was 75.0% in patients with high infiltration of NKC, 45.3% in those with low infiltration of NKC, 80.0% in those with high infiltration of DC and 43.8% in those with low infiltration of DC. These results were statistically different (P<0.01). However multivariate analysis did not show NKC and DC infiltration to be significant prognostic factors. CONCLUSION: NKC and DC intratumoral infiltration of gastric cancer was positively correlated with survival in this study. Although the prognostic significances of NKC and DC intratumoral infiltration were P<0.01 in both NKC and DC in univariated analysis, these results were not permitted as independent prognostic factors in multivariated analysis.

Vibrio vulnificus cytolysin induces hyperadhesiveness of pulmonary endothelial cells for neutrophils through endothelial P-selectin: a mechanism for pulmonary damage by Vibrio vulnificus cytolysin

Vibrio vulnificus cytolysin forms transmembrane pores that are permeable to calcium ions in pulmonary endothelial cells, and has been suggested as an important virulence factor that sequestrate neutrophils primarily in the lung. To elucidate the mechanism we investigated whether the cytolysin affect the expression of endothelial P-selectin and adhesiveness of pulmonary endothelial cells for neutrophils. The cytolysin increased the adhesiveness of CPAE cell, a pulmonary endothelial cell line, for neutrophils in a concentrationand time-dependent manner. The increase of adhesiveness occurred within several minutes after the cytolysin exposure, persisted up to 90 min, and was not affected by cycloheximide. Furthermore, flow cytometric analyses showed that cytolysin enhanced the level of P-selectin on CPAE cell surface. Therefore, these results suggest that the cytolysin-induced hyperadhesiveness of pulmonary endothelial cells for neutrophils is mediated by the mobilization of endothelial P-selectin to the cell surface.

Vibrio vulnificus cytolysin induces hyperadhesiveness of pulmonary endothelial cells for neutrophils through endothelial P-selectin: a mechanism for pulmonary damage by Vibrio vulnificus cytolysin

Vibrio vulnificus cytolysin forms transmembrane pores that are permeable to calcium ions in pulmonary endothelial cells, and has been suggested as an important virulence factor that sequestrate neutrophils primarily in the lung. To elucidate the mechanism we investigated whether the cytolysin affect the expression of endothelial P-selectin and adhesiveness of pulmonary endothelial cells for neutrophils. The cytolysin increased the adhesiveness of CPAE cell, a pulmonary endothelial cell line, for neutrophils in a concentrationand time-dependent manner. The increase of adhesiveness occurred within several minutes after the cytolysin exposure, persisted up to 90 min, and was not affected by cycloheximide. Furthermore, flow cytometric analyses showed that cytolysin enhanced the level of P-selectin on CPAE cell surface. Therefore, these results suggest that the cytolysin-induced hyperadhesiveness of pulmonary endothelial cells for neutrophils is mediated by the mobilization of endothelial P-selectin to the cell surface.

Cholesterol induce oligomerization of Vibrio vulnificus cytolysin specifically

Vibrio vulnificus cytolysin (VVC) has been implicated as one of the important virulence determinants of V. vulnificus that causes serious septicemia and wound infection. An attempt was made to investigate that VVC could act as a ligand which stimulates intracellular signaling systems. Cholesterol dose-dependently blocked VVC hemolytic activity through oli-gomerization of cytolysin. Among cholesterol derivatives including 7-dehydrocholesterol, cholesteryl esters, deoxycholate, and cholestane tested, only 7-dehydrocholesterol induced oligomerization as well as inactivation of VVC. These results show that oligomerization of VVC is completely dependent on three-dimensional structure of cholesterol where specific interaction of cholesterol at oligomerization sites of VVC is very selective. These findings support the idea that cholesterol which constitute many of cellular plasma membrane could be a receptor of VVC on plasma membrane of target cells.

The Utility of Pleural Adenosine Deaminase for Diagnosis of Differentiating Tuberculous Pleural Effusion in Children / 소아알레르기및호흡기학회지

PURPOSE: The aim of this study is to evaluate the value of pleural adenosine deaminase (ADA) in differentiating tuberculous pleural effusion from non tuberculous pleural effusion of children. METHODS: We measured pleural ADA activity in patients with pleural effusion whose age were from seven months to seventeen years from January 1995 to October 2001. By some criteria the patients were grouped to tuberculous pleural effusion, bacterial effusion, mycoplasma effusion, malignant effusion, and other effusion. RESULTS: The mean pleural ADA activity in tuberculous pleural effusion was 86.2+/-27.3 U/L. Pleural ADA activities in bacterial effusion, mycoplasma effusion, malignant effusion, other effusion were 32.6+/-20.1, 22.1+/-15.4, 23.1+/-10.9, 36.7+/-28.4 U/L, respectively. Pleural ADA activity in tuberculous pleural effusion was significantly higher than in any other group(P<0.001). At a level of 50 U/L, the sensitivity, specificity, positive predictive value (ppv), and and negative predictive value(npv) for the identification of tuberculous pleural effusion from nontuberculous pleural effusion were calculated at 93.8%, 84.8%, 81.1%, 95.1%, respectively. CONCLUSION: Pleural ADA is a useful test in the diagnosis of tuberculous pleural effusion of children from nontuberculous pleural effusion.

Effects of Genotype of Tumor Necrosis Factor Alpha Promoter on Bladder Tumor Grade / 대한비뇨기과학회지

Purpose: Several polymorphic sites have been reported in the tumor necrosis factor alpha (TNF-alpha) promoter. Comparative studies on TNF-alpha production with promoter genotype have reported variable results, particularly in the 308 promoter region. Therefore, genetic polymorphism of TNF-alpha promoter region ( 308) was investigated to determine if it was associated with bladder tumor. MATERIALS AND METHODS: The DNA from 113 and 109 respective blood samples of bladder tumor patients and controls was analyzed by a PCR-based restriction fragment length polymorphism (RFLP) method to characterize the genetic polymorphism of the 308 region of the TNF-alpha promoter. TNF-alpha expression was also checked by measuring the mRNA and protein content using a quantitative-competitive PCR and ELISA method, respectively. RESULTS: The difference in the genetic variations of TNF-alpha promoter did not exist between the bladder tumor patients and the control group (p=0.259). The tumor grade was significantly related to the GA genotype (p=0.04). The mRNA levels of TNF-alpha in the GA genotype were significantly higher than those in the GG genotype in bladder tumors (p=0.022). The TNF-alpha serum levels in the GA genotype were significantly higher than those in the GG genotype regardless of whether there was a bladder tumor. In addition, the TNF-alpha serum levels in bladder tumor patients were significantly higher than the controls in either the GG or GA type (GG type, p=0.001; GA type, p=0.009). CONCLUSIONS: The GA genotype of the TNF-alpha promoter region ( 308) had a significant impact on TNF-alpha production and is related to a higher-grade tumor compared to the GG genotype. The TNF-alpha serum levels in the bladder tumor patients were significantly higher than in the controls. This suggests that TNF-alpha might be involved in the tumorigenesis of the bladder.

Evaluation of Imaging Studies in Male Infants less than 3 Months after First Urinary Tract Infection

PURPOSE : To evaluate the frequency of urinary tract anomalies in male neonates less than 3months old who presented with urinary tract infection(UTI) and to evaluate a appropriate imaging approach after first UTI. MATERIALS AND METHODS : During a period of 5 years, from March 1994 to February 1999, 65 male infants less than 3months old(range: 4-92 days, mean: 43 days) with UTI were evaluated. Ultrasound(US) and Voiding cystourethrogram(VCUG) were done in 60 patients. Due to refusal and technological problem, 5 patients were missed. 99mTc-dimercaptosuccinic acid renal scan (99mTc-DMSA renal scan) was recommended to most patients but performed in 40 patients. Renal scan was performed at least 3 months later after urinary tract infection. RESULTS : Urinary tract anomalies were found in 26 of 65 infants. Twenty-six had vesicoureteral reflux(VUR), two had both VUR and double ureter, two had both VUR and posterior urethral valve. In patients with VUR, eight had renal scar or renal atrophies. In case of renal scar or atrophy, grades of VUR were III or above. CONCLUSION : We suggest that US and VCUG should be routinely performed in infants(<3months)with first UTI. 99mTc-DMSA renal scan should be performed only when renal parenchymal damage was observed in US and VUR grade III or above in VCUG.

Clinical Significance of Peripheral Blood CEA mRNA Expression in Gastric Cancer Patients Underwent Curative Resection / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Recent advances in molecular technology have made it possible to detect small numbers of circulating tumor cells in the peripheral blood or bone marrow. Carcinoembryonic antigen (CEA) is an oncofetal antigen that is expressed in epithelial tumor cells. CEA mRNA may be a reliable marker for the detection of tumor cells in the peripheral blood of patients with epithelial cancer. MATERIALS AND METHODS: We analyzed the peripheral blood of 46 patients with gastric cancer who had undergone curative resection. The presence of CEA mRNA was serially monitored using RT-PCR (Preop, Post op 15 day, 2 months (m), 4 m, 6 m, 8 m, 10 m, 12 m). The clinical characteristics, serum CEA level and immunohistochemical staining of tumor tissue were also evaluated. Patients were followed up for 6 to 12 months. RESULTS: There was no significant relationship seen between CEA mRNA RT-PCR positivity in the peripheral blood and sex, stage, serum CEA level or immunohistochemical staining for CEA antigen, During follow up,eight patients experienced recurrence; were positve for CEA mRNA RT-PCR recurrence was seen in 66.7% (6/9) of the patients who before clinical recurrence as compared to 5.4% (2/37) of patients who were negative (p=0.0002). Serial changes of CEA mRNA RT-PCR correlated with clinical recurrence; 100% in the positively converted group (3/3), 0% in the negatively converted group(0/18), 50% in all positive group (3/6) and 10.5% in all negative group (2/19) experienced recurrence, respectively. CONCLUSION: RT-PCR analysis of CEA mRNA in the peripheral blood seems to be a promising tool for the early detection of micrometastatic circulating tumor cells in gastric cancer patients and may be useful in determining patients at high risk for recurrence. However, definitive correlation with recurrence certainly requires a longer follow up duration in further studies.