The small GTP-binding protein Rab25 is associated with tumor formation and progression. However, recent studies have shown discordant effects of Rab25 on cancer cell progression depending on cell lineage. In the present study, we elucidate the underlying mechanisms by which Rab25 induces cellular invasion. We demonstrate that Rab25 increases β1 integrin levels and subsequent activation of EGFR and upregulation of VEGF-A expression, leading to increased Snail expression, epithelial-to-mesenchymal transition and cancer cell invasiveness. Strikingly, we identify that Snail mediates Rab25-induced cancer cell invasiveness through fascin expression and that ectopic expression of Rab25 aggravates metastasis of ovarian cancer cells to the lung. We thus demonstrate a novel role of a β1 integrin/EGFR/VEGF-A/Snail signaling cascade in Rab25-induced cancer cell aggressiveness through induction of fascin expression, thus providing novel biomarkers and potential therapeutic targets for Rab25-expressing cancer cells.
Biomarkers ; Cell Lineage ; Ectopic Gene Expression ; GTP-Binding Proteins ; Lung ; Neoplasm Metastasis ; Ovarian Neoplasms ; Snails ; Up-Regulation ; Vascular Endothelial Growth Factor A

BACKGROUND: Vitamin K antagonist (VKA) to prevent thromboembolism in non-valvular atrial fibrillation (NVAF) patients has limitations such as drug interaction. This study investigated the clinical characteristics of Korean patients treated with VKA for stroke prevention and assessed quality of VKA therapy and treatment satisfaction. METHODS: We conducted a multicenter, prospective, non-interventional study. Patients with CHADS2 ≥ 1 and treated with VKA (started within the last 3 months) were enrolled from April 2013 to March 2014. Demographic and clinical features including risk factors of stroke and VKA treatment information was collected at baseline. Treatment patterns and international normalized ratio (INR) level were evaluated during follow-up. Time in therapeutic range (TTR) > 60% indicated well-controlled INR. Treatment satisfaction on the VKA use was measured by Treatment Satisfaction Questionnaire for Medication (TSQM) after 3 months of follow-up. RESULTS: A total of 877 patients (age, 67; male, 60%) were enrolled and followed up for one year. More than half of patients (56%) had CHADS2 ≥ 2 and 83.6% had CHA2DS2-VASc ≥ 2. A total of 852 patients had one or more INR measurement during their follow-up period. Among those patients, 25.5% discontinued VKA treatment during follow-up. Of all patients, 626 patients (73%) had poor-controlled INR (TTR < 60%) measure. Patients' treatment satisfaction measured with TSQM was 55.6 in global satisfaction domain. CONCLUSION: INR was poorly controlled in Korean NVAF patients treated with VKA. VKA users also showed low treatment satisfaction.
Atrial Fibrillation* ; Drug Interactions ; Follow-Up Studies ; Humans ; International Normalized Ratio ; Male ; Prospective Studies ; Risk Factors ; Stroke ; Thromboembolism ; Vitamin K* ; Vitamins*

PURPOSE: The p21(Waf1/Cip1) protein inhibits the cell cycle by inhibiting the phosphorylation at the G1-->S check point, and the p27(Kip1) protein similarly performs the suppressor function by controlling the p27-mediated G1 arrest. In this study, we analysed the clinical status and survival rates in correlations with p21 and p27 expression patterns in gastric cancer. MATERIALS AND METHODS: Between 1993 and 1997, 192 patients who underwent surgeries in Catholic Medical Center were analysed retrospectively in this study. Immunohistochemical staining was performed and if the nuclei of the tumor cells were stained, we assumed those as positive results. Statistical analysis was based on clinicopathological findings and differences in survival rates. RESULTS: The expression rate of p27 was 28.1% and 15.6% in p21 each. The ratio of T1-2(80.0%) was significantly high in p21 (+), but the ratio of T3-4 (50.6%) was slightly high in p21 (-). There was no statistical significance regarding other factors. The results in p27 was not much different from expression rate of p21 in T-stage. In addition, p27 expression in diffuse type (91.3%) was higher than in intestinal type (62.7%) by Lauren's classification (P <0.05). Also, there was no statistical significance in other factors. In the correlation of p21 and p27, p27 was positive when p21 was positive (53.5%). Conversely, p27 was negative when p21 was negative (76.5%, p <0.05). In the p21 and p27 combination test, there was higher rate of T1-2 (87.5%) in p21 (+)/p27 (+), and higher rate of T3-4 (58.1%) in p21 (-)/p27 (-) (P <0.05). Results showed higher rate of intestinal type (100%) in p21 (+)/p27 (+), and diffuse type (87.0%) was dominant in p21 (-)/p27 (-) (P <0.05) by Lauren's classification. Moreover, there was no statistical significance in the 5-year survival rate in the expression of p21 and p27, and the 5-year survival rate was highest in the case of p21 (+)/p27 (+) without statistical significance. CONCLUSION: In our study, p21(Waf1/Cip1) and p27(Kip1) expressed similar patterns. The expression of p21(Waf1/Cip1) and p27(Kip1) affected the degree of invasiveness of the tumor, and. Combined examination result revealed the correlation of p21(Waf1/Cip1) and p27(Kip1) with Lauren's classification and depth of invasion of the tumor. However, we assumed that little difference between the survival rates depending on expression of p21(Waf1/Cip1) and p27(Kip1) has limited their value as predictable prognostic indicators.
Cell Cycle ; Classification ; Humans ; Phosphorylation ; Retrospective Studies ; Stomach Neoplasms* ; Survival Rate

PURPOSE: In Korea, the number of laparoscopy-assisted distal gastrectomies for early gastric cancer patients has been increasing lately. Although minimally invasive surgery is more beneficial, no reported case of a totally laparoscopic distal gastrectomy has been reported because of difficulty with intracorporeal anastomosis. This study attempts, through our experiences, to determine the feasibility of a totally laparoscopic distal gastrectomy using an intracorporeal gastroduodenostomy in treating early gastric carcinoma. MATERIALS AND METHODS: We investigated surgical results and clinicopatholgic characteristics of eight(8) patients with an early gastric carcinoma who underwent a totally laparoscopic distal gastrectomy at the Department of Surgery, Our Lady of Mercy Hospital, The Catholic University of Korea, between June 2004 and September 2004. The intracorporeal gastroduodenostomy was performed with a delta-shaped ananstomosis by using only laparoscopic linear staplers (Endocutter 45 mm; Ethicon Endosurgery, OH, USA). RESULTS: The operative time was 369.4+/-62.5 minutes (range 275~65 minutes), and the anastomotic time was 45.1+/-14.4 minutes (range 32~0 minutes). The anastomotic time was shortened as surgical experience was gained. The number of laparoscopic linear staplers for an operation was 7.1+/-0.6. The number of lymph nodes harvested was 31.9+/-13.1. There was 1 case of transfusion and no case of conversion to an open procedure. The time to the first flatus was 2.8+/-0.5 days, and the time to the first food intake was 4.1+/-0.8 days. There were no early postoperative complications, and the postoperative hospital stay was 10.0+/-3.9 days. CONCLUSION: A totally laparoscopic distal gastrectomy using an intracorporeal gastroduodenostomy with a delta-shaped anastomosis is technically feasible and can maximize the benefit of laparoscopic surgery for early gastric cancer.
Conversion to Open Surgery ; Eating ; Flatulence ; Gastrectomy* ; Humans ; Korea ; Laparoscopy ; Length of Stay ; Lymph Nodes ; Operative Time ; Postoperative Complications ; Stomach Neoplasms ; Surgical Procedures, Minimally Invasive

PURPOSE: In this study, the level of expression of p14(ARF), p16(INK4a), p53 and pRb was immunohistochemically examined according to the stage of gastric cancer, lymph node metastasis, cell differentiation and Lauren's classification. The effect on survival rate and the associations between the components were examined as well. METHODS: One hundred and fourteen patients who underwent surgery for gastric cancer were studied retrospectively using their paraffin embedded tissue and medical records. Using antibodies of p14(ARF), p16(INK4a), p53 and pRb, immunohistochemical stain was applied and their level of expression examined. RESULTS: The level of p53 expression was high when the stage of gastric cancer was more progressed, the invasiveness higher, lymph node metastasis present and cell differentiation poorer. In contrast, the level of p14ARF expression tended to be lower as the stage was more progressed, but this was not statistically significant. Expression of p16 and pRb did not show any association with stage or other pathologic findings. Expression of p53 and p14(ARF) also had a significant association with survival rate. Survival rate was lower in patients who expressed p53 than in those who did not, but it was higher in who expressed p14ARF than in those who did not. When these two were combined, patients with p14(ARF)(+)/p53(-) had the highest survival rate, whereas those with p14(ARF)(-)/p53(+)had the lowest. This demonstrated that the expressions of p14ART and p53 have value as prognostic indicators. CONCLUSION: From these results, p53 seems closely related to stage and other pathologic findings. Furthermore, p14(ARF) and p53 showed a statistically significant relationship with survival rate, making them valuable as prognostic indicators after surgery. In combination, it would be possible to predict a more accurate prognosis.
Antibodies ; Cell Differentiation ; Classification ; Cyclin-Dependent Kinase Inhibitor p16* ; Humans ; Lymph Nodes ; Medical Records ; Neoplasm Metastasis ; Paraffin ; Prognosis ; Retrospective Studies ; Stomach Neoplasms* ; Survival Rate ; Tumor Suppressor Protein p14ARF*

PURPOSE: While E-cadherin in normal cells induces calcium-dependent cell-cell adhesion, in malignant cell, it plays a role in invasion and metastasis with a reduction of adhesion. Serum soluble E-cadherin is a result of the reduction of the cellular E-cadherin molecule and is found in the circulation of normal individuals, but it is particularly known to be increased in patients with malignancies. Accordingly, through checking the level of serum soluble E-cadherin in patients with gastric cancer and analyzing it in the view of clinicopathology, we investigated whether serum soluble E-cadherin could be translated into a clinicopathologic esult and used as a tumor marker. MATERIALS AND METHODS: The investigation targeted 88 patients who had been diagnosed as having gastric cancer by the Department of Surgery, St. Mary's Hospital, from October 1, 2002, to July 30, 2003, and who had under gone performed surgery. We measured the level of preoperative serum E-cadherin in the 88 patients by unsing ELISA. Among them, we collected gastric cancer tissues from 54 patients and executed immunohistochemistry for E-cadherin. The samples were compared with normal tissues in terms of both serum E-cadherin level and immunohistochemistry level, as well as with other clinicopathologic factors. RESULTS: The mean serum E-cadherin level of the 88 patients was 4368.7 ng/ml and was significantly higher than the level in 12 normal control patients, 3335.5 ng/ml (P=0.016). In terms of clinicopathology, the serum level of E-cadherin was significantly correlated with increasing age (P=0.0006) and was higher in positive venous invasion patients (P=0.0005). When the E-cadherin immunohistochemical stain was compared with the serum E-cadherin level in 54 patients, no significant statistically meaningful result was obtained (P=0.2881). However, 4 patients with serum E-cadherin levels about 6000 ng/ml were classified into the lower expression group (<80%) of E-cadherin immunohistochemicals stain. In the analysis for 36 patients who were early gastric cancer patients, the serum E-cadherin level in lymph-node-metastatic patients was higher than it was in the other patients (P=0.0442). CONCLUSION: The serum E-cadherin level in gastric cancer patients was higher than the level in normal control patients. In advanced gastric cancer patients, that the difference was increased. Also, since the E-cadherin level correlated with the serum E-cadherin level with venous invasion, it can be used as an effective tumor marker for gastric cancer. Particularly, in that the serum E-cadherin level correlated with lymph node metastasis in early gastic cancer, it can be used when a therapeutic method for early gastric cancer is selected.
Cadherins* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Stomach Neoplasms*

PURPOSE: Paraffin-embedded tissue samples from the gastrointestinal tract, which had been diagnosed as tumors of a mesenchymal origin, were reviewed by an immunohistochemical staining method. The prognostic significances of the immunohistochemical subtypes and anatomical locations were also investigated. GIST, as a new grading system, was compared with the pre-existing system for its useful prognostic significance. METHODS: 122 cases were evaluated and classified by immunohistochemical staining for KIT, CD34, actin, desmin, vimentin, S-100 protein and NSE. RESULTS: Positivity for both KIT and CD34 of 92.6 and 73.8%, respectively, indicated that KIT was more effective for the diagnosis of GISTs. The stomach (62.3%) and small bowel (23.7%) were most common organs of GIST. There was no difference in the prognosis between these two organs. Immunophenotypically, the uncommitted, myoid, combined and neural types were 37.7, 23.7, 20.2 and 7%, respectively. There was no significant difference in the prognosis between these types. The old grading system showed no difference between the borderline and malignant groups (P=0.14), whereas, the new grading system showed a significant difference between the intermediate and high risk groups (P=0.01). CONCLUSION: KIT is more useful for the diagnosis of GOSTs. The immunophenotypical classification and anatomical location showed no prognostic significance in GISTs. Therefore, the new grading system might be more useful than older system.
Actins ; Classification ; Desmin ; Diagnosis* ; Gastrointestinal Stromal Tumors* ; Gastrointestinal Tract ; Immunohistochemistry* ; Prognosis ; S100 Proteins ; Stomach ; Vimentin

BACKGROUND: Plasmid-mediated AmpC beta-lactamases (PABL) are cephalosporinases that confer resistance to a wide variety of beta-lactam drugs and that may thereby create serious therapeutic problems. The PABL-producing organisms are a major concern in nosocomial infections and should there-fore be monitored in surveillance studies. Although reported with increasing frequency in Korea, the occurrence and genotypic distributions of PABL in Escherichia coli and Klebsiella pneumoniae remain unknown. METHODS: We tested a total of 911 consecutive, nonduplicate isolates of E. coli and K. pneumoniae at 12 university hospitals and a commercial laboratory in Korea. Antimicrobial susceptibilities were tested using the disk diffusion method. PABL production was determined by the modified Hodge test and multiplex PCR. The PCR differentiated the six PABL-specific families in E. coli and K. pneumoniae. RESULTS: Overall, 110 (12.1%) yielded cefoxitin non-susceptible isolates and that 28 (3.1%) demonstrated PABL producers by multiplex PCR. Based on the species, of 544 E. coli and 367 K. pneumoniae isolates tested, 8 (1.5%) and 20 (5.4%), respectively, demonstrated PABL producers. The genotypes of PCR amplification showed that the MOX, DHA, and CIT family were harbored by 4, 2, and 2 of 8 PABL-producing E. coli, and the DHA, MOX, and EBC family were harbored by 13, 6, and 1 of 20 PABL-producing K. pneumoniae isolates, respectively. CONCLUSIONS: These data confirm that the occurrence of PABL-producing E. coli and K. pneumoniae is relatively high and the kinds of genotypes are variously distributed in Korea.
beta-Lactamases ; Cefoxitin ; Cross Infection ; Diffusion ; Escherichia coli* ; Escherichia* ; Genotype ; Hospitals, University ; Humans ; Klebsiella pneumoniae* ; Klebsiella* ; Korea* ; Multiplex Polymerase Chain Reaction ; Pneumonia ; Polymerase Chain Reaction

Estrogen replacement therapy is known to reduce the incidence of cardiovascular disease and osteoporosis in postmenopausal women. Estrogen has beneficial effect on bone density and adding progesterone to estrogen is known to have synergistic effect. However, the effect of progesterone on bone mineral density had not been precisely evaluated in Korean postmenopausal women. To evaluate the impacts of progesterone on bone mineral density during estrogen replacement therapy, we conducted the randomized 2-year trials of conjugated equine estrogen (Premarin(R) 0.625 mg/day) with or without cyclic progesterone(medroxyprogesterone acetate : MPA 10 mg/day for 12 days) in 105 postmenopausal women. Bone mineral density was measured in the lumbar vertebrae(L2-L4) using dual energy X-ray absorptiometry(DEXA) at the beginning of the treatment, 6 onths, 12 months and 24 months later, respectively. In Premarin only group, bone mineral density at 6 months and 12 months after treatment did not show significant difference from baseline value. But bone mineral density on 24 months after treatment showed significantly increased value(p value<0.05) than that of initial. In Premarin plus MPA group, bone mineral density at 12 months and 24 months after treatment showed significantly increased than baseline(p value<0.05). And compared with Premarin only group, Premarin plus MPA group showed significant increase in spinal bone density after 2 years treatment(p value<0.05). These results suggest that the addition of MPA in estrogen replacement therapy appears to increase in bone mineral density more than unopposed estrogen. Thus combination of estrogen and progesterone appeared to be effective long-term prophylactic treatment regimen upon postmenopausal bone loss.
Bone Density* ; Cardiovascular Diseases ; Estrogen Replacement Therapy* ; Estrogens* ; Estrogens, Conjugated (USP) ; Female ; Humans ; Incidence ; Osteoporosis ; Osteoporosis, Postmenopausal ; Progesterone*

No abstract available.
Axilla*