Homeostatic imbalance between cell proliferation and death in gastric mucosal epithelia may lead to gastritis and gastric cancer. Despite abundant gastrokine 1 (GKN1) expression in the normal stomach, the loss of GKN1 expression is frequently detected in gastric mucosa infected with Helicobacter pylori, as well as in intestinal metaplasia and gastric cancer tissues, suggesting that GKN1 plays an important role in gastric mucosal defense, and the gene functions as a gastric tumor suppressor. In the stomach, GKN1 is involved in gastric mucosal inflammation by regulating cytokine production, the nuclear factor-kappaB signaling pathway, and cyclooxygenase-2 expression. GKN1 also inhibits the carcinogenic potential of H. pylori protein CagA by binding to it, and up-regulates antioxidant enzymes. In addition, GKN1 reduces cell viability, proliferation, and colony formation by inhibiting cell cycle progression and epigenetic modification by down-regulating the expression levels of DNMT1 and EZH2, and DNMT1 activity, and inducing apoptosis through the death receptor-dependent pathway. Furthermore, GKN1 also inhibits gastric cancer cell invasion and metastasis via coordinated regulation of epithelial mesenchymal transition-related protein expression, reactive oxygen species production, and PI3K/Akt signaling pathway activation. Although the modes of action of GKN1 have not been clearly described, recent limited evidence suggests that GKN1 acts as a gastric-specific tumor suppressor. This review aims to discuss, comment, and summarize the recent progress in the understanding of the role of GKN1 in gastric cancer development and progression.
Apoptosis ; Cell Cycle ; Cell Proliferation ; Cell Survival ; Cyclooxygenase 2 ; Epigenomics ; Gastric Mucosa ; Gastritis ; Genes, Tumor Suppressor ; Helicobacter pylori ; Homeostasis ; Inflammation ; Metaplasia ; Neoplasm Metastasis ; Reactive Oxygen Species ; Stomach ; Stomach Neoplasms*

OBJECTIVES: The aim of this study is to investigate correlation between the location of white matter hyperintensities (WMH) and neurocognitive dysfunction in non-demented Korean vascular depression patients. METHODS: A total of 148 subjects diagnosed with first major depressive episode after the age of 60 were included in this study. Subjects were divided into the vascular depression group (n=83) and the non-vascular depression group (n=65) according to the degree of WMH. The degree and location of WMH on T2-weighted images were measured using the Scheltens scale. In addition, several clinical features, including cognitive functions and depression severities, were evaluated. Correlation analysis was performed for examination of the relationships between the location of WMH and neuropsychological functions. RESULTS: Capsular frontal periventricular hyperintensities showed correlation with poorer performance of the word list memory test, constructional recall test, and trail making test A and B. Lateral ventricular hyperintensities showed correlation with poorer performance of verbal fluency test, word list recognition test, and trail making test B. Deep WMH, especially parietal and occipital lesions, showed an association with poorer performance on trail making test B. In addition, deep WMH, but not periventricular WMH, showed an association with Hamilton Depression Scale score. CONCLUSION: Our results suggest that subjects with vascular depression showed significantly poorer performance on neurocognitive tests than those with non-vascular depression. In addition, WMH, depending on their locations, showed different correlations according to details of cognitive dysfunction and severity of depressive symptoms.
Depression ; Humans ; Memory ; Trail Making Test

PURPOSE: Silent mating-type information regulation 2 homologue 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. SIRT1 plays an important role in the regulation of cell death/survival and stress response in mammals. The aim of this study was to investigate whether the SIRT1 gene is involved in the development or progression of gastric cancers. MATERIALS AND METHODS: SIRT1 and p53 genes in 86 gastric cancers were examined for genetic alterations by PCR-single strand conformation polymorphism sequencing, as well as SIRT1 protein expression in 170 gastric cancers by immunohistochemistry. RESULTS: In the genetic analysis, we found SIRT1 and p53 mutations in two and 12 cases, respectively. Two missense mutations, c.599 C>T (T200I) and c.1258 G>A (E420K), were detected in the SIRT1 gene coding region. The SIRT1 and p53 mutation were found in mutually exclusive gastric cancers. The immunohistochemistry revealed that SIRT1 overexpression was found in 95 (55.9%) of 170 gastric cancers. Altered SIRT1 expression was not statistically associated with clinicopathological parameters, including tumor differentiation, location, lymph node metastasis, or p53 expression. Two cases with an SIRT1 mutation showed increased SIRT1 expression. CONCLUSIONS: These results suggest that genetic alterations and overexpression of the SIRT1 gene may contribute to gastric cancer development.
Adenine ; Clinical Coding ; Genes, p53 ; Immunohistochemistry ; Lymph Nodes ; Mammals ; Mutation, Missense ; Neoplasm Metastasis ; Niacinamide ; Stomach Neoplasms

BACKGROUND: The tumor necrosis factor (TNF) is believed to play an important role in the pathophysiology of osteoarthritis (OA). Evidence shows that genetic polymorphisms make substantial contributions to the etiology of OA. METHODS: We investigated the genotypes TNF-alpha and TNF-beta in 301 OA patients and 291 healthy subjects as controls. We employed a polymerase chain reaction-restriction fragment length polymorphism and a polymerase chain reaction-single strand conformation polymorphism assay to identify the genotypes TNFA -G308A and TNFB +G252A, respectively. RESULTS: For TNFA -G308A, the percentages of genotypes GG, AG, and AA were 26.3% (79/301), 62.5% (188/301), and 11.3% (34/301) in OA patients and 88.7% (258/291), 11.3% (33/291), and 0% (0/291) in controls. For TNFB +G252A, the percentages of genotypes GG, AG, and AA were 15.3% (46/301), 41.9% (126/301), and 42.9% (129/301) in OA patients and 12% (35/291), 52.6% (153/291), and 35.4% (103/291) in controls. There were significant differences in genotypes and alleles of TNFA -308 between OA patients and controls (p<0.0001) and in alleles of TNFB +252 (p=0.0325). The risk of OA was significantly higher for carriers of the TNFA -308A allele and the TNFB +252 AA homozygote (p=0.0224). CONCLUSIONS: The results suggest close relationships between TNFA -G308A and TNFB +G252A polymorphisms and individual susceptibility to OA in the Korean population.
Alleles ; Genetic Predisposition to Disease ; Genotype ; Homozygote ; Humans ; Lymphotoxin-alpha ; Osteoarthritis ; Polymorphism, Genetic ; Tumor Necrosis Factor-alpha

PURPOSE: Gastrokine 1 plays an important role in gastric mucosal defense. Additionally, the Gastrokine 1-miR-185-DNMT1 axis has been shown to suppress gastric carcinogenesis through regulation of epigenetic alteration. Here, we investigated the effects of Gastrokine 1 on DNA methylation and gastritis. MATERIALS AND METHODS: Expression of Gastrokine 1, DNMT1, EZH2, and c-Myc proteins, and the presence of Helicobacter pylori CagA protein were determined in 55 non-neoplastic gastric mucosal tissue samples by western blot analysis. The CpG island methylation phenotype was also examined using six markers (p16, hMLH1, CDH1, MINT1, MINT2 and MINT31) by methylation-specific polymerase chain reaction. Histological gastritis was assessed according to the updated Sydney classification system. RESULTS: Reduced Gastrokine 1 expression was found in 20 of the 55 (36.4%) gastric mucosal tissue samples and was closely associated with miR-185 expression. The Gastrokine 1 expression level was inversely correlated with that of DNMT1, EZH2, and c-Myc, and closely associated with the degree of gastritis. The H. pylori CagA protein was detected in 26 of the 55 (47.3%) gastric mucosal tissues and was positively associated with the expression of DNMT1, EZH2, and c-Myc. In addition, 30 (54.5%) and 23 (41.9%) of the gastric mucosal tissues could be classified as CpG island methylation phenotype-low and CpG island methylation phenotype-high, respectively. Reduced expression of Gastrokine 1 and miR-185, and increased expression of DNMT1, EZH2, and c-Myc were detected in the CpG island methylation phenotype-high gastric mucosa. CONCLUSIONS: Gastrokine 1 has a crucial role in gastric inflammation and DNA methylation in gastric mucosa.
Axis, Cervical Vertebra ; Blotting, Western ; Carcinogenesis ; Classification ; CpG Islands ; DNA Methylation* ; DNA* ; Epigenomics ; Gastric Mucosa* ; Gastritis* ; Helicobacter pylori ; Humans* ; Inflammation ; Methylation ; Mucous Membrane ; Phenotype ; Polymerase Chain Reaction ; Proto-Oncogene Proteins c-myc

PURPOSE: The EphB2 receptor, a member of the receptor tyrosine kinase family, is a target gene of the Wnt signaling pathway and may achieve a tumor suppressor function through regulation of cell growth and migration. Our aim was to determine whether an altered expression of EphB2 might be associated with gastric cancer development and, if so, to determine to which pathologic parameter it is linked. MATERIALS AND METHODS: For the construction of the gastric cancer tissue microarray, 83 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression patterns of EphB2 were examined on tissue microarray slides by using immunohistochemistry and were compared using pathologic parameters, including histological type, depth of invasion, lymph node metastatsis, and peritoneal dissemination. RESULTS: The EphB2 protein was expressed in the normal gastric mucosal epithelium, especially in the bottom of the mucosa. We found loss of EphB2 expression in 30 (36.1%) of the 83 gastric cancer tissues. Statistically, loss of EphB2 expression was more common in gastric cancer with lymph-node metastasis. There was no significant correlation between EphB2 expression and depth of invasion, histologic type, or peritoneal dissemination. CONCLUSION: Our findings suggest that loss of EphB2 expression may represent a critical step in gastric carcinogenesis.
Carcinogenesis ; Epithelium ; Genes, Tumor Suppressor ; Humans ; Immunohistochemistry ; Lymph Nodes ; Mucous Membrane ; Neoplasm Metastasis ; Protein-Tyrosine Kinases ; Receptor, EphB2 ; Stomach Neoplasms* ; Wnt Signaling Pathway

BACKGROUND: Rocuronium bromide is a monoquaternary amino steroidal muscle relaxant. Rocuronium is structurally stable and no metabolites of rocuronium have not been observed in humans. The manufacturer recommends that rocuronium can be stored in room temperature for 12 weeks. The aim of this study was to determine if the storage temperature of rocuronium could influence the pharmacodynamics of rocuronium. METHODS: One hundred of patients with a class I or II ASA physical status were enrolled in this study. It was divided to two groups. One (Group '0', n = 50) consists of those who had intravenously administered the rocuronium which had been stored in refrigerator and the other (Group '14', n = 50) consists of those who had intravenously administered the rocuronium which had been stored in room temperature (20-29degrees C, median 25.1degrees C) for 14 days. Before an anesthesia was induced, TOF-Watch(R) was attached and calibrated. The anesthesia was induced with 1microgram/kg of fentanyl and 1.5 mg/kg of propofol intravenously. While the 0.1 Hz of single twitch was applied, 0.45 mg/kg of rocuronium, which is appointed to each group, was injected. Intubation is performed 90 seconds after injection of rocuronium and evaluated the intubating condition as excellent, good, poor, and impossible. RESULTS: There was a statistically significant difference in intubating condition at 90 seconds between two groups. The onset time to twitch depression of 0% in group '14' was prolonged compared to group '0' (P < 0.05). Clinical duration was also shortened in group '14' (P < 0.05). CONCLUSIONS: Compared with the use of rocuronium stored in refrigerator, that stored at room temperature can be expected to have unfavorable intubating condition at 90 seconds after rocuronium injection. Therefore, the storage temperature has some influences on the efficacy of rocuronium.
Anesthesia ; Depression ; Fentanyl ; Humans ; Intubation ; Propofol

PURPOSE: The protein kinase Chk1 is required for cell cycle arrest in response to DNA damage and is shown to play an important role in the G2/M checkpoint. The aim of this study was to investigate the relationship between microsatellite instability and frameshift mutation of the Chk1 gene in gastric cancers. MATERIALS AND METHODS: The microsatellite instability was analyzed in 95 primary gastric carcinomas by using microdissection and 6 microsatellite markers. We also performed single strand conformational polymorphism and sequencing to detect frameshift mutation of the Chk1 gene. RESULTS: We found positive microsatellite instability in 19 (20%) of the 95 gastric cancers, 13 high- and 6 low-frequency microsatellite instability cases. The frameshift mutation of Chk1, which resulted in a truncated Chk1 protein, was detected in two high-frequency microsatellite instability cases. CONCLUSION: These data suggest that the microsatellite instability may contribute to the development of gastric carcinomas through inactivation of Chk1.
Cell Cycle ; Cell Cycle Checkpoints ; DNA Damage ; Frameshift Mutation ; Microdissection ; Microsatellite Instability* ; Microsatellite Repeats* ; Protein Kinases ; Stomach Neoplasms*

BACKGROUND: Osteoarthritis (OA) is a common disease characterized by degenerating joint cartilage in the knee, hip, and hand. A functional single nucleotide polymorphism (SNP) +104T/C; rs143383 in the 5' untranslated region of the growth differentiation factor 5 (GDF5) gene was recently associated with susceptibility to OA in the Japanese and Chinese populations. METHODS: To investigate whether this association is present in the Korean population, the frequency of the polymorphism was investigated in 276 patients with knee OA and 298 healthy subjects as controls. Polymorphism analysis was performed by amplifying the core promoter region of the GDF5 gene and digesting it with the BsiEI restriction enzyme. RESULTS: The frequency of the TT, CT, and CC genotypes was 54.3% (150/276), 41.7% (115/276), and 4.0% (11/276), respectively, in patients with OA, and 53.4% (159/298), 37.9% (113/298), and 8.7% (26/298), respectively, in healthy controls. No significant differences in genotypic or allelic frequencies of the +104T/C SNP of the GDF5 gene were observed between patients with OA and controls. Also, no significant differences in allelic and genotypic frequencies were found when the individuals were stratified by age and gender. CONCLUSIONS: The results suggest that the +104T/C; rs143383 GDF5 core promoter polymorphism is not a risk factor for OA in the Korean population.
5' Untranslated Regions ; Asian Continental Ancestry Group ; Cartilage ; Genotype ; Growth Differentiation Factor 5 ; Hand ; Hip ; Humans ; Joints ; Knee ; Osteoarthritis ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Risk Factors

PURPOSE: KLF6, a member of the KLF family, is a ubiquitous zinc finger tumor suppressor protein that is mutated in several human cancers. Our aim was to determine whether the expression pattern of KLF6 might be associated with gastric cancer development and, if so, to determine to which pathologic parameter it is linked. MATERIALS AND METHODS: For the construction of the gastric cancer tissue microarray, 85 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of KLF6 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. RESULTS: The KLF6 protein was expressed on superficial and foveolar epithelial cells in the gastric mucosa. We found loss of KLF6 expression in 28 (32.9%) of the 85 gastric cancer tissues. There was a significant correlation between loss of KLF6 expression and lymph-node metastasis. However, other pathologic parameters, such as histologic type, depth of invasion, and peritoneal dissemination, were not statistically associated with loss of KLF6 expression. CONCLUSION: Our findings suggest that loss of KLF6 expression may contribute to abnormal regulation of gastrointestinal epithelial cell growth and differentiation and to the development and/or progression of Korean gastric cancer.
Apoptosis ; Epithelial Cells ; Gastric Mucosa ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Stomach Neoplasms* ; Zinc Fingers